Alys Pharmaceuticals Initiates First-in-Class Mast Cell Selective c-Kit Inhibitor Trial for Chronic Urticaria
核心洞察
Alys Pharmaceuticals (搜索) has dosed the first subject in a Phase 1/1b trial of ALY-301, a first-in-class mast cell selective c-Kit (搜索) inhibitor designed to treat Cold Urticaria (搜索), a subtype of Chronic Inducible Urticaria (搜索).
ALY-301 is a bispecific antibody that selectively targets and depletes mast cells while sparing other c-Kit (搜索) positive cells including melanocytes and hematopoietic stem cells, potentially avoiding safety limitations of conventional c-Kit inhibitors.
The multicenter, randomized, double-blind, placebo-controlled study will enroll healthy volunteers and Cold Urticaria (搜索) patients who remain symptomatic despite antihistamines (搜索), with initial data expected in 2026.
Alys Pharmaceuticals (搜索) has achieved a significant milestone in immune-dermatology by dosing the first subject in a Phase 1/1b clinical trial of ALY-301, a first-in-class mast cell selective c-Kit (搜索) inhibitor developed for treating Cold Urticaria (搜索), a subtype of Chronic Inducible Urticaria (搜索). The multicenter study will evaluate both healthy volunteers and patients with Cold Urticaria, with initial data readouts expected in 2026.
Novel Mechanism Addresses Safety Limitations
ALY-301 represents a breakthrough in c-Kit (搜索) inhibition through its unique bispecific antibody design. The drug selectively depletes mast cells by binding both c-Kit and CD203c (搜索), while sparing other c-Kit expressing cells including melanocytes and hematopoietic stem cells. This differentiated profile is designed to enable chronic dosing in mast cell dependent diseases while avoiding the safety limitations associated with conventional c-Kit inhibitors.
Professor Lars French, Chief Medical Officer of Alys Pharmaceuticals (搜索), emphasized the significance of this approach: "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 (搜索), whilst sparing other c-Kit expressing cells including melanocytes and hematopoietic stem cells."
Addressing Significant Unmet Medical Need
Chronic Urticaria (搜索) encompasses a group of mast cell-driven skin diseases characterized by red, itchy wheals or hives that can persist for months or years, severely impacting patient quality of life. The condition includes both spontaneous and inducible forms, with Cold Urticaria (搜索) serving as a representative model for the broader Chronic Urticaria population. Current treatments remain limited, creating substantial unmet medical need in a market projected to reach multiple billion dollars in the coming decade.
Professor Martin Metz, Principal Investigator for ALY-301 and Professor of Dermatology at the Institute of Allergology at the Charité – Universitätsmedizin Berlin & Fraunhofer Institute for Translational Medicine and Pharmacology, highlighted the clinical significance: "Chronic Urticaria (搜索) 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 (搜索) positive cells, while potentially matching the efficacy of reference c-Kit inhibitors, gives it one of the most exciting profiles I have come across."
Clinical Trial Design and Timeline
The Phase 1/1b study (NCT07181369) follows a randomized, double-blind, placebo-controlled design to evaluate the safety, tolerability, and pharmacology of ALY-301. The trial will enroll both healthy volunteers and patients with Cold Urticaria (搜索) who remain symptomatic despite antihistamine treatment. Additionally, the study will assess preliminary signs of efficacy in patient populations.
The first patient was dosed at Charité–Universitätsmedizin Berlin (搜索), with planned expansion to additional sites across Germany following the successful Clinical Trial Application submitted in June 2025. This represents the second clinical program initiated by Alys in 2025 and marks the first clinical trial from the company's Granular platform.
Strategic Pipeline Development
Thibaud Portal, Co-Founder and Chief Operating Officer of Alys Pharmaceuticals (搜索), noted the milestone's broader significance: "Dosing the first subject with ALY-301 marks a major milestone for Alys. With the first ever mast cell selective c-Kit (搜索) 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."
The ALY-301 program represents part of Alys's diverse pipeline targeting multiple dermatological indications, including atopic dermatitis (搜索), chronic spontaneous urticaria, vitiligo (搜索), and systemic mastocytosis (搜索). The company remains on track to deliver multiple clinical Proof-of-Concept readouts by 2027, supported by $100M financing from international investment firm Medicxi (搜索).