Explore the innovative world of Gain Therapeutics in this engaging fireside chat held by Lou Basenese and Jeb Terry at the recent Public Ventures Discovery Day event.
Delve into how we are revolutionizing the treatment of neurodegenerative diseases, including Parkinson’s, with our next-generation Magellanᵀᴹ platform. Gain harnesses AI and physics-based methods to develop best-in-class small molecules for disorders with high unmet medical needs. Hear about the significant strides we’ve made from current Board Member and former Gain CEO Eric Richman. A must-watch for those interested in the intersection of biotechnology, AI, and healthcare advancements.
For a detailed transcript of the event, please refer to the text provided below:
0:00 – 1:09 Introduction and Event Overview
All right, let me tell everyone what’s ahead. I’m going to get the gong. Do we have a gong? Do we have the bell? Does anyone remember the Gong Show? Am I dating myself? Yeah, probably. Listen, we thank you all again for your attention. I love hearing about the engagement. That bodes well for the breakout sessions, which will allow for some Q&A as well.
I want to give you an overview of what to expect this afternoon. We’re going to have a fireside chat format that adheres to the principle: be brief, be sincere, and be seated. I’m going to ask that the executives speak English as well, so we can understand. We’re talking about some science-intensive topics. They can get into the weeds, but they know how to explain these to us laymen in understandable terms. This is important for us to grasp the big picture of these opportunities. Again, this is about Discovery Day, sometimes discovering for the first time, really rediscovering certain companies, and you have to do that from a place of understanding first before we can dig deeper. This is not meant to be exhaustive but to introduce you to new opportunities so you can begin that process.
1:09 – 2:10 Introduction to Gain Therapeutics and AI in Medicine
I’m fortunate to have here a man who will not reveal to you his secret for staying young because he’s actually 85 and looks like he’s 55. He’s working as a director for some secret company that he’s not sharing with us yet. But it is the fountain of youth. Good to see you, my friend Eric. A quick intro here before we jump into the conversation about Gain Therapeutics, which I believe you were the original CEO and then transitioned to the board. That’s right. This is another AI legitimate play. I just read a headline today from Singularity Hub about a company that has now developed the first AI-based drug that has just gotten through phase two clinical trials. Gain is doing something very similar.
I’m not going to get deep into the science here, because we could confuse ourselves really quickly. If I look at the tagline, I think we have some marketing people in here too. So, ‘Unfolding the next generation of allosteric small molecule treatments for neurodegenerative diseases.’ I don’t know what that means, but I’m going to give you an analogy, and you can validate it or not.
2:10 – 4:36 Scientific Analogy and Drug Development Process
My understanding of GAIN’s platform, which is revolutionary, is that they use AI and machine learning to identify drug compounds that would work for rare diseases usually resulting from protein misfolding.
Yes, and then, because that protein is misfolded, downstream from that protein, it causes a lot of negative things to happen. So, my analogy, which is going to be overly simplified, which I want you to correct me if I’m completely wrong, is like when I used to have a yard and I had my hose out there, and it would get kinked and therefore the water wouldn’t flow anymore. It messed me up. I couldn’t do what I needed to do. What you’re doing is essentially developing drugs that unkink that biological kink and allow the body to function as it should.
That’s a great analogy. The kink can be caused by your dog, your car running over the hose, kids, or a variety of things, and this is a very important understanding because proteins govern so many things in your body, and they’re typically the root cause of disease. How do these proteins get messed up? It can be genetic, your genes, it could be inflammation, it could be ageing, so many different things. What we do is focus on that one pathway between damaged protein and disease.
We’re focused on that area, and we try to figure out how we can make that protein work correctly or unkink the hose. Are you developing novel drugs to do the unfolding of the proteins, or are there known compounds? How are you going about that? So, biotech and medicine is an evolution, right? The way these diseases caused by aberrant proteins have been addressed is by giving exogenous proteins.
So I’m sure everybody’s heard of the company Genzyme. This is what they did for rare diseases. You have this rare disease because your protein’s not working, and you get the patient a vial of that protein or enzyme, and because they don’t have a normal protein, you give it to them from that vial, and the disease can be addressed. Now, the next evolution of that is to do that same fixing with small molecules, and that’s where Gain fits in, being able to address that protein.
4:36 – 9:48 Focus on Parkinson’s Disease
Correct protein function by creating a small molecule that binds to that protein in an irreversible way that corrects the misfolding and the problems. So, I want to talk about what you’ve used this platform for. What’s the name of the platform again? It’s called Magellan. Magellan, that’s right. I think that was newly implemented. See, that’s why I didn’t know about it. I want to talk about your lead clinical asset now for addressing Parkinson’s. How many people here are familiar with anyone with Parkinson’s? Yeah, almost everyone in the room. And from my research, there are a lot of candidates looking to at least slow the progression of Parkinson’s.
