Five years after launching Enveda with $55,000 of personal savings, Viswa Colluru, PhD, CEO, saw his initial investment in the AI-powered developer of plant-based treatments more than pay off recently when the company completed a $130 million Series C financing.
Enveda says its latest financing is intended to help the company further develop its platform and its pipeline of 10 development candidates and “multiple” additional discovery programs, with plans to deliver on clinical benchmarks in 2025 and 2026 after having just advanced its lead program into Phase I studies earlier this fall.
Enveda’s pipeline is led by ENV-294, a first-in-class, oral small molecule being developed to treat atopic dermatitis and other inflammatory conditions by combining the advantages of blockbuster drugs now marketed for the skin disorder.
According to Enveda, ENV-294 is designed to deliver the safety of injectable drugs that treat atopic dermatitis (AD) by blocking the interleukin (IL)-4 and IL-13 signaling pathways, such as IL-4 receptor alpha antagonist Dupixent® (dupilumab), co-marketed by Sanofi and Regeneron Pharmaceuticals. IL-13 antagonists indicated for AD include Leo Pharma’s Adbry® (tralokinumab-ldrm), and most recently Eli Lilly’s Ebglyss™ (lebrikizumab-lbkz), approved by the FDA in September.
ENV-294 is also designed to deliver the efficacy and ease of use of oral JAK inhibitors such as Incyte’s Opzelura® (ruxolitinib), AbbVie’s Rinvoq® (upadacitinib), and Pfizer’s Cibinqo® (abrocitinib).
At the end of October, Enveda launched a Phase I trial for ENV-294, the first candidate discovered using the company’s platform.
“It’s a consummation of our thesis as well as our technology, and a robust demonstration of the value proposition and differentiation we can deliver to the industry and patients,” Colluru, who is Enveda’s founder and CEO, told GEN Edge.
ENV-294 is derived from a plant the company won’t disclose, but which Colluru described as “a medicinal plant that has a long history of being used to treat inflammatory conditions.” After identifying the plant, he said, Enveda optimized it to improve its drug-like properties, and identified “a completely new mechanism to treat inflammation that has not been identified and/or drugged before.”
Organize, translate, and apply
ENV-294 emerged from Enveda’s platform, designed to organize, translate, and apply data from the company’s searchable library of plant molecules, most of which the company says have never been studied before. The library has cataloged data on more than a million natural compounds—including more than 38,000 medicinal plants linked to 12,000 human diseases and symptoms.
All of that data is proprietary, and primarily focused on plant compounds, which have historically resisted a platform-wide approach to being characterized. While many companies have been successful working with natural products, Colluru noted, they have largely relied on being able to sequence biosynthetic gene clusters and express them in the lab.
“Plant genomes are extremely complex, and many plant biosynthetic gene clusters resist expression in simple bacterial strains or yeast strains in the lab. They’re actually toxic to them,” Colluru said. “One big reason why we’re going after plants is that other platforms have just not been able to do that. And the second reason is that humans have a long history of sampling plants and deriving extremely successful medicines from them.”
Once a plant molecule is identified, the platform uses AI to accelerate its analysis from one molecule to 10,000 at a time, through a fully automated lab capable of screening the molecules and determining their therapeutic properties at high throughput. Enveda has trained the platform’s machine learning (ML) foundation model, called PRISM (Pretrained Representations Informed by Spectral Masking), on 1.2 billion small molecule mass spectra (MS)—the largest training set of small molecule mass spectra ever assembled, according to the company.
“Our goal is to use ML to be able to interpret MS data so that we can predict the structures and identify molecules that have never been seen by science before, as we believe the 99.9% of unknown natural molecules represents the largest untapped resource for new medicines on the planet,” Colluru and eight co-authors wrote on Enveda’s website in explaining PRISM, built in collaboration with Microsoft using its Azure cloud computing platform.
