Compositions and methods for treating sjogren's disease

Abstract

Composition and methods for treating Sjögren's disease are provided herein using compositions comprising anti-FcRn agents.

Description

COMPOSITIONS AND METHODS FOR TREATING SJOGREN'S DISEASECROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to, and the benefit of, United States Provisional Application No. 63 / 549,525, which was filed on February 4, 2024, United States Provisional Application No. 63 / 657,421, which was filed on June 7, 2024, and United States Provisional Application No. 63 / 707,871, which was filed on October 16, 2024, the disclosure of each of which is hereby incorporated by reference in its entirety.SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which is being submitted herewith electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on February 4, 2025, is named 103693006093_Sequence_Listing.xml and is 24 kilobytes in size.FIELD

[0003] The present application is related to treating patients with Sjogren's disease.BACKGROUND

[0004] Sjogren’s disease, also known as Sjogren’s and Sjogren’s syndrome may occur alone (pSS) or with a comorbid autoimmune condition (secondary Sjogren’s syndrome [sSS]), and disease severity can vary. Sjogren’s syndrome is a chronic, progressive autoimmune disease of unclear etiology typically originating in exocrine glands and capable of affecting the function of almost any organ system in the body. Primary Sjogren’s syndrome results from dysregulated humoral immunity characterized by abnormally high levels of IgG in the blood, the production of auto-reactive IgG, and abnormal B lymphocyte activity. Patients with elevated levels of anti- Ro / SSA autoantibodies in circulation exhibit more severe end-organ involvement in the disease and require glucocorticoid or other immunosuppressive drugs more frequently. The estimated incidence of pSS is approximately 6.92 per 100,000 person-years, and its prevalence isapproximately 60.8 per 100,000 persons. The disease is observed with a ~10-fold greater prevalence in women, and usually appears during the 4th to 7th decade of life, though it can present in adolescent or young adult women and men and very rarely in children.

[0005] There is a high unmet need for new treatment options in pSS that are safe and effective, especially new therapies that demonstrate improved long-term efficacy (i.e., induce and maintain sustained remission) over currently available therapies. In patients with pSS, the pathogenic autoantibodies and associated immune complexes that mediate pSS broadly induce inflammation and extra glandular damage in diverse organs including the skin, joints, lungs, blood vessels, bone marrow, kidneys, central and peripheral nervous system, and lymphatic system, with overall approximately 70% of pSS patients experiencing extra-glandular manifestations. The standardized mortality ratio for pSS is 2.9 to 4.7, suggesting the disease impacts overall survival. Compared to healthy controls, these patients also carry ~5-fold higher risk of lymphoma, which is the extra-glandular SS manifestation associated with the highest mortality risk. Other serious extra-glandular complications associated with pSS occur more frequently, including skin rashes (23% to 67%), myalgia or myositis (-40%), articular inflammation (-50%), renal disease (-30%), neuropathy (-10%), and interstitial lung disease (-10% to 20%), with central nervous system involvement being less common. Patients with mild disease first experience dryness and fatigue, which can be present for years before a pSS diagnosis is made. The most common and disabling symptom experienced by patients with pSS is fatigue, occurring in up to 80% of individuals, with accompanying complaints of pain, depression, and anxiety. These symptoms together result in up to -50% of working-age pSS patients being unable to work due to disability. Fatigue and systemic disease manifestations constitute the most commonly experienced morbidities in pSS patients.

[0006] The current medications comprising the standard of care in pSS can sometimes improve symptoms but do not alter the disease course or restore organ function. No therapy currently used in pSS has been found in robust randomized placebo-controlled studies to be superior to placebo in treating this condition, and no disease-modifying anti-rheumatic drugs (DMARDs) are currently approved for pSS. Thus, there is a need for therapeutics that can be used to treat Sjogren’s Syndrome. The embodiments provided for herein fulfil these needs as well as others.DRAWINGS

[0007] FIG. 1 is a schematic overview of the study detailed in Example 1.

[0008] FIG. 2 is a box plot of change from baseline in albumin (g / L) over time through the end of study. Note: The line inside the box represents the median value. The symbol inside the box represents the mean value. The outer box borders represent the first and third quartiles. The upper and lower whiskers represent the location of the maximum and minimum within the first and third quartiles + / -1.5 times the interquartile range. The circle represents any outliers.

[0009] FIG. 3 is a box plot of change from baseline in total cholesterol (mmol / L) over time through the end of study. Note: The line inside the box represents the median value The symbol inside the box represents the mean value. The outer box borders represent the first and third quartiles. The upper and lower whiskers represent the location of the maximum and minimum within the first and third quartiles + / -1.5 times the interquartile range. The circle represents any outliers.

[0010] FIG. 4 is a graph of the mean (+ / -SE) percent change from baseline values for Immunoglobulin G g / L [IgG] over time. Note: Subjects are required to have at least one valid post-dose blood sample drawn for PD analysis.

[0011] FIG. 5 is a graph of the mean (+ / - SE) percent change from baseline values for C- Reactive Protein mg / L [CRP] over time. Note: Subjects are required to have at least one valid post-dose blood sample drawn for PD analysis.

[0012] FIG. 6 is a graph of the mean (+ / - SE) percent change from baseline values for Erythrocyte Sedimentation Rate mm / h [ESR] over time. Note: Subjects are required to have at least one valid post-dose blood sample drawn for PD analysis.

[0013] FIG. 7 is a graph of the mean (+ / - SE) percent change from baseline values for Immunoglobulin A g / L [IgA] over time. Note: Subjects are required to have at least one valid post-dose blood sample drawn for PD analysis.

[0014] FIG. 8 is a graph of the mean (+ / - SE) percent change from baseline values for Immunoglobulin M g / L [IgM] over time. Note: Subjects are required to have at least one valid post-dose blood sample drawn for PD analysis.

[0015] FIG. 9 is a graph of the mean (+ / - SE) percent change from baseline values for and Rheumatoid Factor lU / m / L [RF]) over time. Note: Subjects are required to have at least one valid post-dose blood sample drawn for PD analysis.

[0016] FIG. 10 is a graph of the mean (+ / - SE) change from baseline values for clinESSDAI score over time through Week 24.

[0017] FIG. 11 is a graph of the mean (+ / - SE) change from baseline values for ESSDAI score over time through Week 24.

[0018] FIG. 12 is a schematic overview of the study detailed in Example 2.

[0019] FIGs. 13A-E are graphs of the mean (+ / - SE) change from baseline values for Vaginal Dryness (FIG. 13 A), Fatigue (FIG. 13B), Joint Pain (FIG. 13C), Eye Dryness (FIG. 13D), and Mouth Dryness (FIG. 13E) over time through Week 24. Q2W, once every 2 weeks; SE, standard error.

[0020] FIG. 14 is a graph of the mean (+ / - SE) proportion of patients with > 50% improvement in unstimulated whole salivary (UWS) flow at Week 24. Q2W, once every 2 weeks; SE, standard error.

[0021] FIGs. 15A-F are graphs of Change from Baseline in ClinESSDAI Score Over Time (FIG. 15A), Change from Baseline in ClinESSDAI Score at Week 24 (FIG. 15B), Response Rate by Selected ClinESSDAI Domains (FIG. 15C), Change from Baseline in ESSPRI Score Over Time (FIG. 15D), Change from Baseline in ESSPRI Score at Week 24 (FIG. 15E), and Change from Baseline in ClinESSDAI Score Over Time by Baseline Autoantibody Levels (FIG. 15F). ClinESSDAI, Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index; ESSPRI, European League Against Rheumatism Sjogren’s Syndrome Patient Reported Index; LS, least squares; Q2W, every 2 weeks; SE, standard error. *P=0.002 for LS mean difference for nipocalimab 15 mg / kg versus placebo. ' The sero-low group consisted ofparticipants with autoantibody levels in the lowest tertile for all 3 autoantibodies. The number of participants in the placebo, nipocalimab 5 mg / kg, and nipocalimab 15 mg / kg groups was 9, 8, and 14 respectively. ‘The sero-medium group consisted of participants with >1 autoantibody above the lowest tertile. The number of participants in the placebo, nipocalimab 5 mg / kg, and nipocalimab 15 mg / kg groups was 37, 37, and 31, respectively.§The sero-high group consisted of participants with autoantibody levels in the highest tertile for all 3 autoantibodies. The number of participants in the placebo, nipocalimab 5 mg / kg, and nipocalimab 15 mg / kg groups was 9, 7, and 8, respectively.

[0022] FIG. 16 is a graph of Change from Baseline in ESSDAI Score Over Time. ESSDAI, European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index; Q2W, every 2 weeks; SE, standard error.

[0023] FIG. 17 is a graph of Correlation between Baseline IgG Autoantibody Levels and ClinESSDAI-4 Scores. ClinESSDAI, Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index. The sero-low group consisted of participants with autoantibody levels in the lowest tertile for all 3 autoantibodies. The sero-medium group consisted of participants with >1 autoantibody above the lowest tertile. The sero-high group consisted of participants with autoantibody levels in the highest tertile for all 3 autoantibodies.

[0024] FIGs. 18A-D are graphs of Nipocalimab Mechanism of Action: Observed Minimum Percent Change from Baseline in Total IgG (FIG. 18A) and anti-Ro52 autoantibody (FIG. 18B), anti-Ro60 autoantibody (FIG. 18C), and anti-La Autoantibody IgG (FIG. 18D) Levels Over Time. IgG, immunoglobulin G; IQR, interquartile range; Q2W, every 2 weeks. “No. of participants” is the number of participants with a non-missing value at both baseline and the postbaseline time point. If a participant missed a planned dose of study intervention at any visit, their data were excluded from all subsequent visits after the first occurrence of a missed dose. Participants were required to have >1 valid post-dose blood sample drawn for pharmacodynamic analysis. Participants included in the anti-Ro60 autoantibody, anti-Ro52 autoantibody, and anti- La autoantibody analyses must have been positive for anti-Ro60 autoantibody, anti-Ro52 autoantibody, or anti-La autoantibody, respectively, at baseline.

[0025] FIGs. 19A-D are graphs of Percent Change from Baseline in Biomarker Levels over Time. ESR, erythrocyte sedimentation rate (FIG. 19A); IgA, immunoglobulin A (FIG. 19B); IgM, immunoglobulin M (FIG. 19C); IQR, interquartile range (FIG. 19D); Q2W, every 2 weeks; RF, rheumatoid factor. Analyses included participants with a nonmissing value at both the baseline and postbaseline time points. If a participant missed a planned dose of study intervention at any visit, their data were excluded from all subsequent visits after the first occurrence of a missed dose. Participants were required to have >1 valid postdose blood sample drawn for pharmacodynamic analysis.

[0026] FIG. 20 is a graph showing simulated IgG lowering over time with the 15 ml / mg IV q2w and 460 mg SC qw nipocalimab dose regimens. Solid line: median concentration of nipocalimab; shaded area: 90% prediction interval.

[0027] FIG. 21 is a graph showing model-predicted ClinESSDAI (%change from baseline) over time for placebo, nipocalimab 15 mg / kg IV Q2W and 460 mg SC QW dose regimens.

[0028] FIGs. 22A-22B are graphs showing model-based predictions for total cholesterol (FIG. 22A) and LDL (FIG. 22B).SUMMARY

[0029] Provided herein is a method of treating Sjogren's disease in a subject in need thereof, the method comprising administering an anti-FcRn agent to the subject.

[0030] In one embodiment of the method, the anti-FcRn agent is administered every week, every two weeks, every three weeks, or monthly.

[0031] In a further embodiment of the method, the anti-FcRn agent is nipocalimab, rozanolixizumab, batoclimab, IMVT-1402, efgartigimod, orilanolimab, SYNT002, ABY- 039, or DX-2507.

[0032] In a yet further embodiment of the method, the anti-FcRn agent is administered at a dose from about 5 mg / kg to about 45 mg / kg, about 5 mg / kg to about 15 mg / kg, about 15 mg / kg to about 45 mg / kg, or about 30 mg / kg to about 45 mg / kg based on the weight of the subject.

[0033] In a yet further embodiment of the method, the anti-FcRn agent is administered at a dose of about 5 mg / kg, about 15 mg / kg, about 30 mg / kg, or about 45 mg / kg based on the weight of the subject.

[0034] In a yet further embodiment of the method, the anti-FcRn agent is administered intravenously or subcutaneously.

[0035] In a yet further embodiment of the method, the anti-FcRn agent is an anti-FcRn antibody comprising:(a) a light chain, which comprises a CDR LI comprising an amino acid sequence of SEQ ID NO: 3, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 4, and a CDR L3 comprising an amino acid sequence of SEQ ID NO: 5; and(b) a heavy chain, which comprises a CDR Hl comprising an amino acid sequence of SEQ ID NO: 6, a CDRH2 comprising an amino acid sequence of SEQ ID NO: 7, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 8.In one embodiment, (a) the light chain of the anti-FcRn antibody comprises a light chain variable region comprising an amino acid sequence of SEQ ID NO: 9; and (b) the heavy chain of the anti- FcRn antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 10. In one embodiment, (a) the light chain of the anti-FcRn antibody comprises an amino acid sequence of SEQ ID NO: 1; and (b) the heavy chain of the anti-FcRn antibody comprises an amino acid sequence of SEQ ID NO: 2.

[0036] In a yet further embodiment of the method, the anti-FcRn agent is nipocalimab.

[0037] In a yet further embodiment of the method, nipocalimab is administered every two weeks intravenously at 10-30 mg / kg based on the weight of the subject.

[0038] In a yet further embodiment of the method, nipocalimab is administered every two weeks intravenously at 15 mg / kg based on the weight of the subject.

[0039] In a yet further embodiment of the method, nipocalimab is administered every week subcutaneously at 200-1000 mg.

[0040] In a yet further embodiment of the method, nipocalimab is administered every week subcutaneously at 200-1000 mg.

[0041] In a yet further embodiment of the method, nipocalimab is administered every week subcutaneously at 230, 460, 690, or 920 mg.

[0042] In a yet further embodiment of the method, nipocalimab is administered via an auto injector.

[0043] In a yet further embodiment of the method, the method provides a clinical benefit as measured by a decrease in Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (clinESSDAI) score in the subject by more than 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, or 17 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

[0044] In a yet further embodiment of the method, the method provides a clinical benefit as measured by a decrease in Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (clinESSDAI) score in the subject by more 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, or 17 from baseline within 24 weeks of initiation of said administering.

[0045] In a yet further embodiment of the method, the method provides a clinical benefit as measured by a decrease in European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ESSDAI) score in the subject by more than 3, 4, 5, , 6, 7, 8, 9, 10, 11, 12, 13, 14,15, or 16 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

[0046] In a yet further embodiment of the method, the method provides a clinical benefit as measured by a decrease in the European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ESSDAI) score in the subject by more than 3, 4, 5, or 6 from baseline within 24 weeks of initiation of said administering.

[0047] In a yet further embodiment of the method, the method provides a clinical benefit as measured by a decrease in Physician's Global Assessment of Disease Activity (PhGA) score inthe subject by more than 10, 12, 14, 16, 18, 20, 25, 27, 30, 33, 38, 43, 48, or 52 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

[0048] In a yet further embodiment of the method, the method provides a clinical benefit as measured by a decrease in PhGA score in the subject by more than 33, 38, 43, 48, or 52 from baseline within 24 weeks of initiation of said administering.

[0049] In a yet further embodiment of the method, the subject achieved ESSDAI-3 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering.

[0050] In a yet further embodiment of the method, the subject achieved ESSDAI-4 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering.

[0051] In a yet further embodiment of the method, the subject achieved clinESSDAI-3 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering.

[0052] In a yet further embodiment of the method, the subject achieved clinESSDAI-4 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering.

[0053] In a yet further embodiment of the method, the subject achieved ESSPRI response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

[0054] In a yet further embodiment of the method, the subject achieved STAR response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

[0055] In a yet further embodiment of the method, the subject achieved DAL response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

[0056] In a yet further embodiment of the method, the subject achieved CRESS response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

[0057] In a yet further embodiment of the method, the subject has an improvement in each of the Sjogren’s symptoms, wherein the Sjogren’s symptoms comprise: fatigue, eye dryness, mouth dryness, joint pain, and vaginal dryness.

[0058] In a yet further embodiment of the method, the subject achieves an improvement in tear production by 5, 10, 15, 20, 25, 30, or 35 mm from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. In one embodiment, the tear production is measured by the Schirmer’s test.

[0059] In a yet further embodiment of the method, the subject achieves an improvement in basal saliva production by 0.02, 0.05, 0.08, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1 mL / min from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. In one embodiment, the basal saliva production is measured by the Unstimulated Salivary Flow Test. In one embodiment, the basal saliva production is measured by the stimulated salivary flow test.

[0060] In a yet further embodiment of the method, the subject achieves a reduction in keratoconjunctivitis sicca (KCS) by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. In one embodiment, the KCS is measured by the ocular surface staining (OSS).

[0061] In a yet further embodiment of the method, the subject has a reduced need for glucocorticoid treatment from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

[0062] In a yet further embodiment of the method, the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 0.8, more than 1, more than 1.2, more than 1.4, more than 1.6, more than 1.8, more than 2, more than 2.2, more than 2.4, more than 2.6, more than 2.8, more than 3, more than 3.2, more than 3.4, more than 3.6, more than 3.8, more than 4, more than 4.2, more than 4.4, more than 4.6, more than 4.8, more than 5, more than 5.2, more than 5.4, more than 5.6, more than 5.8, or more than 6 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

[0063] In a yet further embodiment of the method, the method provides the subject an improvement in health-related quality of life (HRQol) from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. In one embodiment, the HRQol is measured by the 36-item Short Form Health Survey Questionnaire (SF-36) score.

[0064] In a yet further embodiment of the method, the method provides a clinical benefit as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score in the subject by more than 5, 10, 15, 20, 25, 30, 35, or 40 points from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. In a yet further embodiment of the method, the method provides a clinical benefit as measured by an increase in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score in the subject by more than 5, 10, 15, 20, 25, 30, 35, or 40 points from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

[0065] In a yet further embodiment of the method, the subject achieves a Sjogren’sSyndrome Responder Index (SSRI) response greater than or equal to a 20% or 30% improvement from baseline in at least two or three of five domains of the SSRI response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. In one embodiment, the five domains comprise fatigue, oral dryness, ocular dryness, unstimulated whole salivary flow, and erythrocyte sedimentation rate.

[0066] In a yet further embodiment of the method, following said administering the subject has a reduction in autoantibodies in the blood relative to a level prior to said administering. In one embodiment, the autoantibodies are selected from the group consisting of: anti-La (SSB) autoantibodies, anti- Smith, antinuclear antibodies (ANA), anti-phospholipid antibodies, anti- dsDNA antibodies, anti-nRNP (ribonucleoproteins) antibodies, anti-rheumatoid factor antibodies, anti-Ro60 (SSA) autoantibodies, and anti-Ro52 autoantibodies.

[0067] In a yet further embodiment of the method, the method does not significantly decrease level of albumin in the subject compared with baseline.

[0068] In a yet further embodiment of the method, the method does not significantly increase the level of serum total cholesterol in the subject compared with baseline.

[0069] Provided herein is a method of treating Sjogren's disease in a subject in need thereof, the method comprising administering an anti-FcRn antibody to the subject, wherein the anti- FcRN antibody comprises:(a) a light chain, which comprises a CDR LI comprising an amino acid sequence of SEQ ID NO: 3, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 4, and a CDR L3 comprising an amino acid sequence of SEQ ID NO: 5; and(b) a heavy chain, which comprises a CDR Hl comprising an amino acid sequence of SEQ ID NO: 6, a CDR H2 comprising an amino acid sequence of SEQ ID NO: 7, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 8; and wherein the anti-FcRn antibody is administered every week subcutaneously at 460 mg.

[0070] Provided herein is a method of treating Sjogren's disease in a subject in need thereof, the method comprising administering nipocalimab to the subject, wherein the nipocalimab is administered every week subcutaneously at 460 mg.DETAILED DESCRIPTION

[0071] The present disclosure provides methods of treating Sjogren’s disease and related symptoms or pathologies associated with the same with an agent against human neonatal Fc receptor (FcRn). As used herein, Sjogren’s disease includes primary Sjogren’s syndrome (pSS). And in the present application, the terms “Sjogren’s disease (SjD)”, “Sjogren disease”, “Sjogren’s Syndrome (SJS or SS)”, “primary Sjogren’s Syndrome (pSS)”, and “Sjogren Syndrome” are used interchangeably.

[0072] As used herein, the term “FcRn” refers a neonatal Fc receptor that binds to the Fc region of an IgG antibody, e.g., an IgGl antibody. An exemplary FcRn is human FcRn having UniProt ID No. P55899, which is hereby incorporated by reference in its entirety. Without being bound to any particular theory, human FcRn is believed to be responsible for maintaining the half-life of IgG by binding and trafficking constitutively internalized IgG back to the cell surface for the recycling of IgG.

[0073] In some embodiments, the anti-FcRn agent is an anti-FcRn antibody.

[0074] The term “antibody” herein is used in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies,multispecific antibodies (e.g., bispecific antibodies), scFVs, nanobodies, VHH, and antibody fragments so long as they exhibit FcRn antigen-binding activity.

[0075] Additionally, antibody or antibody molecule, as that term is used herein, refers to a polypeptide, e.g., an immunoglobulin chain or fragment thereof, comprising at least one functional immunoglobulin variable domain sequence. An antibody molecule encompasses antibodies (e.g., full-length antibodies) and antibody fragments. In some embodiments, an antibody molecule comprises an antigen binding or functional fragment of a full-length antibody, or a full-length immunoglobulin chain. For example, a full-length antibody is an immunoglobulin (Ig) molecule (e.g., an IgG antibody) that is naturally occurring or formed by normal immunoglobulin gene fragment recombinatorial processes. In some embodiments, an antibody molecule refers to an immunologically active, antigen-binding portion of an immunoglobulin molecule, such as an antibody fragment. An antibody fragment (e.g., a functional fragment) comprises a portion of an antibody, e.g., Fab, Fab', F(ab')2, F(ab)2, variable fragment (Fv), domain antibody (dAb), or single chain variable fragment (scFv). A functional antibody fragment binds to the same antigen as that recognized by the intact (e.g., full-length) antibody. The terms “antibody fragment” or “functional fragment” also include isolated fragments consisting of the variable regions, such as the “Fv” fragments consisting of the variable regions of the heavy and light chains or recombinant single chain polypeptide molecules in which light and heavy variable regions are connected by a peptide linker (“scFv proteins”). In some embodiments, an antibody fragment does not include portions of antibodies without antigen binding activity, such as Fc fragments or single amino acid residues. Exemplary antibody molecules include full length antibodies and antibody fragments, e.g., dAb (domain antibody), single chain, Fab, Fab’, and F(ab’)2 fragments, and single chain variable fragments (scFvs).

[0076] Immunoglobulin chains exhibit the same general structure of relatively conserved framework regions (FRs) joined by three hypervariable regions, also called complementarity determining regions (CDRs). The CDRs from the two chains of each pair are aligned by the framework regions, enabling binding to a specific epitope. From N-terminus to C-terminus, both light and heavy chains comprise the domains FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. The assignment of amino acids to each domain is in accordance with the definitions of kabatSequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987 and 1991)), or Chothia & Lesk J. Mol. Biol. 196:901-917 (1987); Chothia et al. Nature 342:878-883 (1989).

[0077] The term “antibody molecule” also encompasses whole or antigen binding fragments of domain, or single domain, antibodies, which can also be referred to as “sdAb” or “VHH.” Domain antibodies comprise either VH or VL that can act as stand-alone, antibody fragments. Additionally, domain antibodies include heavy-chain-only antibodies (HCAbs). Domain antibodies also include a CH2 domain of an IgG as the base scaffold into which CDR loops are grafted. It can also be generally defined as a polypeptide or protein comprising an amino acid sequence that is comprised of four framework regions interrupted by three complementarity determining regions. This is represented as FR1- CDR1 -FR2-CDR2-FR3-CDR3-FR4. sdAbs can be produced in camelids such as llamas, but can also be synthetically generated using techniques that are well known in the art. The numbering of the amino acid residues of a sdAb or polypeptide is according to the general numbering for VH domains given by Kabat et al. (“Sequence of proteins of immunological interest,” US Public Health Services, NIH Bethesda, MD, Publication No. 91, which is hereby incorporated by reference). According to this numbering, FR1 of a sdAb comprises the amino acid residues at positions 1-30, CDR1 of a sdAb comprises the amino acid residues at positions 31-36, FR2 of a sdAb comprises the amino acids at positions 36-49, CDR2 of a sdAb comprises the amino acid residues at positions 50-65, FR3 of a sdAb comprises the amino acid residues at positions 66- 94, CDR3 of a sdAb comprises the amino acid residues at positions 95-102, and FR4 of a sdAb comprises the amino acid residues at positions 103-113. Domain antibodies are also described in International Publication Nos. W02004 / 041862 and WO2016 / 065323, both of which are hereby incorporated by reference in their entireties.

[0078] In some embodiments, as provided for herein, antibody molecules can be monospecific (e.g., monovalent or bivalent), bispecific (e.g., bivalent, trivalent, tetravalent, pentavalent, or hexavalent), trispecific (e.g., trivalent, tetravalent, pentavalent, hexavalent), or with higher orders of specificity (e.g., tetraspecific) and / or higher orders of valency beyond hexavalency. An antibody molecule can comprise a functional fragment of a light chainvariable region and a functional fragment of a heavy chain variable region, or heavy and light chains may be fused together into a single polypeptide.

[0079] As used herein, the terms “variable region” and “variable domain” refer to the portions of the light and heavy chains of an antibody that include amino acid sequences of complementary determining regions (e.g., CDRL1, CDRL2, CDR L3, CDRH1, CDR H2, and CDR H3) and framework regions. According to the methods used in this disclosure, the amino acid positions assigned to CDRs and FRs are defined according to Kabat (“Sequences of Proteins of Immunological Interest”, 5thEd. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). Using this numbering system, the actual linear amino acid sequence may contain fewer or additional amino acids corresponding to a shortening of, or insertion into, a CDR (defined further herein) or FR (defined further herein) of the variable region. For example, a heavy chain variable region may include a single inserted residue (i.e., residue 52a according to Kabat) after residue 52 of CDR H2 and inserted residues (i.e., residues 82a, 82b, 82c, etc. according to Kabat) after residue 82 of heavy chain FR. The Kabat numbering of residues may be determined for a given antibody by alignment at regions of homology of the sequence of the antibody with a “standard” Kabat numbered sequence.

[0080] As used herein, the terms “complementary determining regions” and “CDRs” refer to the regions of an antibody variable domain or variable region which are hypervariable in sequence and / or form structurally defined loops. A CDR is also known as a hypervariable region. The light chain and heavy chain variable regions each has three CDRs. The light chain variable region contains CDR LI, CDR L2, and CDR L3. The heavy chain variable region contains CDR Hl, CDR H2, and CDR H3. Each CDR may include amino acid residues from a complementarity determining region as defined by Kabat, i.e., about residues 24-34 (CDR LI), 50-56 (CDRL2) and 89-97 (CDR L3) in the light chain variable region and about residues 31-35 (CDR Hl), 50-65 (CDR H2) and 95-102 (CDR H3) in the heavy chain variable region.

[0081] In some embodiments, the anti-FcRn antibody comprises a heavy chain or light chain. In some embodiments, the anti-FcRn antibody comprises a heavy chain and a light chain in a scFv format. In some embodiments, the heavy and light chain are linked with a peptide linker, such a glycine / serine or glycine / alanine linker.

