Methods for treating autoimmune diseases using ILT7 binding proteins

Abstract

The present disclosure relates to a method of treating an autoimmune disorder in a subject in need thereof, comprising administering an immunoglobulin-like transcript 7 (ILT7) binding protein. The present disclosure also relates to a method of reducing plasmacytoid dendritic cells (pDCs) or type I interferon gene signature (IFNGS) in a tissue of a subject in need thereof by administering an ILT7 binding protein to the subject.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 183,886, filed May 4, 2021, U.S. Provisional Patent Application No. 63 / 197,789, filed June 7, 2021, U.S. Provisional Patent Application No. 63 / 242,768, filed September 10, 2021, U.S. Provisional Patent Application No. 63 / 249,953, filed September 29, 2021, and U.S. Provisional Patent Application No. 63 / 326,424, filed April 1, 2022, each of which is incorporated by reference in their entirety for all purposes.

[0002] Description of electronically submitted text files The contents of the text file submitted electronically herewith are incorporated herein by reference in their entirety: Computer-readable copy of sequence listing file name: HOPA_033_05WO_SeqList_ST25.txt, date recorded: May 2, 2022, file size 12,288 bytes.

[0003] Technical Field The present disclosure relates to a method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering an immunoglobulin-like transcript 7 (ILT7) binding protein. [Background technology]

[0004] background The type I interferon (IFN) axis is one of the most important pathways in human disease, and its dysregulation is central to the pathogenesis of many chronic autoimmune diseases, such as systemic lupus erythematosus (SLE). Although the exact pathogenesis of SLE and other autoimmune diseases has not been fully resolved, it is believed that a combination of environmental and genetic factors, together with the accumulation of cellular debris, leads to a breakdown in peripheral immune tolerance characterized by high levels of circulating autoreactive antibodies. Currently available methods are aimed at treating autoimmune diseases, but not at preventing such diseases. Furthermore, conventional treatment options for autoimmune diseases include immunosuppressive drugs that are associated with a wide range of side effects. Thus, there is a need for better alternative therapies to treat and prevent autoimmune diseases. The present disclosure addresses these needs. Summary of the Invention

[0005] overview Methods of treating an autoimmune disorder in a subject in need thereof are provided, the methods comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 100-350 mg. In embodiments, the pharmacologic effective amount is administered in one or more (e.g., 1, 2, or 3) doses on the same day. In embodiments, the autoimmune disease is selected from the group consisting of discoid lupus erythematosus (DLE), systemic lupus erythematosus (SLE), lupus nephritis, dermatomyositis, antisynthetic enzyme inflammatory myositis, and alopecia areata. In embodiments, the autoimmune disease is SLE and the pharmacologic effective amount is about 200 mg. In embodiments, the administering is effective to reduce a) levels of plasmacytoid dendritic cells (pDCs) in a tissue of the subject, b) a type I interferon gene signature (IFNGS), or c) levels of plasmacytoid dendritic cells (pDCs) and type I IFNGS in a tissue of the subject, each compared to the subject's baseline level prior to administering. In embodiments, IFNGS comprises the collective expression levels of SPATS2L, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, RSAD2, RTP4, SIGLEC1, and USP18. In embodiments, the reduction in the level of pDC in the tissue compared to baseline values ​​is at least about 10%, 20%, 25%, 30%, 40%, 50%, 60%, or 70%. In embodiments, the autoimmune disease is lupus nephritis and the pharmacologic effective amount is about 300 mg. In embodiments, following administration, the subject achieves a positive renal response as determined by one or more of an improvement in Glomerular Filtration Rate (eGFR) or 24-hour Urine Protein to Creatinine Ratio (UPCR) compared to the subject's baseline levels prior to administration. In embodiments, the autoimmune disease is discoid lupus erythematosus (DLE) and the pharmacologic effective amount is about 150-300 mg.In an embodiment, administering is effective to reduce one or more of the following: Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score, Cutaneous Lupus Erythematosus Disease Area and Severity Index-Damage (CLASI-D) score, Cutaneous Lupus Activity Physician Global Assessment (CLA-IGA) scale, Discoid Lupus Erythematosus Classification Criteria (DLECC) score, Score of Activity and Damage in Discoid Lupus Erythematosus (SADDLE), development of new discoid lesions, size of lesions, or dyspigmentation of discoid lesions, compared to the subject's baseline level before administering. In an embodiment, the autoimmune disease is alopecia areata, and the pharmacologic effective amount is about 300 mg. In an embodiment, administering is effective to stabilize or reduce hair loss in the subject as determined by stabilization or reduction of Severity of Alopecia Tool (SALT) score and / or Alopecia Density and Extent (ALODEX) score. In embodiments, the ILT7 binding protein is administered with one or more additional therapies. In embodiments, the one or more additional therapies include a corticosteroid. In embodiments, the corticosteroid is prednisone. In embodiments, the administration of the one or more additional therapies is tapered. In embodiments, the pharmacologic effective amount of the ILT7 binding protein is about 150-300 mg. In embodiments, the pharmacologic effective amount of the ILT7 binding protein is about 200-300 mg. In embodiments, the ILT7 binding protein is administered about once every 4 weeks or about once every 12 weeks. In embodiments, the pharmacologic effective amount of the ILT7 binding protein is about 300 mg, and the 300 mg is administered as two doses of 150 mg each.

[0006] A method of treating discoid lupus erythematosus (DLE) in a subject in need thereof is provided, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 100 to about 300 mg.

[0007] A method of treating systemic lupus erythematosus (SLE) in a subject in need thereof is provided, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is from about 200 mg.

[0008] A method of treating lupus nephritis in a subject in need thereof is provided, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is from about 300 mg.

[0009] A method of treating alopecia areata in a subject in need thereof is provided, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is from about 300 mg.

[0010] A method of treating dermatomyositis in a subject in need thereof is provided, the method comprising administering to the subject a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein.

[0011] A method of treating anti-synthetic enzyme inflammatory myositis in a subject in need thereof is provided, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein.

[0012] In embodiments, the pharma- ceutical effective amount of an ILT7 binding protein of any of the methods of treatment provided is from about 100 mg to about 300 mg. In embodiments, the ILT7 binding protein is an antibody comprising heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3, and light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3, comprising the amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. In embodiments, the ILT7 binding protein is an antibody comprising a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1, and / or a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In an embodiment, the ILT7 binding protein is an antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO: 2. In an embodiment, the ILT7 binding protein is non-fucosylated. In an embodiment, the ILT7 binding protein is Daxdilimab. In an embodiment, the administration is subcutaneous. In an embodiment, the subject is administered the ILT7 binding protein every 4 weeks. In an embodiment, the subject is administered the ILT7 binding protein every 12 weeks. In an embodiment, prior to administration, the subject is administered at least one initial dose of the ILT7 binding protein. In an embodiment, the at least one initial dose is administered every two weeks for 1, 2, 3, 4, 5 doses or more. In an embodiment, the at least one initial dose is about 100-300 mg.

[0013] Methods of treating lupus nephritis in a subject in need thereof are provided, the methods comprising administering to the subject a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharma- ceutical effective amount of the ILT7 binding protein is about 100 mg every 2 weeks for up to 4 weeks, followed by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses of 100 mg every 4 weeks. In embodiments, the subject is further administered 100 mg of the ILT7 binding protein every 12 weeks, or 300 mg of the ILT7 binding protein every 12 weeks after said every 4 weeks administration. In embodiments, the 100 mg every 12 weeks or 300 mg every 12 weeks is continued for at least about 104 weeks.

[0014] A method of treating lupus nephritis in a subject in need thereof is provided, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 300 mg every 2 weeks for up to 4 weeks, followed by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses of 300 mg every 12 weeks.

[0015] The methods of the disclosure can be used to treat an autoimmune disorder in a subject in need thereof, to reduce pDCs in a tissue of a subject in need thereof, and to reduce type I IFNGS in a subject in need thereof. The disclosure also relates to a method of reducing plasmacytoid dendritic cells (pDCs) or reducing type I interferon gene signatures (IFNGS) in a tissue of a subject by administering an ILT7 binding protein to a subject in need thereof.

[0016] The present disclosure provides a method of treating an autoimmune disease in a subject in need thereof. In the method, a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein is administered to the subject. In an embodiment, the effective amount of the ILT7 binding protein is about 200 mg. In an embodiment, the subject is administered (a) a first dose, (b) a second dose about 4 weeks after the first dose, (c) a third dose about 12 weeks after the first dose, and (d) a subsequent dose about 12 weeks after the third dose. In an embodiment, the ILT7 binding protein is administered once about every 4 weeks.

[0017] The disclosure also provides a method of reducing pDCs in a tissue of a subject by administering to a subject in need thereof an effective amount of an ILT7 binding protein. In embodiments, the effective amount of an ILT7 binding protein is about 200 mg.

[0018] The present disclosure also provides a method for reducing type I IFNGS in a subject in need thereof.In this method, a pharmacologic effective amount of ILT7 binding protein is administered to a subject in need thereof when the type I IFNGS of the subject in need thereof is elevated compared with the type I IFNGS of normal subject.The pharmacologic effective amount of ILT7 binding protein is about 200mg.

[0019] In an embodiment, the present disclosure provides a method for treating an autoimmune disorder in a subject in need thereof.In the method, a pharmacologic effective amount of ILT7 binding protein is administered to the subject.The pharmacologic effective amount of ILT7 binding protein is about 200mg.The ILT7 binding protein is administered once about every 12 weeks.In addition, the subject is administered a 200mg dose of ILT7 binding protein about 4 weeks after the first dose.

[0020] In an embodiment, the present disclosure provides a method for reducing pDC in a tissue of a subject in need thereof. In the method, a pharmacologic effective amount of an ILT7 binding protein is administered to the subject. The pharmacologic effective amount of the ILT7 binding protein is about 200 mg. The subject is administered (a) a first dose, (b) a second dose about 4 weeks after the first dose, (c) a third dose about 12 weeks after the first dose, and (d) a subsequent dose about 12 weeks after the third dose.

[0021] In an embodiment, the present disclosure provides a method for reducing pDC in a tissue of a subject in need thereof.In the method, a pharmacologic effective amount of ILT7 binding protein is administered to the subject.The pharmacologic effective amount of ILT7 binding protein is about 200mg.The ILT7 binding protein is administered about once every 4 weeks.

[0022] In an embodiment, the present disclosure provides a method for reducing pDC in a tissue of a subject in need thereof.In the method, a pharmacologic effective amount of ILT7 binding protein is administered to the subject.The pharmacologic effective amount of ILT7 binding protein is about 200mg.The ILT7 binding protein is administered once about every 12 weeks.In addition, the subject is administered a 200mg dose of ILT7 binding protein about 4 weeks after the first dose.

[0023] In an embodiment, the disclosure provides a method of treating an autoimmune disorder in a subject in need thereof. In the method, a pharmacologic effective amount of an ILT7 binding protein is administered to the subject. The pharmacologic effective amount of the ILT7 binding protein is about 200 mg. The ILT7 binding protein is an antibody comprising a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1, and / or a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. The subject is administered (a) a first dose, (b) a second dose about 4 weeks after the first dose, (c) a third dose about 12 weeks after the first dose, and (d) a subsequent dose about 12 weeks after the third dose.

[0024] In an aspect, the disclosure provides a method of treating systemic lupus erythematosus (SLE) in a subject in need thereof. In the method, a pharmacologic effective amount of an ILT7 binding protein is administered to the subject. The pharmacologic effective amount of the ILT7 binding protein is about 200 mg. The ILT7 binding protein is an antibody comprising a VH that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1, and / or a VL that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. The subject is administered (a) a first dose, (b) a second dose about 4 weeks after the first dose, (c) a third dose about 12 weeks after the first dose, and (d) a subsequent dose about 12 weeks after the third dose.

[0025] In an embodiment, the disclosure provides a method of treating an autoimmune disorder in a subject in need thereof. In the method, a pharmacologic effective amount of an ILT7 binding protein is administered to the subject. The pharmacologic effective amount of the ILT7 binding protein is about 200 mg. The ILT7 binding protein is an antibody comprising a VH at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1, and / or a VL at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. The ILT7 binding protein is administered about once every four weeks.

[0026] In an embodiment, the disclosure provides a method of treating SLE in a subject in need thereof. In the method, a pharmacologic effective amount of an ILT7 binding protein is administered to the subject. The pharmacologic effective amount of the ILT7 binding protein is about 200 mg. The ILT7 binding protein is an antibody comprising a VH that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1, and / or a VL that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. The ILT7 binding protein is administered about once every four weeks.

[0027] In an embodiment, the disclosure provides a method of treating an autoimmune disorder in a subject in need thereof. In the method, a pharmacologic effective amount of an ILT7 binding protein is administered to the subject. The pharmacologic effective amount of the ILT7 binding protein is about 200 mg. The ILT7 binding protein is an antibody comprising a VH that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1, and / or a VL that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. The ILT7 binding protein is administered once about every 12 weeks. In addition, the subject is administered a 200 mg dose of the ILT7 binding protein about 4 weeks after the first dose.

[0028] In an embodiment, the disclosure provides a method of treating SLE in a subject in need thereof. In the method, a pharmacologic effective amount of an ILT7 binding protein is administered to the subject. The pharmacologic effective amount of the ILT7 binding protein is about 200 mg. The ILT7 binding protein is an antibody comprising a VH that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1, and / or a VL that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. The ILT7 binding protein is administered once about every 12 weeks. In addition, the subject is administered a 200 mg dose of the ILT7 binding protein about 4 weeks after the first dose.

[0029] In an aspect, the disclosure provides a method of treating an autoimmune disorder in a subject in need thereof. In the method, a pharma- ceutical effective amount of an ILT7 binding protein is administered to the subject. The pharma- ceutical effective amount of the ILT7 binding protein is about 200 mg. The ILT7 binding protein is an antibody comprising a VH at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1, and / or a VL at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. These and other embodiments are described below.

[0030] A method of treating alopecia areata in a subject in need thereof is provided, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is between about 250 mg and 350 mg.

[0031] A method of reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject having alopecia areata is provided, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is between about 250 mg and 350 mg.

[0032] In embodiments, administering an ILT7 binding protein reduces plasmacytoid dendritic cells (pDCs) in a subject. In embodiments, the pDCs are circulating pDCs. In embodiments, the reduction in pDCs is reversible. In embodiments, the ILT7 binding protein is administered about once every four weeks.

[0033] A method of treating alopecia areata in a subject in need thereof is provided, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is between about 250 mg and 350 mg, and wherein the ILT7 binding protein is administered about once every four weeks.

[0034] A method is provided for reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject having alopecia areata, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is between about 250 mg and 350 mg, and wherein the ILT7 binding protein is administered about once every four weeks.

[0035] In embodiments, the reduction of pDCs in tissues compared to baseline values ​​ranges from about 1% to about 99%. In embodiments, the reduction of pDCs in tissues compared to baseline values ​​is at least about 50%. In embodiments, the ILT7 binding protein induces antibody-dependent cell-mediated cytotoxicity (ADCC) activity against pDCs. In embodiments, the ILT7 binding protein at least inhibits release of type I interferon (IFN) from pDCs. In embodiments, the type I IFN is IFNα. In embodiments, the ILT7 binding protein binds to ILT7. In embodiments, the ILT7 binding protein is an antibody comprising heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3, and light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3, comprising the amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. In embodiments, the ILT7 binding protein is an antibody comprising a variable heavy chain (VH) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 1, and / or a variable light chain (VL) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 2. In embodiments, the ILT7 binding protein is an antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO: 2. In embodiments, the ILT7 binding protein is non-fucosylated.

[0036] There is provided a method of treating alopecia areata in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is between about 250 mg and 350 mg, and the ILT7 binding protein is an antibody comprising a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1 and / or a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2, and wherein the ILT7 binding protein is administered about once every four weeks.

[0037] There is provided a method of treating alopecia areata in a subject in need thereof, the method comprising administering to the subject a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharma- ceutical effective amount of the ILT7 binding protein is between about 250 mg and 350 mg, and the ILT7 binding protein is an antibody comprising a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1, and / or a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2.

[0038] In embodiments, the ILT7 binding protein is administered with one or more additional therapies. In embodiments, one of the one or more additional therapies is a standard of care therapy. In embodiments, the ILT7 binding protein is administered subcutaneously. In embodiments, the administering is effective to stabilize or reduce hair loss in the subject as determined by a stabilization or reduction in Severity of Alopecia Tool (SALT) score and / or Alopecia Density and Extent (ALODEX) score. In embodiments, the ILT7 binding protein is administered to a mouse with alopecia areata, and the administering is effective to reduce the level of type 1 interferon-inducible myxovirus protein A (MxA) as determined by immunohistochemistry in a biopsy containing a hair follicle of the mouse. In embodiments, the pharmacologic effective amount of the ILT7 binding protein is about 300 mg. In embodiments, the 300 mg amount is administered as two separate doses of 150 mg each administered on the same day. In embodiments, the ILT7 binding protein is daxudilimab. [Brief description of the drawings]

[0039] The accompanying drawings, which are incorporated in and form a part of this specification, illustrate certain example embodiments and / or features, although not exclusively or exclusively. It is intended that the embodiments and figures disclosed herein be considered illustrative and not limiting. [Figure 1]The overall study design is shown: COVID-19: coronavirus disease 2019, OGC: oral glucocorticoids, Q4W: every 4 weeks, Q12W: every 12 weeks, SC: subcutaneous (under the skin), SLE: systemic lupus erythematosus, SLEDAI-2K: SLE Disease Activity Index 2000, W: week. [Diagram 2] 1 shows a clinical trial diagram of Example 2. [Diagram 3] 1 shows an exemplary oral glucocorticoid tapering schedule. [Figure 4] 1 depicts an exemplary test diagram of Example 3. [Diagram 5] Shown is the Severity of Alopecia Tool (SALT) assessment tool from Olsen EA et al., Alopecia areata investigational assessment guidelines--Part II. National Alopecia Areata Foundation. J Am Acad Dermatol. 2004;51(3):440-447. [Figure 6] Olsen EA et al., SALT II: A new take on the Severity of Alopecia Tool (SALT) for determining percentage scalp hair loss. J Am Acad Dermatol. 2016;75(6):1268-1270 and Olsen EA et al., Objective outcome measures: Collecting meaningful data on alopecia areata. J Am Acad Dermatol. 2018;79(3):470-478 e473 show the Alopecia Density and Extent (ALODEX) assessment tool. [Figure 7] The overall study design of Example 4 is shown. CRR: complete renal response, D: day, IP: study drug, MMF: mycophenolate mofetil, MPA: mycophenolic acid, OCS: oral corticosteroids, PRR: partial renal response, Q4W: once every 4 weeks, Q12W: once every 12 weeks, SC: subcutaneous, SFU: safety follow-up, SOC: standard of care, W: week. [Figure 8] The overall study design of Example 5 is shown. LTE: long-term extension, N: total population, Q4W: once every 4 weeks, SC: subcutaneous, SFU: safety follow-up, W: week. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0040] Detailed Description The present disclosure provides a method for treating an autoimmune disorder in a subject with an ILT7 binding protein. In certain embodiments, the ILT-7 binding protein is administered at a dose of 200 mg. In embodiments, the ILT7 binding protein is administered about once every 4 weeks. In other embodiments, the ILT-7 binding protein is administered about once every 12 weeks. In embodiments, the method provides for treating an autoimmune disorder in a subject in need thereof, the subject being determined to have a high blood type I interferon gene signature (IFNGS) level. The present disclosure also provides a method for reducing IFNGS in a subject in need thereof. In embodiments, the ILT7 binding protein is administered to a subject when type I IFNGS is elevated in the subject compared to type I IFNGS in normal subjects. In embodiments, for example, the ILT7 binding protein is administered to a subject with elevated baseline type I IFNGS compared to type I IFNGS in normal subjects. In certain embodiments, the ILT7 binding protein is an antibody. In an embodiment, the antibody is daxudilimab.

[0041] In certain diseases (e.g., autoimmune diseases), activated pDCs secrete significant amounts of type I and type III interferons (IFNs). Type I IFNs are a large group of IFN proteins that help regulate the immune system. Mammalian IFNs are referred to as IFNα, IFNβ, IFNω, IFNε, IFNκ, IFNτ, IFNδ, IFNζ, and IFNυ. In embodiments, the type I IFN that produces type I IFNGS is IFNα. Although the protein levels of type I IFNs cannot be measured directly in a reliable manner, the measurement of IFN-inducible genes serves as a robust surrogate for type 1 IFN protein levels. The expression levels of these type I IFN-inducible genes can be measured in biological samples (e.g., blood, skin, skeletal muscle, etc.) and analyzed as a composite outcome referred to as a "type I interferon gene signature," or "type I IFNGS," or "IFNGS."

[0042] definition Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this subject belongs.All publications, patent applications, patents, and other references mentioned herein are expressly incorporated by reference in their entirety.In case of conflict, the present specification, including definitions, will control.In addition, the materials, methods, and examples described herein are illustrative only and are not intended to be limiting.

[0043] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0044] As used herein, ranges may be expressed as from "about" one particular value and / or to "about" another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values ​​are expressed as approximations, by use of the antecedent "about," it is understood that the particular value forms another embodiment. It will be further understood that each endpoint of the range is significant both in relation to the other endpoint and independently of the other endpoint. As used herein, the term "about" refers to a range that is plus or minus 15% from the stated numerical value within the context of the particular use. For example, about 10 includes a range of 8.5 to 11.5. The term "about" also accounts for the typical error or imprecision in the measurement of the value.

[0045] When referring to a nucleic acid or protein sequence, the term "identity" is used to indicate the similarity between two sequences. Unless otherwise indicated, the percent identity described herein is determined using the BLAST algorithm, available on the World Wide Web at the following address: blast.ncbi.nlm.nih.gov / Blast.cgi, using default parameters.

[0046] By "test biological sample" is intended any biological sample obtained from an individual suffering from, likely suffering from, or suspected of suffering from a disease or condition, such as an autoimmune disorder, and / or exhibiting one or more symptoms thereof, including but not limited to elevated type I IFNGS.

[0047] By "normal biological sample" is intended any biological sample obtained from a normal subject.

[0048] As used herein, the term "subject" refers to any individual (e.g., a human or non-human mammal) for whom a diagnosis, prognosis, or therapy is desired. The term "subject" may refer to a human or non-human mammal suffering from, likely to suffer from, or suspected of suffering from a disease (e.g., an autoimmune disease) or condition. The terms "subject" and "patient" are used interchangeably herein. Although the ILT7 binding protein compositions provided herein are primarily directed to compositions suitable for administration to humans, one of skill in the art will understand that such compositions are generally suitable for administration to any type of subject. In an embodiment, the subject is a mammal. Mammals include primates (e.g., humans, monkeys, chimpanzees, and apes), as well as non-primates (e.g., domestic animals, including laboratory animals (e.g., rabbits and rodents, such as guinea pigs, rats, or mice) and household pets and livestock (e.g., cats, dogs, pigs, cows, sheep, goats, horses, rabbits), as well as non-domestic animals, such as wild animals, birds, reptiles, and fish).

[0049] As used herein, the term "subject in need thereof" includes subjects who can or will benefit from the methods described herein. Subjects in need of treatment include, but are not limited to, those already with a condition or disorder, those susceptible to a condition or disorder, those suspected of having a condition or disorder, and those in need of preventing, ameliorating, or reversing a condition or disorder.

[0050] As used herein, the term "normal subject" refers to any healthy individual (e.g., human or non-human mammal) that is not suffering from a disease or is not suspected of suffering from a disease or condition. The term "normal subject" refers to an individual (e.g., human or non-human mammal) before showing any symptoms associated with an autoimmune disorder, such as elevated type I IFNGS. The normal subject may be, but is not limited to, the same subject as the subject in need of treatment, before the subject shows any symptoms of an autoimmune disease, such as elevated type I IFNGS. In other embodiments, the normal subject and the subject in need of treatment are two different individuals.

[0051] As used herein, "treating" or "treating" describes the management and care of a subject with the goal of combating a disease, condition, or disorder, and includes administration of an ILT7 binding protein used in the methods described herein to alleviate symptoms or complications of a disease, condition, or disorder, or to eliminate a disease, condition, or disorder. Thus, the term "treating" or "treating" refers to both therapeutic and prophylactic or preventative measures, the purpose of which is to prevent, slow (alleviate), or ameliorate the progression of a disease (e.g., an autoimmune disease). Beneficial or desired clinical outcomes include, but are not limited to, alleviation of symptoms, reduction in the extent of the disease, stabilization of the disease state (i.e., not worsening), delay or slowing of disease progression, improvement or alleviation of the disease state, and reversal of the disease (partial or total). The term "treating" also includes treatment of cells or animal models in vitro.

[0052] In embodiments, treatment includes application or administration of an ILT7 binding protein used in the methods described herein to a subject in need thereof or suspected of being in need of such treatment, or application or administration of an ILT7 binding protein used in the methods described herein to a tissue or cell line isolated from a subject in which the subject has a disease, a symptom of a disease, or a predisposition to a disease (e.g., an autoimmune disease). Even if a formal diagnosis has not been confirmed, a subject may be suspected of being in need of a treatment as described herein if the subject exhibits a condition or symptom of a disease by excessive pDC numbers or activity. In embodiments, a subject suspected of being in need of treatment has an elevated baseline blood type I IFNGS level. In other embodiments, treatment is also intended to include application or administration of a pharmaceutical composition comprising an ILT7 binding protein used in the methods described herein to a subject in need thereof or suspected of being in need of such treatment, or application or administration of a pharmaceutical composition comprising an ILT7 binding protein used in the methods described herein to a tissue or cell line isolated from a subject in need thereof, a symptom of a disease, or a predisposition to a disease (e.g., an autoimmune disease).

[0053] The terms "reduce," "reducing," or "reduction" mean a decrease in extent, level, amount, activity, or magnitude compared to an initial value. The reduction need not be statistically significant from one value to the next.

[0054] As used herein, the term "pDC reduction" or "reducing pDCs" refers to a reduction in the level of activated pDCs in a subject or a biological sample taken from a subject (e.g., blood and / or other tissues (skin cells, skin biopsy, etc.)), a reduction in the level of the total number of pDCs in a subject or a biological sample taken from a subject, or both.

[0055] As used herein, the term "high" or "elevated" when used in conjunction with type I IFNGS means that type I IFNGS is at least about 1.1 to about 1000 fold change compared to normal type I IFNGS. By "normal type I IFNGS" is intended type I IFNGS obtained from a normal subject. The terms "high" or "elevated" when used in conjunction with type I IFNGS are used interchangeably. In an embodiment, type I IFNGS is "high" or "elevated" when type I IFNGS used in the methods described herein is at least about 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 fold change compared to type I IFNGS in a normal subject. In aspects, the methods of treatment described herein are applicable when type I IFNGS is elevated at least about four-fold as compared to normal type I IFNGS.

[0056] The terms "administer", "administration", "administering", and the like, when applied to, for example, a subject, cell, tissue, organ, or biological sample, refer to contact of a compound or reagent with the subject, cell, tissue, organ, or biological sample. In the context of a cell, administration includes contact of a reagent with the cell (e.g., in vitro or ex vivo), as well as contact of a reagent with a fluid where the fluid is in contact with the cell. The ILT7 binding proteins used in the methods described herein may be administered to a subject via a variety of routes known in the art. Exemplary routes of administration of the ILT7 binding proteins used in the methods described herein include, but are not limited to, parenteral, oral, mucosal, topical, transdermal, inhalation, sublingual, buccal, rectal, vaginal, and intranasal. The term parenteral as used herein includes subcutaneous injection, intravenous, intramuscular, intrasternal injection or infusion techniques. In aspects, the ILT7 binding proteins used in the methods described herein are administered intravenously. In aspects, the ILT7 binding proteins used in the methods described herein are administered by subcutaneous injection. The terms "administer", "administration" or "administering" can include a single administration or multiple administrations of an ILT7 binding protein used in the methods described herein. For example, multiple administrations involve at least two (i.e., 2, 3, 4, 5, 6, 7, 8, 9, 10 or more) administrations of an ILT7 binding protein used in the methods described herein to a subject.

[0057] A "therapeutically effective amount" or "pharmaceutical effective amount" or "effective amount" of a compound (e.g., an ILT7 binding protein used in the methods described herein) refers to an amount that is sufficient to produce a desired prophylactic, therapeutic, or palliative response in a subject, or an amount that is sufficient to prevent or alleviate one or more symptoms of a disease or condition in a statistically significant manner. When referring to an individual active ingredient administered alone, a therapeutically effective amount refers to that ingredient alone. When referring to a combination, a therapeutically effective amount refers to the combined amount of active ingredients that produces a therapeutic effect, whether administered sequentially or simultaneously. As used herein, the term "therapeutically effective amount" means that an ILT7 binding protein used in the methods described herein, when used as prescribed or indicated, can exert a medically beneficial effect (e.g., cause a reduction in the elevation of type I IFNGS and / or a reduction in pDC in a subject in need thereof) compared to a placebo. A therapeutically effective amount will vary depending on the species and weight of the subject to which it is administered, but can be ascertained using standard techniques.

[0058] Immunoglobulin-like transcript 7 (ILT7) binding protein In general, the terms "ILT7 binding protein", "ILT7 binding molecule" and "ILT7 binding protein used in the methods described herein" are used interchangeably to refer to a protein or molecule that specifically binds to immunoglobulin-like transcript 7 (ILT7). The terms protein and peptide can be used interchangeably herein. In aspects, an ILT7 binding protein used in the methods described herein binds to full length ILT7. In aspects, an ILT7 binding protein used in the methods described herein binds to a fragment of ILT7. In aspects, the fragment of ILT7 that the ILT7 binding protein binds comprises the extracellular domain of ILT7.

[0059] In aspects, the ILT7 binding protein used in the methods disclosed herein binds to any mammalian ILT7. In aspects, the ILT7 binding protein used in the methods disclosed herein binds to human ILT7 or a fragment thereof (e.g., the extracellular portion of human ILT7). In other aspects, the ILT7 binding protein used in the methods disclosed herein binds to cynomolgus ILT7 or a fragment thereof (e.g., the extracellular portion of cynomolgus ILT7). In aspects, the ILT7 binding protein binds to the Ig1 region of ILT7. In aspects, the ILT7 binding protein binds to the Ig2 region of ILT7. In aspects, the ILT7 binding protein binds to human and cynomolgus ILT7.

[0060] In embodiments, the ILT7 binding protein comprises an antibody or antigen-binding fragment thereof. In embodiments, the antibody or antigen-binding fragment thereof is non-fucosylated.

[0061] ILT7 is a cell surface protein unique to plasmacytoid dendritic cells (pDCs) in humans and non-human primates. ILT7 binding proteins, compositions comprising same, and methods of using same are provided. In embodiments, the composition may comprise an effective amount of an anti-ILT7 binding protein.

