ENV-294

Enveda Biosciences’ first-ever clinical readout places its lead eczema drug among the top candidates in an increasingly crowded race to follow the blockbuster immunology treatment Dupixent. The trial was a Phase 1b test that looked at nine adults with moderate-to-severe atopic dermatitis, which is the most common form of eczema. The patients saw an average drop in their Eczema Area and Severity Index, or EASI, scores of 68% after a month of taking an 800 mg once-daily dose. That EASI reduction deepened to 85% after a two-week observation period off the drug. That’s enough to at least put it in play against benchmark treatments on the market and in development. The results were shared with Endpoints News ahead of an official company announcement planned for later Tuesday. The trial was small and the data limited, but it gives the AI-powered drug developer hope that its experimental treatment is working as planned, CEO Viswa Colluru told Endpoints. Colluru said the Boulder, CO-based biotech was satisfied with its safety profile as well: ENV-294 was well-tolerated, with no serious or severe adverse events or treatment-related side effects. The next question will be whether these results hold up in larger trials, including an ongoing, placebo-controlled Phase 2a study that’s expected to produce topline results in the second half of 2026. Tuesday’s Phase 1b results could whet the appetite of both investors and large drugmakers, which have bet aggressively on treatments that could potentially improve upon Sanofi and Regeneron’s Dupixent, an antibody drug given as an injection. Dupixent has been approved for a range of inflammation-driven conditions like eczema and asthma, and last year brought in $17.8 billion in sales. Kymera Therapeutics is also developing a competing drug. The biotech has results from a Phase 1b trial of 22 patients, which showed an average EASI reduction of roughly 62% across two tested doses. That’s helped push the company’s market value to about $6.5 billion. The drug, called KT-621, is oral protein degrader of STAT6, a transcription factor related to Dupixent’s pathway. The Enveda drug’s activity appears to compare well with Dupixent, as well as with aspiring rival programs from Apogee Therapeutics and Corvus Pharmaceuticals . Dupixent, for example, has shown EASI reductions of 50% to 56% at four weeks. Those comparisons come with limits, of course. Unlike Kymera’s study, Enveda also enrolled patients who previously failed to respond to a biologic therapy. Three of its nine enrolled patients fit that criterion. Colluru said he believes that could open a larger potential market of eczema patients down the line for ENV-294. Founded in 2019, Enveda has become an unlikely biotech unicorn, raising a $150 million Series D last fall at a $1 billion-plus valuation. Colluru, an early employee at Recursion, founded the company on the belief that important medicines could be found by mining nature. It built AI models using the transformer architecture that is also behind large language models, to interpret and predict biological and chemical data. “Turns out, transformers are really good,” Colluru said in a January interview with Endpoints on the sidelines of the JP Morgan Healthcare Conference. “Just like you can predict missing words in a sentence, we taught models to predict missing peaks in mass-spec data.” Enveda paired that research with training AI models to interpret SMILES strings, which are like a language for representing chemicals. It has continued to improve these models, but has largely focused its public story on the pipeline of programs like ENV-294. “We’ve been quiet because we like to do molecules over models,” Colluru said. The company, which has about 350 employees roughly split between Boulder and Hyderabad, India, has focused on finding first-in-class medicines in big disease markets. It has yet to disclose ENV-294’s mechanism of action. Colluru described it as completely novel, with origins from searching plants that have long been used to treat symptoms. That led to compounds with anti-inflammatory activity, with one of those chemicals becoming the starting point of ENV-294. As it turned out, the molecule targets a protein complex that Colluru said has not been drugged or even bound to in the public domain of science. He described it as a “China-resistant molecule,” alluding to the idea that China-based drugmakers may be able to quickly develop me-too versions. When asked if it was related to an Enveda patent filing from last January that describes small molecules that modulate Rac2-RhoGDI binding, Colluru declined to comment. That patent application specifically mentions atopic dermatitis and asthma — the lead indications of ENV-294 — and appears to align with how the company has described ENV-294. With the Phase 1b data, Colluru said there has been “serious interest in our data” from pharma companies, while declining to disclose further details. Tuesday’s readout is just the beginning of what’s expected to be a flurry of clinical results for Enveda. The company expects topline data from a Phase 2a atopic dermatitis study of ENV-294 as well as Phase 1 studies for two more drugs, respectively in obesity and inflammatory bowel disease, in the second half of 2026.