[0082] In some embodiments, the anti-FcRn antibody is nipocalimab, efgartigimod, rozanolixizumab, batoclimab, IMVT-1402, orilanolimab, SYNT002, ABY-039, or DX-2507.

[0083] In some embodiments, the anti-FcRn antibody is nipocalimab, which can also be referred to as M281. Nipocalimab is an antibody that binds to FcRn and is described, for example, in US Patent No. 10,676,526, PCT Publication No. W02020 / 023310, and PCT Publication No. W02020 / 018910, all of which are hereby incorporated by reference in their entireties.

[0084] In some embodiments, the anti-FcRn antibody is M281 (nipocalimab). In some embodiments, nipocalimab comprises or consists of: a light chain comprising or consisting of the sequence:QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSE RPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVL GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVET TTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 1); and a heavy chain comprising or consisting of the sequence:EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGAS GSQTRYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWG QGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA LTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEP KSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEV I<FNWYVDGVEVHNAI<TI<PREEQYASTYRVVSVLTVLHQDWLNGI<EYI<CI<VSN KALPAPIEKHSKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALH NHYTQKSLSLSPG (SEQ ID NO: 2).

[0085] In some embodiments, the anti-FcRn antibody has: (a) a light chain sequence that is at least 95%, 96%, 97% 98%, or 99% identical to SEQ ID NO: 1, wherein the CDRL1 comprises the sequence TGTGSDVGSYNLVS (SEQ ID NO: 3), the CDRL2 comprises thesequence GDSERPS (SEQ ID NO: 4), the CDRL3 comprises the sequence SSYAGSGIYV (SEQ ID NO: 5); and (b) a heavy chain sequence that is at least 95%, 96%, 97% 98%, or 99% identical to SEQ ID NO: 2, wherein the CDRH1 comprises the sequence TYAMG (SEQ ID NO: 6), the CDRH2 comprises the sequence SIGASGSQTRYADS (SEQ ID NO: 7), and the CDR H3 comprises the sequence LAIGDSY (SEQ ID NO: 8).

[0086] In some embodiments, the anti-FcRn antibody comprises a light chain variable region comprising an amino acid sequence that is at least 95%, 97%, 99%, or 100% identical to: QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMIYGDSERPSGV SNRFSGSKSGNTASLTISGLQAEDEADYYCSSYAGSGIYVFGTGTKVTVL (SEQ ID NO: 9). In some embodiments, the light chain variable region contains a CDR LI having the sequence of SEQ ID NO: 3, a CDR L2 having the sequence of SEQ ID NO: 4, a CDR L3 having the sequence of SEQ ID NO: 5.

[0087] In some embodiments, the anti-FcRn antibody comprises a heavy chain variable region comprising an amino acid sequence that is at least 95%, 97%, 99%, or 100% identical to: EVQLLESGGGLVQPGGSLRLSCAASGFTFSTYAMGWVRQAPGKGLEWVSSIGASGSQT RYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARLAIGDSYWGQGTMVTVSS (SEQ ID NO: 10). In some embodiments, the heavy chain variable region contains a CDR Hl having the sequence of SEQ ID NO: 6, a CDR H2 having the sequence of SEQ ID NO: 7, and a CDR H3 having the sequence of SEQ ID NO: 8.

[0088] In some embodiments, some of the heavy chains of nipocalimab may comprise an additional Lysine (K) residue at the C-terminus of SEQ ID NO: 2.

[0089] The term “nipocalimab” as used herein is intended to encompass biosimilar anti- FcRn antibodies that are equivalent to the nipocalimab protein developed and marketed by Johnson and Johnson. For example, a biosimilar of nipocalimab may be acceptable to the European Medicines Agency (EMA) and / or the United States Food and Drug Administration (FDA) when it has essentially the same pharmacological effects as the reference product nipocalimab. For example, a biosimilar of nipocalimab may comprise or consist of the same heavy and light chains sequences as nipocalimab, with the exception of a C-terminal modification. For example, the C-terminal amino acid or acids of the heavy chain may beabsent, e.g. compared to SEQ ID NO: 2. The present disclosure extends to the use of antibody that uses the International Nonproprietary Name (INN) “nipocalimab”.

[0090] In some embodiments, the antibodies may further comprise amino acid substitutions, additions, and / or deletions outside of the CDRs (i.e., in framework regions (FRs)). An amino acid substitution, addition, and / or deletion can be a substitution, addition, and / or deletion of one or more amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more). An amino acid substitution, addition, and / or deletion can be a substitution, addition, and / or deletion of eight or fewer, seven or fewer, six or fewer, five or fewer, four or fewer, three or fewer, or two or fewer single amino acids.

[0091] In some embodiments, the antibodies described herein may include amino acid substitutions, additions, and / or deletions in the constant regions (e.g., Fc region) of the antibody that, e.g., lead to decreased effector function, e.g., decreased complement-dependent cytolysis (CDC), antibody-dependent cell-mediated cytolysis (ADCC), and / or antibody-dependent cell- mediated phagocytosis (ADCP), and / or decreased B-cell killing. The constant regions are not involved directly in binding an antibody to its target, but exhibit various effector functions, such as participation of the antibody in antibody-dependent cellular toxicity. In some embodiments, the antibodies described herein are characterized by decreased binding (i.e., absence of binding) to human complement factor Clq and / or human Fc receptor on natural killer (NK) cells. In other embodiments, the antibodies are characterized by decreased binding (i.e., absence of binding) to human FcyRI, FcyRIIA, and / or FcyRIIIA. In some embodiments, the antibodies described herein contain asparagine (N) at position 297 (numbering according to the EU System). In some embodiments, an anti-FcRn antibody described herein is aglycosylated at position 297 (numbering according to the EU System). In some cases, an anti-FcRn antibody described herein does not have an N at position 297 (EU numbering) in any one of SEQ ID NO: 2, such that the antibody is aglycosylated at that position. The resulting effectorless antibody shows very little binding to complement or Fc receptors (i.e., complement Clq binding), indicating low CDC potential. In some embodiments, the Fc region is an effectorless Fc region.

[0092] In some embodiments, the heavy chain of the anti-FcRn antibody comprises a sequence having no more than 5, 4, 3, 2 or 1 single amino acid substitutions relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the light chain of the anti-FcRn antibodycomprises a sequence having no more than 5, 4, 3, 2 or 1 single amino acid substitutions relative to the sequence of SEQ ID NO: 1.

[0093] As used herein, the term “percent (%) identity” refers to the percentage of amino acid (or nucleic acid) residues of a candidate sequence, e.g., an anti-FcRn antibody of the disclosure, that are identical to the amino acid (or nucleic acid) residues of a reference sequence, e.g., a wild-type anti-FcRn antibody, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent identity (i.e., gaps can be introduced in one or both of the candidate and reference sequences for optimal alignment and non-homologous sequences can be disregarded for comparison purposes). Alignment for purposes of determining percent identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, ALIGN, or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. In some embodiments, the percent amino acid (or nucleic acid) sequence identity of a given candidate sequence to, with, or against a given reference sequence (which can alternatively be phrased as a given candidate sequence that has or includes a certain percent amino acid (or nucleic acid) sequence identity to, with, or against a given reference sequence) is calculated as follows:100 x (fraction of A / B)

[0094] where A is the number of amino acid (or nucleic acid) residues scored as identical in the alignment of the candidate sequence and the reference sequence, and where B is the total number of amino acid (or nucleic acid) residues in the reference sequence. In some embodiments where the length of the candidate sequence does not equal to the length of the reference sequence, the percent amino acid (or nucleic acid) sequence identity of the candidate sequence to the reference sequence would not equal to the percent amino acid (or nucleic acid) sequence identity of the reference sequence to the candidate sequence.

[0095] In some embodiments, a reference sequence aligned for comparison with a candidate sequence may show that the candidate sequence exhibits from 50% to 100% identity across the full length of the candidate sequence or a selected portion of contiguous amino acid (or nucleicacid) residues of the candidate sequence. The length of the candidate sequence aligned for comparison purpose is at least 30%, e.g., at least 40%, e.g., at least 50%, 60%, 70%, 80%, 90%, or 100% of the length of the reference sequence. When a position in the candidate sequence is occupied by the same amino acid (or nucleic acid) residue as the corresponding position in the reference sequence, then the molecules are identical at that position. A position may be altered by a substitution, deletion, or insertion. A substitution, deletion, or insertion may comprise a certain number of amino acids (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or more). When describing a substitution, deletion, or insertion of no more than n amino acids, this is meant that the substitution, deletion, or insertion comprises, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or n amino acids. The number or substitutions, deletions, or insertions can comprise a percent of the total sequence (e.g., 1%, 5%, 10%, 15%, 20%, or more) where the number of substitutions, deletions, or insertions alters 5%, 10%, 15%, 20% or more, of the amino acids in the total sequence.

[0096] In some embodiments, the Fc domain of the antibody is not fucosylated. In some embodiments, the Fc domain of the antibody is not glycosylated. In some embodiments, the antibody lacks effector function. In some embodiments, the antibody is an IgGl antibody.

[0097] In some embodiments, the anti-FcRn antibody is efgartigimod (also known as ARGX-113), a modified human IgGl -derived Fc fragment that binds FcRn. In some embodiments, efgartigimod is described in U.S. Patent No. 10,316,073, which is incorporated herein by reference in its entirety. In some embodiments, efgartigimod comprises or consists of a first subunit comprising or consisting of the sequence:DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAI<TI<PREEQYNSTYRVVSVLTVLHQDWLNGI<EYI<CT<VSNI<AL PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALKFHYT QKSLSLSPGK (SEQ ID NO: 11); and a second subunit comprising or consisting of the sequence:DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLYITREPEVTCVWDVSHEDPEVKFN WYVDGVEVHNAI<TI<PREEQYNSTYRVVSVLTVLHQDWLNGI<EYI<C I<VSNI<AL PAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALKFHYT QKSLSLSPGK (SEQ ID NO: 12).

[0098] In some embodiments, the anti-FcRn antibody is rozanolixizumab (also known as UCB7665), a humanized anti-FcRn antibody. In some embodiments, rozanolixizumab is described in U.S. Patent No. 10,233,243, which is incorporated herein by reference in its entirety. In some embodiments, rozanolixizumab comprises or consists of a light chain comprising or consisting of the sequence:DIQMTQSPSSLSASVGDRVTITCKSSQSLVGASGKTYLYWLFQKPGKAPKRLIYL VSTLDSGIPSRFSGSGSGTEFTLTISSLQPEDFATYYCLQGTHFPHTFGQGTKLEIK RTVAAPSVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQE SVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 13); and a heavy chain comprising or consisting of the sequence:EVPLVESGGGLVQPGGSLRLSCAVSGFTFSNYGMVWVRQAPGKGLEWVAYIDS DGDNTYYRDSVKGRFTISRDNAKSSLYLQMNSLRAEDTAVYYCTTGIVRPFLYW GQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGA LTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTKTYTCNVDHKPSNTKVDKRVES KYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFN WYVDGVEVHNAI<TI<PREEQFNSTYRVVSVLTVLHQDWLNGI<EYI<CT<VSNI<GL PSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYT QKSLSLSLGK (SEQ ID NO: 14).

[0099] In some embodiments, the anti-FcRn antibody is batoclimab (also known as IMVT- 1401, RVT1401, HL161BKN, and HBM9161), a fully human, anti-FcRn antibody. In some embodiments, batoclimab is described in U.S. Patent No. 10,544,226, which is incorporatedherein by reference in its entirety. In some embodiments, batoclimab comprises or consists of a light chain comprising or consisting of the sequence:SYVLTQSPSVSVAPGQTARITCGGNNIGSKSVHWYQQKPGQAPVLVVYDDSDRP SGIPERFSASNSGNTATLTISRVEAGDEADYYCQVWDSSSDHWFGGGTKLTVLG QPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETT TPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 15); and a heavy chain comprising or consisting of the sequence:QLLLQESGPGLVKPSETLSLTCTVSGGSLSSSFSYWVWIRQPPGKGLEWIGTIYYS GNTYYNPSLKSRLTISVDTSKNHFSLKLSSVTAADTAVYYCARRAGILTGYLDSW GQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA LTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKRVEP KSCDKTHTCPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPE VI<FNWYVDGVEVHNAI<TI<PREEQYNSTYRVVSVLTVLHQDWLNGI<EYI<C I<VS NKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALH NHYTQKSLSLSPG (SEQ ID NO: 16).

[0100] In some embodiments, the anti-FcRn antibody is IMVT-1402 (also known as HL161ANS), a fully human, anti-FcRn antibody. In some embodiments, IMVT-1402 is disclosed in WO2023 / 235679, which is incorporated herein by reference in its entirety.

[0101] In some embodiments, the anti-FcRn antibody is orilanolimab (also known as ALXN1830 and SYNT001), a humanized anti-FcRn antibody. In some embodiments, orilanolimab is described in U.S. Patent No. 10,626,175, which is incorporated herein by reference in its entirety. In some embodiments, orilanolimab comprises or consists of a light chain variable region comprising or consisting of the sequence:DIQMTQSPSSLSASVGDRVTITCKASDHINNWLAWYQQKPGQAPRLLISGATSLE TGVPSRFSGSGTGKDYTLTISSLQPEDFATYYCQQYWSTPYTFGGGTKVEIK (SEQ ID NO: 17);and a heavy chain variable region comprising or consisting of the sequence:QVQLVQSGAELKKPGASVKLSCKASGYTFTSYGISWVKQATGQGLEWIGEIYPR SGNTYYNEKFKGRATLTADKSTSTAYMELRSLRSEDSAVYFCARSTTVRPPGIW GTGTTVTVSS (SEQ ID NO: 18).

[0102] In some embodiments, the anti-FcRn antibody is SYNT002, a humanized anti-FcRn antibody. In some embodiments, SYNT002 is described in U.S. Patent No. 10,822,417, which is incorporated herein by reference in its entirety. In some embodiments, SYNT002 comprises or consists of a light chain variable region comprising or consisting of the sequence:DIVMTQSPDSLSASVGDRVTITCKASQSVSNDVAWYQQKPGQPPKLLIYYASNR YTGVPDRFSGSGYGTDFTLTISSLQAEDVAVYFCQQDYSSLTFGQGTKLEIK (SEQ ID NO: 19); and a heavy chain variable region comprising or consisting of the sequence:EVQLVESGGGLVKPGGSLKLSCAASGFTFSDYGMHWVRQAPGKGLEWVAYISS GSSHYYADTVKGRFTISRDNAKNTLYLQMNSLRAEDTAMYYCARAESTTTVGD YWGQGTSVTVSS (SEQ ID NO: 20).

[0103] In some embodiments, the anti-FcRn antibody is ABY-039 (also known as Affibody AB), a bivalent antibody-mimetic targeting FcRn. In some embodiments, ABY-039 is described in U.S. Patent No. 10,323,066, which is incorporated herein by reference in its entirety.

[0104] In some embodiments, the anti-FcRn antibody is DX-2507, a fully human anti-FcRn monoclonal antibody. In some embodiments, DX-2507 is described in U.S. Patent No.9,862,768, which is incorporated herein by reference in its entirety. In some embodiments, DX- 2507 comprises or consists of a light chain comprising or consisting of the sequence:QSALTQPASVSGSPGQSITISCTGTGSDVGSYNLVSWYQQHPGKAPKLMITGDSQ RPSGVSNRFSGSKSGNTASLTISGLQAEDEADYYCASTAGSGITVFGTGTKVTVL GQPKANPTVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVE TTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS (SEQ ID NO: 21);and a heavy chain comprising or consisting of the sequence:EVQLLESGGGLVQPGGSLRLSCAASGFTFSEYAMGWVRQAPGKGLEWVSSIGSS GGQTI<YADSVI<GRFTISRDNSI<NTLYLQMNSLRAEDTAVYYC ARLAIGDSYWG QGTMVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGA LTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKRVEP KSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV I<FNWYVDGVEVHNAI<TI<PREEQYNSTYRVVSVLTVLHQDWLNGI<EYI<CT<VSN KALPAPIEKTISKAKGQPREPQVYTLPPSArqEEMTKNQVSLTCLVKGFYPSDIAV EWESNGQPENNYI<TTPPVLDSDGSFFLYSI<LTVDI<SRWQQGNVFSCSVMHEAL HNHYTQKSLSLSPG (SEQ ID NO: 22).

[0105] In some embodiments, the anti-FcRn agent (e.g., nipocalimab) is administered to the subject suffering Sjogren’s disease every week, every two weeks, every three weeks, or monthly. Administration every week may be preferred. In some embodiments, the anti-FcRn agent (e.g., nipocalimab) is administered to the subject suffering Sjogren’s disease every week.

[0106] In some embodiments, the anti-FcRn agent (e.g., nipocalimab) is administered at a dose from about 5 mg / kg to about 45 mg / kg, based on the weight of the subject. In some embodiments, the anti-FcRn agent is administered at a dose from about 5 mg / kg to about 15 mg / kg, based on the weight of the subject. In some embodiments, the anti-FcRn agent is administered at a dose from about 15 mg / kg to about 45 mg / kg, based on the weight of the subject. In some embodiments, the anti-FcRn agent is administered at a dose from about 30 mg / kg to about 45 mg / kg, based on the weight of the subject.

[0107] In some embodiments, the anti-FcRn agent (e.g., nipocalimab) is administered at a dose of about 5 mg / kg, based on the weight of the subject. In some embodiments, the anti-FcRn agent is administered at a dose of about 15 mg / kg, based on the weight of the subject. In some embodiments, the anti-FcRn agent is administered at a dose of about 30 mg / kg, based on the weight of the subject. In some embodiments, the anti-FcRn agent is administered at a dose of about 45 mg / kg, based on the weight of the subject.

[0108] The anti-FcRn agent (e.g., nipocalimab) may be administered by any means. In some embodiments, the anti-FcRn agent is administered intravenously or subcutaneously.

[0109] In some embodiments, the anti-FcRn agent (e.g., nipocalimab) is administered intravenously. In some embodiments, the anti-FcRn agent is administered every two weeks intravenously at 10-30 mg / kg, based on the weight of the subject. In some embodiments, the anti-FcRn agent is administered every two weeks intravenously at 15 mg / kg based on the weight of the subject.

[0110] In some embodiments, the anti-FcRn agent (e.g., nipocalimab) is administered subcutaneously. In some embodiments, the anti-FcRn agent (e.g., nipocalimab) is administered subcutaneously to the subject every week. Administration of the anti-FcRn agent (e.g. nipocalimab) every week subcutaneously may be preferred.

[0111] The anti-FcRn agent (e.g., nipocalimab) may be administered at 200-1 OOOmg. The anti-FcRn agent (e.g., nipocalimab) may be administered at 200-600 mg, 300-700 mg, 400-800 mg, 500-900 mg, or 600-1000 mg. The anti-FcRn agent (e.g., nipocalimab) may be administered at 200-400 mg, 300-500 mg, 400-600 mg, 500-700 mg, 600-800 mg, 700-900 mg, or 800-1000 mg. The anti-FcRn agent (e.g., nipocalimab) may be administered at 200-300 mg, 300-400 mg, 400-500 mg, 500-600 mg, 600-700 mg, 700-800 mg, 800-900 mg, or 900-1000 mg. The anti- FcRn agent (e.g., nipocalimab) may be administered at 230, 460, 690, or 920 mg. In some embodiments, the anti-FcRn agent is administered every week subcutaneously at 200-1000 mg. In some embodiments, the anti-FcRn agent is administered every week subcutaneously at 200- 1000 mg. The anti-FcRn agent (e.g., nipocalimab) may be administered every week subcutaneously at 200-600 mg, 300-700 mg, 400-800 mg, 500-900 mg, or 600-1000 mg. The anti-FcRn agent (e.g., nipocalimab) may be administered every week subcutaneously at 200-400 mg, 300-500 mg, 400-600 mg, 500-700 mg, 600-800 mg, 700-900 mg, or 800-1000 mg. The anti-FcRn agent (e.g., nipocalimab) may be administered every week subcutaneously at 200-300 mg, 300-400 mg, 400-500 mg, 500-600 mg, 600-700 mg, 700-800 mg, 800-900 mg, or 900-1000 mg. In some embodiments, the anti-FcRn agent is administered every week subcutaneously at 230, 460, 690, or 920 mg. Administration of the anti-FcRn agent (e.g., nipocalimab) at 460 mgmay be preferred. In some embodiments, the anti-FcRn agent is administered every week subcutaneously at 460 mg.

[0112] In some embodiments, the anti-FcRn agent is administered subcutaneously via an autoinjector. Administration the anti-FcRn agent (e.g., nipocalimab) every week subcutaneously via an autoinjector may be preferred. In some embodiments, the anti-FcRn agent (e.g., nipocalimab) is administered subcutaneously every week via an autoinjector.

[0113] The anti-FcRn agent (e.g., nipocalimab) may be administered every week subcutaneously at 460 mg. The anti-FcRn agent (e.g., nipocalimab) may be administered every week subcutaneously at 460 mg via an autoinjector. Administration of the anti-FcRn agent (e.g., nipocalimab) subcutaneously at 460 mg may be preferred. Administration of the anti-FcRn agent (e.g., nipocalimab) every week subcutaneously at 460 mg may be preferred.Administration of the anti-FcRn agent (e.g., nipocalimab) every week subcutaneously at 460 mg via an autoinjector may be preferred.

[0114] In some embodiments, the administering of the anti-FcRn agent (e.g. nipocalimab) to a subject suffering Sjogren’s disease provides a clinical benefit as measured by a decrease in clinESSDAI score in the subject by more than 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks, or within 1.5, or 2, or 2.5 or 3 years, of initiation of said administering. In some embodiments, the administering of the anti-FcRn agent provides a clinical benefit as measured by a decrease in clinESSDAI score in the subject by more than 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 from baseline within 24 weeks of initiation of said administering. The administering of the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease may provide a clinical benefit as measured by a decrease in clinESSDAI score in the subject by 5 or more from baseline within 24 weeks of initiation of said administering. The administering of the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease may provide a clinical benefit as measured by a decrease in clinESSDAI score in the subject by 5 or more from baseline within 48 weeks of initiation of said administering.

[0115] In some embodiments, the administering of the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease provides a clinical benefit as measured by a decrease in ESSDAI score in the subject by more than 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 frombaseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks, or within 1.5, or 2, or 2.5, or 3 years, of initiation of said administering. In some embodiments, the administering of the anti-FcRn agent provides a clinical benefit as measured by a decrease in the ESSDAI score in the subject by more than 3, 4, 5, or 6 from baseline within 24 weeks of initiation of said administering. The administering of the anti-FcRn agent (e.g., nipocalimab) may provide a clinical benefit as measured by a decrease in the ESSDAI score in the subject by 3 or more from baseline within 24 weeks of initiation of said administering. The administering of the anti-FcRn agent (e.g., nipocalimab) may provide a clinical benefit as measured by a decrease in the ESSDAI score in the subject by 3 or more from baseline within 48 weeks of initiation of said administering.

[0116] In some embodiments, the administering of the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease provides a clinical benefit as measured by a decrease in PhGA score in the subject by more than 10, 12, 14, 16, 18, 20, 25, 27, 30, 33, 38, 43, 48, or 52 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. In some embodiments, the administering of the anti-FcRn agent provides a clinical benefit as measured by a decrease in PhGA score in the subject by more than 33, 38, 43, 48, or 52 from baseline within 24 weeks of initiation of said administering. The administering of the anti-FcRn agent (e.g., nipocalimab) may provide a clinical benefit as measured by a decrease in PhGA score in the subject by more than 33 from baseline within 24 weeks of initiation of said administering. The administering of the anti-FcRn agent (e.g., nipocalimab) may provide a clinical benefit as measured by a decrease in PhGA score in the subject by more than 33 from baseline within 48 weeks of initiation of said administering.

[0117] In some embodiments, by administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject achieved ESSDAI-3 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering. ESSDAI-3 response may be defined as reduction of the ESSDAI score by 3 or more points from baseline. By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve ESSDAI-3 response within 48 weeks of initiation of said administering. In some embodiments, the subject achieved ESSDAI-4 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering. ESSDAI-4 response may be defined as reduction of the ESSDAI score by 4 or more points from baseline. By administering the anti-FcRn agent (e.g.,nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve ESSDAI-4 response within 48 weeks of initiation of said administering. In some embodiments, the subject achieved clinESSDAI-3 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering. clinESSDAI-3 response may be defined as reduction of the clinESSDAI score by 3 or more points from baseline. By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve clinESSDAI-3 response within 48 weeks of initiation of said administering. In some embodiments, the subject achieved clinESSDAI-4 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering. clinESSDAI-4 response may be defined as reduction of the clinESSDAI score by 4 or more points from baseline. By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve clinESSDAI-4 response within 48 weeks of initiation of said administering. In some embodiments, the subject achieved ESSPRI response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. ESSPRI response may be defined as a decrease in ESSPRI score of >one point from baseline. ESSPRI response may be defined as a decrease in ESSPRI score of >15% from baseline. By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve ESSPRI response within 48 weeks of initiation of said administering. In some embodiments, the subject achieved STAR response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. STAR response may be defined as a composite score of >5 points, for example a composite score of >5 points in the 5 STAR domains (systemic activity, patient-reported outcome, lachrymal gland function, salivary gland function, and biological). By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve STAR response within 48 weeks of initiation of said administering. In some embodiments, the subject achieved DAL response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. DAL response may be defined as reduction from baseline in disease activity level by at least one level in at least one clinESSDAI or ESSDAI domain (e.g., biological, hematological, cutaneous, constitutional, lymphadenopathy and lymphoma, and glandular). By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve DAL response within 48 weeks of initiation of said administering. In some embodiments, the subject achieved CRESS response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.CRESS response may be defined as a response in 3 or more of the 5 CRESS categories (systemic disease activity, patient reported symptoms, tear gland function, salivary gland function, and serological activity) as assessed by the appropriate tests described herein (clinESSDAI, ESSPRI, Schirmer’s test or ocular staining score, unstimulated whole salivary flow or salivary gland ultrasonography, and rheumatoid factor or immunoglobin G level, respectively). By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve CRESS response within 48 weeks of initiation of said administering.

[0118] In some embodiments, by administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject has an improvement in each of the Sjogren’s symptoms, wherein the Sjogren’s symptoms comprise: fatigue, eye dryness, mouth dryness joint pain, and vaginal dryness. By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering from Sjogren’s disease, the subject may have an improvement in at least one of the Sjogren’s symptoms, wherein the Sjogren’s symptoms comprise: fatigue, eye dryness, mouth dryness, joint pain, and vaginal dryness.

[0119] In some embodiments, by administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject achieves an improvement in tear production by 5, 10, 15, 20, 25, 30, or 35 mm from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. In some embodiments, the tear production is measured by the Schirmer’s test. By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve an improvement in tear production by 5 mm from baseline within 48 weeks of initiation of said administering.

[0120] In some embodiments, by administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject achieves an improvement in basal saliva production by 0.02, 0.05, 0.08, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1 mL / min from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. In some embodiments, the basal saliva production is measured by the Unstimulated Salivary Flow Test. By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve an improvement in basal saliva production by 0.02 mL / min from baseline within 48 weeks of initiation of said administering.

[0121] In some embodiments, by administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject achieves a reduction in keratoconjunctivitis sicca (KCS) by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. In some embodiments, the KCS is measured by ocular surface staining (OSS). By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve a reduction in keratoconjunctivitis sicca (KCS) by 1 from baseline within 48 weeks of initiation of said administering.

[0122] In some embodiments, by administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject has a reduced need for glucocorticoid treatment from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve a reduced need for glucocorticoid treatment from baseline within 48 weeks of initiation of said administering.

