To name a company Visionary Pharmaceuticals Inc. and refer to the leadership team as "world changers" takes a certain degree of confidence. And so far, the small, 2010 San Diego-based startup appears to be living up to that promise, with its computational drug discovery platform already yielding programs in cancer and autoimmune disease, while drawing the attention of big pharma firms seeking faster and more efficient screening and optimization methods.

"Now is a really good time for us," acknowledged Gordon Alton, president and CEO of Visionary. "We have a huge number of companies that are very enthusiastic about what we do."

Based in San Diego, the firm is located in the Sorrento Valley biotech hub, in close proximity to Scripps Health, Sanford-Burnham, the Salk Institute and the University of California, San Diego (UCSD), relying on those nearby sources to keep the company's in-house operations as lean as possible. Initial funding came from the three founders: Alton, whose CV includes more than 20 years of structure-based drug discovery experience and stints at Pfizer Inc., Signal Pharmaceuticals Inc. and Celgene Corp.; Chief Scientific Officer Jim Zapf, who has spent 21 years developing small-molecule therapeutics; and Ayse Batova, currently on the faculty at UCSD's Department of Chemistry and boasting 22 years of research experience in the area of molecular cancer therapeutics.

Once the company was "off the ground, that allowed us to acquire some of our technology and initiate lab buildout," Alton explained. Visionary completed a small seed round – under $1 million – with the bulk of its funding to date coming from the NIH – more than $2.5 million so far "and, we think, with more pending."

Visionary's approach is based on the founders' work in structure-based drug design, with the aim of finding a method to speed discovery work from hit to lead optimization.

High-throughput screening has been the method du jour for big pharma, but is not the most conducive to innovation. Companies such as Pfizer "have very large libraries of screening compounds," Alton said. "Every small molecule has to go through high-throughput screens – lots of time and money," leading to compounds that scientists will invariably have to tweak. That's due in part to the fact that many compounds making up the massive libraries were either initially designed for past drug targets or were low on structure-activity relationship measures.

"Most of these are retrospective compounds, not prospective," Alton added.

Visionary's Bindingsights platform is different. For one, it's virtual, comprising a suite of computational tools incorporating open source and commercial software to handle the hit-to-lead process, followed by a structure-based and ligand-based drug design program for lead optimization.

But Alton said what sets Bindingsights apart from other virtual screening platforms is that it looks at "functional action," looking specifically for a "fingerprint of key interactions."

Bindingsights is designed to work with Manifold, a virtual chemical library with more than 250 million compounds described, including the 3-D coordinates for each of those compounds. Essentially, Visionary starts with a hypothesis, looks for functional interactional fingerprints and then "we dock our compounds into Manifold, really around this fingerprint of interaction," he said. "And now we get a set of molecules that appear in Manifold that we believe represent a viable chemical world," indexed for molecular properties. From there, it's a matter of deciding which have the appropriate drug properties, which have known routes of synthesis and "which do we want to work with," he said.

"We can whittle down from 200 million [compounds] in a matter of weeks."

FOCUS ON INNOVATION

Visionary used that method to search Manifold for compounds that have functional interactions with RAR-related orphan receptor gamma, or RORyt, a nuclear receptor that has been linked to both autoimmune disease and cancer. Lead compounds identified by the firm demonstrated impressive early results in animal models of inflammatory bowel disease (IBD).

Expressed in lymphocytes, RORyt is needed to drive the differentiation of IL-17A/F-producing Th17 cells. "It's probably one of the most significant industry targets at this point in time," Alton noted. "IL-17, IL-23 and Th17 cells are all controlled by ROR gamma transcription factor," and that translates into huge opportunities in autoimmune disease.

"Psoriasis is a huge indication right now, and many companies are moving into the clinic," he said.

The approvals of biologics such as Cosentyx (secukinumab, Novartis AG) and Taltz (ixekizumab, Eli Lilly and Co.) have shown success by targeting IL-17A, while studies with IL-23 blockers from Johnson & Johnson and Boehringer Ingelheim GmbH have so far performed well in psoriasis. Targeting RORyt could allow a single drug to hit both of those cytokines.

Most advanced in development, according to Cortellis Clinical Trials Intelligence, is VTP-43742, an RORyt inhibitor from Vitae Pharmaceuticals Inc. Vitae wowed investors earlier this year when it unveiled data from a phase IIa study and outlined plans to move the drug into a lengthier trial. (See BioWorld Today, March 18, 2016.)

Visionary is advancing an IBD program toward the clinic in partnership with the NIH, anticipating a clinical trial within the next year in either IBD or psoriasis, with IND activities underway now. "We're very excited about where we're going," Alton said.

Cancer studies are a possibility, too. Research has indicated that IL-17/A/F along with IL-23 and Th17 are linked to resistance to chemotherapy.

While the firm has fielded interest from pharma, no licensing discussions have really launched yet, but Alton said those will likely start happening next year.

"We really took the approach that we would get founder capital, and get in position to obtain NIH grants – as long as you have what looks like very novel compounds, there is NIH money available," he said. "There are pathways [through which] we could get an IND-enabling grant from the NIH and then grants to fund clinical trials. I believe we could push through at least phase I safety with grant money" in multiple programs.

Alton doesn't see finding a pharma partner as a huge challenge. "As we get close to filing an IND, we're finding a huge appetite from big pharma. Their portfolios and pipelines are really drying up. There's money out there, and companies are again starting to turn to small biotechs," he told BioWorld Today.

"If it's a good molecule, companies are willing to pay for that."

And that's fine with Visionary, which plans to focus on its discovery and early development work – the true innovation part of the equation. "We don't want to build a company and take it all the way on our own," Alton said.

Behind its RORyt program, Visionary is developing compounds targeting SGK1, a serine-threonine protein kinase found on lymphocytes and other cell types and believed to regulate IL-12 and Th17 cell stabilization. Inhibiting SGK1 can reduce Th17 cells at sites of inflammation, but the target also is expressed in a number of tumor types, particularly triple-negative breast cancer.

Currently staffed by five full-time employees, Visionary operates a small lab with core expertise. "At any one time in the week we have perhaps 20 contractors, including medicinal chemists," Alton said, noting that virtual firms and outsourcing have become the norm in biotech. "I think it's a model that everyone has had to go to."