[0062] Examples of ILT7 binding proteins are disclosed and described in PCT Publication No. WO2017 / 156298, U.S. Patent No. US8084585B2, PCT Publication No. WO2021 / 113702, all of which are incorporated herein by reference in their entirety. In an embodiment, the ILT7 to which the ILT7 binding protein binds is located on pDC. In an embodiment, clone ILT70137 in PCT Publication No. WO2017 / 156298 is provided and further described in Table 1 below. In an embodiment, the anti-ILT7 binding protein comprises a sequence that comprises at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity to any one of the sequences in Table 1. In an embodiment, the anti-ILT7 binding protein comprises any one of the sequences in Table 1. Daxzilimab is an antibody that comprises a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO: 2. VIB7734 and HZN7734 refer to daxzilimab.

[0063] Table 1. Exemplary anti-ILT7 mAb sequences TIFF2024516698000002.tif176165

[0064] In an embodiment, the ILT7 binding protein comprises a VH and a VL at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1 and SEQ ID NO:2, respectively. In an embodiment, the VH and VL of the ILT7 binding protein comprise SEQ ID NO:1 and SEQ ID NO:2, respectively. In an embodiment, the VH and VL of the ILT7 binding protein comprise a sequence having at least about 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:1 and / or SEQ ID NO:2, respectively. In an embodiment, the isolated ILT7 binding protein is an ILT7 binding protein that can bind to the same ILT7 epitope as an antibody comprising a VH and a VL selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:2, respectively. In an embodiment, the isolated ILT7 binding protein is an ILT7 binding protein that competitively inhibits the binding of an antibody comprising a VH and a VL selected from the group consisting of SEQ ID NO:1 and SEQ ID NO:2, respectively, to ILT7. In embodiments, an isolated ILT7 binding protein comprises a VH comprising SEQ ID NO: 1. In embodiments, an ILT7 binding protein comprises a VH comprising a sequence having at least about 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:1.

[0065] In embodiments, the isolated ILT7 binding protein comprises a VL comprising SEQ ID NO: 2. In embodiments, the ILT7 binding protein comprises a VL comprising a sequence having at least about 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:2.

[0066] In an embodiment, the isolated ILT7 binding protein is an ILT7 binding protein comprising CDRs: HCDR1, HDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively, selected from the group consisting of SEQ ID NOs: 3 to 8. In an embodiment, the isolated ILT7 binding protein is an ILT7 binding protein comprising CDRs: HCDR1, HDR2, HCDR3, LCDR1, LCDR2, and LCDR3, respectively, selected from the group consisting of SEQ ID NOs: 3 to 8, with at least 1-2, 2-3, or 2-4 residue modifications.

[0067] In an embodiment the ILT7 binding protein comprises or consists of a VH at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 1, and / or a VL at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 2. In an embodiment the isolated ILT7 binding protein is an ILT7 binding protein comprising complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3 comprising the sequences of SEQ ID NOs: 3-8, respectively.

[0068] In embodiments, an ILT7 binding protein used in the methods described herein comprises heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3, and light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3 having the amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. In other embodiments, an ILT7 binding protein used in the methods described herein comprises heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3, and light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3 that are at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0069] In aspects, an ILT7 binding protein used in the methods described herein comprises a heavy chain of SEQ ID NO: 9. In other aspects, an ILT7 binding protein used in the methods described herein comprises a light chain of SEQ ID NO: 10. In aspects, an ILT7 binding protein used in the methods described herein comprises a heavy chain of SEQ ID NO: 9, and a light chain of SEQ ID NO: 10. In other aspects, an ILT7 binding protein used in the methods described herein comprises a heavy chain that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 9, and / or a light chain that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO: 10.

[0070] In an embodiment, the ILT7 binding protein comprises a VH comprising SEQ ID NO:1 and a VL comprising SEQ ID NO:2. In an embodiment, the isolated ILT7 binding protein is an ILT7 binding protein comprising a VH comprising SEQ ID NO:1. In an embodiment, the isolated ILT7 binding protein is an ILT7 binding protein comprising a VL comprising SEQ ID NO:2. In an embodiment, the ILT7 binding protein comprises a sequence having at least about 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity to SEQ ID NO:9 and / or SEQ ID NO:10. In an embodiment, the ILT7 binding protein comprises or consists of SEQ ID NO:9 and / or SEQ ID NO:10. In an embodiment, the ILT7 binding protein is daxudilimab, a human immunoglobulin (Ig) G1 lambda (IgG1λ) non-fucosylated monoclonal antibody (mAb). Daxuzilimab binds to ILT7 on the surface of pDCs, leading to the recruitment of macrophages and natural killer (NK) cells, thus inducing apoptosis and depletion of pDCs in vivo. The non-fucosylation of daxuzilimab is designed to enhance the efficacy of daxuzilimab for antibody-dependent cellular cytotoxicity (ADCC) against pDCs. Because pDCs are the main cell type that secretes type I interferon (IFN) in response to nucleic acid-containing immune complexes, it is hypothesized that depletion of pDCs reduces disease activity in subjects with autoimmune diseases (e.g., alopecia) that are partially driven by abnormally high levels of type I IFN.

[0071] In an embodiment, the ILT7 binding protein has ADCC activity against plasmacytoid dendritic cells (pDCs) in PMBCs.

[0072] In embodiments, the ILT7 binding protein comprises a murine, human, chimeric, humanized, or resurfaced antibody, or an antigen-binding fragment thereof. In embodiments, the ILT7 binding protein comprises an antibody, Fab, Fab', F(ab')2, Fd, single chain Fv or scFv, disulfide-linked Fv, V-NAR domain, IgNar, intrabody, IgGΔCH2, minibody, F(ab')3, tetrabody, triabody, diabody, single domain antibody, DVD-Ig, Fcab, mAb2, (scFv)2, or scFv-Fc. In embodiments, the ILT7 binding protein comprises a monoclonal antibody or an antigen-binding fragment thereof. In embodiments, the ILT7 binding protein comprises daxudilimab. In embodiments, the ILT7 binding protein is daxudilimab.

[0073] In an embodiment, the ILT7 binding protein comprises a heavy chain immunoglobulin constant domain selected from the group consisting of: (a) an IgA constant domain, (b) an IgD constant domain, (c) an IgE constant domain, (d) an IgG1 constant domain, (e) an IgG2 constant domain, (f) an IgG3 constant domain, (g) an IgG4 constant domain, and (h) an IgM constant domain. In an embodiment, the ILT7 binding protein comprises a light chain immunoglobulin constant domain selected from the group consisting of: (a) an Ig kappa constant domain, and (b) an Ig lambda constant domain. In an embodiment, the ILT7 binding protein comprises a human IgG1 constant domain and a human lambda constant domain.

[0074] In an aspect, provided herein is a host cell that produces an ILT7 binding molecule.

[0075] In an aspect, provided herein is an isolated polynucleotide comprising a nucleic acid sequence encoding a VH, wherein the VH comprises an amino acid sequence at least 85%, 90%, 95% identical, or identical to the VH of SEQ ID NO:1.

[0076] In an aspect, provided herein is an isolated polynucleotide comprising a nucleic acid sequence encoding a VL, wherein the VL comprises an amino acid sequence at least 85%, 90%, 95% identical, or identical to the VL of SEQ ID NO:2.

[0077] In embodiments, the nucleic acid is operably linked to a control sequence. In embodiments, an antibody or antigen-binding fragment thereof comprising the VH or VL encoded by the nucleic acid is capable of specifically binding to ILT7.

[0078] In embodiments, the polynucleotide encodes an ILT7 binding molecule provided herein.

[0079] In an aspect provided herein is a vector comprising the polynucleotide.

[0080] In an aspect, provided herein is a polypeptide encoded by a polynucleotide.

[0081] In an aspect, provided herein is a host cell transformed with a polynucleotide provided herein (e.g., a polynucleotide comprising a nucleic acid encoding a VH and a polynucleotide comprising a nucleic acid encoding a VL).

[0082] In aspects, provided herein is a host cell comprising a polynucleotide provided herein (e.g., a polynucleotide comprising a nucleic acid encoding a VH and a polynucleotide comprising a nucleic acid encoding a VL), a vector provided herein, or a polypeptide provided herein. In aspects, the host cell is a mammalian host cell. In aspects, the host cell is an NS0 mouse myeloma cell, a PER.C6® human cell, or a Chinese Hamster Ovary (CHO) cell. In aspects, the host cell lacks the enzyme α-1,6-fucosyltransferase.

[0083] In aspects, the ILT7 binding proteins used in the methods described herein may contain a fucose moiety or they may be non-fucosylated.

[0084] autoimmune disease In aspects, autoimmune diseases may be prevented or treated with any of the ILT7 binding proteins provided herein.

[0085] Examples of autoimmune diseases include, but are not limited to, systemic lupus erythematosus (SLE), discoid lupus erythematosus (DLE), lupus nephritis, cutaneous lupus erythematosus (CLE), Sjogren's syndrome, inflammatory myositis, dermatomyositis, antisynthetic enzyme inflammatory myositis (ASIM), inclusion body myositis, juvenile myositis and polymyositis, systemic sclerosis, diabetes, Hashimoto's disease, autoimmune adrenal insufficiency, true erythrocytic anemia, multiple sclerosis, rheumatic carditis, psoriasis, psoriatic arthritis, rheumatoid arthritis, chronic inflammation, chronic rheumatoid arthritis, vitiligo, alopecia areata, hidradenitis suppurativa, celiac disease, acute and chronic graft-versus-host disease (GVHD), vascular inflammation, myocardial infarction, and type 1 interferonopathy.In an embodiment, the subject shows an elevation of type 1 IFNGS.

[0086] In embodiments, the autoimmune disease is SLE. In further embodiments, the autoimmune disease is CLE. In embodiments, the autoimmune disease is lupus. In embodiments, the lupus is not discoid lupus erythematosus (DLE). In embodiments, the lupus is DLE. In embodiments, the autoimmune disorder is primary DLE. In embodiments, the subject with DLE does not have systemic lupus. In embodiments, the DLE is refractory to other treatments. In embodiments, the subject with DLE has previously been treated with one or more therapies selected from the group consisting of topical steroids, intralesional steroids, antimalarials, tacrolimus, thalidomide, topical tacrolimus, azathioprine, cyclosporine, mycophenolate mofetil, methotrexate, and acitretin.

[0087] In an embodiment, the autoimmune disease is discoid lupus erythematosus (DLE). Discoid lupus erythematosus generally appears as discoid round lesions, mainly on the scalp, face, and ears, and are often red, scaly, and thick. Over time, these can cause scarring, irreversible hair loss, and skin discoloration. With the exception of hydroxychloroquine, there is no approved therapy for the treatment of DLE, and current management consists of unapproved systemic therapies such as thalidomide, and topical therapies with topical steroids or calcineurin inhibitors. Furthermore, DLE does not respond to current standard treatments, estimated to occur in approximately 30% of subjects, and remains the most difficult skin condition to treat. Primary DLE lesions are known to contain increased numbers of pDCs, which indicates elevated production of type I IFN. The expression score of interferon genes in the blood of DLE subjects is also significantly elevated compared to healthy controls. Furthermore, pDCs express immunoglobulin-like transcript 7 (ILT7), a cell surface protein unique to pDCs in humans and non-human primates.

[0088] In an embodiment, the autoimmune disease is Sjogren's syndrome. In an embodiment, the autoimmune disease is dermatomyositis. In an embodiment, the autoimmune disease is dermatomyositis. In an embodiment, the autoimmune disease is antisynthetic enzyme inflammatory myositis. In an embodiment, the autoimmune disease is polymyositis. In an embodiment, the autoimmune disease is systemic sclerosis. In an embodiment, the autoimmune disease is hidradenitis suppurativa. In an embodiment, the autoimmune disease is vitiligo.

[0089] In an embodiment, the autoimmune disease is alopecia areata. Alopecia areata is an acute onset autoimmune disorder characterized by transient non-scarring hair loss in clearly defined areas. It is the second most common type of alopecia after androgen type. The extent of hair loss defines three major AA forms: patchy AA, alopecia totalis (loss of all scalp hair), and alopecia universalis (loss of all body hair). Patchy AA is the most common form. Clinically, AA patches are usually completely bald, smooth, and round or oval. Short smudge hairs less than 4 mm and black dots are commonly observed around the lesion, especially during the acute phase of AA. The scalp, beard area, and eyebrows are most commonly involved, but any area with hair can be affected. In an embodiment, alopecia does not destroy hair follicles.

[0090] The baldness and bald areas may be caused by the inhibition of hair follicle cycle, which represents one of the end results of the pathophysiological process of alopecia that begins with the loss of immune privilege of hair follicles and the subsequent autoimmune attack of the globular area of ​​anagen hair follicles by CD8+ T cells and Th1 cytokines. Genome-wide association studies have identified human leukocyte antigen (HLA) region genes and other immune function genes as being associated with alopecia areata. In an embodiment, CD8+NKG2D+T cells are the effectors of AA pathogenesis. Effector CD8 T cells can be activated by the expression of MHCI and NKG2DL on epithelial cells and exert their cytotoxic effects via IFNg. In addition, CD4 T cells and NK cells are also present around epithelial cells of affected subjects and can secrete a number of proinflammatory cytokines, including IFNg. In an embodiment, the recruitment and activation of NK and T cells around and within the lesion can be caused by pDC and / or type I IFN.

[0091] In embodiments, the autoimmune disease is dermatomyositis. In embodiments, subjects with dermatomyositis experience symptoms including skin rash, muscle weakness, difficulty swallowing, fatigue, scaly skin, calcium deposits, inflammation, and combinations thereof.

[0092] In some embodiments, the autoimmune disease is antisynthetic enzyme inflammatory myositis.In some embodiments, symptoms include muscle inflammation (myositis), inflammation of some joints (polyarthritis), interstitial lung disease, thickening and cracking of the skin of the hands, and a condition called Raynaud's phenomenon, in which the fingers or toes feel numb or tingling in response to cold.Affected subjects also have non-specific symptoms such as fatigue, fever of unknown origin, and unintentional weight loss.

[0093] In an embodiment, the autoimmune disease is lupus nephritis (LN). LN is the most common major organ manifestation of SLE. LN affects approximately 31-60% of lupus patients and is more common in certain ethnicities, such as African-Americans, Asians, and Hispanics. LN occurs when lupus autoantibodies affect the kidney's structures that filter waste products. This causes inflammation of the kidney, which can lead to hematuria, protein in the urine, high blood pressure, impaired kidney function, or even kidney failure.

[0094] In embodiments, subjects with an autoimmune disease described herein contain increased levels of interferon compared to otherwise similar subjects without an autoimmune disease or the same subjects previously diagnosed with an autoimmune disease. For example, in moderate to severe SLE, about 80% of subjects have increased levels of IFN. 高 and a higher proportion of moderate to severe dermatomyositis-positive subjects, antisynthetase myositis-positive subjects, and lupus nephritis-positive subjects were IFN-positive. 高 However, perhaps only about half of patients with Sjögren's syndrome are responsive to IFN. 高 and only about 15% of cases of RA. Therefore, these various diseases require IFN 高 In an embodiment, a majority of subjects with an autoimmune disease are resistant to IFN. 高 Includes.

[0095] method Methods are provided that include an ILT7 binding protein. In an embodiment, the method includes using an ILT7 binding protein in a therapeutic method. In an embodiment, the therapeutic method includes administering an ILT7 binding protein to a subject with an autoimmune disease. In an embodiment, the method includes administering an ILT7 binding protein to a subject with an autoimmune disease, as determined by an in vitro assay, to reduce IFN-. 高 The present invention also includes treating a subject having an autoimmune disease in which the subject is an ILT7 patient, the treating comprising administration of an ILT7 binding protein of the present disclosure.

[0096] Without needing to be bound by theory, the ILT7 binding protein used in the methods described herein induces antibody-dependent cell-mediated cytotoxicity (ADCC) activity against plasmacytoid dendritic cells (pDCs), thereby depleting pDCs. In embodiments, ILT7 binding protein-mediated ADCC causes a reduction in circulating pDCs. In embodiments, ILT7 binding protein-mediated ADCC causes a reduction in local or tissue pDCs. In embodiments, tissues in which pDCS are reduced include, but are not limited to, skin cells, skin biopsies, kidney cells, lung cells, liver cells, heart cells, brain cells, neural tissue, thyroid cells, eye cells, skeletal muscle cells, cartilage, bone tissue, and cells from airway passages. In embodiments, the tissue is a skin biopsy. In more specific embodiments, administering the ILT7 binding protein causes a reduction in skin pDCs. In embodiments, tissues in which pDCS are reduced include, but are not limited to, scalp, eyebrows, nails, and eyelashes. In embodiments, the tissue is a scalp biopsy. In embodiments, administering an ILT7 binding protein causes a reduction in pDCs in tissues that contain hair follicles.

[0097] Normally, pDCs are not present in skin tissue, and immature pDCs are typically only found in blood, thymic lymphoid tissue, tonsils, and lung tissue. Thus, the presence of pDCs in a skin biopsy sample indicates an abnormal condition in which pDCs are recruited to the skin. Thus, the method of the present disclosure comprises administering an ILT7 binding protein to a subject in need of treatment for a condition characterized by the presence of pDCs in the skin of the subject. The method of the present disclosure comprises reducing the level of pDCs in the skin of a subject by administering an ILT7 binding protein to a subject in need of treatment.

[0098] In an embodiment, the presence of pDC in a skin (e.g., scalp) biopsy sample indicates an abnormal condition in which pDC is recruited to the skin. Thus, the method of the present disclosure comprises administering an ILT7 binding protein to a subject in need of treatment for a condition characterized by the presence of pDC in the skin of the subject. In a particular embodiment, the pDC is located in the hair follicle of the subject. In an embodiment, the pDC is located at the bottom of the hair follicle. The method of the present disclosure comprises reducing the level of pDC in the skin of a subject by administering an ILT7 binding protein to a subject in need of treatment.

[0099] In embodiments, subjects have elevated or high levels of pDCs in skin tissue prior to treatment. In embodiments, subjects with high levels of pDCs in skin tissue prior to treatment are more responsive to treatment. In embodiments, subjects with high levels of pDCs in skin tissue are more responsive to treatment. In embodiments, subjects with high levels of pDCs in skin tissue are more responsive to treatment. 2 of skin tissue, at least about 60 pDC / mm 2 of skin tissue, at least about 70 pDC / mm 2 of skin tissue, at least about 80 pDC / mm 2 of skin tissue, at least about 90 pDC / mm 2 of skin tissue, at least about 100 pDC / mm 2 of skin tissue, at least about 110 pDC / mm 2 of skin tissue, at least about 120 pDC / mm 2 of skin tissue, at least about 125 pDC / mm 2 of skin tissue, at least about 150 pDC / mm 2of skin tissue, at least about 175 pDC / mm 2 of skin tissue, at least about 200 pDC / mm 2 In an embodiment, the low pDC level in the skin tissue is ≦10 pDC / mm of skin tissue or more. 2 In an embodiment, the high pDC level in skin tissue is at least about 100 pDC / mm 2 It is considered to be skin tissue.

[0100] In an embodiment, the method of the disclosure comprises administering an ILT7 binding protein used in the methods described herein to suppress type I IFN release from pDCs regardless of the location of the pDCs. In another embodiment, the method of the disclosure comprises administering an ILT7 binding protein to suppress type I IFN release from pDCs in the blood or circulation. In another embodiment, the method of the disclosure comprises administering an ILT7 binding protein to suppress type I IFN release from local pDCs. In another embodiment, the method of the disclosure comprises administering an ILT7 binding protein to suppress type I IFN release from pDCs in the skin of a subject. In an embodiment, the type I IFN whose release is suppressed is IFNα. In an embodiment, ILT7 binding protein-mediated suppression of type I IFN release from pDCs causes a reduction in type I IFNGS.

[0101] In an embodiment, when the autoimmune disease is alopecia, the treatment comprises applying or administering an ILT7 binding protein used in the methods described herein to a subject in need thereof or a subject suspected of needing such treatment, or applying or administering an ILT7 binding protein used in the methods described herein to an isolated tissue (e.g., scalp, eyebrows, nails, and / or eyelashes), where the subject has a disease, symptoms of a disease, or a predisposition to a disease (e.g., alopecia areata). Even if a formal diagnosis has not been confirmed, a subject may be suspected of needing a treatment as described herein if the subject exhibits symptoms of a condition or disease by excessive pDC number or activity. In an embodiment, a subject in need of treatment has a higher baseline blood type I IFNG level compared to an otherwise comparable subject who does not need treatment or is otherwise healthy. In embodiments, treatment is also intended to include application or administration of a pharmaceutical composition comprising an ILT7 binding protein used in the methods described herein to a subject in need thereof or suspected of needing such treatment, or application or administration of a pharmaceutical composition comprising an ILT7 binding protein used in the methods described herein to a tissue or cell line isolated from a subject having a disease, a symptom of a disease, or a predisposition to a disease (e.g., alopecia areata). In embodiments, treatment includes application or administration of an ILT7 binding protein used in the methods described herein to a subject in need thereof or suspected of needing such treatment, or application or administration of an ILT7 binding protein used in the methods described herein to an isolated tissue (e.g., scalp, eyebrows, nails, and / or eyelashes), where the subject has a disease, a symptom of a disease, or a predisposition to a disease (e.g., alopecia areata). A subject may be suspected of being in need of a treatment as described herein, even if a formal diagnosis has not been confirmed, if the subject is exhibiting symptoms of a condition or disease by excessive pDC numbers or activity. In embodiments, a subject in need thereof has elevated baseline blood type I interferon levels (eg, IFNα) as compared to an otherwise similar healthy subject.In embodiments, treatment is also intended to include applying or administering a pharmaceutical composition comprising an ILT7 binding protein used in the methods described herein to a subject in need thereof or suspected of being in need of such treatment, or applying or administering a pharmaceutical composition comprising an ILT7 binding protein used in the methods described herein to a tissue or cell line isolated from a subject having a disease, a symptom of a disease, or a predisposition to a disease (e.g., alopecia areata). In embodiments, the methods provided herein include evaluating the efficacy of daxudilimab compared to a placebo to reduce hair loss in a subject having alopecia areata. The evaluation may be performed at any time. In embodiments, the evaluation is performed prior to, concurrent with, or after administration. In embodiments, the evaluation is performed 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, or 60 weeks after administration of the ILT7 binding protein. In embodiments, the evaluation is performed at weeks 12-36 and / or 40-48. In an embodiment, administration of ILT7 binding protein is effective to reduce hair loss in a treated subject, compared to an otherwise equivalent subject that does not receive the administration.Administration of ILT7 binding protein is effective to reduce hair loss in a treated subject for about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 1 year, 1.5 years, 2 years, 3 years, 4 years, or up to about 5 years.In an embodiment, the treated subject experiences reduced hair loss through about 9 months of treatment with the ILT7 binding protein of the present disclosure.

[0102] The present disclosure provides a method for treating a subject with elevated type I IFNGS, comprising administering an ILT7 binding protein as described herein. A subject may exhibit elevated type I IFNGS if suffering from an autoimmune disorder. Thus, the present disclosure provides a method for treating an autoimmune disorder when the subject exhibits elevated type I IFNGS. In an embodiment, the autoimmune disorder is otherwise asymptomatic. In an embodiment, the method provides for selecting a subject for treatment with an ILT7 binding protein, the method comprising: (i) determining the subject's baseline blood type I IFNGS level; and (ii) selecting a subject with a high baseline blood type I IFNGS level for treatment with an ILT7 binding protein.

[0103] In an embodiment, type I IFNGS is a 21-gene signature. In an embodiment, type I IFNGS in a subject is elevated at least 1.5-fold compared to normal score before treatment. In an embodiment, type I IFNGS in a subject is elevated at least 2-fold compared to normal score before treatment. In an embodiment, a subject with elevated type I IFNGS before treatment responds to treatment. In an embodiment, type I IFNGS is at least about 4-fold, at least about 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, at least about 10-fold, at least about 11-fold, at least about 12-fold, or more compared to normal score before treatment with an ILT7 binding protein used in the methods described herein. In certain embodiments, type I IFNGS is determined from a skin biopsy. In other embodiments, tissue type I IFNGS is determined using IFN-inducible myxovirus protein A (MxA) immunohistochemistry (IHC) test. In a further aspect, expression of IFN-inducible genes in the epidermis is determined using skin tape stripping, RNA isolation, and gene expression profiling (https: / / dermtech.com / wp-content / uploads / Lupus-Reference.pdf).

[0104] In an embodiment, the present disclosure relates to a method for reducing type I interferon gene signature (IFNGS) in a subject in need thereof, the method comprising administering a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein to the subject, wherein the ILT7 binding protein is administered to the subject if type I IFNGS is elevated in the subject compared to type I IFNGS in a normal subject. In an embodiment, the pharmacologic effective amount of the ILT7 binding protein is about 200 mg.

[0105] In embodiments, the type I IFNGS comprises the expression levels of all type I IFN-inducible genes in a biological sample. In other embodiments, the type I IFNGS comprises the expression levels of a subset of type I IFN-inducible genes in a biological sample.

[0106] In embodiments, type I IFNGS is determined by assaying the expression levels of at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 15, at least 20, at least 25, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 200, at least 300, at least 400, or at least 500 type I IFN-inducible genes in a biological sample. In embodiments, type I IFNGS comprises the collective expression levels of two or more type I IFN-inducible genes. In embodiments, the two or more type I interferon (IFN) inducible genes include, but are not limited to, two or more genes selected from SPATS2L, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, RSAD2, RTP4, SIGLEC1, or USP18. In embodiments, type I IFNGS is determined by assaying the collective expression levels of SPATS2L, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, RSAD2, RTP4, SIGLEC1, and USP18. These gene symbols are well known in the art and refer to the human and non-human orthologs of the listed genes.

[0107] (Table 2) Gene symbols and their associated names TIFF2024516698000003.tif158165

[0108] In an embodiment, the expression level of a type I interferon (IFN)-inducible gene is determined by measuring the DNA level (e.g., complementary DNA or cDNA level) of the type I interferon (IFN)-inducible gene in a biological sample. In an embodiment, the expression level of a type I interferon (IFN)-inducible gene is determined by measuring the messenger RNA (mRNA) level of the type I interferon (IFN)-inducible gene in a biological sample. In an embodiment, the type I IFNGS comprises the mRNA level of all type I IFN-inducible genes in a biological sample. In other embodiments, the type I IFNGS comprises the mRNA level of a subset of type I IFN-inducible genes in a biological sample taken from a subject suffering from, likely to suffer from, or suspected of suffering from a disease (e.g., an autoimmune disease). In an embodiment, the type I IFNGS is determined by assaying the mRNA levels of two or more type I interferon (IFN)-inducible genes in a biological sample. In embodiments, type I IFNGS is determined by assaying mRNA levels of 21 type I interferon (IFN)-inducible genes (e.g., SPATS2L, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, RSAD2, RTP4, SIGLEC1, and USP18) in a biological sample. In embodiments, the biological sample is a test biological sample. In other embodiments, the biological sample is a normal biological sample.

[0109] In an embodiment, type I IFNGS is measured in a test biological sample taken from a subject. In another embodiment, pDC is measured in a test biological sample taken from a subject. Biological samples include, but are not limited to, blood, sputum, saliva, skin cells, skin biopsy samples, kidney cells, lung cells, liver cells, heart cells, brain cells, neural tissue, thyroid cells, eye cells, skeletal muscle cells, cartilage, bone tissue, cells from airway passages, and cultured cells. In an embodiment, the biological sample is blood. In another embodiment, the biological sample is tissue. In a more specific embodiment, the sample is tissue that includes skin cells. In another embodiment, the sample is a skin biopsy sample.

[0110] In embodiments, administration of a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof results in about a 1% to about 100% reduction in type I IFNGS in the subject compared to type I IFNGS prior to administration of an ILT7 binding protein used in the methods described herein. In embodiments, administration of a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof results in at least about 1%, at least about 2%, at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% reduction in type I IFNGS in the subject compared to type I IFNGS prior to administration of an ILT7 binding protein used in the methods described herein. In embodiments, administration of a therapeutically effective amount of an ILT7 binding protein results in at least about a 50% reduction in type I IFNGS in a subject.

[0111] In embodiments, administration of an ILT7 binding protein used in the methods described herein to a subject in need thereof results in at least about a 50% reduction in type I IFNGS in the subject compared to type I IFNGS prior to administration of an ILT7 binding protein used in the methods described herein. In embodiments, administration of a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof results in at least about a 50% reduction in type I IFNGS in the subject about 8 hours, about 12 hours, about 24 hours, or about 48 hours after administration of the ILT7 binding protein.

[0112] In embodiments, a subject administered a therapeutically effective amount of an ILT7 binding protein used in the methods described herein exhibits at least about a 50% reduction in type I IFNGS about 24 hours after administration of the ILT7 binding protein compared to type I IFNGS in the subject prior to administration of the ILT7 binding protein.

[0113] In embodiments, the reduction in type I IFNGS persists for at least about 1 day, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 6 days, at least about 7 days, at least about 14 days, at least about 21 days, at least about 28 days, at least about 30 days, at least about 45 days, at least about 60 days, at least about 90 days, or at least about 180 days or more after administering a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof. In embodiments, the reduction in type I IFNGS persists for up to about 30 days after administering a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof. In additional embodiments, the reduction in type I IFNGS persists for up to about 60 days after administering a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof.

[0114] In embodiments, the methods of the present disclosure can be used to monitor the effectiveness of treatment of a condition or disorder by monitoring the levels of type I IFNGS and / or activated pDCs. As discussed above, autoimmune conditions are often characterized by elevated type I IFNGS and / or elevated pDCs, and thus monitoring the effectiveness of treatment can include monitoring type I IFNGS and / or pDC levels.

[0115] Thus, in some aspects, the disclosure provides a method of monitoring the effectiveness of a treatment for an autoimmune disorder or condition, the method comprising: (a) measuring a type I interferon gene signature (IFNGS) in a biological sample taken from the subject to obtain a baseline value of type I IFNGS; and (b) measuring type I IFNGS in a biological sample taken from the subject after administration of a treatment, wherein the treatment comprises administering an ILT7 binding protein, and wherein a reduction in type I IFNGS in step (b) compared to the baseline value indicates that the treatment is effective in the subject.

[0116] In embodiments, the treatment results in a reduction in type I IFNGS compared to baseline values. In embodiments, the reduction in type I IFNGS compared to baseline values ​​ranges from about 1% to about 99%. In embodiments, the reduction in type I IFNGS compared to baseline values ​​is at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%. In embodiments, the reduction in type I IFNGS compared to baseline values ​​is at least about 30%. In embodiments, the reduction in type I IFNGS compared to baseline values ​​is at least about 50%.

