Systemic Sclerosis (SSc) Clinical Trials

• Age ≥18 and ≤75

• Signed informed consent form and ability to adhere to the study visit schedule and comply with other protocol requirements

• Women of childbearing potential must have negative pregnancy tests at screening and baseline, and agree to abstinence or acceptable birth control from 2 weeks prior to the first dose through 1 year after the last dose

• For participants taking corticosteroids, the prednisone (or equivalent) dose must be ≤20 mg/day at 2 weeks prior to Screening and stable for ≥ 14 days before start of Screening

• For participants on immunosuppressives or immunomodulators (other than corticosteroids), all doses must be stable for ≥ 4 weeks prior to Screening

• eGFR as calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation of ≥45 mL/min/1.73 m2 at screening

∙ SSc Inclusion Criteria:

• Meets the 2013 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria for SSc

• Meet criteria a and/or b:

• a. Severe skin involvement defined as mRSS ≥ 30 or active skin disease defined as mRSS ≥ 15 at screening and one or more of the following within the prior 6 months of screening:

• i. An increase in mRSS of ≥ 3 units

• ii. Involvement of 1 new body area with ≥ 2 mRSS units

• iii. 2 new body areas with ≥ 1 mRSS unit

• b. Moderate to severe Interstitial Lung Disease (ILD) defined by evidence of ILD on High-resolution computed tomography (HRCT) and FVC \< 70% of predicted or DLCO (hemoglobin or alveolar volume corrected) \< 70% of predicted or ILD on HRCT and progressive ILD meeting at least 2 of the following 3 criteria within the prior 6 months of screening:

• i. Worsening respiratory symptoms

• ii. Evidence of progression on HRCT, or

• iii. Evidence of absolute decline in FVC ≥ 5%

• 10 years or less since the first non-Raynaud's sign or symptom

• Inadequate response or intolerance to at least one treatment, including cyclophosphamide, methotrexate, MMF/mycophenolic acid, nintedanib, rituximab, or tocilizumab

∙ IIM Inclusion Criteria:

• Diagnosis for IIM as per 2017 ACR/EULAR Classification Criteria

• One positive myositis antibody

• Activity defined as manual muscle testing (MMT-8) score \<136/150

• Creatinine kinase or aldolase ≥ 1.5 x ULN and Clinician Global Assessment ≥ 2 cm with at least one of the following:

‣ Evidence on magnetic resonance imaging (MRI) of active myositis within the last 6 months

⁃ Electromyography (EMG) with active myositis within the last 6 months

⁃ Muscle Biopsy of active myositis within last 6 months

⁃ Global extramuscular activity score ≥2 cm per Clinician global assessment (CGA) using a visual analog scale (VAS) (0-100 mm)

• Note: Participants with DM or ASyS may be eligible despite CK or aldolase \<1.5 × ULN, provided they have a Clinician Global Assessment ≥2 cm and meet at least one of criteria (a)-(d) above OR have a CDASI score of ≥20.

• Inadequate response to treatment defined as ≥ 3 months failure (or intolerance) to at least 2 immunosuppressive therapies (including glucocorticoids)

∙ AAV:

• Meets the 2022 ACR/EULAR classification criteria for Granulomatosis with Polyangiitis (GPA) (Robson 2022) or Microscopic Polyangiitis (MPA) (Suppiah 2022)

• Relapsed or refractory AAV despite repeated treatment with immunosuppressive agents or requiring prolonged and/or repeated courses of unacceptable doses of glucocorticoids to maintain disease control

• Positive test for anti-proteinase-3 (PR3-ANCA) or anti-myeloperoxidase (MPO-ANCA) at screening

• Have at least one major item, or at least 3 other items, or at least 2 renal items on the BVAS version 3

∙ RA Inclusion Criteria:

• Documented diagnosis of RA, meeting the 2010 ACR/EULAR classification criteria

• Rheumatoid Factor (RF) or Anti-Citrullinated Protein Antibody (ACPA) positive

• CRP \>3 mg/L

• Inadequate response, defined as failure to achieve a clinically meaningful improvement (eg, ACR50 response or DAS28-low disease activity \[ie, DAS28 \>3.2\]) after at least 12 weeks of therapy with the following:

‣ At least 1 conventional synthetic DMARD (csDMARD) (eg, methotrexate, leflunomide, sulfasalazine, hydroxychloroquine) AND

⁃ Either of the following:

• i. At least 2 biologic (b) DMARDs (eg, TNF inhibitors, abatacept, anti-IL-6 or anti-IL-6R, rituximab) with distinct mechanisms of action (MoAs)

• OR

• ii. At least 1 bDMARD and at least 1 targeted synthetic DMARD (tsDMARD) (eg, JAK inhibitor)

• AND

• c. Have failed no more than 3 biologics or tsDMARDs with unique mechanisms of action

• Minimum of 6 swollen joint counts (SJCs) and 6 tender joint counts (TJCs) according to joint assessment