Alys Pharmaceuticals has submitted a Clinical Trial Application (CTA) to Germany's Paul-Ehrlich-Institut (PEI) to initiate a Phase 1/1b study of ALY-301, marking a significant milestone in the development of the first mast cell-selective c-Kit inhibitor. The study will evaluate the safety and efficacy of this first-in-class bispecific antibody in healthy volunteers and patients suffering from Cold Urticaria, a subtype of Chronic Inducible Urticaria (CIndU).
Novel Approach to c-Kit Targeting
ALY-301 represents a breakthrough in c-Kit inhibition through its unique bispecific design that binds both c-Kit and CD-203c, enabling selective targeting and depletion of mast cells while sparing other c-Kit positive cells. This differentiated profile addresses a longstanding challenge in the field, where conventional c-Kit targeting agents have been limited by safety concerns due to their indiscriminate effects on various cell types.
"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," said 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. "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."
Addressing Unmet Medical Needs in Cold Urticaria
Cold Urticaria is a chronic skin disease characterized by the appearance of red, itchy wheals or hives after skin exposure to cold temperatures. The condition serves as a well-established clinical model for mast cell-mediated diseases in general and chronic spontaneous urticaria in particular. Current and emerging solutions do not adequately address the significant unmet medical needs experienced by patients, and the limited treatment options contribute to a projected Urticaria market reaching multiple billions within the next ten years.
The upcoming Phase 1/1b trial will be conducted across multiple sites in Germany, evaluating both safety and tolerability in healthy volunteers as well as pharmacokinetics, pharmacodynamics, and early signs of clinical activity in patients with cold urticaria.
Clinical Development Strategy
Professor Martin Metz, Professor of Dermatology at the Institute of Allergology at the Charité – Universitätsmedizin Berlin & Fraunhofer Institute for Translational Medicine and Pharmacology, and Principal Investigator for ALY-301, emphasized the strong preclinical foundation supporting the clinical transition. "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," Metz commented. "It is very exciting to start the clinical journey today, especially since this first clinical trial will yield clinical outcomes from Urticaria patients."
This CTA submission represents the first clinical program to emerge from Alys' Granular platform, which focuses on precise targeting of mast cell biology through advanced antibody engineering. The selective approach is expected to offer a significantly improved safety profile that could enable safe, chronic dosing in multiple mast cell-dependent diseases such as Chronic Urticaria.
Broader Therapeutic Potential
The successful development of ALY-301 could have implications beyond Cold Urticaria, with potential applications in chronic spontaneous urticaria, atopic dermatitis, and systemic mastocytosis. Thibaud Portal, Co-Founder and Chief Operating Officer of Alys Pharmaceuticals, highlighted the broader significance within the current therapeutic landscape.
"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," Portal noted. "ALY-301 is a first-in-class approach that combines the power of c-Kit inhibition with selectivity and safety."
Company Pipeline and Future Outlook
This study marks the second major clinical milestone for Alys Pharmaceuticals, which maintains a diverse pipeline targeting unmet needs in multiple dermatological indications including atopic dermatitis, chronic spontaneous urticaria, vitiligo, and systemic mastocytosis. The company, backed by international investment firm Medicxi with $100M financing, remains on track to deliver multiple clinical Proof-of-Concept readouts by 2027.
The Boston and Lausanne-based company brings together experts across dermatology and advanced scientific fields, with co-founders including 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).
