In February 2024, the FDA put two Phase II studies of zelnecirnon under a clinical hold after a case of liver failure was deemed potentially related to the drug.
RAPT Therapeutics on Monday announced that it will terminate the development of its investigational CCR4 antagonist zelnecirnon after receiving “feedback” from the FDA.
The California biotech did not reveal what the regulator’s feedback was, only announcing that “we do not see a viable path forward for zelnecirnon,” according to RAPT president and CEO Brian Wong.
In February 2024, the FDA slapped clinical holds on a Phase IIb study of zelnecirnon in atopic dermatitis and a Phase IIa trial in asthma. The regulatory pause was triggered by a case of liver failure in the atopic dermatitis study that was classified as a serious adverse event and characterized as “potentially related to zelnecirnon.”
The company expects to identify a new candidate in the first half of 2025, while continuing to look for in-licensing contracts for clinical-stage assets, Wong said on Monday.
RAPT was down by as much as 43% in premarket trading Monday, hitting $1.63 from $2.89 at the previous close.
Designed to be orally available, zelnecirnon is a small molecule drug candidate that works by targeting and disrupting the action of the CCR4 chemokine receptor, which is primarily expressed by helper T cells and which is involved in the inflammatory cascade. According to RAPT’s website, early data have validated this mechanism of action and suggest that targeting CCR4 could “provide an alternative to existing injectable and oral treatments.”
In November 2023, for instance, RAPT published Phase Ia/Ib data showing that once-daily zelnecirnon could improve Eczema Area and Severity Index (EASI) score by 36.3% in patients with moderate to severe atopic dermatitis after four weeks of treatment. Placebo comparators saw a 17% drop in EASI over the same time period.
For two weeks after the end of treatment, patients in the zelnecirnon group showed deepening of response, with EASI scores dropping further to 53.2% after six weeks. RAPT at the time linked this deepening response to zelnecirnon’s mechanism of action, noting that CCR4 is upstream of other cytokines.
RAPT will continue working on its CCR4 pipeline assets, with an eye toward “improved safety margins,” Wong continued in the statement. “We continue to believe that CCR4 remains an exciting target with the potential to provide a safe, oral therapeutic option across a number of inflammatory diseases.”
As per its second quarter earnings report, RAPT suffered a net loss of $58.2 million in the first half of this year. The company in July 2024 laid off 47 employees, or 40% of its headcount, in an effort to “conserve cash resources.” As of June 30, RAPT still had $114.8 million in cash, cash equivalents and marketable securities.
