Cullinan Therapeutics has received approval from the European Medicines Agency (EMA) to initiate a Phase 1 clinical trial of CLN-978, its novel CD19xCD3 bispecific T cell engager, in patients with rheumatoid arthritis. The company plans to begin the trial in the second quarter of 2025 at two prestigious European institutions: FAU Erlangen-Nuremberg in Germany and Università Cattolica del Sacro Cuore in Rome.
The open-label study will evaluate CLN-978 in patients with active, difficult-to-treat rheumatoid arthritis who meet the 2010 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) Classification Criteria. Researchers will assess the drug's safety profile, pharmacokinetics, pharmacodynamics, and effects on disease activity.
"We are pleased to announce the achievement of an important regulatory milestone allowing us to initiate a clinical trial of CLN-978 in rheumatoid arthritis in the second quarter of this year, with leading research institutions in Europe, as we simultaneously advance our systemic lupus erythematosus trial at sites around the globe," said Jeffrey Jones, MD, MBA, Chief Medical Officer at Cullinan Therapeutics.
Dr. Jones emphasized that CLN-978 is the only CD19-targeting T cell engager advancing a global regulatory development plan that includes a U.S. FDA-cleared Investigational New Drug (IND) application. The therapy aims to deliver potent T cell redirecting capabilities with disease-modifying potential, while offering convenient subcutaneous dosing for improved accessibility and treatment flexibility.
Addressing Significant Unmet Needs in Rheumatoid Arthritis
Rheumatoid arthritis affects approximately 5.3 million adults across major markets including the U.S., Europe, Japan, and Australia. Despite advances in treatment options, many patients continue to face challenges with current therapies.
Ricardo Grieshaber-Bouyer, MD, PhD, MHBA, Professor of Clinical Systems Immunology and Head of the Clinical Trials Unit at FAU Erlangen-Nuremberg, who will serve as the global Principal Investigator for this trial, highlighted the persistent challenges in treating rheumatoid arthritis.
"Rheumatoid arthritis remains a challenging disease, where effective treatment is critical to altering its course. Although some patients can achieve remission with current therapies, the majority do not achieve this or lose response and become refractory to treatment," Dr. Grieshaber-Bouyer explained. "This unmet need underscores the importance of advancing novel approaches like CLN-978, which has the potential to offer deeper B cell depletion than existing therapies."
The chronic autoimmune disease is characterized by inflammation of the joints, leading to pain, swelling, stiffness, and permanent joint damage. It typically affects multiple joints simultaneously, particularly the hands, wrists, and feet, though it can also impact other organ systems. While disease-modifying antirheumatic drugs (DMARDs) have improved outcomes for some patients, many continue to rely on chronic immunosuppression, experience inadequate responses, suffer disease flares, and face significant impairments in quality of life.
CLN-978: Mechanism and Potential Advantages
CLN-978 represents a novel approach to treating autoimmune diseases through targeted B cell depletion. The drug is a highly potent CD19xCD3 bispecific T cell engager that triggers redirected lysis of CD19-expressing target cells both in laboratory settings and living organisms.
The molecule is engineered with several key features that distinguish it from other therapies:
- Very high affinity binding to CD19 to efficiently target B cells, including those with very low CD19 expression levels
- Compact molecular size (65 kDa)
- Two single-chain variable fragments: one binding to CD19 and another to CD3 on T cells
- A single-domain antibody that binds to human serum albumin to extend the drug's half-life in the body
Developed entirely by Cullinan's internal team, CLN-978 is a wholly owned asset in the company's portfolio. Its subcutaneous delivery method offers potential advantages over intravenous therapies, potentially improving patient convenience and adherence.
The drug is also being studied for systemic lupus erythematosus at clinical sites across the United States, Europe, and Australia, demonstrating Cullinan's commitment to exploring its potential across multiple autoimmune conditions.
Cullinan's Broader Mission and Approach
Cullinan Therapeutics (Nasdaq: CGEM) focuses on developing modality-agnostic targeted therapies for both autoimmune diseases and cancer. The company has built a diversified portfolio of clinical-stage assets designed to inhibit key disease drivers or harness the immune system to eliminate diseased cells.
The company's approach is anchored in a deep understanding of oncology, immunology, and translational medicine. Cullinan creates differentiated therapeutic concepts, identifies appropriate targets, and selects optimal modalities to develop potentially transformative treatments across various indications.
With CLN-978 now advancing into clinical trials for both rheumatoid arthritis and systemic lupus erythematosus, Cullinan continues to demonstrate its commitment to addressing significant unmet needs in autoimmune diseases through innovative approaches to treatment.
