Topadur Pharma AG, a Swiss clinical-stage biopharmaceutical company, today announced that the Safety Review Committee of its Phase 2a trial has recommended progression to the next planned dose levels. The trial is evaluating lead candidate TOP-N53 for the treatment of systemic sclerosis-associated digital ulcers.
The recommendation follows a review of safety data and the completion of the first patient cohort. No protocol-defined stopping criteria were met, and no serious adverse drug reactions were reported.
TOP-N53 is a novel, bifunctional topical therapeutic candidate designed to improve microcirculation and support tissue repair. By combining nitric oxide (NO) release and phosphodiesterase-5 (PDE5) inhibition in a single small molecule, TOP-N53 aims to enhance cGMP signaling directly at the site of application. Its clinical development builds on a first-in-human Phase 1 study in healthy volunteers, which demonstrated favorable tolerability and increased local skin perfusion following subcutaneous administration.
TOP-N53 holds orphan drug designation in both the US and the European Union for the treatment of systemic sclerosis-associated digital ulcers. The ongoing open-label, vehicle-controlled Phase 2a trial (NCT06954597), conducted in Switzerland and France, evaluates the safety and tolerability of ascending doses of TOP-N53 applied topically to digital ulcers in patients with systemic sclerosis.
TOP-N53 is a key program for Topadur as we investigate the potential of locally acting therapies to address diseases with significant unmet medical needs. With the Safety Review Committee’s recommendation to proceed to the next dose levels, we have reached an important milestone in the clinical development of TOP-N53. We are grateful to the patients and clinical teams whose participation and dedication make it possible to move this clinical trial forward.”
PD Dr. Matthias Schäfer, CEO, Topadur Pharma AG
Systemic sclerosis is a rare autoimmune disease characterized by damage to small blood vessels and fibrosis of the skin and internal organs. About half of patients develop digital ulcers, painful wounds on the fingers that are often slow to heal and prone to recurrence. Treatment options for existing ulcers remain limited, and current drug treatments act systemically. A 2025 consensus report by the World Scleroderma Foundation highlights the significant unmet medical need for local treatment strategies for digital ulcers.
“Even a single digital ulcer can cause significant pain and severely affect a patient’s daily life, making activities as simple as buttoning a shirt or holding a pen difficult,” said Prof. Marie-Elise Truchetet, Department of Rheumatology, CHU de Bordeaux, France, and Principal Investigator at the Bordeaux study site. “There is a clear need for new local treatment options. Evaluating the safety and tolerability of TOP-N53 at increasing doses is an important step towards understanding its potential for patients with digital ulcers.”
The trial is part of a start-up innovation project supported by Innosuisse. Recruitment for the second cohort is scheduled to begin in November at six clinical centers in Switzerland and France, coinciding with the colder months, when new digital ulcers occur more frequently.