Program derived from Montai’s Anthromolecule chemistry demonstrates potent selectivity and efficacy against a triad of key mechanisms implicated in UC

Company’s first development candidate to advance to IND-enabling studies

Montai Therapeutics, a company harnessing AI to decode untapped, diverse chemistry to develop breakthrough medicines for chronic disease, will present preclinical data for the first time on its novel oral NRF2 agonist molecule, MTAI-1025, demonstrating potent and selective efficacy against inflammatory mechanisms of ulcerative colitis (UC). The data will be presented during the American College of Asthma, Allergy and Immunology annual meeting on November 8^th in Orlando.

The NRF2 candidate is the first DC produced by Montai’s CONECTA platform and derived from the company’s Anthromolecule chemistry – a curated set of over 1 billion diverse bioactive molecules. Based on the preclinical results, Montai will advance MTAI-1025 to IND-enabling studies.

“These data demonstrate that MTAI-1025 can effectively attenuate inflammation and promote mucosal protection in vivo in preclinical models, supporting its potential as a first-in-class oral NRF2 therapy for UC, both as a monotherapy or in combination with monoclonal antibodies,” said Lamya Shihabuddin, Ph.D., Montai’s CSO. “This is also an important demonstration of the power of Montai’s platform to deliver potential oral medicines for complex, chronic inflammatory diseases that today are the exclusive domain of biologics.”

Montai’s candidate addresses UC, an autoimmune disease of the gastrointestinal system driven by three primary mechanisms: epithelial barrier dysfunction, chronic mucosal inflammation and oxidative stress. UC has few effective therapies today, including biologic therapies that do not fully address the complex interlinked mechanisms of the disease. MTAI-1025 is a highly potent, selective oral therapy that activates the transcription factor NRF2 (a master regulator of cytoprotective gene networks), which has been shown to promote antioxidant responses, suppress pro-inflammatory signaling, and support epithelial repair in other immune-mediated diseases, but has eluded selective targeting with small molecules.

Preclinical evaluations have indicated the candidate offers a highly promising profile to alleviate the inflammatory mechanisms of UC. Using a colitis mouse model, mice were treated over 14 days with MTAI-1025 (low, medium and high doses, oral daily), placebo, or an anti-IL-12p40 monoclonal antibody (mAb, 10 mg/kg, via intraperitoneal injection). MTAI-1025 elicited a clear dose-dependent reduction in key outcomes measures, such as the UC Disease Activity Index and weight loss, with better efficacy compared to the mAb. Analyses also revealed improved mucosal architecture and reduced inflammatory infiltration, with a marked reduction in pro-inflammatory cytokines, and confirmed NRF2 activation. Importantly, the tolerability profile was favorable with no signs of increased inflammation or necrosis.

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 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. The company has curated and annotated a collection of over 1B Anthromolecules™ and Anthrologs™, which are derived from molecules humans have chronically consumed in food, supplements and herbal medicines. This has enabled efficient access to chemistry with vast untapped structural diversity and the potential to selectively and precisely modulate complex biology. Montai is rapidly advancing a pipeline of first-in-class oral medicines for validated biological pathways in inflammation and immunology – focused on biologic replacements and historically difficult to drug transcription factors. Montai was founded in Flagship Labs in 2019. For more information, please visit www.montai.com or follow us on LinkedIn.

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