Enveda’s primary R&D efforts will focus on inflammation, fibrosis and neurosensory biology within the GI, dermatology and pulmonary therapeutic areas.
Enveda leadership team at a recent offsite in Salt Lake City, UT/company courtesy.
Since its launch in 2019, Enveda Biosciences has raised $124 million to advance its pipeline of nature-based small molecules targeting difficult therapeutic problems, most recently closing a Series B round in the midst of a stingy financing environment.
In an interview with BioSpace, Viswa Colluru, Ph.D., CEO, attributed this success in part to a rejuvenation in the natural chemistry and plant-based medicine space.
Other recent entrants to this field include Flagship Pioneering-backed Montai Health and London-based Pangea Botanica. Founded at the beginning of this rejuvenation, Enveda leverages cutting-edge ML models to identify drug leads from unexplored natural chemistry.
Before founding Enveda, Colluru led multiple drug development and platform projects at Recursion Pharmaceuticals, a Salt Lake City-based biotech engineering drug discovery through digital biology.
Colluru also said the investment “speaks to the promise of the continued delivery of assets by our platform, and our ability to bring those assets forward quickly into preclinical validation.”
Earth’s Most Powerful Library
Colorado-based Enveda is mining “the earth’s most powerful library” for nature-based compounds with the potential to overcome key challenges inherent to small molecules.
“The power comes from the diversity and the diversity leads to rapid new discoveries,” Colluru said.
While it’s long been known that the natural world represents a host of intriguing therapeutic opportunities, “the challenge has been to find, specifically, the natural product families or product scaffolds…that are amenable to the drug discovery process.”
In other words, molecules that can be turned into medicines through the optimization of medicinal chemistry.
Colluru believes Enveda has found the answer in a platform that combines metabolomics and machine learning to predict unknown chemistry at unprecedented accuracy. This is combined with a proprietary knowledge graph that organizes human medicinal plant usage data ranging from the ancient to the cutting-edge to hone the search further.
First, the company sets up a high throughput screen of its “highly diverse” plant metabolite library, deconvolutes active compounds from its sources, and then applies its machine learning-enabled algorithm that reads and translates nature’s chemistry to prioritize those compound families that are lead-like.
Enveda’s drug discovery efforts fall into two categories: one, modulating a complex phenotype or disease manifestation where a novel mechanism might be discovered; and two, attacking targets for which there are limited or no chemical substrates.
“These targets are either undruggable, labeled undruggable or quite nearly undruggable because everybody else’s drug library looks largely the same,” Colluru said.
Three Candidates to IND in 2023
Enveda disclosed that its primary R&D efforts will focus on inflammation, fibrosis and neurosensory biology within the GI, dermatology and pulmonary therapeutic areas.
Whereas Enveda’s original strategy was to go after complex biology wherever it may be found, Colluru said the current market prompted a shift to these three areas, which fit well within the scope of the company’s platform.
“In the context of fewer and fewer earlier deals in a tighter and tighter fundraising market, it becomes much more imperative that we’re a serious drug company ourselves faster.”
These three areas fit the platform because “a lot of the historical use of plants is related to management of chronic diseases and symptoms of chronic diseases,” Colluru said.
In 2022, Enveda predicted and experimentally validated 100 new active molecules from its metabolite library over the span of four months as it scaled its platform. Of those, it selected several to add to its initial pipeline.
Of the three most advanced programs in Enveda’s pipeline, the first is a modulator of neutrophil biology.
“Neutrophils have always been appreciated as important, but there hasn’t been too much progress in being able to leverage them to modify or alleviate chronic inflammation and downstream consequences like fibrosis,” Colluru said.
Idiopathic pulmonary fibrosis (IPF) is the lead indication for this molecule, though Colluru said it could potentially activate a whole range of neutrophilia.
He added that the inhibitor has cleared a tough preclinical bar in IPF with flying colors.
The second program is based around an ion-channel inhibitor that has the potential to be administered both orally and topically, for itch and pain.
“It’s a huge area of unmet need, especially a non-opioid, nonaddictive candidate,” Colluru said, adding that Enveda is exploring multiple clinical and commercial opportunities to quickly prove its effects in chronic and acute pain.
Lastly, Enveda discovered a chemotype that inhibits the NLRP3 inflammasome pathway with a differentiated mechanism.
“Instead of directly binding the inflammasome, we bind another protein that regulates the stability of the inflammasome,” Colluru said.
He believes this chemotype could deliver two, possibly three candidates into the pipeline. The most advanced of these is a gut-restricted molecule for inflammatory bowel disease, colorectal cancer or fibrosis stemming from IBD.
Enveda anticipates submitting an Investigational New Drug application for the first of three assets as early as the end of 2023, with others shortly thereafter.
From left: Hannah Gordon, vice president of platform and August Allen, chief platform officer, at Enveda’s Boulder, Colorado laboratories.
Portfolio Intentions
Colluru was clear that Enveda is in this for the long haul with a north star of delivering drugs to the clinic.
“Our goal is to be a vertically integrated pharma company that predominantly spends its efforts building the technology to harvest assets for internal development,” he said.
As a biotech company taking a portfolio approach based on a technological thesis, Colluru said Enveda has a responsibility to finance sufficient shots on goal.
“I think companies like Enveda or Recursion…have some belief that they are going to beat the batting average in the clinic, either because of the chemical space they play in or the way they interrogate new biology.”
Even if Enveda was five times as successful as the industry average, there would still be a one-in-two chance its molecules would work in people, he said.
Thus, Enveda’s goal is to leverage its current pace of discovery and optimization with a “highly capital-efficient and lean discovery machine.”
Despite the company’s portfolio intentions, partnering is very much on the table.
A hot focus in biotech today is the potential for mechanisms that can either disrupt or create protein-protein interactions.
At the J.P. Morgan Healthcare Conference in January, Enveda unveiled a novel platform that allows it to study how a mixture of compounds can modulate potentially billions of protein-protein interactions in a single experiment.
With this platform maturity, Colluru said Enveda is ready for a partnership. Accordingly, the company recently tapped Vanitha Sekar, Ph.D. as its first chief business officer.
With such ambitious short- and long-term plans, Colluru highlighted one more way the current economic situation could benefit Enveda.
“I think it’s a great time to be in a position of strength and be building because the best possible talent has never been more for the taking.”
