Differentiated profile of ALY-301 designed to enable chronic dosing in mast cell dependent diseases while avoiding the safety limitations of conventional c-Kit inhibitors
Multicenter Phase 1/1b study to enroll both healthy volunteers and patients with Cold Urticaria with initial data readouts expected in 2026
Alys Pharmaceuticals, Inc. (“Alys”), an immune-dermatology focused company, today announces that the first subject has been dosed in a Phase 1/1b study of ALY-301, a first-in-class mast cell selective c-Kit inhibitor for the treatment of Cold Urticaria, a subtype of Chronic Inducible Urticaria (CIndU) that is also considered to be a good model for the broader Chronic Urticaria population.
Chronic Urticaria is a group of mast cell-driven skin diseases characterized by red, itchy wheals or hives that can persist for months or years, severely impacting the quality of life of patients. It includes both spontaneous and inducible forms, such as Cold Urticaria. Current treatments are limited and significant unmet medical need persists, with the global Urticaria market projected to reach multiple billion dollars in the coming decade.
Professor Martin Metz, Professor of Dermatology at the Institute of Allergology at the Charité – Universitätsmedizin Berlin & Fraunhofer Institute for Translational Medicine and Pharmacology, Allergology and Immunology and Principal Investigator for ALY-301, commented: “Chronic Urticaria is a disease where the burden on patients is often underestimated. 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.”
Thibaud Portal, Co-Founder and Chief Operating Officer of Alys Pharmaceuticals,added:“Dosing the first subject with ALY-301 marks a major milestone for Alys. With the first ever mast cell selective c-Kit inhibitor now in the clinical trials, Alys demonstrates its position as a pioneer in the immune-dermatology space, bringing us closer to our goal of delivering innovative treatments to patients with significant unmet needs.”
Professor Lars French, Chief Medical Officer of Alys Pharmaceuticals and Professor of Dermatology: “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.”
ALY-301 is a first-in-class 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.
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.
