Currently, 5.4 million Americans live with Alzheimer’s disease and another million live with Parkinson’s disease — terminal neurodegenerative diseases that steal memory and movement, respectively. There’s no cure for these diseases and only a few treatment options that temporarily reduce their debilitating symptoms for some — but not all — patients. Doctors diagnose up to 60,000 new cases of Parkinson’s each year, and an estimated 16 million Americans will have Alzheimer’s disease by 2050.
Gismo Therapeutics Inc., a biotech startup that moved to Lexington in June 2014, is working to develop new oral medication that could potentially curb these predictions by interrupting the early development of neurodegenerative diseases like Alzheimer’s and Parkinson’s. During the past two years, the company has received several prestigious grants to support its research and development program, which is based on a novel hypothesis of how these neurodegenerative diseases develop and spread in the brain.
Paul Gregor, founder and CEO of Gismo Inc., said that relocating the company to Lexington from New York was a “natural development” for several reasons. One was Kentucky’s SBIR Matching Funds Program from the Kentucky Cabinet for Economic Development. In 2014, Gismo received a highly competitive Small Business Innovation and Research (SBIR) grant from the National Institutes of Health (NIH), National Institute on Aging (NIA) and then successfully competed for Kentucky’s matching funds. The company also received funding from Bluegrass Business Development Partnership, comprising the University of Kentucky, Commerce Lexington and Lexington-Fayette Urban County Government, to establish the company’s laboratories at the Advanced Science & Technology Commercialization Center (ASTeCC) at the University of Kentucky.
“Small companies have limited numbers of people and resources, and this was a good way to double our money so we could focus on the science and research rather than have to start looking for investors right away,” said Gregor. Bruce O’Hara, Gismo Inc.’s director of research operations and professor of biology at the University of Kentucky, also appreciates the resources, expertise and sense of community that he and the Gismo Inc. leadership have found through the SBIR Connect events organized by the Kentucky Science and Engineering Foundation.
“We get together once a month, a small, intimate group of about 12 to 15 people sharing their experiences and learning from each other — everything from what happens when your research moves from Phase 1 to Phase 2 grants, to connecting with accountants who are experienced with SBIR grants,” he said.
Gismo Inc. isn’t the fi rst startup that O’Hara and Gregor have launched together. With a shared entrepreneurial spirit and interest in science and biotech, they’ve been collaborating for two decades, since their postdoctoral days at the NIH. O’Hara’s knowledge of Kentucky’s Matching Funds Program and other local resources helped facilitate the company’s relocation.
“For small startups I found Lexington an even better place to be than Stanford,” he said. The University of Kentucky, and specifi cally the established cadre of researchers at the Sanders Brown Center on Aging (SBCoA), also drew Gismo Inc. to Lexington. Notably, SBCoA is one of the original 10 Alzheimer’s Disease Centers funded by the National Institute on Aging.
“UK is an excellent university with many top-notch scientists and has a very good Alzheimer’s research center at Sanders Brown, and we liked the idea that we would be close to that science and could establish collaborations,” said Gregor.
Gismo Inc. has already established an active collaboration with Dr. Michael (Paul) Murphy’s lab at SBCoA to test the company’s compounds in multiple cellular models of Alzheimer’s disease.
“The matching funds were critical in moving us here, but other things are important too, like these collaborations,” said Gregor. “The matching funds have certain rules — they like us to spend some of the money in Kentucky, and if there were no science here, what could we do here? But there’s such good Alzheimer’s disease research at UK that it was natural for us to come here.”
Which is not to underestimate the breakthrough science that Gismo Inc. brings to the state. The company’s research stems from a novel hypothesis about the root cause of Alzheimer’s and Parkinson’s, with the hope of developing a platform technology that can be used to create drugs for other neurodegenerative disorders that have similar mechanisms of development, such as amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s Disease) and frontotemporal dementia (FTD).
“The old hypothesis is that the amyloid peptide is causing Alzheimer’s,” said Gregor. “There are leading scientists who are proponents of this ‘amyloid only’ hypothesis. But according to our hypothesis, amyloid is necessary but not suffi cient to cause Alzheimer’s.”
Based on their own and other published research, Gregor and his team believe that in order for Alzheimer’s disease to develop, the amyloid peptide must not only be present in the brain but must also interact and bind with a class of complex carbohydrates, glycosaminoglycans, or GAGs, on the surface of the cell membrane. The interaction of the GAG and amyloid peptide, which bind together tightly, causes Alzheimer’s to spread like a viral infection in the brain. Gismo Inc. is working to develop drugs that interrupt this interaction and therefore the development of disease.
“Amyloid diseases like Alzheimer’s and Parkinson’s have a similar general mechanism in that the GAGs are required in addition to amyloid,” explained Gregor. “But we have discovered compounds that can actually inhibit this interaction between the amyloid and GAGs. These compounds are called GISMOs — Glycosaminoglycan Interacting Small Molecules (GISMOs).”
The company recently filed its fi rst patent applications for GISMO compounds and in May 2014 parlayed its promising results into further grant funding from the Michael J. Fox Foundation. The grant was co-awarded to Patrik Brundin, M.D., Ph.D., the Jay Van Andel Endowed Chair in Parkinson’s Research and director of the Center for Neurodegenerative Science at Van Andel Research Institute (VARI) in Grand Rapids, Michigan.
“Dr. Brundin, a highly cited scientist in Parkinson’s research, immediately understood the signifi cance of our approach and appreciated the availability of the GISMO compounds. Under the collaboration, his laboratory will test our GISMO compounds in cellular and animal models for Parkinson’s disease. I think this active collaboration has the promise of generating a new therapeutic for Parkinson’s,” Gregor said.
Gismo Inc. will submit a Phase 2 SBIR grant application by spring of 2015. They plan to complete animal trials in Alzheimer’s and/or Parkinson’s disease by fourth quarter of 2015.
The company also offers an opportunity for investors, with multiple liquidity exits possible. According to Gismo Inc.’s market analysis sources, worldwide sales of drugs to treat Alzheimer’s disease were $4.3 billion in 2012, a market forecast to experience double-digit growth to 2020. Similarly, the global market value for Parkinson’s disease therapeutics is expected to increase from $3.6 billion in 2012 to $5.3 billion by 2022, according to GlobalData, a healthcare market analysis fi rm.
“Drug discovery and development is not particularly fast compared to some other industries,” said Gregor. “But obviously, once you develop something promising, the potential value of these projects is extremely high. Signifi cantly, many biotech-pharma deals are made before drug candidates enter clinical trials, and companies with platform technologies may command higher valuations.”