[0117] In embodiments, the elevation of type I IFNGS in the test biological sample compared to a normal biological sample, or in a subject in need of treatment with an ILT7 binding protein compared to a normal subject, is a fold change of at least about 1.1 to about 1000. Thus, in embodiments, type I IFNGS is elevated by at least about 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 fold in the test biological sample compared to a normal biological sample, or in a subject in need of treatment with an ILT7 binding protein compared to a normal subject. In embodiments, type I IFNGS is elevated by at least about 4 fold in the test biological sample compared to a normal biological sample, or in a subject in need of treatment with an ILT7 binding protein compared to a normal subject.

[0118] In embodiments, the present disclosure is directed to a method of reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein. In embodiments, the pharmacologic effective amount of the ILT-7 binding protein is 150 mg. In embodiments, the pharmacologic effective amount of the ILT-7 binding protein is 200 mg. In embodiments, the pharmacologic effective amount of the ILT-7 binding protein is 300 mg. In embodiments, the ILT7 binding protein is administered about once every four weeks. In embodiments, the ILT7 binding protein is administered about once every twelve weeks. In embodiments, the ILT7 binding protein is administered about once every twelve weeks, and the subject is administered an additional 200 mg dose of the ILT7 binding protein about four weeks after the initial dose. In aspects, the disclosure is directed to a method of reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 200 mg, and the subject is administered a first dose, a second dose about 4 weeks after the first dose, a third dose about 12 weeks after the first dose, and a subsequent dose about 12 weeks after the third dose.

[0119] In an embodiment, the present disclosure is directed to a method of reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein. In an embodiment, the pharmacologic effective amount of the ILT7 binding protein is about 100 mg, 150 mg, 200 mg, 250 mg, or 300 mg. In an embodiment, the ILT7 binding protein is administered about every 4 weeks, every 12 weeks, or a combination thereof. In an embodiment, the ILT7 binding protein is administered every week, every 2 weeks, every 3 weeks, every 4 weeks, every 12 weeks, or a combination thereof. In an embodiment, the ILT-7 binding protein is daxudilimab. In an embodiment, the autoimmune disease is lupus. In an embodiment, the autoimmune disease is SLE. In an embodiment, the autoimmune disease is DLE. In an embodiment, the autoimmune disease is alopecia areata. In an embodiment, the autoimmune disease is dermatomyositis.

[0120] In embodiments, the reduction in pDCs in a subject is about 1% to about 100% compared to pDCs in the subject prior to administration of an ILT7 binding protein used in the methods described herein. In embodiments, the reduction in pDCs in a subject is at least about 1%, at least about 2%, at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% compared to pDCs in the subject prior to administration of an ILT7 binding protein used in the methods described herein. In embodiments, the reduction in pDCs in a subject is at least about 50% compared to pDCs in the subject prior to administration of an ILT7 binding protein used in the methods described herein. Thus, in embodiments, administration of a therapeutically effective amount of an ILT7 binding protein results in at least about a 10% reduction in the total number of pDCs in the subject. In additional embodiments, administration of a therapeutically effective amount of an ILT7 binding protein results in at least about a 10% reduction in activated pDCs in the subject. In embodiments, pDCs are measured in a test biological sample taken from the subject. Thus, in embodiments, administration of a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof results in a reduction in pDCs in a test biological sample taken from the subject. In embodiments, the reduction in pDCs in a test biological sample taken from the subject is at least about 10% compared to pDCs in the test biological sample prior to administration of an ILT7 binding protein used in the methods described herein. In embodiments, the test biological sample is blood. In embodiments, the test biological sample is tissue, including but not limited to skin cells and skin biopsy specimens. In embodiments, the pDCs are circulating pDCs. In other embodiments, the pDCs are pDCs in the skin. In an additional embodiment, the reduction of pDCs is reversible.

[0121] In embodiments, administration of a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof results in at least about a 10% reduction in pDCs in the subject about 5 minutes, about 10 minutes, about 15 minutes, about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 6 hours, about 12 hours, about 24 hours, or about 48 hours after administration of the ILT7 binding protein. In other embodiments, administration of a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof results in at least about a 10% reduction in pDCs in a test biological sample taken from the subject about 5 minutes, about 10 minutes, about 15 minutes, about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 6 hours, about 12 hours, about 24 hours, or about 48 hours after administration of the ILT7 binding protein. In embodiments, administration of a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof results in at least about a 10% reduction in pDCs in the subject about 1 week, 2 weeks, 3 weeks, 1 month, 3 months, 5 months, 8 months, 12 months, or 1.5 years after administration of the ILT7 binding protein. In embodiments, administration of a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof results in at least about a 10% reduction in pDCs in a test biological sample taken from the subject about 12 hours, about 24 hours, or about 48 hours after administration of the ILT7 binding protein.

[0122] In embodiments, the reduction in pDCs persists for at least about 1 day, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 6 days, at least about 7 days, at least about 14 days, at least about 21 days, at least about 28 days, at least about 30 days, at least about 45 days, at least about 60 days, at least about 90 days, or at least about 180 days or more after administering a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof. In embodiments, the reduction in pDCs persists for at least about 30 days after administering a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof. In additional embodiments, the reduction in pDCs persists for at least about 60 days after administering a therapeutically effective amount of an ILT7 binding protein used in the methods described herein to a subject in need thereof.

[0123] In an embodiment, a method for preventing or treating dermatomyositis is provided. In an embodiment, the method comprises administering a composition comprising an effective amount of daxudilimab to treat dermatomyositis. In an embodiment, the administration is effective to reduce or eliminate a symptom of dermatomyositis selected from the group consisting of skin rash, muscle weakness, dysphagia, fatigue, scaly skin, calcification, and inflammation. In an embodiment, the symptom is reduced by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 90%, 120%, 140%, 160%, 180%, or 200% compared to an otherwise similar subject lacking administration.

[0124] evaluation In an embodiment, the method provided herein includes evaluating the effect of daxuzilimab compared to a placebo to reduce or eliminate symptoms of an autoimmune disease. The evaluation of the autoimmune disease can be performed at any time. In an embodiment, the evaluation is performed before, simultaneously with, or after administration of any of the compositions provided herein. In an embodiment, the evaluation is performed 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 24, 30, 40, 45, 48, 50, 52, 60, 64, 70, 80, 90, 100, 104, or 110 weeks after administration of daxuzilimab. In an embodiment, the evaluation is performed 48 weeks after administration.

[0125] In embodiments, the methods provided herein include assessing sustained oral glucocorticoid reduction following administration of daxuzilimab. In embodiments, the assessment includes determining the percentage of subjects on ≧10 mg of oral glucocorticoids achieving ≦7.5 mg / day of prednisone or equivalent OCG at baseline (Day 1). The assessment may be performed at any time. In embodiments, the assessment is performed prior to, concurrent with, or after administration. In embodiments, the assessment is performed at weeks 1-10, 20-40, 30-50, or 1-50. In embodiments, the assessment is performed at weeks 36-48.

[0126] In other aspects, the disclosed methods can be used to reduce Cutaneous Lupus Erythematosus Disease Activity and Severity Index (CLASI) in a tissue of a subject in need thereof. The methods include administering a pharmacologic effective amount of an ILT7 binding protein to a subject. In aspects, the ILT7 binding protein is administered in a dose of 200 mg. In certain aspects, the ILT7 binding protein is administered about once every 4 weeks. In aspects, the ILT7 binding protein is administered about once every 12 weeks. In one aspect, the ILT7 binding protein is administered about once every 12 weeks, and the subject is administered an additional 200 mg dose of the ILT7 binding protein about 4 weeks after the initial dose.

[0127] As used herein, the term "CLASI" refers to the Cutaneous Lupus Erythematosus Disease Activity and Severity Index. The CLASI is a validated instrument for measuring the cutaneous manifestations of CLE. The CLASI is composed of two scores, the first summarizing the inflammatory activity of the disease and the second a measure of the damage caused by the disease. The activity scores include erythema (0-3), scaling / hypertrophy (0-2), mucosal lesions (0-1), recent alopecia (0-1), and non-scarring alopecia (0-3). The damage scores represent pigmentation abnormalities (0-1), scarring / atrophy / panniculitis (0-2), and scalp scarring (0-6). Subjects are asked if the pigmentation abnormalities have persisted for more than 12 months, in which case the pigmentation abnormality score is doubled. Each of the above parameters is measured in 13 different anatomical locations specifically included for their most frequent involvement in CLE. The most severe lesions in each area are measured.

[0128] As used herein, the term "reduced CLASI" refers to a reduction in the level of CLASI-Activity (CLASI-A) score in a subject or in a biological sample taken from a subject (e.g., tissue such as skin cells, skin biopsy samples, etc.), or a reduction in the level of CLASI Impairment (CLASI-D) score in a subject or in a biological sample taken from a subject, or both.

[0129] In embodiments, the methods of the disclosure include evaluating the effect of administration of daxuzilimab compared to placebo to reduce skin disease activity. In embodiments, the evaluation includes determining the percentage of subjects with a CLASI-A score of 10 or greater at baseline (day 1) and achieving a 50% or greater reduction in CLASI-A score from baseline (day 1). Scoring includes evaluating at least one of the inflammatory activity of the disease and / or the damage done by the disease. The evaluation can be performed at any time. In embodiments, the evaluation is performed before, simultaneously with, or after administration. In embodiments, the evaluation is performed 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 weeks after administration of daxuzilimab. In embodiments, the evaluation is performed 12 weeks after administration.

[0130] Thus, in an embodiment, the method of the present disclosure results in a reduction in the CLASI-A score in a subject. In an embodiment, the reduction in the CLASI-A score of a subject involves a reduction in the CLASI-A score of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 points from the baseline value. In an embodiment, the reduction in the CLASI-A score of a subject involves a reduction in the CLASI-A score of at least 4 points from the baseline value. In an embodiment, the reduction in the CLASI-A score of a subject involves a reduction in the CLASI-A score of at least 7 points from the baseline value. In other embodiments, the reduction in the CLASI-A score of a subject involves a reduction in the CLASI-A score of at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% from the baseline value. In embodiments, the reduction in the subject's CLASI-A score involves a reduction in the CLASI-A score of at least 50% from the baseline value. In embodiments, the baseline value is the value of the CLASI-A score in the subject prior to treatment with an ILT7 binding protein used in the methods described herein. In other embodiments, the methods of the disclosure result in a reduction in the CLASI-D score in the subject. In additional embodiments, the methods of the disclosure result in a reduction in the CLASI-A score and a reduction in the CLASI-D score in the subject.

[0131] In embodiments, the method includes assessing lupus low disease activity status (LLDAS) disease activity. In embodiments, the assessment includes measuring the percentage of subjects achieving the LLDAS. The LLDAS is a composite measure of SLE disease activity that measures five criteria: (1) SLEDAI-2K≦4, no activity in major organ systems, (2) no new lupus disease activity, (3) PGA≦1 (scale 0-3), (4) current prednisone or equivalent dose ≦7.5 mg / day, (5) tolerated maintenance dose of immunosuppressant and approved biologic agent. The assessment can be performed at any time. In embodiments, the assessment is performed prior to, concurrent with, or after administration. In embodiments, the assessment is performed 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, or 60 weeks after administration of daxuzilimab. In embodiments, the assessment is performed 48 weeks after administration.

[0132] In embodiments, a subject in need thereof or a sample from a subject in need thereof is evaluated using an in vitro test. Suitable in vitro tests include, but are not limited to, the following: SLE Disease Activity Index 2000 (SLEDAI-2K), British Isles Lupus Assessment Group (BILAG) 2004 index, Physician Global Assessment (PGA), classification criteria for SLE, antinuclear antibody (ANA), anti-dsDNA antibody, anti-Smith antibody, and any combination thereof.

[0133] In embodiments, the subject in need thereof includes at least one or all of the following: being 18 to 70 years of age at the time of signing the informed consent form (ICF); being able to understand and provide written informed consent to comply with all study requirements and complete study assessments prior to any study-related procedures; meeting the 2019 European League Against Rheumatism / American College of Rheumatology classification criteria for SLE (Aringer et al., 2019); disease duration of at least 6 months from time of diagnosis at the time of signing the ICF; active SLE as indicated by the presence of all of the following: SLEDAI-2K total score ≥6 at Screening, excluding fever, SLE headache, or organic brain syndrome; SLEDAI-2K total score ≥4 at Screening and Baseline (Day 1), excluding points attributable to urine or laboratory results, immunological measures, fever, SLE headache, or organic brain syndrome; at least one of the following BILAG 2004 index levels of disease at Screening: BILAG in ≥1 organ system; A disease and / or BILAG B disease in ≥2 organ systems, PGA score ≥1 on a 0-3 visual analog scale (VAS) at screening, at least one of the following at screening per central laboratory: antinuclear antibodies (ANA) ≥1:80, anti-dsDNA antibodies elevated above the normal range established by the central laboratory (i.e., positive result), anti-Smith antibodies above normal (i.e., positive result), ongoing treatment for SLE defined as (a) or (b): (a) treatment with disease-modifying antirheumatic drugs (DMARDs) or immunosuppressants: One of the following drugs will be administered for the treatment of SLE at conventional antirheumatic doses for at least 12 weeks prior to screening (unless discontinued or dose adjusted for documented drug-related toxicity or size / weight) and at a stable dose (including route of administration) for a minimum of 8 weeks prior to screening and maintained through baseline (Day 1): (1) antimalarials (chloroquine, hydroxychloroquine, quinacrine), (2) azathioprine (AZA) or 6-mercaptopurine (6-MP), (3) leflunomide,(4) mycophenolate mofetil (MMF) or mycophenolic acid (MPA), (5) methotrexate (MTX) (if MTX is used, subjects must receive concomitant folic acid or folic acid supplementation), (6) voclosporin (if approved for treatment), and / or (7) GC are permitted but not required if subjects receive at least one other drug listed above. If glucocorticoids are used in combination with tolerated DMARDs or immunosuppressants, they may be on a stable dose for a minimum of 2 weeks prior to screening, with an average daily dose of ≦40 mg PO prednisone (or prednisone equivalent), and a minimum of 2 weeks prior to screening. In addition, the dose of OGC must be maintained stable for at least 2 weeks prior to randomization. PO prednisone (or prednisone equivalent) administered daily or every other day is permitted, and (b) treatment with oral glucocorticoid monotherapy (without concomitant DMARDs or immunosuppressants): mean daily dose of PO prednisone (or prednisone equivalent) ≥ 10 mg ≤ 40 mg for at least 4 weeks prior to screening, and stable dose for at least 2 weeks prior to screening. In addition, the dose of OGC must be maintained stable for at least 2 weeks prior to randomization. PO prednisone (or prednisone equivalent) administered daily or every other day is permitted, and women of childbearing potential must have a negative urine pregnancy test at the time of randomization. Women of childbearing potential are defined as women who are not surgically sterilized (i.e., surgical sterilization includes bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or who are not postmenopausal (defined as 12 months without menses without another medical cause and without follicle-stimulating hormone [FSH] within the postmenopausal range established by a central laboratory, unless receiving postmenopausal hormone replacement therapy). Women of childbearing potential who are sexually active with a nonsterilized male partner must agree to use highly effective contraceptive methods by signing an informed consent and must agree to continue using such precautions until the end of study follow-up or for 3 months (approximately 5 half-lives) after the last dose of study drug if the study is discontinued early. Decisions regarding contraception after this point must be made by the individual.This should be done by the subject and her usual health care provider. Continuous abstinence is an acceptable practice, but periodic abstinence, rhythm methods, and withdrawal methods are not acceptable contraceptive methods. In an embodiment, because mycophenolate may affect the metabolism of hormonal contraceptives and reduce their effectiveness in women receiving MMF or MPA who use hormonal contraceptives for contraception, subjects must employ an additional method of contraception (e.g., a barrier method) and / or unsterilized male subjects who are sexually active with a fertile female partner must agree to use a condom containing spermicide from randomization until 3 months (approximately 5 half-lives) after receipt of the final dose. Because male condoms containing spermicide are not a highly effective method of contraception, it is strongly recommended that male subjects advise their fertile female partners to use a highly effective method of contraception throughout this period.

[0134] In embodiments, the subject in need may not have a history of allergy, hypersensitivity, or anaphylaxis to any component of the provided compositions, previous mAb, and / or human Ig therapy. In embodiments, the subject is not a subject enrolled in another clinical trial with IP within 4 weeks prior to day 1 or within 5 published half-lives, whichever is longer. In embodiments, the subject is not breastfeeding or pregnant, or planning to become pregnant by 6 months after signing the ICF and administering the last dose of IP. In embodiments, the subject does not have a history of drug or alcohol abuse that, in the opinion of the investigator, may affect the subject's safety or compliance with visits or interfere with other study evaluations. In embodiments, the subject has not had major surgery within 8 weeks prior to screening or scheduled elective surgery by day 393 from screening. In embodiments, the subject has not had a spontaneous or induced abortion, stillbirth, or live birth, or is not pregnant, within ≦4 weeks prior to screening. In embodiments, subjects do not have a known history of major immune deficiency or underlying conditions such as known human immunodeficiency virus (HIV) infection, a positive result for HIV infection per a central laboratory, splenectomy, or any underlying condition that, in the opinion of the investigator, renders the subject significantly more susceptible to infection.

[0135] In embodiments, subjects at screening do not have any of the following per central laboratory (tests may be repeated once within the same screening period to confirm results prior to randomization): AST > 2.5 x ULN, ALT > 2.5 x ULN, total bilirubin > 1.5 x ULN (except in cases due to Gilbert's syndrome), serum IgG < 600 mg / dL (or < 6 g / L), neutrophil count < 1000 / μL (or < 1.0 x 10 9 / L) or ≤500 / μL (≤0.5 × 10) if due to active SLE 9 / L), platelet count ≦50,000 / μL (or ≦50×10 9 / L) or ≤250,000 / μL (or ≤25 × 10 9 / L), hemoglobin ≤ 8g / dL (or ≤ 80g / L) or ≤ 7g / dL (≤ 70g / L) if due to active SLE, glycosylated hemoglobin ≥ 8% (or ≥ 0.08), total lymphocyte count ≤ 200 cells / mm 3 , glomerular filtration rate ≤ 30 mL / min / 1.73 m 2 , UPCr≧3mg / mg, confirmed positive test for Hepatitis B serology defined as: Hepatitis B surface antigen (HBsAg), or Hepatitis B core antibody (HBcAb) and Hepatitis B virus (HBV) DNA detected above the lower limit of quantification (LLOQ) by reflex testing by a central laboratory at screening. In embodiments, subjects who are HBcAb positive at screening are tested every 3 months for HBV DNA. In embodiments, if the subject's HBV DNA level is confirmed to be above the LLOQ according to the central laboratory, the study drug is discontinued. In embodiments, the subject does not test positive for Hepatitis C virus antibodies. In embodiments, the subject does not test positive for IFNγ release assay (IGRA) at screening unless they have active tuberculosis or have a documented history of adequate treatment for active or latent TB. In embodiments, subjects with indeterminate IGRA test results may repeat testing, but if the repeat test is also indeterminate, they are excluded from administration of the compositions provided herein. In embodiments, the subject does not have any severe herpes virus family infection (including Epstein-Barr virus, cytomegalovirus [CMV]) at any time prior to randomization, including but not limited to disseminated herpes, herpes encephalitis, recent recurrent herpes zoster (defined as 2 episodes within the past 2 years), or ophthalmic herpes. In embodiments, the subject does not have any herpes zoster, CMV, or Epstein-Barr virus infection that was not completely resolved 12 weeks prior to randomization.

[0136] In aspects, subjects will not have any of the following within 30 days prior to signing the ICF through randomization: ongoing and chronic infections that, in the opinion of the investigator, require antibiotics or antivirals (chronic nail infections are permitted), any infection requiring hospitalization or treatment with IV anti-infectives; subjects with a documented positive SARSCoV-2 test may be rescreened at least 2 weeks after the positive test if asymptomatic and at least 3 weeks after symptomatic COVID-19 illness; and / or clinically significant active infections, including opportunistic infections requiring hospitalization or parenteral antimicrobial treatment within the 2 years prior to randomization.

[0137] In embodiments, the subject has no evidence of acute illness or clinically significant active infection (eg, fever > 38.0°C (> 100.5°F) on day 1).

[0138] In embodiments, subjects have no history of clinically significant cardiac disease, including unstable angina, myocardial infarction within 6 months prior to randomization, congestive heart failure, arrhythmias requiring dynamic therapy except for clinically insignificant extrasystoles or minor conduction abnormalities, or the presence of clinically significant abnormalities on an ECG that, in the opinion of the investigator, would increase the risk of study participation. In embodiments, subjects have no history of cancer within the past 5 years, with the exception of intraepithelial carcinoma of the cervix treated with apparent success with definitive therapy >12 months prior to screening, or basal or squamous cell carcinoma of the skin treated with apparent success with definitive therapy.

[0139] In embodiments, the subject has not received a live attenuated vaccine within 4 weeks prior to day 1. In embodiments, the subject has not received an inactivated (killed) vaccine. In embodiments, the subject has received an inactivated (killed) vaccine.

[0140] In embodiments, subjects are assessed for epidemiological risk of COVID-19 (i.e., recent exposure, high-risk housing) and health-related risk of COVID-19 severity, based on current understanding of risk factors for severe disease, when making decisions regarding the risk of individual participation. Any subject who has COVID-19 or other serious infection, or who may be at high risk for COVID-19 or its complications in the investigator's judgment, should not be randomized.

[0141] In an embodiment, the subject does not have any one of active LN, active severe SLE, or unstable neuropsychiatric SLE. In an embodiment, the subject does not have a diagnosis of non-SLE vasculitis syndrome, mixed connective tissue disease, or rheumatic (overlap) syndrome. In an embodiment, the subject does not use immunosuppressants, biologics, and DMARDs within a protocol-defined washout period.

[0142] Score of Activity and Damage in DLE (SADDLE) In embodiments, the method includes determining a SADDLE score. SADDLE measures the severity of activity (erythema, scaling, induration) and damage (scarring / atrophy and dyspigmentation) due to DLE. The total score ranges from 0 to 195. In embodiments, the method includes determining a change from baseline in the SADDLE score. In embodiments, the mean change in the SADDLE score is determined. In embodiments, the SADDLE score changes by at least about 3%, 5%, 10%, 15%, 20%, 30%, 40%, 50%, 80%, 100%, 150%, 200%, or 400%. In embodiments, the SADDLE score changes by at least about 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, or 120 points.

[0143] Discoid Lupus Erythematosus Classification Criteria (DLECC) Score In embodiments, the methods include determining a change from baseline in the DLECC score, in embodiments, the DLECC score changes by at least about 3%, 5%, 10%, 15%, 20%, 30%, 40%, 50%, 80%, 100%, 150%, 200%, or 400%.

[0144] Severity Alopecia Tool (SALT) In an embodiment, the method includes determining the percent change from baseline in the SALT score of the treated subject. In an embodiment, the subject has moderate to severe AA as assessed by a SALT score of ≧50 and ≦95 at screening and baseline (day 1). The SALT score can be calculated by measuring the percentage of hair loss in each of the four regions of the scalp-vertex (40%), right profile (18%), left profile (18%), and back (24%) and summing to achieve a composite score. The SALT score can be determined at any time point after or before treatment to document the baseline. In an embodiment, the SALT score is determined at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 weeks. In an embodiment, SALT scores are decreased at weeks 12-20 and / or weeks 28-36 in treated subjects compared to untreated subjects.

[0145] In embodiments, administration of the ILT7 binding protein is effective to achieve a % change from baseline in SALT score at weeks 20-30, weeks 22-26, weeks 23-25, weeks 24-28, or weeks 23-26. In embodiments, administration of the ILT7 binding protein is effective to achieve a % change from baseline in SALT score at week 24. In embodiments, administration of the ILT7 binding protein is effective to stabilize or reduce the % change from baseline in SALT score compared to baseline or an otherwise similar subject lacking administration of the ILT7 binding protein. In embodiments, administration of an ILT7 binding protein is effective to stabilize or reduce the percent change from baseline in SALT score by at least about 5%, 10%, 20%, 30%, 40%, 50%, 70%, 90%, 100%, 120%, 140%, 160%, 180%, or up to about 200% compared to baseline or an otherwise similar subject lacking administration of an ILT7 binding protein. In embodiments, treated subjects achieve a ≧50% reduction in SALT compared to baseline.

[0146] In embodiments, the methods include determining the percentage of subjects having absolute SALT scores of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, or 55 or less at weeks 30-40, 35-45, 40-48, 40-45, or 40-50. In embodiments, the methods include determining the percentage of subjects having absolute SALT scores of 10, 20, 30, 50 or less at weeks 40-48.

[0147] Physician-reported outcomes (ClinRO) for eyebrow hair removal Physician-Reported Outcomes (ClinRO) were used to assess eyebrow and eyelash involvement. The ClinRO™ for Eyebrow Alopecia and ClinRO™ for Eyelash Alopecia consist of single-item, 4-point Likert-type response scales to assess the incremental severity of each ClinRO measurement.

[0148] In embodiments, the percentage of subjects achieving a ClinRO with an eyebrow hair loss score of 0 or 1 (full coverage or minimal gaps) and a ≧2 point improvement from baseline (baseline score ≧2 (noticeable gaps to no noticeable hair)) at each visit is determined. In embodiments, the percentage of subjects achieving a ClinRO with an eyelash hair loss score of 0 or 1 (full coverage or minimal gaps) and a ≧2 point improvement from baseline (baseline score ≧2 (noticeable gaps to no noticeable hair)) at each visit is determined. In embodiments, treatment with an ILT7 binding protein is effective in stabilizing or reducing eyelash and / or eyebrow hair loss.

[0149] In embodiments, a subject maintains or achieves a reduction in ClinRO for at least about 1 month, 3 months, 5 months, 8 months, 1 year, 1.5 years, or up to about 2 years after treatment with an ILT7 binding protein of the disclosure.

[0150] Alopecia Density and Extent (ALODEX) Score In an embodiment, the method includes determining an ALODEX score. The ALODEX score combines both the extent and hair density into an overall percentage of scalp hair loss. A density scale of 0-10 relates to the percentage of terminal hair loss, with 100% hair loss equal to 10, 90% equal to 9, 80% equal to 8, 70% equal to 7, 60% equal to 6, 50% equal to 5, 40% equal to 4, 30% equal to 3, 20% equal to 2, 10% equal to 1, and no hair loss equal to 0. The density assignments of each 1% scalp area in a given quadrant are summed and divided by the maximum grade of hair loss (10) to obtain the percentage of hair loss in that quadrant. The scores for each quadrant are then summed to obtain the ALODEX score. In an embodiment, treatment with an ILT7 binding protein of the present disclosure is effective to maintain or reduce the ALODEX score in a treated subject. In embodiments, treatment with an ILT7 binding protein of the disclosure is effective to reduce the ALODEX score by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 points in a treated subject compared to an untreated subject. In embodiments, treatment with an ILT7 binding protein of the disclosure is effective to reduce the ALODEX score by at least about 1-3, 2-4, 1-5, 3-4, 2-5, or 4-5 points in a treated subject compared to an untreated subject.

[0151] Medical Photography In embodiments, medical photography is utilized in the methods described herein. Medical photography can be taken of any tissue of a subject. In embodiments, a photograph of the entire scalp is obtained. In embodiments, a photograph is taken of the eyebrows and / or eyelashes of a subject with hair loss in these areas. Photographs can be taken at any time. In embodiments, photographs are taken before, during, and after treatment. In embodiments, photographs are taken of an area selected from the group consisting of the scalp, eyebrows, and eyelashes. In embodiments, photographs are taken of an area including, but not limited to, a lesion (e.g., a DLE lesion). Any suitable camera can be utilized for the photography.

[0152] In aspects, the methods include determining the density of hair regrowth over time by medical photography. In aspects, digital photography is used to assess hair regrowth within the lesion over time. In aspects, medical photography is used to determine changes in characteristics of the discoid lesions, including but not limited to size and pigmentation abnormalities over time.

[0153] Pharmacokinetics In an embodiment, a subject sample is obtained for pharmacokinetic analysis. Pharmacokinetics includes two pathways: absorption, distribution, and drug elimination, metabolism, and excretion. Any subject sample can be utilized. In an embodiment, the sample includes a blood or serum sample. The sample can be taken for analysis of the concentration of ILT7 binding protein. The sample can be taken at any time. The sample can be taken before, during, and / or after administration of the ILT7 binding protein.

[0154] Pharmacodynamics In an embodiment, a subject's sample is obtained for pharmacodynamic analysis. Blood or serum samples can be taken for PD analysis of ILT7 binding protein at the time of visit and at the time points specified herein. PD analysis of ILT7 binding protein can include, but is not limited to, whole blood transcriptomics (e.g., IFN gene signature), pDC flow cytometry, PBMC (e.g., levels of other circulating cells), serum and plasma biomarkers, and / or blood MxA evaluation.

[0155] immunogenicity In an embodiment, a subject sample is obtained. Suitable samples include, but are not limited to, blood, serum, PBMC, or cell samples. In an embodiment, a sample is taken for analysis of serum ILT7 binding protein anti-drug antibodies (ADA). In an embodiment, if serum ADA is not detected, treatment is continued. In an embodiment, if serum ILT7 binding protein ADA is detected, treatment is continued. Suitable assays for detecting ADA are selected from the group consisting of: enzyme-linked immunosorbent assay (ELISA), radioimmunoprecipitation assay (RIP), electrochemiluminescence immunoassay (ECLIA), surface plasmon resonance immunoassay (SPRIA), and combinations thereof.

[0156] Vital signs In an embodiment, the method provided herein includes obtaining a subject's vital signs. The vital signs are selected from the group consisting of systolic blood pressure, diastolic blood pressure (mmHg), pulse (bpm), body temperature (°C), respiratory rate (breaths / min), weight (kg), and height (cm). In an embodiment, weight and height can be collected to calculate the subject's BMI. Vital signs can be determined at any time, for example, before, during, and after treatment.

[0157] Physical Examination In an embodiment, the method includes performing a physical examination of the subject, the physical examination including evaluating at least one of general appearance, skin, head, eyes, ears, nose, throat, respiratory, cardiovascular, abdominal, neurological, musculoskeletal, and / or lymphatic.

[0158] Physical examinations can be determined at any time, for example, before, during, and after treatment.

