Episode 61: William Korinek - CEO and Co-Founder, Astrocyte Pharmaceuticals

Embark on a journey through the neurons and synapses of brain science with William Korinek, the CEO of Astrocyte Pharmaceuticals. In a conversation that fuses the molecular intricacies of neuroprotection with the humanistic pursuit of medical advancement, Bill reveals his unique path from molecular biologist to biotech innovator. Together, we unravel the complexities of securing funding, the importance of strategic networking, and the scarcity of research dollars for conditions impacting millions globally. His insights into the world of neuroprotection therapies, especially the uncharted potential of astrocytes, promise to leave you enlightened and curious about the future of neurological care.

First In Human is a biotech-focused podcast that interviews industry leaders and investors to learn about their journey to in-human clinical trials. Presented by Vial, a tech-enabled CRO, hosted by Simon Burns, CEO & Co-Founder. Episodes launch weekly on Tuesdays. 

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Chapters

• 0:06 Advancing Neuroprotection Therapies in Healthcare
• 6:45 Advances in Astrocyte Research for Stroke
• 16:28 Advancements in Neuroprotection Therapies

Transcript

Speaker 1: 0:06

You are listening to first in human, where we interview industry leaders and investors to learn about their journey to in human clinical trials presented by Vile, a tech enabled CRO. Hosted by Simon Burns, CEO and co founder featuring special guest host Amy Dometico, VP of Ophthalmology. For this So we are joined by Bill Kornack, CEO and Co Founder of AstraSight Pharmaceuticals, discussing their innovative approaches to addressing unmet needs in stroke, TBI and concussion along with the exciting future of neuroprotection therapies.

Speaker 2: 0:43

Hello, everyone. I'm Amy DelMedico from Vail, and I'm here today with Bill Coronik from AstraCyte Pharmaceuticals. Bill, would you like to give us an introduction and cut some backgrounds on yourself?

Speaker 3: 0:55

Oh, sure. Hello, Amy. Nice to meet you, and thank you for having me on the podcast here. Yeah, so I'm the CEO at AstraCyte Pharmaceuticals. We have a small molecule drug that's moving into a Phase two clinical trials. I guess, for background myself. I was a scientist first. So PhD in molecular biology and Harvard. But I quickly went to the business side, did a number of years at consulting, cheesy consulting to a broad range of biotech and pharma companies, which is great experience, got a lot of the business side of things, financials, And then I I went to Pfizer. And I was there at Pfizer for about ten years. It was great for learning a lot of how big companies, industrialized pharmaceutical drug developments. I was fortunate to not just be in one small group. I was in a group that was able to work across the company. So I was able to work with leadership teams on early discovery through late stage developments across all our therapeutic areas, across, you know, the most small and large molecules. So it was a a great background for seeing, I think, both the kind of a science and business side of things and also working at a very strategic level and operational. So I'll give you a good backdrop to move into a CEO role in a biotech company.

Speaker 2: 2:05

I was gonna say it sounds like you have the perfect CV for the role. So thank you for the background. I wondered if you could share some insights into how you developed as just like pharmaceuticals, and any challenges that you faced along the way?

Speaker 3: 2:19

Yeah. Starting in any company, particularly biotech company is definitely hard. There's a lot of trip hazards, a lot of ways to mess up forming a biotech company. I think the biggest things that you can rely on really are kind of your network. And one of the things about the biotech industry, even though I think the pharmaceutical world has a bad reputation overall, there's a lot of great people in biotech. And if you have a network from your graduate school or earliest jobs or just networking from conferences, People like to help other people. They wanna see companies succeed. They wanna see more therapeutics advancing and clinical trials. They want to see more treatments and cures advanced. So so if you have a network and you're able to reach out, usually, there's a lot of helpful people. And that was great for us in the beginning with ASSA site. We were, like, contact people that pointed us towards lawyers that are very serious starting up biotechs. Financial people that can help you set up your accounts in the right banks and ways to kinda do things to help get a licenses set up of universities. So that network is hugely important when we were able to kinda get to experts that would help us refine our early discovery strategy, our early PK plans, and things that we needed to have, I think, a more sound business plan and as we apply for grants to have those applications that really made sense with all steps of the science and all the disciplines that you need. So definitely forming the a company challenging, leveraging the network, and then, of course, funding. The other biggest challenge for every biotech company is the funding. Some companies that are able to catch up venture capital from the very beginning and have a a pretty robust capital plan. But I'd say the vast majority of biotechs are in that scrappy category, using friends and family, using grants, using angel networks, and acetate's always been in that category. We've been fortunate to get a lot of grant funding over the years. Probably about a third of our funding has come from grants. But it's always up and down. You get enough money to get some good results and those results you you leverage to get some more capital. But that's I mean, just part of the challenge is you really have to breach out to that network and a lot of experts to help you and then find a way to kinda get the the funding against people that this is a a worthwhile opportunity.

Speaker 2: 4:34

Yeah. You can certainly never sit back, can you

Speaker 3: 4:37

Unfortunately, no.

Speaker 2: 4:40

It is nice to see that I think I agree with what you said about. People I think they want to make a difference. And I think everybody is really happy to share their expertise as well. So that's very helpful when you're starting up at a smaller company. So the next question is about the unmet need in neuroprotection, specifically concerning stroke TBI and concussion. Wondered how the latest advancements in neuroprotection therapies are addressing those needs.

