Cullinan Therapeutics, Inc. (Nasdaq: CGEM) has received the green light to begin a global Phase 1 clinical trial evaluating CLN-978, a CD19xCD3 bispecific T cell engager, for the treatment of systemic lupus erythematosus (SLE). The trial, which has already received Human Research Ethics Committee (HREC) approval in Australia, will now expand to include sites in the United States following FDA approval, marking a significant step forward in addressing the unmet needs of SLE patients. SLE affects approximately 430,000 individuals globally, and current treatments often fail to induce treatment-free remission, necessitating lifelong immune suppression.
Trial Design and Objectives
The Phase 1 clinical trial is designed to assess the safety, pharmacokinetics, and initial clinical activity of CLN-978 in patients with moderate to severe SLE. The study will be conducted at multiple sites in Australia and the U.S., focusing on patients with a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score of eight or more who have not responded adequately to at least two standard treatments. The trial comprises two parts: Part A for dose escalation, starting at 10 micrograms, to determine the target dose, and Part B for dose expansion to explore various dose schedules based on Part A results.
The primary goal of the study is to evaluate the safety of CLN-978 in treating active moderate to severe SLE. Secondary objectives include assessing pharmacokinetics, B cell kinetics, immunogenicity, and clinical activity.
CLN-978: A Novel Therapeutic Approach
CLN-978 is a novel, highly potent, half-life extended CD19xCD3 bispecific T cell engager construct. It is engineered to achieve very high affinity binding to CD19, efficiently targeting B cells expressing even low levels of CD19. The inclusion of a human serum albumin (HSA)-binding domain increases the serum half-life of CLN-978, allowing for more patient-friendly subcutaneous dosing and potentially reduced toxicity. Preclinical studies have demonstrated that CLN-978 potently triggers redirected lysis of CD19-expressing target cells in vitro and in vivo.
Jeffrey Jones, MD, MBA, Chief Medical Officer at Cullinan Therapeutics, emphasized the significant unmet medical need for effective SLE treatments, noting that existing therapies often fail to fully control disease activity or prevent long-term organ damage. "We have been focused on rapidly executing our global clinical development strategy for autoimmune diseases, and today’s approval is an important step to treat patients around the world living with SLE," said Dr. Jones. "Our investigational candidate, CLN-978, combines the optimal target (CD19) and modality (T cell engager) for a highly differentiated, potentially best-in-class program."
About Systemic Lupus Erythematosus (SLE)
SLE is a chronic autoimmune disease in which the immune system attacks the body's own tissues and organs. Common manifestations include skin rashes, arthritis, swelling, extreme fatigue, and low fevers. Lupus nephritis (LN), a kidney disease, is a severe complication affecting approximately 40% of SLE patients and carries a 10-year mortality rate of 30%. SLE disproportionately affects women, people of color, and women of childbearing age. Current treatments primarily focus on managing symptoms through lifelong immune suppression, without modifying the underlying disease course.
With the initiation of this Phase 1 trial, Cullinan Therapeutics aims to address the critical need for more effective and convenient treatments for SLE, offering hope for improved outcomes and a better quality of life for patients worldwide.
