Trispecific antibody targeting BCMA, GPRC5d and CD3 for the treatment of multiple myeloma

Abstract

Embodiments of the present disclosure relate to methods of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to the subject to treat the multiple myeloma.

Description

TRISPECIFIC ANTIBODY TARGETING BCMA, GPRC5D AND CD3 FOR THE TREATMENT OF MULTIPLE MYELOMACROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of United States Provisional Application Serial Number 63 / 613,454, filed 21 December 2023, United States Provisional Application Serial Number 63 / 660,768, filed 17 June 2024, and United States Provisional Application Serial Number 63 / 695,975, filed 18 September 2024. The entire content of the aforementioned applications is incorporated herein by reference in its entirety.Sequence Listing

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML file format and is hereby incorporated by reference in its entirety. Said XML copy, created on December 11, 2024, is named JBI6867WOPCTl_SL.xml and is 66,217 bytes in size.TECHNICAL FIELD

[0003] The disclosure provided herein relates to methods of treating multiple myeloma using trispecific antibodies or trispecific binding fragments thereof that bind B-cell maturation antigen (BCMA), G-protein coupled receptor, class C, group 5, member D (GPRC5D), and cluster determinant 3 (CD3).BACKGROUND

[0004] Multiple myeloma (MM) is a malignant plasma cell disorder that accounts for approximately 10% of all hematologic cancers, making it the second most common hematological malignancy and constitutes 2% of all cancer deaths. MM is usually preceded by an asymptomatic precursor state, either monoclonal gammopathy of undetermined significance or smoldering MM present in about 3% of adults over 50 (Kyle 2002, Kyle 2008, Landgren 2009, Weiss 2009). MM is a heterogenous disease and caused mostly by chromosome translocations inter alia t(l 1; 14),t(4; 14),t(8; 14),del(l 3),del(l 7) (Drach et al., (1998) Blood 92(3):802-809; Gertz et al., (2005) Blood 106(8):2837-2840; Facon et al., (2001) Blood 97(6): 1566-1571). MM is more common in men than in women and twice as common in those of African descent compared to those of European descent (Landgren2009). The clinical manifestations of MM are due to the clonal expansion of bone marrow plasma cells, interactions of those cells with the bone marrow microenvironment, and consequences of the monoclonal paraproteins. MM-affected patients may experience a variety of disease-related symptoms due to, bone marrow infiltration, bone destruction, renal failure, immunodeficiency, and the psychosocial burden of a cancer diagnosis. As of 2006, the 5-year relative survival rate for MM was approximately 34% highlighting that MM is a difficult-to-treat disease where there are currently no curative options. The diagnosis of MM is based on the presence of clonal plasma cells and evidence of end-organ damage (“CRAB” features: hypercalcemia, renal failure, anemia, and bone lesions) or biomarkers of malignancy all defined by the International Myeloma Working Group (Rajkumar 2014).

[0005] B-cell maturation antigen, also known as BCMA, CD269, TNFRSF17 (UniProt Q02223), is a member of the tumor necrosis receptor superfamily that is exclusively expressed on B-cell lineage cells, and is selectively induced during plasma cell differentiation (Darce 2007, Tai 2015). BCMA is a non-glycosylated type I transmembrane protein, which is involved in B cell maturation, growth and survival. BCMA is a receptor for two ligands of the TNF superfamily: APRIL (a proliferation-inducing ligand, CD256, TNFSF13), the high- affinity ligand to BCMA, and the B cell activation factor BAFF (THANK, BlyS, B lymphocyte stimulator, TALL-1 and zTNF4), the low-affinity ligand to BCMA. APRIL and BAFF show structural similarity and overlapping yet distinct receptor binding specificity. The negative regulator TACI also binds to both BAFF and APRIL. The coordinate binding of APRIL and BAFF to BCMA and / or TACI activates transcription factor NF-KB and increases the expression of pro-survival Bcl-2 family members (e.g. Bcl-2, Bcl-xL, Bcl-w, Mcl-1, Al) and down regulates expression of pro-apoptotic factors (e.g. Bid, Bad, Bik, Bim, etc.), thus inhibiting apoptosis and promoting survival. This combined action promotes B cell differentiation, proliferation, survival and antibody production (as reviewed in Rickert RC et al., Immunol Rev (2011) 244 (1): 115-133). In line with this finding, BCMA also supports growth and survival of malignant human B cells, including multiple myeloma (MM) cells. Novak et al. found that MM cell lines and freshly isolated MM cells express BCMA and TACI protein on their cell surfaces and have variable expression of BAFF-R protein on their cell surface (Novak et al., (2004) Blood 103(2):689-694).

[0006] The BCMA receptor is a 184 amino acid protein with a 54 amino acid extracellular domain. In addition to expression on the cell surface, BCMA is cleaved by gamma secretaseactivity at the transmembrane domain, generating a ~6 kDa soluble BCMA protein fragment (Laurent 2015). High levels of soluble BCMA were measured in MM patient serum samples (Pillarisetti 2020) and correlated with plasma cell counts (Sanchez 2012). Inhibition of gamma secretase results in significant increase of BCMA surface protein expression in human primary B cells (Laurent 2015) and MM cell lines and bone marrow mononuclear cells (Pillarisetti 2020). BCMA has been established as a validated target in MM with several approved therapeutics (Lonial 2020; Berdeja 2021; Munshi 2021). The selective expression of BCMA on Bcell lineage, specifically mature B cells and plasma cells makes it an ideal target for T-cell therapeutics that have been validated in clinical studies and resulted in several anti-BCMA therapeutic approvals (idecabtagene vicleucel, ciltacabtagene autoleucel, and belantamab mafodotin-blmf).

[0007] The use of anti-BCMA antibodies for the treatment of lymphomas and multiple myeloma are mentioned in W02002066516 and W02010104949. Antibodies against BCMA are described e.g. in Gras M-P. et al. Int Immunol. 7 (1995) 1093- 1106, W0200124811, and W0200124812. Nevertheless, despite the fact that BCMA, BAFF-R and TACI, i.e., B cell receptors belonging to the TNF receptor superfamily, and their ligands BAFF and APRIL are subject to therapies in fighting against cancer, further options for the treatment of such medical conditions are needed.

[0008] G-protein coupled receptor, class C, group 5, member D (GPRC5D) is an orphan, atypical, class C GPCR first identified in 2001 (Brauner-Osborne et al. Biochim Biophys Acta. 1518(3):237-248, 2001). GPRC5D is a 7-transmembrane receptor protein that is classified as a type C G protein-coupled receptor based on the sequence homology score. GPRC5D and other group 5 GPCRs have unusually short amino-terminal domains for class C receptors, and are therefore, predicted to be conformationally similar to class A receptors. In this regard they are unique, with sequence homology to class C GPCRs and predicted structural topology comparable to class A receptors. Functional consequence of GPRC5D activation has not been described and the ligand remains unknown. The gene has three exons and is located on chromosome 12pl3.3 in humans.

[0009] GPRC5D receptor is highly conserved among various species and shares 92% identity with cynomolgus monkey GPRC5D. GPRC5D is predominantly expressed in cells with a plasma cell phenotype and in hard keratinized tissues such as hair follicles (Inoue 2004; Smith 2019; Goldsmith 2021) and is also expressed in malignant plasma cells in patients withmultiple myeloma (Atamaniuk 2012; Frigyesi 2014; Kodama 2019; Pillarisetti 2020). Levels of GPRC5D expression in patients with multiple myeloma correlated well with plasma cell burden and genetic aberrations such as retinoblastoma 1 deletion (Atamaniuk 2012). The limited normal expression of GPRC5D, restricted to the plasma cell lineage and hard keratinized tissues, makes it an ideal target to treat plasma cell disorders.

[0010] The use of anti-GPRC5D antibodies for the treatment of multiple myeloma are mentioned in W02016090329, WO2018017786, WO2018147245, and WO2019154890. Nevertheless, despite the fact that GPRC5D is subject to therapies in fighting against cancer, further options for the treatment of such medical conditions are needed.

[0011] Treatment options for multiple myeloma have improved over time and vary depending on the aggressiveness of the disease, underlying prognostic factors, physical condition of the patient, and existing comorbidities. Therapeutic options include agents such as proteasome inhibitors (Pls) e.g. bortezomib, carfilzomib, ixazomib; immunomodulatory drugs (IMiDs) e.g. lenalidomide, thalidomide, pomalidomide; alkylating agents; monoclonal antibodies (mAbs) e.g. daratumumab, elotuzumab; high-dose chemotherapy e.g. cyclophosphamide, melphalan; anthracy clines eg., doxorubicin; a selective inhibitor of nuclear export e.g. selinexor; an antibody drug conjugate e.g. belantamab mafodotin; histone deacetylase inhibitor; chimeric antigen receptor (CAR) T cell therapy; or a combination of such drugs and consideration of stem cell transplantation. However, despite these improvements, the disease recurs and is associated with additional risk factors (e.g., comorbidities or increasing age), and MM remains incurable.

[0012] Clonal resistance is a common mechanism in relapse refractory myeloma. The mechanism of resistance is poorly understood and hypotheses suggest several possibilities such as antigen escape due to loss or downregulation of tumor surface antigens, evolution of clonal population, chromosomal deletions, anti-apoptotic gene regulation, or T-cell exhaustion. Targeting more than one myeloma tumor antigen and engaging T-cells could lead to efficient killing of malignant plasma cells and minimal residual disease (MRD) negativity. Dual BCMA and GPRC5D targeting enhances antibody avidity and potency, maximizes tumor eradication in presence of a heterogenous cell population, prevents tumor antigen escape (e.g., captures MM cells that do not express enough BCMA or GPRC5D alone), improves tumor efficacy and may mitigate potential for cytokine release syndrome (CRS).Trispecific antibodies that target BCMA, GPRC5D and CD3 are mentioned in WO2022 / 175255.

[0013] There is an unmet need for novel therapeutic options, such as new dosage and treatment regimens, that can potentially address resistance to current therapies and have an optimal benefit-risk profile. In particular in the elderly population, for which stem cell transplantation is often not a viable option, and in patients with refractory disease who exhausted all available therapies, multiple myeloma remains an incurable malignancy and an unmet medical need with significant morbidity and mortality.SUMMARY

[0014] Provided herein is a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of at least about 0.4 mg.

[0015] In one aspect, the disclosure provides a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of at least about 0.4 mg.

[0016] In another aspect, the disclosure provides a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 50 mg and wherein the treatment dose is administered once every four weeks.

[0017] In another aspect, the disclosure provides a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecificantibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 100 mg and wherein the treatment dose is administered once every four weeks.

[0018] In another aspect, the disclosure provides a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 300 mg and wherein the treatment dose is administered once every four weeks.

[0019] In some embodiments, the multiple myeloma is smoldering multiple myeloma (SMM). In some embodiments, the multiple myeloma is extramedullary disease (EMD). In some embodiments, the multiple myeloma is a relapsed or refractory form of multiple myeloma. In some embodiments, the multiple myeloma is a relapsed form of multiple myeloma. In some embodiments, the multiple myeloma is a refractory form of multiple myeloma.

[0020] In an exemplary embodiment of any of the methods disclosed herein, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is the trispecific antibody formed from the amino acid chains having the sequences of SEQ ID Nos: 29, 30 and 31 (this molecule is also herein termed BGCB491; see also the structure in FIG. 1).

[0021] The disclosure provides a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of aBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 50 mg, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is BGCB491 and wherein the subject is a human subject.

[0022] The disclosure provides a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of aBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific bindingfragment thereof once every four weeks at a treatment dose of about 100 mg, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is BGCB491 and wherein the subject is a human subject.

[0023] The disclosure provides a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of aBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 300 mg, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is BGCB491 and wherein the subject is a human subject.

[0024] The skilled person will understand that the described methods may be specified in medical use format, for example in the form of BCMA x GPRC5D x CD3-trispecific antibodies and trispecific antigen-binding fragments for use in the treatment of multiple myeloma. This skilled person will also understand that the methods may be specified in so- called Swiss form, for example in the form of the use of BCMA x GPRC5D x CD3- trispecific antibodies and trispecific antigen-binding fragments for the manufacture of a medicament for the treatment of multiple myeloma. This applies throughout the disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

[0025] FIG. 1. Depiction of BGCB491 trispecific antibody.

[0026] FIG. 2. Mean (SD) Serum Concentration-Time Profile ofBGCB491 After Subcutaneous Administration of Multiple Target Doses in Cohorts 1-8.DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0027] The disclosed methods can be understood more readily by reference to the following detailed description. It is to be understood that the disclosed methods are not limited to the specific methods described and / or shown herein, and that the terminology used herein is for the purpose of describing particular embodiments by way of example only and is not intended to be limiting of the claimed methods. All patents, published patent applications and publications cited herein are incorporated by reference as if set fourth fully herein.

[0028] Unless otherwise defined herein, technical and scientific terms used in the present description have the meanings that are commonly understood by those of ordinary skill in the art. For purposes of interpreting this specification, the following description of terms will apply and whenever appropriate, terms used in the singular will also include the plural and vice versa. In the event that any description of a term set forth conflicts with any document incorporated herein by reference, the description of the term set forth below shall control.

[0029] In an attempt to help the reader of the present application, the description has been separated in various paragraphs or sections. These separations are not considered as disconnecting the substance of a paragraph or section from the substance of another paragraph or section. To the contrary, the present description encompasses all the combinations of the various sections, paragraphs and sentences that can be contemplated.Definitions

[0030] Various terms relating to aspects of the description are used throughout the specification and claims. Such terms are to be given their ordinary meaning in the art unless otherwise indicated. Other specifically defined terms are to be construed in a manner consistent with the definitions provided herein.

[0031] As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to “a cell” includes a combination of two or more cells, and the like.

[0032] The term “about” as used herein when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of up to ±10% from the specified value, as such variations are appropriate to perform the disclosed methods. Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0033] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the disclosure are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

[0034] The term “comprising” is intended to include examples encompassed by the terms “consisting essentially of’ and “consisting of’; similarly, the term “consisting essentially of’ is intended to include examples encompassed by the term “consisting of.” Unless the context clearly requires otherwise, throughout the description and the claims, the words “comprise”, “comprising”, and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense; that is to say, in the sense of “including, but not limited to”.

[0035] “Isolated” means a biological component (such as a nucleic acid, peptide or protein) has been substantially separated, produced apart from, or purified away from other biological components of the organism in which the component naturally occurs, i.e., other chromosomal and extrachromosomal DNA and RNA, and proteins. Nucleic acids, peptides and proteins that have been “isolated” thus include nucleic acids and proteins purified by standard purification methods. “Isolated” nucleic acids, peptides and proteins can be part of a composition and still be isolated if such composition is not part of the native environment of the nucleic acid, peptide, or protein. The term also embraces nucleic acids, peptides and proteins prepared by recombinant expression in a host cell as well as chemically synthesized nucleic acids. An "isolated” antibody or antigen-binding fragment, as used herein, is intended to refer to an antibody or antigen-binding fragment which is substantially free of other antibodies or antigen-binding fragments having different antigenic specificities (for instance, an isolated antibody that specifically binds to BCMA is substantially free of antibodies that specifically bind antigens other than BCMA). An isolated antibody that specifically binds to an epitope, isoform or variant of BCMA or GPRC5D may, however, have cross-reactivity to other related antigens, for instance from other species (such as BCMA or GPRC5D species homologs).

[0036] “Polynucleotide,” synonymously referred to as “nucleic acid molecule,” “nucleotides” or “nucleic acids,” refers to any polyribonucleotide or polydeoxyribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. “Polynucleotides” include, without limitation single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that may be singlestranded or, more typically, double-stranded or a mixture of single- and double-stranded regions. In addition, “polynucleotide” refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The term polynucleotide also includes DNAs or RNAs containing one or more modified bases and DNAs or RNAs with backbones modified for stability or for other reasons. “Modified” bases include, for example, tritylated bases and unusual bases such as inosine. A variety of modifications may be made to DNA and RNA; thus, “polynucleotide” embraces chemically, enzymatically or metabolically modified forms of polynucleotides as typically found in nature, as well as the chemical forms of DNA and RNA characteristic of viruses and cells. “Polynucleotide” also embraces relatively short nucleic acid chains, often referred to as oligonucleotides.

[0037] The meaning of “substantially the same” can differ depending on the context in which the term is used. Because of the natural sequence variation likely to exist among heavy and light chains and the genes encoding them, one would expect to find some level of variation within the amino acid sequences or the genes encoding the antibodies or antigen-binding fragments described herein, with little or no impact on their unique binding properties (e.g., specificity and affinity). Such an expectation is due in part to the degeneracy of the genetic code, as well as to the evolutionary success of conservative amino acid sequence variations, which do not appreciably alter the nature of the encoded protein. Accordingly, in the context of nucleic acid sequences, “substantially the same” means at least 65% identity between two or more sequences. Preferably, the term refers to at least 70% identity between two or more sequences, more preferably at least 75% identity, more preferably at least 80% identity, more preferably at least 85% identity, more preferably at least 90% identity, more preferably at least 91% identity, more preferably at least 92% identity, more preferably at least 93% identity, more preferably at least 94% identity, more preferably at least 95% identity, more preferably at least 96% identity, more preferably at least 97% identity, more preferably at least 98% identity, and more preferably at least 99% or greater identity. The percent identity between two sequences is a function of the number of identical positions shared by the sequences (i.e., % homology = # of identical positions / total # of positions x 100), taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences. The percent identity between two nucleotide oramino acid sequences may e.g. be determined using the algorithm of E. Meyers and W. Miller, Comput. Appl. Biosci 4, 11-17 (1988) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent identity between two amino acid sequences may be determined using the Needleman and Wunsch, J. Mol. Biol. 48, 444-453 (1970) algorithm.

[0038] The degree of variation that may occur within the amino acid sequence of a protein without having a substantial effect on protein function is much lower than that of a nucleic acid sequence, since the same degeneracy principles do not apply to amino acid sequences. Accordingly, in the context of an antibody or antigen-binding fragment, “substantially the same” means antibodies or antigen-binding fragments having 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to the antibodies or antigen-binding fragments described. Other embodiments include antibodies, or antigen-binding fragments, that have framework, scaffold, or other non-binding regions that do not share significant identity with the antibodies and antigen-binding fragments described herein, but do incorporate one or more CDRs or other sequences needed to confer binding that are 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identical to such sequences described herein.

[0039] A “clone” is a population of cells derived from a single cell or common ancestor by mitosis. A “cell line” is a clone of a primary cell that is capable of stable growth in vitro for many generations. In some examples provided herein, cells are transformed by transfecting the cells with DNA.

[0040] The terms “express” and “produce” are used synonymously herein, and refer to the biosynthesis of a gene product. These terms encompass the transcription of a gene into RNA. These terms also encompass translation of RNA into one or more polypeptides, and further encompass all naturally occurring post-transcriptional and post-translational modifications. The expression or production of an antibody or antigen-binding fragment thereof may be within the cytoplasm of the cell, or into the extracellular milieu such as the growth medium of a cell culture.

[0041] The terms “treating” or “treatment” refer to any success or indicia of success in the attenuation or amelioration of an injury, pathology or condition, including any objective or subjective parameter such as abatement, remission, diminishing of symptoms or making the condition more tolerable to the patient, slowing in the rate of degeneration or decline, making the final point of degeneration less debilitating, improving a subject’s physical or mentalwell-being, or prolonging the length of survival. The treatment may be assessed by objective or subjective parameters; including the results of a physical examination, neurological examination, or psychiatric evaluations.

[0042] An "effective amount" or "therapeutically effective amount" refers to an amount effective, at dosages and for periods of time necessary, to achieve a desired therapeutic result. A therapeutically effective amount of a BCMA x GPRC5D x CD3 antibody may vary according to factors such as the disease state, age, sex, and weight of the individual, and the ability of the antibody to elicit a desired response in the individual. A therapeutically effective amount is also one in which any toxic or detrimental effects of the antibody or antibody portion are outweighed by the therapeutically beneficial effects.

[0043] “Antibody” refers to all isotypes of immunoglobulins (IgG, IgA, IgE, IgM, IgD, and IgY) including various monomeric, polymeric and chimeric forms, unless otherwise specified. Specifically encompassed by the term “antibody” are polyclonal antibodies, monoclonal antibodies (mAbs), and antibody-like polypeptides, such as chimeric antibodies and humanized antibodies.

[0044] The term “antigen-binding arm” refers to a portion of an antibody that includes an antigen-binding domain that binds to an antigen (e.g., BCMA, GPRC5D, or CD3), and optionally includes one or more other antibody regions (e.g., Fc domain).

[0045] The term “antigen-binding fragment” refers to a fragment of the antigen-binding arm containing an antigen-binding domain. Antigen-binding fragments include those provided by any known technique, such as enzymatic cleavage, peptide synthesis, and recombinant techniques. Some antigen-binding fragments are composed of portions of intact antibodies that retain antigen-binding specificity of the parent antibody molecule. For example, antigenbinding fragments may comprise at least one variable region (either a heavy chain or light chain variable region) or one or more CDRs of an antibody known to bind a particular antigen. Examples of suitable antigen-binding fragments include, without limitation diabodies and single-chain molecules as well as Fab, F(ab’)2, Fc, Fabc, and Fv molecules, single chain (Sc) antibodies, individual antibody light chains, individual antibody heavy chains, chimeric fusions between antibody chains or CDRs and other proteins, protein scaffolds, heavy chain monomers or dimers, light chain monomers or dimers, dimers consisting of one heavy and one light chain, a monovalent fragment consisting of the VL, VH, CL and CHI domains, or a monovalent antibody as described in W02007059782,bivalent fragments comprising two Fab fragments linked by a disulfide bridge at the hinge region, a Fd fragment consisting essentially of the VH and CHI domains; a Fv fragment consisting essentially of the VL and VH domains of a single arm of an antibody, a dAb fragment (Ward et al., Nature 341, 544-546 (1989)), which consists essentially of a VH domain and also called domain antibodies (Holt et al; Trends Biotechnol. 2003 Nov.;21(11):484-90); camelid or nanobodies (Revets et al; Expert Opin Biol Ther. 2005 Jan.; 5(1): 111-24); an isolated complementarity determining region (CDR), and the like; and trispecific antibodies formed from antibody fragments. All antibody isotypes may be used to produce antigen-binding fragments. Additionally, antigen-binding fragments may include non-antibody proteinaceous frameworks that may successfully incorporate polypeptide segments in an orientation that confers affinity for a given antigen of interest, such as protein scaffolds. Antigen-binding fragments may be recombinantly produced or produced by enzymatic or chemical cleavage of intact antibodies. The phrase “an antibody or antigenbinding fragment thereof’ may be used to denote that a given antigen-binding fragment incorporates one or more amino acid segments of the antibody referred to in the phrase.

[0046] The term “antigen-binding domain” refers to the proteinaceous structure of an antigen-binding arm that exhibits binding affinity for a particular antigen. This proteinaceous structure is mediated by the complementarity determining regions (CDRs) of the antigenbinding domain.

[0047] The terms “CDR”, and its plural “CDRs”, refer to a complementarity determining region (CDR) of which three make up the binding character of a light chain variable region (CDRL1, CDRL2 and CDRL3) and three make up the binding character of a heavy chain variable region (CDRH1, CDRH2 and CDRH3). CDRs contribute to the functional activity of an antibody molecule and are separated by amino acid sequences that comprise scaffolding or framework regions. The exact definitional CDR boundaries and lengths are subject to different classification and numbering systems. CDRs may therefore be referred to herein by Kabat, Chothia, AbM, contact or any other boundary definitions. Despite differing boundaries, each of these systems has some degree of overlap in what constitutes the so called “hypervariable regions” within the variable sequences. CDR definitions according to these systems may therefore differ in length and boundary areas with respect to the adjacent framework region. See for example Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed. NIH Publication No. 91-3242 (1991); Chothia et al., “Canonical StructuresFor the Hypervariable Regions of Immunoglobulins,” J. Mol. Biol. 196:901 (1987); and MacCallum et al., “Antibody -Antigen Interactions: Contact Analysis and Binding Site Topography,” J. Mol. Biol. 262:732 (1996)), each of which is hereby incorporated by reference in its entirety.

[0048] Typically, CDRs form a loop structure that can be classified as a canonical structure. The term “canonical structure” refers to the main chain conformation that is adopted by the antigen binding (CDR) loops. From comparative structural studies, it has been found that five of the six antigen binding loops have only a limited repertoire of available conformations. Each canonical structure can be characterized by the torsion angles of the polypeptide backbone. Correspondent loops between antibodies may, therefore, have very similar three dimensional structures, despite high amino acid sequence variability in most parts of the loops (Chothia et al., “Canonical Structures For the Hypervariable Regions of Immunoglobulins,” J. Mol. Biol. 196:901 (1987); Chothia et al., “Conformations of Immunoglobulin Hypervariable Regions,” I 342:877 (1989); Martin and Thornton, “Structural Families in Loops of Homologous Proteins: Automatic Classification, Modelling and Application to Antibodies,” J. Mol. Biol. 263:800 (1996), each of which is incorporated by reference in its entirety). Furthermore, there is a relationship between the adopted loop structure and the amino acid sequences surrounding it. The conformation of a particular canonical class is determined by the length of the loop and the amino acid residues residing at key positions within the loop, as well as within the conserved framework (i.e., outside of the loop). Assignment to a particular canonical class can therefore be made based on the presence of these key amino acid residues.

[0049] The term "polypeptide" is used interchangeably with the term "protein" and in its broadest sense refers to a compound of two or more subunit amino acids, amino acid analogs or peptidomimetics. The subunits may be linked by peptide bonds. In another embodiment, the subunit may be linked by other bonds, e.g., ester, ether, etc. As used herein the term "amino acid" refers to either natural and / or unnatural or synthetic amino acids, including glycine and both the D and L optical isomers, amino acid analogs and peptidomimetics. A peptide of three or more amino acids is commonly called an oligopeptide if the peptide chain is short. If the peptide chain is long, the peptide is commonly called a polypeptide or a protein. As used herein the term “Fc” refers to the fragment crystallizable domain of an antibody, which comprises two constant heavy chain (CH) regions, CH2 and CH3.Herein, the amino acid residues of the Fc region are typically numbered according to the EU numbering scheme (Edelman, G.M. et al., Proc. Natl. Acad. USA, 63, 78-85 (1969). PMID: 5257969). These residues can be readily assigned according to alternative numbering schemes such as IMGT and Kabat (Kabat, E.A. et al., Sequences of proteins of immunological interest. 5th Edition - US Department of Health and Human Services, NIH publication n° 91-3242, pp 662,680,689 (1991)) numbering as would be readily appreciated by one skilled in the art. For example, L234 according to EU numbering may also be represented as L247 according to Kabat.

[0050] “Specifically binds” or “binds specifically” or derivatives thereof when used in the context of antibodies, or antibody fragments, represents binding via domains encoded by immunoglobulin genes or fragments of immunoglobulin genes to one or more epitopes of a protein of interest, without preferentially binding other molecules in a sample containing a mixed population of molecules. Typically, an antibody binds to a cognate antigen with a Ka of less than about 1x1 O'8M, as measured by a surface plasmon resonance assay or a cellbinding assay. Phrases such as “[antigen]-specific” antibody (e.g., BCMA-specific antibody) are meant to convey that the recited antibody specifically binds the recited antigen.Wherever the term “binds” is used herein it is intended that this encompasses “specifically binds” and the terms may be interchanged as desired.

[0051] As used herein, the term “chimeric” refers to an antibody, or antigen-binding fragment thereof, having at least some portion of at least one variable domain derived from the antibody amino acid sequence of a non-human mammal, a rodent, or a reptile, while the remaining portions of the antibody, or antigen-binding fragment thereof, are derived from a human.

[0052] A “vector” is a replicon, such as plasmid, phage, cosmid, or virus in which another nucleic acid segment may be operably inserted so as to bring about the replication or expression of the segment.

[0053] As used herein, the term "host cell" can be any type of cell, e.g., a primary cell, a cell in culture, or a cell from a cell line. In specific embodiments, the term "host cell" refers to a cell transfected with a nucleic acid molecule and the progeny or potential progeny of such a cell. Progeny of such a cell may not be identical to the parent cell transfected with the nucleic acid molecule, e.g., due to mutations or environmental influences that may occur in succeeding generations or integration of the nucleic acid molecule into the host cell genome.The terms “expression” and “production” are used synonymously herein, and refer to the biosynthesis of a gene product. These terms encompass the transcription of a gene into RNA. These terms also encompass translation of RNA into one or more polypeptides, and further encompass all naturally occurring post-transcriptional and post-translational modifications.

[0054] The term “subject” refers to human and non-human animals, including all vertebrates, e.g., mammals and non-mammals, such as non-human primates, mice, rabbits, sheep, dogs, cats, horses, cows, chickens, amphibians, and reptiles. In an exemplary embodiment of the described methods, the subject is a human.

[0055] The term “redirect” or “redirecting” as used herein refers to the ability of the BCMA x GPRC5D x CD3 antibody to traffic the activity of T cells effectively, from its inherent cognate specificity toward reactivity against GPRC5D and / or BCMA-expressing cells.

[0056] The term “sample” as used herein refers to a collection of similar fluids, cells, or tissues (e.g., surgically resected tumor tissue, biopsies, including fine needle aspiration), isolated from a subject, as well as fluids, cells, or tissues present within a subject. In some embodiments the sample is a biological fluid. Biological fluids are typically liquids at physiological temperatures and may include naturally occurring fluids present in, withdrawn from, expressed or otherwise extracted from a subject or biological source. Certain biological fluids derive from particular tissues, organs or localized regions and certain other biological fluids may be more globally or systemically situated in a subject or biological source. Examples of biological fluids include blood, serum and serosal fluids, plasma, lymph, urine, saliva, cystic fluid, tear drops, feces, sputum, mucosal secretions of the secretory tissues and organs, vaginal secretions, ascites fluids such as those associated with non-solid tumors, fluids of the pleural, pericardial, peritoneal, abdominal and other body cavities, fluids collected by bronchial lavage and the like. Biological fluids may also include liquid solutions contacted with a subject or biological source, for example, cell and organ culture medium including cell or organ conditioned medium, lavage fluids and the like. The term “sample,” as used herein, encompasses materials removed from a subject or materials present in a subject. The relevant aspects of the disclosure may be performed in vitro based on isolated samples as required.

[0057] A “known standard” may be a solution having a known amount or concentration of GPRC5D and / or BCMA, where the solution may be a naturally occurring solution, such as a sample from a patient known to have early, moderate, late, progressive, or static cancer, orthe solution may be a synthetic solution such as buffered water having a known amount of GPRC5D and / or BCMA diluted therein. The known standards, described herein may include GPRC5D and / or BCMA isolated from a subject, recombinant or purified GPRC5D and / or BCMA protein, or a value of GPRC5D and / or BCMA concentration associated with a disease condition.

