TRex Bio Reports Positive Phase 1a Results for TRB-061, Supporting Treg Activation in Atopic Dermatitis
TRex Bio, Inc. (TRexBio), a clinical-stage biotechnology company focused on tissue regulatory T-cell (Treg) biology and the discovery and development of immunoregulatory medicines, has announced unblinded topline results from the first-in-human Phase 1a portion of its ongoing Phase 1a/b clinical trial evaluating TRB-061.
The early-stage findings provide encouraging evidence for the investigational therapy as the company advances its development program in immune-mediated diseases. Across both single ascending dose (SAD) and multiple ascending dose (MAD) cohorts, TRB-061 was generally well tolerated in healthy adults and demonstrated a consistent pharmacokinetic (PK) profile. Researchers also observed selective and reproducible activation and expansion of exploratory biomarkers, including regulatory T cells, following both single and multiple administrations of the investigational medicine.
According to TRexBio, these pharmacodynamic (PD) findings provide preliminary proof of mechanism and support the dose levels selected for the ongoing Phase 1b portion of the clinical program in adults with moderate-to-severe atopic dermatitis.
The results represent an important development milestone for TRexBio as the company seeks to translate its research into tissue-focused immunoregulatory medicines. The company’s approach is centered on the biology of Tregs, immune cells that play an important role in maintaining immune tolerance and controlling excessive inflammation.
TRB-061 Designed to Target Immune Regulation
Atopic dermatitis is a chronic inflammatory skin disease associated with dysregulated immune activity. Patients with moderate-to-severe disease may experience persistent inflammation, itching, skin lesions and impaired quality of life. Although several therapies are available, treatment response can vary, and there remains an ongoing need for medicines that address the underlying mechanisms of immune dysregulation.
TRexBio is developing TRB-061 with the goal of selectively activating and expanding immunoregulatory Tregs. These cells are important components of the immune system because they help suppress excessive immune responses and maintain tissue homeostasis.
The company’s development strategy is based on the potential of tissue Treg biology to restore immune balance and support tissue repair. The Phase 1a results provide early clinical evidence that TRB-061 can influence biological pathways associated with this mechanism in humans.
Johnston Erwin, Chief Executive Officer of TRexBio, said the Phase 1a findings represent an important milestone for the company. He highlighted the therapy’s generally favorable tolerability profile and the observed potential to selectively activate and expand immunoregulatory Tregs in human participants.
Erwin added that the findings increase the company’s confidence in the potential of TRB-061 to restore immune balance and promote tissue repair in people with atopic dermatitis and potentially other immune-mediated diseases.
Phase 1a Trial Evaluated Safety, Pharmacokinetics and Pharmacodynamics
The first-in-human Phase 1a portion of the clinical trial was structured as a randomized, double-blind and placebo-controlled study in healthy adults. Its primary objectives were to evaluate the safety and tolerability of subcutaneously administered TRB-061 while also characterizing its pharmacokinetic and pharmacodynamic properties.
The study incorporated two dose-escalation components: a single ascending dose portion and a multiple ascending dose portion.
In the SAD component, healthy volunteers received a single administration of TRB-061 or placebo at different dose levels. The MAD component evaluated repeated administration, with participants receiving TRB-061 or placebo every four weeks for a total of three doses.
Across both portions of the study, participants were randomized within each cohort at a ratio of 6:2 to receive active treatment or placebo. Four cohorts were evaluated in each part of the trial.
In total, 65 healthy adults participated in the Phase 1a study. The safety data showed that TRB-061 was generally well tolerated across the evaluated dose levels.
Importantly, there were no treatment-related serious adverse events reported during the study. Researchers also observed no dose-limiting toxicities and no treatment-related discontinuations.
All treatment-emergent adverse events were characterized as mild or moderate, providing an encouraging initial safety profile as the company progresses TRB-061 into patient populations.
While Phase 1 studies are primarily designed to assess safety and tolerability rather than demonstrate clinical efficacy, these findings provide an important foundation for continued development.
Consistent Pharmacokinetic Profile Observed
In addition to safety findings, the Phase 1a trial evaluated how TRB-061 behaved in the body following administration.
The investigational therapy demonstrated an approximately dose-proportional pharmacokinetic profile. This means that exposure to TRB-061 generally increased in relation to the administered dose, an observation that can help researchers understand the relationship between dose and drug exposure.
Both single-dose and multiple-dose administration produced consistent PK findings. The data also supported a dosing interval of four weeks or longer, an important consideration for the ongoing clinical development program.
A dosing schedule that allows for relatively infrequent administration could potentially offer practical advantages for patients if the therapy ultimately demonstrates safety and efficacy in later-stage studies. However, the clinical relevance of the dosing interval will depend on results from subsequent trials in patients with disease.
Treg Activation Provides Preliminary Proof of Mechanism
One of the most important aspects of the Phase 1a results was the pharmacodynamic evidence generated following treatment.
TRexBio reported that both single and multiple doses of TRB-061 resulted in selective and reproducible increases in Tregs. Among the observed populations were CD39-positive Tregs, a subset associated with immunoregulatory activity.
The study also identified induction of other immunoregulatory biomarkers, including interleukin-10 (IL-10) and CCR8.
These findings are significant because they provide biological evidence that TRB-061 is engaging pathways relevant to its proposed mechanism of action.
Tregs have an important role in regulating immune responses. In inflammatory and immune-mediated diseases, the balance between immune activation and immune regulation can become disrupted. By increasing or enhancing the activity of specific immunoregulatory T-cell populations, therapeutic approaches targeting Tregs may potentially help restore a more balanced immune environment.
