March 2011

Dr. Stephen Strittmatter

The CURE/Yale BioHaven Entrepreneurship Series finished the current season March 2 with a presentation by Axerion Therapeutics. Speaking were Sylvia McBrinn, president and CEO, and Dr. Stephen Strittmatter, the Vincent Coates Professor of Neurobiology at Yale University School of Medicine.

Axerion was established in New Haven to develop and commercialize intellectual property licensed from Dr. Strittmatter’s laboratory.

The company is focused on developing innovative therapeutics for neurological diseases and injuries with significant unmet medical need, including Alzheimer’s disease and spinal cord injury.

Axerion’s Prion Protein (PrP) project is a novel potential therapeutic approach for patients suffering from Alzheimer’s disease. Axerion is developing small molecule oral compounds to block the binding of ß-amyloid (Aß) oligomers (clumps of Aß peptides) to PrP in the brain, thereby preventing a cascade of events that result in brain dysfunction. Axerion’s technology, if successful, could help slow or halt cognitive decline in Alzheimer’s patients.

With its Nogo Receptor platform, Axerion is developing treatments that have the potential to stimulate regrowth in axons, which are long cellular fibers that electrically connect one nerve cell to another and play a vital role in supporting neurological function. These potential treatments could help to restore function in patients who are suffering from spinal cord injuries, stroke and other central nervous system disorders.

Decoy receptor blocks three ligands

"We've done studies in mice using an antibody that we know is directed against a particular region of prion protein that binds Aß," Dr. Strittmatter said. "When memory-deficit mice are treated with this antibody, the deficit is converted to normal. The antibody in these tests was administered peripherally at high dose, and presumably the material got into the brain, corrected this memory deficit, and actually restored the synaptic markers of neuronal morphology. So in this overall scheme, cellular prion protein is this key first step where Aß oligomers bind to neurons and then trigger this downstream cascade."

"Our second project relates to spinal cord injury," Dr. Strittmatter continued. "Myelin inhibits axons from growing, and it does so through a pathway that involves Nogo and Nogo receptors. There are several ways to block this pathway. What Axerion's developing is a decoy receptor. It binds up all three ligands and blocks the whole pathway. When the spinal cord is cut in control mice, they remained essentially paralyzed for weeks, whereas in Nogo receptor knockout mice, about half the animals initially paralyzed recover walking. We've also studied chronic spinal chord injury in rats. Of the treated animals, a third of them became strong enough to walk during the follow-up period."

Sylvia McBrinn

"We've recruited a team, we've pulled together a board, and, in the words of one venture capitalist, we have 'wicked cool science'," said Sylvia McBrinn. "We got seed funding from Connecticut Innovations and we're in the process of raising series A funding.

"Where is the exit? Well, for Alzheimer's there's a strong interest at the big pharma companies. It’s a disease for which there’s no solution today, just like spinal cord injury, but pharma companies are looking at multiple targets to attack this disease. What’s interesting about our program is that it’s a novel target, and it is additive to other targets that are out there.

"With the Nogo program, even though there is competition out there — Novartis has a Nogo antibody against one ligand, and there’s a program that GSK has — we have the best profile that has likely the best efficacy, and has demonstrated efficacy in chronic spinal cord injury, where these other programs really have not been able to show efficacy, or have not been able to show efficacy in animal lives.  So we’ve got a really good profile in which to invest."

John Puziss of Yale OCR

The speakers were introduced by John Puziss of the Yale Office of Cooperative Research.

The BioHaven series is presented by CURE and the Yale Office of Cooperative Research, with Wiggin and Dana and PricewaterhouseCoopers as lead sponsors. The series is also sponsored by Elm Street Ventures and the Economic Development Corporation of New Haven, with additional support from the Yale Entrepreneurial Institute and the Yale Healthcare & Life Sciences Club.

The company website is at http://www.axeriontherapeutics.com