[0058] The terms “B-cell maturation antigen” and "BCMA" as used herein include human B cell maturation antigen, also known as BCMA, CD269, and TNFRSF17 (UniProt Q02223), which is a member of the tumor necrosis receptor superfamily that is preferentially expressed in differentiated plasma cells. The extracellular domain of human BCMA consists, according to UniProt of amino acids 1 - 54 (or 5-51). The term "antibody against BCMA, anti-BCMA antibody" as used herein relates to an antibody specifically binding to BCMA.

[0059] The terms "G-protein coupled receptor family C group 5 member D" and "GPRC5D" specifically include the human GPRC5D protein, for example as described in GenBank Accession No. BC069341, NCBI Reference Sequence: NP_061124.1 and UniProtKB / Swiss- Prot Accession No. Q9NZD1 (see also Brauner-Osbome, H. et al. 2001, Biochim. Biophys. Acta 1518, 237-248).

[0060] The terms “cluster determinant 3” and “CD3” include the human CD3 protein multisubunit complex. The CD3 protein multi-subunit complex is composed to 6 distinctive polypeptide chains. These include a CD3y chain (SwissProt P09693), a CD36 chain (SwissProt P04234), two CD3s chains (SwissProt P07766), and one CD3 C, chain homodimer (SwissProt 20963), and which is associated with the T cell receptor a and P chain. The term “CD3” includes any CD3 variant, isoform and species homolog which is naturally expressed by cells (including T cells) or can be expressed on cells transfected with genes or cDNA encoding those polypeptides, unless noted.

[0061] A “BCMA x GPRC5D x CD3 antibody” is a trispecific antibody, which comprises three different antigen-binding arms, one of which binds to the antigen BCMA, one of which binds to the antigen GPRC5D, and one of which binds to CD3. The term "multispecific antibody" is used herein in the broadest sense and specifically covers an antibody that has polyepitopic specificity. Multispecific antibodies include, but are not limited to, an antibody comprising a heavy chain variable domain (VH) and a light chain variable domain (VL), where the VHVL unit has polyepitopic specificity, antibodies having two or more VL and VH domains where each VHVL unit binds to a different epitope, antibodies having two or moresingle variable domains with each single variable domain binding to a different epitope, full length antibodies, and antibodies comprising one or more antibody fragments as well as antibodies comprising antibody fragments that have been linked covalently or non- covalently.

[0062] A multispecific antibody can be a bispecific antibody, a trispecific antibody, diabody, or similar molecule (see for instance PNAS USA 90(14), 6444-8 (1993) for a description of diabodies). The bispecific antibodies, trispecific antibodies, diabodies, and the like, provided herein may bind any suitable target in addition to a portion of BCMA or GPRC5D. The term "bispecific antibody" is to be understood as an antibody having two different antigen-binding arms defined by different antibody sequences. The term “trispecific antibody” is to be understood as an antibody having three different antigen-binding arms defined by different antibody sequences. This can be understood as different target binding but includes as well binding to different epitopes in one target.

[0063] The term “humanized antibody” refers to an antibody in which at least one CDR is derived from non-human species and at least one framework is derived from human immunoglobulin sequences. Humanized antibody can include substitutions in the frameworks so that the frameworks can not be exact copies of expressed human immunoglobulin or human immunoglobulin germline gene sequences.

[0064] A “reference sample” is a sample that may be compared against another sample, such as a test sample, to allow for characterization of the compared sample. The reference sample will have some characterized property that serves as the basis for comparison with the test sample. For instance, a reference sample may be used as a benchmark for GPRC5D or BCMA levels that are indicative of a subject having cancer. The reference sample does not necessarily have to be analyzed in parallel with the test sample, thus in some instances the reference sample may be a numerical value or range previously determined to characterize a given condition, such as GPRC5D or BCMA levels that are indicative of cancer in a subject. The term also includes samples used for comparative purposes that are known to be associated with a physiologic state or disease condition, such as GPRC5D- or BCMA- expressing cancer, but that have an unknown amount of GPRC5D or BCMA.

[0065] “Cancer” refers to a broad group of various diseases characterized by the uncontrolled growth of abnormal cells in the body. Unregulated cell division and growth results in the formation of malignant tumors that invade neighboring tissues and can also metastasize todistant parts of the body through the lymphatic system or bloodstream. A “cancer” or “cancer tissue” can include a tumor.

[0066] “Combination” means that two or more therapeutics are administered to a subject together in a mixture, concurrently as single agents or sequentially as single agents in any order.

[0067] “Flat dose” refers to a dose that is administered to a subject without correction for the subject’s specific body weight or body surface area. A flat dose, sometimes referred to as a fixed dose, is therefore provided as an absolute amount of the agent (e.g., mg drug), and not as a weight-based amount that accounts for the subject’s specific weight (e.g. pg / kg or pg drug per kg body weight). For example, a subject weighing 65kg may be administered the same flat dose in milligrams as a subject weighing 85kg. A flat dose may be administered according to a pre-defined class or category of body weight, but is not modified according to the subject’s specific weight. For example, a “Flat Dose A” may be administered if a patient is greater than a pre-defined threshold weight, whereas a different “Flat Dose B” may be administered if the patent is less than the pre-defined threshold weight.

[0068] “Pharmaceutical composition” refers to composition that comprises an active ingredient and a pharmaceutically acceptable carrier.

[0069] “Pharmaceutically acceptable carrier” or “excipient” refers to an ingredient in a pharmaceutical composition, other than the active ingredient, which is nontoxic to a subject.

[0070] “Relapsed” refers to the return of a disease or the signs and symptoms of a disease after a period of improvement after prior treatment with a therapeutic.

[0071] “Refractory” refers to a disease that does not respond to a treatment. A refractory disease can be resistant to a treatment before or at the beginning of the treatment, or a refractory disease can become resistant during a treatment.

[0072] The term “progression,” as used in the context of progression of GPRC5D and / or BCMA -expressing cancer, includes the change of a cancer from a less severe to a more severe state. This may include an increase in the number or severity of tumors, the degree of metastasis, the speed with which the cancer is growing or spreading, and the like. For example, “the progression of colon cancer” includes the progression of such a cancer from a less severe to a more severe state, such as the progression from stage I to stage II, from stage II to stage III, etc.

[0073] The term “regression,” as used in the context of regression of GPRC5D and / or BCMA -expressing cancer, includes the change of a cancer from a more severe to a less severe state. This could include a decrease in the number or severity of tumors, the degree of metastasis, the speed with which the cancer is growing or spreading, and the like. For example, “the regression of colon cancer” includes the regression of such a cancer from a more severe to a less severe state, such as the progression from stage III to stage II, from stage II to stage I, etc.

[0074] The term “stable” as used in the context of stable GPRC5D and / or BCMA-expressing cancer, is intended to describe a disease condition that is not, or has not, changed significantly enough over a clinically relevant period of time to be considered a progressing cancer or a regressing cancer.

[0075] The term “step-up dose” refers to a dose of an active agent that is administered to a subject prior to a treatment dose. A step-up dose is lower than the treatment dose. To prevent or lessen certain toxicities, such as cytokine release syndrome (CRS), a “priming” dose strategy may include one or more lower step-up dose(s) followed by higher treatment doses.

[0076] The term “treatment dose” refers to a dose of the active agent that is administered to a subject to treat a disease. A treatment dose may be administered at a regular dosing interval on a repetitive basis (e.g. weekly, biweekly, monthly). A treatment dose may be preceded by one or more step-up doses.

[0077] As used herein, the term “outpatient” is a patient who attends a hospital or clinic for treatment without staying at the hospital or clinic overnight, and the patient is administered the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof described herein by a health care professional.

[0078] The embodiments described herein are not limited to particular methods, reagents, compounds, compositions or biological systems, which can, of course, vary.BCMA x GPRC5D x CD3 trispecific antibodies

[0079] Any suitable BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof known to those skilled in the art in view of the present disclosure can be used in the disclosure.

[0080] The methods provided herein comprise administering trispecific antibodies that bind to BCMA, GPRC5D, and CD3 (“BCMA x GPRC5D x CD3 trispecific antibodies”), or trispecific binding fragments thereof. Such antibodies or antibody fragments may allow for more specific targeting to particular subsets of cells as compared to antibodies targeting only one or two of these targets.

[0081] In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof comprises any one of the BCMA binding domains described in WO2022 / 175255, the entire content of which is incorporated herein by reference. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof comprises any one of the GPRC5D binding domains described in WO2022 / 175255. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof comprises any one of the CD3 binding domains described in WO2022 / 175255. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody comprises any one of the BCMA x GPRC5D x CD3 trispecific antibodies described in WO2022 / 175255.

[0082] The BCMA x GPRC5D x CD3 trispecific antibodies or binding fragments thereof can be provided by making a molecule which comprises a first antigen-binding arm binding to CD3, a second antigen-binding arm binding to GPRC5D and a third antigen-binding arm binding to the BCMA.

[0083] Accordingly, the methods comprise administering trispecific molecules comprising three different antigen-binding arms which bind BCMA, GPRC5D, and CD3, respectively.

[0084] In some embodiments, the BCMA x GPRC5D x CD3-trispecific antibody or trispecific binding fragment thereof comprises(a) a first antigen-binding arm comprising a first heavy chain variable domain (VH1) and a first light chain variable domain (VL1);(b) a second antigen-binding arm comprising a second heavy chain variable domain (VH2) and a second light chain variable domain (VL2); and(c) a third antigen-binding arm comprising a third heavy chain variable domain (VH3) and a third light chain variable domain (VIA), wherein the first antigen-binding arm binds to an epitope on CD3, the second antigen-binding arm binds to an epitope on GPRC5D, and the third antigen-binding arm binds to an epitope on BCMA.

[0085] In some embodiments, the first antigen-binding arm that binds CD3 comprises a HCDR 1, a HCDR2 and a HCDR3 of the VH1 of SEQ ID NO: 8. In some embodiments, the first antigen-binding arm that binds CD3 comprises a LCDR1, a LCDR2 and a LCDR3 of the VL1 of SEQ ID NO: 7. In some embodiments, the first antigen-binding arm that binds CD3 comprises a HCDR1 comprising the amino acid sequence of GDSVFNNNAAWS (SEQ ID NO: 4), a HCDR2 comprising the amino acid sequence of RTYYRSKWLYD (SEQ ID NO: 5), and a HCDR3 comprising the amino acid sequence of GYSSSFDY (SEQ ID NO: 6). In some embodiments, the first antigen-binding arm that binds CD3 comprises a LCDR1 comprising the amino acid sequence of TGTSSNIGTYKFVS (SEQ ID NO: 1), a LCDR2 comprising the amino acid sequence of EVSKRPS (SEQ ID NO: 2), and a LCDR3 comprising the amino acid sequence of VSYAGSGTLL (SEQ ID NO: 3). In some embodiments, the first antigen-binding arm that binds CD3 comprises the VH1 of SEQ ID NO: 8. In some embodiments, the first antigen-binding arm that binds CD3 comprises the VL1 of SEQ ID NO: 7.

[0086] In some embodiments, the second antigen-binding arm that binds GPRC5D comprises a HCDR1, a HCDR2 and a HCDR3 of the VH2 of SEQ ID NO: 16. In some embodiments, the second antigen-binding arm that binds GPRC5D comprises a LCDR1, a LCDR2 and a LCDR3 of the VL2 of SEQ ID NO: 15. In some embodiments, the second antigen-binding arm that binds GPRC5D comprises a HCDR1 comprising the amino acid sequence of GFSLTNIRMSVS (SEQ ID NO: 12), HCDR2 comprising the amino acid sequence of HIFSNDEKS (SEQ ID NO: 13), and a HCDR3 comprising the amino acid sequence of MRLPYGMDV (SEQ ID NO: 14). In some embodiments, the second antigenbinding arm that binds GPRC5D comprises a LCDR1 comprising the amino acid sequence of RSSQSLVHSDGNTYLS (SEQ ID NO: 9), a LCDR2 comprising the amino acid sequence of KISNRFF (SEQ ID NO: 10), and a LCDR3 comprising the amino acid sequence of MQATQFPHT (SEQ ID NO: 11). In some embodiments, the second antigen-binding arm that binds GPRC5D comprises the VH1 of SEQ ID NO: 16. In some embodiments, the second antigen-binding arm that binds GPRC5D comprises the VL1 of SEQ ID NO: 15.

[0087] In some embodiments, the third antigen-binding arm that binds BCMA comprises a HCDR1, a HCDR2 and a HCDR3 of the VH3 of SEQ ID NO: 24. In some embodiments, the third antigen-binding arm that binds BCMA comprises a LCDR1, a LCDR2 and a LCDR3 of the VL3 of SEQ ID NO: 23. In some embodiments, the third antigen-binding arm that bindsBCMA comprises a HCDR1 comprising the amino acid sequence of GFTFSSYAMS (SEQ ID NO: 20), a HCDR2 comprising the amino acid sequence of AISGSGGSTY (SEQ ID NO: 21), and a HCDR3 comprising the amino acid sequence of DEGYSSGHYYGMDV (SEQ ID NO: 22); and a LCDR1 comprising the amino acid sequence of RASQSISSSFLT (SEQ ID NO: 17). In some embodiments, the third antigen-binding arm that binds BCMA comprises a LCDR2 comprising the amino acid sequence of GASSRAT (SEQ ID NO: 18), and a LCDR3 comprising the amino acid sequence of QHYGSSPMYT (SEQ ID NO: 19). In some embodiments, the third antigen-binding arm that binds BCMA comprises the VH1 of SEQ ID NO: 24. In some embodiments, the third antigen-binding arm that binds BCMA comprises the VL1 of SEQ ID NO: 23.

[0088] In some embodiments, the VH1 and VL1 of the antigen-binding arm that binds to CD3 epitope are present in a diabody, a Fab, Fab’, a F(ab’)2, a Fv, a scFv, a Fd, a disulfide stabilized Fv fragment (dsFv), or a disulfide stabilized diabody (ds diabody).

[0089] In some embodiments, the VH2 and VL2 of the antigen-binding arm that binds to GPRC5D epitope are present in a diabody, a Fab, Fab’, a F(ab’)2, a Fv, a scFv, a Fd, a disulfide stabilized Fv fragment (dsFv), or a disulfide stabilized diabody (ds diabody).

[0090] In some embodiments, the VH3 and VL3 of the antigen-binding arm that binds to BCMA epitope are present in a diabody, a Fab, Fab’, a F(ab’)2, a Fv, a scFv, a Fd, a disulfide stabilized Fv fragment (dsFv), or a disulfide stabilized diabody (ds diabody).

[0091] In one embodiment, the CD3 -binding arm comprises an antigen-binding fragment (Fab), the BCMA-binding arm comprises a single-chain variable fragment (scFv), and the GPRC5D-binding arm comprises a single-chain variable fragment (scFv).

[0092] In some embodiments, the CD3 -binding arm of the trispecific antibody comprises the HC1 and the LC. The HC1 may comprise constant heavy chain regions (CHI, CH2, and CH3) and the VH1. The LC may comprise the VL1. The VH1 and VL1 combine to form the CD3 antigen binding domain.

[0093] In some embodiments, the BCMA-binding arm of the trispecific antibody comprises the HC2. The HC2 may comprise constant heavy chain regions (CH2 and CH3), and a singlechain variable fragment (scFv) attached at the N-terminus of the CH2 region, wherein the scFv comprises the BCMA antigen binding domain.

[0094] In some embodiments, the trispecific antibody further comprises GPRC5D antigenbinding arm attached to the C-terminus of the CH3 region of the CD3 -binding arm to form aCD3 / GPRC5D binding arm. In some embodiments, the BCMA antigen-binding arm comprises a second single-chain variable fragment (scFv). In some embodiments, the CD3 / GPRC5D arm may have the structure: Fab containing the CD3 binding domain, CH2 and CH3 regions, scFv containing the GPRC5D binding domain.

[0095] In some embodiments, the trispecific antibodies of the disclosure include antibodies having a full length antibody structure. "Full length antibody" as used herein refers to an antibody having two full length antibody heavy chains and two full length antibody light chains. A full length antibody heavy chain (HC) includes heavy chain variable and constant domains VH, CHI, CH2, and CH3. A full length antibody light chain (LC) includes light chain variable and constant domains VL and CL. The full length antibody may be lacking the C-terminal lysine (K) in either one or both heavy chains. The term "Fab-arm" or "half molecule" refers to one heavy chain-light chain pair that binds an antigen.BCMA-binding arm

[0096] The BCMA x GPRC5D x CD3 trispecific antibody described herein comprises an antigen-binding arm specific for BCMA. In some embodiments, the BCMA-binding arm binds human BCMA. In some embodiments, the BCMA-binding arm binds to residues 17-26 (LLHACIPCQL (SEQ ID NO: 162)) of BCMA BCMW37 chain.

[0097] Characteristics of some BCMA-specific antibodies or antigen-binding fragments may be found in e.g., WO2022 / 175255, the content of which is herein incorporated by reference in its entirety.

[0098] In one embodiment, the BCMA-binding arm comprises heavy chain CDR1, CDR2, and CDR3 and light chain CDR1, CDR2, and CDR3 of clone BCMB519. In one embodiment, the BCMA-binding arm comprises heavy chain variable domain and light chain variable domain of clone BCMB519.

[0099] In some embodiments, the BCMA-binding arm comprises a heavy chain CDR1 comprising SEQ ID NO: 20, a heavy chain CDR2 comprising SEQ ID NO: 21, and a heavy chain CDR3 comprising SEQ ID NO: 22. In some embodiments, the BCMA-binding arm comprises a heavy chain CDR1 comprising SEQ ID NO: 20, a heavy chain CDR2 comprising SEQ ID NO: 21, a heavy chain CDR3 comprising SEQ ID NO: 22, a light chain CDR1 comprising SEQ ID NO: 17, a light chain CDR2 comprising SEQ ID NO: 18, and a light chain CDR3 comprising SEQ ID NO: 19. The BCMA-binding arm may comprise human framework sequences. In some embodiments, the BCMA-binding arm comprises a heavychain variable domain substantially the same as, or identical to, SEQ ID NO: 24. In some embodiments, the BCMA-binding arm comprises a heavy chain variable domain substantially the same as, or identical to, SEQ ID NO: 24 and a light chain variable domain substantially the same as, or identical to, SEQ ID NO: 23.

[0100] In some embodiments, the BCMA-binding arm comprises humanized antigen-binding fragments. Humanized antigen-binding fragments may be derived from chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab’, F(ab’)2 or other antigen-binding subsequences of antibodies) that contain minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies or antigen-binding fragments are human immunoglobulins (recipient antibody) or antigenbinding fragments in which residues from a complementary-determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity, and capacity. In general, the humanized antibody antigen-binding fragments will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework regions are those of a human immunoglobulin sequence. The humanized antibody antigen-binding fragments may include at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin.GPRC5D-binding arm

[0101] The BCMA x GPRC5D x CD3 -trispecific antibody or trispecific binding fragment thereof described herein comprises an antigen-binding arm specific for GPRC5D.

[0102] In some embodiments, the GPRC5D-binding arm binds human GPRC5D. In some embodiments, the GPRC5D-binding arm binds to one or more residues of a polypeptide having the amino acid sequence of SEQ ID NO: 116.

[0103] Characteristics of some GPRC5D-specific antibodies or antigen-binding fragments may be found in e.g., United States Published Application US2020 / 0231686, the content of which is herein incorporated by reference in its entirety.

[0104] In one embodiment, the GPRC5D-binding arm comprises heavy chain CDR1, CDR2, and CDR3 and light chain CDR1, CDR2, and CDR3 of clone GC5B680. In oneembodiment, the GPRC5D-binding arm comprises heavy chain variable domain and light chain variable domain of clone GC5B680.

[0105] In some embodiments, the GPRC5D-binding arm comprises a heavy chain CDR1 comprising SEQ ID NO: 12, a heavy chain CDR2 comprising SEQ ID NO: 13, and a heavy chain CDR3 comprising SEQ ID NO: 14. In some embodiments, the GPRC5D-binding arm comprises a heavy chain CDR1 comprising SEQ ID NO: 12, a heavy chain CDR2 comprising SEQ ID NO: 13, a heavy chain CDR3 comprising SEQ ID NO: 14, a light chain CDR1 comprising SEQ ID NO: 9, a light chain CDR2 comprising SEQ ID NO: 10, and a light chain CDR3 comprising SEQ ID NO: 11. The GPRC5D-binding arm may comprise human framework sequences. In some embodiments, the GPRC5D-binding arm comprises a heavy chain variable domain substantially the same as, or identical to, SEQ ID NO: 16. In some embodiments, the GPRC5D-binding arm comprises a heavy chain variable domain substantially the same as, or identical to, SEQ ID NO: 16 and a light chain variable domain substantially the same as, or identical to, SEQ ID NO: 15.CD3 -binding arm

[0106] The BCMA x GPRC5D x CD3 -trispecific antibody or trispecific binding fragment thereof described herein comprises an antigen-binding arm that binds CD3. In some embodiments, the CD3-binding arm binds human CD3. In some preferred embodiments, the CD3-specific arm of the BCMA x GPRC5D x CD3 trispecific antibody is derived from a CD3-specific antibody that binds and activates human primary T cells and / or cynomolgus monkey primary T cells. In some embodiments, the trispecific antibodies or trispecific antigen-binding fragments described herein bind to CD3s. In some embodiments, the CD3- binding arm binds to an epitope at the N-terminus of CD3s. In some embodiments, the CD3- binding arm binds to residues 22-35 (QDGNEEMGGITQTP (SEQ ID NO: 161)) of the CD3s chain.

[0107] Human CD3s is described under UniProt P07766 (CD3E HUMAN). An anti CD3s antibody described in the state of the art is SP34 (Yang SJ, The Journal of Immunology (1986) 137; 1097-1100). SP34 reacts with both primate and human CD3. SP34 is available from Pharmingen. A further anti CD3 antibody described in the state of the art is UCHT-1 (see W02000041474). A further anti-CD3 antibody described in the state of the art is BC-3 (Fred Hutchinson Cancer Research Institute; used in Phase I / II trials of GvHD, Anasetti et al.,Transplantation 54: 844 (1992)). SP34 differs from UCHT-1 and BC-3 in that SP-34 recognizes an epitope present on solely the a chain of CD3 (see Salmeron et al., (1991) J. Immunol. 147: 3047) whereas UCHT-1 and BC-3 recognize an epitope contributed by both the a and y chains. The sequence of an antibody with the same sequence as of antibody SP34 is mentioned in W02008119565, W02008119566, W02008119567, W02010037836, W02010037837 and W02010037838. A sequence which is 96% identical to VH of antibody SP34 is mentioned in US8236308 (W02007042261).

[0108] Characteristics of some CD3-specific antibodies or antigen-binding fragments may be found in e.g., WO2019 / 224717, United States Patents No. 11,603,405, United States Published Application US2023 / 322924, the content of each of which is herein incorporated by reference in its entirety.

[0109] In some embodiments, the CD3 -binding arm (or “CD3 -specific arm”) of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is derived from the monoclonal antibody CD3B376. In some embodiments, the CD3-binding arm comprises heavy chain CDR1, CDR2, and CDR3 and light chain CDR1, CDR2, and CDR3 of clone CD3B376.

[0110] In some embodiments, the CD3 -binding arm comprises a heavy chain CDR1 comprising SEQ ID NO: 4, a heavy chain CDR2 comprising SEQ ID NO: 5, and a heavy chain CDR3 comprising SEQ ID NO: 6. In some embodiments, the CD3-binding arm comprises a heavy chain CDR1 comprising SEQ ID NO: 4, a heavy chain CDR2 comprising SEQ ID NO: 5, a heavy chain CDR3 comprising SEQ ID NO: 6, a light chain CDR1 comprising SEQ ID NO: 1, a light chain CDR2 comprising SEQ ID NO: 2, and a light chain CDR3 comprising SEQ ID NO: 3. The CD3-binding arm may comprise human framework sequences. In some embodiments, the CD3-binding arm comprises a heavy chain variable domain substantially the same as, or identical to, SEQ ID NO: 8. In some embodiments, the CD3-binding arm comprises a heavy chain variable domain substantially the same as, or identical to, SEQ ID NO: 8 and a light chain variable domain substantially the same as, or identical to, SEQ ID NO: 7.

[0111] In some embodiments, the CD3 -binding arm is IgG, or a derivative thereof. In some embodiments, the CD3 -specific antibody or antigen-binding fragment from which the CD3- specific arm of the trispecific antibody is derived is IgGl, or a derivative thereof. In some embodiments, for example, the Fc region of the CD3-specific IgGl antibody from which theCD3-binding arm is derived comprises L234A, L235A, and D265S substitutions in its Fc region.

[0112] "Homodimerization" as used herein refers to an interaction of two heavy chains having identical CH3 amino acid sequences. "Homodimer" as used herein refers to an antibody having two heavy chains with identical CH3 amino acid sequences.

[0113] "Heterodimerization" as used herein refers to an interaction of two heavy chains having non-identical CH3 amino acid sequences. "Heterodimer" as used herein refers to an antibody having two heavy chains with non-identical CH3 amino acid sequences.

[0114] The "knob-in-hole" strategy (see, e.g., PCT Inti. Publ. No. WO 2006 / 028936) may be used to generate full length trispecific antibodies. Briefly, selected amino acids forming the interface of the CH3 domains in human IgG can be mutated at positions affecting CH3 domain interactions to promote heterodimer formation. An amino acid with a small side chain (hole) is introduced into a heavy chain of an antibody binding a first antigen and an amino acid with a large side chain (knob) is introduced into a heavy chain of an antibody binding a second antigen. After co-expression of the two antibodies, a heterodimer is formed as a result of the preferential interaction of the heavy chain with a "hole" with the heavy chain with a "knob". Exemplary CH3 substitution pairs forming a knob and a hole are (expressed as modified position in the first CH3 domain of the first heavy chain / modified position in the second CH3 domain of the second heavy chain): T366Y / F405A, T366W / F405W, F405W / Y407A, T394W / Y407T, T394S / Y407A, T366W / T394S, F405W / T394S and T366W / T366 S_L368 A_Y407 V.

[0115] In some embodiments of the trispecific antibody or trispecific binding fragment described herein, one of the Fc domains comprise mutations T366S, L368A and Y407V and the other Fc domain comprises mutation T366W. In some embodiments, the Fc domain of the first heavy chain portion (HC1) of the first antigen binding arm (e.g., CD3 binding arm) comprises mutations T366S, L368A and Y407V, and the Fc domain of the second heavy chain portion (HC2) of the third antigen-binding arm (e.g., the BCMA binding arm) comprises mutation T366W.

[0116] In some embodiments, the trispecific antibodies or antigen-binding fragments are IgG, or derivatives thereof.

[0117] In some embodiments wherein the antibody is of IgGl isotype, the antibody comprises an IgGl Fc region (SEQ ID NO: 158).SEQ ID NO: 158 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP ELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0118] In some embodiments wherein the antibody is of IgGl isotype, the antibody comprises L234A, L235A, and D265S substitutions (underlined) in its Fc region (SEQ ID NO: 159).SEQ ID NO: 159ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAP EAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVSVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPR EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

[0119] In some embodiments wherein the antibody has an IgGl isotype, the antibody contains L234A, L235A, D265S and / or K409R substitution(s) in its Fc region. The antibodies described herein may include these modifications.

[0120] In some embodiments, the Fc domains of a trispecific antibody described herein each comprise one or more mutations selected from L234A, L235A, and D265S. In some embodiments, the Fc domains of HC1 and HC2 each comprise mutations L234A, L235A, and D265S.

[0121] In some embodiments, the Fc domain of one of the heavy chain portions of a trispecific antibody described herein further comprise one or more mutations which reduce Fc binding to protein A. In some embodiments, the Fc domain of the HC1 comprises mutations H435R and / or Y436F, preferably H435R and Y436F.

[0122] In some embodiments of a trispecific antibody described herein, the HC1 comprises, from the N- to C-terminus, the VH1 of the first antigen-binding arm, a CHI domain, the Fc domain, a linker, and the second antigen-binding arm.

[0123] In various embodiments, the scFvs used in trispecific antibodies or trispecific binding fragments described herein comprise, from the N- to C-terminus, a VH, a linker and a VL(VH-L-VL) or the VL, the linker and the VH (VL-L-VH). In some embodiments, the scFv comprises, from the N- to C-terminus, the VL, the linker and the VH (VL-L-VH).

[0124] In some embodiments, the linker comprises the amino acid sequence of SEQ ID NO: 25.

[0125] In some embodiments, the linker comprises the amino acid sequence of SEQ ID NO: 163.

[0126] In one embodiment, a CD3 / GPRC5D coupled HC1 of a BCMA x GPRC5D x CD3 trispecific antibody comprises an amino acid sequence substantially the same as, or identical to, SEQ ID NO: 29.

[0127] In one embodiment, the LC of a BCMA x GPRC5D x CD3 trispecific antibody comprises an amino acid sequence substantially the same as, or identical to, SEQ ID NO: 30.

[0128] In one embodiment, the BCMA binding arm (HC2) comprises an amino acid sequence substantially the same as, or identical to, SEQ ID NO: 31.

[0129] In one embodiment, provided herein is an isolated trispecific antibody, or a trispecific binding fragment thereof, comprising: a) a CD3 binding arm comprising a heavy chain (HC1) and a light chain (LC), wherein the HC1 further comprises the GPRC5D binding arm; and b) a BCMA binding arm, wherein HC1 comprises an amino acid sequence substantially the same as, or identical to, SEQ ID NO: 29, LC comprises an amino acid sequence substantially the same as, or identical to, SEQ ID NO: 30, and the BCMA binding arm comprises an amino acid sequence substantially the same as, or identical to, SEQ ID NO: 31.

[0130] In one embodiment, provided herein is an isolated trispecific antibody, or a trispecific binding fragment thereof, comprising: a) a CD3 binding arm comprising a heavy chain (HC1) and a light chain (LC), wherein the HC1 further comprises the GPRC5D binding arm; and b) a BCMA binding arm, wherein HC1 comprises the amino acid sequence of SEQ ID NO: 29, LC comprises the amino acid sequence of SEQ ID NO: 30, and the BCMA binding arm comprises the amino acid sequence of SEQ ID NO: 31.

[0131] In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody is BGCB491.Treatment of multiple myeloma

[0132] The trispecific antibodies discussed above, for example the BCMA x GPRC5D x CD3 trispecific antibodies discussed above, are for use in treating multiple myeloma (MM).

[0133] The disclosure provides a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of aBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of at least about 0.4 mg.

[0134] In one aspect, the disclosure provides a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of at least about 0.4 mg.

[0135] In another aspect, the disclosure provides a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 50 mg and wherein the treatment dose is administered once every four weeks.

[0136] In another aspect, the disclosure provides a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 100 mg and wherein the treatment dose is administered once every four weeks.

[0137] In another aspect, the disclosure provides a method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecificantibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 300 mg and wherein the treatment dose is administered once every four weeks.Administration

[0138] In particular, the disclosure provides new regimens for administering BCMA x GPRC5D x CD3 trispecific antibodies or trispecific fragments thereof to treat multiple myeloma in a subject.Dosing

[0139] According to the disclosure, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered to a subject at a treatment dose of at least about 0.4 mg.