Enveda's nature-powered AI platform is bearing its first fruits. The biotech on Tuesday reported data from a Phase Ib trial of lead candidate ENV-294 that suggest it may be effective at treating atopic dermatitis (AD) — and more importantly, could be a more tolerable oral treatment than currently available options. The readout comes about seven months after Enveda raised $150 million in a series D to fund the AD study and build out its drug discovery capabilities. The company has compiled the "world’s most powerful chemical library" of plant-derived molecules, comprising 38,000 plants linked to 12,000 human diseases and symptoms. "Once we observe interesting biological activity, we let evolution teach us the biology," Enveda CEO Viswa Colluru told FirstWord in September. "We bring together evolutionary intelligence and artificial intelligence — nature provides the blueprint, and AI gives us the tools to read it — to develop better medicines, faster."Swift symptom improvementsWhile the company isn't sharing specifics on ENV-294's mechanism of action, Colluru said in a company release that it's a non-degrading molecular glue, dubbed a "LOCKTAC," that resets the cellular immune response to chronic inflammation, instead of suppressing individual cytokines.In the Phase Ib trial, Enveda enrolled nine adults with moderate-to-severe AD to receive an oral 800-mg dose of ENV-294 once-daily for 28 days, followed by a 2-week observation period.After 28 days, patients saw a mean reduction of 68% in their Eczema Area and Severity Index (EASI) scores, and that response continued to deepen by day 42 — 14 days after treatment stopped — with patients achieving an 85% reduction. Treatment responses were seen as early as day eight, and because patients continued to improve even after they stopped taking ENV-294, Enveda thinks the experimental drug has "potential for durable disease modification."At day 42, all patients saw a 50% improvement on EASI scores, with 78% reaching EASI-75 and 56% achieving EASI-90. The company also reported "meaningful improvements" in itch reduction from baseline. The early data seem to stack up favourably against leading AD treatments. According to Enveda, the results suggest that "ENV-294 drives a pan-endotype treatment response by reconfiguring cellular immunity to chronic inflammation, rather than the single-axis cytokine blockade employed by current therapies."Across two Phase III trials of Regeneron and Sanofi's Dupixent (dupilumab), the standard-of-care biologic for AD, up to 51% of patients achieved EASI-75 at week 16, and up to 36% reached EASI-90. For AbbVie's Rinvoq (upadacitinib), the go-to JAK inhibitor for AD, EASI-75 achievement rates reached up to 80% at week 16 across the drug's two-trial pivotal programme (see – Spotlight On: KOLs preview trends shaping atopic dermatitis treatment). Staying safeOn the safety front, Enveda said ENV-294 was well tolerated, with no serious or severe adverse events (AEs), and no treatment-related AEs leading to trial discontinuation. The candidate wasn't associated with safety signals seen with existing systemic treatments, including those linked to immunosuppression. Additionally, no clinically meaningful changes were seen in patients' lab work, vital signs or ECGs."What struck me was how well patients tolerated ENV-294 with…a safety profile distinct from what we typically see with systemic immunosuppressants or JAK inhibitors. Equally impressive was the clinical response," said lead investigator Leon Kircik, a clinical professor at Mount Sinai. "For patients living with moderate-to-severe atopic dermatitis, the combination of a rapid, deep response in a well-tolerated, once-daily oral therapy is encouraging."Colluru said ENV-294 is moving through Phase IIa trials in AD and asthma, with a Phase IIb study planned to launch mid-year mid-2026. Enveda is also planning to study the candidate in inflammatory bowel disease and obesity.