TRexBio has initiated dosing of healthy volunteers in its first clinical trial for TRB-061, a novel TNFR2 agonist being developed for the treatment of atopic dermatitis. The milestone represents a significant advancement for the clinical-stage biotechnology company's approach to addressing inflammatory diseases through tissue-targeted immune modulation.
Phase 1a Trial Design and Objectives
The randomized, double-blind, placebo-controlled Phase 1a study (ClinicalTrials.gov Identifier: NCT06934252) will assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of TRB-061 administered subcutaneously in healthy adult volunteers. The study includes assessments of blood-based biomarkers to establish early proof of mechanism, with safety, pharmacokinetic, and pharmacodynamic data from healthy volunteers anticipated in the first half of 2026.
"We believe TRB-061 has the potential to be a best-in-class therapy with multi-indication application," said Johnston Erwin, Chief Executive Officer of TRexBio. "Advancing TRB-061 into clinical development marks a significant milestone for the company and an important step in addressing the significant unmet needs of patients with atopic dermatitis and other inflammatory diseases."
Novel Mechanism of Action
TRB-061 is a novel TNFR2-selective agonist designed to activate and expand effector regulatory T cells (Tregs) in tissues and restore immune balance in inflammatory diseases. TNFR2 is an immune-regulatory receptor highly expressed on Tregs in barrier tissues such as skin and gut. In diseases like atopic dermatitis, impaired Treg function in diseased tissues contributes to chronic inflammation.
The drug candidate selectively activates TNFR2 signaling in Tregs without stimulating other immune cells including natural killer cells, effector T cells, or macrophages. In preclinical models, this selective activity translated to potent expansion of effector Tregs in blood and tissue without any unwanted immune activation.
Addressing Unmet Medical Need
"Despite approved treatments, many patients with atopic dermatitis experience inadequate relief of symptoms and troublesome side effects, highlighting the need for new mechanisms of action," said Ariella Kelman, M.D., Chief Medical Officer of TRexBio. "TRB-061 is designed to modulate immune balance at the tissue level and may offer improved disease control and tolerability."
Atopic dermatitis affects up to 20% of children and 10% of adults, affecting approximately 204 million people worldwide. In moderate-to-severe cases, the chronic inflammatory skin disease is associated with systemic immune activation, extensive body surface area involvement, and substantial quality-of-life impairment.
Development Platform and Future Plans
TRexBio's Deep Biology platform identified TRB-061 for atopic dermatitis through high-resolution transcriptomic mapping and ex vivo validation of TNFR2-driven Treg activity in AD lesions. The platform maps human tissue Treg behavior to disease processes to identify and characterize novel targets for therapeutic intervention.
Following completion of the Phase 1a study, TRexBio plans to initiate a Phase 1b proof-of-concept trial in patients with moderate-to-severe atopic dermatitis. The preclinical data support TRB-061's potential as a tissue-targeted, disease-modifying therapy to selectively restore immune balance where local immune dysregulation drives chronic inflammation.