[0140] In some embodiments, the treatment dose is at least about 0.4 mg, at least about 1.2 mg, at least about 3.6 mg, at least about 10 mg, at least about 20 mg, at least about 30 mg, at least about 40 mg, at least about 50 mg, at least about 80 mg, at least about 100 mg, at least about 120 mg, at least about 200 mg, or at least about 300 mg.

[0141] In an exemplary embodiment, the treatment dose is at least about 50 mg. In an exemplary embodiment, the treatment dose is at least about 100 mg.

[0142] In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 0.4 mg to about 300 mg, about 0.4 mg to about 200 mg, about 0.4 mg to about 120 mg, about 0.4 mg to about 100 mg, about 0.4 mg to about 80 mg, about 0.4 mg to about 50 mg, about 0.4 mg to about 40 mg, about 0.4 mg to about 30 mg, about 0.4 mg to about 20 mg, about 0.4 mg to about 10 mg, about 0.4 mg to about 3.6 mg, about 0.4 mg to about 1.2 mg, about 1.2 mg to about 300 mg, about 1.2 mg to about 200 mg, about 1.2 mg to about 120 mg, about 1.2 mg to about 100 mg, about 1.2 mg to about 80 mg, about 1.2 mg to about 50 mg, about 1.2 mg to about 40 mg, about 1.2 mg to about 30 mg, about 1.2 mg to about 20 mg, about 1.2 mg to about 10 mg, about 1.2 mg to about 3.6 mg, about 3.6 mg to about 300 mg, about 3.6 mg to about 200 mg, about 3.6 mg to about 120 mg, about 3.6 mg to about 100 mg, about 3.6 mg to about 80 mg, about 3.6 mg to about 50 mg, about 3.6 mg to about 40 mg, about 3.6 mg to about 30 mg, about 3.6 mg to about 20 mg, about 3.6 mg to about 10 mg, about 10 mg to about 300 mg, about 10 mg to about 200 mg, about 10 mg to about 120 mg, about 10 mg to about 100 mg, about 10 mg toabout 80 mg, about 10 mg to about 50 mg, about 10 mg to about 40 mg, about 10 mg to about 30 mg, about 10 mg to about 20 mg, about 20 mg to about 300 mg, about 20 mg to about 200 mg, about 20 mg to about 120 mg, about 20 mg to about 100 mg, about 20 mg to about 80 mg, about 20 mg to about 50 mg, about 20 mg to about 40 mg, about 20 mg to about 30 mg, about 30 mg to about 300 mg, about 30 mg to about 200 mg, about 30 mg to about 120 mg, about 30 mg to about 100 mg, about 30 mg to about 80 mg, about 30 mg to about 50 mg, about 30 mg to about 40 mg, about 40 mg to about 300 mg, about 40 mg to about 200 mg, about 40 mg to about 120 mg, about 40 mg to about 100 mg, about 40 mg to about 80 mg, about 40 mg to about 50 mg, about 50 mg to about 300 mg, about 50 mg to about 200 mg, about 50 mg to about 120 mg, about 50 mg to about 100 mg, about 50 mg to about 80 mg, about 80 mg to about 300 mg, about 80 mg to about 200 mg, about 80 mg to about 120 mg, about 80 mg to about 100 mg, about 100 mg to about 300 mg, about 100 mg to about 200 mg, about 100 mg to about 120 mg, about 120 mg to about 200 mg, about 120 mg to about 300 mg, or about 200 mg to about 300 mg. In an exemplary embodiment, the treatment dose is about 50 mg to about 300 mg. In an exemplary embodiment, the treatment dose is about 50 mg to about 100 mg. In an exemplary embodiment, the treatment dose is about 100 mg to about 200 mg.

[0143] In certain embodiments, the treatment dose is about 0.4 mg, about 1.2 mg, about 3.6 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 80 mg, about 100 mg, about 120 mg, about 200 mg, or about 300 mg. In one embodiment, the treatment dose is about 0.4 mg. In one embodiment, the treatment dose is about 1.2 mg. In one embodiment, the treatment dose is about 3.6 mg. In one embodiment, the treatment dose is about 10 mg. In one embodiment, the treatment dose is about 20 mg. In one embodiment, the treatment dose is about 30 mg. In one embodiment, the treatment dose is about 40 mg. In one embodiment, the treatment dose is about 80 mg. In one embodiment, the treatment dose is about 120 mg. In an exemplary embodiment, the treatment dose is about 50 mg. In an exemplary embodiment, the treatment dose is about 100 mg. In an exemplary embodiment, the treatment dose is about 200 mg. In an exemplary embodiment, the treatment dose is about 300 mg.

[0144] In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a first treatment dose for two, three or four cycles, followed by administration at a second treatment dose for subsequent cycles. Insome embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a first treatment dose for two cycles, followed by administration at a second treatment dose for subsequent cycles. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a first treatment dose for three cycles, followed by administration at a second treatment dose for subsequent cycles. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a first treatment dose for four cycles, followed by administration at a second treatment dose for subsequent cycles. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a first treatment dose for five cycles, followed by administration at a second treatment dose for subsequent cycles. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a first treatment dose for six cycles, followed by administration at a second treatment dose for subsequent cycles.

[0145] In some embodiments the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of about 100 mg per cycle for two, three, four, five or six cycles, followed by administration at a treatment dose of about 100 mg per cycle for subsequent cycles. In some embodiments, the first treatment dose is greater than the second treatment dose. In some embodiments, the first treatment dose is about 200 mg per cycle and the second treatment dose is about 100 mg per cycle. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of about 200 mg per cycle for two cycles, followed by administration at a treatment dose of about 100 mg per cycle for subsequent cycles. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of about 200 mg per cycle for four cycles, followed by administration at a treatment dose of about 100 mg per cycle for subsequent cycles.

[0146] The treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof may be a flat dose, as defined herein. Flat dosing may provide advantages compared to dosing according to body weight, such as reduced preparation time, and simpler administration and manufacturing. In preferred embodiments of the disclosure, the treatment dose is a flat dose.

[0147] For example, in some embodiments, the treatment dose a flat dose of at least about 0.4 mg, at least about 1.2 mg, at least about 3.6 mg, at least about 10 mg, at least about 20 mg, at least about 30 mg, at least about 40 mg, at least about 50 mg, at least about 80 mg, at least about 100 mg, at least about 120 mg, at least about 200 mg, or at least about 300 mg. In an exemplary embodiment, the treatment dose is a flat dose of at least about 50 mg. In an exemplary embodiment, the treatment dose is a flat dose of at least about 100 mg.

[0148] In some embodiments, the treatment dose is a flat dose within the range of about 0.4 mg to about 300 mg, about 0.4 mg to about 200 mg, about 0.4 mg to about 120 mg, about 0.4 mg to about 100 mg, about 0.4 mg to about 80 mg, about 0.4 mg to about 50 mg, about 0.4 mg to about 40 mg, about 0.4 mg to about 30 mg, about 0.4 mg to about 20 mg, about 0.4 mg to about 10 mg, about 0.4 mg to about 3.6 mg, about 0.4 mg to about 1.2 mg, about 1.2 mg to about 300 mg, about 1.2 mg to about 200 mg, about 1.2 mg to about 120 mg, about 1.2 mg to about 100 mg, about 1.2 mg to about 80 mg, about 1.2 mg to about 50 mg, about 1.2 mg to about 40 mg, about 1.2 mg to about 30 mg, about 1.2 mg to about 20 mg, about 1.2 mg to about 10 mg, about 1.2 mg to about 3.6 mg, about 3.6 mg to about 300 mg, about 3.6 mg to about 200 mg, about 3.6 mg to about 120 mg, about 3.6 mg to about 100 mg, about 3.6 mg to about 80 mg, about 3.6 mg to about 50 mg, about 3.6 mg to about 40 mg, about 3.6 mg to about 30 mg, about 3.6 mg to about 20 mg, about 3.6 mg to about 10 mg, about 10 mg to about 300 mg, about 10 mg to about 200 mg, about 10 mg to about 120 mg, about 10 mg to about 100 mg, about 10 mg to about 80 mg, about 10 mg to about 50 mg, about 10 mg to about 40 mg, about 10 mg to about 30 mg, about 10 mg to about 20 mg, about 20 mg to about 300 mg, about 20 mg to about 200 mg, about 20 mg to about 120 mg, about 20 mg to about 100 mg, about 20 mg to about 80 mg, about 20 mg to about 50 mg, about 20 mg to about 40 mg, about 20 mg to about 30 mg, about 30 mg to about 300 mg, about 30 mg to about 200 mg, about 30 mg to about 120 mg, about 30 mg to about 100 mg, about 30 mg to about 80 mg, about 30 mg to about 50 mg, about 30 mg to about 40 mg, about 40 mg to about 300 mg, about 40 mg to about 200 mg, about 40 mg to about 120 mg, about 40 mg to about 100 mg, about 40 mg to about 80 mg, about 40 mg to about 50 mg, about 50 mg to about 300 mg, about 50 mg to about 200 mg, about 50 mg to about 120 mg, about 50 mg to about 100 mg, about 50 mg to about 80 mg, about 80 mg to about 300 mg, about 80 mg to about 200 mg, about 80 mg to about 120 mg, about 80 mg to about 100 mg, about 100 mg to about 300 mg, about 100 mg to about 200 mg, about 100 mg to about 120 mg, about 120 mg to about 200mg, about 120 mg to about 300 mg, or about 200 mg to about 300 mg. In an exemplary embodiment, the treatment dose is a flat dose within the range of about 50 mg to about 300 mg. In an exemplary embodiment, the treatment dose is a flat dose within the range of about 50 mg to about 100 mg. In an exemplary embodiment, the treatment dose is a flat dose within the range of about 100 mg to about 200 mg.

[0149] In certain embodiments, the treatment dose is a flat dose of about 0.4 mg, about 1.2 mg, about 3.6 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 80 mg, about 100 mg, about 120 mg, about 200 mg, or about 300 mg. In one embodiment, the treatment dose is a flat dose of about 0.4 mg. In one embodiment, the treatment dose is a flat dose of about 1.2 mg. In one embodiment, the treatment dose is a flat dose of about 3.6 mg. In one embodiment, the treatment dose is a flat dose of about 10 mg. In one embodiment, the treatment dose is a flat dose of about 20 mg. In one embodiment, the treatment dose is a flat dose of about 30 mg. In one embodiment, the treatment dose is a flat dose of about 40 mg. In one embodiment, the treatment dose is a flat dose of about 80 mg. In one embodiment, the treatment dose is a flat dose of about 120 mg. In an exemplary embodiment, the treatment dose is a flat dose of about 50 mg. In an exemplary embodiment, the treatment dose is a flat dose of about 100 mg. In an exemplary embodiment, the treatment dose is a flat dose of about 200 mg. In an exemplary embodiment, the treatment dose is a flat dose of about 300 mg.

[0150] In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a first flat treatment dose for two, three or four cycles, followed by administration at a second flat treatment dose for subsequent cycles. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a first flat treatment dose for two cycles, followed by administration at a second flat treatment dose for subsequent cycles. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a first flat treatment dose for three cycles, followed by administration at a second flat treatment dose for subsequent cycles. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a first flat treatment dose for four cycles, followed by administration at a second flat treatment dose for subsequent cycles. In some embodiments, the first flat treatment dose is greater than the second flat treatment dose. In some embodiments, the first flat treatment dose is about 200 mg per cycle and the second flat treatment dose is about 100mg per cycle. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a flat treatment dose of about 200 mg per cycle for two cycles, followed by administration at a flat treatment dose of about 100 mg per cycle for subsequent cycles.

[0151] In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a flat treatment dose of about 200 mg per cycle for four cycles, followed by administration at a flat treatment dose of about 100 mg per cycle for subsequent cycles.

[0152] The treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof may be a weight-based dose. Therefore, in some embodiments of the disclosure, the treatment dose is a weight-based dose. Such dosages can, for example, be based on the mg / kg dosages provided above according to the following: dose (mg / kg)x body weight (e.g., 50 - 100 kg).Administration route

[0153] In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered intravenously, intramuscularly, intraperitoneally, and / or subcutaneously to the subject. In some embodiments, the treatment dose is administered intravenously or subcutaneously to the subject. In some embodiments, the treatment dose is administered intravenously to the subject. In an exemplary embodiment, the treatment dose is administered subcutaneously to the subject.

[0154] The administration may be performed by continuous infusion over a period of from 2 to 24 hr, such as from 2 to 12 hr. In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof may be administered by slow continuous infusion over a long period, such as more than 24 hours, in order to reduce toxic side effects. In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered intravenously as a bolus or by continuous infusion over a period of time. In an exemplary embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is injected subcutaneously, to exert local as well as systemic therapeutic effects.Administration frequency

[0155] In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered weekly, once every two weeks, once every three weeks, once every four weeks, or once every eight weeks. In some embodiments, the treatment dose is administered weekly. In some embodiments, the treatment dose is administered once every three weeks. In an exemplary embodiment, the treatment dose is administered once every two weeks (biweekly) or once every four weeks. In an exemplary embodiment, the treatment dose is administered once every two weeks (biweekly). In some embodiments, the treatment dose is administered between once every 12 days and once every 16 days. In an exemplary embodiment, the treatment dose is administered once every four weeks. In some embodiments, the treatment dose is administered between once every 24 days and once every 35 days. In an exemplary embodiment, the treatment dose is administered once every eight weeks. In some embodiments, the treatment dose is administered less frequently than once every eight weeks. In some embodiments, the treatment dose is administered between once every 48 days and once every 63 days.

[0156] In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every two weeks for two, three or four cycles, followed by administration once every eight weeks for subsequent cycles. In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every two weeks for two, three or four cycles, followed by administration once every four weeks for subsequent cycles. In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every four weeks for two, three or four cycles, followed by administration once every eight weeks for subsequent cycles. In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every four weeks for six cycles, followed by administration once every eight weeks for subsequent cycles. In some embodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every two weeks for four cycles, followed by administration once every four weeks for subsequent cycles. In someembodiments, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every two weeks for three cycles, followed by administration once every four weeks for subsequent cycles.

[0157] In some embodiments, the dosing schedule is once every two weeks, once every four weeks, or once every eight weeks depending on patient response.Step-up dosing

[0158] In some embodiments, at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered prior to the administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof. In some embodiments, one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered. In some embodiments, two step-up doses of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof are administered.

[0159] Step-up doses are lower than the treatment dose. To prevent or lessen certain toxicities, such as cytokine release syndrome (CRS), a “priming” dose strategy may include one or more lower step-up dose(s) followed by higher treatment doses.

[0160] In some embodiments, the step-up dose(s) of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered intravenously, intramuscularly, intraperitoneally, and / or subcutaneously to the subject. In some embodiments, the step-up dose(s) is administered intravenously or subcutaneously to the subject. In some embodiments, the step-up dose(s) is administered intravenously to the subject. In an exemplary embodiment, the step-up dose(s) is administered subcutaneously to the subject. In some embodiments, the step-up dose(s) is administered using a different administration route than the treatment dose. In an exemplary embodiment, the step-up dose(s) is administered using the same administration route as the treatment dose.

[0161] In an exemplary embodiment, at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof. In some embodiments, the first step-up dose is about 2.5 mg to about 50 mg. In certain such embodiments, the first step-up dose is about 2.5 mg to about 50 mg, about 2.5 mg to about 20mg, about 2.5 mg to about 10 mg, about 2.5 mg to about 5 mg, about 2.5 mg to about 3.6 mg, about 3.6 mg to about 50 mg, about 3.6 mg to about 20 mg, about 3.6 mg to about 10 mg, about 3.6 mg to about 5 mg, about 5 mg to about 50 mg, about 5 mg to about 20 mg, about 5 mg to about 10 mg, or about 20 mg to about 50 mg. In an exemplary embodiment, the first step-up dose is about 2.5 mg to about 5 mg.

[0162] In some embodiments, the first step-up dose is no greater than about 50 mg, no greater than about 20 mg, no greater than about 10 mg, no greater than about 5 mg, no greater than about 3.6 mg, or no greater than about 2.5 mg.

[0163] In certain embodiments, the first step-up dose is about 2.5 mg, about 3.6 mg, about 5 mg, about 10 mg, about 20 mg or about 50 mg. In one embodiment, the first step-up dose is about 2.5 mg. In another embodiment, the first step-up dose is about 3.6 mg. In another embodiment, the first step-up dose is about 5 mg. In a further embodiment, the first step-up dose is about 10 mg. In a further embodiment, the first step-up dose is about 20 mg. In a further embodiment, the first step-up dose is about 50 mg.

[0164] In some embodiments, the first step-up dose is administered about 2-8 days prior to the administration of the treatment dose. In some embodiments, the first step-up dose is administered about one week prior to the administration of the treatment dose. In some embodiments, the first step-up dose is administered about 6-8 days prior to the administration of the treatment dose. In some embodiments, the first step-up dose is administered about 1-5 days prior to the administration of the treatment dose. In some embodiments, the first step-up dose is administered about 2-4 days prior to the administration of the treatment dose.

[0165] In some embodiments, the first step-up dose is subcutaneously administered about 2-8 days prior to the subcutaneous administration of the treatment dose. In some embodiments, the first step-up dose is subcutaneously administered about one week prior to the subcutaneous administration of the treatment dose. In some embodiments, the first step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the treatment dose. In some embodiments, the first step-up dose is subcutaneously administered about 1-5 days (e.g. about 2-4 days) prior to the subcutaneous administration of the treatment dose. In an exemplary embodiment, the first step-up dose is subcutaneously administered about 2-8 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg. In an exemplary embodiment, the first step- up dose is subcutaneously administered about one week prior to the subcutaneousadministration of the treatment dose, and wherein the first step-up dose is about 5 mg. In an exemplary embodiment, the first step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg. In an exemplary embodiment, the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 2.5 mg. In an exemplary embodiment, the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 3.6 mg. In an exemplary embodiment, the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.

[0166] In some embodiments, the first step-up dose is a flat dose. For example, in some embodiments, the first step-up dose is a flat dose of about 2.5 mg to about 50 mg. In certain such embodiments, the first step-up dose is a flat dose of about 2.5 mg to about 50 mg, about 2.5 mg to about 20 mg, about 2.5 mg to about 10 mg, about 2.5 mg to about 5 mg, about 2.5 mg to about 3.6 mg, about 3.6 mg to about 50 mg, about 3.6 mg to about 20 mg, about 3.6 mg to about 10 mg, about 3.6 mg to about 5 mg, about 5 mg to about 50 mg, about 5 mg to about 20 mg, about 5 mg to about 10 mg, or about 20 mg to about 50 mg. In an exemplary embodiment, the first step-up dose is a flat dose of about 2.5 mg to about 5 mg.

[0167] In some embodiments, the first step-up dose is a flat dose of no greater than about 50 mg, no greater than about 20 mg, no greater than about 10 mg, no greater than about 5 mg, no greater than about 3.6 mg, or no greater than about 2.5 mg.

[0168] In certain embodiments, the first step-up dose is a flat dose of about 2.5 mg, about 3.6 mg, about 5 mg, about 10 mg, about 20 mg or about 50 mg. In one embodiment, the first step-up dose is a flat dose of about 2.5 mg. In another embodiment, the first step-up dose is a flat dose of about 3.6 mg. In another embodiment, the first step-up dose is a flat dose of about 5 mg. In a further embodiment, the first step-up dose is a flat dose of about 10 mg. In a further embodiment, the first step-up dose is a flat dose of about 20 mg. In a further embodiment, the first step-up dose is a flat dose of about 50 mg. In some embodiments, at least two step-up doses of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof are administered prior to the administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof. Incertain such embodiments, at least two step-up doses of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof are subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof. In certain such embodiments, the second step-up dose is greater than the first step-up dose.

[0169] In some embodiments, the first step-up dose is no greater than one tenth of the treatment dose. In some embodiments, the first step-up dose is no greater than one twentieth of the treatment dose. In some embodiments, the first step-up dose is no greater than one twenty-fifth of the treatment dose. In some embodiments, the first step-up dose is no greater than one fortieth of the treatment dose. In some embodiments, the second step-up dose is no greater than one half of the treatment dose. In some embodiments, the second step-up dose is no greater than one third of the treatment dose. In some embodiments, the second step-up dose is no greater than one fifth of the treatment dose. In some embodiments, the second step- up dose is no greater than one seventh of the treatment dose. In some embodiments, the first step-up dose is no greater than one tenth of the treatment dose and the second step-up dose is no greater than one half of the treatment dose. In some embodiments, the first step-up dose is no greater than one twentieth of the treatment dose and the second step-up dose is no greater than one third of the treatment dose. In some embodiments, the first step-up dose is no greater than one twenty -fifth of the treatment dose and the second step-up dose is no greater than one fifth of the treatment dose. In some embodiments, the first step-up dose is no greater than one fortieth of the treatment dose and the second step-up dose is no greater than one seventh of the treatment dose.

[0170] In one embodiment, the first step-up dose is about 5 mg. In one embodiment, the first step-up dose is a flat dose of about 5 mg. In one embodiment, the second step-up dose is about 100 mg. In one embodiment, the second step-up dose is a flat dose of about 100 mg. In one embodiment, the first step-up dose is about 5 mg and the second step-up dose is about 100 mg. In one embodiment, the first step-up dose is a flat dose of about 5 mg and the second step-up dose is a flat dose of about 100 mg.

[0171] In some embodiments, the first step-up dose is administered about one week prior to the administration of the second step-up dose. In some embodiments, the first step-up dose is administered about 6-8 days prior to the administration of the second step-up dose. In some embodiments, the first step-up dose is administered about 1-5 days (e.g. about 2-4 days) priorto the administration of the second step-up dose. In some embodiments, the second step-up dose is administered about one week prior to the administration of the treatment dose. In some embodiments, the second step-up dose is administered about 6-8 days prior to the administration of the treatment dose. In some embodiments, the second step-up dose is administered about 1-5 days (e.g. about 2-4 days) prior to the administration of the treatment dose.

[0172] In some embodiments, the first step-up dose is subcutaneously administered about one week prior to the subcutaneous administration of the second step-up dose. In some embodiments, the first step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the second step-up dose. In one embodiment, the first step-up dose is subcutaneously administered about 1-5 days (e.g. about 2-4 days) prior to the subcutaneous administration of the second step-up dose. In some embodiments, the second step-up dose is subcutaneously administered about one week prior to the subcutaneous administration of the treatment dose. In some embodiments, the second step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the treatment dose. In one embodiment, the second step-up dose is subcutaneously administered about 1-5 days (e.g. about 2-4 days) prior to the subcutaneous administration of the treatment dose.

[0173] In an exemplary embodiment, the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the second step-up dose, and wherein the second step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, wherein first step-up dose is about 5 mg and the second step-up dose is about 100 mg.

[0174] In some embodiments, at least three step-up doses of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof are administered prior to the administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof. In certain such embodiments, at least three step-up doses of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof are subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof. In certain such embodiments, the third step-up dose is greater than the second step-updose. In certain such embodiments, the third step-up dose is greater than the second step-up dose and the second step-up dose is greater than the first step-up dose.

[0175] In some embodiments, no step-up doses are administered prior to the administration of the treatment dose.Dosing regimens of the disclosure

[0176] In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 0.4 mg and wherein the treatment dose is subcutaneously administered once every two weeks. In certain embodiments, no step- up doses are administered prior to the administration of the treatment dose.

[0177] In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 1.2 mg and wherein the treatment dose is subcutaneously administered once every two weeks. In certain embodiments, no step- up doses are administered prior to the administration of the treatment dose.

[0178] In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 3.6 mg and wherein the treatment dose is subcutaneously administered once every two weeks. In certain embodiments, no step- up doses are administered prior to the administration of the treatment dose.

[0179] In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 10 mg and wherein the treatment dose is subcutaneously administered once every two weeks. In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every two weeks at a treatment dose of about 10 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 3.6 mg and is administered about 2-4 days prior to the administration of the treatment dose. Often such a dosing regimen comprises further step-up doses prior to administration of the treatment dose. In an alternative embodiment, no step-up doses are administered prior to the administration of the treatment dose.

[0180] In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 20 mg per cycle and wherein thetreatment dose is subcutaneously administered once every two weeks for three cycles, followed by subcutaneous administration once every four weeks for subsequent cycles. In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every two weeks at a treatment dose of about 20 mg per cycle for three cycles, followed by subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 20 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the first cycle. Often such a dosing regimen comprises further step-up doses prior to the first cycle. In an alternative embodiment, no step-up doses are administered prior to the first cycle.

[0181] In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 30 mg and wherein the treatment dose is subcutaneously administered once every two weeks. In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every two weeks at a treatment dose of about 30 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the administration of the treatment dose. Often such a dosing regimen comprises further step-up doses prior to administration of the treatment dose.

[0182] In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 40 mg and wherein the treatment dose is subcutaneously administered once every four weeks. In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 40 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose isabout 5 mg and is administered about 2-4 days prior to the administration of the treatment dose. Often such a dosing regimen comprises further step-up doses prior to administration of the treatment dose.

[0183] In an exemplary embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 50 mg and wherein the treatment dose is subcutaneously administered once every four weeks. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the administration of the treatment dose. In an exemplary embodiment, theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to the administration of the treatment dose. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose. In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 6-8 days prior to the administration of the treatmentdose. Often such dosing regimens comprise further step-up doses prior to administration of the treatment dose.

[0184] In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 80 mg and wherein the treatment dose is subcutaneously administered once every four weeks. In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 80 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the administration of the treatment dose. Often such a dosing regimen comprises further step-up doses prior to administration of the treatment dose.

[0185] In an exemplary embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 100 mg and wherein the treatment dose is subcutaneously administered once every four weeks. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the administration of the treatment dose. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to the administration of the treatment dose. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about one week prior to the administration of the treatment dose. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 6-8 days prior to the administration of the treatment dose. Often such dosing regimens comprise further step-up doses prior to administration of the treatment dose.

[0186] In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the trispecific antibody or binding fragment is administered subcutaneously prior to the treatment dose, wherein the first step-up dose is about 5 mg and is administered 2 to 8 days before the treatment dose.

[0187] In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the trispecific antibody or binding fragment is administered subcutaneously prior to the treatment dose, wherein the first step-up dose is about 5 mg and is administered about one week before the treatment dose.

[0188] In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the trispecific antibody or binding fragment is administered subcutaneously prior to the treatment dose, wherein the first step-up dose is about 5 mg and is administered 6-8 days before the treatment dose.

[0189] In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the trispecific antibody or binding fragment is administered subcutaneously prior to the treatment dose, wherein the first step-up dose is about 5 mg and is administered 2-4 days before the treatment dose.

[0190] In an exemplary embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 100 mg and wherein the treatment dose is subcutaneously administered once every eight weeks. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every eight weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the administration of the treatment dose. Often such dosing regimens comprise further step-up doses prior to administration of the treatment dose.

[0191] In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, per cycle for six cycles, followed by subcutaneous administration once every eight weeks at a treatment dose of about 100 mg per cycle for subsequent cycles. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg per cycle for six cycles, followed by subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every eight weeks at a treatment dose of about 100 mg, optionally 50mg, per cycle for subsequent cycles, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-8 days prior to the the first cycle. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the first cycle. Often such a dosing regimen comprises further step-up dosesprior to the first cycle. In certain embodiments only one step up dose is administered, optionally the step-up dose is about 5 mg and is administered about 2-8 days prior to the first cycle.

[0192] In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg per cycle for six cycles, followed by subcutaneous administration once every eight weeks at a treatment dose of about 100 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the trispecific antibody or binding fragment is administered subcutaneously prior to the first cycle, wherein the first step-up dose is about 5 mg and is administered 2 to 8 days before the first cycle.

[0193] In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, per cycle for six cycles, followed by subcutaneous administration once every eight weeks at a treatment dose of about 50mg per cycle for subsequent cycles. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg per cycle for six cycles, followed by subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every eight weeks at a treatment dose of about 50 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-8 days prior to the the first cycle. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the first cycle. Often such a dosing regimen comprises further step-up doses prior to the first cycle. In certain embodiments only one step up dose is administered, optionally the step-up dose is about 5 mg and is administered about 2-8 days prior to the first cycle.

[0194] In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg per cycle for six cycles, followed by subcutaneous administration once every eight weeks at a treatment dose of about 50 mg per cycle forsubsequent cycles, and wherein at least one step-up dose of the trispecific antibody or binding fragment is administered subcutaneously prior to the first cycle, wherein the first step-up dose is about 5 mg and is administered 2 to 8 days before the first cycle.

[0195] In one embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 120 mg and wherein the treatment dose is subcutaneously administered once every four weeks. In one embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 120 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the administration of the treatment dose. Often such a dosing regimen comprises further step-up doses prior to administration of the treatment dose.

[0196] In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200 mg per cycle for four cycles, followed by subcutaneous administration once every four weeks at a treatment dose of about 100 mg per cycle for subsequent cycles. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200 mg per cycle for four cycles, followed by subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 100 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the first cycle. Alternatively, in certain such embodiments, the first step-up dose is about 5 mg and is administered about one week prior to the first cycle. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200 mg per cycle for four cycles, followed by subcutaneous administration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 100 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle. In certain such embodiments, the at least one step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the first cycle. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 6-8 days prior to the first cycle. Often such a dosing regimen comprises further step-up doses prior to the first cycle.

[0197] In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200 mg per cycle for four cycles, followed by subcutaneous administration once every four weeks at a treatment dose of about 100 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the trispecific antibody or binding fragment is administered subcutaneously prior to the first cycle, wherein the first step-up dose is about 5 mg and is administered 2 to 8 days before the first cycle.

[0198] In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every eight weeks at a treatment dose of about 200 mg per cycle for two cycles, followed by subcutaneous administration once every eight weeks at a treatment dose of about 100 mg per cycle for subsequent cycles. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every eight weeks at a treatment dose of about 200 mg per cycle for two cycles, followed by subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every eight weeks at a treatment dose of about 100 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the first cycle. Often such a dosing regimen comprises further step-up doses prior to the first cycle.

[0199] In an exemplary embodiment, the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is about 300 mg and wherein the treatment dose is subcutaneously administered once every four weeks. In an exemplaryembodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 300 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-8 days prior to the administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to the administration of the treatment dose. In an exemplary embodiment, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 300 mg, and wherein at least two step-up doses of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof are subcutaneously administered prior to the subcutaneous administration of the treatment dose. In certain such embodiments, the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the second step-up dose. In certain such embodiments, the second step-up dose is about 100 mg and is administered about 2-4 days prior to administration of the treatment dose. Often such a dosing regimen comprises further step-up doses prior to administration of the treatment dose.

[0200] Dosage regimens in the above methods of treatment are adjusted to provide the optimum desired response (e.g., a therapeutic response). For example, the dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. Parenteral compositions may be formulated in dosage unit form for ease of administration and uniformity of dosage.

[0201] The efficient dosages and the dosage regimens for the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof may be determined by one skilled in the art.

