Alys Pharmaceuticals Doses First Patient in Phase 1/1b Trial of ALY-301 for Chronic Urticaria

Alys Pharmaceuticals recently announced the dosing of the first subject in a phase 1/1b clinical study of ALY-301, a first-in-class mast cell–selective c-Kit inhibitor being developed for cold urticaria, a subtype of chronic inducible urticaria (CIndU) and a representative model for the broader chronic urticaria population.¹

The phase 1/1b study (NCT07181369) is a randomized, double-blind, placebo-controlled trial evaluating the safety, tolerability, and pharmacology of ALY-301 in both healthy volunteers and patients with cold urticaria who remain symptomatic despite antihistamine therapy.

ALY-301 is a cis-targeting bispecific antibody designed to bind both c-Kit and CD203c, enabling selective depletion of mast cells while sparing other c-Kit–expressing cells such as melanocytes and hematopoietic stem cells. According to the announcement, this profile may allow chronic dosing in mast cell–driven diseases while avoiding the safety concerns seen with conventional c-Kit inhibitors.

“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,” said Martin Metz, MD, professor of dermatology at the Institute of Allergology at Charité – Universitätsmedizin Berlin and principal investigator for ALY-301, in the news release.

Chronic urticaria encompasses mast cell–driven skin diseases marked by recurrent wheals or hives that can last months or years, with limited treatment options and a substantial impact on quality of life.

According to Lars French, MD, Chief Medical Officer of Alys Pharmaceuticals, “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.”

The first patient was dosed at Charité–Universitätsmedizin Berlin, with expansion to additional sites in Germany expected in the upcoming months. Alys Pharmaceuticals’ broader pipeline includes assets targeting atopic dermatitis, chronic spontaneous urticaria, vitiligo, and systemic mastocytosis, with multiple proof-of-concept readouts anticipated by 2027.

“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,” concluded Thibaud Portal, PhD, co-founder and Chief Operating Officer of Alys Pharmaceuticals.

In June 2025, Alys Pharmaceuticals submitted a clinical trial application to Germany's Paul-Ehrlich-Institut, the country's federal institute for vaccines and biomedicines, to initiate the phase 1/1b trial of ALY-301.₂

"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," Brian S. Kim, MD, said in a news release. Kim is the Sol and Clara Kest Professor and vice chair of research at the Icahn School of Medicine at Mount Sinai in New York, New York, and chair of Alys Pharmaceuticals’ scientific advisory board.²

References

1. 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. News release. Alys Pharmaceuticals. October 30, 2025. Accessed November 7, 2025. https://alyspharma.com/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/
2. Alys Pharmaceuticals announces CTA submission for ALY-301, the first mast cell selective c-Kit inhibitor for treatment of cold urticaria. News release. Alys Pharmaceuticals. June 10, 2025. Accessed November 7, 2025. https://www.prnewswire.com/news-releases/alys-pharmaceuticals-announces-cta-submission-for-aly-301-the-first-mast-cell-selective-c-kit-inhibitor-for-treatment-of-cold-urticaria-302476572.html