Four times faster
Enveda says its platform can speed up the discovery of drug candidates four times faster than the 55-month industry average identified in a 2010 study published in Nature Reviews Drug Discovery, and based on conventional drug discovery processes. One in four scaffolds leads to a declared development candidate, compared with the industry average of one in ~40 scaffolds progressing beyond preclinical testing, according to a 2022 study. And while a recent study published in Nature’s Scientific Reports by the Atomwise Artificial Intelligence Molecular Screen (AIMS) Program indicated an industry average of 676 analogs per development candidate, Enveda says it needs 75% fewer analogs or roughly 170.
Over time, Colluru said, the platform can be extended to study samples beyond plants: “Our technologies are tailored to understanding the chemistry of every sample, so we can extend it beyond plants to study human plasma or microbial extracts, everything that forms the chemical layer. And there are aspects perhaps that could help other layers of biology, but those are not our focus.”
Enveda considers inflammatory conditions a key aspect of its portfolio, with several of its first molecules focused on that therapeutic area. In addition to ENV-294, the company’s inflammatory pipeline includes:
• ESN-X, an NLRP3/TL1A pathway+ inhibitor designed to treat inflammatory bowel disease (IBD). ESN-X is in the IND-enabling phase and expected to enter Phase I trials in 2025.
• ESN-D, a preclinical optimization phase TGR5 agonist also being developed for IBD.
• ESN-Y, a gut-preferred, oral TGFβ inhibitor being developed to treat fibrostenotic Crohn’s disease. ESN-Y is ready for IND-enabling studies following the emergence of a development candidate.
• ESN-G, an MRGPRX2 antagonist for multiple inflammatory conditions, also in the optimization phase.
• Two preclinical discovery candidates with an undisclosed novel mechanism, the first-in-class, oral small molecules ESN-B and ESN-B1, both under study in multiple chronic pain conditions. B and B1 are expected to emerge as development candidates in 2025.
• Two other discovery candidates for as-yet unspecified inflammatory conditions that include the TL1A antagonist ESN-T, and the IL-4/13 antagonist ESN-F.
“Great place to play”
“We determined that inflammatory diseases, even before the current I&I [immunology and inflammation] gold rush of the pharma industry was a great place to play because there is a long history of natural products delivering interesting biology and value,” Colluru explained. “It is a market that is growing, and a market that is in need of first-in-class mechanisms that address big areas like, can you have safe oral treatments for an entire class of diseases? So absolutely we focus on inflammatory, but it is not the only area of focus.”
A report published by Nova One Advisor projected the anti-inflammatory drug market to more than double over a decade, growing at a compound annual growth rate of 8.5% from $120.46 billion in 2023 to a projected $130.70 billion this year and $272.35 billion by 2033.
In addition to I&I, Enveda’s 16-program pipeline includes obesity, fibrosis, and neurosensory candidates. In obesity, where several blockbuster glucagon-like peptide 1 (GLP-1) receptor agonists marketed by Novo Nordisk and Lilly have reshaped the market in recent years, Enveda is in IND-enabling phase with ESN-O, a first-in-class, oral small molecule hormone mimetic that the company expects to launch into Phase I trials in mid-2025.
While GLP-1 drugs enable users to lose significant amounts of weight quickly, they require patients to use injectable treatments whose side effects range from taste aversion to weeks and months of nausea, vomiting, and diarrhea. A 2020 retrospective study found that the discontinuation rates associated with GLP-1 receptor agonist drugs were 47.7% at 12 months following the start of treatment, and 70.1% at 24 months, with differences at 24 months for age and dosing frequency.
“Obesity is actually as much, if not more, about keeping weight off as it is about losing weight,” Colluru said. “Ultimately, we think that a market that is 800 million strong [World Health Organization estimate, 2022], approached only in size by hyperlipidemia and potentially hypertension, will be served by an oral once daily pill that you can take for potentially your entire life, that works to keep weight off and or prevents weight regain as the bulk of the market that will crystallize. So, one of the things that we’re working on actively is a molecule that has precisely those properties with a completely new mechanism.”