[0202] A physician, pharmacist or veterinarian having ordinary skill in the art may readily determine and prescribe the effective amount of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof required. For example, the physician or veterinarian could start doses of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof employed in the pharmaceutical composition at levels lower than that required in order to achieve the desired therapeutic effect and graduallyincrease the dosage until the desired effect is achieved. In general, a suitable daily dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof of the present disclosure will be that amount of the compound which is the lowest dose effective to produce a therapeutic effect.

[0203] The dosage may be determined or adjusted by measuring the amount ofBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof of the present disclosure in the blood upon administration by for instance taking out a biological sample and using anti-idiotypic antibodies which target the GPRC5D and / or BCMA antigen binding arms of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof of the present disclosure.

[0204] The doses depend on the desired effect, the duration of the treatment and the route of administration used. In general, the doctor will determine the appropriate dosage depending on the age, weight and any other factors specific to the subject to be treated.

[0205] The dosing regimens may be repeated one or more times as necessary, for example, after six months or twelve months.

[0206] In one embodiment, the trispecific antibody or trispecific binding fragment thereof may be administered by maintenance therapy, such as, e.g., once a week for a period of six months or more.Treatment of multiple myeloma (MM)

[0207] In some embodiments, the multiple myeloma is smoldering multiple myeloma (SMM). In some embodiments, the multiple myeloma is extramedullary disease (EMD). In some embodiments, the multiple myeloma is relapsed, refractory, or malignant, or any combination thereof.

[0208] Various qualitative and / or quantitative methods can be used to determine relapse or refractory nature of the disease. Symptoms that can be associated are for example a decline or plateau of the well-being of the patient or re-establishment or worsening of various symptoms associated with solid tumors, and / or the spread of cancerous cells in the body from one location to other organs, tissues or cells.

[0209] A BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof may also be administered prophylactically in order to reduce the risk of developingmultiple myeloma, delay the onset of the occurrence of an event in multiple myeloma progression, and / or reduce the risk of recurrence when a multiple myeloma is in remission.

[0210] In some embodiments, the multiple myeloma is a high-risk multiple myeloma. Subjects with high-risk multiple myeloma are known to relapse early and have poor prognosis and outcome. Subjects can be classified as having high-risk multiple myeloma is they have one or more of the following cytogenetic abnormalities: t(4; 14)(p 16;q32), t(14; 16)(q32;q23), dell7p, IqAmp, t(4; 14)(pl6;q32) and t(14; 16)(q32;q23), t(4; 14)(pl6;q32) and dell7p, t(14; 16)(q32;q23) and dell7p, or t(4; 14)(p 16;q32), t(14; 16)(q32;q23) and dell7p. In some embodiments, the subject having the high-risk multiple myeloma has one or more chromosomal abnormalities comprising: t(4; 14)(p 16;q32), t(14; 16)(q32;q23), dell7p, IqAmp, t(4; 14)(pl6;q32) and t(14;16)(q32;q23), t(4; 14)(p 16;q32) and dell7p, t(14; 16)(q32;q23) and dell7p; or t(4; 14)(pl6;q32), t(14;16)(q32;q23) and dell7p, or any combination thereof.

[0211] The cytogenetic abnormalities can be detected for example by fluorescent in situ hybridization (FISH). In chromosomal translocations, an oncogene is translocated to the IgH region on chromosome 14q32, resulting in dysregulation of these genes. t(4; 14)(pl6;q32) involves translocation of fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma SET domain containing protein (MMSET) (also called WHSC1 / NSD2), and t(14; 16)(q32;q23) involves translocation of the MAF transcription factor C-MAF. Deletion of 17p (del 17p) involves loss of the p53 gene locus.

[0212] Chromosomal rearrangements can be identified using well known methods, for example fluorescent in situ hybridization, karyotyping, pulsed field gel electrophoresis, or sequencing.

[0213] Particular trispecific antibodies that may be used to treat MM include antibodies BGCB491.

[0214] In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is utilized for the treatment of relapsed or refractory multiple myeloma. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is utilized for the treatment of relapsed multiple myeloma. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is utilized for the treatment of refractory multiple myeloma.

[0215] In some embodiments, the subject is relapsed or refractory to treatment with a prior anti-cancer treatment. In some embodiments, the prior anti-cancer treatment comprises administering at least one of a proteasome inhibitor and immunomodulatory drug, such as bortezomib, carfilzomib, lenalidomide, or pomalidomide. In some embodiments, the subject is relapsed or refractory to treatment with an anti-CD38 antibody, selinexor, lenalinomide, bortezomib, pomalidomide, carfilzomib, elotozumab, ixazomib, melphalan, thalidomide, melphalan flufenamide, venetoclax or any combination thereof. In some embodiments, the anti-CD38 antibody is daratumumab or isatuximab. In some embodiments, the anti-CD38 antibody is daratumumab. In some embodiments, the subject is refractory to treatment with a proteasome inhibitor (PI). In certain such embodiments, the PI is bortezomib, carfilzomib, or ixazomib. In some embodiments, the subject is refractory to treatment with an immunomodulatory agent (IMiD). In certain such embodiments, the IMiD is thalidomide, lenalidomide, or pomalidomide. In some embodiments, the subject is refractory to treatment with CAR-T. In some embodiments, the subject is refractory to treatment with a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 antibody. In some embodiments, the subject is refractory to treatment with two proteasome inhibitors (PI), two immunomodulatory agents, and an anti-CD38 antibody. In some embodiments, the subject is refractory to treatment with a BCMA directed therapy. In some embodiments, the subject is refractory to treatment with a GPRC5D directed therapy. In some embodiments, the subject is refractory to treatment with the last line of prior therapy.

[0216] In some embodiments, the subject receiving the BCMA x GPRC5D x CD3 trispecific antibody or binding fragment thereof has received a prior treatment. In some embodiments, the prior treatment is a BCMA or GPRC directed therapy. In some embodiments, the prior BCMA or GPRC directed therapy is CAR-T therapy. In certain such embodiments, the CAR- T therapy is Carvykti® (ciltacabtagene autoleucel). In some embodiments, the prior BCMA or GPRC directed therapy is a bispecific antibody. In some embodiments, the prior treatment is a BCMA directed therapy. In some embodiments, the prior BCMA directed therapy is CAR-T therapy. In certain such embodiments, the CAR-T therapy is Carvykti® (ciltacabtagene autoleucel), In some embodiments, the prior BCMA directed therapy is a bispecific antibody. In some embodiments, the prior treatment is a GPRC directed therapy, such as a GPRC5D directed therapy. In some embodiments, the prior GPRC directed therapy is CAR-T therapy. In some embodiments, the prior GPRC directed therapy is a bispecificantibody. In other embodiments, the patient is naive to prior BCMA or GPRC directed therapy. In some embodiments, the prior treatment comprises a proteasome inhibitor, an immunomodulatory drug, a CD38 antibody, a bispecific agent, a CAR-T therapy, or any combination thereof. For example, the subject may have received one or more therapeutics, such as proteasome inhibitors (Pls) (e.g., Marizomib (salinosporamide A), Carfilzomib, Ixazomib), immunomodulatory drugs (IMiDs), bispecific agents, CAR-T therapies, and / or anti-CD38 antibodies, for treating multiple myeloma. In certain such embodiments, the PI is bortezomib, carfilzomib or ixazomib. In certain such embodiments, the IMiD is lenalidomide, pomalidomide or thalidomide. In certain such embodiments, the anti-CD38 antibody is daratumumab or isatuximab. In certain such embodiments, the bispecific agent is a BCMA x CD3 bispecific antibody or a GPRC5D x CD3 bispecific antibody. In certain such embodiments, the CAR-T therapy is a BCMA CAR-T therapy. In certain such embodiments, the BCMA CAR-T therapy is Carvykti® (ciltacabtagene autoleucel). In some embodiments, the subject receiving the BCMA x GPRC5D x CD3 trispecific antibody or binding fragment thereof has received a prior PI and a prior IMiD. In some embodiments, the subject receiving the BCMA x GPRC5D x CD3 trispecific antibody or binding fragment thereof has received a prior PI, a prior IMiD, and a prior anti-CD38 antibody. In some embodiments, the subject receiving the BCMA x GPRC5D x CD3 trispecific antibody or binding fragment thereof has received two prior Pls, two prior IMiDs, and a prior anti-CD38 antibody. In some embodiments, the prior treatment is selinexor. In some embodiments, the prior treatment is venetoclax. In some embodiments, the prior treatment is an antibody-drug conjugate. In some embodiments, the subject has received under three lines of prior therapy. In some embodiments, the subject has received over three lines of prior therapy. In some embodiments, the subject has received 1-3 lines of prior therapy. In some embodiments, the subject suffers from relapsed or refractory multiple myeloma and has received prior treatment with a proteasome inhibitor, an immunomodulatory drug (IMiD), and an anti-CD38-based therapy.

[0217] In some embodiments, the subject suffers from relapsed or refractory multiple myeloma and has received 1-3 lines of prior therapy. In certain such embodiments, the subject has received a prior PI. In certain such embodiments, the subject has received prior lenalidomide. In certain such embodiments, the subject has received a prior PI and prior lenalidomide.

[0218] In some embodiments, the subject suffers from relapsed or refractory multiple myeloma and has received autologous BCMA-directed CAR-T. In certain such embodiments, the subject received autologous BCMA-directed CAR-T within 2 to 5 months of the first treatment dose.

[0219] In some embodiments, the subject is administered a premedication. In some embodiments, the premedication is administered before the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered. In some embodiments, the premedication is administered at the same time as the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered.

[0220] In some embodiments, the premedication is tocilizumab.

[0221] In some embodiments, the subject is an outpatient.

[0222] In some embodiments, the subject is administered a prophylactic premedication. In some embodiments, the prophylactic premedication is tocilizumab. In some embodiments, tocilizumab is administered before the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered. In some embodiments, tocilizumab is administered at the same time as the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered. In certain such embodiments, tocilizumab is administered at the same time as administration of the first step-up dose of BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof. In certain embodiments, the tocilizumab is administered intravenously at a dose of 8 mg / kg.

[0223] In some embodiments, the subject is an outpatient and is administered a prophylactic premedication, wherein the prophylactic premedication is tocilizumab.

[0224] In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered as a monotherapy.

[0225] Treatment with a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof according to particular dosing regimens may lead to safe and effective outcomes for subjects in need of treatment for multiple myeloma (MM).

[0226] Thus, in some embodiments, the subject does not exhibit a dose-limiting toxicity (DLT) or Grade 5 treatment emergent adverse event (TEAE) following administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.

[0227] In some embodiments, the method achieves a partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) in the subject. In certain such embodiments, the method achieves a partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) in the subject, according to IMWG criteria.

[0228] In some embodiments, the method achieves a very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) in the subject. In certain such embodiments, the method achieves a very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) in the subject, according to IMWG criteria.

[0229] In some embodiments, the method achieves a complete response (CR) or stringent complete response (sCR) in the subject. In certain such embodiments, the method achieves a complete response (CR) or stringent complete response (sCR) in the subject, according to IMWG criteria.

[0230] In some embodiments, the method achieves a stringent complete response (sCR) in the subject. In certain such embodiments, the method achieves a stringent complete response (sCR) in the subject, according to IMWG criteria.

[0231] In some embodiments, the method achieves an overall response rate of about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% of treated subjects. In one embodiment, the method achieves an overall response rate of about 50% of treated subjects. The overall response rate may be deciphered by calculating the proportion of patients who achieve a partial response, a very good partial response, a complete response, or a stringent complete response.Compositions

[0232] The BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof can be formulated as a pharmaceutical composition. In some embodiments, the pharmaceutical compositions comprise: a) an effective amount of a trispecific antibody or trispecific binding fragment of the present disclosure, and b) a pharmaceutically acceptable carrier, which may be inert or physiologically active. As used herein, the term"pharmaceutically acceptable carriers" includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, and the like that are physiologically compatible.

[0233] In some embodiments, the pharmaceutical composition further comprises one or more excipients. In some embodiments, the one or more excipients include, but are not limited to a buffering agent, a sugar, a surfactant, a chelator, or any combination thereof.

[0234] Examples of suitable carriers, diluents and / or excipients include one or more of water, saline, phosphate buffered saline, dextrose, glycerol, ethanol, and the like, as well as any combination thereof. In many cases, it will be preferable to include isotonic agents, such as sugars, polyalcohols, or sodium chloride in the composition. In particular, relevant examples of suitable carrier include: (1) Dulbecco's phosphate buffered saline, pH.about.7.4, containing or not containing about 1 mg / mL to 25 mg / mL human serum albumin, (2) 0.9% saline (0.9% w / v sodium chloride (NaCl)), and (3) 5% (w / v) dextrose; and may also contain an antioxidant such as tryptamine and a stabilizing agent such as Tween 20®.

[0235] The compositions of the disclosure may be in a variety of forms. These include for example liquid, semi-solid, and solid dosage forms, but the preferred form depends on the intended mode of administration and therapeutic application. Typical preferred compositions are in the form of injectable or infusible solutions.

[0236] Sterile compositions for parenteral administration can be prepared by incorporating the antibody, antibody fragment or antibody conjugate of the present disclosure in the required amount in the appropriate solvent, followed by sterilization by microfiltration. As solvent or vehicle, there may be used water, saline, phosphate buffered saline, dextrose, glycerol, ethanol, and the like, as well as combination thereof. In many cases, it will be preferable to include isotonic agents, such as sugars, polyalcohol’s, or sodium chloride in the composition. These compositions may also contain adjuvants, in particular wetting, isotonizing, emulsifying, dispersing and stabilizing agents. Sterile compositions for parenteral administration may also be prepared in the form of sterile solid compositions which may be dissolved at the time of use in sterile water or any other injectable sterile medium.

[0237] The BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof of the disclosure are used for the treatment of multiple myeloma (MM). In some embodiments, the multiple myeloma is smoldering multiple myeloma (SMM). In some embodiments, the multiple myeloma is extramedullary disease (EMD). In some embodiments, the multiple myeloma is a relapsed or refractory form of multiple myeloma. Insome embodiments, the multiple myeloma is a relapsed form of multiple myeloma. In some embodiments, the multiple myeloma is a refractory form of multiple myeloma.

[0238] Accordingly, the pharmaceutical compositions of the disclosure are useful in the treatment or prevention of multiple myeloma (MM), including SMM (Smoldering Multiple myeloma) and extramedullary disease (EMD). In some embodiments, the multiple myeloma is a relapsed or refractory form of multiple myeloma.

[0239] A therapeutically effective amount of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered to a subject in need thereof. In some embodiments, the subject is a mammal, preferably a human. In some embodiments, the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof will be administered as a solution that has been tested for sterility.EMBODIMENTS

[0240] The disclosure provided herein also provides the following non-limiting embodiments.1. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of at least about 0.4 mg.2. The method of embodiment 1, wherein the treatment dose is a flat dose.3. The method of embodiment 1 or embodiment 2, wherein the treatment dose is about 0.4 mg, about 1.2 mg, about 3.6 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 80 mg, about 100 mg, about 120 mg, about 200 mg, or about 300 mg.4. The method of embodiment 3, wherein the treatment dose is about 0.4 mg.5. The method of embodiment 3, wherein the treatment dose is about 1.2 mg.6. The method of embodiment 3, wherein the treatment dose is about 3.6 mg.7. The method of embodiment 3, wherein the treatment dose is about 10 mg.8. The method of embodiment 3, wherein the treatment dose is about 20 mg.9. The method of embodiment 3, wherein the treatment dose is about 30 mg.10. The method of embodiment 3, wherein the treatment dose is about 40 mg.11. The method of embodiment 3, wherein the treatment dose is about 50 mg.12. The method of embodiment 3, wherein the treatment dose is about 80 mg.13. The method of embodiment 3, wherein the treatment dose is about 100 mg.14. The method of embodiment 3, wherein the treatment dose is about 120 mg.15. The method of embodiment 3, wherein the treatment dose is about 200 mg.16. The method of embodiment 3, wherein the treatment dose is about 300 mg.17. The method of any one of embodiments 1-3, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of about 100 mg per cycle for two, three, four, five or six cycles, followed by administration at a treatment dose of about 100 mg per cycle for subsequent cycles.18. The method of any one of embodiments 1-3, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of about 200 mg per cycle for two, three or four cycles, followed by administration at a treatment dose of about 100 mg per cycle for subsequent cycles.19. The method of embodiment 18, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of about 200 mg per cycle for four cycles, followed by administration at a treatment dose of about 100 mg per cycle for subsequent cycles.20. The method of embodiment 18, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of about 200 mg per cycle for two cycles, followed by administration at a treatment dose of about 100 mg per cycle for subsequent cycles.21. The method of any one of embodiments 1-20, wherein the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered weekly, once every two weeks, once every three weeks, once every four weeks, or once every eight weeks.22. The method of embodiment 21, wherein the treatment dose is administered weekly.23. The method of embodiment 21, wherein the treatment dose is administered once every two weeks.24. The method of embodiment 21, wherein the treatment dose is administered once every three weeks.25. The method of embodiment 21, wherein the treatment dose is administered once every four weeks.26. The method of embodiment 21, wherein the treatment dose is administered once every eight weeks.27. The method of any one of embodiments 1-16, 18-20, wherein the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every two weeks for two, three or four cycles, followed by administration once every four weeks for subsequent cycles.28. The method of embodiment 27, wherein the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every two weeks for three cycles, followed by administration once every four weeks for subsequent cycles.29. The method of any one of embodiments 1-28, wherein the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered intravenously or subcutaneously.30. The method of embodiment 29, wherein the treatment dose is administered subcutaneously.31. The method of any one of embodiments 1-4, 21, 23 and 29-30, wherein the treatment dose is about 0.4 mg and wherein the treatment dose is subcutaneously administered once every two weeks.32. The method of any one of embodiments 1-3, 5, 21, 23 and 29-30, wherein the treatment dose is about 1.2 mg and wherein the treatment dose is subcutaneously administered once every two weeks.33. The method of any one of embodiments 1-3, 6, 21, 23 and 29-30, wherein the treatment dose is about 3.6 mg and wherein the treatment dose is subcutaneously administered once every two weeks.34. The method of any one of embodiments 1-3, 7, 21, 23 and 29-30, wherein the treatment dose is about 10 mg and wherein the treatment dose is subcutaneously administered once every two weeks.35. The method of any one of embodiments 1-3, 9, 21, 23 and 29-30, wherein the treatment dose is about 30 mg and wherein the treatment dose is subcutaneously administered once every two weeks.36. The method of any one of embodiments 1-3, 10, 21, 25 and 29-30, wherein the treatment dose is about 40 mg and wherein the treatment dose is subcutaneously administered once every four weeks.37. The method of any one of embodiments 1-3, 11, 21, 25 and 29-30, wherein the treatment dose is about 50 mg and wherein the treatment dose is subcutaneously administered once every four weeks.38. The method of any one of embodiments 1-3, 12, 21, 25 and 29-30, wherein the treatment dose is about 80 mg and wherein the treatment dose is subcutaneously administered once every four weeks.39. The method of any one of embodiments 1-3, 13, 21, 25 and 29-30, wherein the treatment dose is about 100 mg and wherein the treatment dose is subcutaneously administered once every four weeks40. The method of any one of embodiments 1-3, 13, 21, 26 and 29-30, wherein the treatment dose is about 100 mg and wherein the treatment dose is subcutaneously administered once every eight weeks.41 . The method of any one of embodiments 1-3, 14, 21, 25 and 29-30, wherein the treatment dose is about 120 mg and wherein the treatment dose is subcutaneously administered once every four weeks.42. The method of any one of embodiments 1-3, 16, 21, 25 and 29-30, wherein the treatment dose is about 300 mg and wherein the treatment dose is subcutaneously administered once every four weeks.43. The method of any one of embodiments 1-3, 8 and 27-30, wherein the treatment dose is about 20 mg per cycle and wherein the treatment dose is subcutaneously administered once every two weeks for three cycles, followed by subcutaneous administration once every four weeks for subsequent cycles.44. The method of any one of embodiments 1-3, 13, 15, 18-19 and 29-30, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 200mg per cycle for four cycles, followed by subcutaneous administration once every four weeks at a treatment dose of about 100 mg per cycle for subsequent cycles.45. The method of any one of embodiments 1-3, 13, 15, 18, 20 and 29-30, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered once every eight weeks at a treatment dose of about 200 mg per cycle for two cycles, followed by subcutaneous administration once every eight weeks at a treatment dose of about 100 mg per cycle for subsequent cycles.46. The method of any one of embodiments 1-17, 21-26, and 29-42, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.47. The method of embodiment 46, wherein the first step-up dose is about 2.5 mg to about 50 mg.48. The method of embodiment 46 or embodiment 47, wherein the first step-up dose is about 2.5 mg to about 5 mg.49. The method of embodiment 46 or embodiment 47, wherein the first step-up dose is about 2.5 mg, about 3.6 mg, about 5 mg, about 10 mg, about 20 mg, or about 50 mg.50. The method of embodiment 49, wherein the first step-up dose is about 2.5 mg.51. The method of embodiment 49, wherein the first step-up dose is about 3.6 mg.52. The method of embodiment 49, wherein the first step-up dose is about 5 mg.53. The method of embodiment 49, wherein the first step-up dose is about 10 mg.54. The method of embodiment 49, wherein the first step-up dose is about 20 mg.55. The method of embodiment 49, wherein the first step-up dose is about 50 mg.56. The method of any one of embodiments 46-55, wherein the first step-up dose is subcutaneously administered about 2-8 days prior to the subcutaneous administration of the treatment dose.57. The method of any one of embodiments 46-56, wherein the first step-up dose is subcutaneously administered about one week prior to the subcutaneous administration of the treatment dose.58. The method of any one of embodiments 46-56, wherein the first step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the treatment dose.59. The method of any one of embodiments 46-56, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose.60. The method of any one of embodiments 46-49, 52 and 57, wherein the first step-up dose is subcutaneously administered about one week prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.61. The method of any one of embodiments 46-49, 52 and 58, wherein the first step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.62. The method of any one of embodiments 46-50 and 59, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 2.5 mg.63. The method of any one of embodiments 46-49, 51 and 59, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 3.6 mg.64. The method of any one of embodiments 46-49, 52 and 59, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.65. The method of any one of embodiments 46-64, wherein at least two step-up doses of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof are subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.66. The method of embodiment 65, wherein the second step-up dose is greater than the first step-up dose.67. The method of embodiment 65 or embodiment 66, wherein the first step-up dose is about 5 mg.68. The method of any one of embodiments 65-67, wherein the second step-up dose is about 100 mg.69. The method of any one of embodiments 65-68, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the second step-up dose.70. The method of any one of embodiments 65-69, wherein the second step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose.71. The method of any one of embodiments 65-70, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the second step-up dose, and wherein the second step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, wherein first step-up dose is about 5 mg and the second step-up dose is about 100 mg.72. The method of any one of embodiments 18-20, 27, 28, and 43-45, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle.73. The method of embodiment 72, wherein the first step-up dose is about 2.5 mg to about 50 mg.74. The method of embodiment 73, wherein the first step-up dose is about 5 mg.75. The method of embodiments 72-74, wherein the first step-up dose is subcutaneously administered about 2-8 days prior to the subcutaneous administration of the treatment dose.76. The method of any one of embodiments 72-74, wherein the first step-up dose is subcutaneously administered about one week prior to the first cycle.77. The method of any one of embodiments 72-74, wherein the first step-up dose is subcutaneously administered about 6-8 days prior to the first cycle.78. The method of any one of embodiments 72-74, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the first cycle.79. The method of any one of embodiments 72-74 and 76, wherein the first step-up dose is subcutaneously administered about one week prior to the first cycle, and wherein the first step-up dose is about 5 mg.The method of any one of embodiments 72-74 and 77, wherein the first step-up dose is subcutaneously administered about 6-8 days prior to the first cycle, and wherein the first step-up dose is about 5 mg. The method of any one of embodiments 72-74 and 78, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the first cycle, and wherein the first step-up dose is about 5 mg. The method of embodiment 60, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about one week prior to administration of the treatment dose. The method of embodiment 61, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about 6-8 days prior to administration of the treatment dose. The method of embodiment 56, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about 2-8 days prior to administration of the treatment dose. The method of embodiment 60, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecificbinding fragment thereof once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about one week prior to administration of the treatment dose. The method of embodiment 61, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about 6-8 days prior to administration of the treatment dose. The method of embodiment 62, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to administration of the treatment dose. The method of embodiment 62, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to administration of the treatment dose. The method of embodiment 63, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecificbinding fragment thereof once every two weeks at a treatment dose of about 10 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 3.6 mg and is administered about 2-4 days prior to administration of the treatment dose. The method of embodiment 64, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every two weeks at a treatment dose of about 30 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose. The method of embodiment 64, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 40 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose. The method of embodiment 64, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 50 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose. The method of embodiment 64, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecificbinding fragment thereof once every four weeks at a treatment dose of about 80 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose. The method of embodiment 64, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose. The method of embodiment 64, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every eight weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose. The method of embodiment 64, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 120 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose. The method of embodiment 64, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecificbinding fragment thereof once every four weeks at a treatment dose of about 300 mg, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose. The method of embodiment 71, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 300 mg, and wherein at least two step-up doses of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof are subcutaneously administered prior to the subcutaneous administration of the treatment dose, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the second step-up dose, wherein the second step-up dose is about 100 mg and is administered about 2-4 days prior to administration of the treatment dose. The method of embodiment 81, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every two weeks at a treatment dose of about 20 mg per cycle for three cycles, followed by subcutaneous administration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 20 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to the first cycle. . The method of embodiment 81, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 200 mg per cycle for four cycles, followed by subcutaneous administration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 100 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to the first cycle. . The method of embodiment 75, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 200 mg per cycle for four cycles, followed by subcutaneous administration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 100 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle, wherein the first step-up dose is about 5 mg and is administered about 2-8 days prior to the first cycle. . The method of embodiment 79, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 200 mg per cycle for four cycles, followed by subcutaneous administration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 100 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle, wherein the first step-up dose is about 5 mg and is administered about one week prior to the first cycle. . The method of embodiment 56, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 100 mg per cycle for six cycles, followed by subcutaneous administration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every eight weeks at a treatment dose of about 100 mg per cycle, optionally 50 mg per cycle, for subsequent cycles, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereofis subcutaneously administered prior to the first cycle, wherein the first step-up dose is about 5 mg and is administered about 2-8 days prior to the first cycle. . The method of embodiment 80, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 200 mg per cycle for four cycles, followed by subcutaneous administration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every four weeks at a treatment dose of about 100 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle, wherein the first step-up dose is about 5 mg and is administered about 6-8 days prior to the first cycle. . The method of embodiment 81, wherein the method comprises subcutaneous administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every eight weeks at a treatment dose of about 200 mg per cycle for two cycles, followed by subcutaneous administration of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof once every eight weeks at a treatment dose of about 100 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to the first cycle. . The method of embodiment 85 or embodiment 86, wherein the subject is an outpatient. . The method of any one of embodiments 95, 100 or 105, wherein the subject is administered a prophylactic premedication, wherein the prophylactic premedication is tocilizumab. . The method of embodiment 94, wherein the subject is an outpatient and is administered prophylactic premedication, wherein the prophylactic premedication is tocilizumab.109. The method of any one of embodiments 1-108, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof comprises:(a) a first antigen-binding arm comprising a first heavy chain variable domain (VH1) and a first light chain variable domain (VL1);(b) a second antigen-binding arm comprising a second heavy chain variable domain (VH2) and a second light chain variable domain (VL2);(c) a third antigen-binding arm comprising a third heavy chain variable domain (VH3) and a third light chain variable domain (VL3), wherein the first antigen-binding arm binds to an epitope on cluster of differentiation 3 (CD3), the second antigen-binding arm binds to an epitope on G-protein coupled receptor family C group 5 member D (GPRC5D), and the third antigen-binding arm binds to an epitope on B cell maturation antigen (BCMA).110. The method of embodiment 109, wherein the VH1 and VL1 of first antigen-binding arm are present in a Fab, a diabody, Fab’, a F(ab’)2, a Fv, a scFv, a Fd, a disulfide stabilized Fv fragment (dsFv), or a disulfide stabilized diabody (ds diabody).111 .The method of embodiment 110, wherein the VH1 and VL1 of first antigen-binding arm are present in a Fab.112. The method of any one of embodiments 109-111, wherein the VH2 and VL2 of the second antigen-binding arm are present in a scFv, a diabody, a Fab, Fab’, a F(ab’)2, a Fv, a Fd, a disulfide stabilized Fv fragment (dsFv), or a disulfide stabilized diabody (ds diabody).113. The method of embodiment 112, wherein the VH2 and VL2 of first antigen-binding arm are present in a scFv.114. The method of any one of embodiments 109-113, wherein the VH3 and VL3 of the third antigen-binding arm are present in a scFv, an antibody fragment, a diabody, a Fab, Fab’, a F(ab’)2, a Fv, a Fd, a disulfide stabilized Fv fragment (dsFv), or a disulfide stabilized diabody (ds diabody).115. The method of embodiment 114, wherein the VH3 and VL3 of first antigen-binding arm are present in a scFv.116. The method of any one of embodiments 109-115, wherein the first antigen-binding arm that binds CD3 comprises a heavy chain complementarity determining region (HCDR) 1, a HCDR2 and a HCDR3 of the heavy chain variable domain (VH1) of SEQ ID NO: 8 and a light chain complementarity determining region (LCDR) 1, a LCDR2 and a LCDR3 of the light chain variable domain (VL1) of SEQ ID NO: 7.117. The method of any one of embodiments 109-116, wherein the first antigen-binding arm that binds CD3 comprises a HCDR1 comprising the amino acid sequence of GDSVFNNNAAWS (SEQ ID NO: 4), a HCDR2 comprising the amino acid sequence of RTYYRSKWLYD (SEQ ID NO: 5), and a HCDR3 comprising the amino acid sequence of GYSSSFDY (SEQ ID NO: 6); and a LCDR1 comprising the amino acid sequence of TGTSSNIGTYKFVS (SEQ ID NO: 1), a LCDR2 comprising the amino acid sequence of EVSKRPS (SEQ ID NO: 2), and a LCDR3 comprising the amino acid sequence of VSYAGSGTLL (SEQ ID NO: 3).118. The method of any one of embodiments 109-117, wherein the first antigen-binding arm that binds CD3 comprises the VH1 of SEQ ID NO: 8 and the VL1 of SEQ ID NO: 7.119. The method of any one of embodiments 109-118, wherein the second antigen-binding arm that binds GPRC5D comprises a heavy chain complementarity determining region (HCDR) 1, a HCDR2 and a HCDR3 of the heavy chain variable domain (VH2) of SEQ ID NO: 16 and a light chain complementarity determining region (LCDR) 1, a LCDR2 and a LCDR3 of the light chain variable domain (VL2) of SEQ ID NO: 15.120. The method of any one of embodiments 109-119, wherein the second antigen-binding arm that binds GPRC5D comprises a HCDR1 comprising the amino acid sequence of GFSLTNIRMSVS (SEQ ID NO: 12), HCDR2 comprising the amino acid sequence of HIFSNDEKS (SEQ ID NO: 13), and a HCDR3 comprising the amino acid sequence of MRLPYGMDV (SEQ ID NO: 14); and a LCDR1 comprising the amino acid sequence of RSSQSLVHSDGNTYLS (SEQ ID NO: 9), a LCDR2 comprising the amino acid sequence of KISNRFF (SEQ ID NO: 10), and a LCDR3 comprising the amino acid sequence of MQATQFPHT (SEQ ID NO: 11).121. The method of any one of embodiments 109-120, wherein the second antigen-binding arm that binds GPRC5D comprises the VH2 of SEQ ID NO: 16 and the VL2 of SEQ ID NO: 15.. The method of any one of embodiments 109-121, wherein the third antigen-binding arm that binds BCMA comprises a heavy chain complementarity determining region (HCDR) 1, a HCDR2 and a HCDR3 of the heavy chain variable domain (VH3) of SEQ ID NO: 24 and a light chain complementarity determining region (LCDR) 1, a LCDR2 and a LCDR3 of the light chain variable domain (VL3) of SEQ ID NO: 23.. The method of any one of embodiments 109-122, wherein the third antigen-binding arm that binds BCMA comprises a HCDR1 comprising the amino acid sequence of GFTFSSYAMS (SEQ ID NO: 20), a HCDR2 comprising the amino acid sequence of AISGSGGSTY (SEQ ID NO: 21), and a HCDR3 comprising the amino acid sequence of DEGYSSGHYYGMDV (SEQ ID NO: 22); and a LCDR1 comprising the amino acid sequence of RASQSISSSFLT (SEQ ID NO: 17), a LCDR2 comprising the amino acid sequence of GASSRAT (SEQ ID NO: 18), and a LCDR3 comprising the amino acid sequence of QHYGSSPMYT (SEQ ID NO: 19). . The method of any one of embodiments 109-123, wherein the third antigen-binding arm that binds BCMA comprises the VH3 of SEQ ID NO: 24 and the VL3 of SEQ ID NO: 23. . The method of any one of embodiments 109-124, wherein the first antigen-binding arm that binds CD3 comprises the HCDR1, the HCDR2 and the HCDR3 of the VH1 of SEQ ID NO: 8 and the LCDR1, the LCDR2 and the LCDR3 of the VL1 of SEQ ID NO: 7; the second antigen-binding arm that binds GPRC5D comprises the HCDR1, the HCDR2 and the HCDR3 of the VH2 of SEQ ID NO: 16 and the LCDR1, the LCDR2 and the LCDR3 of the VL2 of SEQ ID NO: 15; and the third antigen-binding arm that binds BCMA comprises the HCDR1, the HCDR2 and the HCDR3 of the VH3 of SEQ ID NO: 24 and the LCDR1, the LCDR2 and the LCDR3 of the VL3 of SEQ ID NO: 23. . The method of any one of embodiments 109-125, wherein the first antigen-binding arm that binds CD3 comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 4, 5, 6, 1, 2, 3, respectively; the second antigen-binding arm that binds GPRC5D comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 12, 13, 14, 9, 10 and 11, respectively; andthe third antigen-binding arm that binds BCMA comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 20, 21, 22, 17, 18 and 19, respectively.127. The method of any one of embodiments 109-126, wherein the first antigen-binding arm that binds CD3 comprises the VH1 of SEQ ID NO: 8 and the VL1 of SEQ ID NO: 7; the second antigen-binding arm that binds GPRC5D comprises the VH2 of SEQ ID NO: 16 and the VL2 of SEQ ID NO: 15; and the third antigen-binding arm that binds BCMA comprises the VH3 of SEQ ID NO: 24 and the VL3 of SEQ ID NO: 23.128. The method of any one of embodiments 109-127, wherein the first antigen-binding arm comprises a Fragment crystallizable (Fc) domain, and the second antigen-binding arm or the third antigen-binding arm comprises a Fc domain.129. The method of embodiment 128, wherein the Fc domains comprise one or more mutations which promote heterodimerization of the Fc domains.130. The method of embodiment 129, wherein the mutations are selected from T366S, L368A, T366W and Y407V (EU numbering).131 .The method of any one of embodiments 128-130, wherein the Fc domains further comprise one or more mutations which reduce Fc binding to a Fey receptor.132. The method of embodiment 131, wherein the Fey receptor is FcyRI, FcyRIIA, Fey RUB, FcyRIIIA, and / or FcyRIIIB.133. The method of embodiment 131 or embodiment 132, wherein the Fc domains comprise one or more mutations selected from L234A, L235A, and D265S (EU numbering).134. The method of any one of embodiments 128-133, wherein the Fc domains further comprise one or more mutations which reduce Fc binding to protein A.135. The method of embodiment 134, wherein the Fc domain comprises mutations H435R and / or Y436F (EU numbering).136. The method of any one of embodiments 109-135, wherein the first antigen-binding arm specifically binds to residues 22-35 (QDGNEEMGGITQTP (SEQ ID NO: 161)) of the CD3s chain.. The method of any one of embodiments 109-136, wherein the first antigen-binding arm specifically binds to CD3 with an affinity of about 1 xlO'8to 1 xlO'7M. . The method of embodiment 137, wherein the first antigen-binding arm specifically binds to CD3 with an affinity of about 2 xlO'8to 4 x 10'8M. . The method of any one of embodiments 109-138, wherein the third antigen-binding arm specifically binds residues 17-26 (LLHACIPCQL (SEQ ID NO: 162)) of BCMA BCMW37 chain. . The method of any one of embodiments 109-139, wherein the third antigen-binding arm specifically binds to BCMA with an affinity of about 1 xlO'10to 1 x IO’7M.. The method of embodiment 140, wherein the third antigen-binding arm specifically binds to BCMA with an affinity of about 2 xlO'10to 9 xlO'10M. . The method of any one of embodiments 109-141, wherein theBCMA x GPRC5D x CD3 trispecific antibody comprises a first antigen-binding arm that binds to an epitope on cluster of differentiation 3 (CD3), a second antigen-binding arm that binds to an epitope on G-protein coupled receptor family C group 5 member D (GPRC5D), and a third antigen-binding arm that binds to an epitope on B cell maturation antigen (BCMA), wherein the first antigen-binding arm comprises a heavy chain (HC1) polypeptide and a light chain (LC) polypeptide, wherein the heavy chain (HC1) polypeptide further comprises the second antigen-binding arm, wherein the trispecific antibody, or the trispecific binding fragment thereof, further comprises a single polypeptide comprising the third antigen-binding arm. . The method of embodiment 142, wherein the HC1 of the first antigen-binding arm comprises the amino acid sequence of SEQ ID NO: 29. . The method of embodiment 142 or embodiment 143, wherein the LC of the first antigen-binding arm comprises the amino acid sequence of SEQ ID NO: 30. . The method of any one of embodiments 142-144, wherein the single polypeptide comprising the third antigen -binding arm comprises an amino acid sequence of SEQ ID NO: 31. . The method of any one of embodiments 142-145, wherein the first antigen-binding arm comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 29, and aLC comprising the amino acid sequence of SEQ ID NO: 30, and the single polypeptide comprising the third antigen-binding arm comprises the amino acid sequence of SEQ ID NO: 31.147. The method of any one of embodiments 109-146, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is an IgGl, IgG2, IgG3, or IgG4 (human) isotype.148. The method of any one of embodiments 109-147, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is an (human) IgGl isotype.149. The method of any one of embodiments 1-148, wherein the multiple myeloma is smoldering multiple myeloma (SMM).150. The method of any one of embodiments 1-148, wherein the multiple myeloma is extramedullary disease (EMD).151 .The method of any one of embodiments 1-148, wherein the multiple myeloma is relapsed or refractory multiple myeloma (RRMM).152. The method of embodiment 151, wherein the relapsed or refractory multiple myeloma is relapsed multiple myeloma.153. The method of embodiment 151, wherein the relapsed or refractory multiple myeloma is refractory multiple myeloma.154. The method of any one of embodiments 1-153, wherein the subject is relapsed or refractory to treatment with a prior anti-cancer treatment.155. The method of embodiment 154, wherein the prior anti-cancer treatment comprises administering at least one of a proteasome inhibitor and immunomodulatory drug, such as bortezomib, carfilzomib, lenalidomide, or pomalidomide.156. The method of embodiment 154, wherein the prior anti-cancer treatment is a CAR-T therapy, such as a BCMA CAR-T therapy.157. The method of any one of embodiments 1-156, wherein the subject is relapsed or refractory to treatment with an anti-CD38 antibody, selinexor, lenalinomide, bortezomib, pomalidomide, carfilzomib, elotozumab, ixazomib, melphalan, thalidomide, melphalan flufenamide, or any combination thereof.. The method of embodiment 157, wherein the anti-CD38 antibody is daratumumab or isatuximab. . The method of embodiment 158, wherein the anti-CD38 antibody is daratumumab.. The method of any one of embodiments 1-159, wherein the subject has received a prior treatment. . The method of embodiment 160, wherein the prior treatment comprises a proteasome inhibitor, an immunomodulatory drug, a CD38 antibody, a bispecific agent, a CAR-T therapy, or any combination thereof. . The method of any one of embodiments 1-161, wherein the subject has received 1-3 lines of prior treatment. . The method of any one of embodiments 1-161, wherein the subject has received over 3 lines of prior treatment. . The method of embodiment 162 or embodiment 163, wherein the subject is relapsed or refractory to the lines of prior treatment. . The method of any one of embodiments 160-164, wherein the prior treatment comprises a BCMA or GPRC directed therapy. . The method of embodiment 165, wherein the BCMA or GPRC directed therapy is a CAR-T therapy. . The method of embodiment 165, wherein the BCMA or GPRC directed therapy is a bispecific antibody. . The method of any one of embodiments 160-164, wherein the subject is naive to prior BCMA or GPRC directed therapy. . The method of any one of embodiments 1-168, wherein the subject is administered a prophylactic premedication. . The method of embodiment 169, wherein the prophylactic premedication is tocilizumab. .The method of any one of embodiments 1-170, wherein the subject is an outpatient.. The method of embodiment 170 or 171, wherein the subject is an outpatient and is administered a prophylactic premedication, wherein the prophylactic premedication is tocilizumab.. The method of any one of embodiments 1-172, wherein theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered as a monotherapy. . The method of any one of embodiments 1-173, wherein the subject does not exhibit a dose-limiting toxicity (DLT) or Grade 5 treatment emergent adverse event (TEAE) following administration of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof. . The method of any one of embodiments 1-174, wherein the method achieves a partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) in the subject, according to IMWG criteria. . The method of any one of embodiments 1-175, wherein the method achieves a very good partial response (VGPR), complete response (CR) or stringent complete response (sCR) in the subject, according to IMWG criteria. . The method of any one of embodiments 1-176, wherein the method achieves a complete response (CR) or stringent complete response (sCR) in the subject, according to IMWG criteria. . The method of any one of embodiments 1-177, wherein the method achieves a stringent complete response (sCR) in the subject, according to IMWG criteria. . The method of any one of embodiments 1-178, wherein the method achieves an overall response rate of about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100% of treated subjects. . The method of any of embodiments 1-179, wherein the subject is a human subject.. The method of embodiment 56, wherein the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg, and wherein at least one step-up dose of the trispecific antibody or binding fragment is administered subcutaneously prior to the treatment dose, wherein the first step-up dose is about 5 mg and is administered 2 to 8 days before the treatment dose. . The method of embodiment 75, wherein the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof is subcutaneously administered onceevery four weeks at a treatment dose of about 200 mg per cycle for four cycles, followed by subcutaneous administration once every four weeks at a treatment dose of about 100 mg per cycle for subsequent cycles, and wherein at least one step-up dose of the trispecific antibody or binding fragment is administered subcutaneously prior to the first cycle, wherein the first step-up dose is about 5 mg and is administered 2 to 8 days before the first cycle.183. The method of embodiment 56, wherein the BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof is subcutaneously administered once every four weeks at a treatment dose of about 100 mg per cycle for six cycles, followed by subcutaneous administration once every eight weeks at a treatment dose of about 100 mg per cycle, optionally about 50 mg per cycle, for subsequent cycles, and wherein at least one step-up dose of the trispecific antibody or binding fragment is administered subcutaneously prior to the first cycle, wherein the first step-up dose is about 5 mg and is administered 2 to 8 days before the first cycle.EXAMPLES

