The first subject has been dosed in Alys Pharmaceuticals, Inc.’s Phase 1/1b study of ALY-301, a first-in-class mast cell selective c-Kit inhibitor for the treatment of cold urticaria.
ALY-301 is a cis-targeting bispecific antibody designed to selectively deplete mast cells by binding both c-Kit and CD203c. This differentiated profile of ALY-301 is expected to enable chronic dosing in mast cell dependent diseases such as chronic urticaria, while avoiding the safety limitations of conventional c-Kit inhibitors.
The trial (NCT07181369) is a randomized, double-blind, placebo-controlled Phase 1/1b study designed to evaluate the safety, tolerability, and pharmacology of ALY-301 in healthy volunteers and patients with cold urticaria who remain symptomatic despite antihistamines. The trial will also assess preliminary signs of efficacy in patients. The first patient has been dosed at Charité—Universitätsmedizin Berlin, with planned expansion to additional sites across Germany in the coming months following the successful outcome of the Clinical Trial Application (CTA) submitted in June 2025.
“ALY-301’s ability to selectively target and deplete mast cells over other c-Kit positive cells, while potentially matching the efficacy of reference c-Kit inhibitors, gives it one of the most exciting profiles I have come across, highlighting the transformative potential of precision-targeted therapies in the immune-dermatology space,” says Martin Metz, MD, Professor of Dermatology at the Institute of Allergology at the Charité—Universitätsmedizin Berlin & Fraunhofer Institute for Translational Medicine and Pharmacology, Allergology and Immunology in Berlin, Germany and Principal Investigator for ALY-301, in a news release.
Lars French, MD, Chief Medical Officer of Alys Pharmaceuticals and Professor and chairman of the Department of Dermatology at the Ludwig Maximilian University (LMU) in Munich, Germany, adds, “The initiation of this clinical trial is particularly exciting, as we will for the first time in patients, be able to assess the promising effects of our unique bispecific antibody ALY-301, designed to selectively inhibit mast cell c-Kit, whilst sparing other c-Kit expressing cells including melanocytes and hematopoietic stem cells. The unique attributes of ALY-301 give it the potential to be a game-changer for the long-term management of chronic urticaria.”
This study is the second clinical program initiated by Alys in 2025 and the first clinical trial from the Company’s Granular platform. The Alys pipeline includes a diverse portfolio of assets targeting unmet needs in indications such as atopic dermatitis, chronic spontaneous urticaria, vitiligo, and systemic mastocytosis. The Company remains on track to deliver multiple clinical Proof-of-Concept (POC) readouts by 2027. The Company entered the clinic in Q1 2025 with the siRNA platform developed by its affiliate Aldena Therapeutics, which offers the potential for long-lasting treatments that could transform the dermatology treatment landscape and is now advancing its mastocyte-selective therapies developed by affiliate Granular Therapeutics.
PHOTO CREDIT: DermNet
