Azitra, Inc. has achieved a significant clinical milestone by dosing the first patient in its Phase 1/2 clinical trial of ATR04-484, a topically applied live biotherapeutic product candidate designed to treat EGFR inhibitor (EGFRi)-associated rash. The FDA has granted Fast Track designation for this program, addressing a condition that impacts approximately 150,000 people in the U.S. annually.
"Dosing the first patient is an important milestone in the advancement of ATR04-484 as a potential treatment for EGFRi associated rash and in the development of our broader ATR-04 technology program," said Francisco Salva, CEO of Azitra. "Given the importance of EGFRi treatments across multiple cancers, there is a critical medical need to reduce the impact of the unique dermatologic toxicities that often accompany EGFRi treatments, often leading to interruption or discontinuation of the treatment."
Addressing a Critical Unmet Medical Need
Targeted cancer therapies, particularly EGFRis, have produced significant treatment advances for patients diagnosed with various tumor types including non-small cell lung cancer (NSCLC) and colorectal cancer. However, these therapies are associated with unique dermatologic toxicities that can severely hamper treatment efforts, causing significant physical and psychological discomfort for patients.
The papulopustular rash represents the earliest and most common dermatologic adverse event of EGFRi treatment, occurring in 50-80% of patients. This side effect often impacts quality of life severely enough to interrupt or stop cancer treatment, creating a significant therapeutic challenge for oncologists and patients alike.
Phase 1/2 Trial Design and Objectives
The multicenter, randomized, double-blind, vehicle-controlled Phase 1/2 clinical study (NCT06830863) is designed to evaluate the safety and tolerability of topical ATR04-484 for treating EGFRi-associated dermal toxicity affecting the face of adult patients. The study employs a 3:1 randomization ratio, with ATR04-484 or its vehicle applied to the face as well as affected areas on the neck, chest, back, and areas around nailbeds.
The key objectives include assessing the safety and tolerability of topical ATR04-484 and evaluating efficacy signals including severity of disease, pruritus, and pain. The study will also examine the bioavailability of ATR04-484 and pharmacodynamic parameters, establishing the foundation for continued clinical development.
Novel Live Biotherapeutic Approach
ATR04-484 represents an innovative approach as a live biotherapeutic product candidate featuring an isolated, naturally derived Staphylococcus epidermidis strain specifically developed for EGFRi-associated skin rash. The candidate was selected based on its preclinical profile demonstrating the ability to reduce IL-36γ and S. aureus levels, both of which are elevated in patients with EGFRi-associated skin rash.
To ensure safety, the strain was engineered by deleting an antibiotic resistance gene and engineering auxotrophy to control the growth of ATR04-484. This careful engineering approach reflects the company's commitment to developing safe and effective live biotherapeutic products.
Azitra's Precision Dermatology Platform
The ATR-04 program is part of Azitra's broader precision dermatology platform, which includes a proprietary library of engineered proteins and topical live biotherapeutic products comprising approximately 1,500 bacterial strains. This platform is enhanced by artificial intelligence and machine learning technology that analyzes, predicts, and helps screen the library of strains for drug-like molecules.
Azitra's lead program, ATR-12, utilizes another engineered strain of S. epidermidis designed to treat Netherton syndrome, a rare, chronic skin disease with no approved treatment options. Netherton syndrome may be fatal in infancy, with those living beyond a year facing profound lifelong challenges.