[0123] In some embodiments, the administering of the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 0.8, more than 1, more than 1.2, more than 1.4, more than 1.6, more than 1.8, more than 2, more than 2.2, more than 2.4, more than 2.6, more than 2.8, more than 3, more than 3.2, more than 3.4, more than 3.6, more than 3.8, more than 4, more than 4.2, more than 4.4, more than 4.6, more than 4.8, more than 5, more than 5.2, more than 5.4, more than 5.6, more than 5.8, or more than 6 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve a decrease in DAS28-CRP by more than 0.8 from baseline within 48 weeks of initiation of said administering.

[0124] In some embodiments, the administering of the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease provides the subject an improvement in health- related quality of life (HRQol) from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. In some embodiments, the HRQol is measured by the 36-item Short Form Health Survey Questionnaire (SF-36) score. By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve an improvementin health-related quality of life (HRQol) from baseline within 48 weeks of initiation of said administering.

[0125] In some embodiments, the administering of the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease provides a clinical benefit as measured by the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) score in the subject by more than 5, 10, 15, 20, 25, 30, 35, or 40 points from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. In some embodiments, the administering of the anti- FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease provides a clinical benefit as measured by an increase in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) score in the subject by more than 5, 10, 15, 20, 25, 30, 35, or 40 points from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. By administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve an increase in the Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-Fatigue) score by more than 5 from baseline within 48 weeks of initiation of said administering.

[0126] In some embodiments, by administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject achieves a SSRI response greater than or equal to a 20% or 30% improvement from baseline in at least two or three of five domains of the SSRI response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering. In some embodiments, the five domains comprise fatigue, oral dryness, ocular dryness, unstimulated whole salivary flow, and erythrocyte sedimentation rate. By administering the anti- FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject may achieve a SSRI response greater than or equal to a 20% improvement from baseline in at least two or three of five domains of the SSRI response within 48 weeks of initiation of said administering.

[0127] In some embodiments, the subject is treated with an oral glucocorticoid. In some embodiments, the subject is not treated with an oral glucocorticoid. In some embodiments, the subject is treated with a non-biologic immunomodulator. In some embodiments, the subject is not treated with an oral glucocorticoid. In some embodiments, the subject is treated with anonsteroidal anti-inflammatory drug (NSAID). In some embodiments, the subject is not treated with a nonsteroidal anti-inflammatory drug (NSAID).

[0128] In some embodiments, by administering the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the subject has a reduction in autoantibodies in the blood. In some embodiments, the autoantibodies are selected from the group consisting of: anti-La (SSB) autoantibodies, anti- Smith, antinuclear antibodies (ANA), anti-phospholipid antibodies, anti- dsDNA antibodies, anti-nRNP (ribonucleoproteins) antibodies, anti-rheumatoid factor antibodies, anti-Ro60 (SSA) autoantibodies, and anti-Ro52 autoantibodies.

[0129] As used herein, the phrase “does not significantly increase” when used in reference to levels (measurements) of albumin means that any increase is less than 20% as compared to the level(s) prior (baseline) to the administration of the antibody or compositions provided for herein. In some embodiments, the administering of the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease does not significantly increase the level of albumin in the subject compared with baseline. In some embodiments, the increase is less than 20%. In some embodiments, the increase is no greater than about 20%, about 19%, about 18%, about 17%, about 16%, about 15%, about 14%, about 13%, about 12%, about 11%, about 10%, about 9%, about 8%, about 7%, about 6%, about 5%, about 4%, about 3%, about 2%, or about 1%. As used herein, a less than 10% increase may be categorized as “not significantly increase.”

[0130] The phrase “does not significantly increase” when used in reference to levels (measurements) of serum total cholesterol means that there is no increase in lipid-lowering therapy.

[0131] As used herein, the term “change” in reference to a baseline refers to a subject having an improvement as compared to that subject’s conditions, scores, symptoms, and the like prior to being treated with the anti-FcRn antibodies as provided for herein.

[0132] ‘Baseline” refers to a subject prior to being treated with a therapeutic, such as the anti-FcRn antibodies, including those provided for herein.

[0133] In some embodiments, nipocalimab is administered to a subject with a baseline IgG level of >8 g / L, >9 g / L, >10 g / L, >11 g / L, >12 g / L, >13 g / L, >14 g / L, or >15 g / L. In someembodiments, nipocalimab is administered to a subject with a baseline IgG level of >10 g / L. In some embodiments, nipocalimab is administered to a subject with a baseline IgG level of >11 g / L. In some embodiments, nipocalimab is administered to a subject with a baseline IgG level of >12 g / L. In some embodiments, nipocalimab is administered to a subject with a baseline IgG level of >13 g / L.

[0134] As used herein, the phrase “does not significantly decrease” when used in reference to levels (measurements) of albumin or serum total cholesterol means that any decrease is less than 10% as compared to the level(s) prior (baseline) to the administration of the antibody or compositions provided for herein. In some embodiments, the administering of the anti-FcRn agent (e.g., nipocalimab) to a subject suffering Sjogren’s disease, the administration does not significantly decrease level of albumin in the subject compared with baseline. In some embodiments, the decrease is less than 10%, or 5%. In some embodiments, the decrease is no greater than about 10%, about 9%, about 8%, about 7%, about 6%, about 5%, about 4%, about 3%, about 2%, or about 1%. As used herein, a less than 10% reduction may be categorized as “not significantly decrease”.

[0135] Efficacy Assessments: In some embodiments, the below evaluations are performed to evaluate the efficacy, safety and tolerability of nipocalimab in participants > 18 years of age with moderate to severe Sjogren’s Syndrome Disease as disclosed in Examples 1-3 below.

[0136] ClinES SD AI / ES SD Al : The ClinESSDAI is a validated tool used in clinical studies to measure the systemic disease activity in patients with SjD. The ClinESSDAI includes 11 domains divided into 3-4 activity levels, where zero represents no activity and low, medium, and high scores can vary in numerical value depending on the domain. A MCII in ClinESSDAI is defined as a decrease of at least 3 points in the composite ClinESSDAI score for the overall SjD population and a decrease of at least 4 points in the population of patients having at least moderate activity (ESSDAI>5). The ESSDAI is a disease activity index from which the ClinESSDAI was derived. The ESSDAI differs from ClinESSDAI by inclusion of the biological domain, which includes B-cell biomarkers, such as, elevated gamma-globulin or IgG serum levels, low complement levels, the presence of cryoglobulinaemia new onset low serum IgG levels, and / or of a monoclonal gammopathy. Exclusion of the biological domain in the ESSDAIthrough use of the ClinESSDAI is appropriate in circumstances involving a therapeutic intervention that targets the B cell-IgG axis, such as nipocalimab, which might result in collinearity between biomarkers and laboratory-based disease outcome measures, or with composite disease measures that include such laboratory values in the disease activity scoring, which introduces substantial mechanistic bias into the ESSDAI for agents such as nipocalimab. The Biological Domain components will include blinded lab values and will be determined separately from other ClinESSDAI domains and blinded after the Week 0 study visit.

[0137] To determine the activity level of some ClinESSDAI domains (eg, pulmonary and muscular domains), procedures are recommended. These tests include (but are not limited to) chest X-ray, HRCT, PFT, EMG, renal, muscular, or cutaneous biopsies, muscular or brain MRI, and NCS. If SjD signs or symptoms warrant any of these tests, they should be performed as a minimum during screening to assess the baseline ClinESSDAI score and repeated at Week 48 to assess the ClinESSDAI score at the end of the placebo-controlled double-blind period. In addition, if a participant develops SjD signs or symptoms during the placebo-controlled doubleblind period that warrants any of above-mentioned tests or procedures, additional testing at Week 48 is also recommended.

[0138] Joint Count Assessment: To be considered as exhibiting SjD activity, an affected joint must be tender and demonstrate at least 1 additional sign of inflammation (eg, observed swelling such as edema or effusion) on physical examination as determined by the joint assessor. Each of 28 joints will be evaluated for SjD activity, observed as tenderness and swelling due to inflammation.

[0139] Schirmer’s Test: The Schirmer’s test determines whether a SjD participant produces enough tears to keep their eyes moist and healthy. To perform this non-invasive test, a paper filter strip is placed inside the lateral corner of the lower eyelids, which are gently held closed for 5 minutes without the use of anesthesia. To reduce variability in the test outcome, eyelids should not be touched unnecessarily prior testing, and the paper filter strips should be carefully placed to prevent reactive tearing upon placement as much as possible. The Schirmer strips should be bent, and the folded end placed carefully over the lower lid margin at the junction of the middle and outer thirds. The Schirmer’s test should be done in a room with dimmed lights at approximatelythe same time at each visit for a given participant (± 1 hour). The amount of wetting (moisture) on the paper reflects the relative level of tear production and determines the severity of dry eye. A normal level of tear production is considered to be >10 millimeters (mm) of tears on the paper.

[0140] Salivary Flow Test: The unstimulated and stimulated whole salivary flow tests are relatively simple tests that assess basal saliva production. Some residual salivary function (defined as any detectable salivary flow assessed using stimulated salivary flow test) is required for inclusion in the study and will be assessed at screening and randomization. The salivary flow measurements are carried out over a period of 2 times 5 minutes, as recommended. The test should be carried out at approximately the same time at each visit, preferably in the morning hours after at least a 90-minute fasting period. This includes refraining from chewing gum or hard candies / lozenges, use of artificial saliva, smoking or any other oral to start of the test. Participants may use (but not swallow) water to moisturize their mouth during this period if deemed necessary. For the unstimulated salivary flow test, the collection tube will be preweighted prior to the test. The participant should be seated with their eyes open, and their heads tilted forward and asked to swallow their saliva once or expectorate before the start of the test. After starting the test, the participant will pool saliva in the floor of the mouth for 1 minute and then spit into the pre- weighed tube. This step is repeated 4 times for a total collection time of 5 minutes. The collection tube is re-weighed, and the volume of saliva is calculated using the specific gravity for water (1 g / mL).

[0141] The stimulated salivary flow test should be performed directly after the unstimulated salivary flow test and participants are allowed to rest for 5 minutes in between tests. Prior to the test, a piece of paraffin wax gum will be placed in a collection tube and pre-weighted. The participant should be seated with their eyes open, and their head tilted forward and asked to swallow their saliva once or expectorate before the start of the test. The participants will chew on the paraffin wax gum according to the pace of a metronome (about 70 strokes per minute)for 1 minute and then spit into the pre-weighed tube. This step is repeated 4 times for a total collection time of 5 minutes. After 5 minutes, the participant spits the remaining saliva and the paraffin wax gum into the collection tube is re-weighed, and the volume of saliva is calculated using the specific gravity for water (1 g / mL).

[0142] The flow rate for normal, unstimulated and stimulated saliva is 0.25 to 0.4 mL / minute and 1.0 to 3.0 mL / minute, respectively. A resting flow rate between 0.1 and 0.25 mL / min (unstimulated) and 0.7 and 1.0 mL / min (stimulated) is considered low and <0.1 (unstimulated) and <0.7 mL / min (stimulated) is considered very low.

[0143] PhGA: The PhGA independent of participants’ assessment is recorded on a VAS with responses ranging from 0 to 100 mm, with the anchors “No SjD Activity” (0) at one end of the scale and “Extremely Active SjD” (100 mm) at the opposite end of the scale. Disease activity can range from 0 representing no disease activity, 100 mm representing the most extremely active disease. The baseline measurement for the PhGA is defined as the closest measurement taken prior to the initiation of the Week 0 administration. To score the PhGA, the investigator should be blinded to all the PRO assessments for a given participant from the same day the PhGA is performed, but the investigator should review the PhGA completed by the investigator for that participant on the prior study visit. No worsening in PhGA defined as no significant deterioration (<10% increase from baseline) using a VAS.

[0144] CRESS: The CRESS is a composite index that consists of 5 items (systemic disease activity, patient-reported symptoms, salivary gland function, tear gland function, and serological activity) designed to assess treatment efficacy in patients with SjD. Assessments of these items include: ClinESSDAI, ESSPRI, Schirmer’s test, unstimulated salivary flow, and RF or IgG level.

[0145] STAR: The STAR composite disease activity score assesses disease features of SjD and is designed to be an efficacy end point in randomized clinical trials. The candidate STAR includes 5 domains (systemic activity, patient reported outcome, lachrymal gland function, salivary gland function, and biological), each with a different weighting. Assessments of these domains (with weighting in parentheses) include: ClinESSDAI (3), ESSPRI (3), Schirmer’s test (1), unstimulated salivary flow (1), and serum IgG level or RF (1). A candidate STAR response is defined as a composite STAR score of >5 points. Other thresholds for defining STAR response will also be analyzed, as appropriate.

[0146] DAS28-CRP: The DAS28-CRP is a composite index composed of 4 components including the number of swollen joints, the number of tender joints, the PtGA and CRP and is an important and validated outcome measure of RA disease activity. DAS28-CRP has also beenused in other autoimmune diseases, including SjD, and was considered a useful tool to evaluate the effect of therapies on articular involvement in patients with SjD.

[0147] Patient-Reported Outcomes: The PRO instruments will be provided in the local language in accordance with local guidelines.

[0148] The PRO instrument must be available for regulators and for IRB / ERC submissions, therefore the PRO instrument or screen shots need to be attached to the protocol or provided in a companion manual with the instruments that will be submitted with the protocol. The PRO and AE data will not be reconciled with one another.

[0149] Sjogren’s Symptoms: For assessment of Sjogren’s Symptoms, participants will be asked to report the worst severity of their ocular, oral, and vaginal dryness and joint pain over the past 24 hours on a 0 to 10 NRS, with the left anchor indicating “No [specific symptom]” and the right anchor, “Severe [specific symptom]”. The items are scored individually, with higher scores reflecting greater symptom severity.

[0150] ESSPRI: The ESSPRI is a patient- reported assessment of the severity of dryness, fatigue, and pain associated with primary Sjogren’s Syndrome. Participants are asked to rate the severity of dryness, fatigue, and pain over the past 2 weeks on an NRS, ranging from 0 “No symptoms (dryness, fatigue or pain)” to 10 “maximal imaginable (dryness, fatigue, pain)”. A global score, calculated as the mean of the 3 domain scores, ranges from 0 to 10, with higher scores reflecting greater (worse) symptom severity. Measurement properties, evaluated in a sample of patients with SjD (n= 395), were found to be adequate. A threshold for a minimum clinically important improvement was found to be a reduction of 1 point on the 0-10 NRS or 15% from baseline.

[0151] FACIT-Fatigue: The FACIT-Fatigue version 4.0 is a 13-item questionnaire that assesses patient-reported fatigue and its impact upon daily activities and function over the past 7 days. Participants will be asked to answer each question using a 5-point Likert-type scale (0=Not at all; 1=A little bit; 2=Somewhat; 3=Quite a bit; and 4=Very much). The interpretation of FACIT-Fatigue score is such that a higher score indicates less fatigue, with a range of possiblescores of 0-52, with 0 being the worst possible score and 52 the best. The FACIT-Fatigue can generally be completed in 5 minutes.

[0152] PtGA: The PtGA is a single item that asks participants to rate the current status of their SjD on a 0-100 mm VAS, with responses ranging from 0 (Very well) to 100 (Very poor). The PtGA will be used to calculate the DAS28-CRP composite index.

[0153] EQ-5D-5L: The EQ-5D-5L Descriptive System is a self-administered, standardized measure of health status in a wide range of health conditions and treatments. It provides a descriptive profile and a single index value for health status that can be used in the clinical and economic evaluation of health care. The recall period for all items is “Today”. The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ-VAS. The EQ-5D descriptive system is comprised of 5 items across the following 5 dimensions: mobility, self-care, usual activities, pain / discomfort and anxiety / depression. The EQ-5D-5L uses a 5-point Likert response scale ranging from “No problems” to “Extreme problems”. The EQ-5D health states defined by the EQ-5D descriptive system can be converted into a single index value using country-specific value sets. The index value facilitates the calculation of quality-adjusted life years that are used to inform economic evaluations of health care interventions. The EQ-5D also includes a VAS (EQ VAS) that has end points labeled "best imaginable health state" and "worst imaginable health state" anchored at 100 and 0, respectively. Participants are asked to indicate how they rate their own health by indicating the point on the EQ VAS which best represents their own health on that day. The EQ-5D-5L can generally be completed in under 2 minutes.SF-36: The SF-36 version 2 is a participant self-administered, 36-item questionnaire measuring HRQoL. The recall period for all items is the past 4 weeks. The SF-36 version 2 Standard includes 8 domains that measure physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality social functioning, role limitations due to emotional problems and mental health. The 8 domains can be aggregated into 2 summary scales that reflect physical and mental health: a PCS and an MCS. Responses to all items are rated on a 3-, 5- or 6-point Likert scale. The SF-36 version 2 Standard can generally be completed in 5-10 minutes. These scales are scored from 0 to 100 with higher scores indicating better health. Another algorithm yields 2 summary scores, the PCS and MCS. These summary scores are alsoscaled with higher scores indicating better health. The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments.Embodiments:1. A composition comprising an anti-FcRn agent for use in treating Sjogren’s disease in a subject in need thereof, wherein the anti-FcRn agent is administered to the subject.2. The use of embodiment 1, wherein the anti-FcRn agent is administered every week, every two weeks, every three weeks, or monthly.3. The use of embodiment 1 or 2, wherein the anti-FcRn agent is nipocalimab, rozanolixizumab, batoclimab, IMVT-1402, efgartigimod, orilanolimab, SYNT002, ABY- 039, or DX-2507.4. The use of any one of the preceding embodiments, wherein the anti-FcRn agent is administered at a dose from about 5 mg / kg to about 45 mg / kg, about 5 mg / kg to about 15 mg / kg, about 15 mg / kg to about 45 mg / kg, or about 30 mg / kg to about 45 mg / kg based on the weight of the subject.5. The use of any one of the preceding embodiments, wherein the anti-FcRn agent is administered at a dose of about 5 mg / kg, about 15 mg / kg, about 30 mg / kg, or about 45 mg / kg based on the weight of the subject.6. The use of any one of the preceding embodiments, wherein the anti-FcRn agent is administered intravenously or subcutaneously.7. The use of any one of the preceding embodiments, wherein the anti-FcRn agent is an anti- FcRn antibody comprising:(a) a light chain, which comprises a CDRL1 comprising an amino acid sequence of SEQ ID NO: 3, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 4, and a CDR L3 comprising an amino acid sequence of SEQ ID NO: 5; and(b) a heavy chain, which comprises a CDR Hl comprising an amino acid sequence of SEQ IDNO: 6, a CDR H2 comprising an amino acid sequence of SEQ ID NO: 7, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 8.8. The use of embodiment 7, wherein (a) the light chain of the anti-FcRn antibody comprises a light chain variable region comprising an amino acid sequence of SEQ ID NO: 9; and (b) the heavy chain of the anti-FcRn antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 10.9. The use of embodiment 7 or 8, wherein (a) the light chain of the anti-FcRn antibody comprises an amino acid sequence of SEQ ID NO: 1; and (b) the heavy chain of the anti-FcRn antibody comprises an amino acid sequence of SEQ ID NO: 2.10. The use of any one of the preceding embodiments, wherein the anti-FcRn agent is nipocalimab.11. The use of any one of the preceding embodiments, wherein nipocalimab is administered every two weeks intravenously at 10-30 mg / kg based on the weight of the subject.12. The use of any one of the preceding embodiments, wherein nipocalimab is administered every two weeks intravenously at 15 mg / kg based on the weight of the subject.13. The use of any one of the preceding embodiments, wherein nipocalimab is administered every week subcutaneously at 200-1000 mg.14. The use of any one of the preceding embodiments, wherein nipocalimab is administered every week subcutaneously at 200-1000 mg.15. The use of any one of the preceding embodiments, wherein nipocalimab is administered every week subcutaneously at 230, 460, 690, or 920 mg.16. The use of any one of embodiments 13-15, wherein nipocalimab is administered via an auto injector.17. The use of any one of the preceding embodiments, wherein the administration of the anti- FcRn agent provides a clinical benefit as measured by a decrease in Clinical European LeagueAgainst Rheumatism Sjogren’s Syndrome Disease Activity Index (clinESSDAI) score in the subject by more than 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 from baseline within 12, 18,24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.18. The use of any one of the preceding embodiments, wherein the administration of the anti- FcRn agent provides a clinical benefit as measured by a decrease in Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (clinESSDAI) score in the subject by more than 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 from baseline within 24 weeks of initiation of said administering.19. The use of any one of the preceding embodiments, wherein the administration of the anti- FcRn agent provides a clinical benefit as measured by a decrease in European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ESSDAI) score in the subject by more than 3, 4, 5, , 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.20. The use of any one of the preceding embodiments, wherein the administration of the anti- FcRn agent provides a clinical benefit as measured by a decrease in the European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ESSDAI) score in the subject by more than 3, 4, 5, or 6 from baseline within 24 weeks of initiation of said administering.21. The use of any one of the preceding embodiments, wherein the administration of the anti- FcRn agent provides a clinical benefit as measured by a decrease in Physician’s Global Assessment of Disease Activity (PhGA) score in the subject by more than 10, 12, 14, 16, 18, 20,25, 27, 30, 33, 38, 43, 48, or 52 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.22. The use of any one of the preceding embodiments, wherein the administration of the anti- FcRn agent provides a clinical benefit as measured by a decrease in PhGA score in the subject by more than 33, 38, 43, 48, or 52 from baseline within 24 weeks of initiation of said administering.23. The use of any one of the preceding embodiments, wherein the subject achieved ESSDAI-3 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering.24. The use of any one of the preceding embodiments, wherein the subject achieved ESSDAI-4 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering.25. The use of any one of the preceding embodiments, wherein the subject achieved clinESSDAI-3 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering.26. The use of any one of the preceding embodiments, wherein the subject achieved clinESSDAI-4 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering.27. The use of any one of the preceding embodiments, wherein the subject achieved ESSPRI response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.28. The use of any one of the preceding embodiments, wherein the subject achieved STAR response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.29. The use of any one of the preceding embodiments, wherein the subject achieved DAL response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.30. The use of any one of the preceding embodiments, wherein the subject achieved CRESS response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.31. The use of any one of the preceding embodiments, wherein the subject has an improvement in each of the Sjogren’s symptoms, wherein the Sjogren’s symptoms comprise: fatigue, eye dryness, mouth dryness, joint pain, and vaginal dryness.32. The use of any one of the preceding embodiments, wherein the subject achieves an improvement in tear production by 5, 10, 15, 20, 25, 30, or 35 mm from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.33. The use of embodiment 32, wherein the tear production is measured by the Schirmer’s test.34. The use of any one of the preceding embodiments, wherein the subject achieves an improvement in basal saliva production by 0.02, 0.05, 0.08, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8,0.9, or 1 mL / min from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.35. The use of embodiment 34, wherein the basal saliva production is measured by the Unstimulated Salivary Flow Test.36. The use of any one of the preceding embodiments, wherein the subject achieves a reduction in keratoconjunctivitis sicca (KCS) by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.37. The use of embodiment 36, wherein the KCS is measured by the ocular surface staining (OSS).38. The use of any one of the preceding embodiments, wherein the subject has a reduced need for glucocorticoid treatment from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.39. The use of any one of the preceding embodiments, wherein the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 0.8, more than 1, more than 1.2, more than 1.4, more than 1.6, more than 1.8, more than 2, more than 2.2, more than 2.4, more than 2.6, more than 2.8, more than 3, more than 3.2, more than 3.4, more than 3.6, more than 3.8, more than 4, more than 4.2, more than 4.4, more than 4.6, more than 4.8, more than 5, more than 5.2, more than 5.4, more than 5.6, more than 5.8, or more than 6 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.40. The use of any one of the preceding embodiments, wherein the method provides the subject an improvement in health-related quality of life (HRQol) from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.41. The use of embodiment 40, wherein the HRQol is measured by the 36-item Short Form Health Survey Questionnaire (SF-36) score.42. The use of any one of the preceding embodiments, wherein the method provides a clinical benefit as measured by the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT- Fatigue) score in the subject by more than 5, 10, 15, 20, 25, 30, 35, or 40 points from baselinewithin 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.43. The use of any one of the preceding embodiments, wherein the subject achieves a Sjogren’s Syndrome Responder Index (SSRI) response greater than or equal to a 20% or 30% improvement from baseline in at least two or three of five domains of the SSRI response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.44. The use of embodiment 43, wherein the five domains comprise fatigue, oral dryness, ocular dryness, unstimulated whole salivary flow, and erythrocyte sedimentation rate.45. The use of any one of the preceding embodiments, wherein the subject has a reduction in autoantibodies in the blood.46. The use of embodiment 45, wherein the autoantibodies are selected from the group consisting of: anti-La (SSB) autoantibodies, anti-Smith, antinuclear antibodies (ANA), anti-phospholipid antibodies, anti-dsDNA antibodies, anti-nRNP (ribonucleoproteins) antibodies, anti-rheumatoid factor antibodies, anti-Ro60 (SSA) autoantibodies, and anti-Ro52 autoantibodies.47. The use of any one of the preceding embodiments, wherein the administration does not significantly decrease level of albumin in the subject compared with baseline.48. The use of any one of the preceding embodiments, wherein the administration does not significantly increase the level of serum total cholesterol in the subject compared with baseline.49. A method of treating Sjogren's disease in a subject in need thereof, the method comprising administering an anti-FcRn antibody to the subject, wherein the anti-FcRn antibody comprises:(a) a light chain, which comprises a CDR LI comprising an amino acid sequence of SEQ ID NO: 3, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 4, and a CDR L3 comprising an amino acid sequence of SEQ ID NO: 5; and(b) a heavy chain, which comprises a CDR Hl comprising an amino acid sequence of SEQ ID NO: 6, a CDR H2 comprising an amino acid sequence of SEQ ID NO: 7, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 8; and wherein the anti-FcRn antibody is administered every week subcutaneously at 460 mg.50. A method of treating Sjogren's disease in a subject in need thereof, the method comprising administering nipocalimab to the subject, wherein the nipocalimab is administered every week subcutaneously at 460 mg.51. A composition comprising an anti-FcRn agent for use in treating Sjogren's disease in a subject in need thereof, wherein the anti-FcRn antibody comprises:(a) a light chain, which comprises a CDR LI comprising an amino acid sequence of SEQ ID NO: 3, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 4, and a CDR L3 comprising an amino acid sequence of SEQ ID NO: 5; and(b) a heavy chain, which comprises a CDR Hl comprising an amino acid sequence of SEQ ID NO: 6, a CDR H2 comprising an amino acid sequence of SEQ ID NO: 7, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 8; and wherein the anti-FcRn antibody is administered to the subject every week subcutaneously at 460 mg.52. A composition comprising nipocalimab for use in treating Sjogren's disease in a subject in need thereof, wherein the nipocalimab is administered to the subject every week subcutaneously at 460 mg.ExamplesExample 1: A Randomized, Placebo-controlled, Double-blind, Multicenter Study to Assess the Efficacy and Safety of Nipocalimab in Adults with Primary Sjogren’s Syndrome (pSS)

[0154] This is a Phase 2, randomized, placebo-controlled, parallel, multicenter, double-blind interventional study in men and women between the ages of 18 to 75 years, inclusive, with active, autoantibody-positive pSS (i.e., Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index [ClinESSDAI] score >6) who were seropositive for anti -Ro IgG autoantibodies. Participants were randomized 1: 1: 1 to intravenous nipocalimab 5 mg / kg or 15 mg / kg or placebo every 2 weeks for 22 weeks. The primary end point was change from baseline in ClinESSDAI score at Week 24.

