Phase 1b Trial of RAY121 in Immunological Diseases (RAINBOW Trial)

This Phase 1b basket trial will investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy of RAY121, a inhibitor of classical complement pathway, after multiple dose administration in patients with immunological diseases such as antiphospholipid syndrome (APS), bullous pemphigoid (BP), Behçet's Syndrome (BS), dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM) and immune thrombocytopenia (ITP).

1. Signed informed consent form 2. Age ≥ 18 and ≤ 85 at the time of signing informed consent form with Karnofsky score ≥ 60 % at screening 3. Ability to comply with the study protocol 4. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods 5. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm 6. APS cohort: Established primary APS defined by the following criteria (at least one of the laboratory criteria and one of the clinical criteria must be met): * Laboratory criteria (aPL profile) * Persistently positive LA test * Persistently positive aCL IgG isotype * Persistently positive aβ2GPI IgG isotype * Clinical criteria * Livedoid vasculopathy and presence of skin ulcer * Acute/chronic aPL nephropathy 7. BP cohort: 1\) Predominant cutaneous lesions 2) Diagnosis with BP with following assessments positive: 1. Positive direct immunofluorescence, and either 2. Positive indirect immunofluorescence, or 3. Positive serology on ELISA for BP180 autoantibody 3) BPDAI score \>= 20 4) Weekly average of daily Peak Pruritus NRS \>=4 5) Accept to take photograph of bullous lesions 8\. BS cohort: 1. Diagnosed with BS 2. Oral ulcers that occurred at least 3 times in the previous 12 month period 3. Have at least 2 oral ulcers over the 4 weeks prior to screening 4. Have at least 2 oral ulcers at Week 0 5. Have prior treatment with at least 1 non-biologic BS therapy 6. Patients who need systemic therapy as whose oral or mucocutaneous ulcers cannot be adequately controlled by topical therapy 9\. DM cohort: 1. Diagnosed with definite or probable inflammatory myopathies and categorized as DM 2. Patients with inadequate response to corticosteroids and/or immune-suppressants or intolerance to DM therapies 3. MMT-8 score \< 142, with at least one abnormality in the following Core Set Measures: * PtGA-VAS \>= 2 cm * PhGA-VAS \>= 2 cm * Global extra-muscular activity \>= 2 cm * At least one muscle enzyme \> 1.5 times ULN * HAQ \>= 0.25 4. Moderate to severe DM defined as CDASI activity score \> 14 10\. IMNM cohort: 1. Clinically Diagnosed with IMNM as anti-HMGCR myopathy or anti-SRP myopathy 2. CK \> 1,000 U/L 3. Patients who have an inadequate response to corticosteroids and/or immunesuppressants or intolerance to IMNM therapies 4. MMT-8 score \< 142 11\. ITP cohort: 1. Confirmed diagnosis of persistent/chronic ITP based on the following criteria: * ITP defined per the current guidelines * Platelet count \ 1.5 × ULN in combination with an elevated total bilirubin \> 1.5 × ULN 19. APS cohort: * 1\) APS associated with other systemic autoimmune disease * 2\) Acute thrombosis (arterial or venous acute thrombosis diagnosis) within 30 days before screening * 3\) Patients with thrombotic APS without any anticoagulation treatment * 4\) Treatment with prohibited medications 20. BP cohort: ・ 1) Initiation of treatment with or increase in the dose of systemic or topical corticosteroid within 2 weeks * 2\) Current treatment with a drug that may cause or exacerbate BP unless the dose has been stable * 3\) Initiation of treatment with topical calcineurin inhibitor, or topical phosphodiesterase (PDE) 4 inhibitor within 7 days * 4\) Treatment with prohibited medications 21. BS cohort: ・ 1) BS-related active major organ involvement-ocular lesions requiring immunosuppressive therapy, pulmonary (e.g., pulmonary artery aneurysm), vascular (e.g., thrombophlebitis), gastrointestinal (e.g., ulcers along the gastrointestinal tract), and central nervous systems (e.g., meningoencephalitis) manifestations * 2\) History of venous or arterial thrombosis within 1 year * 3\) Treatment with prohibited medications 22. DM cohort: ・ 1) PhGA-VAS improvement \>= 3, or clinically relevant improvement between screening and baseline * 2\) Overlap myositis (except for overlap with Sjögren's syndrome), connective tissue disease associated DM, inclusion body myositis, polymyositis, IMNM, juvenile DM or drug-induced myopathy * 3\) Cancer-associated myositis * 4\) Significant muscle damage * 5\) Past history of severe Interstitial lung disease flare, severe non-infectious lung inflammation which required active intervention, or multiple episodes of lung disease * 6\) Severe respiratory muscle weakness * 7\) Severe bulbar palsy * 8\) Treatment with prohibited medications 23. IMNM cohort: ・ 1) PhGA-VAS improvement \>= 3, or clinically relevant improvement between screening and baseline ・ 2) Overlap myositis (except for overlap with Sjögren's syndrome), connective tissue disease associated DM, inclusion body myositis, polymyositis, juvenile DM or druginduced myopathy ・ 3) Cancer-associated myositis ・ 4) Significant muscle damage ・ 5) Past history of severe Interstitial lung disease (ILD) flare, severe non-infectious lung inflammation which required active intervention, or multiple episodes of lung disease ・ 6) Severe respiratory muscle weakness ・ 7) Severe bulbar palsy ・ 8) Treatment with prohibited medications 24. ITP cohort: ・ 1) Secondary ITP ・ 2) Clinical diagnosis or history of Myelodysplastic Syndrome or autoimmune hemolytic anemia ・ 3) History of venous or arterial thrombosis within 12 months ・ 4) Patients who experienced major bleeding within 4 weeks * 5\) Treatment with prohibited medications * 6\) Any laboratory test results meet either of the following criteria at screening: * Hemoglobin \= 10 μIU/mL