CC312 / CytoCares - LARVOL DELTA

Safety Study of CC312 in Adult Patients With Relapsed/Refractory CD19 Positive B-cell Hematologic Malignancies (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: CytoCares Inc | Trial primary completion date: Mar 2025 ➔ Mar 2026

Trial primary completion date • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of CC312 for Relapsed/Refractory Autoimmune Diseases (clinicaltrials.gov) - P1 | N=6 | Recruiting | Sponsor: CytoCares Inc

New P1 trial • Immunology • Inflammatory Arthritis • Lupus • Myositis • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis

Safety and Efficacy Study of CC312 for Moderate to Severe SLE (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: CytoCares Inc

New P1 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

CC312, a novel engineered CD19/CD3/CD28 tri-specific antibody,leads to rapid and deep B-cell depletion and has broad potential for development in autoimmune diseases (EULAR 2025) - "In this active clinical investigation evaluating CC312 for autoimmune diseases, dose-escalation cohorts (5-10 μg) exhibited favorable safety profiles following 1-3 treatment cycles, with no immune effector cell-associated neurotoxicity syndrome (ICANS) or grade ≥2 cytokine release syndrome (CRS). Rapid, near-complete depletion of peripheral CD19-positive B lymphocytes and their effector subsets was achieved at all dose levels, including the minimum tested dose, correlating with clinically meaningful disease improvement. Universal SRI-4 response was observed across the cohorts."

IO biomarker • Late-breaking abstract • Trispecific • Immunology • Infectious Disease • Inflammatory Arthritis • Leukopenia • Lupus • Myositis • Neutropenia • Oncology • Renal Disease • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • CRP • IL2

CC312, a novel engineered CD19/CD3/CD28 tri-specific antibody, leads to rapid and deep B-cell depletion and has broad potential for development in autoimmune diseases (EULAR 2025) - "In the ongoing clinical study of autoimmune diseases, CC312 is evaluated at ascending dose levels via step-up regimen. After short-term treatment, CC312 is well-tolerated, with no grade 3+ CRS or ICANS. Even at the lowest dose level, peripheral B cells and B cells subsets can be rapid and comprehensively depleted, accompanied with improvement or even remission of disease."

IO biomarker • Trispecific • Alopecia • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Myositis • Oncology • Pain • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • IL2

CC312, a CD19-targeting, co-stimulatory CD28 receptor-activating tri-specific T cell engager, for the treatment of autoimmune diseases (EULAR 2025) - "Certain BCDT monoclonal antibodies, e.g. rituximab, are also approved to treat several autoimmune diseases [1], however demonstrate poor B cells depletion in deep tissue which may limit the long-term disease control or remission in patients. CC312’s capacity to induce more complete T cell activation and longer T cell durability of response as well as more potently and thoroughly eliminate pathogenic B cells versus leading bispecific TCE Blincyto has been demonstrated in both ex vivo and in vivo studies. This highlights the importance of CD28 co-stimulation and indicates strong potential benefit of CC312 in achieving the depth of response needed to effectively treat B cell-related autoimmune diseases in the clinical setting."

Trispecific • Immunology • Inflammatory Arthritis • Oncology • CD20 • CD4 • CD8

CC312, a trispecific CD19-targeting co-stimulatory T cell engager, for the treatment of B cell malignancies and autoimmune diseases (AACR 2025) - "Certain BCDT monoclonal antibodies,e.g. rituximab,are also approved to treat autoimmune diseases(ADs), however demonstrate poor B cells depletion in deep tissue which may limit the long-term disease control or remission in patients. CC312's capacity to potently and thoroughly eliminate B cells has been demonstrated in in vitro and in vivo studies as well as in the clinical setting, indicating the potential benefit in treating B cell-related ADs. As the first CD28 co-stimulatory TCE to be explored in ADs, additional clinical studies will be conducted to further evaluate the efficacy and safety in autoimmune patients."

Trispecific • Hematological Malignancies • Oncology • CD20

Beyond antibodies and CAR-T: CC312, a first-in-class, anti-CD19, anti-CD3, anti-CD28 trispecific antibody in treatment with relapsed and/or refractory B-cell malignancies (AACR 2025) - "In this study, CC312 exhibited key advantages over leading CD3xCD19 TCE blinatumomab in multiple clinically relevant in vitro functional assays, demonstrated robust tumor growth inhibition in B cell lymphoma mouse models and achieved thorough depletion of CD19+ B cells and potent activation of T cells in B cell lymphoma patients across dosages while maintaining a favorable safety/tolerability profile. Therefore, via its "Two Signal" co-stimulation approach, CC312 represents a promising candidate for treatment of B cell lymphoma. CC312's clinical benefit will continue to be explored at higher doses as part of ongoing Ph1a dose escalation study."

Trispecific • B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD34 • CD8

Safety Study of CC312 in Autoimmune Disease Patients (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: CytoCares Inc

New P1 trial • Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Immune Thrombocytopenic Purpura • Immunology • Inflammatory Arthritis • Lupus • Myositis • Rheumatoid Arthritis • Rheumatology • Scleroderma • Systemic Lupus Erythematosus • Systemic Sclerosis • Thrombocytopenia • Thrombocytopenic Purpura

Safety Study of CC312 in Adult Patients With Relapsed/Refractory CD19 Positive B-cell Hematologic Malignancies (clinicaltrials.gov) - P1 | N=44 | Recruiting | Sponsor: CytoCares Inc

New P1 trial • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD4 • CD8