Raymond Dingledine, PhD is Emory professor of Pharmacology and co-founder of Emory’s screening facility. His research focuses on the pharmacology of glutamate receptors and the causes of epilepsy. Dingledine’s has received numerous awards such as the ASPET’s Robert R. Ruffolo Career Achievement Award in Pharmacology and election to the National Academy of Medicine. He has published over 200 research papers, served as editor of “Molecular Pharmacology,” and sat on the editorial board of “Molecular Interventions.” Ray is also co-founder of Emory start-up NeurOp. In this interview he shares some of his thoughts and experiences as co-founder of a company.
Raymond Dingledine, PhD
Tell me about your background/research interests. Were you always interested in research with commercial potential?
Raymond Dingledine, PhD is Emory professor of Pharmacology and co-founder of Emory’s screening facility. His research focuses on the pharmacology of glutamate receptors and the causes of epilepsy. Dingledine’s has received numerous awards such as the ASPET’s Robert R. Ruffolo Career Achievement Award in Pharmacology and election to the National Academy of Medicine. He has published over 200 research papers, served as editor of Molecular Pharmacology, and sat on the editorial board of Molecular Interventions. Ray is also co-founder of Emory start-up NeurOp. In this interview he shares some of his thoughts and experiences as co-founder of a company.
Tell me about your background/research interests. Were you always interested in research with commercial potential?
I became interested in the properties of glutamate receptors in the early 80’s. There were a number of amazing discoveries in the 80’s and 90’s that led to the gradual emergence of glutamate receptors as a major focus in neuroscience. One of the goals and recognitions early in this work was that NMDA receptor antagonists should be useful eventually as anti-ischemic compounds for cerebral ischemia, like stroke. The problem was that NMDA receptors play so many roles in the brain in daily activity that blocking them is simply not tolerated.
The field of pharmacology inherently has a therapeutic goal, so yes, I’ve always been interested in contributing to the long history of solving medical problems with new drugs. Stroke is a huge problem that has no solution right now other than try to dissolve the clot quickly. Steve Traynelis, another faculty member in Pharmacology, and I had been studying the molecular properties of NMDA receptors for quite a while. We discovered that there are some compounds that exert a pH-dependent block of NMDA receptors in such a way that the drugs are more potent at acidic pH. The idea is that you should be able to give a dose of an NMDA receptor blocker that does not affect NMDA receptors in healthy tissue. As soon as a stroke appears, oxygen is shut off to that part of the brain and you begin releasing lactate and other acidic metabolites, so there’s a local drop in pH. The idea is that our compounds would selectively target the penumbra of strokes that feature a low pH and that would solve the last problem in the long path of developing NMDA antagonists for clinical use.
Tell me a little about NeurOp. What do you market?
We don’t currently market anything. We formed the company in 2002 or 2003 to develop a first-in-class NMDA receptor antagonist. We now have developed a NMDA receptor antagonist internally that has just finished going through Phase I clinical trials with no unexpected toxicities, so we are at the point now of developing a Phase II trial.
When you formed NeurOp did you have the antagonist you wanted or was it something you had to produce?
Human Brain
When we formed NeurOp, we had nothing to license – what we had was a novel idea. The rationale for forming NeurOp, in hindsight, was basically a personal development. For about three years before NeurOp, I had considered several jobs at large pharma companies to essentially oversee the development of many NeurOp-like projects. I talked these opportunities over with a friend of mine named Sol Snyder from Johns Hopkins. He gave me pretty good advice, which was to keep my day job and accomplish my need to give back to society by forming one or more small purpose-built companies. So that’s what we did. Steve Traynelis, Jim McNamara (Duke) and I started NeurOp after that and I decided to stay at Emory in my academic roles.
What was your initial role in NeurOp? What is your role now?
Originally, I was a founder and member of the board of directors. I have the same role there today as a member of the board of directors. The difference is today, NeurOp is led by highly experienced former pharmaceutical executives and business-types. So, although in the early days I and the other founders had more of a decision-making role, now it’s a more traditional board of directors. I give advice to the CEO and he takes it or leaves it.