[0159] Lab Test In an embodiment, the method includes performing a laboratory test. The test can be selected from the group consisting of a urinalysis for women of childbearing potential, hematology, chemistry panel (with or without liver function tests), and serum pregnancy test (screening). In an embodiment, the laboratory test evaluates the levels of cell counts, cytokines, chemokines, gene expression, and combinations thereof. In an embodiment, the laboratory test evaluates the levels of one or more of IFN-α, IL-17, and IFNγ. In an embodiment, the laboratory test includes determining the level of eGFR. In an embodiment, the laboratory test includes determining the level of UPCR. In an embodiment, the method includes determining the level of eGFR≧60 mL / min / 1.73 m 2 In one embodiment, the method includes determining the proportion of subjects who achieve a CRR as measured by one or more of: an eGFR not less than 15% below baseline levels, a 24-hour UPCR > 0.5 mg / mg, or a combination thereof. In one embodiment, the method includes determining the proportion of subjects who achieve a CRR as measured by one or more of: an eGFR > 60 mL / min / 1.73 m 2 The proportion of subjects achieving ORR as measured by one or more of: eGFR not 15% below baseline level; or improvement in 24-hour UPCR. Improvement in UPCR may be determined by baseline UPCR ≦3.0 mg / mg: <1.0 mg / mg, or for subjects with baseline UPCR >3.0 mg / mg: >50% improvement from baseline and ≦3.0 mg / mg.

[0160] In an embodiment, the method comprises determining the level of IFN in a subject with an autoimmune disease and determining whether the subject has a higher level of IFN as determined by an in vitro assay and compared to an otherwise comparable healthy subject. 高 and treating the subject with an ILT7 binding protein of the present disclosure if 高 comprises a level of IFN that is at least about 5%, 10%, 15%, 20%, 25%, or 30% higher than the average level of a pool of healthy subjects or the healthy baseline level of the subject.

[0161] Quality of life In embodiments, the method includes determining quality of life. In embodiments, administration of the compositions provided herein is effective to improve the quality of life of the treated subject. Quality of life can be assessed by one or more of the following: Patient Global Assessment (PGA), Patient Global Impression Change (PGIC) scale, Dermatology Life Quality Index (DLQI) questionnaire, Cutaneous Lupus Erythematosus Quality of Life (CLE-QoL) questionnaire, or EQ-5D-5L questionnaire. In embodiments, the score improves (increases or decreases) by at least about 1, 3, 5, 10, 20, 30, 50, 60, 80, or 100 points. In embodiments, the score decreases after treatment with the compositions provided herein. In embodiments, the score decreases by at least 5%, 10%, 20%, 30%, or 40% after treatment.

[0162] Pharmaceutical Compositions The present disclosure also relates to pharmaceutical compositions comprising the ILT7 binding proteins used in the methods described herein. In an aspect, the present disclosure provides the use of the ILT7 binding proteins used in the methods described herein in the manufacture of a medicament for treating a subject.

[0163] In embodiments, a composition may comprise from about 100 mg / mL to about 170 mg / mL of anti-ILT7 binding protein. In embodiments, a composition may comprise from about 110 mg / mL to about 150 mg / mL of anti-ILT7 binding protein. In embodiments, a composition may comprise from about 120 mg / mL to about 150 mg / mL of anti-ILT7 binding protein. In embodiments, a composition may comprise from about 140 mg / mL to about 160 mg / mL of anti-ILT7 binding protein. In embodiments, a composition may comprise from about 145 mg / mL to about 155 mg / mL of anti-ILT7 binding protein.

[0164] In embodiments, the composition comprises about 100 mg / mL, 102 mg / mL, 104 mg / mL, 106 mg / mL, 108 mg / mL, 110 mg / mL, 112 mg / mL, 114 mg / mL, 116 mg / mL, 118 mg / mL, 120 mg / mL, 122 mg / mL, 124 mg / mL, 126 mg / mL, 128 mg / mL, 130 mg / mL, 132 mg / mL, 134 mg / mL, 136 mg / mL, 138 mg / mL, 140 mg / mL, 142 mg / mL, 144 mg / mL, 146 mg / mL, 148 mg / mL, 150 mg / mL, 152 mg / mL, 154 mg / mL, 156 mg / mL, 158 mg / mL, 160 mg / mL, 162 mg / mL, 164 mg / mL, 166 mg / mL, 168 mg / mL, 170 mg / mL, 172 mg / mL, 174 mg / mL, 176 mg / mL, 178 ... mg / mL, 146 mg / mL, 148 mg / mL, 150 mg / mL, 155 mg / mL, 160 mg / mL, or up to about 170 mg / mL, at least about 100 mg / mL, 102 mg / mL, 104 mg / mL, 106 mg / mL, 108 mg / mL, 110 mg / mL, 112 mg / mL, 114 mg / mL, 116 mg / mL, 118 mg / mL, 120 mg / mL, 122 mg / mL, 124 mg / mL, 126 mg / mL, 128 mg / mL, 130 mg / mL g / mL, 132mg / mL, 134mg / mL, 136mg / mL, 138mg / mL, 140mg / mL, 142mg / mL, 144mg / mL, 146mg / mL, 148mg / mL, 150mg / mL, 155mg / mL, 160mg / mL, or up to about 170mg / mL, or at most about: 100mg / mL, 102mg / mL, 104mg / mL, 106mg / mL, 108mg / mL, 110mg / mL, 112mg / mL, 114mg / mL, 11 The anti-ILT7 binding protein may comprise 6 mg / mL, 118 mg / mL, 120 mg / mL, 122 mg / mL, 124 mg / mL, 126 mg / mL, 128 mg / mL, 130 mg / mL, 132 mg / mL, 134 mg / mL, 136 mg / mL, 138 mg / mL, 140 mg / mL, 142 mg / mL, 144 mg / mL, 146 mg / mL, 148 mg / mL, 150 mg / mL, 155 mg / mL, 160 mg / mL, or up to about 170 mg / mL of the anti-ILT7 binding protein.

[0165] In embodiments, a therapeutically effective amount of an ILT7 binding protein used in the methods described herein ranges from about 0.1 mg to about 1000 mg. In other embodiments, a therapeutically effective amount of an ILT7 binding protein used in the methods described herein ranges from about 50 mg to about 300 mg. In embodiments, a therapeutically effective amount of an ILT7 binding protein used in the methods described herein is about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, about 450 mg, or about 500 mg in a single dose. In embodiments, a therapeutically effective amount of an ILT7 binding protein used in the methods described herein is about 200 mg in a single dose. A therapeutically effective amount of an ILT7 binding protein used in the methods described herein may be administered to a subject in need thereof in a single dose or in multiple doses. In embodiments, a therapeutically effective amount of an ILT7 binding protein used in the methods described herein ranges from about 0.1 mg to about 1000 mg. In embodiments, a therapeutically effective amount of an ILT7 binding protein used in the methods described herein ranges from about 50 mg to about 300 mg. In embodiments, a therapeutically effective amount of an ILT7 binding protein used in the methods described herein is about 150 mg, about 175 mg, about 200 mg, about 225 mg, about 250 mg, about 275 mg, about 300 mg, about 325 mg, about 350 mg, about 375 mg, about 400 mg, about 450 mg, or about 500 mg in a single dose. In embodiments, a therapeutically effective amount of an ILT7 binding protein used in the methods described herein is about 300 mg in a single dose. In embodiments, the ILT7 binding protein is administered in a dose of about 20-50 mg, 30-50 mg, 40-60 mg, 50-100 mg, 50-200 mg, 100-150 mg, 50-150 mg, 100-200 mg, 100-250 mg, 50-300 mg, 200-250 mg, 200-300 mg, 150 mg-300 mg, 150-350 mg, or 175-375 mg. A therapeutically effective amount of an ILT7 binding protein used in the methods described herein may be administered to a subject in need thereof in a single dose or in multiple doses.

[0166] In embodiments, the therapeutically effective amount of the ILT7 binding protein comprises an administration of at least about 300 mg. In embodiments, at least two administrations of the ILT7 binding protein are required to achieve a therapeutically effective dose. In embodiments, the administration comprises two subcutaneous injections of the ILT7 binding protein. The subcutaneous injections may be administered as two 1.5 mL injections of the ILT7 binding protein. In embodiments, the treatment regimen comprises one administration of the ILT7 binding protein about every four weeks.

[0167] The method includes administering a pharma- tically effective amount of an ILT7 binding protein to a subject. In embodiments, the ILT7 binding protein is administered at a dose of 100 mg, 150 mg, 200 mg, 250 mg, and / or 300 mg. In embodiments, the ILT7 binding protein is administered about once every four weeks. In embodiments, the ILT7 binding protein is administered about once every twelve weeks. In embodiments, the ILT7 binding protein is administered about once every twelve weeks, and the subject is administered an additional 300 mg dose of the ILT7 binding protein about four weeks after the initial dose.

[0168] In an embodiment, the disclosure is directed to a method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 200 mg. In an embodiment, the pharmacologic effective amount is about 300 mg. In an embodiment, the autoimmune disorder is lupus. In an embodiment, the autoimmune disease is SLE. In certain embodiments, the ILT7 binding protein is administered about once every 2 weeks, about once every 3 weeks, about once every 4 weeks, about once every 5 weeks, about once every 6 weeks, about once every 8 weeks, about once every 10 weeks, about once every 12 weeks, about once every month, about once every 2 months, about once every 3 months, about once every 4 months, or about once every 6 weeks. In an embodiment, the ILT7 binding protein is administered about once every 4 weeks. In embodiments, the ILT7 binding protein is administered about once every 12 weeks. In embodiments, the ILT7 binding protein is administered about once every 12 weeks and the subject is administered an additional 200 mg dose of the ILT7 binding protein about 2, 3, or 4 weeks after the first dose. In embodiments, the ILT7 binding protein is administered about once every 12 weeks and the subject is administered an additional 200 mg dose of the ILT7 binding protein about 4 weeks after the first dose. In one embodiment, the disclosure is directed to a method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharma- ceutical effective amount of the ILT7 binding protein is about 200 mg, and the subject is administered a first dose, a second dose about 4 weeks after the first dose, a third dose about 12 weeks after the first dose, and subsequent doses every 12 weeks after the third dose. In one aspect, the disclosure is directed to a method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharma- ceutical effective amount of the ILT7 binding protein is about 200 mg, and wherein the ILT7 binding protein is administered about once every four weeks. In an aspect, the ILT7 binding protein is administered about once every twelve weeks, and wherein the subject is administered an additional 200 mg dose of the ILT7 binding protein about four weeks after the initial dose.In an embodiment, the ILT-7 binding protein is daxudilimab. In an embodiment, the autoimmune disease is lupus. In an embodiment, the autoimmune disease is SLE. In an embodiment, the autoimmune disease is DLE. In an embodiment, the autoimmune disease is dermatomyositis. In an embodiment, the autoimmune disease is alopecia areata.

[0169] In embodiments, the autoimmune disease treated with the ILT7 binding protein is DLE. In embodiments, the ILT7 binding protein is administered at a dose of 50mg, 60mg, 70mg, 75mg, 80mg, 90mg, 100mg, 110mg, 120mg, 125mg, 130mg, 140mg, 150mg, 160mg, 170mg, 175mg, 180mg, 190mg, 200mg, 210mg, 220mg, 225mg, 230mg, 240mg, 250mg, 260mg, 270mg, 275mg, 280mg, 290mg, 300mg, 325mg, or 350mg. In embodiments, the ILT7 binding protein is administered about once every week, about once every 2 weeks, about once every 3 weeks, about once every 4 weeks, about once every 5 weeks, about once every 6 weeks, about once every 7 weeks, about once every 8 weeks, about once every 9 weeks, about once every 10 weeks, about once every 11 weeks, about once every 12 weeks, about once every 13 weeks, about once every 14 weeks, about once every 15 weeks, about once every 16 weeks, about once every 20 weeks, or about once every month, about once every 2 months, about once every 3 months, about once every 4 months, about once every 6 months. In embodiments, the ILT7 binding protein is administered at a dose of about 120mg-200mg every 4 weeks, 50-300mg every 4 weeks, or 150mg-300mg every 12 weeks / quarter. In aspects, the ILT7 binding protein is administered at a dose of about 150 mg every 4 weeks, 50-300 mg every 4 weeks, or 150 mg-300 mg every 12 weeks / quarter. In embodiments, one or more loading doses are administered first, followed by one or more maintenance doses. In aspects, the ILT-7 binding protein is daxudilimab.

[0170] In embodiments, the autoimmune disease treated with the ILT7 binding protein is SLE. In embodiments, the ILT7 binding protein is administered at a dose of 50mg, 60mg, 70mg, 75mg, 80mg, 90mg, 100mg, 110mg, 120mg, 125mg, 130mg, 140mg, 150mg, 160mg, 170mg, 175mg, 180mg, 190mg, 200mg, 210mg, 220mg, 225mg, 230mg, 240mg, 250mg, 260mg, 270mg, 275mg, 280mg, 290mg, 300mg, 325mg, or 350mg. In embodiments, the ILT7 binding protein is administered about once every week, about once every 2 weeks, about once every 3 weeks, about once every 4 weeks, about once every 5 weeks, about once every 6 weeks, about once every 7 weeks, about once every 8 weeks, about once every 9 weeks, about once every 10 weeks, about once every 11 weeks, about once every 12 weeks, about once every 13 weeks, about once every 14 weeks, about once every 15 weeks, about once every 16 weeks, about once every 20 weeks, or about once every month, about once every 2 months, about once every 3 months, about once every 4 months, about once every 6 months. In embodiments, the ILT7 binding protein is administered at a dose of about 120mg-200mg every 4 weeks, 50-300mg every 4 weeks, or 150mg-300mg every 12 weeks / quarter. In aspects, the ILT7 binding protein is administered at a dose of about 150 mg every 4 weeks, 50-300 mg every 4 weeks, or 150 mg-300 mg every 12 weeks / quarter. In embodiments, one or more loading doses are administered first, followed by one or more maintenance doses. In aspects, the ILT-7 binding protein is daxudilimab.

[0171] In an embodiment, the ILT7 binding protein is administered about once every 4 weeks. In an embodiment, the ILT7 binding protein is administered about once every 12 weeks. In one embodiment, the ILT7 binding protein is administered about once every 12 weeks, and the subject is administered an additional 200 mg dose of the ILT7 binding protein about 4 weeks after the first dose. In an embodiment, the pharmacologic effective amount of the ILT7 binding protein is about 200 mg, and the subject is administered a first dose, a second dose about 4 weeks after the first dose, a third dose about 12 weeks after the first dose, and subsequent doses every 12 weeks after the third dose. In one embodiment, the ILT-7 binding protein is daxudilimab. In an embodiment, the autoimmune disease is lupus. In a particular embodiment, the autoimmune disease is SLE.

[0172] In embodiments, the autoimmune disease treated with the ILT7 binding protein is dermatomyositis / antisynthetic enzyme inflammatory myositis (DM / ASIM). In some embodiments, the ILT7 binding protein is administered at a dose of 50 mg, 60 mg, 70 mg, 75 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 125 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 175 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 225 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 275 mg, 280 mg, 290 mg, 300 mg, 325 mg, or 350 mg. In embodiments, the ILT7 binding protein is administered about once every week, about once every 2 weeks, about once every 3 weeks, about once every 4 weeks, about once every 5 weeks, about once every 6 weeks, about once every 7 weeks, about once every 8 weeks, about once every 9 weeks, about once every 10 weeks, about once every 11 weeks, about once every 12 weeks, about once every 13 weeks, about once every 14 weeks, about once every 15 weeks, about once every 16 weeks, about once every 20 weeks, or about once every month, about once every 2 months, about once every 3 months, about once every 4 months, about once every 6 months. In embodiments, the ILT7 binding protein is administered at a dose of about 120mg-200mg every 4 weeks, 50-300mg every 4 weeks, or 150mg-300mg every 12 weeks / quarter. In aspects, the ILT7 binding protein is administered at a dose of about 150 mg every 4 weeks, 50-300 mg every 4 weeks, or 150 mg-300 mg every 12 weeks / quarter. In embodiments, one or more loading doses are administered first, followed by one or more maintenance doses. In aspects, the ILT-7 binding protein is daxudilimab.

[0173] In embodiments, the autoimmune disease treated with the ILT7 binding protein is lupus nephritis. In embodiments, the ILT7 binding protein is administered at a dose of 50mg, 60mg, 70mg, 75mg, 80mg, 90mg, 100mg, 110mg, 120mg, 125mg, 130mg, 140mg, 150mg, 160mg, 170mg, 175mg, 180mg, 190mg, 200mg, 210mg, 220mg, 225mg, 230mg, 240mg, 250mg, 260mg, 270mg, 275mg, 280mg, 290mg, 300mg, 325mg, or 350mg. In embodiments, the ILT7 binding protein is administered about once every week, about once every 2 weeks, about once every 3 weeks, about once every 4 weeks, about once every 5 weeks, about once every 6 weeks, about once every 7 weeks, about once every 8 weeks, about once every 9 weeks, about once every 10 weeks, about once every 11 weeks, about once every 12 weeks, about once every 13 weeks, about once every 14 weeks, about once every 15 weeks, about once every 16 weeks, about once every 20 weeks, or about once every month, about once every 2 months, about once every 3 months, about once every 4 months, about once every 6 months. In embodiments, the ILT7 binding protein is administered at a dose of about 120mg-200mg every 4 weeks, 50-300mg every 4 weeks, or 150mg-300mg every 12 weeks / quarter. In aspects, the ILT7 binding protein is administered at a dose of about 150 mg every 4 weeks, 50-300 mg every 4 weeks, or 150 mg-300 mg every 12 weeks / quarter. In embodiments, one or more loading doses are administered first, before one or more maintenance doses. In aspects, the ILT-7 binding protein is daxzilimab. In aspects, the LN is treated with 100 mg daxzilimab at baseline, week 2, and week 4, followed by 100 mg daxzilimab every 4 weeks. In aspects, the LN is treated with a dose of 300 mg daxzilimab at baseline, week 2, and week 4, followed by 300 mg daxzilimab every 4 weeks. In aspects, the LN is treated with a dose of 100 mg or 300 mg daxzilimab every 12 weeks.

[0174] In aspects, the disclosure is directed to a method of reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 300 mg. In aspects, the ILT7 binding protein is administered about once every four weeks. In aspects, the disclosure is directed to a method of reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 300 mg, and the subject is administered a first dose, a second dose about four weeks after the first dose, and an additional dose every four weeks for a total of nine doses. In aspects, the present disclosure relates to a method of reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 300 mg, and wherein the ILT7 binding protein is administered about once every four weeks. In aspects, the ILT-7 binding protein is daxudilimab.

[0175] In an embodiment, the present disclosure relates to a method for treating alopecia areata in a subject in need thereof, the method comprises administering a pharmacologic effective amount of immunoglobulin-like transcript 7 (ILT7) binding protein to the subject, and the pharmacologic effective amount of ILT7 binding protein is about 100mg or 300mg.In an embodiment, the ILT7 binding protein is administered about once every 2 weeks, about once every 3 weeks, about once every 4 weeks, about once every 5 weeks, about once every 6 weeks, about once every 8 weeks, about once every 10 weeks, about once every 12 weeks, about once every month, about once every 2 months, about once every 3 months, about once every 4 months or about once every 6 weeks.In an embodiment, the ILT7 binding protein is administered about once every 4 weeks.In an embodiment, the ILT7 binding protein is administered about once every 12 weeks. In embodiments, the ILT7 binding protein is administered at a dose of about 150 mg every 4 weeks, about 50 to about 300 mg every 4 weeks, or about 150 mg to about 300 mg every 12 weeks / quarter. In embodiments, the ILT7 binding protein is administered once about every 4 weeks, and the subject is administered an additional 300 mg dose of the ILT7 binding protein about 4 weeks after the initial dose. In embodiments, the ILT7 binding protein is administered once about every 4 weeks, and the subject is administered an additional 300 mg dose of the ILT7 binding protein about 4 weeks after the initial dose. In an aspect, the present disclosure is directed to a method of treating alopecia areata in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 300 mg, and the subject is administered a first dose, a second dose about 4 weeks after the first dose, a third dose about 12 weeks after the first dose, and subsequent doses every 12 weeks after the third dose. In an aspect, the present disclosure is directed to a method of treating alopecia areata in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 300 mg, and the ILT7 binding protein is administered once about every 4 weeks. In embodiments, the ILT7 binding protein is administered about once every 12 weeks, and the subject receives an additional 300 mg dose of the ILT7 binding protein about 4 weeks after the initial dose.In embodiments, the ILT7 binding protein is administered at a dose of about 120 mg to about 200 mg every 4 weeks, about 50 mg to about 300 mg every 4 weeks, or about 150 mg to about 300 mg every 12 weeks / quarter. In embodiments, the ILT7 binding protein is administered at a dose of about 150 mg every 4 weeks, about 50 mg to about 300 mg every 4 weeks, or about 150 mg to about 300 mg every 12 weeks / quarter. In embodiments, the ILT-7 binding protein is daxudilimab.

[0176] In embodiments, administration of the compositions provided herein results in a decrease in the level of pDCs in a tissue of a treated subject compared to the subject's baseline level prior to administration, which decrease is at least about 3%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85% 90%, 100%, 120%, 130%, 140%, 150%, 200%, 250%, 300%, 400%, or up to about 500%.

[0177] In an embodiment, the autoimmune disease treated with ILT7 binding protein is alopecia areata.In an embodiment, the ILT7 binding protein is administered at a dose of 50mg, 60mg, 70mg, 75mg, 80mg, 90mg, 100mg, 110mg, 120mg, 125mg, 130mg, 140mg, 150mg, 160mg, 170mg, 175mg, 180mg, 190mg, 200mg, 210mg, 220mg, 225mg, 230mg, 240mg, 250mg, 260mg, 270mg, 275mg, 280mg, 290mg, 300mg, 325mg, or 350mg. In embodiments, the ILT7 binding protein is administered about once every week, about once every 2 weeks, about once every 3 weeks, about once every 4 weeks, about once every 5 weeks, about once every 6 weeks, about once every 7 weeks, about once every 8 weeks, about once every 9 weeks, about once every 10 weeks, about once every 11 weeks, about once every 12 weeks, about once every 13 weeks, about once every 14 weeks, about once every 15 weeks, about once every 16 weeks, about once every 20 weeks, or about once every month, about once every 2 months, about once every 3 months, about once every 4 months, about once every 6 months. In embodiments, the ILT7 binding protein is administered at a dose of about 120mg-200mg every 4 weeks, 50-300mg every 4 weeks, and 150mg-300mg every 12 weeks / quarter. In aspects, the ILT7 binding protein is administered at a dose of about 150 mg every 4 weeks, 50-300 mg every 4 weeks, and / or 150 mg-300 mg every 12 weeks / quarter. In embodiments, one or more loading doses are administered initially, followed by one or more maintenance doses. In aspects, the ILT-7 binding protein is daxudilimab.

[0178] In embodiments, the ILT7 binding protein is administered about once every 4 weeks. In embodiments, the ILT7 binding protein is administered about once every 12 weeks. In embodiments, the ILT7 binding protein is administered about once every 12 weeks, and the subject is administered an additional 300 mg dose of the ILT7 binding protein about 4 weeks after the first dose. In embodiments, the pharmacologic effective amount of the ILT7 binding protein is about 300 mg, and the subject is administered the first dose and additional doses about every 4 weeks for a total of 9 doses. In embodiments, the ILT-7 binding protein is daxudilimab.

[0179] In embodiments, any of the compositions provided are administered with one or more standard-of-care (SOC) or combination therapies. In embodiments, the SOC therapy includes a corticosteroid. Exemplary corticosteroids include dexamethasone, hydrocortisone, methylprednisolone, and prednisone. In embodiments, the corticosteroid is prednisone. In embodiments, the method includes tapering the SOC therapy. Suitable tapering schedules are provided herein. In embodiments, the tapering schedule includes reducing the corticosteroid to a prednisone equivalent dose of ≦7.5 mg / day by week 12 and to a prednisone equivalent dose of ≦2.5 mg / day by week 24. In embodiments, the SOC therapy includes an immunosuppressant. In embodiments, the immunosuppressant includes mycophenolic acid. In embodiments, the methods are effective to reduce or eliminate autoimmune disease in subjects administered an ILT7 binding protein of the present disclosure in combination with SOC therapy, compared to otherwise similar subjects administered SOC therapy alone.

[0180] In an embodiment, the pharmaceutical composition of the present disclosure comprises an ILT7 binding protein disclosed herein and one or more pharma- ceutically acceptable carriers, diluents, or excipients. In this regard, "pharma-ceutically acceptable carriers, diluents, or excipients" includes, but is not limited to, any adjuvant, carrier, excipient, glidant, sweetener, diluent, preservative, dye / colorant, flavor enhancer, surfactant, wetting agent, dispersant, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier that may or may not be approved by the U.S. Food and Drug Administration as acceptable for use in humans or veterinary medicine. For example, suitable carriers are known to those skilled in the art and include stabilizers, diluents, and buffers. Suitable stabilizers include carbohydrates such as sorbitol, lactose, mannitol, starch, sucrose, dextran, and glucose, and proteins such as albumin or casein. Suitable diluents include saline, Hank's balanced salts, and Ringer's solution. Suitable buffering agents include alkali metal phosphates, alkali metal carbonates, or alkaline earth metal carbonates.

[0181] In embodiments, the pharmaceutical compositions of the present disclosure may further comprise one or more auxiliary substances, such as one or more lipids, phospholipids, carbohydrates, and lipopolysaccharides. In embodiments, the pharmaceutical compositions of the present disclosure optionally comprise one or more additional active substances.

[0182] In an embodiment, the pharmaceutical composition of the present disclosure may be prepared by techniques known to those skilled in the art. General considerations in the formulation and / or manufacture of pharmaceutical compositions can be found, for example, in Remington: The Science and Practice of Pharmacy 21st ed., Lippincott Williams & Wilkins, 2005 (incorporated herein by reference in its entirety). In general, the ILT7 binding protein or fragment thereof used in the methods described herein is mixed with a carrier to form a solution, suspension, or emulsion. One or more of the additives discussed herein may be added to the carrier or may be added thereafter. The pharmaceutical composition of the present disclosure may be an aqueous solution, emulsion, or suspension, or may be a dry preparation. In an embodiment, the pharmaceutical composition of the present disclosure may be dried or lyophilized, for example, by lyophilization or spray drying, for storage or formulation purposes. They may then be reconstituted into a liquid composition by adding a suitable liquid carrier, or may be administered in a dry formulation using methods known to those skilled in the art. In embodiments, the ILT7 binding proteins used in the methods described herein are stored as a lyophilized powder and then reconstituted into a liquid composition prior to administration to a subject in need thereof.

[0183] The choice of administration of pharmaceutical composition will depend on the formulation selected.The pharmaceutical composition of the present disclosure is administered in a manner compatible with the dosage formulation and in such amount that is therapeutically effective.In an embodiment, the pharmaceutical composition of the present disclosure is formulated into preparations in solid, semi-solid, liquid, or gas form, including but not limited to tablets, capsules, powders, granules, ointments, solutions, suppositories, injections, inhalants, gels, microspheres, and aerosols.

[0184] In embodiments, pharmaceutical compositions comprising ILT7 binding proteins used in the methods described herein may be in solid or liquid form. In embodiments, the carrier(s) are particulate, such that the compositions are, for example, in tablet or powder form. In other embodiments, the carrier(s) are liquid, such that the compositions are, for example, oral syrups, injectable liquids, or aerosols (e.g., useful for inhalation administration). When intended for oral administration, pharmaceutical compositions comprising ILT7 binding proteins used in the methods described herein may be in either solid or liquid form, with semi-solid, semi-liquid, suspension, and gel forms being included as forms considered herein as either solid or liquid.

[0185] In embodiments, as a solid composition for oral administration, the pharmaceutical composition comprising an ILT7 binding protein used in the methods described herein can be formulated in the form of a powder, granule, compressed tablet, pill, capsule, chewing gum, wafer, etc. In embodiments, such solid compositions typically contain one or more inert diluents or edible carriers. In embodiments, one or more of the following may further be present: binders (e.g., carboxymethylcellulose, ethylcellulose, microcrystalline cellulose, gum tragacanth, or gelatin), excipients (e.g., starch, lactose, or dextrin), disintegrants (e.g., alginic acid, sodium alginate, Primogel, corn starch, etc.), lubricants (e.g., magnesium stearate or Sterotex), glidants (e.g., colloidal silicon dioxide), sweeteners (e.g., sucrose or saccharin), flavors (e.g., peppermint, methyl salicylate, or orange flavor), and colorants.

[0186] In an embodiment, when the pharmaceutical composition of the present disclosure is in the form of a capsule (e.g., a gelatin capsule), it may contain a liquid carrier (e.g., polyethylene glycol or oil) in addition to the materials disclosed herein. Oral formulations may also contain commonly used excipients such as, for example, pharmaceutical grades of saccharin, cellulose, magnesium carbonate, and the like.

[0187] In embodiments, the pharmaceutical composition of the present disclosure is in the form of a liquid (e.g., an elixir, syrup, solution, emulsion, or suspension). In embodiments, the liquid may be for oral administration or delivery by injection. In embodiments, when intended for oral administration, the pharmaceutical composition of the present disclosure includes one or more of a sweetener, a preservative, a dye / colorant, and a flavor enhancer in addition to the ILT7 binding protein used in the methods described herein. In embodiments, a pharmaceutical composition intended for administration by injection may include one or more of a surfactant, a preservative, a wetting agent, a dispersing agent, a suspending agent, a buffer, a stabilizer, and an isotonic agent. In embodiments, the pharmaceutical composition of the present disclosure is administered intravenously to a subject in need thereof. In embodiments, the pharmaceutical composition of the present disclosure is administered by subcutaneous injection to a subject in need thereof.

[0188] In embodiments, liquid pharmaceutical compositions comprising ILT7 binding proteins for use in the methods described herein, whether they are in a solution, suspension, or other similar form, may contain one or more of the following components: sterile diluents (e.g., water for injection, saline (e.g., saline, Ringer's solution, isotonic sodium chloride)), fixed oils (e.g., synthetic mono- or diglycerides that may function as solvents or suspending media), polyethylene glycol, glycerin, propylene glycol, or other solvents, antibacterial agents (e.g., benzyl alcohol or methylparabens), antioxidants (e.g., ascorbic acid or sodium bisulfite), chelating agents (e.g., ethylenediaminetetraacetic acid), buffers (e.g., acetates, citrates, or phosphates), and agents for adjusting osmolarity (e.g., sodium chloride or dextrose). In embodiments, the preparations may be enclosed in glass or plastic ampoules, disposable syringes, or multiple dose vials. In embodiments, the injectable pharmaceutical compositions are preferably sterile.