[0241] The following examples are provided to supplement the prior disclosure and to provide a better understanding of the subject matter described herein. These examples should not be considered to limit the described subject matter. It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be apparent to persons skilled in the art and are to be included within, and can be made without departing from, the true scope of the disclosure.EXAMPLE 1 : Molecule Design, Sequence, and Structure ofBGCB491 trispecific antibody

[0242] BGCB491 is an immunoglobulin (Ig) G1 trispecific antibody that can bind simultaneously or independently to the epsilon subunit of the cluster of differentiation 3 receptor complex (CD3e) (Uniprot ID: P07766) on T lymphocytes (T cells), and to GPRC5D (G-protein coupled receptor family C group 5 member D, Uniprot ID: Q9NZD1) and BCMA (B cell maturation antigen, TNFRSF17, Uniprot ID: Q02223) on tumor cells. The antibody features mutations of L234A, L235A, and D265S in the constant region (Fc) to abolish interaction with Fc receptors and heterodimerization is enhanced using the knobs-into-holesplatform mutations f The anti-CD3e “hole” chain also featured “RF” mutations (H435R, Y436F) to disrupt protein A binding of monomeric and homodimerized hole chains2. The molecule comprises an anti-CD3e Fab region on the “hole, RF” chain and an anti-GPRC5D scFv v-region fused onto the C-terminus. The “knob” chain features the anti-BCMA scFv. The trispecific antibody was developed to evaluate the therapeutic potential of dual tumor targeting GPRC5D and BCMA and CD3 for T cell redirection. An illustration of BGCB491 is depicted in FIG. 1.

[0243] The trispecific BGCB491 antibody was generated by co-expression of the anti-CD3 heavy chain (HC) A fused to the C-terminal anti-GPRC5D scFv and anti-CD3 light chain (LC) with the anti-BCMA scFv fused to “knob” containing heavy chain B. The anti-CD3 variable region (VR000017350) was discovered by immunizing transgenic humanized rats [OmniRat (OMT™)] with recombinant CD3s protein. The anti-GPRC5d variable region (VR000038761) featured in BGCB491 is derived from the mAb GC5B680, discovered by immunizing transgenic humanized mice [Ablexis] with DNA encoding GPRC5d. The parent v-region (VR000029832) contained an “NSS” motif in the HC framework 3 region which presented a risk for N-linked glycosylation and which represented a mutation from the IGHV2-26*01 germline. The site was mutated back to the germline sequence “STS” to eliminate the risk for N-linked glycosylation, and this change resulted in the final variable region VR000038761. The anti-BCMA variable region (VR000003260) featured in BGCB491 is derived from the mAb BCMB519, discovered by immunizing transgenic humanized mice [Ablexis] with recombinant BCMA protein. No further modifications were made to this v-region. Both the anti-GPRC5D and anti-BCMA v-regions were formatted as single-chain fragment variable (scFv) in the final molecule.

[0244] The amino acid sequence for the BGCB491 heavy chains and light chain, as deduced from the cDNA sequence (SEQ ID Nos: 165, 166, and 167) of BGCB491 and confirmed by peptide mapping and mass spectrometry is shown below (Table 1). The complementaritydetermining regions (CDRs) are defined according to ABM numbering. The Gin residue at position 1 of BGCB491 heavy chain 1, Gin residue at position 1 of BGCB491 light chain, and Glu residue at position 1 of BGCB491 heavy chain 2 constitute the N-termini of the mature chains. Both heavy chains comprising BGCB491 IgGl AAS have the following point mutations: L234A, L235A, and D265S. Heavy chain 1 from BGCB491 features the “hole” mutations: T366S, L368A, Y407V and the RF mutations: H435R, Y436F, while heavy chain2 features the “knob” mutation: T366W. The knobs-into-holes mutations promote heterodimerization of the Fc3. The “RF” mutations disrupt binding to protein A. The mutations for FcyR receptor silencing (AAS) and the knobs-into-holes mutations are underlined in the sequences below.Table 1. Amino Acid Sequence of BGCB491EXAMPLE 2: A Phase 1, First-in-Human, Dose Escalation Study of BGCB491, a Trispecific Antibody, in Participants with Relapsed or Refractory Multiple Myeloma - study design

[0245] This is a Phase 1, first-in-human, open-label, multicenter, dose-escalation study conducted in 2 parts: Part 1 (Dose Escalation) and Part 2 (Dose Expansion).The study consists of a Screening Period (up to 28 days before first dose of study drug) and a Treatment Period, and a Posttreatment Follow-up Period (up to 16 weeks).Primary objective(s)

[0246] The primary objective for Part 1 (Dose Escalation) is to identify the recommendedPhase 2 dose(s) (RP2D[s]) and schedule(s) to be safe for BGCB491.

[0247] The primary objective for Part 2 (Dose Expansion) is to characterize the safety and tolerability of BGCB491 at the RP2D(s) selected and in disease subgroups (eg, prior BCMA / GPRC5D-directed therapy, extramedullary disease [EMD], AL amyloidosis); as of September 2024 (e.g. prior BCMA / GPRC5D-directed therapy, EMD, earlier lines of therapy etc).Secondary objectives• To characterize the pharmacokinetics (PK) of BGCB491,• To assess the immunogenicity of BGCB491, and• To evaluate the preliminary anticancer activity of BGCB491 in participants with relapsed or refractory MM or previously treated AL amyloidosis.Primary Endpoints

[0248] Part 1 (Dose Escalation): Frequency and type of DLTs; incidence and severity of AEs.

[0249] Part 2 (Dose Expansion): Frequency and severity of AEs and assessment of laboratory values.Secondary Endpoints• Serum concentrations and PK parameters of BGCB491• Presence of antidrug antibodies to BGCB491• Response as defined by IMWG 2016 response criteria.• Duration of response (DOR) and time to response (TTR) where response is defined by IMWG 2016 criteria.• Response as defined by International Amyloidosis Consensus Criteria• DOR and TTR where response is defined by International Amyloidosis Consensus CriteriaExploratory Endpoints• To explore relationships among PK, PD, AE profiles, and preliminary anticancer activity• To investigate predictive biomarkers of response or resistance to BGCB491• To investigate the immunoregulatory activity of BGCB491• To evaluate levels of soluble BCMA• To evaluate antitumor activity of BGCB491 by assessment of MRD negativity status in participants with MM• AL amyloidosis cohort only: to evaluate organ response for kidney, heart, liver• To assess participant-reported changes in smell, taste and other oral-related sensation after study treatmentHypothesis

[0250] No formal hypothesis testing is being conducted. The study is evaluating the clinical hypothesis that BGCB491 can be safely administered at the selected RP2D(s) such that the dose-limiting toxicity (DLT) rate is 28% or lower.Study design

[0251] This is a Phase 1, first-in-human, open-label, multicenter, dose-escalation study being conducted in 2 parts: dose escalation (Part 1) and dose expansion (Part 2).

[0252] The study is enrolling participants with relapsed or refractory MM who have been treated with a proteasome inhibitor, an immunomodulatory drug (IMiD), and an anti-CD38- based therapy. As of September 2024, the study is enrolling participants with relapsed or refractory MM who have been treated with a proteasome inhibitor, IMiD agent, and an anti- CD38-based therapy for the treatment of MM for Part 1. For Part 2, the study may enroll the following:(A) participants with relapsed or refractory MM who have been treated with a proteasome inhibitor, IMiD agent, and an anti-CD38-based therapy for the treatment of MM; or(B) participants with relapsed or refractory MM who have received 1 to 3 prior line(s) of therapy, including a PI and lenalidomide; or(C) participants with relapsed or refractory MM who have received autologous BCMA- directed CAR-T within 2 to 5 months of first dose of study treatment. These participants must also have one of the following disease characteristics:1. Stage 3 by ISS, and / or2. High risk cytogenetics (del 17p, t(14; 16), t(4; 14), amplQ), and / or3. Presence of EMD prior to CAR-T administration.

[0253] An AL amyloidosis cohort is enrolling participants with previously treated systemic AL amyloidosis with at least 1 organ involvement, including those with Mayo Cardiac Stage <11 and Mayo Cardiac Stage <IIIa, in Part 2. The AL amyloidosis cohorts are enrolling participants with previously treated systemic AL amyloidosis who are not candidates for available AL amyloidosis therapy with established clinical benefit and with at least 1 organinvolvement, and those with Mayo Cardiac Stage <IIIa with left ventricular ejection fraction (LVEF) >45%.

[0254] The overall aim of the study is to evaluate the safety, pharmacokinetics, immunogenicity, and antitumor activity of BGCB491.

[0255] The study consists of a Screening Period, a Treatment Period, and a Posttreatment Follow-up Period.

[0256] Approximately up to 100 participants are being evaluated in Part 1. The number of participants being enrolled depends on the number of dose escalations needed to reach the RP2D(s), the number of participants enrolled at each dose level, and the frequency of DLT. Part 1 (Dose Escalation) is designed to determine one or more doses and schedules (for further study in Part 2) for BGCB491, generally by testing successively higher doses, beginning at a starting dose of 0.4 mg BGCB491. For each dose level, the assessment of safety, efficacy, PK, and PD is being conducted. The assessment of safety for a given cohort includes review of the adverse events for the participants in that cohort and assessment of the proportion of participants in the cohort that experience a DLT. For expansion into Part 2, at least 6 participants for a given dose regimen must be studied in the DLT Evaluable Analysis Set with <28% experiencing a DLT at that dose and schedule. Multiple dose levels / schedules are being enrolled in parallel.

[0257] In Part 2, approximately 40 participants (as of September 2024, 20 participants) are being evaluated at each of the RP2Ds selected for study and in disease subgroups (eg, prior BCMA / GPRC5D-directed therapy, EMD, AL amyloidosis); as of September 2024 (e.g. prior BCMA / GPRC5D-directed therapy, EMD, earlier lines of therapy etc) may be evaluated. The objective of a cohort in Part 2 is to further characterize the safety, tolerability, PK, and PD of as well as preliminarily evaluate the efficacy of a dose and schedule of BGCB491 for participants with relapsed or refractory MM or previously treated AL amyloidosis. During Part 2, for each RP2D and in disease subgroups (eg, prior BCMA / GPRC5D-directed therapy, EMD, AL amyloidosis); as of September 2024 (e.g. prior BCMA / GPRC5D-directed therapy, EMD, earlier lines of therapy etc), safety data are being evaluated after every 10 participants complete the DLT Evaluation Period or discontinue earlier. Cumulative safety, efficacy, PK, PD, and other clinical data from a cohort are being evaluated. If it is determined that the dose and schedule being studied in that cohort may have an unfavorable balance of benefit and risk in that cohort, enrollment to that cohort may be stopped. A new expansion cohort may thenbe initiated with a lower RP2D or different dosing schedule based on all available safety, clinical activity, PK, and pharmacodynamic data.Study duration

[0258] BGCB491 is being initially administered at a starting dose of 0.4 mg SC Q2W. Step- up dose(s) may be explored to mitigate the occurrence of cytokine-mediated toxicities.Participants are continuing to receive study drug until disease progression (according to IMWG 2016 criteria for participants with MM) or hematologic progression (according to International Amyloidosis Consensus Criteria for participants with AL amyloidosis), unacceptable toxicity, withdrawal of consent, start of subsequent anticancer therapy, or end of study. The duration of study treatment and study treatment administration schedule may change based on emerging safety, pharmacokinetic, and biomarker data.Study dosing schedule / RegimenTreatment dose schedules:

[0259] Q2W dosing: As of September 2024, “Q2W” means that the treatment dose is administered once every 2 weeks (+ / - 2 days). There must be at least 12 days and no more than 16 days between each full treatment dose administration.

[0260] Q4W dosing: As of September 2024, “Q4W” means that there must be at least 24 days and no more than 35 days between each full treatment dose administration.

[0261] Q8W dosing: As of September 2024, “Q8W” means that there must be at least 48 days and no more than 63 days between each full treatment dose administration.Study participant population

[0262] Adult participants >18 years of age with measurable relapsed or refractory MM who have been treated with a proteasome inhibitor, an IMiD agent, and an anti-CD38-based therapy.

[0263] As of September 2024, the study is enrolling participants with relapsed or refractory MM who have been treated with a proteasome inhibitor, IMiD agent, and an anti-CD38- based therapy for the treatment of MM for Part 1. For Part 2, the study may enroll the following:(A) participants with relapsed or refractory MM who have been treated with a proteasome inhibitor, IMiD agent, and an anti-CD38-based therapy for the treatment of MM; or(B) participants with relapsed or refractory MM who have received 1 to 3 prior line(s) of therapy, including a PI and lenalidomide; or(C) participants with relapsed or refractory MM who have received autologous BCMA- directed CAR-T within 2 to 5 months of first dose of study treatment. These participants must also have one of the following disease characteristics:1. Stage 3 by ISS, and / or2. High risk cytogenetics (del 17p, t(14; 16), t(4; 14), amplQ), and / or3. Presence of EMD prior to CAR-T administration.

[0264] For the AL amyloidosis cohort in Part 2, previously treated, adult participants >18 years of age with at least 1 organ involvement, including those with Mayo Cardiac Stage <11 and Mayo Cardiac Stage <IIIa. The AL amyloidosis cohorts are enrolling participants with previously treated systemic AL amyloidosis who are not candidates for available AL amyloidosis therapy with established clinical benefit and with at least 1 organ involvement, and those with Mayo Cardiac Stage <IIIa with left ventricular ejection fraction (LVEF) >45%.Inclusion criteria for Participants with Relapsed or Refractory Multiple Myeloma

[0265] Each participant must satisfy all of the following criteria to be enrolled in the study:• Age o >18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.• Type of Participant and Disease Characteristic o Participant must have documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria. o Participant must have relapsed or refractory disease and have been treated with a proteasome inhibitor, IMiD agent, and an anti-CD38-based therapy for the treatment of MM.Participant must have measurable disease at screening as defined by at least one of the following: serum monoclonal protein (M-protein) level >0.5 g / dL; or urine M-protein level >200 mg / 24 hours; or serum Ig free light chain (FLC) >10 mg / dL and abnormal serum Ig kappa lambda FLC ratio. For participants without measurable disease in the serum, urine, or involved FLC, presence of 1 or more focus of EMD which meets the following criteria: extramedullary plasmacytoma not contiguous with a bone lesion, at least 1 lesion >2 cm (at its greatest dimension) diameter on whole body PET-CT (or whole body MRI approved by sponsor), and not previously radiated. As of September 2024, Part 2(C) participants are not required to have measurable disease. Participant must have clinical laboratory values meeting the following criteria prior to treatment: i) Hemoglobin level >8 g / dL (>5 mmol / L) (without prior RBC transfusion within 7 days prior to the laboratory test; recombinant human erythropoietin use is permitted) ii) Platelet count >50xl09 / L (without transfusion support in the 7 days prior to the laboratory test) iii) Absolute neutrophil count (ANC) >1.0* 109 / L (without use of G-CSF or GM-CSF within the 7 days prior to the date of the laboratory test or 14 days for pegylated G-CSF) iv) Alanine aminotransferase (ALT) <3 times the upper limit of normal (ULN) v) Aspartate aminotransferase (AST) <3 times ULN vi) Creatinine clearance: estimated glomerular filtration rate (eGFR) of >30 mL / min based upon Modified Diet in Renal Disease formula calculation vii) Total bilirubin <1.5 times ULN (isolated total bilirubin >1.5x ULN with conjugated [direct] bilirubin <ULN is allowed for those participants with known Gilbert’s syndrome) viii) Corrected serum calcium for albumin 14 mg / dL (<3.5 mmol / L) or free ionized calcium <6.5 mg / dL (<1.6 mmol / L)o Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. An ECOG performance status of 0 means that the participant is fully active, able to carry on all pre-disease performance without restriction; an ECOG performance status of 1 means that the participant is restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light housework, office work).• Sex and Contraceptive / Barrier Requirements o A female participant of childbearing potential must have a negative highly sensitive pregnancy test (e.g. serum P-hCG test) at screening and a negative urine or serum pregnancy test within 72 hours before the start of study treatment administration and must agree to further serum or urine pregnancy tests during the study. o A female participant must be: i) Not of childbearing potential, or ii) Of childbearing potential and practicing at least 1 highly effective method of contraception and agrees to remain on a highly effective method while receiving study drug and until 6 months after last dose. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study drug. o A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment as anticancer treatments may impair fertility. o A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 3 months after receiving the last dose of study treatment. If partner is a female person of childbearing potential, the male participant must use condom (with or without spermicide) and the partner must also be practicing a highly effective method of contraception. A male participant who is vasectomizedmust still use a condom (with or without spermicide), but the partner is not required to use contraception. o A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 3 months after receiving the last dose of study drug. Male participants should consider preservation of sperm prior to study treatment as anticancer treatments may impair fertility.• Informed consent o The participant must sign an informed consent form (ICF) (or their legally acceptable representative must sign) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study. o The participant must be willing and able to adhere to the lifestyle restrictions specified in the study protocol.Inclusion criteria for Participants with Previously Treated AL Amyloidosis