What your lead asset, Gain’s lead asset, has done is the potential to reverse Parkinson’s. So, why don’t you share with us why targeting Parkinson’s first, what you saw in the early years, the animal models, and now you’ve just moved into the clinic? Right, so just a little bit about my background. I’ve spent most of my career developing drugs for diseases that had no cures. These are orphan drugs, they call them, for rare diseases. An example is RSV. You can hear about this today on the TV, about RSV vaccines.
I developed the first RSV drug back in 1989. It was the first time that a drug for RSV was licensed, and it was a hyperimmune globulin. So it became a fraction of blood. Now it’s a vaccine. So, things change over time. But I’ve spent most of my career developing drugs for diseases you’ve never heard of. Nobody heard of RSV at that time. And I developed the first drug for hereditary angioedema. Now there are seven drugs on the market. This is the first disease that people have ever heard of that I’ve worked on. So I don’t have to spend a lot of time explaining what Parkinson’s disease is.
But in general, it’s a neurodegenerative disease, and it’s progressive. When I first started working with Gain, I was working at a venture capital firm and a very good friend of mine, the founder of the company, told me about this treatment for Parkinson’s. I thought he was crazy. You know, like I would never invest in something so complex. So it’s good to know that it’s not just us. No, because I love what you guys do because you have big dreams. You look for transformational technologies, transformational companies, but you have to have a clear regulatory path, clear clinical path, clear science, and all of you guys are very, very focused on that. You don’t just sort of blur your eyes and think, ‘Okay, they’ll get there.’
So you saw those things in Gain, and that’s what made you decide to join? Yes, exactly right. What we’re doing at Gain is very similar to what happened 15 years ago in oncology. When you talked about breast cancer, it was like, ‘Oh my gosh, somebody has breast cancer.’ It’s terrible, and the patient would go on chemotherapy, and everybody would be preparing to make this patient as comfortable as possible. But it wasn’t until you were able to genetically define patients that had HER2 positive, HER2 negative, BRCA gene, that you could make any progress in oncology. It’s the same thing now in neuroscience and CNS because Parkinson’s is not one disease. It’s a neurodegenerative disease.
But if you look at biomarkers and populations, all of this is made public by the Michael J. Fox Foundation. The first time I looked at this, I thought, ‘Okay, nobody really knows what’s going on here.’ But there is one little segment of patients that have Parkinson’s disease that has a mutation and causes an enzyme to not work. So that’s our focus, a genetically defined population of Parkinson’s disease. And that was sufficient for me to get from ‘no possible way’ to ‘wow, now we have a pathway.’
And then fast forward, where are you now? You’re getting into it. You just started the first clinical trial, phase one. Did you just start phase one? – What’s the trial design? How many patients? How long is it going to take? – It’s a typical phase one study. It’s healthy individuals, and we just completed the single ascending dose, and now we’re doing multiple ascending doses. So far, everybody’s doing well. – No toxic side effects or anything like that? – Zero so far, you never know what’s going to happen tomorrow, but we’re quite confident that the product based on the animal studies that we have done and all of the investigation in various assays and studies will be safe in humans.
9:48 – 14:48 Future Prospects and Industry Challenges
So honestly, I mean, you’re familiar with Q-bioformal, which we backed, right? So that’s really just teaching the bodies, generating a natural immune response. Is there anything with what GAIN’s doing? Is it similar to that standpoint where there’s lower risk potential because you’re essentially giving an enzyme that should unfold a protein and open things up? It’s a very good question, actually, and Q is a great company. If you haven’t looked at it, this is a tremendously undervalued company. I’ll give you the hundred dollars later. No, I did not say that for any regular. There are several companies that are very undervalued because of the dynamics and biotechnology and pharmaceuticals over the past two years. But all we’re doing is fixing, in a very temporary way, an enzyme that is not in the correct shape.
So it’s like me trying to walk through that door, and my arms are stuck out wide because I have some genetic mutation where I can’t put my arms down. Take the pill, and all of a sudden, you can put your arms down and walk through the door. That’s all we’re doing. And so we’re not changing, we’re not using genetic therapy, we’re not gene editing, we’re not doing all of these crazy things that, you know, luckily somebody else is working on them, but I think it’s a very pragmatic low-risk strategy for repairing that enzyme. The question is, what percentage of patients with Parkinson’s have this enzyme mutation?
It’s been described in the literature as up to 15%. So that is about 150,000 patients in the U.S. Well, this is—well, Lou brought up something very interesting that he said that, you know, in one of our studies, we showed that when we gave our drug to mice that had Parkinson’s disease that we were able to actually reverse it. And so this has never been shown before. This is very unusual, and it was a really interesting finding. And this is an industry-accepted assay. So, you know, Merck does it, Biogen, everybody does this assay, but we were able to actually show reversal. And then we looked at it in mice that didn’t have that genetic defect, that genetic mutation. And we were able to see improvements, increases in enzyme levels, and improvements in the symptoms, and they were able to hang on this wire, it’s called the wire hang test, longer. So we think that if we pursue this strategy the drug will be, to a certain degree, helpful in other patients besides that narrowly defined genetic population.