[0189] In other aspects, the pharmaceutical composition comprising an ILT7 binding protein used in the methods described herein may be intended for topical administration, in which case the carrier may suitably comprise a solution, emulsion, ointment, or gel base. In aspects, the base may comprise, for example, one or more of the following: petrolatum, lanolin, polyethylene glycol, beeswax, mineral oil, diluents (e.g., water, and alcohol), and emulsifiers and stabilizers. In other aspects, thickeners may be present in pharmaceutical compositions for topical administration. In aspects, when intended for transdermal administration, the pharmaceutical composition of an ILT7 binding protein used in the methods described herein may be included in a transdermal patch or iontophoretic device.

[0190] In an embodiment, the pharmaceutical composition comprising the ILT7 binding protein used in the methods described herein is intended for rectal administration, for example, in the form of a suppository. In the case of a suppository, the binder and carrier may include, for example, polyalkalene glycol or triglyceride. In an embodiment, the composition for rectal administration contains an oil base as a suitable non-irritating excipient. Such bases include, but are not limited to, lanolin, cocoa butter, or polyethylene glycol.

[0191] In embodiments, pharmaceutical compositions comprising ILT7 binding proteins used in the methods described herein include dosage units that can be administered as an aerosol. The term aerosol is used to describe a variety of systems, from those of colloidal nature to systems comprised of pressurized packages. In embodiments, delivery is accomplished by liquefied or compressed gas, or by a suitable pump system that dispenses the active ingredient. In embodiments, aerosols of ILT7 binding proteins used in the methods described herein can be delivered in single-phase, two-phase, or three-phase systems to deliver the active ingredient(s). In other embodiments, delivery of the aerosol includes the necessary containers, activators, valves, subcontainers, etc., which together can form a kit. Those skilled in the art can easily determine the particular aerosol formulation and delivery mode.

[0192] The pharmaceutical compositions of the present disclosure may be administered in a suitable non-toxic pharmaceutical carrier, may be contained in microcapsules, microbeads, and / or may be contained in a sustained release implant.

[0193] In aspects, pharmaceutical compositions of the present disclosure include materials that form a coating shell around the active ingredients. In aspects, the materials that form the coating shell are typically inert, and may be selected from, for example, sugar, shellac, and other enteric coating agents.

[0194] In embodiments, pharmaceutical compositions of the present disclosure, in solid or liquid form, include an agent that binds to an ILT7 binding protein used in the methods described herein, thereby aiding in the delivery of an ILT7 binding protein used in the methods described herein. In embodiments, suitable agents acting in this capacity include proteins or liposomes.

[0195] In an embodiment, the pharmaceutical composition administered to the subject takes the form of one or more dosage units, for example, a tablet may be a single dosage unit, and a container of the ILT7 binding protein used in the methods described herein in aerosol form may hold multiple dosage units. The actual methods of preparing such dosage forms are known or will be apparent to those skilled in the art. See, for example, Remington: The Science and Practice of Pharmacy, 20th Edition (Philadelphia College of Pharmacy and Science, 2000). The composition administered will, in any case, contain a therapeutically effective amount of the ILT7 binding protein used in the methods described herein or a pharma- ceutically acceptable salt thereof to aid in the treatment of the disease or condition of interest, in accordance with the teachings herein.

[0196] In an embodiment, the pharmaceutical composition of the present disclosure comprises one or more additional therapeutically active substances. In another embodiment, a therapeutically effective dose of the pharmaceutical composition of the present disclosure is administered to a subject in need thereof in combination with one or more additional therapeutically active substances. As used herein, "combination" refers to a combination comprising an ILT7 binding protein used in the methods described herein and one or more additional therapeutically active substances, each of which may be administered serially (sequentially), concurrently or simultaneously.

[0197] The pharmaceutical compositions of the present disclosure are desirably administered at several intervals to maintain therapeutic levels.The pharmaceutical compositions of the present disclosure can be used in conjunction with other bactericidal or bacteriostatic methods.

[0198] Although the description of pharmaceutical compositions provided herein is primarily directed to pharmaceutical compositions suitable for administration to humans, it will be understood by those skilled in the art that such compositions are generally suitable for administration to any type of subject. In an embodiment, the subject is a mammal. In an embodiment, the mammal includes primates (e.g., humans, monkeys, chimpanzees, and apes), as well as non-primates (e.g., laboratory animals and livestock, including household pets and farm animals (e.g., cats, dogs, pigs, cows, sheep, goats, horses, rabbits)), and non-domestic animals (e.g., wild animals, birds, etc.).

[0199] kit Kits comprising anti-ILT7 binding proteins are also provided. In embodiments, the kit comprises a) a pharmaceutical composition comprising an anti-ILT7 binding protein for use in treating alopecia in a subject in need thereof, and b) instructions describing how to administer the pharmaceutical composition to a subject in need thereof.

[0200] The kits can include an anti-ILT7 binding protein (e.g., in liquid or lyophilized form), or a pharmaceutical composition that includes an anti-ILT7 binding protein. In addition, such kits can include a means for administering the anti-ILT7 binding protein (e.g., a syringe or prefilled pen) and instructions for use. These kits may also contain additional therapeutic agents.

[0201] In an aspect, the container is included in the kit and can be a vial. The vial can contain a lyophilized dosage form of the composition provided herein. In an embodiment, the vial can contain a liquid dosage form of the composition provided herein. In an embodiment, the container is a vial and contains approximately 1 mL, 1.25 mL, 1.5 mL, 1.75 mL, 2 mL, 2.25 mL, 2.5 mL, 2.75 mL, 3 mL, 3.25 mL, 3.5 mL, 3.75 mL, 4 mL, 4.25 mL, 4.5 mL, 4.75 mL, 5 mL, 5.25 mL, 5.5 mL, 5.75 mL, 6 mL, 6.25 mL, 6.5 mL, 6.75 mL, 7 mL, 7.25 mL, 7.5 mL, 7.75 mL, 8 mL, 8.25 mL, 8.5 mL, 8.75 mL, 9 mL, 9.25 mL, 9.5 mL, 9.75 mL, 10 mL of solution.

[0202] Numbered embodiments Without limiting the scope of the appended claims, the present disclosure describes the following numbered embodiments.

[0203] Embodiment Set 1 1. A method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 200 mg.

[0204] 2. A method of reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 200 mg.

[0205] 3. A method for reducing type I interferon gene signature (IFNGS) in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the ILT7 binding protein is administered to the subject if the type I IFNGS is elevated in the subject compared to the type I IFNGS in a normal subject, and wherein the pharmacologic effective amount of the ILT7 binding protein is about 200 mg.

[0206] 4. The method of embodiment 3, wherein the type I IFNGS is measured in a test biological sample taken from the subject, the test sample being selected from the group consisting of blood, sputum, saliva, skin cells, skin biopsy samples, kidney cells, lung cells, liver cells, heart cells, brain cells, neural tissue, thyroid cells, eye cells, skeletal muscle cells, cartilage, bone tissue, and cultured cells.

[0207] 5. The method of embodiment 4, wherein the test biological sample is blood, skin cells, or a skin biopsy sample.

[0208] 6. The method of any one of the preceding embodiments, wherein said type I IFNGS is elevated at least about 4-fold in said test biological sample as compared to an otherwise comparable normal biological sample.

[0209] 7. The method of any one of the preceding embodiments, wherein said type I IFNGS comprises the collective expression level of two or more type I interferon (IFN)-inducible genes.

[0210] 8. The method of embodiment 7, wherein the two or more type I interferon (IFN)-inducible genes are selected from the group consisting of SPATS2L, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, RSAD2, RTP4, SIGLEC1, and USP18.

[0211] 9. The method of embodiment 7, wherein the type I IFNGS comprises the collective expression levels of all of SPATS2L, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, RSAD2, RTP4, SIGLEC1, and USP18.

[0212] 10. The method of embodiment 7, wherein said type I IFN Gs is determined by assaying the mRNA levels of said two or more type I interferon (IFN)-inducible genes in said test biological sample.

[0213] 11. The method of embodiment 8, wherein said type I IFNGS is determined by assaying mRNA levels of SPATS2L, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, RSAD2, RTP4, SIGLEC1, and USP18 in the test biological sample.

[0214] 12. The method of any one of the preceding embodiments, wherein said administering said ILT7 binding protein reduces plasmacytoid dendritic cells (pDCs) in said subject.

[0215] 13. The method of embodiment 12, wherein said pDCs are circulating pDCs.

[0216] 14. The method of embodiment 12 or 13, wherein said reduction of said pDCs is reversible.

[0217] 15. The method of any one of the preceding embodiments, wherein reducing said type I IFNGS treats an autoimmune disease in said subject.

[0218] 16. The method of any one of the preceding embodiments, wherein the ILT7 binding protein is administered about once every four weeks.

[0219] 17. The method of any one of embodiments 1-15, wherein the ILT7 binding protein is administered about once every 12 weeks.

[0220] 18. The method of embodiment 17, wherein the subject is administered an additional 200 mg dose of the ILT7 binding protein about 4 weeks after the initial dose.

[0221] 19. A method of treating an autoimmune disease in a subject in need thereof, the method comprising administering to the subject a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharma- ceutical effective amount of the ILT7 binding protein is about 200 mg, and the subject is administered a) a first dose, b) a second dose about 4 weeks after the first dose, c) a third dose about 12 weeks after the first dose, and d) a subsequent dose about 12 weeks after the third dose.

[0222] 20. A method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 200 mg, and the ILT7 binding protein is administered about once every four weeks.

[0223] 21. A method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 200 mg, and the ILT7 binding protein is administered once about every 12 weeks, and the subject is administered an additional 200 mg dose of the ILT7 binding protein about 4 weeks after an initial dose.

[0224] 22. A method of reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 200 mg, and the subject is administered a) a first dose, b) a second dose about 4 weeks after the first dose, c) a third dose about 12 weeks after the first dose, and d) a subsequent dose about 12 weeks after the third dose.

[0225] 23. A method of reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 200 mg, and the ILT7 binding protein is administered about once every four weeks.

[0226] 24. A method of reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 200 mg, the ILT7 binding protein is administered once about every 12 weeks, and the subject is administered an additional 200 mg dose of the ILT7 binding protein about 4 weeks after an initial dose.

[0227] 25. The method of any one of embodiments 22-24, wherein said reduction in pDCs in said tissue compared to baseline values ​​ranges from about 1% to about 99%.

[0228] 26. The method of any one of embodiments 22-25, wherein said reduction in pDCs in said tissue compared to said baseline value is at least about 50%.

[0229] 27. The method of any one of embodiments 1-26, wherein the subject has high blood type I IFNGS levels prior to administration of the ILT7 binding protein.

[0230] 28. The method of any one of embodiments 1-27, wherein the subject has high pDC levels in a tissue biopsy prior to administration of the ILT7 binding protein.

[0231] 29. The method of any one of embodiments 1-28, wherein the subject has an autoimmune disease, and the autoimmune disease is systemic lupus erythematosus (SLE), lupus nephritis, cutaneous lupus erythematosus (CLE), Sjogren's syndrome, inflammatory myositis, such as dermatomyositis, inclusion body myositis, juvenile myositis and polymyositis, systemic sclerosis, diabetes, Hashimoto's disease, autoimmune adrenal insufficiency, true erythrocytic anemia, multiple sclerosis, rheumatic carditis, psoriasis, psoriatic arthritis, rheumatoid arthritis, chronic inflammation, chronic rheumatoid arthritis, vitiligo, alopecia areata, hidradenitis suppurativa, celiac disease, acute and chronic graft-versus-host disease (GVHD), vasculitis, myocardial infarction, type 1 interferonopathy, and combinations thereof.

[0232] 30. The method of embodiment 29, wherein the autoimmune disease is SLE.

[0233] 31. The method of embodiment 29, wherein the autoimmune disease is CLE.

[0234] 32. The method of embodiment 29, wherein the autoimmune disease is lupus.

[0235] 33. The method of any one of embodiments 1-32, wherein the subject does not have discoid lupus erythematosus (DLE).

[0236] 34. The method of any one of embodiments 1-32, wherein the subject has DLE.

[0237] 35. The method of any one of the preceding embodiments, wherein the ILT7 binding protein is administered by subcutaneous injection.

[0238] 36. The method of any one of the preceding embodiments, wherein administration of said ILT7 binding protein results in at least about a 50% decrease in said type I IFNGS in said subject compared to said type I IFNGS prior to administration of said ILT7 binding protein.

[0239] 37. The method of any one of the preceding embodiments, wherein said ILT7 binding protein induces antibody-dependent cell-mediated cytotoxicity (ADCC) activity against pDCs.

[0240] 38. The method of any one of embodiments 1-37, wherein said ILT7 binding protein at least inhibits the release of type I interferon (IFN) from pDCs.

[0241] 39. The method of embodiment 38, wherein said type I IFN is IFNα.

[0242] 40. The method of any one of the preceding embodiments, wherein said ILT7 binding protein binds to ILT7.

[0243] 41. The method of any one of the preceding embodiments, wherein the subject is determined to have high blood type I IFNGS levels prior to administration of the ILT7 binding protein.

[0244] 42. The ILT7 binding protein, Heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3, and light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3, each comprising the amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. The method of any one of the preceding embodiments, wherein the antibody comprises:

[0245] 43. The ILT7 binding protein, a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1, and / or a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2. The method of any one of the preceding embodiments, wherein the antibody comprises:

[0246] 44. The ILT7 binding protein, An antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO: 2. 2. The method of any one of the preceding embodiments, wherein

[0247] 45. The method of any one of the preceding embodiments, wherein said ILT7 binding protein is non-fucosylated.

[0248] 46. ​​A method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharma- ceutical effective amount of the ILT7 binding protein is about 200 mg, and the ILT7 binding protein is an antibody comprising a variable heavy chain (VH) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1 and / or a variable light chain (VL) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2, wherein the subject is administered a) a first dose, b) a second dose about 4 weeks after the first dose, c) a third dose about 12 weeks after the first dose, and d) a subsequent dose about 12 weeks after the third dose.

[0249] 47. A method of treating systemic lupus erythematosus in a subject in need thereof, the method comprising administering to the subject a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharma- ceutical effective amount of the ILT7 binding protein is about 200 mg, and the ILT7 binding protein is an antibody comprising a variable heavy chain (VH) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1 and / or a variable light chain (VL) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2, wherein the subject is administered a) a first dose, b) a second dose about 4 weeks after the first dose, c) a third dose about 12 weeks after the first dose, and d) a subsequent dose about 12 weeks after the third dose.

[0250] 48. A method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharma- ceutical effective amount of the ILT7 binding protein is about 200 mg, and the ILT7 binding protein is an antibody comprising a variable heavy chain (VH) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1 and / or a variable light chain (VL) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2, and wherein the ILT7 binding protein is administered about once every four weeks.

[0251] 49. A method of treating systemic lupus erythematosus in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 200 mg, and the ILT7 binding protein is an antibody comprising a variable heavy chain (VH) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1 and / or a variable light chain (VL) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2, and wherein the ILT7 binding protein is administered about once every 4 weeks.

[0252] 50. A method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharma- ceutical effective amount of the ILT7 binding protein is about 200 mg, and the ILT7 binding protein is an antibody comprising a variable heavy chain (VH) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1 and / or a variable light chain (VL) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2, wherein the ILT7 binding protein is administered once about every 12 weeks, and wherein the subject is administered an additional 200 mg dose of the ILT7 binding protein about 4 weeks after the initial dose.

[0253] 51. A method of treating systemic lupus erythematosus in a subject in need thereof, the method comprising administering to the subject a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharma- ceutical effective amount of the ILT7 binding protein is about 200 mg, and the ILT7 binding protein is an antibody comprising a variable heavy chain (VH) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1 and / or a variable light chain (VL) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2, wherein the ILT7 binding protein is administered once about every 12 weeks, and wherein the subject is administered an additional 200 mg dose of the ILT7 binding protein about 4 weeks after the initial dose.

[0254] 52. A method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharma- ceutical effective amount of the ILT7 binding protein is about 150-350 mg, and the ILT7 binding protein is an antibody comprising a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1 and / or a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2.

[0255] 53. The method of any one of embodiments 1-52, wherein the ILT7 binding protein is administered with one or more additional therapies.

[0256] 54. The method of embodiment 53, wherein one of the one or more additional therapies is a standard of care therapy.

[0257] 55. The method of any one of embodiments 1-54, wherein administration of said ILT7 binding protein reduces the occurrence of disease flares in said subject.

[0258] 56. The method of embodiment 53, wherein the one or more additional therapies comprises a glucocorticoid.

[0259] 57. The method of any one of embodiments 53-56, wherein administration of the one or more additional therapies is tapered.

[0260] 58. The method of any one of embodiments 53-57, wherein the autoimmune disorder is selected from the group consisting of discoid lupus erythematosus (DLE), systemic lupus erythematosus (SLE), lupus nephritis, dermatomyositis / antisynthetic enzyme inflammatory myositis (DM / ASIM), and alopecia areata.

[0261] 59. The method of embodiment 58, wherein the autoimmune disorder is DLE and the pharmacologic effective amount of the ILT7 binding protein is about 300 mg.

[0262] 60. The method of embodiment 58, wherein the autoimmune disorder is SLE and the pharmacologic effective amount of the ILT7 binding protein is about 200 mg.

[0263] 61. The method of embodiment 58, wherein the autoimmune disorder is lupus nephritis and the pharmacologic effective amount of the ILT7 binding protein is about 300 mg.

[0264] 62. A method of treating discoid lupus erythematosus (DLE) in a subject in need thereof, comprising administering to the subject a pharma- ceutically effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein.

[0265] 63. The method of embodiment 62, wherein the DLE is primary DLE.

[0266] 64. The method of embodiment 62 or 63, wherein the subject does not have systemic lupus.

[0267] 65. The method of any one of embodiments 62-64, wherein the DLE is refractory.

[0268] 66. The method of embodiment 65, wherein the DLE is refractory to one or more therapies selected from the group consisting of topical steroids, intralesional steroids, antimalarials, tacrolimus, thalidomide, opicartacrolimus, azathioprine, cyclosporine, mycophenolate mofetil, methotrexate, and acitretin.

[0269] 67. The method of any one of embodiments 62-66, wherein the ILT7 binding protein is an antibody.

[0270] 68. The method of embodiment 67, wherein the antibody comprises heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3, and light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3 having the amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8.

[0271] 69. The method of embodiment 67 or 68, wherein the antibody comprises a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:1, and a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identical to SEQ ID NO:2.

[0272] 70. A method of treating alopecia areata in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is between about 250 mg and 350 mg.

[0273] 71. A method for reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject having alopecia areata, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is between about 250 mg and 350 mg.

[0274] 72. The method of any one of the preceding embodiments, wherein said administering said ILT7 binding protein reduces plasmacytoid dendritic cells (pDCs) in said subject.

[0275] 73. The method of embodiment 71 or 72, wherein the pDCs are circulating pDCs.

[0276] 74. The method of embodiment 72 or 73, wherein said reduction of said pDCs is reversible.

[0277] 75. The method of any one of embodiments 70-74, wherein the ILT7 binding protein is administered about once every 4 weeks.

[0278] 76. A method of treating alopecia areata in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is between about 250 mg and 350 mg, and the ILT7 binding protein is administered about once every four weeks.

[0279] 77. A method of reducing plasmacytoid dendritic cells (pDCs) in a tissue of a subject having alopecia areata, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is between about 250 mg and 350 mg, and the ILT7 binding protein is administered about once every four weeks.

[0280] 78. A method according to any one of embodiments 71 to 77, wherein the reduction in pDCs in the tissue compared to baseline values ​​ranges from about 1% to about 99%.

[0281] 79. The method of any one of embodiments 71-78, wherein said reduction in pDCs in said tissue compared to said baseline value is at least about 50%.

[0282] 80. The method of any one of the preceding embodiments, wherein said ILT7 binding protein induces antibody-dependent cell-mediated cytotoxicity (ADCC) activity against pDCs.

[0283] 81. The method of any one of embodiments 71-80, wherein said ILT7 binding protein at least inhibits the release of type I interferon (IFN) from pDCs.

[0284] 82. The method of embodiment 81, wherein said type I IFN is IFNα.

[0285] 83. The method of any one of embodiments 70-82, wherein said ILT7 binding protein binds to ILT7.

[0286] 84. The ILT7 binding protein, Heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3, and light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3, each comprising the amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. The method of any one of embodiments 70 to 83, wherein the antibody comprises:

[0287] 85. The ILT7 binding protein, a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1, and / or a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2. The method of any one of embodiments 70 to 84, wherein the antibody comprises:

[0288] 86. The ILT7 binding protein, An antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO: 2. The method of any one of embodiments 70 to 85, wherein

[0289] 87. The method of any one of embodiments 70-86, wherein the ILT7 binding protein is non-fucosylated.

[0290] 88. A method of treating alopecia areata in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 250 mg to 350 mg, and the ILT7 binding protein is an antibody comprising a variable heavy chain (VH) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1 and / or a variable light chain (VL) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2, and wherein the ILT7 binding protein is administered about once every 4 weeks.

[0291] 89. A method of treating alopecia areata in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is between about 250 mg and 350 mg, and the ILT7 binding protein is an antibody comprising a variable heavy chain (VH) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1 and / or a variable light chain (VL) at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2.

[0292] 90. The method of any one of embodiments 70-89, wherein the ILT7 binding protein is administered with one or more additional therapies.

[0293] 91. The method of embodiment 90, wherein one of the one or more additional therapies is a standard of care therapy.

[0294] 92. The method of any one of embodiments 70-91, wherein the ILT7 binding protein is administered subcutaneously.

[0295] 93. The method of any one of embodiments 70-92, wherein the administering is effective to stabilize or reduce hair loss in the subject as measured by a stabilization or reduction in the Severity of Alopecia Tool (SALT) score and / or the Alopecia Density and Extent (ALODEX) score.

[0296] 94. The method of any one of embodiments 70-93, wherein the ILT7 binding protein, when administered to a mouse having alopecia areata, is effective to reduce levels of type 1 interferon-inducible myxovirus protein A (MxA) in a biopsy comprising a hair follicle of the mouse, as determined by immunohistochemistry.

[0297] 95. The method of any one of embodiments 70-94, wherein the pharma- ceutically effective amount of the ILT7 binding protein is about 300 mg.

[0298] 96. The method of embodiment 95, wherein the 300 mg is administered as two doses of 150 mg each.

[0299] 97. The method of any one of embodiments 70-96, wherein the ILT7 binding protein is daxzilimab.

[0300] 98. A method of treating lupus nephritis in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 300 mg, and the ILT7 binding protein is administered about once every four weeks.

[0301] 99. A method of treating lupus nephritis in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 100 mg, and the ILT7 binding protein is administered about once every four weeks.

[0302] 100. The method of embodiment 98 or 99, wherein the subject is administered one or more initial doses of the ILT7 binding protein prior to being administered the ILT7 binding protein every four weeks.

[0303] 101. The method of embodiment 100, wherein said initial dose of said ILT7 binding protein is administered about once every two weeks.

[0304] 102. The method of any one of embodiments 98-101, wherein the subject is administered at least 4, 5, 6, 7, 8, 9, 10, 11, 12 or more doses of the ILT-7 protein every 4 weeks, followed by assignment to maintenance therapy.

[0305] 103. The method of embodiment 102, wherein the maintenance dose is administered once every 12 weeks.

[0306] 104. The method of any one of embodiments 98-103, wherein the ILT7 binding protein is administered with one or more additional therapies.

[0307] 105. The method of embodiment 104, wherein one of the one or more additional therapies is a corticosteroid.

[0308] 106. The method of embodiment 105, wherein administration of the corticosteroid is tapered.

[0309] 107. A method of treating DLE in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 300 mg, and the ILT7 binding protein is administered about once every four weeks.

[0310] 108. A method of treating DLE in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 150 mg, and the ILT7 binding protein is administered about once every four weeks.

[0311] 109. The method of embodiment 107 or 108, wherein said administering is effective to reduce one or more of the following: Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score, Cutaneous Lupus Erythematosus Disease Area and Severity Index-Damage (CLASI-D) score, Cutaneous Lupus Activity Physician Global Assessment (CLA-IGA) scale, Discoid Lupus Erythematosus Classification Criteria (DLECC) score, Score of Activity and Damage in Discoid Lupus Erythematosus (SADDLE), development of new discoid lesions, size of lesions, or dyspigmentation of discoid lesions.

[0312] Embodiment Set 2 1. A method of treating an autoimmune disorder in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 100-350 mg.

[0313] 2. The method of embodiment 1, wherein the autoimmune disease is selected from the group consisting of discoid lupus erythematosus (DLE), systemic lupus erythematosus (SLE), lupus nephritis, dermatomyositis, antisynthetic enzyme inflammatory myositis, and alopecia areata.

[0314] 3. The method of embodiment 2, wherein the autoimmune disease is SLE and the pharmacologic effective amount is about 200 mg.

[0315] 4. The method of any one of the preceding embodiments, wherein said administering is effective to reduce a) the level of plasmacytoid dendritic cells (pDCs) in a tissue of said subject, b) a type I interferon gene signature (IFNGS), or c) the level of plasmacytoid dendritic cells (pDCs) and said type I IFNGS in said tissue of said subject, each of which is compared to said subject's baseline level prior to said administering.

[0316] 5. The method of embodiment 4, wherein the IFNGS comprises the collective expression levels of SPATS2L, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, RSAD2, RTP4, SIGLEC1, and USP18.

[0317] 6. The method of embodiment 4, wherein the reduction in the level of said pDC in said tissue compared to baseline values ​​is at least about 10%, 20%, 25%, 30%, 40%, 50%, 60%, or 70%.

[0318] 7. The method of embodiment 2, wherein the autoimmune disease is lupus nephritis and the pharmacologic effective amount is about 300 mg.

[0319] 8. The method of embodiment 7, wherein after said administration, said subject achieves a positive renal response as measured by one or more of an improvement in glomerular filtration rate (eGFR) or 24-hour urinary protein to creatinine ratio (UPCR) compared to said subject's baseline levels prior to said administration.

[0320] 9. The method of embodiment 2, wherein the autoimmune disease is discoid lupus erythematosus (DLE) and the pharmacologic effective amount is about 150-300 mg.

[0321] 10. The method of embodiment 9, wherein said administering is effective to reduce one or more of the Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) score, Cutaneous Lupus Erythematosus Disease Area and Severity Index-Damage (CLASI-D) score, Cutaneous Lupus Activity Physician Global Assessment (CLA-IGA) scale, Discoid Lupus Erythematosus Classification Criteria (DLECC) score, Score of Activity and Damage in Discoid Lupus Erythematosus (SADDLE), development of new discoid lesions, size of lesions, or pigmentation abnormalities of discoid lesions, compared to the subject's baseline level prior to administration.

[0322] 11. The method of embodiment 2, wherein the autoimmune disease is alopecia areata and the pharmacologic effective amount is about 300 mg.

[0323] 12. The method of embodiment 11, wherein said administering is effective to stabilize or reduce hair loss in the subject as measured by a stabilization or reduction in the Severity of Alopecia Tool (SALT) score and / or an Alopecia Density and Extent (ALODEX) score.

[0324] 13. The method of any one of the preceding embodiments, wherein said ILT7 binding protein is administered with one or more additional therapies.

[0325] 14. The method of embodiment 13, wherein the one or more additional therapies comprises a corticosteroid.

[0326] 15. The method of embodiment 14, wherein said corticosteroid is prednisone.

[0327] 16. The method of any one of embodiments 13-15, wherein administration of the one or more additional therapies is tapered.

[0328] 17. The method of embodiment 1, wherein said pharma- ceutical effective amount of said ILT7 binding protein is about 150-300 mg.

[0329] 18. The method of embodiment 17, wherein said pharma- ceutical effective amount of said ILT7 binding protein is about 200-300 mg.

[0330] 19. The method of any one of the preceding embodiments, wherein the ILT7 binding protein is administered about once every 4 weeks, or about once every 12 weeks.

[0331] 20. The method of any one of the preceding embodiments, wherein the pharma- ceutical effective amount of the ILT7 binding protein is about 300 mg, and said 300 mg is administered as two doses of 150 mg each.

[0332] 21. A method of treating discoid lupus erythematosus (DLE) in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 100 to about 300 mg.

[0333] 22. A method of treating systemic lupus erythematosus (SLE) in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is from about 200 mg.

[0334] 23. A method of treating lupus nephritis in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is from about 300 mg.

[0335] 24. A method of treating alopecia areata in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is from about 300 mg.

[0336] 25. A method of treating dermatomyositis in a subject in need thereof, comprising administering to the subject a pharma- ceutical effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein.

[0337] 26. A method of treating anti-synthetic enzyme inflammatory myositis in a subject in need thereof, comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein.

[0338] 27. The method of embodiment 25 or 26, wherein said pharma- ceutical effective amount of said ILT7 binding protein is from about 100 mg to about 300 mg.

[0339] 28. The ILT7 binding protein, Heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3, and light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3, each comprising the amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. The method of any one of the preceding embodiments, wherein the antibody comprises:

[0340] 29. The ILT7 binding protein, a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1, and / or a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:2. 29. The method of embodiment 28, wherein the antibody comprises

[0341] 30. The ILT7 binding protein, An antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO: 2. 30. The method of embodiment 29, wherein

[0342] 31. The method of any one of the preceding embodiments, wherein said ILT7 binding protein is non-fucosylated.

[0343] 32. The method of any one of the preceding embodiments, wherein said ILT7 binding protein is daxzilimab.

[0344] 33. The method of any one of the preceding embodiments, wherein the administering is subcutaneous administration.

[0345] 34. The method of any one of embodiments 21-33, wherein the subject is administered the ILT7 binding protein every 4 weeks.

[0346] 35. The method of any one of embodiments 21-33, wherein the subject is administered the ILT7 binding protein every 12 weeks.

[0347] 36. The method of any one of embodiments 21-35, wherein prior to said administering, said subject is administered at least one initial dose of said ILT7 binding protein.

[0348] 37. The method of embodiment 36, wherein the at least one initial dose is administered in 1, 2, 3, 4, 5 or more doses every two weeks.

[0349] 38. The method of embodiment 36 or 37, wherein the at least one initial dose is about 100 to 300 mg.

[0350] 39. A method of treating lupus nephritis in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 100 mg every 2 weeks for up to 4 weeks, followed by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses of 100 mg every 4 weeks.

[0351] 40. The method of embodiment 39, wherein the subject is further administered 100 mg of an ILT7 binding protein every 12 weeks, or 300 mg of an ILT7 binding protein every 12 weeks following said every 4 weeks administration.

[0352] 41. The method of embodiment 40, wherein said 100 mg every 12 weeks, or said 300 mg every 12 weeks, is continued for at least about 104 weeks.

