South San Francisco-based TRex Bio, Inc. (TRexBio) has reported positive Phase Ia results for TRB-061, a selective tumor necrosis factor receptor 2 (TNFR2) agonist being developed for atopic dermatitis (AD). The healthy-volunteer study provided initial human evidence that the drug can selectively expand regulatory T cells (Tregs), supporting the company's proposed mechanism ahead of Phase Ib testing in patients.
In single ascending-dose cohorts, TRB-061 was generally well tolerated, with no treatment-related serious adverse events, dose-limiting toxicities, or treatment-related discontinuations. All treatment-emergent adverse events were mild or moderate. Pharmacokinetics were approximately dose proportional, while pharmacodynamic testing showed reproducible expansion of Tregs, including CD39-positive Tregs, together with increases in the immunoregulatory biomarkers IL-10 and CCR8.
The PK/PD profile supports dosing every four weeks or potentially longer, according to TRexBio. The company selected 24 mg and 50 mg doses for the ongoing Phase Ib portion of the study in adults with moderate-to-severe AD, with topline results expected in mid-2027. That study will assess Treg expansion in lesional skin as well as peripheral blood, providing an early test of whether the pharmacodynamic activity observed in healthy volunteers translates into affected tissue and clinical benefit.
TRB-061 takes a different approach from approved AD therapies, which primarily block inflammatory cytokines or downstream signaling pathways. TNFR2 is highly expressed on activated Tregs, immune cells that help restrain excessive inflammatory responses. Selective agonism of the receptor is intended to expand and enhance these immunoregulatory cells without activating TNFR1, which mediates many of the pro-inflammatory effects associated with tumor necrosis factor signaling. TRexBio has previously presented translational data identifying altered Treg programs in AD skin and supporting TNFR2 as a regulator of local immune homeostasis.