[0155] A placebo comparator (in addition to standard-of-care background therapy) was used in this study through Week 22 to allow for blinded, placebo-controlled evaluation of the efficacy and safety of nipocalimab in participants with pSS.

[0156] At selected sites, an optional labial salivary gland biopsy sub study was conducted to evaluate the molecular and histologic changes from baseline in participants with pSS. In addition, ocular surface staining (OSS) was conducted at selected sites to assess the change in keratoconjunctivitis sicca (KCS) from baseline in participants with pSS.

[0157] Clinical and laboratory evidence of disease activity was evaluated and assessed by a committee of the sponsor or designee to verify that participants were meeting inclusion / exclusion criteria and to ensure data quality and consistency.

[0158] Efficacy, safety, PK, immunogenicity, PD, biomarkers, and digital health measures were assessed. Pharmacogenomic blood samples were collected from participants who consent to the collection of these samples (where local regulations permit).

[0159] The primary efficacy analysis was performed after all participants have completed Week 24 efficacy assessments (or discontinued). Every reasonable effort was made to keep concomitant medications stable. Beginning at the screening visit, all concomitant therapies and all changes in concomitant therapies were recorded throughout the study.

[0160] Key safety assessments include adverse event (AE)s, serious adverse event (SAE)s, adverse events of special interest (AESI), clinical laboratory parameters (hematology, chemistry, including lipid panel, and urinalysis), vital signs, systolic and diastolic blood pressures over time, and Aes temporally associated with infusion, including hypersensitivity reactions.

[0161] A diagram of the study design is provided in FIG. 1.

[0162] A target of approximately 150 participants were planned to be enrolled in this study.Participants would be randomly assigned into 3 treatment groups in a 1: 1: 1 ratio to receive intravenous (IV) nipocalimab 5 mg / kg or 15 mg / kg or placebo every 2 weeks through Week 22 in addition to stable, protocol-permitted, standard-of-care therapy.

[0163] The total duration of the study would be up to 36 weeks and consists of 3 study periods: a 6- week screening period, a 24- week double blind treatment period, and a 6- week follow-up period (8 weeks post last study intervention administration).• Group 1: placebo IV every 2 weeks (q2w)Participants will receive placebo IV q2w through Week 22.• Group 2: nipocalimab 5 mg / kg IV q2wParticipants will receive nipocalimab 5 mg / kg IV q2w through Week 22.• Group 3: nipocalimab 15 mg / kg IV q2wParticipants will receive nipocalimab 15 mg / kg IV q2w through Week 22.EFFICACY EVALUATIONS

[0164] Investigator assessments and patient-reported outcomes (PROs) of efficacy include the following:• ESSDAI / ClinESSDAI• Joint count assessment• Schirmer’s Test• Ocular Staining Score (OSS)• Unstimulated Salivary Flow Test• Physician’s Global Assessment of Disease Activity (PhGA)• PRO measures to assess: ESSPRI, FACIT-Fatigue, Sjogren’s Symptoms (SS), SF-36 v2, Hospital Anxiety and Depression Scale (HADS), WLQ, PtGAPHARMACOKINETIC EVALUATIONS

[0165] Serum samples were used to evaluate the PK of nipocalimab.IMMUNOGENICITY EVALUATIONS

[0166] Antibodies to nipocalimab were evaluated in serum samples collected from all participants. Additionally, serum samples were collected at the final visit from participants who discontinued study intervention or were withdrawn from the study.PHARMACODYNAMIC AND BIOMARKER EVALUATIONS

[0167] Pharmacodynamic markers were evaluated using blood, saliva and tear samples collected at visits as planned. Biomarker assessments were made to examine the biological response to treatment and to identify biomarkers that are relevant to nipocalimab treatment response and / or pSS, where local regulations permit. Assessments include the evaluation of relevant biomarkers in serum, plasma, whole blood, saliva, tears, peripheral blood mononuclear cells, and salivary gland biopsy samples (optional) collected as planned where local regulations permit.PHARMACOGENOMIC (DNA) EVALUATIONS

[0168] Participation in pharmacogenomic research is optional. A pharmacogenomic blood sample was collected from participants who consent separately to this component of the study to allow for pharmacogenomic research, where local regulations permit.SAFETY EVALUATIONS

[0169] Key safety assessments include Aes, SAEs, AESI, laboratory parameters (hematology and chemistry, including lipid panel, and urinalysis), vital signs, systolic and diastolic blood pressures over time, and Aes temporally associated with infusion, including hypersensitivity reactions.STATISTICAL METHODS

[0170] Statistical Analyses

[0171] General Considerations

[0172] Simple descriptive summary statistics, such as n, mean, SD, median, IQ range, minimum, and maximum for continuous variables, and counts and percentages for discrete variables were used to summarize most data. In addition, graphical data displays (eg, line plots) and participant listings might also be used to summarize / present the data.

[0173] The chi-squared test or Cochran-Mantel-Haenszel (CMH) test stratified by stratification factors was used to compare categorical variables such as the proportion of participants responding to treatment, unless otherwise stated. In general, ANOVA with the stratification factors as independent variables was used for analyzing continuous variables, unless otherwise stated. All statistical tests were performed at a=0.10 (2-sided).

[0174] Efficacy analyses and study population summaries were based on the Full Analysis Set, which was defined as all randomized participants who received at least one dose of study intervention, unless otherwise stated. Participants included in the efficacy analyses were summarized according to their assigned intervention group regardless of whether or not they received the assigned intervention.

[0175] Safety, PK and immunogenicity analyses were based on the Safety Analysis Set, PK Analysis Set, and Immunogenicity Analysis Set, respectively.

[0176] The objectives and end points of the study are listed in Table 1.Table 1.

[0177] The primary end point is change from baseline in clinESSDAI score at Week 24.The primary estimand is defined as follows:• Treatment:- Nipocalimab 5 mg / kg q2w in addition to standard of care through Week 22- Nipocalimab 15 mg / kg q2w in addition to standard of care through Week 22- Placebo q2w in addition to standard of care through Week 22Standard of care includes symptomatic medications / procedures (including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues), and / or one immunomodulator (Table 22A), with or without low-dose glucocorticosteroids (<10 mg / day prednisone equivalent, Table 22B).• Population: Participants with pSS• Variable: Change from baseline in clinESSDAI at Week 24• Inter current Events:- Participants who experienced at least one of the following events will be considered Treatment Failures. o Discontinuation of study intervention prior to Week 24 for any reason o Initiation or increase medications for pSS- (2) Discontinuation of study intervention due to Coronavirus Disease 2019 (COVID- 19) pandemic situation or confirmed COVID 19 infectionFor both types of intercurrent events, hypothetical strategy which envisages that participants would not have these events will be used. Data from the time an intercurrent event occurred and onward will not be utilized.• Population-level Summary: Difference in the means of the variable between treatment armsThe primary analysis used MMRM with change from baseline in clinESSDAI at Week 24 as the dependent variable and baseline clinESSDAI, treatment, study visit, treatment by study visit interaction and stratification factors for randomization as independent variables. No missing data imputation would be performed explicitly. Comparisons were carried out at a 2-sided 0.1 level of significance to evaluate the treatment difference between individual nipocalimab arms and placebo.

[0178] Given the hypothesis-generating nature of the study, no multiplicity control was planned.

[0179] The following sensitivity analyses would also performed:• Same analysis as the primary analysis but assume the participants with intercurrent event(s) to have 0 change from baseline. This analysis is corresponding to a supplementary estimand which is the same as the primary estimand but employs a composite strategy for the first type of intercurrent events (ie, Treatment Failures) assuming the worst outcome.• Same analysis as the primary analysis but assume both types of intercurrent events have no impact on the treatment effect. Data points collected after intercurrent events would be included in the analysis. This analysis is corresponding to a treatment policy estimand.

[0180] The following major secondary end points were summarized by treatment group. For between group comparisons, p- values were reported. However, no multiplicity control was planned.• Change from baseline in ESSPRI score at Week 24• Improvement of >4 points from baseline in ESSDAI (minimal clinically important improvement) at Week 24Improvement of >4 points from baseline in clinESSDAI score (minimal clinically important improvement) at Week 24ESSPRI response defined as a decrease of > one point or a decrease of >15% from baseline (minimal clinically important improvement) at Week 24• Disease response according to the STAR composite score at Week 24• Improvement in disease activity level in at least one clinESSDAI or ESSDAI domain (biological, hematological, cutaneous, constitutional, lymphadenopathy and lymphoma, and glandular) at Week 24• Improvement from baseline in >3 of 5 Composite of Relevant End points for Sjogren’s Syndrome (CRESS) categories at Week 24Efficacy Assessments

[0181] All efficacy evaluations and clinROs, including joint assessments, were performed consistently by the same study investigator or sub investigator at every visit for each individual participant to achieve comparable measures over time. The investigator or investigator- designated assessor was a rheumatologist or physician with other equivalent subspecialty training (eg, clinical allergy / immunology) and expertise in the clinical evaluation and management of pSS and other rheumatologic diseases (eg, SLE, RA, etc).

[0182] Clinical EULAR Sjogren’s Syndrome Disease Activity Index (clinESSDAI) is a validated tool used in clinical studies to measure the systemic disease activity in patients with Sjogren’s syndrome. The clinESSDAI includes 11 domains divided into 3-4 activity levels, where zero represents no activity and low, medium, and high scores can vary in numerical value depending on the domain. ClinESSDAI excludes the IgG and related biomarker criteria in the ESSDAI biological domain. A minimal clinically important improvement in clinESSDAI is defined as a decrease of at least 3 or 4 points in the composite clinESSDAI score. The ESSDAI is a disease activity index from which the clinESSDAI was derived. The ESSDAI differs from clinESSDAI by inclusion of the biological domain, which includes B-cell biomarkers, such as, elevated gamma globulin or IgG serum levels, low complement levels, the presence of cryoglobulinaemia new onset low serum IgG levels, and / or of a monoclonal gammopathy. Exclusion of the biological domain in the ESSDAI through use of the clinESSDAI is appropriatein circumstances involving a therapeutic intervention that targets the B cell-IgG axis, such as nipocalimab, which might result in collinearity between biomarkers and laboratory-based disease outcome measures, or with composite disease measures that include such laboratory values in the disease activity scoring. The Biological Domain components would include blinded lab values and would be determined separately from other ClinESSDAI domains and blinded after the Week 0 study visit.

[0183] Joint assessments were performed at scheduled visits. To be considered as exhibiting pSS activity, an affected joint must be tender and demonstrate at least 1 additional sign of inflammation (eg, observed swelling such as edema or effusion) on physical examination as determined by the joint assessor. Each of 28 joints were evaluated for pSS activity, observed as tenderness and swelling due to inflammation.

[0184] The Schirmer’s test determines whether a pSS participant produces enough tears to keep their eyes moist and healthy. To perform this non-invasive test, a piece of filter paper with millimeter (mm) marks on it is placed inside the lateral corner of the lower eyelids, which are gently held closed for 5 minutes without the use of anesthesia. The length of the strip that is wetted in 5 minutes is the number reported. The Schirmer’s test was done at approximately the same time at each visit for a given participant. The amount of wetting (moisture) on the paper reflects the relative level of tear production and determines the severity of dry eye. A normal level of tear production is considered to be >10 millimeters (mm) of tears on the paper. Requirements for obtaining from topical ophthalmic agents are outlined in Table 22A. The Schirmer’s test should precede the OSS evaluation if they occur on the same day.

[0185] The unstimulated whole salivary flow rate (unstimulated salivary flow test) is a relatively simple test that assesses basal saliva production. Some residual salivary function (defined as unstimulated salivary flow rate >0.01 mL / min) was required for inclusion in the study and would assessed at screening and randomization. The unstimulated salivary flow measurement was carried out over a period of 15 minutes, as recommended (Navazesh M et al., Measuring salivary flow Challenges and opportunities. The Journal of the American Dental Association, 2008. D01:https: / / doi.org / 10.14219 / jada.archive.2008.0353). The test was carried out at approximately the same time at each visit, preferably in the morning hours after at least a 2hour fasting period (includes refraining from chewing gum or hard candies / lozenges, use of artificial saliva, drinking water or any other oral) to start of the test. Participants should be asked to swallow their saliva once or expectorate before the start of the test and then to spit into a preweighed tube for 15 minutes. The collection tube is re-weighed, and the volume of saliva is calculated using the specific gravity for water (1 g / mL). The flow rate for normal, unstimulated saliva is 0.25 to 0.4 mL / minute. A resting flow rate between 0.1 and 0.25 mL / min is considered low and < 0.1 is considered very low.

[0186] The SICCA ocular staining score or ocular surface staining (OSS) is a quantitative, simplified method of grading keratoconjunctivitis sicca-related changes (KCS) ocular damage in patients with or without pSS as described by Whitcher JP et al., A simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjogren’s Syndrome International Registry. Am J Ophthalmol. 2010;149(3):405-415. Utilizing Lissamine Green dye for the conjunctivae and fluorescein for the corneas, ophthalmologists or optometrists, experienced in the evaluation and management of KCS use a slit lamp to grade the corneas and conjunctivae of each eye based on the type, severity, and location of dye staining. The OSS gives equal numerical weight to corneal and conjunctival involvement and is easily applied in clinical practice. Each eye receives its own numeric score ranging from 0 to 12. This procedure will only be performed on participants at selected sites and may be done <5 days in advance of study visit.

[0187] Physician’s Global Assessment of Disease Activity (PhGA) (Divi C et al., Development of the Sjogren’s Syndrome Responder Index, a data-driven composite end point for assessing treatment efficacy, Rheumatology. 2015;54(9):1699-1708) independent of participants’ assessment is recorded on a visual analog scale (VAS) with responses ranging from 0 to 100 mm, with the anchors “No Sjogren’s Syndrome Activity” (0) at one end of the scale and “Extremely Active Sjogren’s Syndrome” (100 mm) at the opposite end of the scale. Disease activity can range from 0 representing no disease activity, 100 mm representing the most extremely active disease. The baseline measurement for the PhGA is defined as the closest measurement taken prior to the initiation of the Week 0 administration. To score the PhGA, the investigator should be blinded to all the PRO assessments for a given participant from the same day the PhGA is performed, but the investigator should review the PhGA completed by theinvestigator for that participant on the prior study visit. No worsening in PhGA defined as no significant deterioration (<10% increase from baseline) using a VAS (Divi 2015).

[0188] The Sjogren’s Syndrome Responder Index (SSRI) is a composite index capable of detecting therapeutic responses in patients with primary Sjogren’s syndrome. The five outcome measures in the SSRI center on objective and subjective sicca symptoms, including fatigue score, oral dryness score, ocular dryness score, unstimulated whole saliva flow, and erythrocyte sedimentation rate (ESR). An SSRI-20 response is defined as a >20% improvement in at least two of these five outcome measures.

[0189] Patient-reported Outcomes (PRO) instruments were provided in the local language in accordance with local guidelines. The PRO instrument were available for regulators and for IRB / ERC submissions, therefore the PRO instrument or screen shots were attached to the protocol or provided in a companion manual with the instruments that were submitted with the protocol. The PRO and AE data were not reconciled with one another.

[0190] The European League Against Rheumatism (EULAR) Sjogren’s Syndrome Patient- Reported Index (ESSPRI) is a patient-reported assessment of the severity of dryness, fatigue, and pain associated with primary Sjogren’s Syndrome (Seror R et al., EULAR Sjogren’s Syndrome Patient Reported Index (ESSPRI): development of a consensus patient index for primary Sjogren’s syndrome. Ann Rheum Dis. 2011;70(6):968-972). Patients were asked to rate the severity of dryness, fatigue and pain over the past 2 weeks on a numeric rating scale (NRS), ranging from 0 “No symptoms (dryness, fatigue or pain)” to 10 “maximal imaginable (dryness, fatigue, pain)”. A global score, calculated as the mean of the 3 domain scores, ranges from 0 to 10, with higher scores reflecting greater (worse) symptom severity. Measurement properties, evaluated in a sample of patients with pSS (n= 395), were found to be adequate (Seror R et al., Validation of EULAR primary Sjogren’s syndrome disease activity (ESSDAI) and patient indexes (ESSPRI). Ann Rheum Dis. 2015;74(5):859-866). A threshold for a minimum clinically important improvement was found to be a reduction of 1 point on the 0-10 NRS or 15% from baseline (Seror R et al., Defining disease activity states and clinically meaningful improvement in primary Sjogren’s syndrome with EULAR primary Sjogren’s syndrome disease activity (ESSDAI) and patient-reported indexes (ESSPRI). Ann Rheum Dis. 2016;75(2):382-389).

[0191] The Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-fatigue) version 4.0 is a 13 -item questionnaire formatted for participant self administration that assesses patient-reported fatigue and its impact upon daily activities and function over the past 7 days. Participants will be asked to answer each question using a 5-point Likert-type scale (0=Not at all; 1=A little bit; 2=Somewhat; 3=Quite a bit; and 4=Very much). The interpretation of FACIT- Fatigue score is such that a higher score indicates less fatigue, with a range of possible scores of 0-52, with 0 being the worst possible score and 52 the best. The FACIT Fatigue can generally be completed in 5 minutes (Celia D et al., Fatigue in cancer patients compared with fatigue in the general United States population. Cancer. 2002; 94(2):528-538; Lai JS et al., Validation of the functional assessment of chronic illness therapy-fatigue scale in patients with moderately to severely active systemic lupus erythematosus, participating in a clinical trial. J Rheumatol.2011;38(4):672-679; Yellen SB et al., Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. J Pain Sympt Manage. 1997;13;63-74).

[0192] For assessment of Sjogren’s symptoms, participants will be asked to report the worst severity of their ocular, oral, and vaginal dryness and joint pain over the past 7 days on a 0 to 10 numeric rating scale, with the left anchor indicating “No [specific symptom]” and the right anchor, “Severe [specific symptom]”. The items are scored individually, with higher scores reflecting greater symptom severity.

[0193] The Short Form Health Survey 36 Standard (SF-36) version 2 is a participant selfadministered, 36-item questionnaire measuring health-related quality of life (HRQoL). The recall period for all items is the past 4 weeks. The SF-36 version 2 Standard includes 8 domains that measure physical functioning, role limitations due to physical health problems, bodily pain, general health, vitality social functioning, role limitations due to emotional problems and mental health. The 8 domains can be aggregated into 2 summary scales that reflect physical and mental health: a physical component summary (PCS) and an mental component summary (MCS). Responses to all items are rated on a 3-, 5- or 6-point Likert scale. The SF-36 version 2 Standard can generally be completed in 5-10 minutes (Quality Metric Inc. User’s Manual for the SF-36v2 Health Survey. 3rdedition; 2011 : https: / / www.qualitymetric.com / health-surveys / the-sf-36v2- health- survey / . Accessed 11 March 2021).

[0194] These scales are scored from 0 to 100 with higher scores indicating better health. Another algorithm yields 2 summary scores, the PCS and MCS. These summary scores are also scaled with higher scores indicating better health (Ware J et al., “The SF-36 Health Survey: Development and Use in Mental Health Research and the IQOLA Project.” International Journal of Mental Health. 1994;23(2):49-73). The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, allowing comparison of relative burden of different diseases and the relative benefit of different treatments.

[0195] Hospital Anxiety and Depression Scale (HADS) is a 14-item instrument developed to detect states of anxiety and depression. The items are divided into 2 subscales: 1 for anxiety (HADS-A) and 1 for depression (HADS-D; Zigmond AS et al., The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983;67:361-370). Each subscale score ranges from 0 to 21. Scores >8 identify mild cases, scores 11 to 15 identify moderate cases, and scores >16 identify severe cases (Snaith RP. The Hospital Anxiety And Depression Scale. Health and Quality of Life Outcomes. 2003 Aug, 1 :29).

[0196] The Work Limitations Questionnaire (WLQ) is a 25-item self-report questionnaire that asks respondents to rate their level of difficulty or ability to perform specific job demands to assess health- related work productivity loss (Lerner D et al., The Work Limitations Questionnaire. Med Care 2001 Jan; 39(1): 72-85). The 25 items are aggregated into 4 scales: time management, physical demands, mental-interpersonal, and output. Scale scores range from 0 (limited none of the time) to 100 (limited all of the time) and represent the reported amount of time in the prior 2 weeks that respondents were limited on-the-job. Using an algorithm, WLQ scale scores can be converted into an estimate of productivity loss (or gain).

[0197] The Patient’s Global Assessment of Disease Activity (PtGA) is a single item that asks participants to rate the current status of their pSS on a 0-100 mm visual analog scale (VAS), with responses ranging from 0 (Very well) to 100 (Very poor). The PtGA would be used to calculate the DAS28 composite index.

[0198] Composite of relevant end points for Sjogren’s Syndrome (CRESS) is a composite index that consists of 5 items (systemic disease activity, patient reported symptoms, salivary gland function, tear gland function, and serological activity) designed to assess treatmentefficacy in patients with pSS. Assessments of these items include: clinESSDAI, ESSPRI, Schirmer’s test or ocular staining score, unstimulated whole salivary flow or salivary gland ultrasonography, and rheumatoid factor or immunoglobin G level. (Arends S et al., Composite of Relevant End points for Sjogren’s Syndrome (CRESS) [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https: / / acrabstracts.org / abstract / composite-of-relevant-end points-for-sjogrens- syndrome-cress / . Accessed March 22, 2021).

[0199] The Sjogren’s Tool for Assessing Response (STAR) composite disease activity score assesses disease features of pSS and is designed to be an efficacy end point in randomized clinical trials. The candidate STAR includes 5 domains (systemic activity, patient reported outcome, lachrymal gland function, salivary gland function, and biological), each with a different weighting. Assessments of these domains (with weighting in parentheses) include: clinESSDAI (3), ESSPRI (3), Schirmer’s test or ocular staining score (1), unstimulated whole salivary flow or ultrasound (1), and serum immunoglobin G level or rheumatoid factor (1). A candidate STAR response is defined as a composite STAR score of >5 points. Other thresholds for defining STAR response will also be analyzed, as appropriate. (Seror R et al., Development and preliminary validation of the Sjogren’s Tool for Assessing Response (STAR): a consensual composite score for assessing treatment effect in primary Sjogren’s syndrome. Ann Rheum Dis. 2022; 81.979- 989).

[0200] The DAS28-CRP is a statistically derived index combining tender joints (28 joints), swollen joints (28 joints), CRP, and PtGA of Disease Activity. The DAS28-CRP is a continuous parameter and is defined as follows:DAS28-CRP = 0.56 x SQRT(TEN28) + 0.28 x SQRT(SW28) + 0.36 x In (CRP+1) + 0.014 x GH + 0.96

[0201] The set of 28 joint count is based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) 1, MCP2, MCP3, MCP4, MCP5, proximal interphalangeal (PIP) 1, PIP2, PIP3, PIP4, PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. TEN28 is 28-joint count for tenderness. SQRT(TEN28) is square root of TEN28. SW28 is 28-joint count for swelling.SQRT(SW28) is square root of SW28. Ln (CRP+1) is natural logarithm of (CRP value [mg / L] + 1). GH is PtGA of Disease Activity on a VAS of 100 mm.

[0202] International Digit Symbol Substitution Test -Symptoms (IDSSTS) is a brief, commonly used, and universally understood cognitive function test that requires a participant to match symbols to numbers according to a key provided. The participant copies the symbol into spaces below a row of numbers. The number of correct symbols within the allowed time (3 minutes) constitutes the score.

[0203] The Detection (DET) test is a measure of psychomotor function and uses a well- validated simple reaction time paradigm with playing card stimuli. In this test, the playing cards all depict the same joker. The subject is asked to press the Yes key as soon as the card in the center of the screen turns face up. The software measures the speed and accuracy of each response. The duration of the test is 3 minutes.

[0204] The Identification (IDN) test is a measure of visual attention and uses a well- validated choice reaction time paradigm with playing card stimuli. In this test, the playing cards are all either red or black jokers. The subject is asked whether the card displayed in the center of the screen is red. The subject responds by pressing the Yes key when the joker card is red and No when it is black. The software measures the speed and accuracy of each response. The duration of the test is 3 minutes.Pharmacokinetic Analyses

[0205] Serum nipocalimab concentrations over time were summarized for each treatment group using descriptive statistics. Descriptive statistics were calculated at each sampling timepoint.

[0206] If sufficient data are available, a population PK analysis using a nonlinear mixed- effects modeling approach would be used to characterize the disposition characteristics of nipocalimab. Details were given in a population PK analysis plan, and the results of the population PK analysis would be presented in a separate technical report.Immunogenicity Analyses

[0207] The incidence of antibodies to nipocalimab would be summarized for all participants who received at least 1 dose of nipocalimab and had appropriate samples for detection of antibodies to nipocalimab (i.e., participants with at least 1 sample obtained after their first dose of nipocalimab).

[0208] The incidence of neutralizing antibodies (Nabs) to nipocalimab would be summarized for participants who were positive for antibodies to nipocalimab and had samples evaluable for Nabs.Biomarkers Analyses

[0209] Change in biomarkers over time might be summarized by treatment group. Associations between baseline levels and changes from baseline in select biomarkers and clinical response might be explored. Results of biomarker analyses might be summarized in a separate technical report.Pharmacokinetic / Pharmacodynamic Analyses

[0210] If data permit, the relationship between serum concentrations of nipocalimab and the efficacy measures and / or relevant PD biomarkers / end points might be explored when appropriate. If any visual trend was observed, additional analysis might be conducted. Analyses results might be summarized in a separate technical report.Pharmacogenomic Analyses

[0211] Genetic (deoxyribonucleic acid [DNA]) analyses might be conducted only in participants who signed the consent form to participate in the pharmacogenomic sampling. These analyses were considered exploratory and might be summarized in a separate technical report.Digital Health - Actigraphy Analyses

[0212] The raw data sampled by the actigraphy watch sensors would be transformed into derived digital health end points, assessing the changes from baseline on physical activity, mobility and sleep parameters through Week 24. End points include, but are not limited to, step count, activity count, sleep time, sleep efficiency, and percent mobile time.

[0213] Additional actigraphy end points might be derived using emerging algorithms. Associations between actigraphy end points and primary and secondary end points might be explored. All actigraphy related analyses were considered exploratory and would be summarized in a separate technical report.