[0353] 42. A method of treating lupus nephritis in a subject in need thereof, the method comprising administering to the subject a pharmacologic effective amount of an immunoglobulin-like transcript 7 (ILT7) binding protein, wherein the pharmacologic effective amount of the ILT7 binding protein is about 300 mg every 2 weeks for up to 4 weeks, followed by 300 mg every 12 weeks for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 or more doses. EXAMPLES

[0354] Example 1: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of VIB7734 (Daxzilimab) for the Treatment of Moderately to Severely Active Systemic Lupus Erythematosus A Phase II, multicenter, international, double-blind, randomized, placebo-controlled, parallel-group study will be conducted to evaluate the efficacy and safety of daxzilimab in subjects with moderately to severely active systemic lupus erythematosus (SLE).

[0355] The target population is adults aged 18 to 70 years with moderately to severely active (recent flare or chronic active disease) SLE as defined by the SLE Disease Activity Index 2000 (SLEDAI-2K), British Isles Lupus Assessment Group (BILAG) 2004 index, and Physician Global Assessment (PGA). In this study, approximately 195 subjects will be randomized in a 1:1:1 ratio (65 subjects per group) to receive daxzilimab 200 mg (SC) every 4 weeks, daxzilimab 200 mg (SC) every 12 weeks with an additional dose of 200 mg (SC) at week 4, or placebo. To maintain blinding, subjects randomized to the daxzilimab 200 mg SC every 12 weeks dosing regimen will receive SC placebo injections at unscheduled dosing visits every 12 weeks. Randomization will be stratified by SLE Disease Activity Index 2000 (SLEDAI-2K) total score at screening (>=10 or <=10) and baseline (Day 1) prednisone or equivalent oral glucocorticoid (OGC) dose (>=10 mg or <=10 mg).

[0356] The study will include a screening period of approximately 4 weeks (days -28 to -1), randomization on day 1, treatment and evaluations through week 48, and a safety follow-up (SFU) period of 8 weeks (through week 56). Under exceptional circumstances, such as delayed test results, drug washout, or COVID-19 impact, the screening period may be extended by 2 weeks with approval from the medical monitor. The study will be conducted on an outpatient basis. For all doses, IP will be administered by site staff in the clinic, and subjects will be observed for at least 60 minutes after the first and second doses. Subjects who stop dosing early before week 44 will be followed through week 56. Subjects will not be automatically removed from the study if an IP dose is missed.

[0357] A long-term extension (LTE) study for safety and efficacy may be offered as part of a separate protocol to subjects who complete the Week 48 visit. Subjects who enter the LTE study directly after completing the Week 48 visit will not complete the SFU period visit.

[0358] The study design is summarized in Figure 1.

[0359] The primary objective is to evaluate the effect of daxuzilimab compared to placebo in reducing SLE disease activity at Week 48 in subjects treated with SoC therapy. The primary objectives will be measured according to the following criteria: Proportion of subjects achieving BILAG-Based Composite Lupus Assessment (BICLA) response and OGC dose ≦7.5 mg / day and ≦day 1 dose of prednisone or equivalent at Week 48. Subjects will be assessed for BICLA and oral glucocorticoids at Week 48. A BICLA response is defined as meeting all of the following criteria compared to baseline (Day 1): - Improvement in BILAG2004 indices (all baseline [day 1] BILAG A improved to B / C / D, all baseline [day 1] BILAG B improved to C / D, new BILAG B ≤ 1, no new BILAG A) No deterioration in SLEDAI-2K total score. No significant deterioration in PGA score (≦10% increase). No use of restricted medications above the protocol tolerance threshold prior to evaluation. ○There will be no cancellation of IP.

[0360] The efficacy objectives of the study are: To assess the effect of daxzilimab compared to placebo in reducing skin disease activity at week 12. Evaluations will measure the proportion of subjects with a baseline (day 1) CLASI-A score ≥ 10 and a ≥ 50% reduction from baseline (day 1) in CLASI-A score at week 12. Scoring will consist of (1) inflammatory activity of the disease, and (2) disease damage. To evaluate the effect of daxzilimab compared with placebo in reducing SLE disease activity at 48 weeks. o Evaluations will measure the proportion of subjects achieving SRI-4 response and OGC dose ≦7.5 mg / day and ≦baseline (Day 1) dose of prednisone or equivalent at Week 48. SRI-4 (SLE Responder Index) refers to meeting all criteria compared to baseline (e.g., no worsening of symptoms). To evaluate the effect of daxzilimab compared to placebo on sustained reduction in OGC from weeks 36 to 48. Evaluations will measure the proportion of subjects achieving an OCG ≥ 10 mg prednisone or equivalent at baseline (Day 1) and an OCG ≤ 7.5 mg / day prednisone or equivalent at Weeks 36-48. To evaluate the effect of daxzilimab compared with placebo in achieving low disease activity at 48 weeks. Evaluations will measure the proportion of subjects achieving a lupus low disease activity status (LLDAS) at week 48. The LLDAS is a composite measure of SLE disease activity that measures five criteria: (1) SLEDAI-2K ≤ 4 with no activity in major organ systems, (2) no new lupus disease activity, (3) PGA ≤ 1 (scale 0-3), (4) current prednisone or equivalent dose ≤ 7.5 mg / day, and (5) tolerated maintenance dose of immunosuppressant and approved biologic agents.

[0361] exploratory purpose (1) To evaluate the effect of VIB7734 compared to placebo on reducing the occurrence of moderate-to-severe flares by week 48 as determined by annualized flare rate. A flare is defined as either ≥ 1 new BILAG A item or ≥ 2 new BILAG B items compared to the previous visit. (2) To evaluate the effect of VIB7734 compared to placebo on various disease activity measures at week 48 and over time as determined by BICLA, BILAG2004 index, SRI-4, SRI-5, SRI-6, SRI-7, or SRI-8, SLEDAI-2K, CLASI, OGC dose, joint counts, major clinical response, partial clinical response, minimal disease activity, disease remission, and exposure-response relationships. (3) To explore potential associations of genetic variation, gene expression, and circulating protein profiles with VIB7734 response as determined by changes in levels of exploratory biomarkers over time. (4) To evaluate the effect of VIB7734 compared to placebo on participant-reported health-related quality of life and health assessment at week 48 as determined by the change in the Motor and Cognitive Fatigue Scale, Hospital and Anxiety Depression Scale, Cambridge Neuropsychological Test Automated Battery, Patient Global Assessment, Patient Global Impression Change, and Lupus Quality of Life. (5) To evaluate the effect of VIB7734 compared to placebo on organ damage at week 48 as determined by the change in the Systemic Lupus Erythematosus International Collaborating Clinics / American College of Rheumatology Damage Index.

[0362] Pharmacokinetic / pharmacodynamic / immunogenicity objectives To characterize the pharmacokinetics, pharmacodynamics, and immunogenicity of VIB7734 as determined by VIB7734 concentration, changes in pDC, and anti-drug antibody rates.

[0363] Inclusion Criteria: To be included in this study, each subject must meet all of the following criteria: 1.Age 18 to 70 years at the time of signing the Informed Consent Form (ICF). 2. Willing and able to understand and provide written informed consent prior to undergoing any study-related procedures, comply with all study requirements, and complete study evaluations. 3. Meet the 2019 European League Against Rheumatism / American College of Rheumatology classification criteria for SLE (Aringer et al, 2019). 4.Disease duration of at least 6 months from time of diagnosis at the time of signing the ICF. 5. Active SLE as indicated by the presence of all of the following: • SLEDAI-2K total score ≥ 6 at screening, excluding fever, SLE headache, or organic brain syndrome. • SLEDAI-2K total score ≥ 4 at screening and baseline (Day 1), excluding those attributable to urine or laboratory results, immunological measurements, fever, SLE headache, or organic brain syndrome. At least one of the following BILAG 2004 index levels of disease at screening: BILAG A disease in ≥ 1 organ system, o BILAG B disease in ≥ 2 organ systems. • PGA score ≥1 on a visual analog scale (VAS) of 0–3 at screening. 6. At the time of screening by the central laboratory, have at least one of the following: ●Antinuclear antibody (ANA) ≧1:80. • Anti-dsDNA antibodies are elevated above the normal range established by the central laboratory (i.e., a positive result). • Anti-Smith antibodies are elevated above normal levels (i.e., a positive result). 7. Ongoing treatment for SLE defined as (a) or (b): a. Treatment with disease-modifying antirheumatic drugs (DMARDs) or immunosuppressants: Any of the following medications administered at conventional antirheumatic doses for treatment of SLE for at least 12 weeks prior to screening (unless discontinued or dose adjusted for documented drug-related toxicity or size / weight) and at a stable dose (including route of administration) for a minimum of 8 weeks prior to screening and maintained through baseline (Day 1): i. Antimalarial drugs Chloroquine Hydroxychloroquine Quinacrine ii. Azathioprine (AZA) or 6-mercaptopurine (6-MP) iii. Leflunomide iv. Mycophenolate mofetil (MMF) or mycophenolic acid (MPA) v. Methotrexate (MTX) (if MTX is used, subjects must also supplement with folic or folinic acid) vi. Voclosporin (if approved for treatment) vii.GCs are permitted but not required if the subject is receiving at least one other drug listed above. If GCs are used concomitantly with an acceptable DMARD or immunosuppressant, they must be on a stable dose for at least 2 weeks prior to screening, with an average daily dose of PO prednisone (or prednisone equivalent) ≦40 mg for a minimum of 2 weeks prior to screening. In addition, the dose of OGCs must be stable and maintained for at least 2 weeks prior to randomization. Daily or alternate-day dosing of PO prednisone (or prednisone equivalent) is permitted. b. Treatment with OGC monotherapy (without concomitant DMARDs or immunosuppressants): i. Average daily dose of PO prednisone (or prednisone equivalent) ≥ 10 mg ≤ 40 mg for at least 4 weeks prior to screening, and stable dose for at least 2 weeks prior to screening. In addition, the dose of OGC must be maintained stable for at least 2 weeks prior to randomization. Daily or alternate day dosing of PO prednisone (or prednisone equivalent) is permitted. 8. Women of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at randomization. Women of childbearing potential are defined as women who are not surgically sterile (i.e., surgical sterilization includes bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or who are not postmenopausal (defined as 12 months without menses without another medical cause, unless receiving postmenopausal hormone replacement therapy, and with follicle-stimulating hormone (FSH) within the postmenopausal range established by a central laboratory). Females of childbearing potential who are sexually active with an unsterilized male partner must agree to use highly effective contraception by signing an informed consent and must agree to continue using such precautions until the end of study follow-up or for 3 months (approximately 5 half-lives) after the last dose of study drug if the study is discontinued early. Decisions regarding contraception after this point must be made by the subject and their usual health care provider. Although abstinence is an acceptable practice, periodic abstinence, rhythm methods, and withdrawal methods are not acceptable methods of contraception. Please note that mycophenolate may affect the metabolism of hormonal contraceptives and reduce their effectiveness in women receiving MMF or MPA who are using hormonal contraceptives for contraception, therefore subjects must use an additional method of contraception (e.g., a barrier method). 9. Unsterilized male subjects who are sexually active with a female partner of fertile potential must agree to use condoms containing spermicide from randomization until 3 months (approximately 5 half-lives) after receipt of the last dose. Because male condoms containing spermicide are not a highly effective method of contraception, it is strongly recommended that male subjects advise their female partners of fertile potential to use a highly effective method of contraception throughout this entire period.

[0364] Exclusion criteria: 1. Any individual involved in the conduct of the study, their employees, or any immediate family member of such an individual. 2. Any condition that, in the opinion of the investigator, may interfere with the evaluation of the IP or the subject's safety or interpretation of the study results. 3. History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP or to previous mAb or human Ig therapy. 4. Participation in another clinical trial by IP within 4 weeks prior to Day 1 or within 5 published half-lives, whichever is longer. 5. Women who are breastfeeding or pregnant, or who are planning to become pregnant between signing the ICF and 6 months after receiving the last dose of IP. 6. History of drug or alcohol abuse that, in the opinion of the investigator, may affect the subject's safety or compliance with visits or interfere with other study evaluations. 7. Major surgery within 8 weeks prior to screening or elective surgery planned up to 393 days after screening. 8. Spontaneous or induced abortion, stillbirth or live birth, or pregnancy within ≤ 4 weeks prior to screening. 9. Known history of major immunodeficiency or underlying condition such as known human immunodeficiency virus (HIV) infection, positive result for HIV infection per central laboratory, splenectomy, or any underlying condition that, in the opinion of the investigator, renders the subject significantly more susceptible to infection. 10. One of the following by a central laboratory at screening (tests may be repeated once within the same screening period to confirm results prior to randomization): ●AST ≥ 2.5 × ULN, ●ALT ≥ 2.5 × ULN, Total bilirubin ≥ 1.5 × ULN (excluding cases due to Gilbert syndrome), Serum IgG ≦600mg / dL (or ≦6g / L), Neutrophil count ≦1000 / μL (or ≦1.0×10 9 / L) or ≤500 / μL (≤0.5 × 10) if due to active SLE 9 / L), Platelet count ≦50,000 / μL (or ≦50×10 9 / L) or ≦250,000 / μL (≦25×10 9 / L), Hemoglobin ≤ 8g / dL (or ≤ 80g / L) or ≤ 7g / dL (≤ 70g / L) if due to active SLE; Glycosylated hemoglobin ≥ 8% (or ≥ 0.08), Total lymphocyte count ≦200 cells / mm 3 , Glomerular filtration rate ≦30mL / min / 1.73m 2 , ●Spot UPCr ≥ 3mg / mg (> 339mg / mmol). 11. Have confirmed positive Hepatitis B serology defined as: Hepatitis B surface antigen (HBsAg), or - Hepatitis B core antibody (HBcAb) and Hepatitis B virus (HBV) DNA are detected above the lower limit of quantification (LLOQ) by central laboratory reflex testing at the time of screening. Note that subjects who are HBcAb positive at screening will be tested every 3 months for HBV DNA. If the subject's HBV DNA level is confirmed to be above the LLOQ by the central laboratory, study drug will be discontinued. 12. Hepatitis C virus antibody test positive. 13. Positive IFN-γ release assay (IGRA) at screening unless they have documented active TB or a history of adequate treatment for active or latent TB. Subjects with indeterminate IGRA test results may have repeat testing but will be excluded if repeat testing is also indeterminate. 14. Any severe herpes virus family infection (including Epstein-Barr virus, cytomegalovirus [CMV]), including but not limited to disseminated herpes, herpes encephalitis, recent recurrent herpes zoster (defined as 2 episodes within the past 2 years), or ophthalmic herpes, at any time prior to randomization. 15. Any herpes zoster, CMV, or Epstein-Barr virus infection that was not completely resolved 12 weeks prior to randomization. 16. Within 30 days prior to signing the ICF, either: Clinically significant active infection, including ongoing and chronic infections requiring antibiotics or antivirals, in the opinion of the investigator (chronic nail infections are permitted); Any infection requiring hospitalization or treatment with IV anti-infectives, Subjects with a documented positive SARSCoV-2 test may be rescreened at least 2 weeks after the positive test if asymptomatic and at least 3 weeks after symptomatic COVID-19 illness. 17. Opportunistic infection requiring hospitalization or parenteral antibacterial treatment within 2 years prior to randomization. 18. Evidence of any acute illness or clinically significant active infection. 19. History of clinically significant cardiac disease, including unstable angina and / or myocardial infarction and / or congestive heart failure within 6 months prior to randomization, or any cardiac condition, including but not limited to: inadequately controlled arrhythmias, presence of clinically significant abnormalities on ECG that, in the opinion of the investigator, would increase the risk of study participation. 20. History of cancer within the past 5 years, except as follows: • intraepithelial neoplasia of the cervix, treated with apparent success with definitive therapy ≥12 months prior to screening, or • Basal or squamous cell carcinoma of the skin that has been treated with apparent success with definitive therapy. 21. Receipt of live attenuated vaccines within 4 weeks prior to Day 1. Administration of inactivated (killed) vaccines is acceptable. 22. Subjects should be assessed for epidemiological risk of COVID-19 (i.e., recent exposure, high-risk housing) and health-related risk of COVID-19 severity, based on current understanding of risk factors for severe disease, when making decisions regarding the risk of individual participation. Subjects who have COVID-19 or other significant infections or who, in the investigator's judgment, may be at high risk for COVID-19 or its complications should not be randomized. 23. Active LN or active severe or unstable neuropsychiatric SLE (e.g., aseptic meningitis, cerebral vasculitis, myelopathy, demyelinating syndromes [ascending, transverse, acute inflammatory demyelinating polyradiculopathy]), acute confusional state, impaired level of consciousness, psychosis, acute stroke or stroke syndrome, cranial neuropathy, status epilepticus, cerebellar ataxia, multiple mononeuritis) In the opinion of the investigator or medical monitor, the protocol-specified SoC is insufficient and a more aggressive treatment approach such as IV cyclophosphamide (e.g., high-dose IV pulse GC therapy, MMF >3 gm / day (MPA >2.16 gm / day), or escalation of MMF / MPA from baseline dose, and / or other treatments not permitted by the protocol may be indicated) is utilized. 24. Diagnosis of non-SLE vasculitis syndrome, mixed connective tissue disease, or rheumatic (overlap) syndrome. 25. Use of immunosuppressants, biologics, and DMARDs within the protocol-defined washout period.

[0365] Example 2: Open-Label Extension Study to Evaluate the Long-Term Safety and Tolerability of Daxuzilimab in Subjects with Systemic Lupus Erythematosus (SLE) A Phase 2, multicenter, open-label extension (OLE) study will be conducted to evaluate the long-term safety and tolerability of daxuzilimab in subjects who completed the treatment period of the RECAST SLE clinical trial. The RECAST SLE study is a Phase 2, randomized, double-blind, placebo-controlled efficacy and safety study of daxuzilimab for the treatment of moderately to severely active systemic SLE. The study will enroll approximately 195 subjects. The SLE Open-Label Extension (OLE) study (HZN-DAX-204) is a long-term OLE study of daxuzilimab plus standard of care in subjects who completed the treatment period of the RECAST SLE protocol. All subjects who enter the OLE, regardless of treatment assigned in the RECAST SLE study, will be treated subcutaneously (SC) with daxuzilimab every 12 weeks (Q12W) in addition to standard of care SLE therapy.

[0366] To allow for sequential dosing of subjects, initiation of this OLE study should occur immediately following completion of the RECAST SLE treatment period (i.e., first OLE dose [Day 1] coinciding with Week 48 / Visit 14 of the RECAST SLE study).

[0367] The primary and secondary objectives, as well as associated endpoints, are detailed below. Briefly, the primary objective of this study is to evaluate the long-term safety and tolerability of daxuzilimab 200 mg every 12 weeks in adult subjects with moderately to severely active SLE. This will be assessed by summarizing adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). Local injection site tolerability, vital signs, physical examination, electrocardiogram, and laboratory tests will also be performed to support safety findings.

[0368] (Table 3) Primary purpose, secondary purpose, exploratory purpose TIFF2024516698000004.tif233165

[0369] treatment Subjects will be treated with open-label daxuzilimab 200 mg subcutaneously (SC) every 12 weeks (Q12W) for 48 weeks at the study site (see Figure 2). Daxuzilimab will be administered as two 1.0 mL SC injections. A summary of treatment is provided in Table 4.

[0370] Table 4. Description of study drugs and administration TIFF2024516698000005.tif106165

[0371] During the treatment period, telemedicine visits (e.g., telephone or video calls) will occur every 4 weeks between in-clinic visits to assess the subject's current disease status, OGC taper schedule, safety, and concomitant medications. After the treatment period (Weeks 0-48), study subjects will enter an 8-week safety follow-up period (Weeks 48-56) (see activity schedule in Table 5).

[0372] Table 5. Exemplary activity schedule TIFF2024516698000006.tif179165TIFF2024516698000007.tif195165TIFF20245166980 00008.tif196165TIFF2024516698000009.tif228165TIFF2024516698000010.tif142165

[0373] Inclusion criteria (1) Willing and able to understand and provide written informed consent, comply with all study requirements, and complete study evaluations prior to undergoing any study-related procedures. (2) Must be eligible for and receiving IP (daxuzilimab or placebo) and must have completed the treatment period (through day 337) of the RECAST SLE study. Subjects who discontinue IP early for RECAST SLE are not eligible for the study. (3) Women of childbearing potential must have a negative urine pregnancy test on day 1. Women of childbearing potential are defined as women who are not surgically sterilized (i.e., surgical sterilization includes bilateral salpingectomy, bilateral oophorectomy, or hysterectomy) or who are not postmenopausal (defined as 12 months without menses without another medical cause, unless receiving hormone replacement therapy after menopause, and without follicle-stimulating hormone [FSH] within the postmenopausal range established by the central laboratory during the RECAST SLE study screening period). Once a female subject becomes postmenopausal during the study (i.e., 12 months without menstruation without another medical cause, unless receiving hormone replacement therapy after menopause), FSH testing will be performed in a central laboratory. If FSH levels are within the postmenopausal range, the female subject will not require subsequent contraception. Women of childbearing potential who are sexually active with an unsterilized male partner must agree to use highly effective contraception by signing an ICF, and agree to continue using such precautions until the end of study follow-up or for 3 months (approximately 5 half-lives) after the last dose of study drug if the study is discontinued early, and to refrain from egg retrieval / egg donation during this period. After this point, decisions regarding contraception should be made by the subject and their usual health care provider. Female subjects participating in the SLE OLE are expected to maintain the same form of contraception they used during the RECAST SLE study. Please note that mycophenolic acid may affect the metabolism of hormonal contraceptives and reduce their effectiveness in women receiving MMF or mycophenolic acid (MPA) who are using hormonal contraceptives for contraception, therefore subjects must use an additional method of contraception (e.g., a barrier method).(4) Unsterilized male subjects who are sexually active with a female partner of fertile potential should agree to use condoms containing spermicide from day 1 through 3 months (approximately 5 half-lives) after administration of the final dose. Because male condoms containing spermicide are not a highly effective method of contraception, it is strongly recommended that male subjects advise their female partners of fertile potential to use a highly effective method of contraception throughout this entire period.

[0374] Exclusion criteria (1) Any condition or change during the RECAST SLE study that, in the opinion of the investigator or sponsor, would interfere with the evaluation and interpretation of the subject's safety and would alter the risk-benefit associated with IP administration. (2) Participation in another clinical trial with IP during the RECAST SLE study. (3) Planned elective surgery that, in the opinion of the investigator or sponsor, may interfere with the evaluation and interpretation of the subject's safety. (4) Any herpes zoster, cytomegalovirus, or Epstein-Barr virus infection that has not completely resolved before Visit 1. (5) Clinically significant active infection at Visit 1, including ongoing and chronic infections requiring antibiotics or antivirals, in the opinion of the investigator (chronic nail infections are permitted). (6) Pregnant or breastfeeding women. Criteria for prior and concomitant therapy: (7) Receipt of prohibited medications during the RECAST SLE study. Receipt of restricted medications during the RECAST SLE study must be discussed with the sponsor's medical monitor and agreed upon prior to enrollment in the study.

[0375] Reasons for cancellation An individual subject will not receive further daxuzilimab if the subject experiences any of the following: (1) receipt of an intolerable medication or therapy, (2) a grade 3 or higher allergic reaction to daxuzilimab, (3) a grade 3 or higher infection considered related to daxuzilimab, (4) any other adverse event that, in the opinion of the investigator and / or sponsor and medical monitor, prohibits further treatment, (5) withdrawal of consent from further treatment with daxuzilimab, or (6) the subject meets one or more exclusion criteria or does not meet all inclusion criteria for study participation and is not medically responsible. (7) potential safety risks associated with continuation identified in consultation with the monitor, (8) pregnancy or intention to become pregnant, (9) any of the following liver function abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 8 × upper limit of normal (ULN), ALT or AST ≥ 5 × ULN for more than 2 weeks, ALT or AST ≥ 3 × ULN and total bilirubin ≥ 2 × ULN or international normalized ratio ≥ 1.5 without alternative explanation, ALT or AST ≥ 3 × ULN with the occurrence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and / or eosinophilia (≥ 5%).

[0376] Combination Therapy - Combination Drugs for Standard Treatment of Systemic Lupus Erythematosus Under Investigation Immunosuppressants, if administered during the RECAST SLE study, must be maintained constant throughout the treatment period, with the exception of oral glucocorticoids (OGCs) and nonsteroidal anti-inflammatory drugs (NSAIDs). Background therapy may only be changed for documented safety issues. Toxicity / events must be confirmed as documented AEs. Dose may be returned to OLE baseline (Day 1) levels when toxicity / events resolve and clinically indicated. Initiation of any new immunosuppressant or immunomodulator therapy or an increase in dose above the levels used on Day 1 of the OLE may result in discontinuation of the subject's IP (at the discretion of the Sponsor's Medical Monitor).

[0377] Glucocorticoids (GCs). Oral GCs are permitted but not required for study participation. Oral GCs other than prednisone may be used orally (PO) at equivalent doses. Because the goal of this OLE is to determine the lowest clinically appropriate level of steroids, including cessation of steroids, by week 36 that can be delivered while maintaining response, investigators are strongly encouraged to taper the OGC dose as tolerated after subjects enroll in the study. Tapering and burst guidance is outlined below. During the study, investigators may contact the medical monitor to discuss tapering or burst scenarios, as appropriate.

[0378] Oral glucocorticoid tapering guidance. Oral GC tapering should begin by week 4 of the clinical trial. An example of a recommended OGC tapering regimen is provided in Figure 3. However, due to variability in subject response to OGC treatment and tolerability of tapering, investigators will have flexibility in how to taper the OGC dose at each visit, but investigators are encouraged to taper monthly by at least 1 mg / day. Tapering of OGC should be attempted unless at least one of the following criteria is met: (1) there is new or worsening organ system(s) affected by SLE; (2) there is increasing skin involvement; (3) there is new or worsening joint involvement. If there are scenarios outside of these listed criteria in which the investigator determines tapering is not appropriate, the medical monitor should be notified and the reasons for not tapering should be discussed.

[0379] Glucocorticoid Burst Guidance. Investigators are encouraged to limit the use of GC bursts throughout clinical trials as far as clinically feasible. GC bursts are permitted at the investigator's discretion.

[0380] Increased oral glucocorticoids for surgery and prevention of adrenal insufficiency. Increased oral glucocorticoids for surgery and prevention of adrenal insufficiency are tolerated as clinically indicated.

[0381] Other Permitted Drugs Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: If used during the RECAST SLE study, it is recommended that they be maintained at a stable dose during the OLE study unless a dose change, discontinuation, or initiation is necessary for documented safety reasons.

[0382] Anti-COVID therapeutic antibodies Aspirin. Low-dose aspirin (≦350 mg / day) may be used for cardiovascular prophylaxis. This is permitted in addition to the use of NSAIDs as specified below.

[0383] Prevention and treatment of osteoporosis. Vitamin D and calcium supplementation, and treatment of osteoporosis, as needed, are permitted in accordance with local standard treatment guidelines.

[0384] Herbal supplements may be continued during the study. It is recommended that the dose and preparation be kept constant unless discontinued all together. It is recommended not to start or restart herbal supplements once discontinued during the study.

[0385] Medications for the treatment of injection site reactions. These may include local or systemic antihistamines, topical GCs, paracetamol, or NSAIDs.

[0386] NSAIDs. NSAIDs may be used as needed (PRN) during the OLE. Subjects taking NSAIDs (including cyclooxygenase 2 inhibitors; topical, prescription, or OTC) on a regular schedule for SLE symptoms at OLE baseline (Day 1) may continue to take them at a stable dose throughout the study. NSAIDs should not be taken on visit days until all assessments have been completed. Subjects may have their dose adjusted during the study for documented toxicity / safety reasons. Any NSAIDs (prescription, OTC, or topical) should not be used above the maximum tolerated dose according to local guidelines.

[0387] Opioids. If present at OLE baseline (Day 1), stable doses of up to 40 mg / day morphine equivalents are permitted. Initiation of opioids and / or PRN dosing after Day 1 of the OLE for SLE is not recommended and should not exceed 40 mg / day or equivalent (if prescribed). These may be titrated during the study as tolerated. Pain medications, including opiates, may be used at a fixed dose or PRN for temporary relief of symptoms not attributable to SLE, but are then strongly recommended to be avoided for 24 hours prior to each study visit.

[0388] Acetaminophen. Short-acting acetaminophen (paracetamol) may be initiated or continued for pain management during the study at approved doses. Pain medications should not be used within a minimum of 6-12 hours (based on known duration of effect) of a scheduled clinic visit.

[0389] Topical Therapies for CLE. Concomitant use of topical therapies for CLE (e.g., GC, pimecrolimus) is permitted. Topical therapy must be the same as that used in the 2 weeks prior to the OLE baseline (Day 1), and the dose and frequency of application must remain constant. During the study, topical therapy may be reduced or discontinued based on clinical symptoms and the investigator's discretion. If skin symptoms recur, the same topical therapy may be resumed up to the dose used at the OLE baseline (Day 1). If necessary, new dermatological medications may be used for the duration of the study. Subjects are also encouraged to use sunscreen (listed as a concomitant medication for SLE) and avoid sun exposure during the study. Topical moisturizers are also permitted.

[0390] Any medication (except those prohibited by the protocol) that is deemed necessary for the subject's welfare and would not interfere with the study medication may be administered at the investigator's discretion.

