RAPT Therapeutics Discontinues Zelnecirnon Program After FDA Feedback, Stock Plummets
核心洞察
RAPT Therapeutics halts the development of zelnecirnon (RPT193) for inflammatory disorders (搜索) following unfavorable feedback from the FDA after a clinical hold.
The FDA's decision followed a serious adverse event involving liver injury and a subsequent transplant in a patient during zelnecirnon trials.
RAPT will focus on next-generation CCR4 (搜索) compounds with improved safety profiles and anticipates identifying a new candidate in the first half of 2025.
RAPT Therapeutics has ceased its clinical program for zelnecirnon (RPT193), an investigational drug targeting inflammatory disorders (搜索), following discussions with the U.S. Food and Drug Administration (FDA). The decision comes after the FDA previously placed the zelnecirnon trials on clinical hold in February due to a serious adverse event (SAE) that led to a patient requiring a liver transplant.
Program Termination and FDA Feedback
According to RAPT Therapeutics' CEO, Brian Wong, the company does not see a "viable path forward for zelnecirnon" based on the FDA's feedback. The Phase IIa (NCT05935332) and Phase IIb (NCT05399368) trials, which were evaluating zelnecirnon in asthma (搜索) and atopic dermatitis (搜索) patients, respectively, have been formally terminated.
The company's stock price experienced a significant drop, with shares plummeting 48% at market open on November 11, reflecting investor concerns about the program's discontinuation. RAPT Therapeutics currently has a market capitalization of $54.3 million.
CCR4 as a Therapeutic Target
Zelnecirnon is a CCR4 (搜索) antagonist. CCR4 is a chemokine receptor expressed on various immune cells, including T helper 2 (TH2) cells, regulatory T cells (Tregs), mast cells, and skin-homing lymphocyte Ag–positive T cells. Inhibiting CCR4 aims to dampen the inflammatory response in inflammatory disorders (搜索). However, the precise functional pathway remains not fully understood.
Despite the setback with zelnecirnon, RAPT Therapeutics remains optimistic about CCR4 (搜索) as a therapeutic target. The company plans to advance its next-generation CCR4 compounds, emphasizing improved safety margins for inflammatory disease. They anticipate identifying a new candidate in the first half of 2025.
Focus on Tivumecirnon and In-Licensing
With the discontinuation of zelnecirnon, RAPT Therapeutics' primary clinical-stage asset is now tivumecirnon (FLX475), another CCR4 (搜索) antagonist. Tivumecirnon is currently being evaluated both as a monotherapy and in combination with Merck’s Keytruda (pembrolizumab) in a Phase 2 trial (NCT03674567). Earlier data from 32 patients in the trial showed an objective response rate (ORR) of 15.6%.
RAPT Therapeutics is also actively seeking in-licensing opportunities for clinical-stage assets to expand its pipeline.