[0266] Each participant must satisfy all of the following criteria to be enrolled in the study:• Age o >18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.• Type of Participant and Disease Characteristic o Initial histopathological diagnosis of amyloidosis based on detection by IHC and polarizing light microscopy of green bi-refringent material in congo red- stained tissue specimens (in an organ other than bone marrow) or characteristic electron microscopy appearance. o Considerations for specific populations where other types of amyloidosis may be encountered: For male participants 70 years of age or older who have cardiac involvement only and participants of African descent (Black participants), confirmatory amyloid typing (IHC, mass spectrometry, immunoelectron microscopy) of AL amyloid in a tissue biopsy is recommended to rule out other types of amyloidosis such as age-related amyloidosis or hereditary amyloidosis (ATTR mutation).Measurable disease at screening defined by at least one of the following: Serum involved free light chain (iFLC) >50 mg / L or difference between involved and uninvolved free light chains (dFLC) >50 mg / L; serum M- protein >0.5 g / dL. Participant received at least 3 cycles of 1 prior line of therapy or a total of at least 2 cycles of 2 or more prior lines of therapy for AL amyloidosis with 1 of the following hematologic responses: i) Refractory disease, defined as failure to achieve partial response (PR) or better; ii) Suboptimal hematologic response, defined as failure to achieve very good partial response (VGPR); iii) VGPR with persistent organ dysfunction or deteriorating organ functions; iv) Relapsed disease, defined as hematologic progression per the International Society of Amyloidosis criteria (Palladini 2012a; Palladini 2021). Participant must have one or more organs impacted by systemic AL amyloidosis: i) Heart - echocardiogram (ECHO): mean wall thickness >12mm, no other cardiac cause or an elevated NT -proBNP (>332 ng / L) in the absence of renal failure (defined as chronic kidney disease stage 5 (GFR<15) or requirement for dialysis) or atrial fibrillation ii) Kidney - 24-hour urine protein >0.5 g / day, predominantly albumin iii) Liver - Total liver span >15 cm in the absence of heart failure or alkaline phosphatase >1.5 times institutional upper limit of normal iv) Gastrointestinal Tract - direct biopsy verification with symptoms v) Lung - Direct biopsy verification with symptoms, interstitial radiographic pattern. Participant must have LVEF >45%. Participant must have pretreatment serum albumin >2.5 g / dL. Participant must have clinical laboratory values meeting the following criteria prior to treatment:i) Hemoglobin level >8 g / dL (>5 mmol / L) (without prior RBC transfusion within 7 days prior to the laboratory test; recombinant human erythropoietin use is permitted) ii) Platelet count >50xl09 / L (without transfusion support in the 7 days prior to the laboratory test) iii) ANC > 1.0* 109 / L (without use of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM- CSF) within the 7 days prior to the date of the laboratory test or 14 days for pegylated G-CSF) iv) ALT <3 times ULN v) AST <3 times ULN vi) Creatinine clearance: estimated glomerular filtration rate (eGFR) of >30 mL / min based upon Modified Diet in Renal Disease formula calculation vii) Total bilirubin <1.5 times ULN (isolated total bilirubin >1.5x ULN with conjugated [direct] bilirubin <ULN is allowed for those participants with known Gilbert’s syndrome) viii) Corrected serum calcium for albumin <14 mg / dL (<3.5 mmol / L) or free ionized calcium <6.5 mg / dL (<1.6 mmol / L) o Participant must have an ECOG performance status of 0 or 1.• Sex and Contraceptive / Barrier Requirements o A female participant of childbearing potential must have a negative highly sensitive pregnancy test (e.g. serum P-hCG test) at screening and a negative urine or serum pregnancy test within 72 hours before the start of study treatment administration and must agree to further serum or urine pregnancy tests during the study. o A female participant must be: i) Not of childbearing potential, or ii) Of childbearing potential and practicing at least 1 highly effective method of contraception and agrees to remain on a highly effective method while receiving study drug and until 6 months after last dose. The investigator should evaluate the potential for contraceptive methodfailure (eg, noncompliance, recently initiated) in relationship to the first dose of study drug. o A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment as anticancer treatments may impair fertility. o A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 3 months after receiving the last dose of study treatment. If partner is a female person of childbearing potential, the male participant must use condom (with or without spermicide) and the partner must also be practicing a highly effective method of contraception. A male participant who is vasectomized must still use a condom (with or without spermicide), but the partner is not required to use contraception. o A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 3 months after receiving the last dose of study drug. Male participants should consider preservation of sperm prior to study treatment as anticancer treatments may impair fertility.• Informed consent o The participant must sign an ICF (or their legally acceptable representative must sign) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study. o The participant must be willing and able to adhere to the lifestyle restrictions specified in the study protocol.Exclusion criteria for Participants with Relapsed or Refractory Multiple Myeloma

[0267] Any potential participant who meets any of the following criteria are excluded from participating in the study:• Medical Conditions:Central nervous system involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, whole brain MRI and lumbar cytology are required during screening. Active plasma cell leukemia, Waldenstrom’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary light chain amyloidosis. Pulmonary compromise requiring supplemental oxygen used to maintain adequate oxygenation. Any serious underlying medical conditions, such as: i) Evidence of active viral, bacterial, or systemic fungal infection requiring ongoing antiviral, antibacterial, or antifungal treatment. ii) Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before start of study treatment (exception: Participants with vitiligo, type I diabetes, and prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing are eligible regardless of when these conditions were diagnosed). iii) Disabling psychiatric conditions, substance abuse (eg, alcohol or drug abuse), severe dementia, or altered mental status. iv) Any other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site, to understand the informed consent, or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being of the participant) or that could prevent, limit, or confound the protocol- specified assessments. Have prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s). History of stroke or seizure within 6 months prior to the first dose of study treatment. History of any of the following cardiac conditions:i) New York Heart Association stage III or IV congestive heart failure. ii) Myocardial infarction, unstable angina, or coronary artery bypass graft <6 months prior to enrollment. iii) History of clinically significant ventricular arrhythmia or unexplained syncope not believed to be vasovagal in nature or due to dehydration. iv) History of severe nonischemic cardiomyopathy. v) Screening 12-lead triplicate ECG showing an average baseline QTcF interval of >470 msec. o Known allergies, hypersensitivity, or intolerance to excipients of BGCB491.• Prior / Concomitant Therapy or Clinical Study Experience: o Prior antitumor therapy as follows, in the specified time frame prior to the first dose of study treatment: i) Targeted therapy, epigenetic therapy, mAb treatment, or treatment with an investigational drug or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less. ii) Gene-modified adoptive cell therapy (eg, CAR modified T cells, natural killer cells) within 90 days. As of September 2024, this does not apply to Part 2(C) participants. iii) Prior treatment with CD3 -redirecting therapy within 21 days prior to first dose of study treatment (Note: Prior exposure to BCMA or GPRC5D targeting agents may be allowed after discussion with the sponsor). As of September 2024, this does not apply to Part 2(B) or Part 2(C) participants. Additionally, as of November 2024, the exclusion criteria have been clarified to specify that participants must not have received autologous stem cell transplant, CAR-T therapy, or anti-CD38 monoclonal antibody if these treatments are eligible, available, and accessible to the participant. iv) Conventional chemotherapy within 21 days. v) PI therapy within 14 days. vi) Immunomodulatory agent therapy within 7 days.vii) Radiotherapy within 14 days. However, if palliative focal radiation was used, the participant is eligible irrespective of the end date of radiotherapy. o Received a cumulative dose of corticosteroids equivalent to >140 mg of prednisone within the 14-day period before the start of study treatment administration. o Nonhematologic toxicity from prior anticancer therapy that has not resolved to baseline level or to less than or equal to Grade 1 (except alopecia, tissue post- RT fibrosis [any grade] or peripheral neuropathy <3). o Stem cell transplantation: i) Allogeneic stem cell transplant within 6 months before the start of study treatment administration. Participants who received an allogeneic transplant must be off all immunosuppressive medications for >42 days without signs of graft-versus-host disease. ii) Received an autologous stem cell transplant <12 weeks before the start of study treatment administration. o Trauma or major surgery (eg, requiring general anesthesia) within 2 weeks, or participant will not have fully recovered from surgery, or participant has surgery planned during the time he or she is expected to participate in the study. Participants with planned surgical procedures to be conducted under local anesthesia may participate. o Pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study drug. As of September 2024, female participants who are assessed by investigator as possibly in the early pregnancy despite the negative pregnancy test are also excluded. o Plans to father a child while enrolled in this study or within 3 months after the last dose of study drug.• Diagnostic assessments: o Known history of HIV infection. o Active hepatitis B infection according to local laboratory range or other clinically active liver disease.o Active hepatitis C infection as measured by positive HCV RNA testing. Participants with a history of Hepatitis C virus antibody positivity must undergo HCV RNA testing. o Participant has received a live attenuated vaccine within 4 weeks before the first dose of study treatment.• Weight: o Participant has a body weight <40 kg at screening or at the time of their first administration of study drug.• Additional Prior / Concomitant Therapy or Clinical Study Experience: o As of September 2024, for Part 2(B) participants, had prior CD3 -redirecting therapy. o As of September 2024, for Part 2(C) participants, had progressive disease or refractory disease per IMWG after CAR-T administration.Exclusion criteria for Participants with Previously treated AL AmyloidosisAny potential participant who meets any of the following criteria is excluded from participating in the study:• Medical conditions: o Central nervous system involvement or clinical signs of meningeal involvement of AL amyloidosis. If either is suspected, whole brain MRI and lumbar cytology are required during screening. o Any form of non-AL amyloidosis, including but not limited to ATTR amyloidosis. o Previous or current diagnosis of symptomatic multiple myeloma per IMWG criteria. o Active plasma cell leukemia, Waldenstrom’s macroglobulinemia, or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes). o Pulmonary compromise requiring supplemental oxygen used to maintain adequate oxygenation. o Any serious underlying medical conditions, such as:i) Evidence of active viral, bacterial, or systemic fungal infection requiring ongoing antiviral, antibacterial, or antifungal treatment. ii) Active autoimmune disease requiring systemic immunosuppressive therapy within 6 months before start of study treatment (exception: participants with vitiligo, type I diabetes, and prior autoimmune thyroiditis that is currently euthyroid based on clinical symptoms and laboratory testing are eligible regardless of when these conditions were diagnosed). iii) Disabling psychiatric conditions, substance abuse (eg, alcohol or drug abuse), severe dementia, or altered mental status. iv) Any other issue that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site, to understand the informed consent, or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being of the participant) or that could prevent, limit, or confound the protocol- specified assessments. Have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is likely to interfere with any study endpoints of safety or the efficacy of the study treatment(s). History of stroke or seizure within 6 months prior to the first dose of study treatment. Previous or current diagnosis of symptomatic multiple myeloma, including the presence of lytic bone disease, plasmacytomas, >60% plasma cells in the bone marrow, or hypercalcemia. Evidence of significant cardiovascular conditions as specified below: i) NT-ProBNP >8500 ng / L. ii) New York Heart Association (NYHA) classification IIIB or IV heart failure. iii) Heart failure that in the opinion of the investigator is on the basis of ischemic heart disease (eg, prior myocardial infarction with documented history of cardiac enzyme elevation and ECG changes) oruncorrected valvular disease and not primarily due to AL amyloid cardiomyopathy. iv) For participant with congestive heart failure, cardiovascular-related hospitalizations within 4 weeks prior to enrollment. v) Inpatient admission to a hospital for unstable angina or myocardial infarction within the last 6 months prior to first dose or percutaneous cardiac intervention with recent stent within 6 months or coronary artery bypass grafting within 6 months. vi) Participant with a history of sustained ventricular tachycardia or aborted ventricular fibrillation or with a history of atrioventricular nodal or sinoatrial (SA) nodal dysfunction for which a pacemaker / implantable cardioverter defibrillator (ICD) is indicated but not placed (Participant who do have a pacemaker / ICD are allowed on study). vii) Screening 12-lead electrocardiogram (ECG) showing a baseline QT interval corrected by Fridericia’s formula (QTcF) >500 msec. Participant who have a pacemaker may be included regardless of calculated QTcF interval. viii) Supine systolic blood pressure <100 mmHg, or symptomatic orthostatic hypotension, defined as a decrease in systolic blood pressure upon standing of >20 mmHg despite medical management (eg, midodrine, fludrocorti sones) in the absence of volume depletion. o Macroglossia that impairs swallowing difficulty. o Known allergies, hypersensitivity, or intolerance to excipients of BGCB491.• Prior / Concomitant Therapy or Clinical Study Experience o Prior antitumor therapy as follows, in the specified time frame prior to the first dose of study treatment: i) Targeted therapy, epigenetic therapy, mAb treatment, or treatment with an investigational drug or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less. ii) Gene-modified adoptive cell therapy (eg, CAR-modified T cells, natural killer cells) within 90 days.iii) Prior treatment with CD3 -redirecting therapy within 21 days prior to first dose of study treatment (note: Prior exposure to BCMA or GPRC5D targeting agents may be allowed after discussion with the sponsor). iv) Conventional chemotherapy within 21 days. v) PI therapy within 14 days. vi) Immunomodulatory agent therapy within 7 days. vii) Radiotherapy within 14 days. However, if palliative focal radiation was used, the participant is eligible irrespective of the end date of radiotherapy. Received a cumulative dose of corticosteroids equivalent to >140 mg of prednisone within the 14-day period before the start of study treatment administration. Nonhematologic toxicity from prior anticancer therapy that has not resolved to baseline level or to less than or equal to Grade 1 (except alopecia, tissue post- RT fibrosis [any grade] or peripheral neuropathy <3). Stem cell transplantation: i) Allogeneic stem cell transplant within 6 months before the start of study treatment administration. Participants who received an allogeneic transplant must be off all immunosuppressive medications for >42 days without signs of graft-versus-host disease. ii) Received an autologous stem cell transplant <12 weeks before the start of study treatment administration. Trauma or major surgery (eg, requiring general anesthesia) within 2 weeks, or participant will not have fully recovered from surgery, or participant has surgery planned during the time he or she is expected to participate in the study. Participants with planned surgical procedures to be conducted under local anesthesia may participate. Pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study drug. As of September 2024, female participants who are assessed by investigator as possibly in the early pregnancy despite the negative pregnancy test are also excluded.o Plans to father a child while enrolled in this study or within 3 months after the last dose of study drug.• Diagnostic assessments: o Known history of HIV infection. o Active hepatitis B infection according to local laboratory range or other clinically active liver disease. o Active hepatitis C infection as measured by positive HCV RNA testing. Participants with a history of Hepatitis C virus antibody positivity must undergo HCV RNA testing. o Participant has received a live attenuated vaccine within 4 weeks before the first dose of study treatment.• Weight: o Participant has a body weight <40 kg at screening or at the time of their first administration of study drug.Efficacy evaluations

[0268] Efficacy assessments for MM are being conducted per the IMWG 2016 criteria and for AL amyloidosis are being conducted per the International Amyloidosis Consensus criteria. As of September 2024, for participants in Part 2, patient-reported outcomes (PROs) may be assessed.Pharmacokinetic and immunogeneticity evaluations

[0269] Blood samples are being collected from all participants for the measurement of serum concentrations of BGCB491 for pharmacokinetic (PK) analyses. An exploratory population PK-based approach may also be applied for BGCB491. The detection and characterization of antibodies to BGCB491 are being performed using validated assay methods to enable interpretation of the antidrug antibody data.Pharmacodynamic and immunogenicity evaluations

[0270] Bone marrow aspirates and whole blood are being collected from participants. Screening bone marrow aspirate samples are being used to characterize the clonal plasmacells and their immune microenvironment and identify predictive biomarkers of response by gene expression profiling. Bone marrow and whole blood are being evaluated for immune infiltration and markers of immune-cell activation and / or exhaustion as well as BCMA and GPRC5D expression and immune checkpoint ligands such as PD-L1. Using next-generation sequencing, bone marrow aspirate is being assessed for minimal residual disease. Serum cytokine profiling is being performed at various timepoints during the study.Safety evaluations

[0271] The safety of BGCB491 is being assessed by physical examinations, ECOG performance status, clinical laboratory tests, vital signs, and adverse event (AE) monitoring. The severity of AEs are being assessed using NCI-CTCAE Version 5.0, except for grading of cytokine-release syndrome and neurologic / psychiatric AEs that meet the criteria for immune effector cell-associated neurotoxicity syndrome, which are being assessed based on the ASTCT guidelines. Concomitant medication use is being recorded.EXAMPLE 3: A Phase 1, First-in-Human, Dose Escalation Study of BGCB491, a Trispecific Antibody, in Participants with Relapsed or Refractory Multiple Myeloma- pharmacokinetics and product metabolism

[0272] Preliminary PK data are available from 18 participants with RRMM. Participants were administered BGCB491 subcutaneously (SC) at target doses ranging from 0.4 to 80 mg biweekly (Q2W) or every 4 weeks (Q4W) after the first target dose treatment, with or without step-up dose(s). All step-up doses were administered 2-4 days before the treatment dose.

[0273] The dosing cohorts were as follows:• Cohort 1 : 0.4 mg of BGCB491 SC Q2W without a step-up dose.• Cohort 2: 1.2 mg of BGCB491 SC Q2W without a step-up dose.• Cohort 3: 3.6 mg of BGCB491 SC Q2W without a step-up dose.• Cohort 4: 10 mg of BGCB491 SC Q2W without a step-up dose.• Cohort 5: 10 mg of BGCB491 SC Q2W, with a 3.6 mg step-up dose.• Cohort 6: 30 mg of BGCB491 SC Q2W, with a 5 mg step-up dose.• Cohort 7: 40 mg of BGCB491 SC Q4W, with a 5 mg step-up dose.• Cohort 8: 80 mg of BGCB491 SC Q4W, with a 5 mg step-up dose.

[0274] Mean PK concentrations from each treatment group is shown in Figure 2. The mean serum concentration of BGCB491 increased following the first target dose SC administration at all dose levels. Mean values for Cmax and AUCT of BGCB491 increased with increasing dose levels. Concentrations of BGCB491 accumulated after multiple doses with Q2W dosing.

[0275] The preliminary PK data following the first SC treatment dose are presented in Table 2 below.Table 2: Preliminary PK data following the first SC treatment dose in MM subjects

[0276] The above preliminary PK data relating to 0.4 mg to 80 mg doses of BGCB491 give confidence that greater doses than the doses administered to cohorts 1-8 will provide high serum concentration of BGCB491 over an extended time period, thereby indicating that greater and / or less frequent doses of BGCB491 may be administered.EXAMPLE 4: A Phase 1, First-in-Human, Dose Escalation Study of BGCB491, a Trispecific Antibody, in Participants with Relapsed or Refractory Multiple Myeloma- efficacy and pharmacodynamics

[0277] As of 13th December 2023, data were available for 36 participants (21 participants were not evaluable) who received at least one dose of BGCB491 and had at least one posttreatment disease assessment or discontinued study for any reason. Best overall response was assessed by the investigator.

[0278] The 57 participants in the participant analysis set were from 12 dosing cohorts:• Cohort 1 : 0.4 mg of BGCB491 SC Q2W without a step-up dose.• Cohort 2: 1.2 mg of BGCB491 SC Q2W without a step-up dose.• Cohort 3: 3.6 mg of BGCB491 SC Q2W without a step-up dose.• Cohort 4: 10 mg of BGCB491 SC Q2W without a step-up dose.• Cohort 5: 10 mg of BGCB491 SC Q2W, with a 3.6 mg step-up dose.• Cohort 6: 30 mg of BGCB491 SC Q2W, with a 5 mg step-up dose.• Cohort 7: 40 mg of BGCB491 SC Q4W, with a 5 mg step-up dose.• Cohort 8: 80 mg of BGCB491 SC Q4W, with a 5 mg step-up dose.• Cohort 9: 120 mg of BGCB491 SC Q4W, with a 5 mg step-up dose.• Cohort 10: 50 mg of BGCB491 SC Q4W, with a 5 mg step-up dose.• Cohort 11 : 100 mg of BGCB491 SC Q4W, with a 5 mg step-up dose.• Cohort 12: 300 mg of BGCB491 SC Q4W, with a 5 mg step-up dose.

[0279] Cohorts 1-8 have the same dosing schedule as cohorts 1-8 of Example 3. All step-up doses were administered 2-4 days prior to the treatment dose.

[0280] As of 24th June 2024, data were available for 68 subjects who received at least one dose of BGCB491 and had at least one post-treatment disease assessment or discontinued study for any reason. Best overall response was assessed by the investigators.

[0281] The 68 subjects as of the clinical cutoff of 24th June 2024 were from 13 dosing cohorts. Cohorts 1-12 have the same dosing schedule as Cohorts 1-12 mentioned above (in Example 4).

[0282] Cohort 13: 300 mg of BGCB491 SC Q4W, with a first step up dose of 5 mg and a second step up dose of 100 mg. The first step-up dose was administered 2-4 days prior to thesecond step-up dose, and the second step-up dose was administered 2-4 days prior to the treatment dose.

[0283] As of 21st November 2024, data were available for 133 subjects who received at least one dose of BGCB491 and had at least one post-treatment disease assessment or discontinued study for any reason. Best overall response was assessed by the investigators.

[0284] The 133 subjects as of the clinical cutoff of 21st November 2024 were from 24 dosing cohorts. Cohorts 1-13 have the same dosing schedule as Cohorts 1-13 mentioned above (in Example 4). No data for cohort 19 are available at the 21st November 2024 cutoff.

[0285] Cohort 14: 50 mg of BGCB491 SC Q4W, with a step up dose of 2.5 mg. The step-up dose was administered 2-4 days prior to the treatment dose.

[0286] Cohort 15: 50 mg of BGCB491 SC Q4W, with a step up dose of 5 mg. The step-up dose was administered 6-8 days prior to the treatment dose.

[0287] Cohort 16: 3 X 20 mg of BGCB491 SC Q2W, followed by 20 mg of BGCB491 SC Q4W, starting with dose 4.

[0288] Cohort 17: 3 X 20 mg of BGCB491 SC Q2W, with a step up dose of 5 mg, followed by 20 mg of BGCB491 SC Q4W, starting with dose 4. The step-up dose was administered 2- 4 days prior to the first treatment dose.

[0289] Cohort 18: 100 mg of BGCB491 SC Q4W, with a step up dose of 5 mg. The step-up dose was administered 6-8 days prior to the treatment dose.

[0290] Cohort 19: 100 mg of BGCB491 SC Q4W, with a step up dose of 5 mg. The step-up dose was administered 6-8 days prior to the treatment dose. The subject is an outpatient.

[0291] Cohort 20: 4 X 200 mg of BGCB491 SC Q4W, with a step up dose of 5 mg, followed by 100 mg of BGCB491 SC Q4W, starting with dose 5. The step-up dose was administered 6-8 days prior to the first 200mg treatment dose. [ 5 (SU) — > 200 Q4W x 4 doses — 100 Q4W starting with Dose 5]

[0292] Cohort 21 : 4 X 200 mg of BGCB491 SC Q4W, with a step up dose of 5 mg, followed by 100 mg of BGCB491 SC Q4W, starting with dose 5. The step-up dose was administered 2-4 days prior to the first 200mg treatment dose. Together with the step up dose 8 mg / kg tocilizumab were administered intravenously. [5 (SU) given with prophylactic toci — > 200 Q4W x 4 doses —> 100 Q4W starting with Dose 5]

[0293] Cohort 22: 100 mg of BGCB491 SC Q4W, with a step up dose of 5 mg. The step-up dose was administered 2-4 days prior to the treatment dose. Together with the step up dose 8 mg / kg tocilizumab were administered intravenously. The subject is an outpatient.

[0294] Cohort 23: 100 mg of BGCB491 SC Q8W, with a step up dose of 5 mg. The step-up dose was administered 2-4 days prior to the treatment dose. Together with the step up dose optionally 8 mg / kg tocilizumab were administered intravenously.

[0295] Cohort 24: 2 X 200 mg of BGCB491 SC Q8W, with a step up dose of 5 mg, followed by 100 mg of BGCB491 SC Q8W, starting with dose 3. The step-up dose was administered 2-4 days prior to the first 200mg treatment dose. Together with the step up dose optionally 8 mg / kg tocilizumab were administered intravenously. [5 (SU) — > 200 Q8W x 2 doses — 100 Q8W starting with Dose 3]

[0296] Treatment response was assessed according to the IMWG 2016 criteria. These criteria are summarised in Table 3 below:Table 3: International Myeloma Working Group 2016 Response CriterianoCR=complete response; FLC=free light chain; Ig=immunoglobulin; MR=minimal response; PC=plasma cell; PR=partial response; sCR=stringent complete response; SPD=sum of the products of the maximal perpendicular diameters of measured lesions; VGPR=very good partial response. Results

[0297] As of 13th December 2023, based on IMWG 2016 criteria, treatment response (MR or better) was observed in 22 participants across all dose levels (see “clinical benefit” row). An overall response was observed in 21 participants across all dose levels. A very good partial response or better was observed in 13 participants, and a complete response or better was observed in 5 participants. Table 4a presents treatment response by dose level (including both confirmed and unconfirmed) as of 13th December 2023.Table 4a: Summary of Overall Best Response based on Investigator Assessment; Safety Analysis Set (as of 13th December 2023)CI = confidence interval.Best overall response includes confirmed and unconfirmed responses.

[0298] As of 24th June 2024, based on IMWG 2016 criteria, treatment response (MR or better) was observed in 49 subjects (see “clinical benefit” row of Table 4d) in the Response Evaluable Set. The Response Evaluable Set comprises subjects who received at least one treatment dose of BGCB491 and had at least one adequate post-baseline disease assessment. Additionally, the Response Evaluable Set also comprises subjects who received at least one treatment dose of BGCB491 who died, progressed or discontinued all study drugs for any reason, if they received at least one adequate post-baseline disease assessment or not.

[0299] An overall response was observed in 48 subjects across all dose levels. A very good partial response or better was observed in 41 subjects, and a complete response or better was observed in 16 subjects. Tables 4b, 4c and 4d present treatment response by dose level as of 24th June 2024. For these tables, best overall response includes confirmed and unconfirmed responses.Table 4b: Summary of Overall Best Response based on Investigator Assessment - Cohorts 1- 5 (as of 24th June 2024)Table 4c: Summary of Overall Best Response based on Investigator Assessment - Cohorts 6- 10 (as of 24th June 2024)Table 4d: Summary of Overall Best Response based on Investigator Assessment - Cohorts11-13 and totals (as of 24th June 2024)

[0300] As of the data cut-off on November 21, 2024, treatment response was evaluated in133 response-evaluable subjects who received at least one dose of BGCB491 and had at least one adequate post-baseline disease assessment or met predefined criteria for evaluability, using the International Myeloma Working Group (IMWG) 2016 criteria. An overall response (partial response or better) was observed in 94 of 133 subjects, including 41 subjects who achieved a stringent complete response (sCR) or complete response (CR) and 80 subjects who achieved a very good partial response (VGPR) or better. The highest proportion ofoverall responders was observed in the 100 mg dose cohorts, where 23 / 26 of subjects achieved an overall response. Clinical benefit, defined as overall response plus minimal response (MR), was observed in the same 94 subjects, as no minimal responses were reported.

[0301] At the 100 mg dose (Cohorts 11 and 18), most subjects achieved an overall response.Similarly, in the 300 mg dose cohorts (Cohorts 12 and 13), most subjects achieved an overall response. At the 50 mg dose (Cohorts 10, 14, and 15), over half of subjects achieved an overall response.Table 4e: Summary of Overall Best Response based on Investigator Assessment; Response Evaluable Analysis SetESC 0.4 ESC 1.2 ESC 3.6 ESC 10 ESC ESC 5 / 30 ESC 5 / 40 ESC 5 / 80 mg mg mg mg 3.6 / 10 mg mg mg mgCohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 Cohort 7 Cohort 8Analysis set: Response evaluable 1 1 3 3 2 3 3 4Response categoryStringent complete response (sCR) 0 0 1 0 1 0 1 2Unconfirmed 0 0 0 0 0 0 0 0Complete response (CR) 0 0 0 0 0 0 1 0Unconfirmed 0 0 0 0 0 0 0 0Very good partial response(VGPR) 0 0 1 1 1 1 0 0Unconfirmed 0 0 0 0 1 0 0 0Partial response (PR) 0 0 0 0 0 1 0 0Unconfirmed 0 0 0 0 0 0 0 0Minimal response (MR) 0 0 0 0 0 0 0 0Stable disease (SD) 1 1 0 2 0 0 1 1Progressive disease (PD) 0 0 1 0 0 1 0 1Not evaluable (NE) 0 0 0 0 0 0 0 0Missing 0 0 0 0 0 0 0 0Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Data cut-off date:21NOV2024.Table 4f: Summary of Overall Best Response based on Investigator Assessment; Response Evaluable Analysis SetESC ESC NOESC ESC 5 / 50 ESC ESC 5 / 100 / 300 ESC ESC 5 / 50 SU / 20 mg5 / 120 mg mg 5 / 100 mg 5 / 300 mg mg Cohort 2.5 / 50 mg mg Cohort Q2WCohort 9 Cohort 10 Cohort 11 Cohort 12 13 Cohort 14 15 Cohort 16Analysis set: Response evaluable 4 14 17 10 3 2 10 2Response categoiyStringent complete response (sCR) 2 1 8 3 2 0 1 0Unconfirmed 1 0 0 0 0 0 1 0Complete response(CR) 0 4 1 3 0 0 1 0Unconfirmed 0 0 0 0 0 0 0 0Veiy good partial response (VGPR) 1 3 5 2 1 1 2 1Unconfirmed 0 0 0 0 0 0 0 0Partial response (PR) 0 1 0 0 0 1 2 0Unconfirmed 0 1 0 0 0 0 0 0Minimal response (MR) 0 0 0 0 0 0 0 0Stable disease (SD) 0 4 3 2 0 0 2 1Progressive disease(PD) 1 1 0 0 0 0 1 0Not evaluable (NE) 0 0 0 0 0 0 0 0Missing 0 0 0 0 0 0 1 0Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Table 4g: Summary of Overall Best Response based on Investigator Assessment; Response Evaluable Analysis SetESC 5SU / 20 ESC ESCQ2W / 20 ESC 5 / 100 ESC 5 / 200 5 / 200 / 100 ESC 5 / 100 ESC 5 / 100 5 / 200 / 100Q4W mg mg Q4W mg Q4W mg Q4W mg Q4W mg Q8W mg Q8WCohort 17 Cohort 18 Cohort 20 Cohort 21 Cohort 22 Cohort 23 Cohort 24Analysis set: Response evaluable 3 9 10 10 10 4 5Response categoryStringent complete response (sCR) 2 2 1 0 1 0 0Unconfirmed 0 0 0 0 0 0 0Complete response(CR) 0 2 1 0 0 0 0Unconfirmed 0 0 1 0 0 0 0Very good partial response (VGPR) 0 4 5 6 3 0 1Unconfirmed 0 0 0 0 2 0 0Partial response (PR) 0 1 1 1 4 1 1Unconfirmed 0 0 0 0 1 1 1Minimal response (MR) 0 0 0 0 0 0 0Stable disease (SD) 1 0 2 3 1 3 3Progressive disease(PD) 0 0 0 0 0 0 0Not evaluable (NE) 0 0 0 0 1 0 0Missing 0 0 0 0 0 0 0Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Table 4h: Summary of Overall Best Response based on Investigator Assessment; Response Evaluable Analysis SetResponse categoryStringent complete response (sCR) 7 2 2 10 1 5 28Unconfirmed 1 1 0 0 0 0 2Table 4h: Summary of Overall Best Response based on Investigator Assessment; Response Evaluable Analysis Set300 mg50 mg 20 mg 100 mg 200 mg Q4WCohort 1 to Cohort 10, Cohort 16 Cohort 11 Cohort 20 Cohort 129 14 & 15 & 17 & 18 & 21 & 13 TotalComplete response(CR) 1 5 0 3 1 3 13Unconfirmed 0 0 0 0 1 0 1Very good partial response (VGPR) 5 6 1 9 11 3 39Unconfirmed 1 0 0 0 0 0 3Partial response (PR) 1 4 0 1 2 0 14Unconfirmed 0 1 0 0 0 0 4Minimal response (MR) 0 0 0 0 0 0 0Stable disease (SD) 6 6 2 3 5 2 31Progressive disease(PD) 4 2 0 0 0 0 6Not evaluable (NE) 0 0 0 0 0 0 1Missing 0 1 0 0 0 0 1Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Overall Best Response in particular patient groupsBCMA or GPRC Directed Therapy Exposed patients

[0302] As of 24th June 2024, data were available for 24 subjects in the ResponseEvaluable Set who were exposed to prior BCMA or GPRC directed therapy. Best overall response was assessed by the investigators. The 24 subjects as of 24th June 2024 were from the 13 dosing cohorts (Cohorts 1-13 which are described above in Example 4).