[0214] The inclusion and exclusion criteria for enrolling participants in this study are described below.Inclusion Criteria

[0215] Each potential participant must satisfy all of the following criteria during Screening to be enrolled in the study:Age1. Must be 18 to 75 years of age (inclusive) at the time of consent. (In regions where the legal age of consent is older than 18 years and the participant is under the legal age, signed informed consent must be obtained from both the participant and his or her legally acceptable representative).Disease Characteristics2. Meets classification criteria for primary pSS by the 2016 American College of Rheumatology (ACR) / European League Against Rheumatism classification criteria at the time of Screening (results either obtained during screening or documented in the participant’s medical history are acceptable to fulfill these criteria for Schirmer’s test, unstimulated salivary flow test, ocular staining score, or labial salivary gland biopsy), had moderately-to-severely active disease diagnosed no less than 26 weeks prior to screening, as defined by a total Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ClinESSDAI) score >6, and were seropositive for anti-Ro60 autoantibodies and / or anti-Ro52 IgG autoantibodies. .3. If on oral glucocorticoid therapy, must be on a stable dose at <10 mg / day of prednisone equivalent for >4 weeks prior to study intervention4. At screening is seropositive for antibodies to pSS-associated antigen A (Ro / SSA)5. Has residual salivary gland function as defined by unstimulated whole salivary flow >0.01 mL / min6. Total clinESSDAI score >6, inclusive7. Must demonstrate at least one of the following at screening:• elevated inflammatory marker (i.e., hs-CRP),OR• elevated rheumatoid factor (RF)OR• at least low activity in the hematological domain of ESSDAIOR• at least low activity in the biological domain of ESSDAI.ANDAt least low activity in at least one of the following ESSDAI domains: cutaneous, articular, glandular, constitutional, and lymphadenopathy.Note (applicable to this entire eligibility criterion 7): Demonstrating at least low activity in both the biological and hematologic domains would satisfy this eligibility criterion.8. A score of >5 in at least one of the ESSPRI subcategories of dryness and / or fatigue9. Schirmer’s test >1 mm per 5 minutes, inclusive, in at least one eyeSex and Contraceptive / Barrier RequirementsContraceptive (birth control) use by men or women should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies.Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent with local regulations regarding the use of contraceptive methods for participants in clinical studies.10. A woman of childbearing potential must have a negative highly sensitive urine pregnancy test (P-human chorionic gonadotropin [P-hCG]) at screening and a negative urine (P-hCG) test at Week 0 prior to administration of study intervention.11. A woman must be: a. Not of childbearing potentialOR b. Of childbearing potential and o Practicing a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) and agreed to remain on a highly effective method while receiving study intervention and until 30 days after last dose - the end of relevant systemic exposure. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention. o If using oral hormonal contraceptives for birth control and receiving MMF / MPA, a woman must, in addition to the oral hormonal contraceptive, utilize a barrier method of birth control (e.g., either an occlusive cap [diaphragm or cervical / vault caps] plus spermicidal foam / gel / film / cream / suppository if available in their locale) or theirpartner must agree to use a condom with spermicidal foam / gel / film / cream / suppository if available in their locale, during the study and for at least 30 days after receiving the last administration of study intervention12. A woman must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 30 days after receiving the last administration of study intervention.13. A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for at least 90 days after receiving the last administration of study intervention.In addition, male participants with female partners who are of childbearing potential are to be highly encouraged to inform their partner to use highly effective contraception methods that result in a low failure rate (less than 1% per year).14. A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum of 90 days after receiving the last administration of study intervention.Vaccination History15. It was recommended to be up to date on all age-appropriate vaccinations prior to screening per routine local medical guidelines. It was strongly recommended that participants would have completed a locally-approved (or emergency use-authorized) Coronavirus Disease 2019 (COVID-19) vaccination regimen at least 2 weeks prior to study-related visits or procedures. Study participants should, follow applicable local vaccine labelling, guidelines, and standard of care for patients receiving immune targeted therapy when determining an appropriate interval between vaccination and study enrollment.General16. Must sign an ICF indicating that he or she understood the purpose of, and procedures required for, the study and was willing to participate in the study. (In regions where the legal age of consent is older than 18 years and the participant is under the legal age, signed informed consent must be obtained from both the participant and his or her legally acceptable representative).17. Must sign a separate ICF if he or she agrees to provide optional DNA samples for research where local regulations permit. Refusal to give consent for the optional DNA samples does not exclude a participant from participation in the study.18. Must be willing and able to adhere to all specified requirements, including but not limited to completion of the required assessments, adherence to the visit schedule, and compliance with the lifestyle restrictions as specified in this protocol.19. Must sign a separate ICF if he or she agrees to participate in optional salivary gland biopsy substudy. Refusal to give consent for the optional substudy does not exclude a participant from participation in the study.20. Must be able to read and write.Exclusion Criteria

[0216] Any potential participant who meets any of the following criteria will be excluded from participating in the study:Coexisting Medical Conditions or Past Medical History1. Has a history of severe and / or uncontrolled, hepatic (eg, viral / alcoholic / autoimmune hepatitis / cirrhosis and / or metabolic liver disease), gastrointestinal, renal, pulmonary, cardiovascular, psychiatric, neurological, or musculoskeletal disorder, hypertension, severe uncontrolled fibromyalgia, and / or any other medical or uncontrolled autoimmune rheumatic or systemic inflammatory condition(s) (e.g., diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis) when this condition constitutes the primary disease process) thatmight interfere with participant’s full participation in the study, and / or might jeopardize the safety of the participant or the validity of the study results.Note: Any condition for which, in the opinion of the investigator or sponsor, participation would not be in the best interest of the participant (e.g., compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments.2. Has experienced MI, unstable ischemic heart disease, or stroke within 12 weeks of screening.3. Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his / her pSS or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant.4. Currently has a malignancy or has a history of malignancy within 3 years before screening (with the exception of localized basal cell carcinoma and / or squamous cell carcinoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months [defined as a minimum of 12 weeks] before the first study intervention administration or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first study intervention administration).5. Has known allergies, hypersensitivity, or intolerance to nipocalimab or its excipients.6. Has shown a previous severe immediate hypersensitivity reaction, such as anaphylaxis, to therapeutic proteins (e.g., mAbs).7. Has any unstable or progressive manifestation of pSS that is likely to warrant escalation in therapy beyond permitted background medications and / or has severely active pSS as evaluated and assessed by the investigator or sponsor.8. Has a clinESSDAI pulmonary domain score >6.9. Has Sjogren’s Syndrome overlap syndromes where another confirmed autoimmune rheumatic or systemic inflammatory condition (ie, RA, SLE, scleroderma, IBD) is the primary diagnosis or has clinical manifestations that, in the opinion of the investigator, or the sponsor or sponsor’s representative, are likely to interfere with the investigator’s ability to assess pSS manifestations.10. Diagnosis of any other non-SS sicca syndrome (e.g., due to head and neck radiation, sarcoidosis, chronic graft-versus-host disease etc. according to the requirements in the 2016 EULAR / ACR primary Sjogren’s Syndrome classification criteria).11. Severe uncontrolled fibromyalgia causing significant symptoms or signs, including limiting fatigue, pain, generalized tenderness and / or cognitive dysfunction that would interfere with the investigator’s ability to assess pSS activity and / or response to treatment is excluded. Active fibromyalgia requiring an escalation in medication within the 90 days prior to first study administration intervention to control symptoms is excluded. Participants with well controlled fibromyalgia and are on stable treatment for 90 days prior to randomization may otherwise be allowed.12. Has taken opioid pain medications (any dose), not otherwise allowed elsewhere in this protocol, to treat pSS- or fibromyalgia-related symptoms within 8 weeks of screening.13. Any history of non-Hodgkin’s Lymphoma related to pSS.14. Has any blasts or tumor cells noted on a peripheral blood smear at screening.15. Had major surgery (e.g., requiring general anesthesia [although not all procedures requiring general anesthesia would necessarily be major]) within 3 months before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study.Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate.16. Is (anatomically or functionally) asplenic.17. History of moderate or severe substance or alcohol use disorder according to Diagnostic and Statistical Manual of Mental Disorders 5thedition (DSM-V) criteria, except nicotine or caffeine, within 1 year before screening.18. Prior history of refractive eye surgeries (including but not limited to laser assisted in situ keratomileusis, photorefractive keratectomy, and laser epithelial keratomileusis) within 3 years or less from screening.19. Has had cataract surgery within 6 months prior to randomization and new installation of lacrimal punctal plugs within 4 weeks of randomization; however, patients with existing lacrimal punctal plugs may enroll and have these plugs replaced as necessary during the study).20. Has had a full-thickness corneal transplantation (penetrating keratoplasty); however, participants who have had endothelial keratoplasty >1 year prior to first administration of study intervention are not excluded.21. Has a history of catastrophic anti-phospholipid syndrome (APS). Participants with a history of non-catastrophic APS must be adequately controlled with anticoagulation and / or anti-platelet therapy using medications permitted in this protocol and in accordance with local guidelines. The suitability of the participant to participate in the study must be discussed with the medical monitor and / or sponsor before the participant is randomized.22. Has a chest X-ray (radiograph) suggestive of interstitial lung disease and confirmed by review of medical records.23. Screening laboratory tests a. Hemoglobin <8.0 g / dL b. White blood cell count (WBCs) <3.0 x 103 / pL, unless the leukopenia is due to pSS c. Neutrophils <500 / pLd. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations must be within 2 times the ULN range for the laboratory conducting the test e. Direct (conjugated) bilirubin >1.0 mg / dL f. Estimated glomerular filtration rate (eGFR) <30 mL / min per 1.73 m2g. Serum total IgG <6 g / L (<600 mg / dL)Concomitant or Previous Medical Therapies Received24. Prednisone-equivalent >10 mg / day alone, including immediate and extended- release oral formulations,ORPrednisone-equivalent at any dose, regardless of formulation, if concomitant with more than one immunosuppressive agent (e.g., methotrexate, azathioprine, mycophenolic acid, mycophenolate mofetil, leflunomide, systemic cyclosporine A)ORUse of pulse glucocorticoids (prednisone equivalent >125 mg per day) within 90 days prior to randomization.25. Has used oral cyclophosphamide within 3 months or IV cyclophosphamide within 6 months prior to the first administration of study intervention.26. Medications known to cause dry mouth AND that in the judgement of the investigator or sponsor would compromise the validity of the study results, including medications which have been dose-adjusted in less than 4 weeks prior to screening AND cannot be maintained throughout the study at the dose(s) in use at screening. The use of such medications that are required standard of care for non pSS related conditions AND have been used at stable doses for >4 weeks prior to screening AND >10 weeks beforefirst administration of study intervention AND are anticipated to remain at stable dosing throughout the study may be permitted and may NOT preclude participation in the study.27. Use of topical ophthalmic glucocorticoid agent(s) within the previous 8 weeks prior to first administration of study intervention.28. Initiation of any antimalarial (e.g., hydroxychloroquine) or any immunosuppressive (methotrexate, azathioprine, mycophenolic acid, mycophenolate mofetil, leflunomide) within the 12 weeks prior to first administration of study intervention, or adjustment of dosing of these agents within 8 weeks of first study intervention. See Table 22A for maximal allowed doses.29. Is currently using other IgG Fc-conjugated therapeutic agents, including factor or enzyme replacement therapy, not specifically included or allowed in other criteria.30. Has received any B cell depleting drug (e.g., rituximab, anti-BAFF monoclonal antibody).31. Has received a single B cell-targeting (but nondepleting) therapy within 3 months of screening; or received more than 1 previous B cell-targeting therapy, within 6 months prior to screening.32. Eculizumab or any anti-C5 agents within 6 months prior to screening.33. Use of biologic medications within the past 90 days, or 5 half-lives prior to first administration of study intervention, whichever is greater. Examples include, anti-tumor necrosis factor (TNF) medication (e.g., infliximab, golimumab, certolizumab pegol, etanercept, CT-P13, and adalimumab), other biologic medications (e.g., tocilizumab, alefacept, efalizumab, natalizumab, abatacept, anakinra, brodalumab, secukinumab, ixekizumab), or agents whose mechanism of action targets interleukin (IL)-l, IL-2, IL-6, IL- 17, cytotoxic T-lymphocyte-associated protein (CTLA)-4 or other T cell-inhibitors, or interferon pathways (e.g., anifrolumab), or exogenous IL-2 therapy, within the past 90 days, or 5 half-lives prior to first administration of the study intervention, whichever is greater.34. Has received topical cr earn / ointment preparations of cyclosporine A, high potency topical glucocorticoids (e.g., World Health Organization [WHO] Classification, Group I to III), or other topical immunomodulatory agents (such as tacrolimus, pimecrolimus) covering a body surface area (BSA) of >20% within 4 weeks prior to first administration of study intervention.35. Has received adrenocorticotropic hormone (ACTH) administered by injection within 1 month prior to the first administration of study intervention.36. Has received epidural, IV, IM, intra-articular (IA), intrabursal, or intralesional administration of glucocorticoids within 6 weeks prior to the first administration of study intervention.37. Has comorbidities (other than pSS, e.g., asthma, chronic obstructive pulmonary disease) which have required 3 or more courses of systemic glucocorticoids within the previous 12 months.38. Has received plasmapheresis, immunoadsorption therapy, or intravenous immunoglobulin (IVIg) within 6 months prior to screening.39. Has received a live vaccine within 4 weeks before the first administration of study intervention, or has a known need to receive a live vaccine during the study or within at least 8 weeks (including BCG) after the last administration of study intervention in this study.40. Use of complementary therapies, including traditional / Chinese medicines, herbs, ointments, or procedures (e.g., acupuncture), that have the potential to activate (e.g., echinacea) or inhibit (e.g., Tripterygium wilfordii Hook F) the immune system is prohibited within 6 weeks of first administration of study intervention. In addition, use of complementary therapies, including traditional / Chinese medicines and herbs, that have the potential to interact with antithrombotic agents (e.g., St. John’s Wort) is prohibited within 6 weeks of first administration of study intervention in those taking antithrombotic agents. Any questions or concerns with the use of these therapies should be discussed with the study sponsor and / or medical monitor.41. Has taken any disallowed therapies with the indicated time periods as noted in Table 22A or 22B before the planned first administration of study intervention, unless otherwise specified elsewhere in the protocol.Prior / Concurrent Clinical Study Experience42. Has received an investigational antibody or biologic therapy (other than those listed elsewhere in this section) within 6 months prior to the first administration of study intervention, or received any other investigational therapy, including an investigational medical device, or new investigational agent within 3 months or 5 half-lives (whichever is longer) prior to the first administration of study intervention or is currently enrolled in another study using an investigational intervention or procedure.43. Is currently breastfeeding, pregnant, intends to become pregnant during the study, or is planning egg donation during the study or within 30 days after the last dose of study intervention.44. Is planning to father a child while enrolled in this study or donate sperm within 90 days after the last dose of study intervention.Infections or Predisposition to Infections45. Has a severe infection (e.g., pneumonia, tuberculosis, biliary tract infection, diverticulitis, Clostridioides difficile infection, cytomegalovirus, pneumocystosis, aspergillosis) requiring parenteral anti-infectives and / or hospitalization, and / or is assessed as serious / clinically significant by the Investigator, within 8 weeks prior to Screening. The patient may be re-screened after the 8-week exclusionary period has passed. Any participant with an infection requiring oral anti-infectives (e.g., sinusitis, bronchitis, uncomplicated urinary tract infection) within 4 weeks prior to or during screening will be excluded.46. Has a chronic infection (e.g., bronchiectasis, chronic osteomyelitis, chronic pyelonephritis) or requires chronic treatment with anti-infectives (e.g., antibiotics, antivirals).47. History of being human immunodeficiency virus (HIV)l or HIV2 antibodypositive, or tests positive for HIV at screening.48. Is seropositive for hepatitis B virus (HBV) infection49. Is seropositive for antibodies to hepatitis C virus (HCV), unless they satisfy one of the following conditions:Has a history of successful treatment, defined as being negative for HCV RNA at least 24 weeks after completing antiviral treatment, and has a negative HCV RNA test result at screening,ORWhile seropositive, has a negative HCV RNA test result at least 24 weeks prior to screening and a negative HCV RNA test at the screening.50. COVID- 19 infection:During the 6 weeks prior to baseline, has had any of the following (regardless of vaccination status):(a) confirmed SARS-CoV-2 infection (test positive), OR(b) suspected SARS-CoV-2 infection (clinical features of COVID-19 without documented test results), OR(c) close contact with a person with known or suspected SARS-CoV-2 infectionException: may be included with a documented negative result for a validatedSARS CoV-2 test:- obtained at least 2 weeks after conditions (a), (b), (c) above (timed from resolution of key clinical features if present, eg, fever, cough, dyspnea)ANDwith absence of all conditions (a), (b), (c) above during the period between the negative test result and the baseline study visitNOTE on COVID-related exclusion:The field of COVID-related testing (for presence of, and immunity to, the SARS CoV-2 virus) is rapidly evolving. Additional testing may be performed as part of screening and / or during the study if deemed necessary by the investigator and in accordance with current regulations / guidance from authorities / standards of care.Precaution: for those who may carry a higher risk for severe COVID- 19 illness, follow guidance from local health authorities when weighing the potential benefits and risks of enrolling in the study, and during participation in the study.Other Exclusions51. A current diagnosis of anxiety and / or depression, according to DSM-V, unless the condition(s) have been on well-controlled and on stable therapy for at least 3 months prior to screening and is managed with an intervention or therapy that can be maintained throughout the study.52. Lives in an institution on court or authority order.53. Is an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.54. Has any condition for which, in the opinion of the investigator or the sponsor or sponsor’s representative, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol- specified assessments.55. Is unwilling or unable to undergo multiple venipunctures because of poor tolerability or lack of easy venous access or has / or requires a central venous catheter.56. Has a history of active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening.57. Has received a bacille Calmette-Guerin vaccine (BCG) vaccination within 12 months before first administration of study intervention.Note: Investigators must ensure that all study enrollment criteria have been met at screening. If a participant’s clinical status changes (including any available laboratory results or receipt of additional medical records) after screening but before the first dose of study intervention is given such that the participant no longer meets all eligibility criteria, then the participant must be excluded from participation in the study.STUDY RESULTS

[0217] The study randomized 163 adults with active SjD. Of the 163 participants, 56 were randomized to the placebo group, 53 to the nipocalimab 5 mg / kg group, and 54 to the nipocalimab 15 mg / kg group. The majority of participants were white (90.8%) and 92.6% of the participants were female. The mean age was 48.1 years, ranging from 20 to 73 years (Attachment 3). The mean baseline clinESSDAI score was 9.9 (SD=3.49), the mean baseline ESSDAI score was 8.9 (SD=3.44), and the mean baseline ESSPRI score was 7.08 (SD=1.23). A total of 30 participants (10 [17.9%] participants in the placebo group, 8 [15.1%] participants in the nipocalimab 5 mg / kg group, and 12 [22.2%] participants in the nipocalimab 15 mg / kg group) discontinued study treatment. The most common reason for study treatment discontinuation was withdrawal by subject (4 [7.1%] participants in the placebo group, 4 [7.5%] participants in the nipocalimab 5 mg / kg group and 6 [11.1%] participants in the nipocalimab 15mg / kg group).Primary efficacy end point:

[0218] Based on the hypothetical strategy estimand analysis of the primary efficacy end point (change from baseline in clinESSDAI score at Week 24), the least squares (LS) Mean and associated 90% confidence intervals were: -3.74 (-4.74, -2.75) in the placebo group, -4.08 (-5.10, -3.07) in the nipocalimab 5 mg / kg group, and -6.40 (-7.43, -5.36) in the nipocalimab 15 mg / kg group. The LS Mean difference between nipocalimab 15 mg / kg and placebo groups were -2.65 (-4.03, -1.28) (p=0.002), and the LS Mean difference between nipocalimab 5 mg / kg and placebo groups were -0.34 (-1.71, 1.03) (p=0.681) (Table 2).

[0219] Supplementary sensitivity analyses of the primary end point at Week 24 based on the composite strategy (Table 3) and treatment policy estimands (Table 4) yield numerically greater improvement in the nipocalimab 15 mg / kg group than in the placebo group.

[0220] Mean (+ / - SE) change from baseline values for clinESSDAI score over time through week 24 is also shown in the graph in FIG. 10.Table 2. Primary End point Analysis (Primary Estimand, Hypothetical Strategy): Summary of Change From Baseline in ClinESSDAI Score at Week 24 Using a Mixed Effects Repeated Measures Model (MMRM); Full Analysis SetNipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wAnalysis set: Full 56 53 54Subjects evaluable for change from baseline in clinESSDAI score at week 24aN 44 42 40Mean (SD) -3.3 (4.72) -3.8 (3.22) -6.7 (4.50)Median -3.0 -3.0 -6.0Range (-16; 14) (-9; 2) (-17; 0)IQ range (-6.0; 0.0) (-6.0; -1.0) (-9.0; -3.0)LS Mean (90% CI)b-3.74 (-4.74, -2.75) -4.08 (-5.10, -3.07) -6.40 (-7.43, -5.36)LS Mean difference (90% CI)b-0.34 (-1.71, 1.03) -2.65 (-4.03, -1.28) p-valueb0.681 0.002Key: clinESSDAI = Clinical European League Against Rheumatism (EDLAR) Sjogren’s Syndrome Disease Activity Index a Intercurrent Event (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to C0V1D-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were considered to have missing data at and after this event. b The LS mean, LS mean difference, confidence intervals and p-value are based on a mixed effects repeated measures model (MMRM) with baseline score, study treatment, visit, region, baseline steroid use, baseline anti- malarial use, and an interaction of treatment and visit as terms in the model.Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s Syndrome.Table 3. Primary End point Analysis (Supplementary Estimand 1, Composite Strategy): Summary of Change From Baseline in ClinESSDAI Score at Week 24 Using a Mixed Effects Repeated Measures Model (MMRM); Full Analysis SetNipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wAnalysis set: Full 56 53 54Subjects evaluable for change from baseline in clinESSDAI score at week 24aN 56 52 53Mean (SD) -2.6 (4.39) -3.1 (3.26) -5.0 (4.86)Median -1.0 -3.0 -4.0Range (-16; 14) (-9; 2) (-17; 0)IQ range (-5.0; 0.0) (-6.0; 0.0) (-8.0; 0.0)LS Mean (90% CI)b-2.69 (-3.60, -1.78) -3.34 (-4.28, -2.39) -5.14 (-6.08, -4.20)LS Mean difference (90% CI)b-0.65 (-1.92, 0.62) -2.45 (-3.71, -1.19) p-valueb0.398 0.002Key: clinESSDAI = Clinical European League Against Rheumatism (EULAR) Sjogren’s Syndrome Disease Activity Index a Intercurrent Event (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were assigned 0 as the change from baseline in clinESSDAI after this event. b The LS mean, LS mean difference, confidence intervals and p-value are based on a mixed effects repeated measures model (MMRM) with baseline score, study treatment, visit, region, baseline steroid use, baseline anti- malarial use, and an interaction of treatment and visit as terms in the model.Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s Syndrome.Table 4. Primary End point Analysis (Supplementary Estimand 2, Treatment Policy Strategy): Summary of Change From Baseline in ClinESSDAI Score at Week 24 Using a Mixed Effects Repeated Measures Model (MMRM); Full Analysis SetNipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wAnalysis set: Full 56 53 54Subjects evaluable for change from baseline in clinESSDAI score at week 24 / final efficacy visitaN 50 48 48Mean (SD) -3.6(5.12) -3.5 (3.27) -6.0 (4.61)Median -3.0 -3.0 -6.0Range (-20; 14) (-9, 2) (-17, 4)IQ range (-6.0; 0.0) (-6.0; 0.0) (-8.5; -3.0)LS Mean (90% CI)b-3.81 (-4.76, -2.85) -3.71 (-4.68, -2.74) -6.02 (-7.00, -5.04)LS Mean difference (90% CI)b0.10 (-1.21, 1.41) -2.21 (-3.53, -0.90) p-valueb0.897 0.006Key: clinESSDAI = Clinical European League Against Rheumatism (EULAR) Sjogren’s Syndrome Disease Activity Index a Intercurrent Event (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were not considered to affect the outcome, and the observed values collected at and after the event are used regardless of presence of ICEs. b The LS mean, LS mean difference, confidence intervals and p-value are based on a mixed effect repeated measures model (MMRM) with baseline score, study treatment, visit, region, baseline steroid use, baseline anti- malarial use. and an interaction of treatment and visit as terms in the model.Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s SyndromeSupportive efficacy end points:

[0221] Based on the hypothetical strategy estimand analysis of the continuous supportive efficacy end point (change from baseline in ESSDAI score at Week 24), the LS Mean and associated 90% confidence intervals were: -2.82 (-3.67, -1.98) in the placebo group, -3.34 (-4.20, -2.48) in the nipocalimab 5 mg / kg group, and -4.61 (-5.49, -3.73) in the nipocalimab 15 mg / kg group. The LS Mean difference between nipocalimab 15 mg / kg and placebo groups was -1.79 (- 2.94, -0.63) (p=0.012) and the LS Mean difference between nipocalimab 5 mg / kg and placebo groups was -0.52 (-1.67, 0.63) (p=0.454) (Table 5). A graph showing change from baseline in ESSDAI score over time through Week 24 is shown in FIG. 11.

[0222] Supplementary analysis of the supportive efficacy end point at Week 24 based on the treatment policy estimand also yields numerically greater improvement in the nipocalimab 15 mg / kg group than in the placebo group (Table 6).