I mean, what an amazing world we live in, right? We can take science and drugs and see if a mouse can hang onto a wire long enough and tell from that that it could potentially reverse a neurogenetic disease. I mean, we live in interesting and amazing times. – Yeah, well— – Jeff, I don’t want you to just sit there and look pretty and smile. (Jeff laughs) Come on, what questions do you have for— – Well, obviously, you’ve mentioned the size of the population, and you might mention kind of if the drug is successful, what kind of cost is it offset? What’s the cost-benefit analysis for the healthcare system in general? Obviously, good news for the patient.
The patients, this is a chronic, progressive, debilitating disease that affects not only the patient but the families of the patients. It’s devastating to these families. So, the cost of treating these patients, there is really… no drug today that can address Parkinson’s disease. What’s interesting about our approach is that you can actually do a genetic test. In some states, I think there are three or four states that do it at birth, just automatically see whether or not you have what’s called a GBA1 mutation. If you have that GBA1 mutation, then you’re flagged. You know to watch over time. You can speak with your physician, and your physician will know that you are at a higher risk of developing Parkinson’s disease. So our goal is to be able to detect these patients early, provide the drugs that they have normal enzyme levels, and they never have those symptoms. So that’s really the way that we envision.
So it would be a preventative once-a-day pill, or what’s the dosing that you’re going to be thinking? >> The way we think about it, it’s very difficult to identify patients early on, okay? So the way we think about it is basically slowing the progression of the disease. So if you’re able to identify somebody, you know, mid—and by the way, this genetic mutation causes the most devastating form of Parkinson’s disease with the earliest onset.
14:48 – 19:53 Concluding Remarks and the Future of CNS Disorders Treatment
So if you can catch them early, you can most likely avoid a very long course of disease.
– Okay, and it is a once-a-day pill?
– It’s being designed today as once a day, yes.
– And so would this potentially eliminate the need for deep brain stimulation?
– Yes.
– Wow.
– Yes, or depending on the patient, I don’t know which patients benefit from deep brain stimulation. there may be combination strategies early on to be able to catch it early on, but this is early, what we have seen, and we’ve done some experiments, we’ve done some collaborations with pharmaceutical companies and academic centres and published this data, is that this pathway for this enzyme is not only important for Parkinson’s disease, but it’s also a culprit in Lewy Body Dementia and Alzheimer’s disease. And we don’t have the resources to study everything. We’re focused on the genetically defined population of Parkinson’s disease, but our potential partners that we will likely work with to bring this product to market and commercialize it are very interested in those other indications. And that just makes the market much, much larger.
Given this, there are 3,000 studies on Parkinson’s. Parkinson’s and Lewy body dementia are massively funded programs. Might that suggest the ability to partner with someone sooner than later and not necessarily at the end of phase two? What would be your guidance on that probability or possibility? We have done some collaborations. That wire hang test was not our idea. It was one of the collaborators who asked us to do that assay. But I think they’re going to look for safety data because this is such a large population. They’re going to be very focused on safety. And so once we have this phase one data, which will be later this year, I think that the discussions we have ongoing now will really accelerate.
So, given the encouraging signs so far, we’re out of time, but I want to give you, out of respect, 30 seconds. Tell us the secret to anti-ageing.
– My wife tells me it’s fat. Is there anything else you want to add to the end before we break? I would just say that my background is in venture capital and starting biotech companies, really transformational companies. This is why I like MDB so much because I was trained and my first job was working with Healthcare Ventures, a venture firm in New York. We started a company called Genetic Therapy Inc. back in 1987, the first gene therapy company. Just yesterday, a gene therapy product was approved. This is 35 years later. We also started Human Genome Sciences, the first company to sequence the human genome. We started another company, which I ended up at, called Metamune. We sold that company for 15.6 billion for a disease that no one even knew about, and couldn’t even spell RSV. So, what I like about GAIN is I think it’s going to be transformational in central nervous system disorders and neurodegeneration. And we’re going to get through these clinical studies, we’re going to, you know, I’m very confident about the people that we have working there, but I do see a transformation in CNS. Just like Dallas-based, not Dallas, Plano-based company, you may know Rihanna Pharmaceuticals, right? Seven billion dollar acquisition, 5,000 patients per year, that’s their market, is 5,000 patients. So think about the value of Parkinson’s disease and talk about big market opportunities. It’s the asymmetric return potential that Jeff talked about in the beginning.
So, well, thank you, Eric, always a pleasure. Thank you very much.
– All right, you have 10 minutes to provide some feedback, grab some snacks, and we’re going to end with the magic mushrooms.