[0303] As of 24th June 2024, based on IMWG 2016 criteria, treatment response (MR or better) was observed in 14 subjects (see “clinical benefit” row of Table 5c) who were exposed to BCMA or GPRC directed therapy in the Response Evaluable Set. An overall response was observed in 13 subjects. A very good partial response or better was observedin 10 subjects, and a complete response or better was observed in 6 subjects. Tables 5a-5c present treatment response by dose level as of 24th June 2024. For these tables, best overall response includes confirmed and unconfirmed responses. Table 5a: Summary of Overall Best Response based on Investigator Assessment - BCMA or GPRC Directed Therapy Exposed - Cohorts 1 -5 (as of 24th June 2024)Table 5b: Summary of Overall Best Response based on Investigator Assessment - BCMA or GPRC Directed Therapy Exposed - Cohorts 6-10 (as of 24th June 2024)Table 5c: Summary of Overall Best Response based on Investigator Assessment - BCMA or GPRC Directed Therapy Exposed - Cohorts 11-13 and totals (as of 24th June 2024)5

[0304] As of the data cut-off on November 21, 2024, treatment response was evaluated for28 response-evaluable subjects previously exposed to BCMA or GPRC-directed therapy, with responses assessed by investigators using IMWG 2016 criteria. An overall response (partial response or better) was observed in 15 of 28 subjects (53.6%), including 7 subjects (25%) who achieved a stringent complete response (sCR) or complete response (CR) and10 12 subjects (42.9%) who achieved a very good partial response (VGPR) or better. Clinicalbenefit, defined as overall response plus minimal response (MR), was observed in the same 15 subjects, as no minimal responses were reported.55.6% of subjects in Cohorts 1 to 9 achieved an overall response, with 44.4% achieving VGPR or better and 22.2% achieving sCR or CR. In the 50 mg dose cohorts (Cohorts 10, 14, and 15), 60% of subjects achieved an overall response, with 40% achieving VGPR or better and 40% achieving sCR or CR. Similarly, in the 100 mg dose cohorts (Cohorts 11 and 18), 40% of subjects achieved an overall response, with 40% achieving VGPR or better and 20% achieving sCR or CR. The 300 mg dose cohorts (Cohorts 12 and 13) showed comparable efficacy, with 60% of subjects achieving an overall response, 60% achieving VGPR or better, and 40% achieving sCRorCR.Table 5d: Summary of Overall Best Response based on Investigator Assessment; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis SetESCESC 0.4 ESC 1.2 ESC 3.6 ESC 10 3.6 / 10 ESC 5 / 30 ESC 5 / 40 ESC 5 / 80 mg mg mg mg mg mg mg mgCohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 Cohort 7 Cohort 8Analysis set: ResponseEvaluable 0 0 1 2 1 1 0 3Response categoiyStringent complete response (sCR) 0 0 0 0 0 0 0 1Unconfirmed 0 0 0 0 0 0 0 0Complete response (CR) 0 0 0 0 0 0 0 0Veiy good partial response (VGPR) 0 0 0 1 0 0 0Unconfirmed 0 0 0 0 1 0 0 0Partial response (PR) 0 0 0 0 0 1 0 0Unconfirmed 0 0 0 0 0 0 0 0Minimal response (MR) 0 0 0 0 0 0 0 0Stable disease (SD) 0 0 0 1 0 0 0 1Progressive disease(PD) 0 0 1 0 0 0 0 1Not evaluable (NE) 0 0 0 0 0 0 0 0Overall response (sCR+CR+VGPR+PR) 0 0 0 1 1 1 0 1Clinical benefit (Overall response + MR) 0 0 0 1 1 1 0 1VGPR or better (sCR + CR + VGPR) 0 0 0 1 1 0 0 1CR or better (sCR +CR) 0 0 0 0 0 0 0 1Table 5d: Summary of Overall Best Response based on Investigator Assessment; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis SetNote: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Data cut-off date:21NOV2024.Table 5e: Summary of Overall Best Response based on Investigator Assessment; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis SetESC ESC NOESC ESC 5 / 50 ESC ESC 5 / 100 / 300 ESC ESC 5 / 50 SU / 20 mg5 / 120 mg mg 5 / 100 mg 5 / 300 mg mg Cohort 2.5 / 50 mg mg Cohort Q2WCohort 9 Cohort 10 Cohort 11 Cohort 12 13 Cohort 14 15 Cohort 16Analysis set: ResponseEvaluable 1 5 5 5 0 0 0 0Response categoiyStringent complete response (sCR) 1 1 0 1 0 0 0 0Unconfirmed 1 0 0 0 0 0 0 0Complete response(CR) 0 1 1 1 0 0 0 0Veiy good partial response (VGPR) 0 0 1 1 0 0 0 0Unconfirmed 0 0 0 0 0 0 0 0Partial response (PR) 0 1 0 0 0 0 0 0Unconfirmed 0 1 0 0 0 0 0 0Minimal response (MR) 0 0 0 0 0 0 0 0Stable disease (SD) 0 1 3 2 0 0 0 0Progressive disease(PD) 0 1 0 0 0 0 0 0Not evaluable (NE) 0 0 0 0 0 0 0 0Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Table 5f: Summary of Overall Best Response based on Investigator Assessment; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis SetESC 5SU / 20 ESC ESCQ2W / 20 ESC 5 / 100 ESC 5 / 200 5 / 200 / 100 ESC 5 / 100 ESC 5 / 100 5 / 200 / 100Q4W mg mg Q4W mg Q4W mg Q4W mg Q4W mg Q8W mg Q8WCohort 17 Cohort 18 Cohort 20 Cohort 21 Cohort 22 Cohort 23 Cohort 24Analysis set: ResponseEvaluable 0 0 0 0 4 0 0Response categoryStringent complete response (sCR) 0 0 0 0 0 0 0Unconfirmed 0 0 0 0 0 0 0Complete response(CR) 0 0 0 0 0 0 0Very good partial response (VGPR) 0 0 0 0 1 0 0Unconfirmed 0 0 0 0 0 0 0Partial response (PR) 0 0 0 0 1 0 0Unconfirmed 0 0 0 0 1 0 0Minimal response (MR) 0 0 0 0 0 0 0Stable disease (SD) 0 0 0 0 1 0 0Progressive disease(PD) 0 0 0 0 0 0 0Not evaluable (NE) 0 0 0 0 1 0 0Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response. Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Table 5g Summary of Overall Best Response based on Investigator Assessment; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis Set300 mg50 mg 20 mg 100 mg 200 mg Q4W Cohort 1 to Cohort 10, Cohort 16 Cohort 11 Cohort 20 Cohort 129 14 & 15 & 17 & 18 & 21 & 13 TotalAnalysis set: ResponseEvaluable 9 5 0 5 0 5 28Response categoryStringent complete response (sCR) 2 1 0 0 0 1 4Unconfirmed 1 0 0 0 0 0 1Table 5g Summary of Overall Best Response based on Investigator Assessment; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis Set300 mg50 mg 20 mg 100 mg 200 mg Q4WCohort 1 to Cohort 10, Cohort 16 Cohort 11 Cohort 20 Cohort 129 14 & 15 & 17 & 18 & 21 & 13 TotalComplete response(CR) 0 1 0 1 0 1 3Very good partial response (VGPR) 2 0 0 1 0 1 5Unconfirmed 1 0 0 0 0 0 1Partial response (PR) 1 1 0 0 0 0 3Unconfirmed 0 1 0 0 0 0 2Minimal response (MR) 0 0 0 0 0 0 0Stable disease (SD) 2 1 0 3 0 2 9Progressive disease(PD) 2 1 0 0 0 0 3Not evaluable (NE) 0 0 0 0 0 0 1Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.BCMA or GPRC Directed Therapy Exposed patients: Exposed to Prior CAR-T Subgroup

[0305] As of 24th June 2024, data were available for 8 subjects in the Response Evaluable Set who were exposed to prior BCMA or GPRC directed therapy which was a prior CAR-T therapy.Best overall response was assessed by the investigators. The 8 subjects as of 24th June 2024 were from some of the 13 dosing cohorts (Cohorts 1-13 which are described above in Example 4).

[0306] As of 24th June 2024, based on IMWG 2016 criteria, treatment response (MR or better) was observed in 7 subjects (see “clinical benefit” row of Table 6c) who were exposed to prior CAR-T therapy in the Response Evaluable Set. An overall response was observed in 7 subjects. A very good partial response or better was observed in 5 subjects, and a complete response or better was observed in 4 subjects. Tables 6a-6c present treatment response by dose level as of24th June 2024. For these tables, best overall response includes confirmed and unconfirmed responses.Table 6a: Summary of Overall Best Response based on Investigator Assessment - Exposed to Prior CAR-T subgroup - Cohorts 1-5 (as of 24th June 2024)Table 6b: Summary of Overall Best Response based on Investigator Assessment - Exposed toPrior CAR-T subgroup - Cohorts 6-10 (as of 24th June 2024)Table 6c: Summary of Overall Best Response based on Investigator Assessment - Exposed toPrior CAR-T subgroup - Cohorts 11-13 and totals (as of 24th June 2024)

[0307] As of the data cut-off on November 21, 2024, treatment response was evaluated for 11 response-evaluable subjects previously exposed to CAR-T therapy targeting BCMA or GPRC.Responses were assessed using the International Myeloma Working Group (IMWG) 2016 criteria. An overall response (partial response or better) was observed in 9 of 11 subjects, including 6 subjects who achieved a very good partial response (VGPR) or better, and 4 subjects who achieved a complete response (CR) or stringent complete response (sCR). Clinical benefit, defined as overall response plus minimal response (MR), was observed in the same 9 subjects.

[0308] Among 3 response-evaluable subjects in Cohorts 1 to 9, 2 achieved an overall response, with 1 achieving VGPR or better. In the 50 mg dose cohorts (Cohorts 10, 14, and 15), both response-evaluable subjects achieved an overall response, with 1 achieving VGPR or better. At the 100 mg dose (Cohorts 11 and 18), the single response-evaluable subject achieved both an overall response and VGPR or better. In the 300 mg dose cohorts (Cohorts 12 and 13), both response-evaluable subjects achieved an overall response, with both achieving VGPR or better, including 1 achieving sCR.Table 6d: Summary of Overall Best Response based on Investigator Assessment by Exposed to Prior CAR-T Subgroup; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis SetESC 0.4 ESC 1.2 ESC 3.6 ESC 10 ESC ESC 5 / 30 ESC 5 / 40 ESC 5 / 80 mg mg mg Cohort mg Cohort 3.6 / 10 mg mg Cohort mg Cohort mg CohortCohort 1 Cohort 2 3 4 Cohort 5 6 7 8Analysis set: BCMA or GPRC Directed Therapy Exposed in Response Evaluable 0 0 1 2 1 1 0 3Subgroup: Exposed toPrior CAR-T 0 0 0 2 0 1 0 0Response categoiyStringent complete response (sCR) 0 0 0 0 0 0 0 0Complete response(CR) 0 0 0 0 0 0 0 0Veiy good partial response (VGPR) 0 0 0 1 0 0 0 0Partial response (PR) 0 0 0 0 0 1 0 0Unconfirmed 0 0 0 0 0 0 0 0Minimal response (MR) 0 0 0 0 0 0 0 0Stable disease (SD) 0 0 0 1 0 0 0 0Progressive disease(PD) 0 0 0 0 0 0 0 0Not evaluable (NE) 0 0 0 0 0 0 0 0Overall response(sCR+CR+VGPR+PR) 0 0 0 1 0 1 0 0Clinical benefit (Overall response + MR) 0 0 0 1 0 1 0 0Table 6d: Summary of Overall Best Response based on Investigator Assessment by Exposed to Prior CAR-T Subgroup; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis SetNote: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Data cut-off date:21NOV2024.Table 6e: Summary of Overall Best Response based on Investigator Assessment by Exposed to Prior CAR-T Subgroup; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis SetESC ESC NOESC ESC 5 / 50 ESC ESC 5 / 100 / 300 ESC ESC 5 / 50 SU / 20 mg5 / 120 mg mg 5 / 100 mg 5 / 300 mg mg Cohort 2.5 / 50 mg mg Cohort Q2WCohort 9 Cohort 10 Cohort 11 Cohort 12 13 Cohort 14 15 Cohort 16Analysis set: BCMA orGPRC Directed TherapyExposed in ResponseEvaluable 1 5 5 5 0 0 0 0Subgroup: Exposed toPrior CAR-T 0 2 1 2 0 0 0 0Response categoiyStringent complete response (sCR) 0 1 0 1 0 0 0 0Complete response(CR) 0 0 1 1 0 0 0 0Veiy good partial response (VGPR) 0 0 0 0 0 0 0 0Partial response (PR) 0 1 0 0 0 0 0 0Unconfirmed 0 1 0 0 0 0 0 0Minimal response (MR) 0 0 0 0 0 0 0 0Stable disease (SD) 0 0 0 0 0 0 0 0Progressive disease(PD) 0 0 0 0 0 0 0 0Not evaluable (NE) 0 0 0 0 0 0 0 0Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Table 6f: Summary of Overall Best Response based on Investigator Assessment by Exposed to Prior CAR-T Subgroup; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis SetESC 5SU / 20 ESC ESCQ2W / 20 ESC 5 / 100 ESC 5 / 200 5 / 200 / 100 ESC 5 / 100 ESC 5 / 100 5 / 200 / 100Q4W mg mg Q4W mg Q4W mg Q4W mg Q4W mg Q8W mg Q8WCohort 17 Cohort 18 Cohort 20 Cohort 21 Cohort 22 Cohort 23 Cohort 24Analysis set: BCMA orGPRC Directed TherapyExposed in ResponseEvaluable 0 0 0 0 4 0 0Subgroup: Exposed toPrior CAR-T 0 0 0 0 3 0 0Response categoryStringent complete response (sCR) 0 0 0 0 0 0 0Complete response(CR) 0 0 0 0 0 0 0Very good partial response (VGPR) 0 0 0 0 1 0 0Partial response (PR) 0 0 0 0 1 0 0Unconfirmed 0 0 0 0 1 0 0Minimal response (MR) 0 0 0 0 0 0 0Stable disease (SD) 0 0 0 0 1 0 0Progressive disease(PD) 0 0 0 0 0 0 0Not evaluable (NE) 0 0 0 0 0 0 0Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Table 6g: Summary of Overall Best Response based on Investigator Assessment by Exposed to Prior CAR-T Subgroup; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis Set300 mg50 mg 20 mg 100 mg 200 mg Q4WCohort 1 to Cohort 10, Cohort 16 Cohort 11 Cohort 20 Cohort 12 9 14 & 15 & 17 & 18 & 21 & 13 TotalAnalysis set: BCMA orGPRC Directed TherapyExposed in ResponseEvaluable 9 5 0 5 0 5 28Table 6g: Summary of Overall Best Response based on Investigator Assessment by Exposed to Prior CAR-T Subgroup; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis Set300 mg50 mg 20 mg 100 mg 200 mg Q4WCohort 1 to Cohort 10, Cohort 16 Cohort 11 Cohort 20 Cohort 129 14 & 15 & 17 & 18 & 21 & 13 TotalSubgroup: Exposed toPrior CAR-T 3 2 0 1 0 2 11Response categoryStringent complete response (sCR) 0 1 0 0 0 1 2Complete response(CR) 0 0 0 1 0 1 2Very good partial response (VGPR) 1 0 0 0 0 0 2Partial response (PR) 1 1 0 0 0 0 3Unconfirmed 0 1 0 0 0 0 2Minimal response (MR) 0 0 0 0 0 0 0Stable disease (SD) 1 0 0 0 0 0 2Progressive disease(PD) 0 0 0 0 0 0 0Not evaluable (NE) 0 0 0 0 0 0 0Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response. Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.BCMA or GPRC Directed Therapy Exposed patients: Exposed to Prior Bi-specific Antibodies Subgroup

[0309] As of 24th June 2024, data were available for 14 subjects in the Response Evaluable Set who were exposed to prior BCMA or GPRC directed therapy which was a prior bi-specific antibodies therapy. Best overall response was assessed by the investigators. The 14 subjects as of 24th June 2024 were from some of the 13 dosing cohorts (Cohorts 1-13 which are described above in Example 4).

[0310] As of 24th June 2024, based on IMWG 2016 criteria, treatment response (MR or better) was observed in 5 subjects (see “clinical benefit” row of Table 7c) who were exposed to prior bi-specific antibodies therapy in the Response Evaluable Set. An overall response was observed in 4 subjects. A very good partial response or better was observed in 3 subjects, and a complete response or better was observed in 1 subject. Tables 7a-7c present treatment response by dose level as of 24th June 2024. For these tables, best overall response includes confirmed and unconfirmed responses.Table 7a: Summary of Overall Best Response based on Investigator Assessment - Exposed to Prior Bi-specific antibodies subgroup - Cohorts 1-5 (as of 24th June 2024)Table 7b: Summary of Overall Best Response based on Investigator Assessment - Exposed toPrior Bi-specific antibodies subgroup - Cohorts 6-10 (as of 24th June 2024)Table 7c: Summary of Overall Best Response based on Investigator Assessment - Exposed toPrior Bi-specific antibodies subgroup - Cohorts 11-13 and totals (as of 24th June 2024)

[0311] As of the data cut-off on November 21, 2024, treatment response was evaluated for 16 response-evaluable subjects who had prior exposure to bi-specific antibodies therapy targeting BCMA or GPRC. Using the International Myeloma Working Group (IMWG) 2016 criteria, an overall response (partial response or better) was observed in 4 of 16 subjects, with 4 subjects achieving a very good partial response (VGPR) or better and 1 subject achieving a complete response (CR) or stringent complete response (sCR). Clinical benefit, defined as overall response plus minimal response (MR), was observed in the same 4 subjects.

[0312] Dose-level analysis showed varied responses across cohorts. Among 5 response- evaluable subjects in Cohorts 1 to 9, 2 achieved an overall response and VGPR or better, including 1 achieving sCR. In the 50 mg dose cohorts (Cohorts 10, 14, and 15), no subjects achieved an overall response or VGPR or better. At the 100 mg dose (Cohorts 11 and 18), 1 of 4 response-evaluable subjects achieved an overall response and VGPR or better. In the 300 mg dose cohorts (Cohorts 12 and 13), 1 of 3 response-evaluable subjects achieved an overall response and VGPR or better.Table 7d: Summary of Overall Best Response based on Investigator Assessment by Exposed to Prior Bi-specificAntibodies Subgroup; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis Set>ESC 0.4 ESC 1.2 ESC 3.6 ESC 10 ESC ESC 5 / 30 ESC 5 / 40 ESC 5 / 80 mg mg mg Cohort mg Cohort 3.6 / 10 mg mg Cohort mg Cohort mg CohortCohort 1 Cohort 2 3 4 Cohort 5 6 7 8Analysis set: BCMA orGPRC Directed TherapyExposed in ResponseEvaluable 0 0 1 2 1 1 0 3Subgroup: Exposed toPrior Bi-specificAntibodies 0 0 1 0 1 0 0 3Response categoryStringent complete response (sCR) 0 0 0 0 0 0 0 1Table 7d: Summary of Overall Best Response based on Investigator Assessment by Exposed to Prior Bi-specrfic Antibodies Subgroup; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis SetNote: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Data cut-off date:21NOV2024.Table 7e: Summary of Overall Best Response based on Investigator Assessment by Exposed to Prior Bi-specific Antibodies Subgroup; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis SetSubgroup: Exposed toPrior Bi-specificAntibodies 0 2 4 3 0 0 0 0Response categoiyStringent complete response (sCR) 0 0 0 0 0 0 0 0Complete response(CR) 0 0 0 0 0 0 0 0Veiy good partial response (VGPR) 0 0 1 1 0 0 0 0Unconfirmed 0 0 0 0 0 0 0 0Partial response (PR) 0 0 0 0 0 0 0 0Minimal response (MR) 0 0 0 0 0 0 0 0Stable disease (SD) 0 1 3 2 0 0 0 0Progressive disease(PD) 0 1 0 0 0 0 0 0Not evaluable (NE) 0 0 0 0 0 0 0 0Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Table 7e: Summary of Overall Best Response based on Investigator Assessment by Exposed to Prior Bi-specific Antibodies Subgroup; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis SetESC 5SU / 20 ESC ESCQ2W / 20 ESC 5 / 100 ESC 5 / 200 5 / 200 / 100 ESC 5 / 100 ESC 5 / 100 5 / 200 / 100Q4W mg mg Q4W mg Q4W mg Q4W mg Q4W mg Q8W mg Q8WCohort 17 Cohort 18 Cohort 20 Cohort 21 Cohort 22 Cohort 23 Cohort 24Analysis set: BCMA orGPRC Directed TherapyExposed in ResponseEvaluable 0 0 0 0 4 0 0Subgroup: Exposed toPrior Bi-specificAntibodies 0 0 0 0 2 0 0Response categoiyStringent complete response (sCR) 0 0 0 0 0 0 0Complete response(CR) 0 0 0 0 0 0 0Veiy good partial response (VGPR) 0 0 0 0 0 0 0Unconfirmed 0 0 0 0 0 0 0Partial response (PR) 0 0 0 0 0 0 0Minimal response (MR) 0 0 0 0 0 0 0Stable disease (SD) 0 0 0 0 1 0 0Progressive disease(PD) 0 0 0 0 0 0 0Not evaluable (NE) 0 0 0 0 1 0 0Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Table 7f: Summary of Overall Best Response based on Investigator Assessment by Exposed to Prior Bi-specific Antibodies Subgroup; BCMA or GPRC Directed Therapy Exposed in Response Evaluable Analysis SetSubgroup: Exposed toPrior Bi-specificAntibodies 5 2 0 4 0 3 16Response categoryStringent complete response (sCR) 1 0 0 0 0 0 1Complete response(CR) 0 0 0 0 0 0 0Very good partial response (VGPR) 1 0 0 1 0 1 3Unconfirmed 1 0 0 0 0 0 1Partial response (PR) 0 0 0 0 0 0 0Minimal response (MR) 0 0 0 0 0 0 0Stable disease (SD) 1 1 0 3 0 2 8Progressive disease(PD) 2 1 0 0 0 0 3Not evaluable (NE) 0 0 0 0 0 0 1Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.BCMA or GPRC Directed Therapy Naive patients

[0313] As of 24th June 2024, data were available for 44 subjects in the Response Evaluable Set who were naive to prior BCMA or GPRC directed therapy. Best overall response was assessed by the investigators. The 44 subjects as of 24th June 2024 were from the 13 dosing cohorts (Cohorts 1-13 which are described above in Example 4).

[0314] As of 24th June 2024, based on IMWG 2016 criteria, treatment response (MR or better) was observed in 35 subjects (see “clinical benefit” row of Table 8c) who were naive to BCMA or GPRC directed therapy in the Response Evaluable Set. An overall response was observed in 35 subjects. A very good partial response or better was observed in 31 subjects, and a complete response or better was observed in 10 subjects. Tables 8a-8c present treatment response by dose level as of 24th June 2024. For these tables, best overall response includes confirmed and unconfirmed responses.Table 8a: Summary of Overall Best Response based on Investigator Assessment - BCMA or GPRC Directed Therapy Naive - Cohorts 1-5 (as of 24th June 2024)Table 8b: Summary of Overall Best Response based on Investigator Assessment - BCMA or GPRC Directed Therapy Naive - Cohorts 6-10 (as of 24th June 2024)Table 8c: Summary of Overall Best Response based on Investigator Assessment - BCMA orGPRC Directed Therapy Naive - Cohorts 11-13 and totals (as of 24th June 2024)

[0315] As of the data cut-off on November 21, 2024, treatment response was evaluated for 105 BCMA or GPRC- directed therapy naive subjects using the International Myeloma Working Group (IMWG) 2016 criteria. An overall response (partial response or better) was observed in 79 of 105 subjects, with 68 subjects achieving a very good partial response (VGPR) or better and 34 subjects achieving a complete response (CR) or stringent complete response (sCR). Clinical benefit, defined as overall response plus minimal response (MR), was achieved in the same 79 subjects.

[0316] At the 100 mg dose, all 21 response-evaluable subjects achieved an overall response. Similarly, at the 300 mg dose, all 8 response-evaluable subjects achieved VGPR or better.>Table 8d: Summary of Overall Best Response based on Investigator Assessment; BCMA or GPRC Directed Therapy Naive in Response Evaluable Analysis Set>ESC 0.4 ESC 1.2 ESC 3.6 ESC 10 ESC ESC 5 / 30 ESC 5 / 40 ESC 5 / 80 mg mg mg Cohort mg Cohort 3.6 / 10 mg mg Cohort mg Cohort mg CohortCohort 1 Cohort 2 3 4 Cohort 5 6 7 8Analysis set: ResponseEvaluable 1 1 2 1 1 2 3 1Response categoiyStringent complete response (sCR) 0 0 1 0 1 0 1 1Unconfirmed 0 0 0 0 0 0 0 0Complete response(CR) 0 0 0 0 0 0 1 0Unconfirmed 0 0 0 0 0 0 0 0Veiy good partial response (VGPR) 0 0 1 0 0 1 0 0Unconfirmed 0 0 0 0 0 0 0 0Partial response (PR) 0 0 0 0 0 0 0 0Unconfirmed 0 0 0 0 0 0 0 0Minimal response (MR) 0 0 0 0 0 0 0 0Table 8d: Summary of Overall Best Response based on Investigator Assessment; BCMA or GPRC Directed Therapy Naive in Response Evaluable Analysis SetESC 0.4 ESC 1.2 ESC 3.6 ESC 10 ESC ESC 5 / 30 ESC 5 / 40 ESC 5 / 80 mg mg mg Cohort mg Cohort 3.6 / 10 mg mg Cohort mg Cohort mg CohortCohort 1 Cohort 2 3 4 Cohort 5 6 7 8Stable disease (SD) 1 1 0 1 0 0 1 0Progressive disease(PD) 0 0 0 0 0 1 0 0Not evaluable (NE) 0 0 0 0 0 0 0 0Missing 0 0 0 0 0 0 0 0Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Data cut-off date:21NOV2024.Table 8e: Summary of Overall Best Response based on Investigator Assessment; BCMA or GPRC Directed Therapy Naive in Response Evaluable Analysis SetESC ESC NOESC ESC 5 / 50 ESC ESC 5 / 100 / 300 ESC ESC 5 / 50 SU / 20 mg5 / 120 mg mg 5 / 100 mg 5 / 300 mg mg Cohort 2.5 / 50 mg mg Cohort Q2WCohort 9 Cohort 10 Cohort 11 Cohort 12 13 Cohort 14 15 Cohort 16Analysis set: ResponseEvaluable 3 9 12 5 3 2 10 2Response categoiyStringent complete response (sCR) 1 0 8 2 2 0 1 0Unconfirmed 0 0 0 0 0 0 1 0Complete response(CR) 0 3 0 2 0 0 1 0Unconfirmed 0 0 0 0 0 0 0 0Veiy good partial response (VGPR) 1 3 4 1 1 1 2 1Unconfirmed 0 0 0 0 0 0 0 0Partial response (PR) 0 0 0 0 0 1 2 0Unconfirmed 0 0 0 0 0 0 0 0Minimal response (MR) 0 0 0 0 0 0 0 0Stable disease (SD) 0 3 0 0 0 0 2 1Progressive disease(PD) 1 0 0 0 0 0 1 0Not evaluable (NE) 0 0 0 0 0 0 0 0Missing 0 0 0 0 0 0 1 0Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response.Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Table 8f: Summary of Overall Best Response based on Investigator Assessment; BCMA or GPRC Directed Therapy Naive in Response Evaluable Analysis SetESC 5SU / 20 ESC ESCQ2W / 20 ESC 5 / 100 ESC 5 / 200 5 / 200 / 100 ESC 5 / 100 ESC 5 / 100 5 / 200 / 100Q4W mg mg Q4W mg Q4W mg Q4W mg Q4W mg Q8W mg Q8WCohort 17 Cohort 18 Cohort 20 Cohort 21 Cohort 22 Cohort 23 Cohort 24Analysis set: ResponseEvaluable 3 9 10 10 6 4 5Response categoiyStringent complete response (sCR) 2 2 1 0 1 0 0Unconfirmed 0 0 0 0 0 0 0Complete response(CR) 0 2 1 0 0 0 0Unconfirmed 0 0 1 0 0 0 0Veiy good partial response (VGPR) 0 4 5 6 2 0 1Unconfirmed 0 0 0 0 2 0 0Partial response (PR) 0 1 1 1 3 1 1Unconfirmed 0 0 0 0 0 1 1Minimal response (MR) 0 0 0 0 0 0 0Stable disease (SD) 1 0 2 3 0 3 3Progressive disease(PD) 0 0 0 0 0 0 0Not evaluable (NE) 0 0 0 0 0 0 0Missing 0 0 0 0 0 0 0Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response. Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.Table 8g: Summary of Overall Best Response based on Investigator Assessment; BCMA or GPRC Directed Therapy Naive in Response Evaluable Analysis Set300 mg50 mg 20 mg 100 mg 200 mg Q4WCohort 1 to Cohort 10, Cohort 16 Cohort 11 Cohort 20 Cohort 129 14 & 15 & 17 & 18 & 21 & 13 TotalAnalysis set: ResponseEvaluable 15 21 5 21 20 8 105Response categoiyStringent complete response (sCR) 5 1 2 10 1 4 24Table 8g: Summary of Overall Best Response based on Investigator Assessment; BCMA or GPRC Directed Therapy Naive in Response Evaluable Analysis Set300 mg50 mg 20 mg 100 mg 200 mg Q4WCohort 1 to Cohort 10, Cohort 16 Cohort 11 Cohort 20 Cohort 129 14 & 15 & 17 & 18 & 21 & 13 TotalUnconfirmed 0 1 0 0 0 0 1Complete response(CR) 1 4 0 2 1 2 10Unconfirmed 0 0 0 0 1 0 1Very good partial response (VGPR) 3 6 1 8 11 2 34Unconfirmed 0 0 0 0 0 0 2Partial response (PR) 0 3 0 1 2 0 11Unconfirmed 0 0 0 0 0 0 2Minimal response (MR) 0 0 0 0 0 0 0Stable disease (SD) 4 5 2 0 5 0 22Progressive disease(PD) 2 1 0 0 0 0 3Not evaluable (NE) 0 0 0 0 0 0 0Missing 0 1 0 0 0 0 1Note: Response was assessed by investigators, based on International Myeloma Working Group consensus criteria for response. Percentages are calculated with the number of subjects in response evaluable analysis set as denominator.Note: Best overall response includes confirmed and unconfirmed responses.EXAMPLE 5: A Phase 1, First-in-Human, Dose Escalation Study of BGCB491, a Trispecific Antibody, in Participants with Relapsed or Refractory Multiple Myeloma - patient demographics and prior therapies

[0317] The demographics, prior therapies, and refractory status to prior therapies of 68 subjects with RRMM who were in the Safety Analysis Set, as of 24th June 2024, are summarized in Tables 9a-9c, 10a- 10c, and 1 la-11c below.

