Viswa Colluru, PhD, founder and CEO of Enveda Biosciences talks to Lu Rahman about the company’s chemical search engine and its work harnessing the complexity of the natural world to tackle today’s biggest healthcare challenges.
LR: Describe what Enveda does and some of its current work / initiatives.
VC: Enveda is building the first high-resolution chemical map of the natural world to inspire new medicines for the toughest diseases. By harnessing advancements in machine learning and metabolomics, our platform works like a chemical ‘search engine’, predicting exciting new drug-like chemicals with increased potential for clinical success.
We recently raised our seed round of $4.9 million from leading investors. We are working on growing our metabolomics dataset, building the next iteration of our platform, and advancing our portfolio through preclinical development. We are simultaneously building out a clinical development team around a focused therapeutic area to advance new drugs to the clinic. We are also in conversation with partners that want to leverage our access to unique chemistry to solve difficult biological problems such as undruggable targets or RNA biology.
LR: Why is the company focused on natural product drug discovery in particular?
VC: Our chemical search engine can be used to efficiently tackle any chemical space. However, we’ve chosen to initially focus on the plant world for a number of compelling reasons. First, natural products are unique in that they are both validated and untapped. They were, in fact, the first source of pharmaceuticals, yielding drugs that helped treat billions of patients, like Artemisinin (Nobel Prize winning discovery for the treatment of malaria), aspirin (needs no introduction!), morphine, metformin (used by hundreds of millions of diabetics), statins (revolutionised cardiovascular disease treatment), penicillin, and cannabidiol (recently approved by FDA for treatment of rare forms of epilepsy), were all discovered from nature. In fact, 33 per cent of the small molecule drugs (and 20 per cent of all drugs) approved between 1981 and 2020 were inspired by nature. Yet, it is estimated that the natural world largely remains a mystery. On average, we are able to attach a chemical formula to only 5% of the chemicals in a given plant sample using conventional analytical methods. However, the industry pivoted to using synthetic libraries during the molecular biology revolution. Since this time, we have made significant advancements in areas like metabolomics and machine learning, making it possible to leverage the molecules found in the natural world for modern drug discovery.
Second, the molecules found in the natural world are incredible. Plants produce secondary metabolites that have evolved under intense evolutionary pressure over 450 million years to interact with conserved biological domains across microbes and herbivores, including mammals. Therefore, it is no surprise that natural products are predicted to cover more bioactive space than synthetic libraries.
Third, we believe that these molecules will translate very well into therapeutics. They have coevolved among humans for thousands of years, with the use of plants as medicine being a universal trait of cultures across the world.
LR: Explain how your platform works and the benefits it offers researchers – in what ways can it help provide molecular insight into the potential of drugs derived from nature?
VC: Our platform unlocks massive high-potential chemical space for drug discovery in the form of natural products. The process of identifying drugs from nature used to be slow, laborious, and failure-prone. For example, unknown molecules would have to be isolated and analysed for biological activity individually, a process which failed for the large majority of molecules that are present in low quantities. In contrast, our platform acts like a powerful search engine, cataloging every molecule in every sample, accurately predicting interesting chemicals contained therein, and what modifications might be promising to derive new therapeutics. We are already seeing incredible promise in traditionally challenging areas of biology, such as undruggable targets, and emerging therapeutic modalities that seek to act on non-protein targets.
LR: Are there any cost / resource savings its use can provide?
VC: Within the area of finding active molecules in natural samples, our platform is a 100X improvement. For example, researchers were trying to find the active antiviral molecule in Euphorbia dendroides for years, a medicinal plant historically used for the treatment of warts since ancient Rome. Our platform was able to identify the active molecule in just a few hours.
Within the broad area of drug discovery also, our systematised discovery and validation process can significantly cut the cost, accelerate the discovery timeline, and improve the likelihood of success of the drug candidates. Drug discovery is an incredibly inefficient process. Only one in 10 molecules discovered in the lab ultimately go on to successful human trials, even after years of preclinical research. Failure in clinical trials is driven by the inability to produce a desired therapeutic effect at a non-toxic dose. Plants that have a long history of use, however, are much more likely to contain successful drug candidates. When starting with a molecule derived from a medicinal plant, we are taking advantage of millennia of human experience. These molecules have been safely ingested at doses that cause biological activity, and our platform allows us to harness those clues. By starting with these molecules, we hope to weed out much of the trial failures that come from lack of efficacy and toxicity.
LR: We are hearing about increasing work being done in the field of metabolomics – how does this platform assist researchers looking at this area of expertise?
VC: Metabolomics is one of the fastest growing technologies today. It refers to the study of metabolites, or the chemicals produced by an organism during metabolism. Complementing advances like genomics (study of the underlying genetic code), transcriptomics (the transcribed RNA), and proteomics (the translated proteins), metabolomics provides the most accurate readout of an organism’s physiological state. Previously, a lot of focus was on “targeted” metabolomics, where methods were optimised to study a small number of metabolites that were previously nominated to be important (like cholesterol, for example). Recently, many new exciting signals are being obtained through “untargeted” metabolomics, where all molecules in a sample are analysed. Our platform is inspired by some pioneering work done in untargeted metabolomics by Dr. Pieter Dorrestein, our scientific co-founder and professor at UC San Diego. His work created the first cloud-based database for untargeted metabolomics data and several cutting-edge algorithms for their analysis.
LR: Where does the company see the natural products drug discovery market heading and where are the main challenges and opportunities ahead?
VC: We see enormous potential in natural product drug discovery. A small glimpse of this came in the form of the recent $7.2B acquisition of GW Pharma for their pipeline of CBD and CBD-derived rare disease molecules. Even though the use of cannabis to treat epilepsy dates back in history to 2,700 B.C.E and the first formal published study of the effectiveness of hemp extract for the treatment of seizures came in 1843, the active molecule came to be discovered as the non-psychoactive cannabidiol only by chance a few years ago. Formal clinical trials quickly established its efficacy, leading to their landmark FDA approval in 2018. But overall, the market is fairly immature. There are thousands of other plants with a similar rich history of human use but with unknown active molecules. At Enveda, we are at the forefront of this pursuit: we have assembled the largest anthropological dataset of medicinal plants to help guide our chemical search engine towards molecules that will have the same impact on medicine as aspirin, metformin, and statins.
However, there are certainly challenges. The largest being that natural products challenge the status quo of drug discovery. For example, despite a long history of successful use, effective drug candidates like CBD would have been missed with the traditional drug discovery process. Typical high-throughput drug discovery processes start from druggable protein targets, such as neurotransmitter receptors in the case of seizures, and find molecules that bind to and influence their activities. How exactly CBD reduces seizures remains unknown, but it doesn’t prevent CBD from being a highly effective medicine for drug-resistant epilepsy. In order to convince pharmaceutical companies that now is the right time to return to the natural world for inspiration in drug development, we will have to lead the way ourselves in generating critical proof points earlier on in the development lifecycle. With our technology platform, world-class team, and early results, we are well on our way there!
Viswa Colluru founded Enveda after leading cross-functional teams across innovation, product strategy, and translational biology as an early employee at Recursion Pharmaceuticals. He holds a Ph.D. in immuno-oncology from the University of Wisconsin-Madison, where he developed new therapeutic agents for the treatment of prostate cancer.