The observed changes in Tregs and associated biomarkers therefore provide preliminary support for TRB-061’s intended biological activity.
At the same time, the company has not yet established whether these biomarker changes will translate into meaningful clinical improvements for patients with atopic dermatitis. That question will be addressed through the ongoing clinical development program.
Dose Selection for Phase 1b
The combined safety, PK and PD findings from the Phase 1a study have supported the selection of two dose levels for continued evaluation.
TRexBio is now evaluating 24 mg and 50 mg doses in the Phase 1b portion of the Phase 1a/b trial.
Moving into a patient population represents an important transition for the program. While the Phase 1a trial was conducted in healthy adults and focused primarily on safety and biological activity, the Phase 1b study is designed to assess TRB-061 in adults living with moderate-to-severe atopic dermatitis.
The Phase 1b study will continue to evaluate safety and pharmacokinetics while expanding the pharmacodynamic analysis. Researchers will assess biomarkers in both blood and skin, allowing the company to investigate the biological effects of TRB-061 in the tissues directly affected by atopic dermatitis.
The study will also include exploratory assessments of clinical activity. These measures are intended to provide early information about whether the biological effects observed in healthy volunteers may translate into potential therapeutic activity in patients.
Focus on Skin and Blood Biomarkers
The inclusion of both blood and skin biomarkers in Phase 1b is particularly relevant to the company’s tissue-focused development strategy.
Atopic dermatitis is fundamentally a disease involving the skin, where immune dysregulation contributes to chronic inflammation and tissue damage. Evaluating biomarkers in affected skin may therefore provide additional insight into whether TRB-061 is influencing the local immune environment.
Blood-based biomarkers can offer information about systemic pharmacodynamic activity, while skin measurements may help researchers understand local biological effects.
Together, these assessments could provide a more comprehensive picture of how TRB-061 affects immune regulation following treatment.
Potential Beyond Atopic Dermatitis
Although the current clinical program is focused on moderate-to-severe atopic dermatitis, TRexBio believes that the underlying approach could have broader applications in immune-mediated diseases.
The company’s research is centered on tissue Treg biology and the potential role of these cells in maintaining immune balance and tissue health. If TRB-061 demonstrates meaningful clinical activity in atopic dermatitis, future research could potentially explore its application in additional diseases characterized by inappropriate or excessive immune activation.
However, further clinical evidence will be required before determining the broader therapeutic potential of the program.
The Phase 1b study is consequently an important next step in establishing whether the biological activity demonstrated in healthy adults can be reproduced in patients and whether those changes are associated with improvements in disease-related outcomes.
TRexBio expects to report topline results from the ongoing Phase 1b trial in mid-2027. These results are expected to provide additional information regarding the safety, pharmacokinetic and pharmacodynamic profile of TRB-061 in adults with moderate-to-severe atopic dermatitis.
The upcoming data will also be important for evaluating biomarkers measured in blood and skin and for assessing exploratory indicators of clinical activity.
Overall, the Phase 1a findings provide an encouraging foundation for the continued development of TRB-061. The absence of treatment-related serious adverse events, dose-limiting toxicities or treatment-related discontinuations, combined with an approximately dose-proportional PK profile, supports continued clinical evaluation.
Equally important, the observed activation and expansion of Tregs, including CD39-positive Tregs, along with changes in IL-10 and CCR8, provide early evidence that the investigational medicine is engaging its intended immunoregulatory pathways.
As TRexBio advances TRB-061 into Phase 1b, the company will seek to determine whether this proof of mechanism can translate into meaningful biological and clinical effects in patients with atopic dermatitis. The results could help define the future development path for TRB-061 and potentially inform the broader application of tissue Treg-based approaches in immune-mediated diseases.
About TRB-061
TRB-061 is a novel, selective, investigational TNFR2 agonist designed to activate and expand Tregs in inflamed tissues and restore immune balance without stimulating unwanted immune cells. TNFR2 is a crucial regulator of immune homeostasis, supporting tissue repair and counteracting inflammation. Defects in TNFR2 signaling are linked to multiple autoimmune and inflammatory diseases.
Selective agonism of TNFR2 by TRB-061 may represent a new therapeutic approach for long-term inflammatory disease control. TRB-061 is currently being evaluated in a randomized, double-blind, placebo-controlled Phase 1b study in patients with moderate-to-severe AD. The study includes exploratory PD endpoints assessing Treg expansion in blood and skin, as well as clinical assessments of disease activity.
About Atopic Dermatitis
Atopic dermatitis (“AD”) is a chronic inflammatory skin disease characterized by rash, itching, and skin barrier dysfunction. AD affects approximately 16 million American adults and an estimated 225 million individuals globally. In moderate-to-severe cases, AD is associated with systemic immune activation, extensive body surface area involvement, and substantial quality-of-life impairment. While approved biologics have improved outcomes for some patients, close to 50% of AD patients discontinue current therapies within two years.
About TRexBio
TRexBio is a clinical-stage biotechnology company focused on tissue Treg biology for the discovery and development of immunoregulatory medicines designed to restore immune balance and promote tissue repair to address unmet needs of patients with autoimmune and inflammatory diseases.
The Company’s Deep Biology platform decodes Treg functionality in human tissue, mapping key drivers of immune dysregulation and uncovering novel targets and insights that inform drug discovery and translational efforts. This platform has generated multiple therapeutic development candidates across TRexBio’s wholly owned pipeline and through collaborations with leading pharmaceutical partners. TRexBio is led by an experienced management team and headquartered in South San Francisco, California.