Alys Pharmaceuticals Submits ALY-301 Clinical Trial Application in Germany for Cold Urticaria

Cold urticaria | Image Credit: © DermNet

Alys Pharmaceuticals recently announced it has submitted a clinical trial application to Germany's Paul-Ehrlich-Institut in order to initiate a phase 1/1b trial of ALY-301 for cold urticaria.¹ The study will assess the efficacy and safety of the mast cell selective c-Kit inhibitor in the subtype of chronic inducible urticaria.

The submission marks the first clinical trial stemming from Alys’ proprietary Granular platform, an antibody engineering framework designed to target mast cell biology with precision. ALY-301 represents a first-in-class bispecific antibody engineered to selectively inhibit c-Kit, a receptor critical for mast cell survival,² while sparing other c-Kit–expressing cells.

For patients with cold urticaria, the condition can have a significant impact on quality of life and often lacks satisfactory treatment options.³ While c-Kit inhibition has long been recognized for its therapeutic potential in mast cell diseases, most prior attempts have been limited by safety concerns.⁴

According to Alys Pharmaceuticals, the distinct selectivity of ALY-301 is expected to enable safe, long-term administration, potentially opening the door to treatment of a wider spectrum of mast cell-associated disorders beyond cold urticaria, such as chronic spontaneous urticaria, atopic dermatitis, and systemic mastocytosis.

The upcoming phase 1/1b trial will be conducted across multiple sites in Germany. In addition to evaluating the safety and tolerability of ALY-301 in healthy volunteers, the study will assess pharmacokinetics, pharmacodynamics, and early signs of clinical activity in patients with cold urticaria.

"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 Kim, MD, Sol and Clara Kest professor of dermatology and vice chair of research at the Icahn School of Medicine at Mount Sinai, said in a news release.¹

Kim, who also serves as chair of Alys’ Scientific Advisory Board, emphasized that ALY-301 uniquely targets activated mast cells while sparing other cell populations that have historically contributed to adverse effects with non-selective c-Kit inhibitors.

Martin Metz, MD, a global authority on urticaria and principal investigator for the ALY-301 trial, echoed this sentiment: "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."

"It is very exciting to start the clinical journey today, especially since this first clinical trial will yield clinical outcomes from urticaria patients."

The ability to deliver safe and effective chronic c-Kit inhibition through selective mast cell targeting is an exciting breakthrough,” said Metz, who holds appointments at the Charité – Universitätsmedizin Berlin and the Fraunhofer Institute.

Thibaud Portal, co-Founder and chief operating officer of Alys Pharmaceuticals, highlighted the broader significance of ALY-301 within the evolving therapeutic landscape for allergic diseases.

"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 said.¹ "With its expected safety margin and broad applicability across multiple diseases, this marks another pivotal moment for Alys in our journey to bring innovative treatments to patients."

References

1. 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 June 11, 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
2. Tsai M, Valent P, Galli SJ. KIT as a master regulator of the mast cell lineage. J Allergy Clin Immunol. 2022;149(6):1845-1854. doi:10.1016/j.jaci.2022.04.012
3. Hochstadter EF, Ben-Shoshan M. Cold-induced urticaria: challenges in diagnosis and management. BMJ Case Rep. 2013;2013:bcr2013010441. Published 2013 Jul 8. doi:10.1136/bcr-2013-010441
4. El-Agamy DS. Targeting c-kit in the therapy of mast cell disorders: current update. Eur J Pharmacol. 2012;690(1-3):1-3. doi:10.1016/j.ejphar.2012.06.030