Despite all the advances in drug research and development, the human proteome remains largely untapped – of the estimated 20,000 proteins, only about 600 are currently targeted by FDA-approved drugs. That leaves a lot of opportunity on the table for Vividion Therapeutics Inc., a San Diego-based firm launching Thursday with a $50 million series A investment co-led by Arch Venture Partners and Versant Ventures.
Funds from the round, which also included participation by founding investor Cardinal Partners, will be used to advance Vividion's proteome-wide ligand and target discovery platform, described by Executive Chairman Tom Daniel as a "robust platform that can really change how chemical drugs are first identified and then developed."
Most of the drugs on the market today are designed to target proteins; however, only a fraction of those protein targets are considered by existing methodologies to be truly druggable – i.e. capable of binding a small molecule or antibody.
"The industry is pretty inefficient still, and a lot of space in the proteome is undruggable," Daniel said. The impetus that lead to the founding of Vividion in 2014 began with scientist Ben Cravatt, chair of the Department of Chemical Physiology at The Scripps Research Institute (TSRI), whose work focused "on the really fundamental problem in drug discovery," that is, getting beyond the conventional target-centric approach that typically nets a limited number of hits and leads.
Work by Cravatt and his team at TSRI, published last year in Nature, demonstrated a method of widening that net by developing a way to find ligands – the binding partners – for proteins previously believed to be undruggable. Using a fragment-based ligand discovery approach, researchers attached those fragments to molecules that bind covalently to the amino acid cysteine. What they found was that the human proteome contains many "ligandable" cysteines, including in proteins not shown previously to interact with small molecules.
Cravatt's work looked at "what targets could be engaged by ligands, and [asked], 'Could you in fact map those interactions and, in so doing, find ways to extend the druggability profile?" Daniel said. The team continued working on that target identification approach, "coupling it with truly innovation chemistry" from TSRI scientists Phil Baran and Jin-Quan Yu.
"The other really great power of the technology is the application of novel chemistry to expand the chemical matter in a much more focused way than had been possible in the past," Daniel told BioWorld Today. "So I think we will have very rich and efficient small libraries that can do exceptional things.
"We intend to illustrate that you can do things with this that you can't do with traditional approaches," he added. "There's a lot of enthusiasm."
It also helps that Cravatt has a solid reputation for moving research from academia into startups. The TSRI scientists previously helped to found proteome company Activx Biosciences Inc. and, more recently, Cardinal-backed Abide Therapeutics Inc. (See BioWorld Today, July 11, 2001, and May 5, 2013.)
In fact, it was in part the connection to Abide that helped bring Daniel aboard. Before stepping down last year, Daniel spent a decade as president of global research and early development at Summit, N.J.-based Celgene Corp., which inked a deal for Abide's serine hydrolase-targeting technology in 2014. (See BioWorld Today, March 3, 2014.)
Joining Daniel on the board are Arch's Kristina Burow, Versant's Tom Woiwode and Paul Schimmel, professor at TSRI and biopharma veteran who has founded or co-founded several companies to date and has served on the boards of both Abide and Activx.
The number of employees at Vividion – the name comes from "vivid ion," referencing the ion mobility mass spectrometry used in Cravatt's work – is "expanding as we speak," Daniel said.
The company is not yet disclosing any of its potential targets, but it has sights set on developing internal programs. It also will engage in partnering talks, including early stage opportunities that can offer the dual advantage of bolstering investment and validating the platform technology.
Daniel said the firm will look for "which proteins have the greatest opportunity for therapeutic value" and then will "try to set land speed records moving from ligands to leads to candidates." The $50 million series A will help expand the platform and deliver clinical value, he added, though he declined to say how long the funds might sustain operations.
"We raised the capital to illustrate that this could fundamentally change how small molecules are discovered," he said. "It's now on our shoulders to make that potential a reality, but we are very, very optimistic that this can be not just an incremental contribution but a really substantial change in the way folks think about making chemical drugs."