Alys Pharmaceuticals has submitted a clinical trial application (CTA) in Germany for ALY-301, a first-in-class bispecific antibody targeting c-Kit and CD-203c with mast cell selectivity. The Phase 1/1b study will assess safety and preliminary efficacy in healthy volunteers and patients with cold urticaria.

Cold urticaria is a subtype of chronic inducible urticaria (CIndU) triggered by exposure to cold temperatures, resulting in red, itchy wheals or hives. It is considered a representative model for mast cell-mediated diseases, including chronic spontaneous urticaria. Treatment options remain limited despite increasing prevalence, and the global urticaria market is expected to reach several billion dollars in value within the next decade.

ALY-301 is the first mast cell-selective c-Kit inhibitor to reach the clinic. The bispecific antibody binds both c-Kit and CD-203c to selectively deplete mast cells while sparing other c-Kit positive cell types. This approach aims to overcome the chronic safety concerns typically associated with indiscriminate c-Kit inhibition, allowing for safe long-term dosing across a range of mast cell-driven diseases.

The study, which will take place at multiple sites across Germany, marks the first clinical application of Alys’ Granular platform – a suite of antibody engineering tools designed to precisely target mast cell biology.

“ALY-301 is the only c-Kit antibody designed to target activated mast cells while avoiding off-target effects,” said professor Brian Kim, vice chair of research at Icahn School of Medicine at Mount Sinai and head of Alys’ scientific advisory board. “This could result in a transformational drug profile for ALY-301 with broad impact across allergic diseases.”

Professor Martin Metz, principal investigator for the ALY-301 study and professor of dermatology at the Institute of Allergology at the Charité – Universitätsmedizin Berlin, said the clinical program is built on a strong non-clinical foundation.

“The concept to enable safe and effective chronic dosing of a c-Kit agent through mast cell selectivity has been robustly supported in preclinical work,” he said. “It’s exciting to now generate patient outcomes.”

According to Thibaud Portal, co-founder and chief operating officer at Alys, interest in c-Kit as a drug target has grown significantly in recent years, but past efforts have been limited by toxicity concerns.

“ALY-301 combines the power of c-Kit inhibition with selectivity and safety,” he said. “With broad potential across several indications, this is another pivotal step in our effort to bring innovative treatments to patients.”

This trial represents Alys’ second clinical milestone. The company’s pipeline includes candidates for conditions such as atopic dermatitis, vitiligo, chronic spontaneous urticaria, and systemic mastocytosis, with several proof-of-concept readouts expected by 2027.