[0318] The 68 subjects in the Safety Analysis Set were from 13 dosing cohorts (Cohorts 1-13): • Cohort 1: 0.4 mg of BGCB491 SC Q2W without a step-up dose.• Cohort 2: 1.2 mg of BGCB491 SC Q2W without a step-up dose.• Cohort 3: 3.6 mg of BGCB491 SC Q2W without a step-up dose.• Cohort 4: 10 mg of BGCB491 SC Q2W without a step-up dose.• Cohort 5: 10 mg of BGCB491 SC Q2W, with a 3.6 mg step-up dose.• Cohort 6: 30 mg of BGCB491 SC Q2W, with a 5 mg step-up dose. • Cohort 7: 40 mg of BGCB491 SC Q4W, with a 5 mg step-up dose.• Cohort 8: 80 mg of BGCB491 SC Q4W, with a 5 mg step-up dose.• Cohort 9: 120 mg of BGCB491 SC Q4W, with a 5 mg step-up dose.• Cohort 10: 50 mg of BGCB491 SC Q4W, with a 5 mg step-up dose.• Cohort 11: 100 mg of BGCB491 SC Q4W, with a 5 mg step-up dose. • Cohort 12: 300 mg of BGCB491 SC Q4W, with a 5 mg step-up dose.• Cohort 13: 300 mg of BGCB491 SC Q4W, with a 5 mg (first) step-up dose and a 100 mg (second) step-up dose.

[0319] All step-up doses were administered 2-4 days prior to the treatment dose. Table 9a: Summary of Demographics - Cohorts 1-5 (as of 24th June 2024)Table 9b: Summary of Demographics - Cohorts 6-10 (as of 24th June 2024)Table 9c: Summary of Demographics - Cohorts 11-13 and totals (as of 24th June 2024)

[0320] As of the data cut-off on November 21, 2024, the Safety Analysis Set included 144 subjects with relapsed or refractory multiple myeloma (RRMM) across 24 dosing cohorts.

[0321] Baseline Eastern Cooperative Oncology Group (ECOG) performance scores were evenly distributed between 0 and 1.

[0322] Tables 9d-9g provide an overview of the baseline demographics and characteristics of the study population.Table 9d: Summary of Demographics and Baseline Characteristics; Safety Analysis SetESC 0.4 ESC 1.2 ESC 3.6 ESC 10 ESC ESC 5 / 30 ESC 5 / 40 ESC 5 / 80 mg Cohort mg Cohort mg Cohort mg Cohort 3.6 / 10 mg mg Cohort mg Cohort mg Cohort1 2 3 4 Cohort 5 6 7 8Analysis set: Safety 1 1 3 3 2 3 3 4Age, (years) N 1 1 3 3 2 3 3 4Mean(SD) 60.358.0 (-) 73.0 (-) 55.3 (7.64) 70.0 (8.54) 59.0 (0.00) 67.0 (7.21) (12.86) 62.3 (0.96)Median 58.0 73.0 57.0 71.0 59.0 69.0 55.0 62.5Range (58; 58) (73; 73) (47; 62) (61; 78) (59; 59) (59; 73) (51; 75) (61; 63)< 65 Years 1 0 3 1 2 1 2 4>= 65 Years 0 1 0 2 0 2 1 0Sex N 1 1 3 3 2 3 3 4Female 0 0 1 1 1 1 1 2Male 1 1 2 2 1 2 2 2Race N 1 1 3 3 2 3 3 4Asian 0 0 0 0 0 0 0 0Table 9d: Summary of Demographics and Baseline Characteristics; Safety Analysis SetESC 0.4 ESC 1.2 ESC 3.6 ESC 10 ESC ESC 5 / 30 ESC 5 / 40 ESC 5 / 80 mg Cohort mg Cohort mg Cohort mg Cohort 3.6 / 10 mg mg Cohort mg Cohort mg Cohort1 2 3 4 Cohort 5 6 7 8Black or African American 0 0 0 0 0 0 0 0White 1 1 2 3 1 3 3 4Multiple 0 0 0 0 0 0 0 0Not Reported 0 0 1 0 1 0 0 0Unknown 0 0 0 0 0 0 0 0Missing 0 0 0 0 0 0 0 0Ethnicity N 1 1 3 3 2 3 3 4Hispanic or Latino 0 0 0 0 0 1 1 0Not Hispanic or Latino 0 0 2 3 1 2 2 4Not reported 1 1 1 0 1 0 0 0Unknown 0 0 0 0 0 0 0 0Missing 0 0 0 0 0 0 0 0Weight, kg N 1 1 3 3 2 3 3 4Mean(SD) 73.40 64.00 76.40 72.10 67.07 70.6086.80 (-) 94.00 (-) (16.985) (19.487) (5.091) (7.908) (9.646) (16.236)Median 86.80 94.00 64.20 67.50 76.40 76.00 69.00 73.00Range (86.8; (94.0; (63.0; (43.0; (72.8; (63.0; (56.6; (49.9;86.8) 94.0) 93.0) 81.5) 80.0) 77.3) 75.6) 86.5)Height, cm N 1 1 3 3 2 3 3 4Mean(SD) 163.33 165.00 163.50 167.67 168.67 168.50184.00 (-) 180.00 (-) (7.095) (18.083) (16.263) (12.014) (14.012) (9.469)Median 184.00 180.00 162.00 163.00 163.50 167.00 168.00 168.50Range (184.0; (180.0; (157.0; (148.0; (152.0; (156.0; (155.0; (157.0;184.0) 180.0) 171.0) 184.0) 175.0) 180.0) 183.0) 180.0)Body surface area, m2N 1 1 3 3 2 3 3 4Mean(SD) 1.82 1.71 1.86 1.83 1.77 1.812.11 (-) 2.17 (-) (0.245) (0.358) (0.155) (0.120) (0.182) (0.256)Median 2.11 2.17 1.70 1.75 1.86 1.83 1.87 1.87Range (2.1; 2.1) (2.2; 2.2) (1.7; 2.1) (1.3; 2.0) (1.8; 2.0) (1.7; 1.9) (1.6; 1.9) (1.5; 2.0)Baseline ECOG score N 1 1 3 3 2 3 3 40 1 0 1 1 1 0 2 31 0 1 2 2 1 3 1 1Key: ECOG=Eastern Cooperative Oncology Group Note: N’s for each parameter reflect non-missing values. Data cut-off date:21NOV2024.Table 9e: Summary of Demographics and Baseline Characteristics; Safety Analysis SetESC ESC NOESC 5 / 120 ESC 5 / 50 ESC 5 / 100 ESC 5 / 300 5 / 100 / 300 ESC ESC 5 / 50 SU / 20 mg mg Cohort mg Cohort mg Cohort mg Cohort mg Cohort 2.5 / 50 mg mg Cohort Q2W9 10 11 12 13 Cohort 14 15 Cohort 16Analysis set: Safety 4 14 17 10 3 2 10 2Age, (years)N 4 14 17 10 3 2 10 2Mean(SD) 64.8 64.8 65.4(12.42) 64.9(8.79) (10.53) 63.8 (9.44) 60.0(8.66) 59.5 (3.54) (10.15) 65.5 (4.95)Median 66.5 65.5 68.0 60.0 55.0 59.5 64.0 65.5Range (50; 76) (49; 82) (43; 75) (54; 80) (55; 70) (57; 62) (44; 79) (62; 69)< 65 Years 2 6 7 6 2 2 5 1>=65 Years 2 8 10 4 1 0 5 1SexN 4 14 17 10 3 2 10 2Female 1 5 9 5 2 0 4 1Male 3 9 8 5 1 2 6 1Race N 4 14 17 10 3 2 10 2Asian 0 2 1 0 0 1 0 0Black or AfricanAmerican 1 3 0 0 0 0 2 0White 3 8 12 9 3 1 5 1Multiple 0 0 0 0 0 0 0 0Not Reported 0 1 4 1 0 0 3 1Unknown 0 0 0 0 0 0 0 0Missing 0 0 0 0 0 0 0 0EthnicityN 4 14 17 10 3 2 10 2Hispanic or Latino 1 0 1 0 0 0 1 0 Not Hispanic orLatino 1 12 8 8 3 2 7 1Not reported 1 2 5 0 0 0 2 1Unknown 1 0 3 2 0 0 0 0Missing 0 0 0 0 0 0 0 0Weight, kgN 4 14 17 10 3 2 10 2Mean(SD) 67.65 74.01 75.58 78.91 79.47 93.20 74.01 60.45(7.870) (14.677) (15.474) (16.641) (9.469) (2.546) (11.127) (6.293)Median 64.80 68.90 77.10 76.50 74.00 93.20 73.45 60.45Range (62.0; (56.0; (42.7; (49.9; (74.0; (91.4; (57.6; (56.0;79.0) 100.0) 96.0) 105.8) 90.4) 95.0) 94.0) 64.9)Height, cm N 4 14 17 10 3 2 10 2Mean(SD) 163.00 171.04 167.73 168.80 180.33 179.50 170.32 160.00(10.551) (9.332) (10.120) (7.193) (15.373) (2.121) (6.556) (14.142)Median 161.50 172.00 169.00 171.00 173.00 179.50 170.50 160.00Range (152.0; (149.0; (149.0; (157.0; (170.0; (178.0; (162.0; (150.0;177.0) 186.0) 190.0) 177.0) 198.0) 181.0) 186.0) 170.0)Table 9e: Summary of Demographics and Baseline Characteristics; Safety Analysis SetESC ESC NOESC 5 / 120 ESC 5 / 50 ESC 5 / 100 ESC 5 / 300 5 / 100 / 300 ESC ESC 5 / 50 SU / 20 mg mg Cohort mg Cohort mg Cohort mg Cohort mg Cohort 2.5 / 50 mg mg Cohort Q2W9 10 11 12 13 Cohort 14 15 Cohort 16Body surface area, m2N 4 14 17 10 3 2 10 2Mean (SD) 1.75 1.87 1.87 1.91 1.99 2.16 1.87 1.64(0.148) (0.225) (0.235) (0.206) (0.204) (0.017) (0.150) (0.158)Median 1.68 1.79 1.93 1.90 1.89 2.16 1.85 1.64Range (1.7; 2.0) (1.5; 2.3) (1.4; 2.2) (1.5; 2.2) (1.9; 2.2) (2.1; 2.2) (1.6; 2.1) (1.5; 1.8)Baseline ECOG scoreN 4 14 17 10 3 2 10 20 1 2 8 4 3 0 7 11 3 12 9 6 0 2 3 1Key: ECOG=Eastern Cooperative Oncology Group Note: N’s for each parameter reflect non-missing values.Table 9f: Summary of Demographics and Baseline Characteristics; Safety Analysis SetESC 5 SU / 20 ESC ESC Q2W / 20 ESC 5 / 100 ESC 5 / 200 5 / 200 / 100 ESC 5 / 100 ESC 5 / 100 5 / 200 / 100 Q4W mg mg Q4W mg Q4W mg Q4W mg Q4W mg Q8W mg Q8W Cohort 17 Cohort 18 Cohort 20 Cohort 21 Cohort 22 Cohort 23 Cohort 24Analysis set: Safety 3 9 11 10 10 10 9Age, (years)N 3 9 11 10 10 10 9Mean (SD) 57.7 (11.02) 61.1 (9.84) 66.3 (9.85) 65.4 (11.43) 70.5 (8.81) 69.9 (8.74) 57.8 (9.91) Median 57.0 63.0 66.0 66.5 71.5 72.0 57.0 Range (47; 69) (46; 73) (51; 80) (44; 78) (60; 87) (54; 82) (39; 73)< 65 Years 2 5 4 4 4 3 7>= 65 Years 1 4 7 6 6 7 2SexN 3 9 11 10 10 10 9Female 2 4 4 5 1 4 5Male 1 5 7 5 9 6 4RaceN 3 9 11 10 10 10 9Asian 0 0 1 0 0 0 0Black or AfricanAmerican 0 0 2 0 1 2 2White 2 7 8 7 8 6 4Multiple 0 2 0 0 0 0 0Not Reported 1 0 0 3 1 1 1Unknown 0 0 0 0 0 1 1Missing 0 0 0 0 0 0 1EthnicityN 3 9 11 10 10 10 9Hispanic or Latino 1 0 2 2 0 0 0Not Hispanic orLatino 2 8 9 7 9 8 5Not reported 0 1 0 1 1 1 2Unknown 0 0 0 0 0 1 1Missing 0 0 0 0 0 0 1Weight, kgN 3 9 11 10 10 10 9Mean (SD) 74.60 84.87 79.61 78.69 84.60 87.28 79.51 (7.454) (14.112) (15.761) (24.572) (21.288) (19.772) (14.408)Median 70.60 80.30 74.60 72.85 75.05 85.60 83.20Range (70.0; 83.2) (65.3; 104.4) (65.0; 112.0) (53.5; 142.3) (63.0; 123.6) (58.4; 123.0) (60.4; 96.0)Height, cmN 3 9 11 10 10 10 9Mean (SD) 169.67 168.72 171.94 172.42 176.17 175.34 170.69 (11.150) (12.882) (8.601) (8.263) (6.795) (12.666) (6.872)Median 174.00 167.00 174.00 175.65 174.00 180.25 170.20Range (157.0; (149.0; (157.0; (157.0; (166.0; (156.0; (163.0; 178.0) 186.0) 185.4) 182.0) 191.0) 188.0) 185.0)Table 9f: Summary of Demographics and Baseline Characteristics; Safety Analysis SetESC 5SU / 20 ESC ESCQ2W / 20 ESC 5 / 100 ESC 5 / 200 5 / 200 / 100 ESC 5 / 100 ESC 5 / 100 5 / 200 / 100Q4W mg mg Q4W mg Q4W mg Q4W mg Q4W mg Q8W mg Q8WCohort 17 Cohort 18 Cohort 20 Cohort 21 Cohort 22 Cohort 23 Cohort 24Body surface area, m2N 3 9 11 10 10 10 9Mean (SD) 1.87 (0.033) 1.99 (0.202) 1.94 (0.211) 1.93 (0.297) 2.02 (0.275) 2.05 (0.283) 1.94 (0.200)Median 1.87 1.99 1.96 1.90 1.93 2.03 1.98Range (1.8; 1.9) (1.7; 2.2) (1.7; 2.4) (1.5; 2.6) (1.7; 2.5) (1.6; 2.5) (1.7; 2.2)Baseline ECOG scoreN 3 9 11 10 10 10 90 1 4 6 7 4 6 31 2 5 5 3 6 4 6Key: ECOG=Eastern Cooperative Oncology GroupNote: N’s for each parameter reflect non-missing values.Table 9g: Summary of Demographics and Baseline Characteristics; Safety Analysis Set50 mg 20 mg 100 mg 200 mg 300 mgCohort 1 to Cohort 10, Cohort 16 & Cohort 11 & Cohort 20 & Q4W Cohort9 14 & 15 17 18 21 12 & 13 TotalAnalysis set: Safety 24 26 5 26 21 13 144Age, (years) N 24 26 5 26 21 13 144Mean (SD) 63.1 (8.66) 64.7 (8.95) 60.8 (9.23) 63.5 (10.25) 65.9 (10.37) 62.9 (9.06) 64.4 (9.63)Median 61.5 64.5 62.0 66.0 66.0 59.0 64.0Range (47; 78) (44; 82) (47; 69) (43; 75) (44; 80) (54; 80) (39; 87)< 65 Years 16 13 3 12 8 8 74>= 65 Years 8 13 2 14 13 5 70Sex N 24 26 5 26 21 13 144Female 8 9 3 13 9 7 59Male 16 17 ...

Claims

CLAIMS1. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or a trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of at least about 0.4 mg.

2. The method of claim 1, wherein the treatment dose is at least about 50 mg.

3. The method of claim 1 or claim 2, wherein the treatment dose is a flat dose.

4. The method of claim 1 or claim 3, wherein the treatment dose is about 0.4 mg, about 1.2 mg, about 3.6 mg, about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg, about 80 mg, about 100 mg, about 120 mg, about 200 mg, or about 300 mg.

5. The method of any one of claims 1-4, wherein the treatment dose is about 50 mg, about 100 mg or about 300 mg.

6. The method of claim 5, wherein the treatment dose is about 50 mg.

7. The method of claim 5, wherein the treatment dose is about 100 mg.

8. The method of claim 5, wherein the treatment dose is about 300 mg.

9. The method of any one of claims 1-4, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of about 200 mg per cycle for four cycles, followed by administration at a treatment dose of about 100 mg per cycle for subsequent cycles.

10. The method of any one of claims 1-4, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered at a treatment dose of about 200 mg per cycle for two cycles, followed by administration at a treatment dose of about 100 mg per cycle for subsequent cycles.

11. The method of any one of claims 1-10, wherein the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every four weeks.

12. The method of any one of claims 1-10, wherein the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every eight weeks.

13. The method of any one of claims 1-10, wherein the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every two weeks for three cycles, followed by administration once every four weeks for subsequent cycles.

14. The method of any one of claims 1-6 and 11, wherein the treatment dose is about 50 mg and wherein the treatment dose is administered once every four weeks.

15. The method of any one of claims 1-5, 7, and 11, wherein the treatment dose is about 100 mg and wherein the treatment dose is administered once every four weeks.

16. The method of any one of claims 1-5, 7, and 12, wherein the treatment dose is about 100 mg and wherein the treatment dose is administered once every eight weeks.

17. The method of any one of claims 1-5, 8 and 11, wherein the treatment dose is about 300 mg and wherein the treatment dose is administered once every four weeks.

18. The method of any one of claims 1, 3, 4 and 13, wherein the treatment dose is about 20 mg per cycle and wherein the treatment dose is administered once every two weeks for three cycles, followed by administration once every four weeks for subsequent cycles.

19. The method of any one of claims 1-4, 10, and 11, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every four weeks at a treatment dose of about 200 mg per cycle for four cycles, followed by administration once every four weeks at a treatment dose of about 100 mg per cycle for subsequent cycles.

20. The method of any one of claims 1-4, 10, and 12, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered once every eight weeks at a treatment dose of about 200 mg per cycle for two cycles, followed by administration once every eight weeks at a treatment dose of about 100 mg per cycle for subsequent cycles.21 . The method of any one of claims 1-8, 11, and 14-17, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.

22. The method of claim 21, wherein the first step-up dose is about 2.5 mg or about 5 mg.

23. The method of claim 22, wherein the first step-up dose is about 2.5 mg.

24. The method of claim 22, wherein the first step-up dose is about 5 mg.

25. The method of any one of claims 21-24, wherein the first step-up dose is subcutaneously administered about 2-8 days prior to the subcutaneous administration of the treatment dose.

26. The method of any one of claims 21-24, wherein the first step-up dose is subcutaneously administered about one week prior to the subcutaneous administration of the treatment dose.

27. The method of any one of claims 21-24, wherein the first step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the treatment dose.

28. The method of any one of claims 21-24, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose.

29. The method of any one of claims 21-22 and 24-25, wherein the first step-up dose is subcutaneously administered about 2-8 days prior to the subcutaneousadministration of the treatment dose, and wherein the first step-up dose is about 5 mg.

30. The method of any one of claims 21-22, 24 and 26, wherein the first step-up dose is subcutaneously administered about one week prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.

31. The method of any one of claims 21-22, 24 and 27, wherein the first step-up dose is subcutaneously administered about 6-8 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.

32. The method of any one of claims 21-23 and 28, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 2.5 mg.

33. The method of any one of claims 21-22, 24 and 28, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, and wherein the first step-up dose is about 5 mg.

34. The method of any one of claims 9-10, 13, and 18-20, wherein at least one step-up dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the first cycle.

35. The method of claim 34, wherein the first step-up dose is about 5 mg.

36. The method of claim 34 or claim 35, wherein the first step-up dose is subcutaneously administered about one week prior to the first cycle.

37. The method of claim 34 or claim 35, wherein the first step-up dose is subcutaneously administered about 6-8 days prior to the first cycle.

38. The method of claim 34 or claim 35, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the first cycle.

39. The method of any one of claims 1-8, 11-12, 14-17, and 21-33, wherein at least two step-up doses of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof are subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.

40. The method of claim 39, wherein the second step-up dose is greater than the first step-up dose.41 . The method of claim 39 or claim 40, wherein the first step-up dose is about 5 mg.

42. The method of any one of claims 39-41, wherein the second step-up dose is about 100 mg.

43. The method of any one of claims 39-42, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the second step-up dose.

44. The method of any one of claims 39-43, wherein the second step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose.

45. The method of any one of claims 39-44, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the second step-up dose, and wherein the second step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose, wherein first step-up dose is about 5 mg and the second step-up dose is about 100 mg.

46. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 50 mg and wherein the treatment dose is administered once every four weeks.

47. The method of claim 46, wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.

48. The method of claim 47, wherein the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to administration of the treatment dose.

49. The method of claim 47, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose.

50. The method of claim 47, wherein the first step-up dose is about 5 mg and is administered about one week prior to administration of the treatment dose.51 . The method of claim 47, wherein the first step-up dose is about 5 mg and is administered about 6-8 days prior to administration of the treatment dose.

52. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 100 mg and wherein the treatment dose is administered once every four weeks.

53. The method of claim 52, wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.

54. The method of claim 53, wherein the first step-up dose is about 5 mg and is administered about 2-8 days prior to administration of the treatment dose.

55. The method of claim 53, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose.

56. The method of claim 53, wherein the first step-up dose is about 2.5 mg and is administered about 2-4 days prior to administration of the treatment dose.

57. The method of claim 53, wherein the first step-up dose is about 5 mg and is administered about one week prior to administration of the treatment dose.

58. The method of claim 53, wherein the first step-up dose is about 5 mg and is administered about 6-8 days prior to administration of the treatment dose.

59. A method of treating multiple myeloma in a subject in need thereof, comprising administering a therapeutically effective amount of a BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof, to the subject to treat the multiple myeloma, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered at a treatment dose of about 300 mg and wherein the treatment dose is administered once every four weeks.

60. The method of claim 59, wherein at least one step-up dose of theBCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.

61. The method of claim 60, wherein the first step-up dose is about 5 mg and is administered about 2-4 days prior to administration of the treatment dose.

62. The method of any one of claims 59-61, wherein at least two step-up doses of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof are subcutaneously administered prior to the subcutaneous administration of the treatment dose of the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof.

63. The method of claim 62, wherein the first step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the second step-up dose, and wherein the second step-up dose is subcutaneously administered about 2-4 days prior to the subcutaneous administration of the treatment dose,wherein first step-up dose is about 5 mg and the second step-up dose is about 100 mg.

64. The method of any one of claims 1-63, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof comprises:(a) a first antigen-binding arm comprising a first heavy chain variable domain (VH1) and a first light chain variable domain (VL1);(b) a second antigen-binding arm comprising a second heavy chain variable domain (VH2) and a second light chain variable domain (VL2);(c) a third antigen-binding arm comprising a third heavy chain variable domain (VH3) and a third light chain variable domain (VL3), wherein the first antigen-binding arm binds to an epitope on cluster of differentiation 3 (CD3), the second antigen-binding arm binds to an epitope on G-protein coupled receptor family C group 5 member D (GPRC5D), and the third antigen-binding arm binds to an epitope on B cell maturation antigen (BCMA).

65. The method of claim 64, wherein the VH1 and VL1 of first antigen-binding arm are present in a Fab, the VH2 and VL2 of the second antigen-binding arm are present in a scFv, and the VH3 and VL3 of the third antigen-binding arm are present in a scFv.

66. The method of claim 64 or claim 65, wherein the first antigen-binding arm that binds CD3 comprises a HCDR1 comprising the amino acid sequence of GDSVFNNNAAWS (SEQ ID NO: 4), a HCDR2 comprising the ammo acid sequence of RTYYRSKWLYD (SEQ ID NO: 5), and a HCDR3 comprising the amino acid sequence of GYSSSFDY (SEQ ID NO: 6); and a LCDR1 comprising the ammo acid sequence of TGTSSNIGTYKFVS (SEQ ID NO: 1), a LCDR2 comprising the amino acid sequence of EVSKRPS (SEQ ID NO: 2), and a LCDR3 comprising the amino acid sequence of VSYAGSGTLL (SEQ ID NO: 3).

67. The method of any one of claims 64-66, wherein the first antigen-binding arm that binds CD3 comprises the VH1 of SEQ ID NO: 8 and the VL1 of SEQ ID NO: 7.

68. The method of any one of claims 64-67, wherein the second antigen-binding arm that binds GPRC5D comprises a HCDR1 comprising the amino acid sequence of GFSLTNIRMSVS (SEQ ID NO: 12), HCDR2 comprising the amino acid sequence of HIFSNDEKS (SEQ ID NO: 13), and a HCDR3 comprising the amino acid sequence of MRLPYGMDV (SEQ ID NO: 14); and a LCDR1 comprising the ammo acid sequence of RSSQSLVHSDGNTYLS (SEQ ID NO: 9), a LCDR2 comprising the amino acid sequence of KISNRFF (SEQ ID NO: 10), and a LCDR3 comprising the amino acid sequence of MQATQFPHT (SEQ ID NO: 11).

69. The method of any one of claims 64-68, wherein the second antigen-binding arm that binds GPRC5D comprises the VH2 of SEQ ID NO: 16 and the VL2 of SEQ ID NO: 15.

70. The method of any one of claims 64-69, wherein the third antigen-binding arm that binds BCMA comprises a HCDR1 comprising the amino acid sequence of GFTFSSYAMS (SEQ ID NO: 20), a HCDR2 comprising the amino acid sequence of AISGSGGSTY (SEQ ID NO: 21), and a HCDR3 comprising the amino acid sequence of DEGYSSGHYYGMDV (SEQ ID NO: 22); and a LCDR1 comprising the ammo acid sequence of RASQSISSSFLT (SEQ ID NO: 17), a LCDR2 comprising the amino acid sequence of GASSRAT (SEQ ID NO: 18), and a LCDR3 comprising the amino acid sequence of QHYGSSPMYT (SEQ ID NO: 19).

71. The method of any one of claims 64-70, wherein the third antigen-binding arm that binds BCMA comprises the VH3 of SEQ ID NO: 24 and the VL3 of SEQ ID NO: 23.

72. The method of any one of claims 64-71, wherein the first antigen-binding arm that binds CD3 comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 4, 5, 6, 1, 2, 3, respectively; the second antigen-binding arm that binds GPRC5D comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 12, 13, 14, 9,10 and 11, respectively; and the third antigen-binding arm that binds BCMA comprises the HCDR1, the HCDR2, the HCDR3, the LCDR1, the LCDR2 and the LCDR3 of SEQ ID NOs: 20, 21, 22, 17, 18 and 19, respectively.

73. The method of any one of claims 64-72, wherein the first antigen-binding arm that binds CD3 comprises the VH1 of SEQ ID NO: 8 and the VL1 of SEQ ID NO: 7; the second antigen-binding arm that binds GPRC5D comprises the VH2 of SEQ ID NO: 16 and the VL2 of SEQ ID NO: 15; and the third antigen-binding arm that binds BCMA comprises the VH3 of SEQ ID NO: 24 and the VL3 of SEQ ID NO: 23.

74. The method of any one of claims 64-73, wherein the BCMA x GPRC5D x CD3 trispecific antibody comprises a first antigen-binding arm that binds to an epitope on cluster of differentiation 3 (CD3), a second antigen-binding arm that binds to an epitope on G-protein coupled receptor family C group 5 member D (GPRC5D), and a third antigen-binding arm that binds to an epitope on B cell maturation antigen (BCMA), wherein the first antigen-binding arm comprises a heavy chain (HC1) polypeptide and a light chain (LC) polypeptide, wherein the heavy chain (HC1) polypeptide further comprises the second antigen-binding arm, wherein the trispecific antibody, or the trispecific binding fragment thereof, further comprises a single polypeptide comprising the third antigen-binding arm.

75. The method of claim 74, wherein the HC1 of the first antigen-binding arm comprises the amino acid sequence of SEQ ID NO: 29.

76. The method of claim 74 or claim 75, wherein the LC of the first antigen-binding arm comprises the amino acid sequence of SEQ ID NO: 30.

77. The method of any one of claims 74-76, wherein the single polypeptide comprising the third antigen-binding arm comprises an amino acid sequence of SEQ ID NO: 31.

78. The method of any one of claims 74-77, wherein the first antigen-binding arm comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 29, and a LC comprising the amino acid sequence of SEQ ID NO: 30, and the singlepolypeptide comprising the third antigen-binding arm comprises the amino acid sequence of SEQ ID NO: 31.

79. The method of any one of claims 64-78, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is an (human) IgGl isotype.

80. The method of any one of claims 1-79, wherein the multiple myeloma is smoldering multiple myeloma (SMM).81 . The method of any one of claims 1-79, wherein the multiple myeloma is extramedullary disease (EMD).

82. The method of any one of claims 1-79, wherein the multiple myeloma is relapsed or refractory multiple myeloma (RRMM).

83. The method of claim 82, wherein the relapsed or refractory multiple myeloma is relapsed multiple myeloma.

84. The method of claim 82, wherein the relapsed or refractory multiple myeloma is refractory multiple myeloma.

85. The method of any one of claims 1-84, wherein the subject is relapsed or refractory to treatment with a prior anti-cancer treatment.

86. The method of claim 85, wherein the prior anti-cancer treatment comprises administering at least one of a proteasome inhibitor and immunomodulatory drug, such as bortezomib, carfilzomib, lenalidomide, or pomalidomide.

87. The method of claim 85, wherein the prior anti-cancer treatment is a CAR-T therapy, such as a BCMA CAR-T therapy.

88. The method of any one of claims 1-87, wherein the subject has received a prior treatment.

89. The method of claim 88, wherein the prior treatment comprises a proteasome inhibitor, an immunomodulatory drug, a CD38 antibody, a bispecific agent, a CAR- T therapy, or any combination thereof.

90. The method of any one of claims 1-89, wherein the subject has received 1-3 lines of prior treatment.

91. The method of any one of claims 1-89, wherein the subject has received over 3 lines of prior treatment.

92. The method of claim 90 or claim 91, wherein the subject is relapsed or refractory to the lines of prior treatment.

93. The method of any one of claims 90-92, wherein the prior treatment comprises a BCMA or GPRC directed therapy.

94. The method of claim 93, wherein the BCMA or GPRC directed therapy is a CAR-T therapy.

95. The method of claim 93, wherein the BCMA or GPRC directed therapy is a bispecific antibody.

96. The method of any one of claims 88-92, wherein the subject is naive to prior BCMA or GPRC directed therapy.

97. The method of any one of claims 1-96, wherein the subject is administered a prophylactic premedication.

98. The method of claim 97, wherein the prophylactic premedication is tocilizumab.

99. The method of any one of claims 1-98, wherein the subject is an outpatient.

100. The method of claim 98 or claim 99, wherein the subject is an outpatient and is administered a prophylactic premedication, wherein the prophylactic premedication is tocilizumab.

101. The method of any of claims 1-100, wherein the BCMA x GPRC5D x CD3 trispecific antibody or trispecific binding fragment thereof is administered as a monotherapy.

102. The method of any one of claims 1-101, wherein the subject is a human subject.

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