[0391] Prohibited drugs Biologic immunomodulators (including but not limited to belimumab, abatacept, or rituximab) Bone marrow, stem cell (e.g., mesenchymal stem cell), or solid organ transplants Cyclophosphamide ●GC - Intralesional - Intradermal for alopecia - Adrenocorticotropic hormone (ACTH) analogues (e.g., Acthar®, Synacthen®) - Dehydroepiandrosterone -Topical use (permitted per permitted drug) if used in accordance with the inclusion and exclusion criteria. Ig therapy Test drug ●IPP-201101(Lupuzor(trademark)) IV corticosteroids ≥ 1 g methylprednisolone or equivalent Janus kinase inhibitors (e.g., tofacitinib [Xeljanz®], baricitinib [Olumiant®], upadacitinib [Rinvoq™], filgotinib, peficitinib) Live or attenuated vaccines, including Bacille-Calmette-Guerin (sponsors are encouraged to ensure that all subjects are up to date on required vaccinations prior to study entry) Minocycline Plasmapheresis, plasma exchange, or Therakos® photopheresis Thalidomide and thalidomide derivatives (e.g., lenalidomide [Thalomid®, Revlimid®]) Local calcineurin or mammalian target of rapamycin (mTOR) inhibitors (e.g., pimecrolimus [e.g., Elidel®], sirolimus) Sulfasalazine Systemic mTOR inhibitors (e.g., sirolimus [Rapamune®])

[0392] Restricted medications Because daxuzilimab is an investigational immunomodulatory agent, non-protocol permitted changes to immunomodulatory or immunosuppressive agents in the study are strongly discouraged. If a subject begins any of the following during the treatment period or increases their dose above the OLE baseline (Day 1) dose, the Investigator must immediately notify the Sponsor's Medical Monitor, who will determine if the subject can continue to receive IP. Antimalarial drugs: - Chloroquine - Hydroxychloroquine - Quinacrine ●AZA Cyclosporine - Cyclosporine eye drops are permitted for use during the study. - Lifitegrast eye drops (Xiidra eye drops) are permitted for use during the study. Danazol Dapsone ●GC -Methylprednisolone ≥ 80 mg / day intramuscularly or equivalent. - Total methylprednisolone ≥ 80 mg or equivalent intra-articular / tendon sheath / bursa injection. - IV ≥ 40 mg / day but ≤ 1 g / day of methylprednisolone or equivalent. - OGC o ≥ 40 mg / day of prednisone or equivalent. ○ Treatment above the OLE baseline (Day 1) dose for a dosing period of ≥ 14 days. - Long biological half-life (e.g., dexamethasone, betamethasone). - SC or intramuscular precursors (e.g. ACTH). Intra-articular drugs other than GC Leflunomide 6-Mecaptopurine (6-MP) ●MPA ●MMF - Changing the route of administration of MTX or PO, SC, or intramuscular MTX Sulfasalazine Tacrolimus Voclosporin

[0393] evaluation (1) Completion and Review Process for Lupus Assessments. An appropriately trained and qualified investigator will complete lupus assessments, including, but not limited to, the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), and joint counts. The SLEDAI-2K, Physician Global Assessment (PGA), and CLASI must be administered by the investigator or an appropriately qualified physician, unless sponsor approval has been obtained in advance for other clinically trained site personnel with documented appropriate assessment experience. Joint count assessments may, at the investigator's discretion, be completed by other site personnel who are qualified to perform assessments and have at least one year of experience performing joint count assessments.

[0394] (2) Systemic Lupus Erythematosus Disease Activity Index 2000. The SLEDAI-2K index consists of a list of organ symptoms, each with a definition. A qualified investigator or designated physician completes the SLEDAI-2K assessment and determines whether each symptom is "present" or "absent" within the past 4 weeks. The assessment also includes blood and urine collections to assess the SLEDAI-2K laboratory categories. The SLEDAI-2K assessment consists of 24 lupus-related items. It is a weighted instrument, where the descriptors are multiplied by the "weight" of the organ. For example, the renal descriptor is multiplied by 4 and the central nervous system (CNS) descriptor is multiplied by 8. These weighted organ symptoms are summed into a final score. The SLEDAI-2K score is a valid, reliable, and sensitive clinical assessment of lupus disease activity. The SLEDAI-2K calculated using a 30-day window prior to clinical and laboratory visits has been shown to be similar to the SLEDAI-2K with a 10-day window (Touma et al., 2010). In this study, a 28-day window (± the accepted visit window) is used.

[0395] (3) Modified SLEDAI-2K flare index. The National Evaluation of Estrogen Safety in Classical Lupus Erythematosus (SELENA)-Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) flare index (SFI) is a composite outcome of the SELENA-SLEDAI, PGA (range 0–3), treatment changes, and some additional items (Arora et al., 2020; Petri et al., 2005). Thanou et al. (2014) developed a modified version of the classic SFI in which drug criteria are excluded from the classic SFI (Thanou et al., 2014; Thanou et al., 2018). In this OLE study, the SLEDAI-2K was used instead of the SELENA-SLEDAI, and thus a modified SLEDAI-2K flare index was used, with scoring as follows (28-day recall period): (A) Mild or moderate flare in expert clinician opinion: (i) ≥3 point change in SLEDAI-2K score (but not exceeding 12 points), (ii) New / worsening: discoid, photosensitive, profundus, cutaneous vasculitis, bullous lupus, nasopharyngeal ulcer, pleuritis, pericarditis, arthritis, fever (SLE), PGA score increase of ≥1.0 but not exceeding 2.5. (B) Severe flare: (i) change in SLEDAI-2K score to ≥12, (ii) new / worsening: CNS-SLE, vasculitis, nephritis, myositis, platelets ≤60,000, hemolytic anemia: hemoglobin ≤70 g / L or decrease in hemoglobin ≥30 g / L, hospitalization for SLE activity, increase in PGA ≥2.5.

[0396] (4) Physician Global Assessment. The PGA represents the physician's overall assessment of the average SLE disease severity over the past 4 weeks on a visual analog scale with disease activity ranging from 0 (no disease) to 3 (severe). The PGA for a given subject should be completed by the same physician whenever possible. The PGA is a modification of the classical analog scale in that it is fixed with numbers from 0 to 3, demarcating none, mild, moderate, and severe disease. The number 3 indicates severe disease and is at the end of the scale. It refers to the most severe disease possible and reflects not the most severe disease observed in a particular subject, but the most severe disease ever observed in all SLE subjects. Thus, the path made by the physician along this scale should not substantially approach this edge. Disease above a rated 2.5 is very severe. The range of moderate disease covers approximately 1.5 to 2.4. Mild disease is below 1.5. This instrument is like a logarithmic scale, allowing for a larger distance or boundary between milder and moderate symptoms. When scoring the PGA, it is necessary to review the score from the previous visit and move the mark compared to the score from the previous visit. This is a global assessment that takes into account all aspects of the subject's lupus disease activity. It should not reflect non-lupus medical conditions.

[0397] (5) Lupus Low Disease Activity Status. Lupus Low Disease Activity Status (LLDAS) is a composite measure of SLE disease activity used in clinical trials (Franklyn et al., 2016). LLDAS is defined and measured by achieving all five of the following criteria: SLEDAI-2K ≤ 4, no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis, fever), no hemolytic anemia or gastrointestinal activity, no new lupus disease activity compared to previous assessment (SLEDAI-2K), PGA ≤ 1 (scale 0-3), current prednisone (or equivalent) dose ≤ 7.5 mg / day, and well-tolerated standard maintenance doses of immunosuppressants and approved biologic agents.

[0398] (6) Reduction of oral glucocorticoids.

[0399] (7) Systemic Lupus International Collaborating Clinics / American College of Rheumatology Damage Index. The Systemic Lupus International Collaborating Clinics / American College of Rheumatology (SLICC / ACR) Damage Index (SDI) was developed to assess irreversible damage in SLE subjects occurring after disease onset, independent of its cause (SLE activity, therapy, comorbidities). Damage (i.e., irreversible damage since onset of SLE) is usually defined as a clinical feature that must be present continuously for at least 6 months to be scored. In addition, some irreversible events such as myocardial infarction or cerebrovascular accidents are scored as damage at the time of their occurrence. Briefly, damage is defined for 12 organ systems: peripheral vascular, ophthalmic, neuropsychiatric, renal, pulmonary, cardiovascular, gastrointestinal, musculoskeletal, cutaneous, endocrine (diabetes), gonadal, and malignant. Damage over time may be stable or may increase up to 47 points, but the number of points must not decrease.

[0400] (8) Cutaneous Lupus Erythematosus Disease Area and Severity Index. The CLASI is a validated index used to evaluate skin lesions in SLE and is composed of two separate scores: the first score summarizes the inflammatory activity of the disease; the second score is a measure of the damage done by the disease. The activity score takes into account erythema, scaling / hypertrophy, mucosal lesions, recent alopecia, and non-scarring alopecia. The damage score represents pigmentation abnormalities, scarring / atrophy / panniculitis, and scarring of the scalp. Subjects are asked if the pigmentation abnormalities have lasted for more than 12 months, in which case the pigmentation abnormality score is doubled. Each of the above parameters is measured in 13 different anatomical locations, which are specifically included because they are most frequently involved in CLE. The most severe lesions in each area are measured.

[0401] (9) 28 joint count. The painful, swollen, and tender joint counts are based on the left and right shoulder, elbow, wrist, metacarpophalangeal joint (MCP)1, MCP2, MCP3, MCP4, MCP5, proximal interphalangeal joint (PIP)1, PIP2, PIP3, PIP4, and PIP5 joints of the upper limbs, and the left and right knees of the lower limbs. At the start of the joint count (before the evaluation of tenderness and swelling), subjects are asked whether they have experienced or are experiencing pain in any of the 28 joints within the past 30 days. An active joint for the calculation of the SLEDAI-2K is defined as a joint that has pain and signs of inflammation (i.e., tenderness, swelling, or effusion). Each of the 28 joints is then evaluated separately for tenderness (by palpating the joint) and swelling. Joints with intra-articular injections within 4 weeks cannot be evaluated. The joint count assessment includes questions regarding limitations in range of motion and the impact of joint symptoms on basic and functional activities of daily living.

[0402] (10) Safety assessment is presented in Table 5.

[0403] (11) Physical Examination A complete physical examination will be performed at the Week 0 [Day 1] and Week 48 visits. A focused physical examination should be performed at all other visits. A focused physical examination should always include evaluation of the head, ears, eyes, nose, throat, lungs, heart, abdomen, skin, and extremities. Any medically significant change from the screening physical examination will be recorded as an AE unless it is considered symptomatic of SLE and captured on the SLEDAI-2K or CLASI.

[0404] (12) Vital Signs. Vital signs, blood pressure (mmHg), pulse rate (beats / min), respiratory rate (breaths / min), and temperature (°C), as well as weight (kg), will be obtained as outlined in Table 5 using clinically acceptable methods and devices as outlined therein. Vital signs should be measured in a sitting position with the subject at rest in this position for at least 5 minutes before each reading and, if possible, should be obtained before blood draw. Vital signs should be checked before and after IP administration as follows: within 15 minutes before administration of IP, but not more than 30 minutes on days when ECG is performed; and every 30 minutes (± 5 minutes) for 60 minutes after administration or until stable, whichever is later (first 2 study visits only). If an anaphylactic or hypersensitivity reaction occurs after SC administration of IP, vital signs will be obtained more frequently based on the investigator's judgment and depending on the severity of the reaction.

[0405] (13) Electrocardiogram. A computerized 12-lead ECG will be performed at the visits specified in Table 5. The investigator or qualified designee will review and indicate whether the ECG is normal, abnormal but not clinically significant, or abnormal and potentially clinically significant. The ECG should be performed after vital signs have been examined and the patient has been at rest in the supine position for 10 minutes.

[0406] (14) Local Injection Tolerability Assessment. Daxuzilimab will be administered by study site staff in the clinic and each subject will be assessed for local injection tolerability 60 minutes after the first and second doses (Day 1 and Week 12) are administered. The investigator or designee will assess the injection site at their visit and document the presence or absence of local tolerability / injection site reactions and open an AE in case of local injection site tolerability. Additional local injection tolerability assessments will be conducted at additional time points specified in Table 5. Additional follow-up after Week 48 may be performed for any ongoing injection site reactions.

[0407] (15) Clinical Safety Laboratory Tests. All protocol required laboratory tests, as defined in Table 5, should be performed in the central laboratory at the visits specified in Table 5, in accordance with the laboratory manual. Abnormal laboratory findings associated with underlying disease are not considered clinically significant unless the investigator determines that the findings are more severe than would be expected for the subject's condition. During participation in the study, all laboratory tests whose values ​​are determined to be clinically significantly abnormal should be repeated as soon as possible (preferably within 24-48 hours) until the values ​​return to normal or baseline, or until the investigator or medical monitor determines that they are not clinically significant. Exemplary laboratory tests are shown in Table 6.

[0408] (Table 6) Clinical tests TIFF2024516698000011.tif183165TIFF2024516698000012.tif125165

[0409] If the isolated Hepatitis B core on the RECAST SLE test is positive, Hepatitis B DNA testing (Reflex DNA testing) will continue to be performed every 12 weeks. If the central laboratory confirms that the subject's Hepatitis B viral DNA level is above the lower limit of quantification, IP will be discontinued.

[0410] Pharmacokinetics. Serum for PK analysis will be collected at the visits specified in Table 4 and analyzed using validated bioanalytical methods.

[0411] Pharmacodynamics. Whole blood for assessment of pDC levels by flow cytometry will be collected at the visits specified in Table 4. Daxudilimab binds to ILT7 on the surface of pDCs leading to recruitment of macrophages and NK cells, thus inducing apoptosis and a reduction in the number of pDCs.

[0412] Biomarker Assessment. Whole blood will be drawn and processed into serum, plasma, and peripheral blood mononuclear cells (PBMCs) at the time points specified in Table 4. Samples will be collected for assessment of IFNα (serum) and myxovirus resistance protein A (whole blood). The following additional samples will be collected and evaluated for exploratory biomarkers related to daxudilimab mechanism of action or SLE disease activity: serum (e.g., autoantibody profile, cytokine / chemokine profile, and other proteins or factors related to SLE disease pathways), plasma (e.g., complement split products), whole blood transcriptomics (e.g., IFN gene signature or genes associated with disease activity), PBMCs (e.g., frequency and / or gene expression of immune cell populations).

[0413] Immunogenicity Assessment. Serum for immunogenicity ADA analysis will be collected at the visits specified in Table 4 and evaluated using a validated immunoassay. Serum samples will be screened for antibodies that bind daxuzilimab and titers of confirmed positive samples will be reported. Other analyses can be performed to further characterize the immunogenicity of daxuzilimab. Antibodies can be further characterized and / or evaluated for their ability to neutralize the activity of daxuzilimab.

[0414] (16) Pregnancy testing. Urine pregnancy testing will be performed in women of childbearing potential during treatment and followed up at the investigational site using a dipstick as shown in Table 5.

[0415] (17) Quality of Life Assessments. Quality of life and pharmacoeconomic assessments will be conducted at the visits specified in Table 5.

[0416] (18) Patient Global Assessment. Subjects complete the Patient Global Assessment (PtGA). The PtGA is a single-item question that considers all the ways in which illness and health conditions may be affecting the subject at this time. Subjects should consider the previous week when answering this question. Responses range from "very good" to "very poor" on a 100 mm visual analog scale.

[0417] (19) Patient Global Impression of Change. The Patient Global Impression of Change is a self-rating scale asking subjects to describe changes in activity limitations, symptoms, feelings, and overall quality of life associated with their condition on the following scale: 1 (much improved), 2 (much improved), 3 (slightly improved), 4 (no change), 5 (slightly worse), 6 (much worse), and 7 (much worse).

[0418] (20) Lupus Quality of Life. The Lupus Quality of Life (LupusQoL) is a 34-item SLE-specific health-related quality of life measure. The instrument consists of eight domains: physical health [8 items], pain [3 items], planning [3 items], intimate relationships [2 items], burden to others [3 items], emotional health [6 items], body image [5 items], and fatigue [4 items].

[0419] Example 3: Phase 2a, open-label, proof-of-concept study of daxuzilimab for the treatment of moderate to severe alopecia areata This is a Phase 2a, multicenter, open-label, proof-of-concept trial evaluating the preliminary efficacy, safety, tolerability, PK, and PD of daxzilimab in subjects with moderate-to-severe AA with ≥50% and ≤95% total scalp hair loss as defined by screening and Day 1 SALT scores. Subjects will be 18-65 years of age (inclusive) and have a current episode of hair loss of at least approximately 3 months and less than 7 years, with an investigator assessment that hair regrowth is possible, there is no evidence of active regrowth at baseline, and there is no known history of significant regrowth in the past 6 months. Approximately 30 subjects will be enrolled and will receive daxzilimab 300 mg subcutaneously every 4 weeks for 32 weeks. The trial will consist of a screening period of up to 30 days with enrollment on Day 1. Subjects will be treated with daxzilimab 300 mg every 4 weeks through Week 32. The primary endpoint assessment will occur during the Week 24 visit. At week 24, the efficacy of treatment in reducing hair loss will be evaluated. Long-term safety and efficacy after the treatment period will also be evaluated. Subjects who discontinue treatment early will be followed up through week 48, unless they withdraw consent to participate in the study or are lost to follow-up. Subjects who discontinue the study early and do not plan to participate in the post-treatment follow-up period will be asked to complete an Early Termination (ET) visit.

[0420] For scheduled study visits, subjects will visit the study center on 14 occasions: Screening, Day 1, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, and Week 48 (early termination [ET]).

[0421] Efficacy will be assessed by assessment of the SALT score, ALODEX score, ClinRO Scale™ for Eyebrow Alopecia, and ClinRO Scale™ for Eyelash Alopecia. Photographs of the entire scalp of all subjects, and of the eyebrows and eyelashes of subjects with alopecia in these areas at baseline, will also be taken to assess changes in hair growth during the study.

[0422] Blood samples will be collected from all subjects to characterize the PK, PD, and immunogenicity of daxuzilimab.

[0423] Safety will be assessed by collecting AEs, SAEs, AESIs, performing local injection site tolerability assessments, recording vital signs, performing physical examinations and ECGs, and evaluating clinical laboratory results.

[0424] A total of up to 30 subjects will receive daxuzilimab in the trial. Sample size was determined by the need to evaluate potential efficacy, safety, and tolerability, as well as PK / PD. An exemplary trial diagram is shown in Figure 1.

[0425] treatment This study involves administration of daxuzilimab 300 mg (two 1.5 mL injections) SC every 4 weeks for 32 weeks. On Day 1 and Week 4, subjects will be under observation for at least 1 hour after IP administration. IP will be provided by the sponsor. Further details are found in Table 7.

[0426] (Table 7) Treatment TIFF2024516698000013.tif74165

[0427] Inclusion criteria All subjects must meet all of the following criteria to be eligible for study participation at either the Screening and Day 1 visits, or only at the designated visits (Screening or Day 1) listed in the criteria: 1. Written informed consent and any locally required approvals (e.g., Health Insurance Portability and Accountability Act in the United States) obtained from the subject prior to performing any protocol-related procedures, including screening assessments. 2. Adult males and females aged 18-65 years (inclusive) at the time of informed consent. 3. Willingness and ability to comply with prescribed treatment protocols and evaluations throughout the duration of the trial. 4. Willing to maintain the same hairstyle and color (hair products, process, timing of salon appointments, etc.) for the duration of the study. 5. Clinical diagnosis of moderate to severe AA - defined as the presence of ≥ 50% and ≤ 95% total scalp hair loss at screening and baseline (Day 1) as defined by SALT score. 6. Duration of the current hair loss episode ≥ 3 months and < 7 years at Screening and Day 1, and Investigator assessment that hair regrowth is possible. Total duration since diagnosis of AA can be ≥ 7 years. 7. No evidence of active regrowth at baseline and no known history of significant regrowth within the past 6 months as judged by the investigator. 8. Females of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1. 9. For female subjects of childbearing potential who engage in sexual intercourse that may lead to pregnancy: Subjects must agree to use highly effective methods of contraception from at least 4 weeks prior to Day 1 until at least 6 months (approximately 5 half-lives) after the last IP dose or until the end of the study and must refrain from egg retrieval / egg donation during this period. Highly effective methods of contraception include hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, injectable, or implant), intrauterine device or system, vasectomized partner(s) (only if vasectomy was performed ≥ 4 months prior to screening), tubal ligation, or double barrier methods (e.g., male condom and cervical cap, male condom and diaphragm, and male condom and contraceptive sponge). Note: In countries where double barrier methods are not accepted as highly effective contraception, this option should not be considered. Note: Subjects must have been taking a stable dose of hormonal contraception for at least 4 weeks prior to Day 1. Note: The above list of contraceptive methods does not apply to subjects who abstain for at least 4 weeks prior to Day 1 and who remain abstinent from penile-vaginal intercourse throughout the study and for at least 6 months after the last IP dose or until the end of the study, whichever is longer. The reliability of sexual abstinence must be evaluated in relation to the duration of the clinical trial and the subject's preferred usual lifestyle. Periodic abstinence (calendar, symptom-temperature, postovulatory methods) is not permitted. Note: A non-fertile female subject is defined as follows: - Women who have undergone surgical sterilization (hysterectomy, bilateral oophorectomy, bilateral salpingectomy). - Female subjects who have stopped menstruating for at least 12 months prior to the screening visit without another medical cause and are not capable of conceiving as confirmed by Follicle Stimulating Hormone (FSH) testing (see Laboratory Reference Ranges for confirmation levels). 10. For male subjects engaging in sexual intercourse that may result in pregnancy, subjects must agree to use one of the highly effective methods of contraception listed in Inclusion Criterion #9 from Day 1 until at least 6 months (approximately 5 half-lives) after the last IP dose and must refrain from donating sperm during this period. If the male subject's female partner uses any of the hormonal contraceptives listed above, this method of contraception must be used by the female partner from at least 4 weeks prior to Day 1 until at least 6 months after the last dose of daxuzilimab.

[0428] Exclusion criteria: Subjects are ineligible to participate in the study if they meet any of the following criteria at Screening and / or Day 1 visit, as applicable: (1) Individuals involved in the conduct of the trial, their employees, or close relatives of such individuals. (2) Any clinically significant medical condition or physical / laboratory / ECG / vital sign abnormalities that, in the opinion of the investigator, may place the subject at undue risk or interfere with the evaluation of the IP or interpretation of the trial results. (3) History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP or to previous monoclonal antibody (mAb) or human immunoglobulin (Ig) therapy. (4) Subject has had excessive sun exposure, is planning travel to a sunny climate, or has used a tanning booth within 4 weeks prior to Day 1, or is unwilling to minimize natural and artificial sun exposure during the trial. If sun exposure cannot be avoided, the use of sunscreen products and protective clothing is recommended. (5) Spontaneous or induced abortion within 4 weeks prior to screening, or stillbirth or live birth. (6) Lactating or pregnant women, or women planning to become pregnant from the time of signing the ICF until 6 months after administration of the last dose of IP or until the end of the study, whichever is longer. (7) History of drug or alcohol abuse that, in the opinion of the investigator, may affect the subject's safety or compliance with visits or interfere with other study evaluations. (8) Major surgery within 8 weeks prior to screening, or elective surgery planned during the study. (9) Known history of major immunodeficiency, or underlying condition such as known human immunodeficiency virus (HIV) infection, positive result for HIV infection, splenectomy, or any underlying condition that, in the opinion of the investigator, renders the subject significantly more susceptible to infection. (10) Any of the following at screening (the test may be repeated once within the same screening period to confirm the result before Day 1): Aspartate aminotransferase (AST) ≥ 2.5 × upper limit of normal (ULN) Alanine aminotransferase (ALT) ≥ 2.5 × ULN Total bilirubin ≥ 1.5 × ULN (excluding cases due to Gilbert syndrome) Serum immunoglobulin G (IgG) ≦600mg / dL (or ≦6g / L) Neutrophil count ≤ 1000 / μL (or ≤ 1.0 × 10 9 / L) Platelet count ≤ 50,000 / μL (or ≤ 50 × 10 9 / L) Hemoglobin ≦8g / dL (or ≦80g / L) Total lymphocyte count ≤ 200 cells / mm 3 Glomerular filtration rate (Dietary Modification in Renal Disease [MDRD]) ≤ 30 mL / min / 1.73 m 2 Spot urine protein-to-creatinine ratio (UPCr) ≥ 3mg / mg

[0429] (11) Test positive for hepatitis B serology defined as: hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb or anti-HBc). (12) Test positive for hepatitis C virus antibodies. (13) Active tuberculosis (TB) or positive TB test at screening. Subjects will be evaluated for latent TB infection using the purified protein derivative (PPD) test or the QuantiFERON-TB Gold test. Subjects who show evidence of latent TB infection (either PPD ≥ 5 mm induration or positive QuantiFERON-TB Gold test), regardless of Bacille Calmette-Guerin vaccination status, will not be permitted to participate in the trial unless they have a documented history of adequate treatment for active or latent TB. Subjects with indeterminate test results may have repeat testing, but will be excluded if repeat testing is also indeterminate. (14) Any severe herpes virus family infection (including Epstein-Barr virus, cytomegalovirus [CMV]), including but not limited to disseminated herpes, herpes encephalitis, recent recurrent herpes zoster (defined as 2 episodes within the past 2 years), or ophthalmic herpes, at any time prior to Day 1. (15) Any herpes zoster, CMV, or Epstein-Barr virus infection that was not completely resolved 12 weeks prior to Day 1. (16) Any of the following within 30 days prior to signing the ICF through Day 1: -Clinically significant active infection, in the opinion of the investigator, including ongoing and chronic infections requiring antibiotics or antivirals (chronic nail infections are permitted).Note: Subjects with limited recurrence of oral or genital herpes between signing of the ICF and Day 1 may be eligible based on the investigator's judgment. Any infection requiring hospitalization or treatment with intravenous (IV) anti-infectives. Subjects with a documented positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test may be rescreened at least 2 weeks after the positive test if asymptomatic and at least 3 weeks after resolution of symptomatic coronavirus disease 2019 (COVID-19) illness.

[0430] (17) Opportunistic infection requiring hospitalization or parenteral antimicrobial therapy within 2 years prior to Day 1. (18) Evidence of acute illness or clinically significant active infection (e.g., fever ≥ 38.0°C (≥ 100.5°F) on Day 1). (19) History of clinically significant cardiac disease, including unstable angina, myocardial infarction within 6 months prior to Day 1, congestive heart failure, arrhythmias requiring dynamic therapy except for clinically insignificant premature beats or minor conduction abnormalities, or the presence of clinically significant abnormalities on an ECG if, in the opinion of the investigator, this increases the risk of study participation. (20) History of cancer or lymphoproliferative disorder within 5 years prior to Day 1, except as follows: Neoplastic in situ of the cervix treated with apparent success with definitive therapy ≥ 12 months prior to screening, or Non-metastatic basal cell or squamous cell carcinoma of the skin that has been treated with apparent success with definitive therapy.

[0431] (21) Receipt of live or live attenuated vaccines within 8 weeks prior to Day 1, or planned administration of live or attenuated vaccines during the study and up to 4 weeks after the last IP dose. (22) Non-live and non-attenuated live vaccines against COVID-19 (e.g., RNA-based vaccines, protein-based vaccines, and non-replicating viral vector-based vaccines) are not permitted within 4 weeks prior to Day 1 and within 2 weeks of each study visit. (23) Subjects should be assessed for epidemiological risk of COVID-19 (i.e., recent exposure, high-risk housing) and health-related risk of COVID-19 severity, based on current understanding of risk factors for severe disease, when making decisions regarding the risk of individual participation. Subjects with COVID-19 or other significant infections, or who, in the investigator's judgment, may be at high risk for COVID-19 or its complications, should not be enrolled. (24) Subjects who have donated ≥ 50 mL of blood or plasma within 30 days of screening, or ≥ 499 mL of blood or plasma within 56 days of screening (during a clinical trial or at the time of blood bank donation), or who plan to donate blood or plasma during participation in the trial or up to 6 months after the last IP dose, whichever is longer. (25) Transfusion of blood, packed red blood cells, or platelets, or treatment with plasmapheresis or plasma exchange within 8 weeks prior to Day 1 and throughout the duration of study participation.

[0432] Disease-related exclusion criteria (26) At screening and by Day 1, evidence of active form of other inflammatory skin disease(s) or other skin conditions (e.g., psoriasis, seborrheic dermatitis, lupus) that, in the opinion of the investigator, may preclude the assessment of AA and the assessment of the activity scale. (27) Presence of another form of alopecia (excluding androgenetic alopecia). (28) History of pattern hair loss in men or women ≥ Hamilton stage III or ≥ Ludwig stage II. (29) History or presence of hair transplantation. (30) History or presence of scalp micropigmentation (Note: eyebrow microblading is permitted).

[0433] Prior and Concomitant Therapy Criteria (31) Use of steroids (systemic and intralesional), anthralin, squaric acid, diphenylcyclopropenone (DPCP), dinitrochlorobenzene (DCNB), Protopic, minoxidil, or any other medication that, in the investigator's opinion, may affect hair regrowth within 4 weeks of the Day 1 visit. Intranasal and inhaled corticosteroids are permitted, as are eye and ear drops containing corticosteroids. (32) Use of platelet-rich plasma infusions in the last 12 weeks prior to Day 1. (33) Topical medications that may affect AA, including but not limited to topical corticosteroids, calcineurin inhibitors, antimicrobials, and medical devices, within 2 weeks of the Day 1 visit. Topical corticosteroids are permitted except on the scalp, eyebrows, and eyelids. (34) Subjects who have been previously treated with any biologic B cell depleting therapy (e.g., rituximab, ocrelizumab, or ofatumumab) or other B cell targeted therapy (e.g., belimumab) within the 12 months prior to Day 1. (35) Subjects who have received previous treatment with pDC inhibitory therapy (e.g., anti-ILT7, anti-blood dendritic cell antigen 2 [BDCA2]). (36) Inadequate response to an appropriate trial of an oral Janus kinase (JAK) inhibitor. Prior exposure to a topical JAK inhibitor is permitted, regardless of response. (37) Subjects who have received any biologic or conventional disease-modifying antirheumatic drug (DMARD), immunosuppressant (e.g., cyclosporine, methotrexate, or azathioprine), JAK inhibitor, interferon (IFN) blockade therapy, or antiproliferative agent (if the last dose was taken a. within 8 weeks prior to Day 1 or b. within the drug-specific 5 half-life elimination period (if greater than 8 weeks)). (38) Subject has received any commercial or investigational biologic agent within 12 weeks or within 5 half-lives (whichever is longer) prior to Day 1. (39) Subject is currently receiving or has received a non-biologic IP or device within 4 weeks or within 5 published half-lives (whichever is longer) prior to Day 1. (40) Subject has received any ultraviolet (UV)-B phototherapy (including tanning beds), psoralen-UV-A (PUVA) treatment, or excimer laser within 4 weeks prior to Day 1.

[0434] Combination therapy All medications taken within the 4 weeks prior to screening and during the study must be recorded (including over-the-counter medications, vitamins, herbs / natural products, and antacids). In addition, use of any prohibited medications must be recorded within the time frame listed in the exclusion criteria. No rescue medications or treatments are allowed in this study.

[0435] Permitted Therapies The following therapies are allowed: intranasal and inhaled corticosteroids, eye and ear drops containing corticosteroids, sunscreen products and protective clothing are allowed if sun exposure cannot be avoided, topical corticosteroids are allowed except on the scalp, eyebrows, and eyelids, and non-live and non-attenuated live vaccines against COVID-19 (e.g., RNA-based vaccines, protein-based vaccines, and non-replicating viral vector-based vaccines) are allowed ≥4 weeks prior to Day 1 and ≥2 weeks prior to each study visit.

[0436] Prohibited Therapies or Procedures Prohibited therapies or procedures are listed in Table 8.

[0437] Table 8. Summary of Prohibited Drugs, Products, and Procedures TIFF2024516698000014.tif242165

[0438] Efficacy analysis The percent change from baseline in SALT scores at Week 24 will be summarized with descriptive statistics. All other efficacy endpoints will be analyzed descriptively, with summary statistics for continuous endpoints and frequency distributions for binary endpoints.

