Alys Pharmaceuticals Submits CTA for ALY-301, a c-Kit Inhibitor for Cold Urticaria

12 June 2025
Alys Pharmaceuticals, an innovative company focused on immune-dermatology, has taken a significant step forward by submitting a Clinical Trial Application (CTA) to the Paul-Ehrlich-Institut (PEI) in Germany. This application aims to launch a Phase 1/1b study of ALY-301, a groundbreaking bispecific antibody, in both healthy individuals and patients with Cold Urticaria, a specific type of Chronic Inducible Urticaria (CIndU).

Cold Urticaria is a persistent skin condition characterized by the appearance of red, itchy wheals or hives when skin is exposed to cold temperatures. This condition serves as a recognized clinical model for studying mast cell-related diseases, including chronic spontaneous urticaria. Despite existing treatments, there remains a substantial unmet need for effective therapies, with the Urticaria market expected to grow significantly in the coming decade.

ALY-301 stands out as the first mast cell-selective c-Kit inhibitor introduced in clinical settings. This bispecific antibody uniquely targets both c-Kit and CD-203c, concentrating its effects on mast cells while bypassing other c-Kit positive cells. With this targeted approach, ALY-301 is anticipated to provide a safer option for chronic dosing in several mast cell-dependent disorders, particularly Chronic Urticaria.

The upcoming trial will assess the safety and effectiveness of ALY-301 across multiple locations in Germany. This CTA submission marks the inaugural clinical initiative stemming from Alys' Granular platform, which leverages advanced antibody engineering to precisely target mast cell biology.

Professor Brian Kim, an esteemed dermatologist and Vice Chair of Research at the Icahn School of Medicine at Mount Sinai, as well as Head of Alys Pharmaceuticals Scientific Advisory Board, highlights the uniqueness of ALY-301. He notes its ability to selectively target activated mast cells while minimizing off-target effects, which could lead to a transformative drug profile for ALY-301 with potentially revolutionary impacts on Chronic Urticaria and other allergic conditions.

Professor Martin Metz, a distinguished dermatologist at the Charité – Universitätsmedizin Berlin and Fraunhofer Institute for Translational Medicine and Pharmacology, and Principal Investigator for ALY-301, expressed enthusiasm about the clinical commencement. He emphasized the innovative concept behind ALY-301 that promises safe and effective chronic dosing via mast-cell selectivity, a notion supported by exhaustive non-clinical research.

Thibaud Portal, Co-Founder and Chief Operating Officer of Alys Pharmaceuticals, underscored the growing focus on solving Urticaria and other allergic diseases with c-Kit targeting strategies. He observed that while c-Kit targeting is notably potent, non-selective approaches have faced chronic safety issues. ALY-301 offers a pioneering method combining c-Kit inhibition power with enhanced selectivity and safety. Portal believes this development signals a pivotal moment for Alys in their quest to deliver innovative treatments to patients.

The launch of this study represents the second major clinical achievement for Alys Pharmaceuticals. The company’s diverse pipeline addresses unmet needs in conditions such as atopic dermatitis, chronic spontaneous urticaria, vitiligo, and systemic mastocytosis. Alys is on track to deliver multiple clinical Proof-of-Concept (POC) results by 2027.

Alys Pharmaceuticals operates from Boston and Lausanne and focuses exclusively on immuno-dermatology. Supported by a $100M investment from Medicxi, Alys boasts a world-class leadership team with expertise in dermatology and advanced scientific fields, including co-founders from renowned institutions such as UMass Chan Medical School, Icahn School of Medicine at Mount Sinai, LMU Munich, Gustave Roussy, and Georgia Institute of Technology. Thibaud Portal leads the company as a dermatology expert and COO. Alys is advancing its mastocyte-selective therapies via its affiliate Granular Therapeutics after entering the clinic in early 2025 with a siRNA platform developed by Aldena Therapeutics.

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