[0223] Based on the composite strategy estimand, a numerically higher proportion of participants achieved the binary supportive efficacy end point (ESSDAI-3 response) at Week 24 in both the nipocalimab 5 mg / kg and nipocalimab 15 mg / kg groups when compared to placebo (placebo: 33.9%; nipocalimab 5 mg / kg: 43.4%; nipocalimab 15 mg / kg: 50.0%) (Table 7).Table 5. Tertiary / Exploratory End point Analysis (Primary Estimand, HypotheticalStrategy): Summary of Change From Baseline in ESSDAI Score at Week 24 Using a MixedRepeated Measures Model (MMRM); Full analysis SetNipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wAnalysis set: Full 56 53 54Subjects evaluable for change from baseline in ESSDAI score at week 24aN 44 42 40Mean (SD) -2.5 (3.76) -3.2 (3.14) -4.9 (3.89)Median -2.0 -3.0 -4.5Range (-14; 10) (-9, 3) (-15, 1)IQ range (-5.0; 0.0) (-6.0; -1.0) (-6.5; -2.0)LS Mean (90% CI)b-2.82 (-3.67, -1.98) -3.34 (-4.20, -2.48) -4.61 (-5.49, -3.73)LS Mean difference (90% CI)b-0.52 (-1.67, 0.63) -1.79 (-2.94, -0.63) p-valueb0.454 0.012Key: ESSDAI = European League Against Rheumatism (EULAR) Sjogren’s Syndrome Disease Activity Index a Intercurrent Event (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were considered to have missing data at and after this event. b The LS mean, LS mean difference, confidence intervals and p-value are based on a mixed effect repeated measures model (MMRM) with baseline score, study treatment, visit, region, baseline steroid use, baseline anti- malarial use, and an interaction of treatment and visit as terms in the model.Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s Syndrome.Note: Change from baseline in ESSDAI measures the change from baseline (post baseline - baseline) in ESSDAI score where a negative change reflects improvement, and a positive change reflect worsening.Table 6. Tertiary / Exploratory End point Analysis (Supplementary Estimand, TreatmentPolicy Strategy): Summary of Change From Baseline In ESSDAI Score at Week 24 Using a Mixed Effects Repeated Measure Model (MMRM): Full Analysis SetNipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wAnalysis set: Full 56 53 54Subjects evaluable for change from baseline in ESSDAI score at week 24 / final efficacy visit1N 50 48 48Mean (SD) -2.7 (4.15) -2.9 (3.21) -4.4 (3.89)Median -2.0 -3.0 -4.0Range (-17; 10) (-9; 4) (-15; 4)IQ range (-5.0; 0.0) (-5.5; 0.0) (-6.0; -1.0)LS Mean (90% CI)b-2.93 (-3.75, -2.11) -3.08 (-3.91, -2.24) -4.42 (-5.26, -3.58)LS Mean difference (90% CI)b-0.15 (-1.26, 0.97) -1.48 (-2.60, -0.37) p-valueb0,829 0,029Key: ESSDAI = European League Against Rheumatism (EULAR) Sjogren’s Syndrome Disease Activity Index a Intercurrent Event (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were not considered to affect the outcome, and the observed values collected at and after the event are used regardless of presence of ICEs. b The LS mean, LS mean difference, confidence intervals and p-value are based on a mixed effects repeated measures model (MMRM) with baseline score, study treatment, visit, region, baseline steroid use, baseline anti- malarial use, and an interaction of treatment and visit as terms in the model.Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s Syndrome.Note: Change from baseline in ESSDAI measures the change from baseline (post baseline - baseline) in ESSDAI score where a negative change reflects improvement, and a positive change reflects worsening.Table 7. Tertiary / Exploratory End point Analysis (Primary Estimand, CompositeStrategy): Number of Subjects Who Achieved ESSDAI-3 Response at Week 24 Using aCMH Test; Full Analysis SetNipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wAnalysis set: Full 56 53 54Subjects evaluable for ESSDAI-3 response 56 53 54 at week 24a19 (33.9%) 23 (43.4%) 27 (50.0%)Subjects achieving ESSDAI-3 response39.5% (-5.8%; 16.1% (0.8%;Difference in proportion (90% CI)b24.8%) 31.4%) p-valueb0.332 0.172Key: ESSDAI = European League Against Rheumatism (EULAR) Sjogren’s Syndrome Disease Activity Index a Intercurrent Event (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were considered not to have achieved ESSDAI-3 response after this event. b The difference and confidence interval are based on the unstratrfied Wald statistics and the p-value is based on a Cochran-Mantel-Haenszel (CMH) test with region, baseline steroid use, and baseline anti-malarial use as stratification factors. If the Mantel Fleiss criterion is not satisfied, then the p-value is based on the Fisher’s exact test (p-value represented with *).Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s Syndrome.Note: ESSDAI-3 response is a reduction of the composite ESSDAI score by at least 3 points from baseline.Secondary efficacy end points:

[0224] Based on the FAS analysis (N=163) using the hypothetical strategy estimand for continuous end points and the composite strategy estimand for binary end points:Compared to those treated with placebo, participants treated with nipocalimab 15 mg / kg achieved a numerically greater improvement in mean change from baseline in ESSPRI score at Week 24; the LS Mean difference between nipocalimab 15 mg / kg and placebo groups was -0.41 (-1.03, 0.20) (p-value = 0.268) and the LS Mean difference between nipocalimab 5 mg / kg and placebo groups was 0.62 (0.01, 1.23) (p= 0.094) (Table 8).A numerically higher proportion of participants achieved ESSDAI-4 response at Week 24 in both the nipocalimab 5 mg / kg and 15 mg / kg groups when compared to placebo (placebo: 28.6%; nipocalimab 5 mg / kg: 34.0%, p=0.648; nipocalimab 15 mg / kg: 46.3%, p=0.138) (Table 9).A numerically higher proportion of participants achieved clinESSDAI-4 response at Week 24 in both the nipocalimab 5 mg / kg and nipocalimab 15 mg / kg groups when compared to placebo (placebo: 33.9%; nipocalimab 5 mg / kg: 37.7%, p=0.766; nipocalimab 15 mg / kg: 51.9%, p=0.138) (Table 10).A numerically higher proportion of participants achieved ESSPRI response at Week 24 in the nipocalimab 15 mg / kg group when compared to placebo (placebo: 50.0%; nipocalimab 5 mg / kg: 39.6%, p=0.280; nipocalimab 15 mg / kg: 55.6%, p=0.788) (Table 11).A numerically higher proportion of participants achieved STAR response at Week 24 in both the nipocalimab 5 mg / kg and nipocalimab 15 mg / kg groups when compared to placebo (placebo: 39.3%; nipocalimab 5 mg / kg: 50.9%, p=0.218; nipocalimab 15 mg / kg: 63.0%, p=0.017) (Table 12).A numerically higher proportion of participants achieved DAL response at Week 24 in both the nipocalimab 5 mg / kg and nipocalimab 15 mg / kg groups when compared to placebo (placebo: 33.9%; nipocalimab 5 mg / kg: 52.8%, p=0.047; nipocalimab 15 mg / kg: 53.7%, p=0.046) (Table 13).A numerically higher proportion of participants achieved CRESS response at Week 24 in both the nipocalimab 5 mg / kg and nipocalimab 15 mg / kg groups when compared to placebo (placebo: 17.9%; nipocalimab 5 mg / kg: 43.4%, p=0.006; nipocalimab 15 mg / kg: 48.1%, p=0.001) (Table 14).Table 8. Secondary End point Analysis (Primary Estimand, Hypothetical Strategy):Summary of Change From Baseline in ESSPRI Score at Week 24 Using a Mixed Effects Repeated Measures Model (MMRM); Full Analysis setNipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wAnalysis set: Full 56 53 54Subjects evaluable for change from baseline in ESSPRI score at week 24aN 44 43 41Mean (SD) -1.8(2.01) -1.2 (1.90) -2.3 (1.74)Median -1.7 -0.7 -2.7Range (-7; 2) (-7; 2) (-6; 1)IQ range (-2.8; -0.3) (-2.0; 0.3) (-3.7; -0.7)LS Mean (90% CI)b-1.91 (-2.36, -1.46) -1.29 (-1.75, -0.83) -2.32 (-2.79, -1.85)LS Mean difference (90% CI)b0.62 (0.01, 1.23) -0.41 (-1.03, 0.20) p-valueb0.094 0.268Key: ESSPRI = European League Against Rheumatism (EULAR) Sjogren’s Syndrome Patient Reported Index a Intercurrent Event (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were considered to have missing data at and after this event. b The LS mean, LS mean difference, confidence intervals and p-value are based on a mixed effects repeated measures model (MMRM) with baseline score, study treatment, visit, region, baseline steroid use, baseline anti- malarial use. and an interaction of treatment and visit as terms in the model.Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s Syndrome.Note: Change from baseline in ESSPRI score measures the change from baseline (post baseline - baseline) in the patient-reported assessment of the severity of dryness, fatigue, and pain associated with primary Sjogren’s where areflects i and areflectsTable 9. Secondary End point Analysis (Primary Estimand, Composite Strategy): Number of Subjects Who Achieved ESSDAI-4 response at Week 24 Using a CMH Test; Full Analysis set_ Nipocalimab _Placebo _ 5 mg / kg q2w _ 15 mg / kg q2wAnalysis set: Full 56 53 54Subject evaluable for ESSDAI-4 response at 56 53 54 week 24aSubjects achieving ESSDAI-4 response1116 (28.6%) 18 (34.0%) 25 (46.3%)Difference in proportion (90% CI)b5.4% (-9.2%; 17.7% (2.8%;20.0%) 32.7%) p-valueb0.648 0.138Key: ESSDAI =European League Against Rheumatism (EULAR) Sjogren’s Syndrome Disease Activity Index a Intercurrent (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were considered not to have achieved ESSDAI-4 response after this event. b The difference and confidence interval are based on the unstratrfied Wald statistics and the p-value is based on a Cochran-Mantel-Haenszel (CMH) test with region, baseline steroid use, and baseline anti-malarial use as stratification factors. If Mantel Fleiss criterion is not satisfied, then the p-value is based on the Fisher’s exact test (p-value represented with *).Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s Syndrome.Note: ESSDAI-4 response is a reduction of the composite ESSDAI score by at least 4 points from baseline.Table 10. Secondary End point Analysis (Primary Estimand, Composite Strategy):Number of Subjects Who Achieved ClinESSDAI-4 Response at Week 24 Using a CMHTest; Full Analysis SetNipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wAnalysis set: Full 56 53 54Subject evaluable for clinESSD A 1-4 56 53 54 response at week 24aSubjects responsenachieving clinESSD AIM 19 (33.9%)0 / is «i o« / r * ZU ( / . / / o) Zo ( J l.y / o)Difference in proportion (90% CI)b3.8% (-11.3%;0 / 0.18 9%) t / .y / o (2. / o; 33.2 / 0) p-valueb0.766 0.138Key: clinESSDAI = Clinical European League Against Rheumatism (EULAR) Sjogren’s Syndrome Disease Activity Index a Intercurrent (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were considered not to have achieved clinESSDAI -4 response after this event. b The difference and confidence interval are based on the unstratrfied Wald statistics and the p-value is based on a Cochran-Mantel-Haenszel (CMH) test with region, baseline steroid use, and baseline anti-malarial use as stratification factors. If Mantel Fleiss criterion is not satisfied, then the p-value is based on the Fisher’s exact test (p-value represented with *).Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s Syndrome.Note: clinESSDAI-4 response is a reduction of the composite clinESSDAI score by at least 4 points from baseline.Table 11. Secondary End point Analysis (Primary Estimand, Composite Strategy):Number of Subjects Who Achieved ESSPRI Response at Week 24 Using a CMH Test; FullAnalysis SetNipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wAnalysis set: Full 56 53 54Subject evaluable for ESSPRI response at 56 53 54 week 24aSubjects achieving ESSPRI response328 (50.0%) 21 (39.6%) 30 (55.6%)Difference in proportion (90% CI)b-10.4% (-26.0%; 5.6% (-10.1%;5.2%) 21.2%) p-valueb0.280 0.788Key: ESSPRI = European League Against Rheumatism (EULAR) Sjogren’s Syndrome Disease Activity Index a Intercurrent (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were considered not to have achieved ESSPRI response after this event. b The difference and confidence interval are based on the unstratrfied Wald statistics and the p-value is based on a Cochran-Mantel-Haenszel (CMH) test with region, baseline steroid use, and baseline anti-malarial use as stratification factors. If the Mantel Fleiss criterion is not satisfied, then the p-value is based on the Fisher’s exact test (p-value represented with *).Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s Syndrome.Note: ESSPRI response is a reduction of one point or a decrease of >15% in the ESSPRI score from baseline.Table 12. Secondary End point Analysis (Primary Estimand, Composite Strategy):Number of Subjects Who Achieved STAR Response at Week 24 Using a CMH Test; FullAnalysis SetNipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wAnalysis set: Full 56 53 54Subject evaluable for STAR response at 56 53 54 week 24aSubjects achieving STAR response322 (39.3%) 27 (50.9%) 34 (63.0%)Difference in proportion (90% CI)b11.7% (-3.9%; 23.7% (8.4%;27.2%) 38.9%) p-valueb0.218 0.017Key: STAR = Sjogren’s Tool for Assessing Response, clinESSDAI = Clinical European League Against Rheumatism (EULAR) Sjogren’s Syndrome Disease Activity Index, ESSPRI = EULAR Sjogren’s Syndrome Patient Reported Index a Intercurrent Event (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were considered not to have achieved STAR response after this event. b The difference and confidence interval are based on the unstratrfied Wald statistics and the p-value is based on a Cochran-Mantel-Haenszel (CMH) test with region, baseline steroid use, and baseline anti-malarial use as stratification factors. If the Mantel Fleiss criterion is not satisfied, then the p-value is based on the Fisher’s exact test (p-value represented with *).Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s Syndrome.Note: A STAR response is defined as a composite score of >5 points in the 5 STAR domains, with weighting in parentheses: i) decrease of >3 in clinESSDAI score (3), ii) decrease of >1 point or >15% from baseline in ESSPRI score (3), iii) abnormal Schirmer’s test at baseline and an increase of >5 mm or normal Schirmer’s test at baseline and no change to abnormal, or abnormal ocular staining score at baseline and a decrease of >2 points, or normal ocular staining score at baseline and no change to abnormal (1), iv) increase of >25% in unstimulated whole saliva or any increase if score is 0 at baseline (1), v) decrease of >25% in rheumatoid factor or decrease of >10% in lgG (l).Table 13. Secondary End point Analysis (Primary Estimand, Composite Strategy):Number of Subjects Who Achieved DAL Response at Week 24 using a CMH Test, FullAnalysis SetNipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wAnalysis set: Full 56 53 54Subject evaluable for DAL response at week 56 53 5424aSubjects achieving DAL response319 (33.9%) 28 (52.8%) 24 (53.7%)Difference in proportion (90% CI)b18.9% (3.6%; 19.8% (4.53%;Key: DAL =Disease Activity Level a Intercurrent Event (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were considered not to have achieved DAL response after this event. b The difference and confidence interval are based on the unstratrfied Wald statistics and the p-value is based on a Cochran-Mantel-Haenszel (CMH) test with region, baseline steroid use, and baseline anti-malarial use as stratification factors. If the Mantel Fleiss criterion is not satisfied, then the p-value is based on the Fisher’s exact test (p-value represented with *).Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment-Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s Syndrome.Note: DAL response is a reduction from baseline in disease activity level by at least one level in at least one clinESSDAI orESSDAI domain (e.g., biological, hematological, cutaneous, constitutional, lymphadenopathy and lymphoma, and glandular).Table 14. Secondary End point Analysis (Primary Estimand, Composite Strategy):Number of Subjects Who Achieved CRESS Response at Week 24 using a CMH Test; FullAnalysis SetNipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wAnalysis set: Full 56 53 54Subject evaluable for CRESS response at 56 53 54 week 24aSubjects achieving CRESS response310 (17.9%) 23 (43.4%) 26 (48.1%)Difference in proportion (90% CI)b25.5% (11.5%; 30.3% (16.3%;39.5%) 44.3%) p-valueb0.006 0.001Key: CRESS = Composite of Relevant End points for Sjogren’s Syndrome, clinESSDAI = Clinical European League Against Rheumatism (EULAR) Sjogren’s Syndrome Disease Activity Index, ESSPRI = EULAR Sjogren’s Syndrome Patient Reported Index a Intercurrent Event (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were considered not to have achieved CRESS response after this event. b The difference and confidence interval are based on the unstratrfied Wald statistics and the p-value is based on a Cochran-Mantel-Haenszel (CMH) test with region, baseline steroid use; and baseline anti-malarial use as stratification factors. If the Mantel Fleiss criterion is not satisfied, then the p-value is based on the Fisher’s exact test (p-value represented with *).Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s Syndrome.Note: A CRESS response is defined as a response in >3 of the following 5 categories: i) clinESSDAI score <5 (low disease activity), ii) decrease of >1 point or >15% from baseline in ESSPRI score, iii) abnormal Schirmer’s test at baseline(<5 mm) and an increase of >5 mm, or normal Schirmer s test at baseline and no change to abnormal, iv) increase of >25% in unstimulated whole saliva or any increase if score is 0 at baseline, v) decreaseof >25% in rheumatoid factor or decrease of >10% inSelected tertiary / exploratory end points:

[0225] Based on the FAS analysis (N=163) using the hypothetical strategy estimand for continuous end points and the composite strategy estimand for binary end points:Compared to those treated with placebo, participants treated with nipocalimab 5 mg / kg or nipocalimab 15 mg / kg achieved a numerically greater improvement in mean change from baseline in PhGA at Week 24; the LS Mean difference between nipocalimab 5 mg / kg group and placebo groups was -2.26 (-8.50, 3.99) and the LS Mean difference between nipocalimab 15 mg / kg and placebo groups was -14.50 (-20.81, -8.19) (Table 15).• Improvements observed in the nipocalimab 15 mg / kg group were numerically greater than in the placebo group for all change from baseline in Sjogren’s symptoms (fatigue, eye dryness, mouth dryness, joint pain) at Week 24 (Table 16).Table 15. Tertiary / Exploratory End point Analysis (Primary Estimand, Hypothetical Strategy): Summary of Change From Baseline in PhGA at Week 24 Using a Mixed Effects Repeated Measures Model (MMRM): Full Analysis SetNipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wAnalysis set: Full 56 53 54Subjects evaluable for change from baseline in PhGA at week 24aN 44 43 41Mean (SD) -24.0 (21.48) -25.3 (16.42) -38.5 (20.95)Median -25.0 -21.0 -43.0Range (-80; 10) (-63; 8) (-70; 5)IQ range (-36.5; -5.5) (-39.0; -15.0) (-52.0; -24.0)LS Mean (90% CI)b-24.26 (-28.91, -26.51 -38.76-19.61) (-31.27, -21.76) (-43.62, -33.91)LS Mean difference (90% CI)b -2.26 (-8.50, 3.99) -14.50(-20.81, -8.19) p-valueb0.550 <0.001Key: PhGA = Physician’s Global Assessment of Disease Activity a Intercurrent Event (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that metTreatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to C0V1D-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were considered to have missing data at and after this event. b The LS mean, LS mean difference, confidence intervals and p-value are based on a mixed effects repeated measures model (MMRM) with baseline score, study treatment, visit, region, baseline steroid use, baseline anti- malarial use, and an interaction of treatment and visit as terms in the model.Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted the reason for replacement should not be due to primary Sjogren’s Syndrome.Note: Change from baseline in PhGA measures the change from baseline (post baseline - baseline) in Sjogren’sreflectsTable 16. Tertiary / Exploratory End point Analysis (Primary Estimand, HypotheticalStrategy): Summary of Change From Baseline in Sjogren’s Symptoms at Week 24 Using a Mixed Effects Repeated Measure Model (MMRM); Full Analysis SetNipocalimabAnalysis set: Full 56 53 54Fatigue:Subject evaluable for change from baseline in fatigue score at week 24a44 43 41Mean (SD) -2.1 (2.78) -1.1 (2.08) -2.5 (1.94)Median -2.0 -1.0 -2.0Range (-9; 3) (-8; 2) (-7; 1)IQ range (-4.0; -0.5) (-2.0; 0.0) (-4.0; -1.0)LS Mean (90% CI)b -2.10 (-2.65, -1.56) -1.17 (-1.73, -0.61) -2.40 (-2.97, -1.83)LS Mean difference (90% CI)b0.93 (0.20, 1.67) -0.29 (-1.03, 0.45) p-valueb0.036 0.512Eye dryness:Subject evaluable for change from baseline in eye dryness score at week 24a44 43 41Mean (SD) -1.9 (2.93) -0.9 (1.82) -2.5 (2.16)Median -2.0 -1.0 -3.0Range (-8; 6) (-6; 3) (-6; 4)IQ range (-3.5; 0.0) (-2.0; 0.0) (-4.0; -1.0)LS Mean (90% CI)b-2.19 (-2.76. -1.62) -0.99 (-1.56, -0.41) -2.56 (-3.14, -1.97)LS Mean difference (90% CI)b1.20 (0.46, 1.95) -0.37 (-1.12, 0.39) p-valueb0.008 0.420Mouth dryness:Subject evaluable for change from baseline in mouth dryness score at week 24a44 43 41Mean (SD) -1.9 (2.71) -1.2 (2.13) -2.4 (2.28)Median -1.5 -1.0 -3.0Range (-8; 3) (-7; 3) (-6; 3)IQ range (4.0; 0.0) (-2.0; 0.0) (-4.0; -1.0)LS Mean (90% CI)b-2.19 (-2.75. -1.62) -1.36 (-1.93, -0.78) -2.65 (-3.23, -2.06)LS Mean difference (90% CI)b0.83 (0.08, 1.58) -0.46 (-1.21, 0.30) p-valueb0.069 0.319Vaginal dryness:Subject evaluable for change from baseline in vaginal dryness score at week 24a36 37 32Mean (SD) -1.3 (3.23) -0.8 (2.37) -2.1 (2.45)Median -1.0 0.0 -2.0Range (-8; 9) (-7; 3) (-8; 4)IQ range (-4.0; 0.5) (-2.0; 1.0) (-4.0; -1.0)LS Mean (90% CI)b-1.37 (-2.07, -0.66) -1.12 (-1.82, -0.43) -2.29 (-3.01, -1.57)LS Mean difference (90% CI)b0.24 (-0.66, 1.15) -0.93 (-1.86, 0.00) p-valueb0.657 0.100NipocalimabPlacebo 5 mg / kg q2w 15 mg / kg q2wJoint pain:Subjects evaluable for change from baseline in joint pain score at week 24a44 43 41Mean (SD) -1.3 (2.80) -1.1 (2.43) -1.7 (2.66)Median -1.5 -1.0 -2.0Range (-7; 5) (-8; 5) (-6; 3)IQ range (-3.0; 0.5) (-2.0; 0.0) (-4.0; 0.0)LS Mean (90% CI)b-1.23 (-1.85, -0.62) -1.15 (-1.77, -0.53) -1.50 (-2.13, -0.86)LS Mean difference (90% Cl)b0.08 (-0.73, 0.90) -0.26 (-1.09, 0.56) p-valueb0.867 0.597 a Intercurrent Event (ICE) Strategies: Subjects who initiated or adjusted concomitant medication that met Treatment Failure (TF) criteria (ICE1), or discontinued study intervention prior to Week 24 for any reason unrelated to CO VID-19 (ICE2), or discontinued study intervention prior to Week 24 due to CO VID-19 pandemic situation or confirmed CO VID-19 infection (ICE3), were considered to have missing data at and after this event. b The LS mean, LS mean difference, confidence intervals and p-value are based on a mixed effects repeated measures model (MMRM) with baseline score, study treatment, visit, region, baseline steroid use, baseline anti- malarial use, and an interaction of treatment and visit as terms in the model.Note: Substitution of an agent with a similar mechanism of action at an equivalent or lower dose is not considered a Treatment Failure (TF). Where replacement of a medication is permitted, the reason for replacement should not be due to primary Sjogren’s Syndrome.Note: Change from baseline in Sjogren’s symptom severity score measures the change from baseline (post baseline - baseline) in Sjogren’s symptom severity, where a negative change reflects improvement, and a positive change reflects worsening.Note: Subjects who tick ‘Does not apply to me’ will not be counted in the subjects evaluable row.

[0226] End point Definitions• Change from baseline in ESSDAI score: Measures the change from baseline (post baseline - baseline) in systemic disease activity as measured by ESSDAI score where a negative change reflects improvement, and a positive change reflects worsening.ESSDAI-3 response: Reduction of the composite ESSDAI score by at least 3 points from baseline.• Change from baseline in ESSPRI score: Measures the change from baseline (post baseline - baseline) in the patient-reported assessment of the severity of dryness, fatigue, and pain associated with SjD, where a negative change reflects improvement, and a positive change reflects worsening.• ESSDAI-4 response: Reduction of the composite ESSDAI score by at least 4 points from baseline.• clinESSDAI-4 response: Reduction of the composite clinESSDAI score by at least 4 points from baseline.• ESSPRI response is a reduction of > one point or a decrease of >15% in the ESSPRI score from baseline.• STAR response: A composite score of >5 points in the 5 STAR domains (systemic activity, patient-reported outcome, lachrymal gland function, salivary gland function, and biological). If a subject meets the STAR response criteria, regardless of missing data, then the subject is a responderTable 17. STAR response criteria and instructions• DAL response: Reduction from baseline in disease activity level by at least one level in at least one clinESSDAI or ESSDAI domain (e.g., biological, hematological, cutaneous, constitutional, lymphadenopathy and lymphoma, and glandular).• CRESS response: A response in >3 of 5 CRESS categoriesTable 18. Overview of the Composite of Relevant End points in Sjogren’s Syndrome (CRESS): definition of response of the 5 complementary items• Change from baseline in PhGA: Measures the change from baseline (post baseline - baseline) in Sjogren’s Syndrome Activity, where a negative change reflects improvement, and a positive change reflects worsening.• Change from baseline in Sjogren’s Symptoms: Measures the change from baseline in Sjogren’s Symptoms, where a negative change reflects improvement, and a positive change reflects worsening. Sjogren’s Symptoms questionnaire is a novel patient- reported assessment of the severity of key symptoms associated with Sjogren’s disease. The Sjogren’s Symptoms questionnaire includes 5 items assessing the severity of a patient’s vaginal dryness, fatigue, joint pain, eye dryness, and mouth dryness, each at its worst over the past 7 days on a 0 to 10 numeric rating scale, where higher scores indicate greater symptom severity.Safety:

[0227] Through Week 24, 1.8% (n=l), 3.9% (n=2) and 1.9% (n=l) of the participants had at least one adverse event of special interest (AESI) in the placebo, nipocalimab 5 mg / kg, and nipocalimab 15 mg / kg groups, respectively, none of which were deemed related to study treatment by the investigator.

[0228] One serious adverse event (SAE) was deemed related to study treatment, in which a participant in the nipocalimab 5 mg / kg group experienced an anaphylactic reaction. No other SAEs were deemed related to the study treatment by the investigators.

[0229] No participants exposed to nipocalimab experienced major adverse cardiovascular events (MACE: cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke), while two participants in the placebo group experienced MACE.

[0230] The following AEs were not reported in any of the nipocalimab or placebo groups:• Death• Treatment-emergent hypoalbuminemia with albumin <20 g / L• Opportunistic infections

[0231] The most common AE System Organ Class (SOC) was infections and infestations, reported in 42.9% (n=24), 60.4% (n=32), 51.9% (n=28) of participants in the placebo, nipocalimab 5 mg / kg, and nipocalimab 15 mg / kg groups, respectively. Graphical representations of albumin and total cholesterol levels over time are provided in FIGs. 2 and 3, respectively.Analysis Sets

[0232] The full and safety analysis sets included all randomized participants who received >1 dose (partial or complete) of any study intervention and were used for the efficacy and safety analyses, respectively. The pharmacodynamic analysis set included all randomized participants who received >1 complete dose of nipocalimab and had >1 valid postdose blood sample drawn for pharmacodynamic biomarker analysis.Intercurrent Events

[0233] An intercurrent event (ICE) occurred when a participant discontinued study intervention prior to Week 24 for any reason or initiated or changed concomitant medication that met treatment failure criteria. The hypothetical strategy, which excluded data from the time an ICE occurred and onward and then imputed the outcome, was the primary estimand for continuous end points. The composite strategy, where ICEs were considered treatment failures, was the primary estimand for binary end points.Biomarkers

[0234] A graph of the mean (+ / -) percent change from baseline values for Immunoglobulin G g / L [IgG] over time is shown in FIG. 4. A graph of the mean (+ / -) percent change from baseline values for C-Reactive Protein mg / L [CRP] over time is shown in FIG. 5. A graph of the mean (+ / -) percent change from baseline values for Erythrocyte Sedimentation Rate mm / h [ESR] over time is shown in FIG. 6. A graph of the mean (+ / -) percent change from baseline values for Immunoglobulin A g / L [IgA] over time is shown in FIG. 7. A graph of the mean (+ / -) percent change from baseline values for Immunoglobulin M g / L [IgM] over time is shown in FIG. 8. A graph of the mean (+ / -) percent change from baseline values for and Rheumatoid Factor lU / m / L [RF]) over time is shown in FIG. 9.Summary of results

[0235] The results show that the anti-FcRn agent nipocalimab significantly improved clinESSDAI scores in subjects with Sjogren’s disease compared to placebo. Nipocalimab treatment also significantly improved ESSDAI scores in subjects with Sjogren’s disease compared to placebo. Nipocalimab treatment further numerically improved a range of patient outcomes, including ESSPRI (which has never shown a positive outcome in any studies of moderate-to-severe Sjogren’s), and those clinical symptoms which are reported as amongst the most important to Sjogren’s patients, such as vaginal dryness.Example 2: A Randomized, Placebo-controlled, Double-blind, Multicenter Phase 3 Study to Assess the Efficacy and Safety of Nipocalimab in Adults with Moderate to Severe Sjogren’s Disease (SjD)Study Design

[0236] This study includes 2 identical double-blind, placebo-controlled, parallel-group, multicenter studies to evaluate the efficacy, safety, and tolerability of nipocalimab in participants >18 years of age with moderate to severe SjD (defined as ClinESSDAI score >5) who are seropositive for antibodies to Ro / SSA and on SOC background therapy. Randomization in a 1 : 1 ratio into each study will be stratified by geographical region (East Europe, Western Europe, North America, LATAM, and APAC), baseline ClinESSDAI score, and baseline IgG levels;within each stratum, participants in each study will then be randomized in a 3:2 ratio to receive nipocalimab or placebo, respectively.

[0237] The primary analysis will be performed after all participants have completed Week 48 efficacy assessment (or discontinued earlier). Efficacy, PK, immunogenicity, biomarkers, and safety will be assessed according to the SoA. The analysis will be performed for each study separately. At the Week 48 visit, eligible participants from both studies will have the option to enter an open-label LTE. Eligibility for the open-label LTE will be based on meeting the following criteria:1. Completion of the double-blind period; participants who withdraw consent from study participation and / or have permanently discontinued study intervention prior to Week 48 will not be eligible to enter the open-label LTE; and2. In the judgment of the investigator, the potential benefit of (continuing) nipocalimab treatment outweighs the potential risks for the participant.