[0439] Safety analysis The occurrence of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and adverse events of special interest (AESIs) are summarized by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) and Preferred Term (PT), as well as severity and relationship to IP. Other safety parameters, including but not limited to laboratory assessments and vital signs, are also summarized as appropriate.

[0440] Pharmacodynamic and biomarker analysis Observed counts, along with changes from baseline and percent change, will be summarized descriptively, as appropriate.

[0441] Pharmacokinetic analysis Serum concentrations at each visit will be summarized descriptively. Additional PK analyses may be performed as necessary and reported separately from the clinical trial report.

[0442] Anti-drug antibodies Anti-drug antibody (ADA) rates are determined.

[0443] Planned Analysis The primary analysis will occur when the last subject completes week 24 or discontinues before the scheduled week 24 visit. All data available at the time of data cutoff (including data collected after week 24) will be included in the primary analysis. The final analysis will occur when all subjects have completed the study.

[0444] Evaluation Schedule A description of the procedures to be performed at each visit is depicted in Table 9. Unless otherwise noted, evaluations scheduled for Day 1 must be performed prior to IP dosing. The recommended order for performing the study evaluations is as follows, with the exception of collection of blood samples for analysis of serum daxuzilimab ADA and PK samples (which must be performed prior to IP dosing at the visits specified in Table 9): Investigator assessment, vital signs, 12-lead ECG, medical photographs, and blood draws.

[0445] Clinical evaluation of AA will be performed by an experienced, licensed dermatologist (board certified or equivalent) or other suitably qualified and experienced designee.

[0446] Table 9: Evaluation schedule for Example 3 TIFF2024516698000015.tif231155TIFF2024516698000016.tif227161TIFF2024516698000017.tif228160TIFF2024516698000018.tif225158

[0447] Efficacy will be assessed by assessment of the SALT score, ALODEX score, Physician-Reported Outcomes (ClinRO) Eyebrow Hair Loss Scale™, and the ClinRO Eyelash Hair Loss Scale™. Photographs of the entire scalp of all subjects, and of the eyebrows and eyelashes of subjects with hair loss in these areas at baseline, will also be taken to assess changes in hair growth during the study.

[0448] Blood samples will be collected from all subjects to characterize the PK, PD, and immunogenicity of daxuzilimab.

[0449] The study objectives and endpoints are provided in Table 10.

[0450] Table 10: Objectives and Endpoints TIFF2024516698000019.tif173165TIFF2024516698000020.tif133165

[0451] 1) Severity of Alopecia Tool (SALT) To participate, subjects must have moderate to severe AA as assessed by a SALT score of 50 or greater and 95 or less at screening and baseline (Day 1). The SALT score is a tool to determine the extent of hair loss based on the percentage of scalp surface area involved on the top, back, and each side of the scalp in AA. The investigator will determine the percentage of scalp hair loss in each quadrant, multiply this by the total scalp area bounded by that quadrant, and sum the numbers obtained for each quadrant to obtain a total percentage of scalp hair loss with a maximum score of 100. The SALT assessment tool is provided in Figure 2.

[0452] Density and extent of alopecia (ALODEX) The ALODEX score combines both the extent and hair density into an overall percentage of scalp hair loss. A density scale of 0 to 10 relates to the percentage of terminal hair loss, with 100% hair loss equal to 10, 90% equal to 9, 80% equal to 8, 70% equal to 7, 60% equal to 6, 50% equal to 5, 40% equal to 4, 30% equal to 3, 20% equal to 2, 10% equal to 1, and no hair loss equal to 0. The density assignments for each 1% scalp area in each quadrant are summed and divided by the maximum grade of hair loss (10) to obtain the percentage of hair loss in that quadrant. The scores for each quadrant are then summed to obtain the ALODEX score. The ALODEX assessment is provided in FIG. 3.

[0453] Physician-reported outcomes (ClinRO) for eyebrow and eyelash hair loss The ClinRO™ for Eyebrow Alopecia and the ClinRO™ for Eyelash Alopecia consist of single-item, 4-point Likert-type response scales to assess the incremental severity of each ClinRO measurement. The ClinRO is provided in FIG.

[0454] Medical Photography Medical photography of the entire scalp of all subjects, and of the eyebrows and eyelashes of subjects with hair loss in these areas at baseline, will be performed at the visits specified in the schedule in Table 9. To obtain comparable photographs, care will be taken to use the same camera, same magnification, and same settings for each photograph at each visit.

[0455] Pharmacokinetics Blood samples will be collected for analysis of daxuzilimab concentrations 2 hours (± 5 minutes) after dosing on Day 1 and prior to dosing at all other visits specified in Table 9 for all subjects who received ≥ 1 dose of daxuzilimab.

[0456] Pharmacodynamics Blood samples will be collected for daxzilimab PD analyses at the visits and time points specified in Table 9. Daxzilimab PD analyses include, but are not limited to, whole blood transcriptomics assessment (e.g., IFN gene signature), pDC flow cytometry, PBMC (e.g., levels of other circulating cells), serum and plasma biomarkers, and blood MxA.

[0457] immunogenicity Blood samples will be collected for analysis of serum daxuzilimab ADA.

[0458] Vital signs The following vital signs will be recorded in the sitting or supine position after sitting comfortably for at least 5 minutes: systolic and diastolic blood pressure (mmHg), pulse (bpm), temperature (°C), and respiratory rate (breaths / min) at the visits specified in Table 9. To calculate BMI, weight (kg) and height (cm) will be collected and recorded at the visits specified in Table 9. Height will be recorded only once at the screening visit and the same value will be used to calculate BMI at other visits.

[0459] Physical Examination The following areas / systems will be included, at a minimum, in the focused physical examination performed at the visit as specified in Table 9: (1) general appearance, (2) dermatology (except AA), (3) head, eyes, ears, nose, and throat (HEENT), (4) respiratory, (5) cardiovascular, (6) abdominal, (7) neurology, (8) musculoskeletal, and (9) lymphatic.

[0460] Lab Test Laboratory tests will be performed at the visits specified in Table 9. Tests will include urinalysis, blood tests with differential, a standard chemistry panel (chemistry will include liver function tests), and a serum pregnancy test (screening) for women of childbearing potential (WOCBP). A urine pregnancy test will be performed for WOCBP (performed at the investigator's site) at the visits specified in Table 9. The specific tests in these panels are listed in Table 11.

[0461] (Table 11) Clinical tests TIFF2024516698000021.tif180167

[0462] electro-cardiogram A 12-lead ECG will be performed as a safety assessment at the visits specified in Table 4. Clinically significant findings on the ECG will require the subject to be excluded from study participation. All clinically significant values ​​will be reported as AEs.

[0463] Tolerability assessment of local injections The assessor's local injection tolerability assessment will occur approximately 30 minutes after dosing at the visits specified in Table 9 (can occur at any time during Week 36 as daxuzilimab will not be administered). The investigator or designee will assess the injection site at their visit and document the presence or absence of local tolerability / injection site reactions, and open an AE in the case of local injection site tolerability. Additional follow-up after Week 36 can be performed for any ongoing injection site reactions.

[0464] Adverse events An adverse event (AE) is any undesirable medical occurrence in a subject administered a medicinal product, not necessarily causally related to this treatment. Thus, an AE can be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease that is temporarily associated with the use of daxuzilimab, whether or not it is considered related to daxuzilimab. A treatment-emergent adverse event (TEAE) is any condition that was not present before treatment with daxuzilimab but appeared after treatment, was present at the start of treatment but worsened during treatment, or was present at the start of treatment but resolved and then re-emerged while the individual was on treatment (regardless of the intensity of the AE at the start of treatment). A serious adverse event (SAE) or reaction is any undesirable medical occurrence, at any dose, that causes any of the following outcomes: resulting in death, being life-threatening, requiring hospitalization or an extension of an existing hospitalization, causing persistent or significant disability / incapacity, and / or causing congenital anomalies / birth defects. Utilize the guidelines outlined in the Common Terminology Criteria for Adverse Events (CTCAE).

[0465] cancel An individual subject will not receive any further daxuzilimab if any of the following occurs in the subject: · Receipt of medications that have been proven effective in treating AA. -CTCAE grade 3 or higher allergic reaction to daxuzilimab. -CTCAE grade 3 or higher infection considered related to daxzilimab. Any other AE that, in the opinion of the Investigator and / or Sponsor, or Medical Monitor, prohibits further treatment. Withdrawal of consent from further treatment with daxuzilimab. The subject meets one or more of the exclusion criteria or is determined not to have met all of the inclusion criteria for study participation and has a potential safety risk associated with continuation identified in consultation with the medical monitor. · Pregnancy or determination of pregnancy. Any of the following liver dysfunctions: - ALT or AST ≥ 8 × ULN, - ALT or AST ≥ 5 × ULN for > 2 weeks, - ALT or AST ≥ 3xULN and total bilirubin ≥ 2xULN, - ALT or AST ≥ 3 x ULN with the development of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and / or eosinophilia (≥ 5%).

[0466] Example 4: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Daxzilimab for Treating Active Proliferative Lupus Nephritis A Phase 2, multicenter, international, double-blind, randomized, placebo-controlled trial will be conducted to evaluate the efficacy and safety of daxuzilimab in subjects with lupus nephritis (LN). The target population will be adults aged 18 to 80 years with documented active and proliferative lupus nephritis (LN). The maximum study duration per subject will be approximately 116 weeks, which includes a screening period of approximately 4 weeks (days -28 to -1), a treatment period of 104 weeks, and a safety follow-up (SFU) period of 8 weeks (12 weeks after the administration of the last study intervention at week 100).

[0467] Objectives and Endpoints The primary objective is to evaluate the efficacy of daxuzilimab in combination with SOC compared to placebo in combination with SOC in subjects with active, proliferative LNs. The primary objective will be measured according to the following criteria: Proportion of subjects achieving CRR at Week 48 and sustained through Week 52. CRR is defined as meeting all of the following: (i) eGFR ≥ 60 mL / min / 1.73 m 2 , or not 15% lower than baseline, (ii) 24-h UPCR ≤ 0.5 mg / mg, and (iii) no discontinuation of study intervention prior to evaluation or use of restrictive medications above protocol-accepted thresholds.

[0468] The secondary objective is to evaluate the ORR (defined as CRR+PRR) with daxuzilimab versus placebo in subjects with active, proliferative LNs. The secondary objective is measured according to the following criteria: the proportion of subjects achieving ORR at week 48 and sustained through week 52. PRR is defined as meeting all of the following: (i) eGFR ≥ 60 mL / min / 1.73 m2 or not 15% below baseline, (ii) improvement in 24-hour UPC for subjects with baseline UPCR ≤ 3.0 mg / mg: < 1.0 mg / mg, and for subjects with baseline UPCR > 3.0 mg / mg: > 50% improvement from baseline and ≤ 3.0 mg / mg, and (iii) no discontinuation of study intervention or use of restricted medications above protocol tolerance thresholds prior to evaluation. Other secondary objectives of the study are as follows: To evaluate the change from baseline in eGFR with daxzilimab versus placebo in subjects with active, proliferating LNs. Change from baseline in eGFR at week 52. To evaluate the ability of daxudilimab versus placebo to improve oral corticosteroid (OCS) dose requirements in subjects with active, proliferative LN. Proportion of subjects able to taper their OCS to ≤ 2.5 mg / day prednisone equivalent by Week 24 and maintain this dose through Week 52. Sustained reduction in OCS dose: ■ Prednisone equivalent dose ≤ 2.5 mg / day by week 24 and not to exceed this dose until week 52; and ■ No discontinuation of the study intervention or use of restricted medications above protocol acceptable thresholds prior to evaluation. To characterize the pharmacokinetics (PK) and immunogenicity of daxzilimab in subjects with active, proliferative LN. Serum concentrations of daxzilimab. - Rate of anti-drug antibodies (ADA) and ADA titers to daxuzilimab during the study period. To evaluate the safety and tolerability of daxzilimab in combination with SOC in subjects with active, proliferative LN. - Incidence of treatment-emergent adverse events (TEAEs). - Incidence of treatment-emergent serious adverse events (TESAEs). - Incidence of adverse events of special interest (TEAESI): hypersensitivity reactions including anaphylaxis, severe (grade 3 or higher) viral infection / reactivation, herpes zoster, opportunistic infections, and malignancies (excluding non-melanoma skin cancer). The exploratory objectives and endpoints of the study are as follows: To evaluate the effect of daxuzilimab versus placebo on measures of LN disease activity in subjects with active, proliferating LNs. Exploratory endpoints are: Proportion of subjects achieving alternative CRR (aCRR) at Week 52. aCRR is defined as meeting all of the following: ○eGFR≧60mL / min / 1.73m 2 , or not 15% lower than baseline. ○24 hour UPCR<0.5mg / mg a . o Urinary sediment is inactive (defined as <10 red blood cells [RBC] / high power field [hpf]). No discontinuation of the study intervention or use of restricted medications above protocol acceptable thresholds prior to evaluation. • Proportion of subjects achieving renal response (CRR, ORR, aCRR) over time. • Change from baseline in UPCR over time. ●Change from baseline in eGFR over time. ●eGFR≧60mL / min / 1.73m 2 or the proportion of subjects not 15% lower than baseline over time. • Time to achieve sustained renal response (CRR, ORR, aCRR) through 52 weeks. • Time to achieve renal response (CRR, ORR, aCRR) sustained through 52 weeks and tapered OCS to ≤ 2.5 mg / day prednisone equivalent by week 24 and maintained through 52 weeks. ii. To evaluate the time to first renal flare in subjects with active, proliferating LNs. Time to first renal flare at 1 year after achieving PRR or CRR and maintaining it for at least one subsequent visit. Renal flare is defined as an increase in spot UPCR and / or decline in renal function due to active LNs in subjects who achieved PRR or CRR and maintained it for at least one subsequent visit. Flare is characterized as either proteinuria or nephritis. a) Proteinuria flare: (1) A decrease of ≤20% in eGFR. (2) In subjects who achieved CRR: spot UPCR. (3) 1.0 mg / mg in two urine samples obtained at least 2 weeks apart. (4) In subjects who achieved PRR: a >50% increase in spot UPCR from the average of the last two measurements when PRR criteria were met, and a spot UPCR of >2.0 mg / mg in two urine samples obtained at least 2 weeks apart. b) Nephritic flare: ≥20% decrease in eGFR compared to the average of the previous two visits not explained by changes in comorbidities or concomitant medications. After non-systemic lupus erythematosus (SLE) causes have been corrected or excluded, the decrease in eGFR must be confirmed for at least two samples at least 5 days apart. One measurement is acceptable if it leads to an increase in OCS or immunosuppressive therapy. iii. To evaluate the effect of daxzilimab versus placebo on SLE disease activity and damage in subjects with active, proliferating LNs. ●Changes in Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores over time. Changes in non-renal components of the SLEDAI-2K score over time. • Change in Systemic Lupus International Collaborating Clinic / American College of Rheumatology (SLICC / ACR) Damage Index (SDI) over time. • Change in Glucocorticoid Toxicity Index (GTI) score over time. iv. Evaluate change from baseline in patient-reported outcome scores with daxuzilimab vs. placebo in subjects with active, proliferative LNs. ●Changes in Physician Global Assessment (PGA) scores over time. ●Changes in Patient Global Assessment (PtGA) scores over time. ●Changes in Patient Global Impression-Change (PGI-C) scores over time. v. To characterize the pharmacodynamics (PD) of daxuzilimab in subjects with active, proliferative LNs. • Changes from baseline in PD biomarkers, including blood pDC, IFN-α, myxovirus protein A (MxA), and IFN gene signature levels. • Association between proteinuria and serum concentrations of daxzilimab. vi. To explore potential associations of genetic variation, gene expression, and circulating and urinary cellular and protein profiles with daxudilimab response. ●Changes in blood biomarkers over time. • Changes in urinary biomarkers over time. ●Changes in whole blood gene expression over time. vii. To evaluate changes in renal biopsy tissue in subjects with active, proliferative LN. • Change from baseline in International Society of Nephrology (ISN) / Renal Pathology Society (RPS) [ISN / RPS] classification and National Institutes of Health (NIH) activity and chronicity indices. • Changes from baseline in pDC and other tissue biomarkers.

[0469] Test Design An overview of the trial design is depicted in the schematic provided in Figure 7.

[0470] Approximately 210 subjects will be randomized in a 1:1:1 ratio (70 subjects per group) to receive either daxuzilimab (SC) or placebo (SC) in addition to background SOC therapy, as described below in Table 12. Randomization will be stratified by: Pre-randomization urine protein-to-creatinine ratio (UPCR) < 3.0 mg / mg vs. ≥ 3.0 mg / mg; ● Screening eGFR < 60 mL / min / 1.73 m2 vs. ≥ 60 mL / min / 1.73 m2.

[0471] Table 12. Treatment assignment in year 1 TIFF2024516698000022.tif44165

[0472] At Week 64, subjects from all three treatment arms (above) will be assigned to a quarterly dosing maintenance regimen based on the renal responses observed at Weeks 48 and 52, as described in Table 13 below.

[0473] Table 13. Treatment assignment in year 2 TIFF2024516698000023.tif126165

[0474] Subjects may participate in the study on a daily oral corticosteroid (OCS) at a maximum dose of 0.5 mg / kg / day prednisone equivalent (not to exceed 40 mg / day) and must be on a stable dose for at least 10 days prior to randomization. In addition, subjects will receive a 500 mg methylprednisolone pulse on the day of randomization, except for subjects already taking OCS prior to participation, who will receive a ≥ 500 mg methylprednisolone pulse within 10 days prior to randomization, followed by a taper of OCS. For subjects who are not already taking mycophenolate mofetil (MMF) prescribed prior to randomization, MMF administration will begin with 500 mg twice daily (BID) for a total daily dose of 1 gm / day for the first week, increasing to 1 gm twice daily for a total daily dose of 2 gm / day for the second and subsequent weeks (i.e., starting on day 8). Equivalent doses of mycophenolic acid (MPA) may be used as an alternative to MMF.

[0475] The trial includes a screening period of approximately 4 weeks (day -28 to day -1), a treatment period with randomization on day 1, followed by treatment through week 104 (with final dose administered at week 100) (19 doses total across all treatment arms with quarterly dosing maintenance regimens assigned at week 64 based on renal response observed at weeks 48 and 52), and an 8-week SFU period (through week 112). Under exceptional circumstances, such as delayed test results, drug washout, or the impact of COVID-19, the screening period may be extended by 2 weeks with approval from the medical monitor.

[0476] Rescue therapy in case of worsening LN may be administered at the investigator's discretion as clinically indicated. Rescue therapy includes initiation of any new treatment for lupus or LN, or an increase from baseline in SOC background therapy (MMF / MPA or corticosteroids).

[0477] Primary efficacy endpoint assessments will occur at Weeks 48 and 52. The final assessment of the double-blind treatment period will occur at Week 104. The SFU period will begin after completion of the Week 104 EOT visit and will last for 8 weeks. All subjects will continue to receive SOC immunosuppressive background therapy with MMF / MPA and OCS unless the subject has normally discontinued OCS. Subjects will follow all study requirements and return to the clinical site for an End of Study visit at Week 112 for final safety evaluation.

[0478] Inclusion criteria All subjects must meet / provide all of the following criteria to be eligible for study participation: 1. Written informed consent and any locally required approvals prior to performing any protocol-related procedures and screening assessments. 2. Willingness and ability to comply with prescribed treatment protocols and evaluations throughout the duration of the clinical trial. 3. Adult male or female aged 18 to 80 years. 4.Meets the 2019 European League Against Rheumatism / American College of Rheumatology classification criteria for systemic lupus erythematosus (SLE). 5. Have at least one of the following as screened by a central laboratory: ●Antinuclear antibody (ANA) ≧1:80. • Anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies are elevated above the normal range established by the central laboratory (i.e., a positive result). • Anti-Smith antibodies are elevated above normal levels (i.e., a positive result). 6. Diagnosis of proliferative LN based on a renal biopsy obtained within 6 months prior to signing the Informed Consent Form (ICF) or during the screening period: Class III (± Class V) or Class IV (± Class V) LN. Study entry requires submission of a screening biopsy specimen for evaluation. 7. Urinary protein to creatinine ratio ≥ 1.5 mg / mg (113.17 mg / mmol) obtained by 24-hour urine collection at the following times: At the start of screening, and • Within 14 days of the planned randomization date. 8. Estimated glomerular filtration rate ≥ 35 mL / min / 1.73 m2. 9. For female subjects, serum beta-human chorionic gonadotropin (β-hCG) test is negative. 10. Females of childbearing potential must have negative serum and urine pregnancy tests and men must agree to use appropriate contraception not to impregnate their female partners and to refrain from donating sperm during the study.

[0479] Exclusion criteria Subjects are ineligible to participate in the study if they meet any of the following criteria at Screening and / or Day 1 visit, as applicable: 1. Weight >160 kg (352 lbs) at screening. 2. History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP or to previous monoclonal antibody (mAb) or human immunoglobulin (Ig) therapy. 3. Known intolerance to ≤1.0 gm / day MMF or equivalent doses of MPA. 4. Participation in another clinical trial with an investigational drug within 4 weeks prior to Day 1 or within 5 published half-lives, whichever is longer. 5. Women who are breastfeeding or pregnant, or who are planning to become pregnant between signing the ICF and 6 months after receiving the last dose of IP. 6. History of drug or alcohol abuse. 7.Major surgery within 8 weeks prior to screening or elective surgery planned between screening and end of study. 8. Spontaneous or induced abortion, stillbirth or live birth, or pregnancy ≤ 4 weeks prior to screening through randomization. 9. Diagnosis of pure class V membranous LN based on a renal biopsy obtained within 6 months prior to signing the ICF or during the screening period. 10. History of dialysis within 12 months prior to signing the ICF or anticipated need for renal replacement therapy (dialysis or kidney transplant) within 12 months after enrollment. 11. History of renal disease (e.g., diabetic nephropathy) or current renal disease (other than LN) that, in the investigator's opinion, could interfere with LN assessment and confound disease activity assessment. 12. Known history of major immunodeficiency or underlying condition such as known human immunodeficiency virus (HIV) infection, positive result for HIV infection per central laboratory, splenectomy, or any underlying condition that, in the opinion of the investigator, renders the subject significantly more susceptible to infection. 13. During screening, one of the following per central laboratory: Aspartate aminotransferase >2.5 × upper limit of normal (ULN), Alanine aminotransferase >2.5×ULN, Total bilirubin >1.5 × ULN (except in cases due to Gilbert syndrome), Serum IgG < 600 mg / dL (or < 6 g / L), Neutrophil count <1000 / μL (or <1.0×10 9 / L), or <500 / μL (<0.5 × 10) if due to active SLE 9 / L), Platelet count <50,000 / μL (or <50×10 9 / L), or <25,000 / μL (<25 × 10 9 / L), Hemoglobin <8g / dL (or <80g / L), or <7g / dL (<70g / L) if due to active SLE; Glycosylated hemoglobin >8% (or >0.08), Total lymphocyte count < 200 cells / mm 3 . 14. Have confirmed positive Hepatitis B serology defined as: Hepatitis B surface antigen, or • Hepatitis B core antibody (HBcAb) and Hepatitis B virus (HBV) DNA detected above the lower limit of quantification (LLOQ) by reflex testing. 15. Hepatitis C virus antibody test positive. 16. Active tuberculosis (TB) or positive IFN-gamma release assay (IGRA) test at screening. 17. Any severe herpes virus family infection. 18. Any herpes zoster, CMV, or Epstein-Barr virus infection. 19. Within 30 days prior to signing the ICF and up until randomization, any of the following: clinically significant active infection requiring antibiotics or antiviral medications; Any infection requiring hospitalization or treatment with intravenous anti-infective drugs, ●Subjects with documented positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or at epidemiological risk for COVID-19. 20. Opportunistic infection requiring hospitalization or parenteral antibacterial treatment within 2 years prior to randomization. 21. Any acute illness or evidence of clinically significant active infection on Day 1. 22. Clinically significant cardiac disease, including unstable angina, myocardial infarction, or congestive heart failure within 6 months prior to randomization (including the presence of inadequately controlled arrhythmias and electrocardiogram (ECG) abnormalities). 23. History of cancer within the past 5 years, except as follows: • intraepithelial neoplasia of the cervix treated with apparent success with definitive therapy ≥12 months prio...

Claims

1. 1. A pharmaceutical composition comprising an immunoglobulin-like transcript 7 (ILT7) binding protein for use in a method of treating an autoimmune disorder in a subject in need thereof, said method comprising administering a pharmacologic effective amount of an ILT7 binding protein to said subject, wherein said pharmacologic effective amount of said ILT7 binding protein is about 100-350 mg.

2. 2. The composition of claim 1, wherein the autoimmune disease is selected from the group consisting of discoid lupus erythematosus (DLE), systemic lupus erythematosus (SLE), lupus nephritis, dermatomyositis, antisynthetic enzyme inflammatory myositis, and alopecia areata.

3. 3. The composition of claim 1 or 2, wherein the ILT7 binding protein is administered with one or more additional therapies, optionally wherein the additional therapies include a corticosteroid.

4. 3. The composition of claim 1 or 2, wherein the ILT7 binding protein is administered about once every 4 weeks or about once every 12 weeks.

5. 3. The composition of claim 1 or 2, wherein the pharma- ceutically effective amount of the ILT7 binding protein is about 100 mg, about 150 mg, about 200 mg, or about 300 mg.

6. 1. A pharmaceutical composition comprising an immunoglobulin-like transcript 7 (ILT7) binding protein for use in a method of treating discoid lupus erythematosus (DLE) in a subject in need thereof, said method comprising administering to said subject a pharmacologic effective amount of an ILT7 binding protein, said pharmacologic effective amount of said ILT7 binding protein being from about 100 mg to about 300 mg.

7. 1. A pharmaceutical composition comprising an immunoglobulin-like transcript 7 (ILT7) binding protein for use in a method of treating systemic lupus erythematosus (SLE) in a subject in need thereof, said method comprising administering to said subject a pharmacologic effective amount of an ILT7 binding protein, said pharmacologic effective amount of said ILT7 binding protein being from about 100 mg to about 300 mg.

8. 1. A pharmaceutical composition comprising an immunoglobulin-like transcript 7 (ILT7) binding protein for use in a method of treating lupus nephritis in a subject in need thereof, said method comprising administering to said subject a pharmacologic effective amount of an ILT7 binding protein, said pharmacologic effective amount of said ILT7 binding protein being from about 100 mg to about 300 mg.

9. 1. A pharmaceutical composition comprising an immunoglobulin-like transcript 7 (ILT7) binding protein for use in a method of treating alopecia areata in a subject in need thereof, said method comprising administering to said subject a pharmacologic effective amount of an ILT7 binding protein, said pharmacologic effective amount of said ILT7 binding protein being from about 100 mg to about 300 mg.

10. A pharmaceutical composition comprising an immunoglobulin-like transcript 7 (ILT7) binding protein for use in a method of treating dermatomyositis in a subject in need thereof, the method comprising administering a pharmacologic effective amount of an ILT7 binding protein to the subject.

11. A pharmaceutical composition comprising an immunoglobulin-like transcript 7 (ILT7) binding protein for use in a method of treating anti-synthetic enzyme inflammatory myositis in a subject in need thereof, the method comprising administering a pharmacologic effective amount of an ILT7 binding protein to the subject.

12. 12. The composition of claim 10 or 11, wherein the pharma- ceutically effective amount of the ILT7 binding protein is from about 100 mg to about 300 mg.

13. The ILT7 binding protein is Heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3, and light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3, comprising the amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. The composition of claim 1 or 2, which is an antibody comprising:

14. The ILT7 binding protein is a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1, and / or a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:

2. The composition of claim 13, which is an antibody comprising:

15. The ILT7 binding protein is An antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO:

2. The composition of claim 13, wherein

16. 3. The composition of claim 1 or 2, wherein the ILT7 binding protein comprises a heavy chain comprising SEQ ID NO: 10 and a light chain comprising SEQ ID NO:

9.

17. 8. The composition of claim 6 or 7, wherein the subject is administered the ILT7 binding protein every 4 weeks or every 12 weeks.

18. The composition of claim 6 or 7, wherein prior to said administration, the subject is administered at least one initial dose of the ILT7 binding protein, wherein said at least one initial dose is administered in 1, 2, 3, 4, 5 or more doses every two weeks.

19. The ILT7 binding protein, Heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3, and light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3, comprising the amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. The composition of claim 6 or 7, which is an antibody comprising:

20. The ILT7 binding protein, a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1, and / or a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:

2. The composition of claim 19, which is an antibody comprising:

21. The ILT7 binding protein, An antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO:

2.

20. The composition of claim 19, wherein 22. The composition of claim 6 or 7, wherein the ILT7 binding protein comprises a heavy chain comprising sequence number 10 and a light chain comprising sequence number 9.

23. The composition of claim 8 or 9, wherein the subject is administered the ILT7 binding protein every 4 weeks or every 12 weeks.

24. The composition of claim 8 or 9, wherein prior to said administration, the subject is administered at least one initial dose of the ILT7 binding protein, wherein the at least one initial dose is administered in 1, 2, 3, 4, 5 or more doses every two weeks.

25. The ILT7 binding protein, Heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3, and light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3, comprising the amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. The composition of claim 8 or 9, which is an antibody comprising:

26. The ILT7 binding protein, a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1, and / or a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:

2. The composition of claim 25, which is an antibody comprising:

27. The ILT7 binding protein, An antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO:

2.

26. The composition of claim 25, wherein 28. The composition of claim 8 or 9, wherein the ILT7 binding protein comprises a heavy chain comprising SEQ ID NO:10 and a light chain comprising SEQ ID NO:

9.

29. The composition of claim 10 or 11, wherein the subject is administered the ILT7 binding protein every 4 weeks or every 12 weeks.

30. The composition of claim 10 or 11, wherein prior to said administration, the subject is administered at least one initial dose of the ILT7 binding protein, wherein the at least one initial dose is administered in 1, 2, 3, 4, 5 or more doses every two weeks.

31. The ILT7 binding protein, Heavy chain complementarity determining regions (HCDRs) HCDR1, HDR2, HCDR3, and light chain complementarity determining regions (LCDRs) LCDR1, LCDR2, and LCDR3, comprising the amino acid sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively. The composition of claim 10 or 11, which is an antibody comprising:

32. The ILT7 binding protein, a variable heavy chain (VH) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:1, and / or a variable light chain (VL) that is at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identical to SEQ ID NO:

2. The composition of claim 31 , which is an antibody comprising:

33. The ILT7 binding protein, An antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO:

2.

32. The composition of claim 31 , 34. The composition of claim 10 or 11, wherein the ILT7 binding protein comprises a heavy chain comprising SEQ ID NO:10 and a light chain comprising SEQ ID NO:9.

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