Montai Therapeutics Doses First Participants in Phase 1 Clinical Trial of MTAI-1025, a Novel Oral NRF2 Agonist for Ulcerative Colitis

First clinical-stage program leveraging Montai’s CONECTA® platform designed to directly address inflammation, oxidative stress and epithelial barrier dysfunction through a differentiated oral mechanism

Phase 1 study will evaluate safety, tolerability, pharmacokinetics and pharmacodynamic activity; topline data expected mid-2027

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Montai Therapeutics, a biotechnology company harnessing AI to decode untapped chemistry and develop breakthrough medicines for chronic disease, today announced that the company has completed dosing participants in the first single-ascending dose cohort of a Phase 1 clinical trial evaluating MTAI-1025, a novel oral NRF2 agonist in development for the treatment of ulcerative colitis (UC), a chronic inflammatory bowel disease. MTAI-1025 is the first therapeutic candidate from Montai’s pipeline to enter clinical development.

MTAI-1025 is designed to selectively activate NRF2, a transcriptional regulator of cellular responses to oxidative stress and inflammation, with the potency, selectivity and safety profile aligned for chronic dosing in UC. Through NRF2 activation, MTAI-1025 has the potential to directly address three interconnected components of UC pathophysiology - mucosal inflammation, oxidative stress and epithelial barrier dysfunction - through a single oral therapy. In preclinical studies, MTAI-1025 has demonstrated a favorable tolerability profile and signals of therapeutic activity, including dose-dependent improvement in disease activity and improved histopathology versus standard anti-IL-12/IL23 monoclonal antibodies.

“Dosing the first participants with MTAI-1025 is an important milestone for Montai, marking the translation of our CONECTA® platform from discovery into the clinic,” said Lamya Shihabuddin, PhD, Chief Scientific Officer of Montai. “Current therapies for ulcerative colitis primarily target inflammation, yet epithelial barrier dysfunction and oxidative stress are also central components of disease biology. MTAI-1025 was designed to address these interconnected mechanisms through selective NRF2 activation, creating the potential for a differentiated oral treatment for patients with UC that could break the efficacy ceiling that limits current therapies. We are eager to begin evaluating MTAI-1025 in humans and to advance toward studies in patients with ulcerative colitis.”

The Phase 1 study is a randomized, placebo-controlled study evaluating single and multiple ascending doses of MTAI-1025 in healthy volunteers. The study will assess safety, tolerability, and pharmacokinetics, as well as exploratory pharmacodynamic measures of NRF2 pathway activation. Participants will be randomized 3:1 to receive MTAI-1025 or placebo. Initial findings from the study are expected to be available by mid-2027. For more information, visit the study overview.

Montai is building a robust therapeutic pipeline by leveraging its AI-driven CONECTA platform to engineer potent, highly selective oral therapies as alternatives to biologics and combination therapies for a range of challenging chronic inflammatory diseases. With the platform, Montai identified novel chemistry to create MTAI-1025 as a potential next-generation NRF2 therapy with the potency, selectivity and safety profile to support chronic dosing among large populations. MTAI-1025 represents the first candidate in Montai’s pipeline to enter clinical studies

About Montai Therapeutics

Montai is harnessing AI to decode untapped diverse chemistry to develop breakthrough oral medicines that can address persistent unmet needs in chronic inflammatory disease. With the CONECTA^® platform, Montai has built the world’s leading foundation models for decoding the complex language between nature’s bioactive chemistry and human biology – supercharging the drug discovery process with unprecedented optionality and predictability.

Montai is advancing a pipeline of novel oral medicines for validated biological pathways in inflammation and immunology focused on biologic replacements and historically difficult to drug transcription factors. Its lead program, MTAI-1025, is a novel oral NRF2 agonist in clinical development for ulcerative colitis. Montai was founded in Flagship Labs in 2019. For more information, please visit www.montai.com or follow us on LinkedIn.