Phase 1 Trial of CLN-978 of Cullinan Therapeutics Gets US FDA Clearance

Phase 1 Trial of CLN-978 of Cullinan Therapeutics Gets US FDA Clearance

By, Admin 18 October 2024

Cullinan Therapeutics gets US FDA clearance to proceed phase 1 trial of CLN-978 in patients with moderate to severe systemic lupus erythematosus

Overview

Cullinan Therapeutics, Inc., a biopharmaceutical company focused on developing modality-agnostic targeted therapies, announced that the US Food and Drug Administration (FDA) cleared the company’s Investigational New Drug (IND) Application for CLN-978 and its global phase 1 clinical trial may proceed in the US to assess CLN-978 in patients with moderate to severe systemic lupus erythematosus (SLE).  

Trial enrollment criteria

  • The trial will enroll patients with a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score of eight or greater and who have had an inadequate response to at least two treatments, including one immunosuppressive or biologic standard-of-care agent. 
  • Part A is a dose escalation phase that will determine the target dose for further development, with a starting dose of 10 micrograms. 
  • Part B is a dose expansion phase which will explore multiple dose schedules informed by data from Part A of the study.  

Objectives

  • The primary objective of the study is to evaluate the safety of CLN-978 for treatment of active moderate to severe SLE. 
  • Secondary objectives include pharmacokinetics, B cell kinetics, immunogenicity, and clinical activity.

Words from the CMO: Cullinan Therapeutics

  • We are pleased to continue progressing our global phase 1 clinical trial in the US with FDA clearance of our IND Application,” said Jeffrey Jones, MD, MBA, chief medical officer, Cullinan Therapeutics. 
  • There remains a significant unmet medical need among patients with systemic lupus erythematosus, as current therapies often fail to fully control disease activity and prevent long-term organ damage. CLN-978, our novel bispecific T cell engager, targets CD19, offering a highly differentiated approach to deliver the potency of T cell redirecting therapy with off-the-shelf access and convenient dosing through subcutaneous administration.”

The company previously announced in September that it was cleared to initiate its global clinical trial in Australia (NCT06613360).  

About the novel molecule: CLN-978

  • CLN-978 is a novel, highly potent CD19xCD3 bispecific T cell engager. CLN-978 triggers redirected lysis of CD19-expressing target cells in vitro and in vivo. 
  • CLN-978 is engineered to achieve very high affinity binding to CD19 to efficiently target B cells, including those with very low CD19 levels. 
  • Small in molecular size (65 kDa), CLN-978 contains two single-chain variable fragments, one binding with very high affinity to the CD19 target and the other binding to CD3 on T cells, and a single-domain antibody binding to human serum albumin to extend serum half-life. 
  • CLN-978 was developed by an internal Cullinan team and is a wholly owned asset. 
  • CLN-978 has the potential to offer a convenient, off-the-shelf, subcutaneously delivered therapeutic option for patients with autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis.  

About the disease: Systemic lupus erythematosus (SLE)

  • • Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease in which the immune system attacks a patient’s own tissues. 
  • The most common manifestations of SLE include skin rashes, arthritis, swelling in the feet, and around the eyes, extreme fatigue, and low fevers. 
  • Lupus nephritis (LN) is a kidney disease and the most common severe manifestation of SLE. 
  • Approximately 40% of patients with SLE develop LN, which has a 10-year 30% mortality rate. 
  • The prevalence of SLE in the US is estimated at 160,000 to 320,000 cases and SLE affects approximately 3.4 million individuals globally. 
  • SLE is more prevalent in women and people of colour. 
  • It occurs most often in people between the ages of 15 and 45 years but can occur in childhood or later in life as well. 
  • Currently available treatments do not routinely induce treatment-free remission, and most patients require lifelong immune suppression that treats symptoms without modifying the course of disease.

About Cullinan Therapeutics, Inc

  • Cullinan Therapeutics, Inc. is a biopharmaceutical company dedicated to creating new standards of care for patients. 
  • Cullinan has strategically built a diversified portfolio of clinical-stage assets that inhibit key drivers of disease or harness the immune system to eliminate diseased cells in both autoimmune diseases and cancer. 
  • Cullinan’s portfolio encompasses a wide range of modalities, each with the potential to be best and/or first in class.