[0238] All eligible participants, after signing the open-label LTE ICF, will be enrolled in the open-label LTE and will receive nipocalimab 460 mg SC qw. For participants who enroll in the open-label LTE, the assessments done at the Week 48 visit of the double-blind period will serve as the first visit of the open-label LTE, and participants will receive their first dose of open-label nipocalimab after completion of the Week 48 visit assessments. Participants who are not eligible for participation in the LTE will return to the study center approximately 6 weeks after their last study intervention administration to complete the final safety assessments. The end of each of the 2 studies is considered as the last visit for the last participant in the respective study.Number of Participants

[0239] The 2 studies will be conducted with a total sample size of 600 participants.First, participants will be randomized in a 1: 1 ratio to 1 of the 2 studies for a total of 300 participants per study.Secondly, the 300 participants assigned to each study will be randomized in a 3:2 ratio to receive nipocalimab 460 mg SC qw or placebo SC qw for 48 weeks.Study Arms and Duration

[0240] The total duration of the study is up to 156 weeks and consists of 4 study periods: a 6-week screening period, a 48-week double-blind period, a 96-week open-label LTE, and a 6- week safety follow-up period (after last study intervention administration).During double-blind period:

[0241] Group 1: Nipocalimab in addition to SOC - Participants will receive nipocalimab 460 mg SC qw in addition to SOC from Week 0 through Week 47.

[0242] Group 2: Placebo in addition to SOC - Participants will receive placebo SC qw in addition to SOC from Week 0 through Week 47.

[0243] During open-label LTE: - Participants will receive nipocalimab 460 mg SC qw in addition to SOC from Week 48 through Week 143.EFFICACY EVALUATIONS

[0244] Investigator assessments and PROs of efficacy include the following: ClinESSDAI / ESSDAI, Joint count assessment, Schirmer’s Test, Unstimulated Salivary Flow Test, Stimulated Salivary Flow Test, PhGA, CRESS, STAR, DAS28-CRP, concomitant treatment for dryness symptoms, Oral glucocorticoid tapering.

[0245] PRO measures: Sjogren’s Symptoms Questionnaire for dryness and joint pain, ESSPRI, FACIT-Fatigue, PtGA, EQ-5D-5L, SF-36.

[0246] The Phase 3 clinical development program for nipocalimab in SjD include 2 identical double-blind, placebo-controlled, parallel-group, multicenter, studies to evaluate the efficacy, safety and tolerability of nipocalimab in participants > 18 years of age with moderate to severe SjD (defined as European Alliance of Associations for Rheumatology [EULAR]Sjogren’s Syndrome Disease Activity Index [ESSDAI] score >5). The 2 studies will be conducted under this one protocol (FIG. 12). All participants will be randomized to receive nipocalimab 460 mg SC QW or placebo SC QW for 48 weeks. Randomization will be stratified by region, baseline ClinESSDAI score, and baseline IgG levels.

[0247] Primary end point will be change in ClinESSDAI score from baseline to 48 weeks in all randomly assigned participants. The primary efficacy analysis will be performed after all participants have completed Week 48 efficacy assessment (or discontinued earlier). Additional secondary end points will be evaluated for all applicable visits between baseline through Week 48.

[0248] At the Week 48 visit, eligible participants will have the option to enter a 48 week open-label long-term extension (LTE). All participants enrolling in the LTE will receive nipocalimab 460 mg SC QW. For participants who enroll in the LTE, the assessments done at the Week 48 visit of the double-blind phase will serve as baseline (first visit) of the LTE, and participants will receive their first dose of open label nipocalimab after completion of the Week 48 visit assessments. Patients who decline participation in the LTE, or who are not eligible for participation, or who discontinue prematurely from the study and do not qualify for the LTE, will return to the study center approximately 6 weeks after their last study intervention administration to complete the final safety assessments.

[0249] The end of study is considered as the last visit for the last participant in the study.

[0250] Sequence and duration of study phases / periods:• Screening Period: < 6 weeks• Double-blind Period: 48 weeks (week 1-48)• Open-label Long-Term Extension Period: 96 weeks (week 48-144)• Safety Follow-up Period: 6 weeks (up to week 152)

[0251] End of study definition:The end of study is considered as the last visit for the last participant in the study.• The final data from the study site will be sent to the sponsor (or designee) after completion of the final participant assessment at that study site, in the time frame specified in the clinical trial agreement.• A participant will be considered to have completed the study if he or she has completed assessments through Week 48.Key study measures:

[0252] Efficacy (ClinROs): ClinESSDAI, ESSDAI, STAR, CRESS, joint count assessment / DAS28-CRP, Schirmer’s Test, Ocular Staining Score (OSS), unstimulated Salivary Flow Test, Stimulated Salivary Flow Test, Physician’s Global Assessment of Disease Activity (PhGA)

[0253] Efficacy (PROs): Sjogren’s Symptoms Joint Pain, Sjogren’s Symptoms Dryness, FACIT-Fatigue, ESSPRI, SF-36 v2, EQ-5D, Patient’s Global Assessment of Disease Activity (PtGA)

[0254] Safety: AEs, SAEs, AESIs, clinical laboratory parameters (chemistry including lipid panel, hematology, coagulation and urinalysis), vital signs.

[0255] PK: Serum nipocalimab concentrations, anti-drug antibodies to nipocalimab and neutralizing antibodies (NAb) to nipocalimab.

[0256] PD and Biomarkers: Immunoglobulin profile (IgG / IgM / IgE / IgA) and IgG subtypes, antibodies to SjD-associated antigens (anti-Ro60 / SSA autoantibodies and / or anti-Ro52 / TRIM21 autoantibodies, and anti-SSB / La autoantibodies), RF, complement markers, CRP, and ESR will be analyzed. Select biomarkers, such as total IgG and anti-Ro autoantibodies, may be used in PK-PD modeling. Transcriptomics (RNA expression analysis on whole blood), and targeted cytokine analysis (on serum) may be used to evaluate the changes in gene expression profiles that may correlate with biologic response relating to SjD and / or the action of nipocalimab andmay also be used to identify population subgroups that respond differently to nipocalimab treatment.Treatment:- Nipocalimab 460 mg SC qw in addition to SOC- Placebo in addition to SOC

[0257] Population: Participants >18 years of age with moderate to severe SjD who are seropositive for antibodies to Ro / SSA.

[0258] Variable / end point: Change from baseline in ClinESSDAI score at Week 48.

[0259] Population-level Summary: Difference in the means of the variable between nipocalimab and placebo.

[0260] ICEs:- (1) Initiation or adjustment of concomitant medication that meets treatment failure criteria- (2) Treatment discontinuation prior to Week 48 due to lack of efficacy or AE of worsening SjD- (3) Treatment discontinuation prior to Week 48 not due to lack of efficacy or AE of worsening SjD

[0261] For ICEs 1-2, strategy reflected in the Variable attribute, where patients with ICEs are considered to have no change from baseline to each study visit starting after first ICE through Week 48. The ICE-3 is addressed with a hypothetical strategy; from the time the ICE occurred and onward, patients will be considered to have a value consistent with other patients in the same treatment group at that visit, based on MAR.

[0262] The primary analysis of the primary end point will use the primary estimand of the primary end point and be based on an ANCOVA model with change from baseline inClinESSDAI score at Week 48 as the dependent variable and baseline ClinESSDAI score, treatment, and stratification factors for randomization as independent variables.

[0263] To evaluate the robustness of the composite and hypothetical strategies for the primary estimand regarding the assumptions of missing data, a tipping point sensitivity analysis will be performed; more details will be provided in the SAP.Secondary End points

[0264] The primary estimands for key secondary end points at Week 48 have the same attributes as the primary estimand of the primary end point, except for attributes of variable / end point, population-level summary, and strategy used for ICEs.Objectives and End pointsTable 19A.Table 19B. Objectives and End pointsTable 19C. Description of InterventionsInclusion CriteriaTable 20.Exclusion CriteriaTable 21.

[0265] The disclosures of each and every patent, patent application, and publication cited herein are hereby incorporated herein by reference in their entirety. While various embodiments have been disclosed with reference to specific aspects, it is apparent that other aspects and variations of these embodiments may be devised by others skilled in the art without departing from the true spirit and scope of the embodiments. The appended claims are intended to be construed to include all such aspects and equivalent variations.Glucocorticoid Therapy

[0266] Participants who are receiving oral glucocorticoids at screening must be on a stable dose equivalent to an average daily dose of no more than 10 mg / day prednisone (or equivalent), for at least 4 weeks prior to the first administration of study intervention. Participants receiving this medication at screening must have been receiving this medication for at least 6 weeks prior to randomization.

[0267] Starting from Week 8 and continuing through Week 36, gradual tapering is required for participants receiving glucocorticoids >5 mg / day prednisone (or equivalent) at baseline, aiming for a target glucocorticoid dose of <5 mg / day prednisone (or equivalent) through Week 48, unless safety or tolerability issues necessitate a change in glucocorticoid dose. Investigators may continue to taper glucocorticoid dose beyond <5 mg / day. No glucocorticoid dose change is permitted between Week 36 and Week 48. Reduction of glucocorticoid dose can be initiated during LTE at investigator’s discretion.

[0268] On treatment days, tapering will start after all assessments have been completed and investigational product has been administered. Tapering can be started on the scheduled studyvisit day (e.g.,Week 8 visit) based on clinical manifestations and the laboratory values from the previous visit.

[0269] Investigators have flexibility on how glucocorticoid dose is reduced at each visit. As general rule participants with a daily dose of <10 mg prednisone (or equivalent) taper at 1 mg q2w. In case not all required tablet sizes are available to comply with the lower doses of protocol-defined taper, small variations in daily glucocorticoid use up to 0.5 mg / day are allowed to make the taper feasible. If tablets need to cut in half or in quarters, this should preferably be performed by site staff. If a participant received glucocorticoids other than prednisone or prednisolone, the investigator should contact the sponsor designee / medical monitor to ensure that the taper is appropriately adjusted for the glucocorticoid equivalency compared with prednisone.

[0270] If a participant experiences worsening of SjD disease activity while tapering glucocorticoids, further dose decreases may be suspended, and / or their glucocorticoid dose may be temporarily increased (e.g., one prior glucocorticoid taper dose level or up to a maximum of baseline glucocorticoid dose) if deemed necessary by the investigator. If glucocorticoid tapering is interrupted, investigators are encouraged to resume tapering within 4 weeks.

[0271] Considerations for Glucocorticoid Use During Study: Week 0 to Week 36

[0272] Between Week 0 and Week 36, an increase in glucocorticoid dose for increased SjD disease activity is not allowed. A participant receiving a steroid dose above baseline dose may continue in the study but may be considered as treatment failure for assessments of disease activity at Week 48.

[0273] An increase in glucocorticoids for non-SjD causes (e.g., prophylactic therapy before surgery [stress-dose glucocorticoids]), therapy for certain infections, acute exacerbation of asthma or COPD, or other condition (e.g., contact dermatitis or symptoms of adrenal insufficiency or corticosteroid withdrawal) may be allowed ONCE. This might include a non- SjD glucocorticoid dose up to < 20mg / day of prednisone (or equivalent) for up to a total of 14 days and tapered to less than or equal to the baseline dose by the end of the 14th day and by the Week 36 visit day. The dosage, duration, and non-SjD indication must be clearly indicated in the CRF.

[0274] Participants who receive more than 1 glucocorticoid burst or require a daily dose of>20 mg / day of prednisone (or equivalent) for non-SjD related activity, or who violate any of the criteria above, may continue in the study, but will be considered treatment failure for subsequent assessments of disease activity.

[0275] Considerations for Glucocorticoid Use During Study: Week 36 to Week 48

[0276] No change in glucocorticoids is permitted after Week 36 until Week 48 (except for the management of AEs or prophylaxis for adrenal insufficiency as described below).Participants who receive an increase in glucocorticoids after Week 36 may be considered treatment failure for subsequent assessments of disease activity. Glucocorticoids dose above baseline level will be defined as treatment failure for subsequent assessment of disease activity.

[0277] Other Considerations for Glucocorticoid Use During Study

[0278] Dose adjustment in glucocorticoid is allowed at the investigator’s discretion during the open-label LTE as long as the glucocorticoid dose does not exceed the baseline (Week 0) dose of glucocorticoids. Further glucocorticoid dose reductions during the open-label LTE are encouraged.Table 22A. Permitted Concomitant MedicationsTable 22B. Summary of Permitted Glucocorticoid UseProhibited Therapies

[0279] Use of biologies included in this Section is prohibited for 5 half-lives or 90 days prior to the first administration of study intervention, whichever is greater, unless specified elsewhere in the protocol. The use of small molecule therapies listed in this Section is prohibited for 14 days prior to screening, unless otherwise specified elsewhere in this protocol. Use of additional immunosuppressants or immunomodulators will trigger treatment failure rules. Use of additional immunosuppressants or immunomodulators, other than those explicitly allowed in the inclusion / exclusion criteria are prohibited.

[0280] Prohibited therapies include, but are not limited to, the following:

[0281] Biologies:- Other Fc-conjugated therapeutic agents, including factor or enzyme replacement therapy, not specifically included in other criteria- B cell-depleting therapy or B cell- or lymphocyte-targeted therapies used to treat autoimmune disease (including but not limited to obinutuzumab, belimumab, rituximab, other anti-CD20 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab], B lymphocyte stimulator-receptor fusion protein [BR3] [eg, atacicept], anti-BAFF [e.g., tabalumab])- Anti-interferon medication (eg, anifrolumab)- Anti-TNF medication (eg, infliximab, golimumab, certolizumab pegol, etanercept, CTP13, and adalimumab)- T-cell inhibitors (eg, alefacept, abatacept)- Complement inhibitors (eg, eculizumab)- Inhibitors of interleukins, including anti -IL- 1 (eg, canakinumab, anakinra), anti -IL-6 (eg, tocilizumab), and anti-IL-17 (eg, brodalumab, secukinumab, and ixekizumab)- Interleukin-2 inhibitors or exogenous IL-2 therapy- Other biologies including but not limited to: natalizumab

[0282] Small molecules:- Prednisone >10 mg / day- Parenteral glucocorticosteroids- Cyclosporine A or its derivatives (oral or topical ointment / cream preparations) except for ophthalmic use- Use of cytotoxic drugs within 3 months prior to first administration of study intervention (or 6 months for IV) is prohibited, including but not limited to, cyclophosphamide, chlorambucil, nitrogen mustard, or other alkylating agents- Calcineurin inhibitors (eg, tacrolimus, pimecrolimus, or sirolimus)- JAK / TYK2 inhibitors (eg, tofacitinib, baricitinib)- Toll-like receptor inhibitors are prohibited within 5 half-lives prior to screening- Thalidomide or lenalidomide- Dapsone- Adrenocorticotropic hormone by injectionEpidural, IV and IM glucocorticoidsTopical preparations of any of the therapies noted here, unless specifically allowed, are prohibited- Other systemic immunomodulatory agents not listed elsewhere are prohibited within 5 half-lives prior to screening

[0283] Other therapies:- Medications known to cause significant dry mouth, including but not limited to some antihistamines (oral), selective serotonin reuptake inhibitors or other anxiolytics or anti-depressants, anti-psychotics, anti-seizure medications, anti-hypertensive medications, anti-nausea medications, anti-diarrheal medications, and diuretics, UNLESS the medication(s) are required, SOC treatments for non-SjD comorbidities AND can be safely maintained at stable dosing throughout the study, including at screening, as judged by the investigator. After randomization, the initiation and transient use of such agents that do not confound study assessments, or dose adjustments required or consistent with SOC, as judged by the investigator, are permitted but must be documented- Opioid analgesic medications, EXCEPT within the parameters outlined in permitted concomitant medications- IVIG- Plasmapheresis- Plasma exchange

[0284] Use of other therapies are also prohibited as noted below:- Any investigational intervention (including investigational vaccines) or use of an invasive investigational medical device unless specifically allowed elsewhere in this protocol.The use of complementary therapies (eg, herbs, ointments, acupuncture, or traditional Chinese medicines) that have the potential to activate or inhibit the immune system is prohibited within 4 weeks prior to first administration of study intervention.Primary End point / Estimand Analysis

[0285] The primary clinical question of interest is the following:

[0286] For adults with moderate to severe SjD, who are seropositive for antibodies to Ro / SSA, what is the effect of assigning nipocalimab 460 mg SC qw versus placebo in addition to SOC treatment on the change from baseline in ClinESSDAI score at Week 48, where patients who experience ICEs of initiation or adjustment of concomitant medication that meets treatment failure criteria or treatment discontinuation prior to Week 48 due to lack of efficacy or AE of worsening SjD are considered to have no change from baseline to each study visit starting after first ICE through Week 48 and patients who experience an ICE of treatment discontinuation prior to Week 48 not due to lack of efficacy or AE of worsening SjD are considered to have, at each study visit starting after first ICE through Week 48, a value consistent with other patients in the same treatment group at that visit, based on MAR.

[0287] The corresponding primary estimand of the primary end point has the following attributes:

[0288] Treatment:- Nipocalimab 460 mg SC qw in addition to SOC- Placebo in addition to SOC

[0289] Population: Participants >18 years of age with moderate to severe SjD who are seropositive for antibodies to Ro / SSA.

[0290] Variable / end point: Change from baseline in ClinESSDAI score at Week 48.

[0291] Population-level Summary: Difference in the means of the variable between nipocalimab and placebo.

[0292] ICEs and Corresponding Handling StrategiesTable 23A.

[0293] Supplementary estimand 1 (treatment policy estimand):

[0294] The treatment policy estimand is defined to support the primary estimand of the primary end point. In its definition, the only components that change from the definition of the primary estimand of the primary end point are the variable and strategy used for addressing ICEs 1-3.- Variable / end point: Change from baseline in ClinESSDAI score at Week 48- ICEs and Corresponding Handling StrategyTable 23B.

[0295] Supplementary estimand 2 (while on treatment estimand):

[0296] The while on treatment estimand is defined to support the primary estimand of the primary end point. In its definition, the components that change from the definition of the primary estimand of the primary end point are the variable and strategy used for addressing ICEs 1-3.- Variable / end point: Change from baseline in ClinESSDAI score to last observation on treatment, up to Week 48 or first ICE, whichever occurs earlier- ICEs and Corresponding Handling StrategyTable 23C.

[0297] Analysis of the primary end point

[0298] The primary analysis of the primary end point will use the primary estimand of the primary end point and be based on an ANCOVA model with change from baseline in ClinESSDAI score at Week 48 as the dependent variable and baseline ClinESSDAI score, treatment, and stratification factors for randomization as independent variables.

[0299] Supplementary analyses of the primary end point

[0300] Treatment policy estimand

[0301] The supplementary analysis of the primary end point will use the treatment policy estimand and be based on an ANCOVA model with change from baseline in ClinESSDAI scoreat Week 48 as the dependent variable and baseline ClinESSDAI score, treatment, and stratification factors for randomization as independent variables.

[0302] While on treatment estimand

[0303] The supplementary analysis of the primary end point will use the while on treatment estimand and be based on an ANCOVA model with change from baseline in ClinESSDAI score at Week 48 as the dependent variable and baseline ClinESSDAI score, treatment, study visit, and stratification factors for randomization as independent variables.

[0304] Sensitivity analyses of the primary end point

[0305] To evaluate the robustness of the composite and hypothetical strategies (ICEs 1-2 and ICE 3, respectively) for the primary estimand regarding the assumptions of missing data, a tipping point sensitivity analysis will be performed; more details will be provided in the SAP.

[0306] Other sensitivity analyses of the primary end point may include imputing data affected by ICEs as the worst ClinESSDAI score from baseline to the first ICE, the worst ClinESSDAI score observed for that treatment arm, and jump-to-reference multiple imputation. A sensitivity analysis to explore the impact of oral glucocorticoid tapering / usage on the primary end point may be performed.

[0307] Secondary End points / Estimand Analysis

[0308] Primary estimand for secondary end points:

[0309] The primary estimands for key secondary end points at Week 48 have the same attributes as the primary estimand of the primary end point, except for attributes of variable / end point, population-level summary, and strategy used for ICEs defined below.Table 23D.Supplementary estimands for secondary end points:Supplementary estimand 1 (treatment policy estimand):

[0310] Supplementary estimand 1 has the same components as the primary estimands for key secondary end points, except for the variable and strategy used for ICEs. For binary end points, the variable / end point responder status is based on the observation at Week 48. For continuous end points, the variable / end point is change from baseline in the variable at Week 48. The treatment policy strategy will be used to address all ICEs in supplementary estimand 1 for each key secondary end point.

[0311] Supplementary estimand 2 (while on treatment estimand):

[0312] Supplementary estimand 2 has the same components as the primary estimands for key secondary end points, except for the variable and strategy used for ICEs. For binary end points, the variable / end point responder status is based on the last observation on treatment, up to Week 48 or first ICE, whichever occurs earlier. For continuous end points, the variable / end point is change from baseline in the variable to last observation on treatment, up to Week 48 or first ICE, whichever occurs earlier. The while on treatment strategy will be used to address all ICEs in supplementary estimand 2 for each key secondary end point.Biomarker Analyses

[0313] The biomarker analyses will be used to understand SjD, characterize the effects of nipocalimab to identify PD markers and biomarkers relevant to treatment, and to determine if these markers can predict response to nipocalimab. The biomarker analysis may include but are not limited to serum immunoglobulins, autoantibodies, inflammatory markers, whole blood RNA profile, and other categories of biomarkers potentially involved in the development and the progression of SjD.

[0314] Biomarker analyses may include but are not limited to:- Total antibody (eg, IgG, IgM, IgA), IgG subclasses, and broader autoantibody profiling- Serum biomarker measurements, for example, inflammatory proteins, complement, cytokines, and chemokines- Changes in gene expression profiles in blood (RNA) over time- Changes in autoantibody and soluble proteins in salivaChange in biomarkers including, but not limited to, CRP, ESR, total IgG, IgGl, IgG2, IgG3, IgG4, and autoantibodies (Anti-Ro60 / SSA autoantibodies, anti-Ro52 / TRIM21 autoantibodies, anti-La / SSB autoantibodies, and RF) over time may be summarized by treatment group. Associations between baseline levels and changes from baseline in select biomarkers and clinical response may be explored.

[0315] AbbreviationsACR American College of Rheumatology ADA anti-drug antibodies AE adverse event AESI AE of special interest AIMS External User Guide for Adjudication Information Management System ALP alkaline phosphatase ALT alanine aminotransferase ANA anti-nuclear antibodies ANCOVA analysis of covariance anti-HBc hepatitis B core antibody anti-HBs hepatitis B surface antibody APAC Asia Pacific aPTT activated partial thromboplastin time APS anti-phospholipid syndrome AST aspartate aminotransferase AUC area under the curve AxMP Auxiliary Medicinal Product (also known as NIMP) BAFF B-cell activating factor BCG bacilli Calmette-Guerin / 8 -hCG -human chorionic gonadotropin BUN blood urea nitrogen BYOD bring-your-own-device CBC complete blood count CIC circulating immune complex CIDP chronic inflammatory demyelinating polyneuropathy Cmax maximum observed serum concentration ClinRO clinician-reported outcomeClinESSDAI Clinical European League Against Rheumatism Sjogren’s Syndrome DiseaseActivity IndexCOPD chronic obstructive pulmonary diseaseCOVID-19 Coronavirus Disease 2019CPK creatine phosphokinaseCRESS Composite of Relevant End points in Sjogren’s SyndromeCRF case report form(s) (paper or electronic as appropriate for this study)CRO Contract Research OrganizationCRP C-reactive proteinCT computed tomographyCTCAE Common Terminology Criteria for Adverse EventsDAS28 Disease Activity Score-28DBL database lockDDI drug-drug interactionDILI drug- induced liver injuryDMARD disease-modifying antirheumatic drugDMC Data Monitoring CommitteeEAC Event Adjudication CommitteeECG electrocardiogram eDC electronic data captureEEA European Economic Area eGFR estimated glomerular filtration rateEMG electromyographyEQ-5D EuroQol Five Dimensions Descriptive SystemEQ-5D-5L 5-level EuroQol Five Dimensions Instrument (consisting of the EQ-5D and theEuroQol Visual Analog Scale [EQ-VAS])EQ-VAS EuroQol visual analog scaleERC Ethics Review CommitteeESR erythrocyte sedimentation rateESSDAI EULAR Sjogren’s Syndrome Disease Activity IndexESSPRI EULAR Sjogren’s Syndrome Patient Reported IndexET early terminationEULAR European Alliance of Associations for RheumatologyFACIT-Fatigue Functional Assessment of Chronic Illness Therapy FatigueFc fragment crystallizableFcRn endogenous neonatal fragment crystallizable receptorFIH first-in-humanFNAIT fetal and neonatal alloimmune thrombocytopeniaFOIA Freedom of Information ActFSH follicle-stimulating hormoneFVC forced vital capacityGCP Good Clinical Practice gMG generalized myasthenia gravisHAQ-DI Health Assessment Questionnaire-Disability IndexHBsAg hepatitis B surface antigenHBV hepatitis B virusHCV hepatitis C virusHDFN hemolytic disease of the fetus and newbornHDL high-density lipoproteinHIV human immunodeficiency virusHRCT high-resolution computed tomographyHRQoL Health-Related Quality of lifeHRT hormone replacement therapyHV healthy volunteerIB Investigator's BrochureICE intercurrent eventICF informed consent formICH International Council for HarmonisationIEC Independent Ethics CommitteeIFU Instructions for UseIg immunoglobulinIGRA interferon gamma release assayIIM idiopathic inflammatory myositisILD interstitial lung diseaseIM Intramuscular(ly)IMP Investigational Medicinal ProductINR international normalized ratioIP Intraperitoneal(ly)IRB Institutional Review BoardIV intravenous(ly)IVIG intravenous immunoglobulinIWRS interactive web response systemJEISR Janssen Electronic Inbound Safety ReportingLATAM Latin AmericaLDA low disease activityLDH lactate dehydrogenaseLDL low-density lipoproteinLS least squaresLTE long-term extensionLTM local trial manager mAb monoclonal antibodyMACE major adverse cardiovascular eventsMAD multiple ascending doseMAR missing at randomMCII minimal clinically important improvementMCS mental component scoreMedDRA Medical Dictionary for Regulatory ActivitiesMG-ADL Myasthenia Gravis Activities of Daily LivingMNAR missing not at randomMRI magnetic resonance imagingN / A not applicableNAb neutralizing antibodiesNCS nerve conduction studiesNHYA New York Heart AssociationNIMP Non-Investigational Medicinal ProductNRS numeric rating scaleNS AID nonsteroidal anti-inflammatory drugPCC protocol clarification communicationPCS physical component scorePD pharmacodynamic(s)PFS-AI pre-filled syringe-autoinjectorPFT pulmonary function testPhGA Physician’s Global Assessment of Disease ActivityPI principal investigatorPK pharmacokinetic(s)PQC Product Quality ComplaintPRO patient-reported outcomePtGA Patient’s Global Assessment of Disease ActivityPT / INR prothrombin time / international normalized ratio q2w every 2 weeks q4w every 4 weeksQMG Quantitative Myasthenia Gravis qw weeklyRA rheumatoid arthritisRBC red blood cellRF rheumatoid factorRNA ribonucleic acidRO receptor occupancyRo / SSA Ro / pSS-associated antigen ARTSM Randomization and Trial Supply Management (eg, IWRS)SAD single ascending doseSAE serious adverse eventSAP statistical analysis planSC subcutaneous(ly)SD standard deviationSF-36 Short Form Health Survey 36 StandardSGOT serumglutamic-oxaloacetic transaminaseSGPT serumglutamic-pyruvic transaminaseSIPPM Site Investigational Product Procedures ManualSjD Sjogren's DiseaseSLE systemic lupus erythematosusSoA Schedule of ActivitiesSOC standard of careSSc systemic sclerosisSTAR Sjogren’s Tool for Assessing ResponseSUS AR suspected unexpected serious adverse reactionTB tuberculosisTIC / SIC tender joint count / swollen joint countTMDD target-mediated drug dispositionTNF tumor necrosis factorTSH thyroid-stimulating hormoneULN upper limit of normalVAS visual analog scaleVLDL very-low-density lipoprotein wAIHA warm autoimmune hemolytic anaemiaWBC white blood cellExample 3: An Assessment of the Efficacy of Nipocalimab on Symptoms of Primary Sjogren’s Syndrome (pSS)

[0316] The worst severity of patient symptoms of fatigue, joint pain, mouth dryness, eye dryness, and vaginal dryness were measured using a questionnaire. The questionnaire asked the patients to indicate the worst severity of the given symptom over the prior 7 days using a numerical rating scale from 0 to 10 (i.e., no symptoms to most severe, respectively). The questionnaire was provided to and completed by the patients multiple times during the study period as described in Example 1 above.