Beyond obesity and inflammation
Beyond obesity and inflammation, Enveda’s pipeline includes programs designed to treat:
• Fibrosis: ESN-A, a first-in-class, oral small molecule that has reached development candidate status and is ready for IND-enabling studies. ESN-A has an undisclosed novel mechanism that according to Enveda has shown potent efficacy in multiple preclinical models of fibrosis. Also, ESN-Y2, an inhaled TGFβ inhibitor being studied in multiple lung fibrotic conditions, and expected to emerge as a development candidate by year’s end.
• Skin disorders: ESN-C, an MRPGRX4 antagonist for cholestatic pruritus, a symptom of cholestatic liver diseases. ESN-C has completed IND-enabling studies. Also, ESN-Y1, a locally injected TGFβ inhibitor being studied in multiple dermal fibrotic conditions.
• Liver disorders: ESN-X1, an NLRP3/TL1A Pathway+ Inhibitor being studied in multiple liver conditions. The first-in-class, oral single-target, multi-cytokine inhibitor is ready for IND-enabling studies following selection of a development candidate.
• Neuro, cardiometabolic disorders: ESN-X2, a first-in-class, brain-penetrant oral small molecule that offers what Enveda calls “multi-biologic in a pill” potential via a novel single target for treating multiple neurological and cardiometabolic disorders. ESN-X2 is an NLRP3/TL1A pathway+ inhibitor that has reached development candidate status and is ready for IND-enabling studies. Also, ESN-N, a topical NRF2 agonist that is under study for various unspecified neurosensory conditions, and expected to be a development candidate by year’s end.
Based in Boulder, CO, Enveda also has operations in the Genome Valley of Hyderabad, India, staffed by a workforce that has grown to about 250 people.
“We probably would expect to grow by about 10% or so as we take molecules into the clinic and build out early clinical development teams that are experts in individual disease areas, as well as the science and operations of clinical execution,” Colluru said.
Enveda announced the closing of its Series C on November 21, just five months after it completed $55 million in Series B2 funding. The company raised $51 million in Series B1 equity financing in April 2023, on top of a $68 million Series B in December 2022 and an oversubscribed $51 million Series A in June 2021.
Colluru said the Series C brings Enveda’s total capital funding to $360 million.
Venture capital firms Kinnevik and FPV led the Series C financing, with participation from new and existing investors that included Baillie Gifford, Premji Invest, Lingotto Innovation, Lux Capital, Dimension Capital, True Ventures, Cresset Partners, The Nature Conservancy, and Henry R. Kravis, the co-founder and co-executive chairman of KKR, the global investment firm founded in 1976.
“Potentially epoch-defining”
“We believe that Enveda is an outstanding and potentially epoch-defining company, at the intersection of biology and technology,” stated James Anderson, managing partner and CIO, Lingotto Innovation. “I’ve been fortunate enough to be a long-term investor in several truly great companies over the last decades, from Amazon to Tesla to Tencent. I hope to see Enveda follow an equivalent path in essential efforts to improve the healthcare system.”
Colluru is the youngest PhD graduate from UW Madison’s CMB Class of 2011. Eight years later, he was the first innovation scientist and product manager at Recursion, a leader in AI-powered drug discovery, before setting out to launch Enveda with his $55,000 in personal savings. The company’s name (pronounced en-VAY-da) combines the English word “enable” with the Sanskrit word “veda,” or knowledge.
“Enveda was started with a simple idea: How can we bring billions of years of evolutionary intelligence into the modern drug discovery laboratory in a way that is scientific, scalable, and deterministic?” Colluru recalled.
In addition to his desire to see his ideas come to life, Colluru said his company was launched after applying the regret minimization framework popularized by Amazon founder Jeff Bezos after he left his job at a Wall Street investment bank and moved to Seattle to launch the global online retail giant in 1994:
Years later, Bezos recalled: “I knew that when I was 80 I was not going to regret having tried this. I was not going to regret participating in this thing called the Internet that I thought was going to be a really big deal. I knew that if I failed I wouldn’t regret that. But I knew the one thing I might regret is not having ever tried. And I knew that would haunt me every day”.
Said Colluru: “I knew that if I didn’t do it, I would regret it my whole life.”