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NCATS’ Small Business Funding Helps Launch New Platform for Rare Diseases Drug Discovery

In early 2013, Christopher Gibson, an M.D./Ph.D. student at the University of Utah, was exploring potential treatments for cerebral cavernous malformation (CCM), a rare disorder in which misshapen, weakened vessels leak blood into the brain and cause strokes. He had hoped his Ph.D. research would complement his planned future work as a cardiothoracic surgeon treating patients with related conditions. Science intervened: While developing an approach to screen existing drugs for their potential to treat CCM, Gibson saw a way to expand that method into an enterprise to discover hundreds of treatments for thousands of diseases. Deferring his goal of becoming a physician, and with support from NCATS’ Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs, Gibson founded a rapidly growing drug discovery company that has, in its first year, attracted more than $3.5 million in private investments.

The SBIR and STTR programs are among the tools in NCATS’ arsenal to catalyze innovation in translational science. Often, academic scientists like Gibson make important discoveries in the laboratory but lack the resources and know-how to carry those ideas into the realm of commercialization, where new interventions can be developed and delivered to patients. The NCATS SBIR and STTR programs bridge this translational gap by providing grants, contracts and technical assistance to small businesses and research organizations focused on advancing translational research and technologies that will improve disease prevention, detection and treatment.

An Idea Is Born

Gibson’s idea was born the day a computer beat biologists at their own game. He and his colleagues were screening for potential CCM drugs using human endothelial cells, which make up the inner walls of blood vessels. The researchers genetically engineered the cells to display CCM-like defects, which included abnormal levels of proteins that normally keep vessels intact. After screening more than 2,000 drugs, the team had a pair of highly trained cell biologists compete against an automated computer program — developed by scientists at the Broad Institute — to select the drugs that most effectively reversed the CCM cells’ defects.

: Front row (left to right): Britt McPartland, Gaelle Mercenne, Han Han, Mason Victors and JD White. Back row: (left to right) Ian Quigley, Ashwin Purohit, Tim Considine, Chadwick Davis (slightly down in the line), Chris Gibson and Blake Borgeson

Recursion Pharmaceuticals co-founder and CEO Chris Gibson, Ph.D. (back row, second from right), and his team have developed more than 200 rare disease models on which to test potential drug therapies. (Recursion Pharmaceuticals Photo).

Using microscopic imaging to visualize changes in these cells, the biologists and the computer each selected 39 drugs that appeared to normalize the cells. Remarkably, there was no overlap between the biologists’ and computer’s sets of chosen compounds. To confirm the findings, the researchers screened both sets in another batch of CCM cells, this time measuring the agents’ abilities to normalize dysfunctional cell behavior. One compound from the biologists’ set reversed the defect; to the scientists’ surprise, seven of the computer’s compounds did so.

“That moment convinced me that the computer was seeing what humans can’t. I realized that our high-throughput screening approach, coupled with automated computer analysis, could enable us to much more quickly and efficiently discover potential treatments, not just for CCM but for any number of other rare genetic diseases,” Gibson said. “And screening with existing drugs — repurposing — means that potential therapies can reach patients much sooner than starting from scratch.”

Seeing an opportunity to expand and commercialize this platform, in summer 2013, Gibson enrolled in Stanford Ignite, an entrepreneurship training program through the Stanford University Graduate School of Business. He worked with classmates to further develop his idea, ultimately pitching it to a panel of investors and industry experts.

During the program, Gibson realized that he could take his platform much further than he had first envisioned. “Our initial idea was to start a company and repeat our CCM approach for several other diseases,” Gibson explained. “But the brainstorming at the Stanford Ignite program made us think bigger. We realized, ‘Why focus on one disease at a time? Why not use automation and robotics to carry out high-throughput drug repurposing screens for lots of rare diseases in parallel?’”

From the Ground Up

In November 2013, Gibson and his partners founded Recursion Pharmaceuticals. Gibson received his Ph.D. the following month, and in spring 2014, he applied for NCATS SBIR Phase 2 funding, a $1 million award granted to applicants who already have established the technical merit and feasibility of a project.

Although he wouldn’t find out until many months later that he had received the award, Gibson did know early on that his application had received a very high score. That score — and, later, the SBIR award — helped Recursion attract an additional $3.5 million in private investments.

“The investors specifically said that our SBIR score was instrumental in validating the scientific feasibility of our endeavor,” Gibson said. The SBIR award also garnered attention from major pharmaceutical companies, and negotiations are underway with several large firms. “The SBIR award helped legitimize our project in the eyes of both investors and the pharmaceutical industry and thus was instrumental in getting the company off the ground.”

The SBIR award and private investments quickly enabled Recursion to establish a core group of employees and a few initial rare disease models. The company has continued to grow rapidly.

“Recursion represents a truly pioneering approach, and I’m excited to watch how the company’s stellar team fosters its innovative platform to advance medical science and, hopefully, promising therapies for patients,” said Craig Wegner, Ph.D., head of the Boston Emerging Innovations Unit, Scientific Partnering & Alliances, within AstraZeneca’s Innovative Medicines and Early Development Biotech Unit.

Looking into the Future

Today Recursion has 10 full-time employees and is actively recruiting for at least six more full-time positions. In addition to CCM, the team has developed more than 200 rare disease models on which to test potential therapies and is currently working to validate 12 promising repurposed drug candidates for several rare diseases.

Han Han, Ph.D., reviews his notes.

Han Han, Ph.D., reviews his lab notebook before initiation of a high-throughput experiment. (Recursion Pharmaceuticals Photo/Heather Nan)

“The large number of currently untreatable rare diseases and the fact that each one can affect multiple organs make the traditional ‘one disease at a time/one organ at a time’ translational model untenable,” said NCATS Director Christopher P. Austin, M.D. “Recursion’s approach to transforming drug discovery for rare diseases is a great potential way to tackle this problem.”

But Gibson and Recursion are just getting started. “Our goal over the next 10 years is to help bring 100 or more new treatments to patients by generating lead therapeutic candidates through the Recursion platform,” Gibson said.

Although the team began with rare diseases, the platform can be adapted to study any number of common diseases and conditions. Already, the Recursion scientists have begun pilot studies to use their system to screen for potential therapies for viral infections, aging, inflammation and cancer.

“The platform can be used to test the effects of thousands of drugs on any biological process of interest,” Gibson said. “It not only can help us discover new therapies but also learn more about basic biology as a whole. Any scientist with a good idea should consider the SBIR/STTR program. It has been transformational for us.”

 

Posted March 2016

Last updated: 08-04-2016
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