[0317] 163 participants were randomized. The nipocalimab 15-mg / kg group had a significant reduction in ClinESSDAI score at Week 24 versus the placebo group (least squares mean difference, -2.65; 90% confidence interval, -4.03 to -1.28; P =0.002). Nipocalimab was associated with dose-dependent reductions in total IgG antibody and anti-Ro autoantibody and anti-La autoantibody levels from Weeks 2 through 24. Numerical improvements were observed in key patient-reported outcomes. The safety profile of nipocalimab was comparable to placebo, with similar rates of adverse events and serious adverse events across groups. The results show that the symptoms improved in patients during the study, with greater numerical improvements reported by patients receiving nipocalimab 15 mg / kg intravenously every two weeks compared to those receiving either placebo or nipocalimab 5 mg / kg iv every two weeks (FIGs. 13A-E).

[0318] An unstimulated salivary flow measurement was carried out over a period of15 minutes, as described in. The patients were asked to refrain from any oral intake for at least 2 hours prior to start of the test. Participants were asked to swallow their saliva once or expectorate before the start of the test and then to spit into a pre-weighed tube for 15 minutes. The collection tube was re-weighed, and the volume of saliva produced was calculated using the specific gravity for water (1 g / mL). As shown in FIG. 14, the proportion of patients that exhibited at leasta 50% increase in their unstimulated salivary flow from baseline at week 24 was greatest in the nipocalimab 15 m / g / kg group (0.327) compared to the placebo group (0.16) or the nipocalimab 5 mg / kg group (0.18).

[0319] 163 participants with active SjD were randomized and received >1 dose of nipocalimab 5 mg / kg (n=53), nipocalimab 15 mg / kg (n=54), or placebo (n=56) and were part of efficacy and safety analyses. Key demographic and baseline characteristics were generally balanced across groups (Table 24). The majority of participants were white and female. The mean age was 48.1 years (range: 20-73 years). The mean (SD) baseline ClinESSDAI, ESSDAI, and ESSPRI scores were 9.9 (3.49), 8.9 (3.44), and 7.08 (1.23).Table 24. Baseline Study Population Characteristics.Activity Index; DMARD, disease-modifying antirheumatic drug; ESSDAI, European LeagueAgainst Rheumatism Sjogren’s Syndrome Disease Activity Index; ESSPRI, European LeagueAgainst Rheumatism Sjogren’s Syndrome Patient Reported Index; FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue; PhGA, Physician’s Global Assessment of Disease Activity; PtGA, Patient's Global Assessment of Disease Activity; Q2W, every 2 weeks; SD, standard deviation.Primary Efficacy End Point

[0320] The nipocalimab 15 mg / kg group met the primary end point: the reduction in ClinESSDAI score from baseline at Week 24 was significantly greater compared with placebo (LS mean [90% confidence interval (CI)], -6.40 [-7.43 to -5.36] vs -3.74 [-4.74 to -2.75]; LS mean difference [90% CI], -2.65 [-4.03 to -1.28]; P=0.002; FIGs. 15A-F; Table 25). Reduction in ClinESSDAI score from baseline to Week 24 was similar with nipocalimab 5mg / kg versus placebo (LS mean [90% CI], -4.08 [-5.10 to -3.07] vs -3.74 [-4.74 to -2.75]; P=0.68).Table 25. Efficacy End Points for Nipocalimab 5 mg / kg and Nipocalimab 15 mg / kg VersusPlacebo.CI, confidence interval; ClinESSDAI, Clinical European League Against Rheumatism Sjogren’sSyndrome Disease Activity Index; CRESS, Composite of Relevant Endpoints for Sjogren’s Syndrome; DAL, disease activity level; ESSPRI, European League Against Rheumatism Sjogren’s Syndrome Patient Reported Index; LS, least squares; PhGA, Physician Global Assessment of Disease Activity; Q2W, every 2 weeks; STAR, Sjogren’s Tool for Assessing Response.*Compared with the placebo group using a mixed-effects repeated measures model with baseline score, study treatment, visit, region, baseline steroid use, baseline antimalarial use, and a treatment-by-visit interaction as terms in the model. For continuous end points, participants who experienced an intercurrent event per protocol were considered to have missing data thereafter. ^Compared with the placebo group using a Cochran-Mantel-Haenszel test with region, baseline steroid use, and baseline antimalarial use as stratification factors. For binary composite end points, participants who experienced intercurrent events were considered nonresponders after the event.‘DAL response is a reduction from baseline in DAL by >1 level in >1 ClinESSDAI or ESSDAI domain (e.g., articular, hematological, cutaneous, and constitutional). DALs range from 0 to 2 or 0 to 3 depending on the domain.Secondary and Exploratory Efficacy End Points

[0321] The nipocalimab 15 mg / kg group exhibited a numerical reduction in ESSDAI score at Week 24 compared with placebo (LS mean [90% CI], -4.61 [-5.49 to -3.73] vs -2.82 [-3.67 to -1.98]; FIG. 16). Additionally, participants receiving nipocalimab 15mg / kg had consistent numerical improvement versus placebo across most additional efficacy end points, including STAR, CRESS, DAL response, and PhGA at Week 24 (Table 25). Nipocalimab 15 mg / kgtreatment resulted in numerically greater reductions from baseline in ESSPRI score from Week 12 through Week 24 (FIGs. 15A-F). Numerical improvement was observed in patient-reported fatigue, joint pain, eye dryness, and mouth dryness. There was also a numerical improvement in patient-reported vaginal dryness in the nipocalimab 15 mg / kg group compared with placebo (LS mean difference [90% CI], -0.93 [-1.86 to 0.00]; FIGs. 13A-E). The proportion of participants exhibiting >50% improvement in salivary flow was 2-fold higher with nipocalimab 15mg / kg versus placebo (FIG. 14). Secondary efficacy outcomes were generally similar between nipocalimab 5 mg / kg and placebo.

[0322] In the post hoc subgroup analysis, improvement in ClinESSDAI score appeared to be greater in participants with higher numbers and / or levels of autoantibodies (FIGs. 15 A-F; FIG. 17). At Week 24, there was a LS mean (90% CI) treatment difference versus placebo of -3.47 [-5.84 to -1.11] in the sero-high group compared with -2.11 [-4.84 to 0.63] in the sero- low group with nipocalimab 15mg / kg.Clinical Biomarkers

[0323] There were dose-dependent reductions in total IgG, anti-Ro60 autoantibody, anti- Ro52 autoantibody, and anti-La autoantibody levels from Weeks 2 through 24 of nipocalimab treatment (FIGs. 18A-D), describing nipocalimab’s proposed mechanism of action. At Week 24, there was a median (interquartile range [IQR]) predose (minimum) reduction of 60.9% (45.7% to 65.9%) in total IgG with nipocalimab 15 mg / kg. Total IgG and autoantibody levels returned to baseline within 8 weeks of the last nipocalimab administration. Nipocalimab treatment appeared to be associated with reduced ESR and RF compared with placebo throughout the 24-week treatment period (FIGs. 19A-D). The median (IQR) changes in IgA and IgM at Week 24 were 6.0% (-1.0% to 12.2%) and -10.5% (-22.0% to -4.1%) with nipocalimab 15mg / kg versus -1.2% (-6.2% to 3.7%) and 2.5% (-6.5% to 10.0%) with placebo.Safety

[0324] Nipocalimab was well-tolerated, with no major safety signals observed. No deaths or opportunistic infections were reported. No participants exposed to nipocalimab experienced major adverse cardiovascular events (MACE; cardiovascular death, nonfatal myocardialinfarction, and nonfatal stroke); 2 participants in the placebo group experienced MACE. The most common AEs were infections and infestations: 60.4% (n=32), 51.9% (n=28), and 42.9% (n=24) of participants in the nipocalimab 5 mg / kg, nipocalimab 15 mg / kg, and placebo groups, respectively. Gastrointestinal disorders were reported in 17.0% (n=9), 37.0% (n=20), and 16.1% (n=9) in the nipocalimab 5 mg / kg, nipocalimab 15 mg / kg, and placebo groups, respectively. Activation of latent virus was infrequently reported across groups. The most common AE by preferred term was headache. No serious AEs were deemed related to the study treatment by investigators.

[0325] Among participants with available postbaseline IgG values, there was a greater proportion with minimum postbaseline IgG <6g / L in the nipocalimab 5 mg / kg (25.5% [n=l 3 / 51 ]) and 15 mg / kg (50.0% [n=26 / 52]) groups compared with placebo (1.8% [n=l / 56]; Table 26). No participants had total IgG <lg / L during the study. There was no clear association between hypogammaglobulinemia and serious AEs. In all participants through the end of the study, infections that were severe or required IV anti-infective or surgical management occurred in 3.8% (n=2 / 53), 1.9% (n=l / 54), and 1.8% (n=l / 56) of participants in the nipocalimab 5 mg / kg, nipocalimab 15 mg / kg, and placebo groups, respectively, with no clear association with level of hypogammaglobulinemia in those with available postbaseline IgG values. An imbalance was observed between the placebo and nipocalimab 15mg / kg groups in the incidence of diarrhea in participants with an IgG nadir between 1 and <3g / L.Table 26. Observed Predose (Minimum) Postbaseline IgG Levels through the End of the StudyIgG, immunoglobulin G; Q2W, every 2 weeks.

[0326] No participants developed severe hypoalbuminemia (albumin <20g / L). Mean (standard error) changes from baseline in albumin (-6.9% [0.8%]), low-density lipoproteincholesterol (+6.6% [2.5%]), and total cholesterol (+8.3% [1.9%]) at Week 24 with nipocalimab 15mg / kg were not clinically significant and did not result in any change in related therapy during the study.Discussion and Conclusion

[0327] Nipocalimab 15 mg / kg met the primary end point and led to significant improvement over placebo in ClinESSDAI score at 24 weeks in the study, the first trial of an FcRn blocker in SjD. Improvements in ClinESSDAI were generally greatest in the participants with the highest baseline levels of anti-Ro autoantibodies and anti-La autoantibodies and appeared to be associated with substantial nipocalimab-induced reductions in autoreactive and total IgG antibodies. Nipocalimab 15 mg / kg also demonstrated substantial numeric improvements in STAR, CRESS, DAL response, and PhGA at Week 24. Furthermore, nipocalimab 15 mg / kg treatment resulted in numerical improvements in patient-reported outcomes, including ESSPRI, eye dryness, mouth dryness, vaginal dryness, fatigue, and joint pain. Both nipocalimab doses were well-tolerated, with no major safety signals identified. The clinical efficacy of nipocalimab and associated reductions in autoreactive and total IgG antibodies support a pathogenic role for IgG autoantibodies in SjD and provide evidence that potent FcRn blockade by nipocalimab is effective for SjD treatment.

[0328] There were no instances of severe hypoalbuminemia, nor any AEs associated with the observed mild decreases in serum albumin in the study. Neither nipocalimab regimen tested resulted in clinically meaningful changes in albumin or cholesterol levels, in contrast to other FcRn blockers.In conclusion, FcRn blockade by nipocalimab 15 mg / kg improved clinical outcomes versus placebo in participants with moderately-to-severely active SjD.Example 4: Dose Selection for the Phase 3 Study (Example 2)

[0329] For the Phase 3 study (detailed in Example 2), the nipocalimab dose regimen is 460 mg SC administered weekly (QW) based on simulation of the 15 mg / kg IV biweekly dosing regimen (used in the Phase 2 study detailed in Example 1). Model-based simulations were conducted to support this selected dose regimen for Phase 3.PK-IgG Simulation

[0330] PK / PD simulations were conducted using the updated PK-RO-IgG model with the Phase 2 data for 1000 individuals. As shown in FIG. 20, transitioning from a less frequent dosing interval (ie, IV dosing every other week) to a more frequent dosing interval (ie, SC dosing every week) will lead to an additional 9% median pre-dose IgG lowering (IV 63.3% vs SC 72.3%) and less peak to trough fluctuation, with a similar median average %IgG lowering (IV 71.8% vs SC 74.0%) and similar median maximum %IgG reduction (IV 78.2% vs SC 75.9%) (FIG. 20 and Table 27). As there is minimal difference for average %IgG lowering between the posologies, similar efficacy will be achieved from the 460 mg SC dose regimen compared to the previously studied 15 mg / kg IV Q2W regimen as IgG is a biomarker of efficacy.Table 27: Summary of predicted changes in IgG with administration of nipocalimab at 15 mg / kg IV Q2W and 460 mg SC QWclinESSDAI Simulation

[0331] Model-based simulations using the final clinESSDAI model, integrating the updated PK-RO-IgG model, were further conducted to evaluate and support the dose regimen selection for the Phase 3 study in patients with SjD. As shown in FIG. 21, in addition to the placeboresponse, the 460 mg SC QW dose regimen is predicted to provide comparable clinESSDAI lowering compared to the studied 15 mg / kg IV Q2W regimen. The predicted median clinESSDAI lowering is 4.6 points, which is similar to the predicted reduction of 4.4 points with the dose regimen of 15 mg / kg IV Q2W (FIG. 21 & Table 28). Predictions for clinESSDAI responses are provided up to Week 24 to align with the study duration of the Phase 2 study (Example 1).Table 28: Summary of predicted changes in clinESSDAI with administration of nipocalimab at 15 mg / kg IV Q2W and 460 mg SC QWLipid Simulations

[0332] Model-based simulations were performed to compare the change in total cholesterol and LDL associated with nipocalimab dosing for the two dosing regimens, using a population similar to SJD patients in the Phase 2 study (Example 1). The effect on lipids is predicted to be similar between 15 mg / kg IV Q2W and 460 mg SC QW regimens, with minimal differences (<2%) between the two regimens (FIG. 22A and 22B). A summary of model-predicted total cholesterol and LDL changes from baseline, as well as the probabilities of total cholesterol and LDL going above clinically relevant thresholds at Week 24, was also provided (Table 29).Table 29: Summary of Model-predicted Total Cholesterol and LDL Response at Week 24Software

[0333] Population PK, PK-IgG, PK-IgG-clinESSDAI, and PK-lipid models were developed using nonlinear mixed-effects modeling methods performed using NONMEM (version 7.4, Icon Development Solutions, Ellicott City, MD, USA). The use of NONMEM, including model qualification procedures, was within the environment of a compatible front-end program (Pearlspeaks NONMEM [PsN] version 4.6.0) in a validated environment, HP3 GxP. The first-order conditional estimation method with interaction (FOCE-I) in NONMEM was employed for model runs.Data processing, diagnostic graphics, exploratory analyses, postprocessing of the NONMEM outputs, and statistical analysis were performed using the R software (version 3.6.2 or above). Population PK and PKPD model-based simulations were conducted using R.SUMMARY AND CONCLUSIONSPopulation PK / PK-IgG analysis

[0334] The external validation using the previously established HV IV-SC PK / RO and IgG models identified high variability of nipocalimab PK and high IgG baseline in the SjD participants’ data in the Phase 2 Study (Example 1).

[0335] The PK / RO and IgG models were updated based on the pooled healthy participant studies and SjD data of the Phase 2 Study. The observed time course of nipocalimab concentrations in SjD and healthy participants were adequately described by a two- compartment QSS TMDD model. The covariate effect of body weight on CL, Q, Vc and Vp was a prioriincluded in the model. Model diagnostics did not show an apparent effect of additional covariates on model parameters.

[0336] The observed IgG concentration-time data after IV administration of nipocalimab in SjD and healthy participants were adequately described by an indirect response model.Population (SjD vs healthy participants) was included as a covariate on IgG baseline. Model diagnostics did not show an apparent effect for any of the other evaluated covariates on model parameters.

[0337] The 460 mg QW SC regimen was found to provide a similar average %IgG median lowering via simulations relative to the 15 mg / kg Q2W IV regimen at steady-state in SjD population (predicted change of 71.8% for 15 mg / kg IV Q2W vs. 74.0% for 460 mg SC QW, respectively) and would result in 9% greater minimum (predose) IgG median lowering (63.3% for 15 mg / kg IV Q2W vs. 72.3% for 460 mg SC QW, respectively). clinESSDAI analysis

[0338] The total change of clinESSDAI scores from baseline was modeled as a combined effect of placebo response and the treatment effect, both of which were modeled using a linear relationship.

[0339] The treatment effect was delayed relative to the IgG profile, which was the driver of efficacy in the model. A delayed IgG effect compartment accounted for the lag in clinESSDAI changes relative to IgG reductions. Covariate analysis identified the individual baseline clinESSDAI score as a significant co variate for both the placebo response and the treatment effect.

[0340] As there is minimal difference for average %IgG reduction for the 2 routes of administration, the 460 mg SC QW is expected to produce a similar magnitude of clinESSDAI improvement as 15 mg / kg IV Q2W.Lipid analysis

[0341] Total cholesterol time course was adequately captured by an indirect response model. The concentration of nipocalimab-FcRn complex was chosen as the driver for the elevation in lipid levels over time by decreasing the degradation rate of total cholesterol.

[0342] LDL was linked to total cholesterol through a direct linear relationship. No significant covariate effect was identified among the tested patient-specific factors, including demographics and baseline disease status.Similar effects for lipids are expected with the 460 mg SC QW regimen, with a predicted higher increase of -1-2% for 460 mg SC QW vs. 15 mg / kg IV Q2W for both total cholesterol and LDL.

Claims

What is claimed is:

1. A method of treating Sjogren's disease in a subject in need thereof, the method comprising administering an anti-FcRn agent to the subject.

2. The method of claim 1, wherein the anti-FcRn agent is administered every week, every two weeks, every three weeks, or monthly.

3. The method of claim 1 or 2, wherein the anti-FcRn agent is nipocalimab, rozanolixizumab, batoclimab, IMVT-1402, efgartigimod, SYNT001, SYNT002, ABY-039, or DX-2507.

4. The method of any one of the preceding claims, wherein the anti-FcRn agent is administered at a dose from about 5 mg / kg to about 45 mg / kg, about 5 mg / kg to about 15 mg / kg, about 15 mg / kg to about 45 mg / kg, or about 30 mg / kg to about 45 mg / kg based on the weight of the subject.

5. The method of any one of the preceding claims, wherein the anti-FcRn agent is administered at a dose of about 5 mg / kg, about 15 mg / kg, about 30 mg / kg, or about 45 mg / kg based on the weight of the subject.

6. The method of any one of the preceding claims, wherein the anti-FcRn agent is administered intravenously or subcutaneously.

7. The method of any one of the preceding claims, wherein the anti-FcRn agent is an anti-FcRn antibody comprising:(a) a light chain, which comprises a CDR LI comprising an amino acid sequence of SEQ ID NO: 3, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 4, and a CDR L3 comprising an amino acid sequence of SEQ ID NO: 5; and(b) a heavy chain, which comprises a CDR Hl comprising an amino acid sequence of SEQ ID NO: 6, a CDRH2 comprising an amino acid sequence of SEQ ID NO: 7, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 8.

8. The method of claim 7, wherein (a) the light chain of the anti-FcRn antibody comprises a light chain variable region comprising an amino acid sequence of SEQ ID NO: 9; and (b) the heavy chain of the anti-FcRn antibody comprises a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 10.

9. The method of claim 7 or claim 8, wherein (a) the light chain of the anti-FcRn antibody comprises an amino acid sequence of SEQ ID NO: 1; and (b) the heavy chain of the anti-FcRn antibody comprises an amino acid sequence of SEQ ID NO: 2.

10. The method of any one of the preceding claims, wherein the anti-FcRn agent is nipocalimab.

11. The method of any one of the preceding claims, wherein nipocalimab is administered every two weeks intravenously at 10-30 mg / kg based on the weight of the subject.

12. The method of any one of the preceding claims, wherein nipocalimab is administered every two weeks intravenously at 15 mg / kg based on the weight of the subject.

13. The method of any one of the preceding claims, wherein nipocalimab is administered every week subcutaneously at 200-1000 mg.

14. The method of any one of the preceding claims, wherein nipocalimab is administered every week subcutaneously at 200-1000 mg.

15. The method of any one of the preceding claims, wherein nipocalimab is administered every week subcutaneously at 230, 460, 690, or 920 mg.

16. The method of any one of claims 13-15, wherein nipocalimab is administered via an auto injector.

17. The method of any one of the preceding claims, wherein the method provides a clinical benefit as measured by a decrease in Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (clinESSDAI) score in the subject by more than 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 from baseline within 4, 8, 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

18. The method of any one of the preceding claims, wherein the method provides a clinical benefit as measured by a decrease in Clinical European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (clinESSDAI) score in the subject by more than 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or 17 from baseline within 24 weeks of initiation of said administering.

19. The method of any one of the preceding claims, wherein the method provides a clinical benefit as measured by a decrease in European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ESSDAI) score in the subject by more than 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

20. The method of any one of the preceding claims, wherein the method provides a clinical benefit as measured by a decrease in the European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (ESSDAI) score in the subject by more than 3, 4, 5, or 6 from baseline within 24 weeks of initiation of said administering.

21. The method of any one of the preceding claims, wherein the method provides a clinical benefit as measured by a decrease in Physician's Global Assessment of Disease Activity (PhGA) score in the subject by more than 10, 12, 14, 16, 18, 20, 25, 27, 30, 33, 38, 43, 48, or 52 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

22. The method of any one of the preceding claims, wherein the method provides a clinical benefit as measured by a decrease in PhGA score in the subject by more than 33, 38, 43, 48, or 52 from baseline within 24 weeks of initiation of said administering.

23. The method of any one of the preceding claims, wherein the subject achieved ESSDAI-3 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering.

24. The method of any one of the preceding claims, wherein the subject achieved ESSDAI-4 response within 12, 18, 24, 30, 36, 42, 48, or 52 weeks of initiation of said administering.

25. The method of any one of the preceding claims, wherein the subject achieved clinESSDAI-3 response within 24 weeks of initiation of said administering.

26. The method of any one of the preceding claims, wherein the subject achieved clinESSDAI-4 response within 24 weeks of initiation of said administering.

27. The method of any one of the preceding claims, wherein the subject achieved ESSPRI response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

28. The method of any one of the preceding claims, wherein the subject achieved STAR response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

29. The method of any one of the preceding claims, wherein the subject achieved DAL response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

30. The method of any one of the preceding claims, wherein the subject achieved CRESS response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

31. The method of any one of the preceding claims, wherein the subject has an improvement in each of the Sjogren’s symptoms, wherein the Sjogren’s symptoms comprise: fatigue, eye dryness, mouth dryness, joint pain, and vaginal dryness.

32. The method of any one of the preceding claims, wherein the subject achieves an improvement in tear production by 3, 5, 10, 15, 20, 25, 30, or 35 mm from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

33. The method of claim 32, wherein the tear production is measured by the Schirmer’s test.

34. The method of any one of the preceding claims, wherein the subject achieves an improvement in basal saliva production by 0.02, 0.05, 0.08, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, or 1 mL / min from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

35. The method of claim 34, wherein the basal saliva production is measured by the Unstimulated Salivary Flow Test.

36. The method of any one of the preceding claims, wherein the subject achieves a reduction in keratoconjunctivitis sicca (KCS) by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

37. The method of claim 36, wherein the KCS is measured by the ocular surface staining (OSS).

38. The method of any one of the preceding claims, wherein the subject has a reduced need for glucocorticoid treatment from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

39. The method of any one of the preceding claims, wherein the method provides a clinical benefit as measured by a decrease in DAS28-CRP by more than 0.8, more than 1, more than 1.2, more than 1.4, more than 1.6, more than 1.8, more than 2, more than 2.2, more than 2.4, more than 2.6, more than 2.8, more than 3, more than 3.2, more than 3.4, more than 3.6, more than 3.8, more than 4, more than 4.2, more than 4.4, more than 4.6, more than 4.8, more than 5, more than 5.2, more than 5.4, more than 5.6, more than 5.8, or more than 6 from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

40. The method of any one of the preceding claims, wherein the method provides the subject an improvement in health-related quality of life (HRQol) from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

41. The method of claim 40, wherein the HRQol is measured by the 36-item Short Form Health Survey Questionnaire (SF-36) score.

42. The method of any one of the preceding claims, wherein the method provides a clinical benefit as measured by the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT- Fatigue) score in the subject by more than 5, 10, 15, 20, 25, 30, 35, or 40 points from baseline within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

43. The method of any one of the preceding claims, wherein the subject achieves a Sjogren's Syndrome Responder Index (SSRI) response greater than or equal to a 20% or 30% improvement from baseline in at least two or three of five domains of the SSRI response within 12, 18, 24, 30, 36, 42, 48 or 52 weeks of initiation of said administering.

44. The method of claim 43, wherein the five domains comprise fatigue, oral dryness, ocular dryness, unstimulated whole salivary flow, and erythrocyte sedimentation rate.

45. The method of any one of the preceding claims, wherein the subject has a reduction in autoantibodies in the blood.

46. The method of claim 45, wherein the autoantibodies are selected from the group consisting of: anti-La (SSB) autoantibodies, anti-Smith, antinuclear antibodies (ANA), anti-phospholipid antibodies, anti-dsDNA antibodies, anti-nRNP (ribonucleoproteins) antibodies, anti-rheumatoid factor antibodies, anti-Ro60 (SSA) autoantibodies, and anti-Ro52 autoantibodies.

47. The method of any one of the preceding claims, wherein the method does not significantly decrease level of albumin in the subject compared with baseline.

48. The method of any one of the preceding claims, wherein the method does not significantly increase the level of serum total cholesterol in the subject compared with baseline.

49. A method of treating Sjogren's disease in a subject in need thereof, the method comprising administering an anti-FcRn antibody to the subject, wherein the anti-FcRn antibody comprises:(a) a light chain, which comprises a CDR LI comprising an amino acid sequence of SEQ ID NO: 3, a CDR L2 comprising an amino acid sequence of SEQ ID NO: 4, and a CDR L3 comprising an amino acid sequence of SEQ ID NO: 5; and(b) a heavy chain, which comprises a CDR Hl comprising an amino acid sequence of SEQ ID NO: 6, a CDR H2 comprising an amino acid sequence of SEQ ID NO: 7, and a CDR H3 comprising an amino acid sequence of SEQ ID NO: 8; and wherein the anti-FcRn antibody is administered every week subcutaneously at 460 mg.

50. A method of treating Sjogren's disease in a subject in need thereof, the method comprising administering nipocalimab to the subject, wherein the nipocalimab is administered every week subcutaneously at 460 mg.