Alys Pharmaceuticals announces CTA submission for ALY-301, the first mast cell selective c-Kit inhibitor for treatment of Cold Urticaria

• ALY-301 is a first-in-class bispecific antibody targeting c-Kit and CD-203c with mast cell selectivity 
• Designed to enable safe dosing in chronic conditions and deliver clinical proof-of concept in a Phase 1/1b study 

BOSTON and LAUSANNE, Switzerland, June 10, 2025 /PRNewswire/ -- Alys Pharmaceuticals, Inc. ("Alys"), an immune-dermatology focused company, today announces the submission of a Clinical Trial Application (CTA) to Germany's Paul-Ehrlich-Institut (PEI) to initiate a Phase 1/1b study of ALY-301 in healthy volunteers and patients suffering from Cold Urticaria, a subtype of Chronic Inducible Urticaria (CIndU).

Cold Urticaria is a chronic skin disease where red, itchy wheals or hives appear after the skin is exposed to cold temperatures. It is a well-established clinical model for mast cell-mediated diseases in general, and chronic spontaneous urticaria in particular. Current and emerging solutions do not address the significant unmet medical needs experienced by patients. In conjunction with limited treatment options, the Urticaria market is projected to reach multiple billions within the next ten years.

ALY-301 is the first mast cell-selective c-Kit inhibitor to enter the clinic. It is a cis-targeting bispecific antibody binding c-Kit and CD-203c, allowing selective targeting and depletion of mast cells over other c-Kit positive cells. This differentiated profile of ALY-301 is expected to offer a significantly improved safety profile over conventional c-Kit targeting agents and enable safe, chronic dosing in multiple mast-cell dependent diseases such as Chronic Urticaria.

The trial will evaluate the safety and efficacy of ALY-301 at multiple sites across Germany. This CTA submission is the first clinical program to emerge from Alys' Granular platform, which is focused on the precise targeting of mast cell biology through advanced antibody engineering.

Professor Brian Kim, Sol and Clara Kest Professor of Dermatology and Vice Chair of Research at Icahn School of Medicine at Mount Sinai and Head of Alys Pharmaceuticals Scientific Advisory Board, said: "ALY-301 offers a truly differentiated approach. It is the only c-Kit antibody designed to target activated mast cells while avoiding off-target effects. Unleashing the proven efficacy of c-Kit inhibition on mast cells, while sparing all other cell-types that have been associated with significant side effects, should result in a transformational drug profile for ALY-301 and could have a revolutionary impact on Chronic Urticaria and several other allergic indications." 

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: "The concept behind ALY-301, to enable safe and effective chronic dosing of a c-Kit agent through mast-cell selectivity, has been strongly supported across all non-clinical studies. It is very exciting to start the clinical journey today, especially since this first clinical trial will yield clinical outcomes from Urticaria patients."

Thibaud Portal, Co-Founder and Chief Operating Officer of Alys Pharmaceuticals, added: "Recently, there has been intense attention to solving Urticaria and other allergic diseases, with keen interest in c-Kit targeting. Data have demonstrated the remarkable potency of the mode of action, but indiscriminate c-Kit targeting has been coupled with chronic safety challenges. ALY-301 is a first-in-class approach that combines the power of c-Kit inhibition with selectivity and safety. With its expected safety margin and broad applicability across multiple diseases, this marks another pivotal moment for Alys in our journey to bring innovative treatments to patients."

This study marks the second major clinical milestone for Alys Pharmaceuticals. 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 (LMU, Munich), Craig Mello (UMass Chan Medical School), Eric Deutsch (Gustave Roussy) 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.