Steve Traynelis and I had a necessity to maintain a bit of an arm’s length with the goings on at NeurOp for conflict of interest reasons, so we were not involved directly in designing all of the pre-clinical studies. NeurOp was a fully functioning company with medicinal chemists, neuroscientists, clinical trialists, and clinicians. My role initially was as one of the decision makers, but now I’m more of an advisor to this company.
Was NeurOp your first venture into the world of startups? What expertise did you bring to the formation of this company?
NeurOp was my first startup. My business expertise at the time was limited to having served on advisory boards for companies like Merck, Lilly, Bristol Meyers, smaller companies. I’ve learned a lot along the way. At the beginning, we were such a small endeavor that everybody had to do everything, so there was no real distinction between the scientific and the business decisions. Today the business expertise is held by our leadership and other people on the board and my main contribution is on the scientific side.
How did you go about putting together the executive team of NeurOp? In what capacities had you worked with your current collaborators in the past?
The other two founders, Steve Traynelis and Jim McNamara from Duke, have been longtime scientific collaborators. I had worked with Jim since the late 70’s and Steve since the mid 80’s. We respect and complement one another’s expertise. Jim is a neurologist and Steve is a world class molecular pharmacologist. Dennis Liotta and Jim Snyder from Emory’s Chemistry department played major roles especially in the beginning in compound design.
We recruited a startup CEO, Vince La Terza who had previously been director of Emory’s OTT, so he knew his way around the local and southeast startup business communities. Then we got busy trying to raise money. It was extremely challenging. In the early days, we had nothing to license. We had an idea, we had some commercially available compounds, and a few that hadn’t been well characterized yet that were proprietary. We must have given 100 dog and pony shows to potential investors, both pharmaceutical company partners or venture capital angels.
We basically got two messages. One was “We like you boys, but you’re too early. Come back when you’ve been in man.” The second response was, “NMDA, oh my god.” The idea of the second one was that the pharmaceutical industry had already by that time spent more than a billion dollars in failed clinical trials for NMDA receptor antagonists and the general thought was that we shouldn’t be wasting our time on something that wouldn’t work. Most people were not really interested in the novel strategy of incorporating pH dependence to develop a conditional blocker, so it was very challenging.
We are right now trying to figure out what the best indication would be for a Phase II trial and we’re considering different stroke mechanisms or indications as well as pain and a couple of other ideas.
Has OTT been involved in the formation and success of your start up? If so, how?
In the early days, OTT was pretty passive, and I would say probably did not contribute very much. When Todd Sherer came along, the whole game shifted, and they are now the best they’ve ever been during my time at Emory. As NeurOp gained the ability to generate compounds on its own through its own medicinal chemists, the patents began shifting from Emory to NeurOp so for this effort, OTT didn’t contribute very much. Having said that, they were critical in licensing the compounds and they also helped us with the Georgia Research Alliance. GRA played a major role early on, eventually investing $450k.
What advice would you give a researcher interested in forming their own startup, based on the experience you’ve had with NeurOp?
We founded NeurOp too early when we basically only had an idea. We should have developed compounds internally at Emory and been closer to the point of having a clinical candidate before launching a company. I was influenced by my own need to get something going at the time and I should have held back on that. My advice would be to think carefully on the timing of the launch of a new company.
Three months ago, I cofounded a second company called Pyrefin to advance novel anti-inflammatory compounds through clinical trials. Our potential clinical indications are cognitive decline in epilepsy, endometriosis, arthritis, and potentially gliomas, all of which have been strongly benefitted by our compounds. The thing is, our science underpinning Pyrefin is about ten years ahead of where we were when we had founded NeurOp. Unless we run into unexpected toxicities or other problems during development, we’re done with basic discovery for the moment and we’ve selected clinical candidates and their backups.
Another piece of advice is something that was positive from both NeurOp and Pyrefin. Make sure that you are compatible with your cofounders. There will be inevitable questions about which direction to take, but if you respect one another and have an actual friendship, those conversations are so much easier to handle.