Alys Pharmaceuticals doses first subject in Phase 1/1b trial of ALY-301, a first-in-class mast cell selective c-Kit inhibitor for Chronic Urticaria

• 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

BOSTON and LAUSANNE, Switzerland , Oct. 30, 2025 /PRNewswire/ -- 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.

About Alys Pharmaceuticals

Alys Pharmaceuticals, Inc. ("Alys") is a Boston and Lausanne-based cutting edge pure-play immuno-dermatology company. Alys is backed by international investment firm Medicxi with $100M financing. Alys has a world class leadership team that brings together experts across dermatology and advanced scientific fields, including co-founders John Harris (UMass Chan Medical School), Brian Kim (Icahn School of Medicine at Mount Sinai), Lars French, Craig Mello (UMass Chan Medical School) and Mark Prausnitz (Georgia Institute of Technology). Alys is led by dermatology specialist, co-founder, and COO Thibaud Portal. 

Its pipeline includes programs targeting multiple dermatological indications, including atopic dermatitis, vitiligo, chronic urticaria, psoriasis and mastocytosis. 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.

For further information, please visit www.alyspharma.com.