For Immediate Release
Calixis Announces Commencement of a Phase 2 Trial of Oral KIT Inhibitor THB335 in Chronic Spontaneous Urticaria
Randomized, double-blind, placebo-controlled study of once-daily THB335 in adults who remain symptomatic despite antihistamines, including patients who have failed or are intolerant to advanced therapies.
Calixis, Inc., a clinical-stage biopharmaceutical company developing oral therapies for mast cell–driven diseases, today announced the commencement of its Phase 2 clinical trial of THB335, an investigational oral inhibitor of KIT, in adults with chronic spontaneous urticaria (CSU) who remain symptomatic despite standard-of-care treatment.
THB335 is a potent, selective, oral small-molecule inhibitor of KIT, the receptor tyrosine kinase essential for the survival and function of mast cells — the central effector cells that drive the hives, itch, and angioedema of CSU. By inhibiting KIT, THB335 is designed to reduce mast cell number and activity, addressing a root driver of disease rather than downstream mediators alone. In a completed Phase 1 program, once-daily THB335 was generally well tolerated and produced dose-dependent reductions in serum tryptase, a biomarker of mast cell burden.
“Despite available treatments, many people with chronic spontaneous urticaria continue to live with unpredictable hives, relentless itch, and swelling that disrupts sleep, work, and daily life. THB335 is designed to go after a root cause of the disease — the mast cell — with the convenience of a once-daily pill. The start of our Phase 2 study is an important milestone for Calixis and, we hope, a step toward a meaningful new option for patients.”
— Eben Tessari, Chief Executive Officer of CalixisAbout the Phase 2 Trial
THB335-201 is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating the efficacy and safety of THB335 in adults with CSU who remain symptomatic despite standard-of-care second-generation H1-antihistamine (sgAH) therapy. The study is enrolling a broad CSU population — including patients who have failed or are intolerant to advanced therapies such as omalizumab — and plans to enroll approximately 81 participants across sites in the United States and Europe.
Eligible participants are adults aged 18 to 85 with a diagnosis of CSU for at least six months who remain symptomatic (UAS7 ≥ 16 and weekly Itch Severity Score ≥ 8) despite treatment with an sgAH at up to four times the labeled dose. Participants are randomized 1:1:1 to receive one of two dose levels of once-daily oral THB335, or placebo, added to their stable background antihistamine therapy, for a 12-week treatment period followed by a 4-week follow-up.
The primary endpoint is the change from baseline in the weekly Urticaria Activity Score (UAS7) at Week 12. Secondary endpoints include the proportion of participants achieving well-controlled disease (UAS7 ≤ 6) at Weeks 4, 8, and 12 and complete response (UAS7 = 0) at Week 12; changes in itch and hive severity scores and in the Urticaria Control Test; and the safety and tolerability of THB335.
About Chronic Spontaneous Urticaria
Chronic spontaneous urticaria is a mast cell–driven inflammatory skin condition defined by the recurrence of itchy hives (wheals), angioedema, or both for six weeks or longer without an identifiable external trigger. It is estimated to affect approximately 0.5–1% of the population at some point in their lives, is roughly twice as common in women, and can persist for years. Many patients remain symptomatic despite standard-of-care H1-antihistamines, and some continue to experience burdensome disease despite advanced therapies, leaving a need for new oral options.
About THB335
THB335 is an investigational, orally administered, potent and selective small-molecule inhibitor of KIT being developed by Calixis for mast cell–driven diseases, beginning with CSU. In a Phase 1 program in healthy volunteers (single- and multiple-ascending-dose cohorts), THB335 exhibited a pharmacokinetic profile supportive of once-daily dosing, with a half-life of approximately 40 hours, and produced dose-dependent reductions in serum tryptase — a biomarker of mast cell burden — of approximately 13% to 84% from baseline at Day 15. THB335 was generally well tolerated. THB335 has not been approved by any regulatory authority, and its safety and efficacy have not been established.
About Calixis
Calixis, Inc. is a clinical-stage biopharmaceutical company based in Cambridge, Massachusetts, developing oral therapeutics targeting mast cells for immunologic and inflammatory diseases, led by its lead program THB335 in chronic spontaneous urticaria. Calixis was formed in 2025 and has raised $45M in Series A capital from blue-chip life-science investors. For more information, visit www.calixisbio.com.
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Forward-looking statements. This press release contains forward-looking statements regarding Calixis's clinical development plans and the potential of THB335. Such statements involve risks and uncertainties, and actual results may differ materially. THB335 is investigational and has not been approved by the U.S. Food and Drug Administration or any other regulatory authority; its safety and efficacy have not been established. Calixis undertakes no obligation to update these statements except as required by law.