Speaker 3: 5:06

Yeah. I think in terms of an area of unmet need and level of R and D research dollars that are going into it, I think this might be one of the biggest disparities out there in the world of pharmaceuticals. Curious if someone has a a greater example, but you think about, you know, this stroke in particular in the US is kinda balancing between the third, fourth, fifth, leading cause of death. But worldwide is the number two cause of death. And it's one of the greatest cause of disability. You know, there's more years lost to disability from stroke and all other neuroscience indications combined. Alzheimer's, hunting germs, Parkinson's, everything. Nursing homes are filled with people who had strokes. So you think about that tremendous need that's out there and the billings of dollars that go into healthcare for people who have had strokes, and there's very little r and d dollars. It's just been an area that's not garnered much venture investment, much pharmaceutical research. It's up and down in that realm. And so I think that disparity is is staggering. And then, right now, I think about a dozen companies that have true interventional therapeutics, advancing of Phase two, Phase three type trial. Compare that to oncology or Alzheimer's or many of the other indications that have hundreds and hundreds of attempts shots and goals is, you know, provide a new therapeutic. Stroke is still just been an area where there's only a few companies pushing it forward. There's gonna be a breakthrough that I think in the next five, ten years, you're gonna see some great advances. Hopefully, we're one of them. But it's just it's a huge opportunity given what's changed in the last decade. But it's again a tremendous unmet need. And it's unfortunate there's not more R and D dollars out there trying to help these patients.

Speaker 2: 6:43

It's crazy that there's such a disparity. Do you think that some of it may be important due to the fact that acute trials, particularly stroke trials are really difficult to conduct?

Speaker 3: 6:52

So I think it's two things. One, it is challenging to conduct the trials, but it's not impossible. There's also challenging clinical trials that people you know, find ways to make them work. I think the bigger things when you just look at the economics, there were you know, a number of attempts in some big trials that failed in the nineties and early two thousands. And with those failures, people kinda backed away. They just kinda said that it's too hard to do a clinical trial and stroke. It's just too random in terms of what the actual underlying injury is and what the outcomes are gonna be it's too hard. Therefore, we're just wanting to try. And once you kind of step away from a disease, you kinda lose your experts. You kinda lose touch with developments and what's happening. And so it's kinda harder to come back in and realize what's changed. So you've actually seen the device companies and have really made a lot of progress in this space. And they've been the ones blazing the trail, which is Usually, I think drug companies kind of lead some of the device companies, but this one, the device companies have really pioneered how they do clinical trials in the space, which has been fantastic. This open the door for therapeutic companies now to follow their path.

Speaker 2: 7:57

Interesting. So you can learn the lessons from the device trials.

Speaker 3: 8:00

Exactly.

Speaker 2: 8:01

Yeah. Very helpful. So I wondered for listeners that maybe unfamiliar with AstraCyte, could you give a high level overview of their critical function in the brain and whitancing them hold so much promise for a neuroprotective therapies.

Speaker 3: 8:14

Yeah. So for the last kind of hundred years, neuroscience and the central nervous has really been all about the neurons. You know, they were the exciting cells. They train out signals. Go back and forth. Go to like occurrence. And the rest of the brain has always been thought of as this gap biller, glue cells, or glia cells, or just gap biller, so that people named them. And it's only in the last kind of twenty, thirty years where the researchers started exploring more why are all these themselves so important, why are they conserved? I mean, I can share two quick anecdotes. When Albert Einstein died, they actually did a study of his brain. And they thought, you know, was there something different about his brain relative to the normal human brain? Was it bigger or was it more dense? Was there's, you know, something And in all aspects his brain looked like the typical human brain except for one little side note finding which was that the ratio of astrocytes to neurons was higher. I get a higher density of astrocytes in his brain than typical. So people didn't make much of that at the time, but I would be a second anecdote too. The ratio of asthates to neurons and, like, the frontal cortex of your brain is aorta one. Asteroids are the most common cell there. They're very conserved. And in some species, it's actually higher. And if I can give an example, whales and dolphins have astutect syndrome ratios that are in the seven to one range. And it's very interesting because these are animals that people think of as on the smartest end of the spectrum above animals. And at the same time, they can dive underwater for, you know, many, many minutes and, you know, how we're in some cases. And that relates to how we treat, you know, strokes and, you know, where there's stress in the brain, low oxygen environments, these animals with higher ratios of acetates to neurons actually can survive longer in those low oxygen environments. So there's a lot of interesting things about acid that people are starting to study and I understand their role as kind of the more important central caretakers cell in the brain. And now we all know there's several large pharma that have entire programs now that are about asoside dysfunction, glial cell dysfunction, and how it's really associated with many of the neurological diseases that we see out there. So only in the last, like, twenty, thirty years, though, as you know, because it's an overlooked area, and now it's definitely starting to explode a bit.

Speaker 2: 10:29

Fascinating. That was so interesting. I didn't nail that. So your answer is AST-four, and it works by targeting the astrocyte, so it would just be discussing. Why is this approach been overlooked historically in neuroprotection research? And what do you think is exciting about its potential?

Speaker 3: 10:46

So, carrying on with astrocyte here, we like to think of the analogy of parents and children that neurons are, like, children. They're just very specialized in what they do. They just kind of really the most part are sending those axon signal And they're still specialized that they really don't care for themselves. You know, they're really dependent upon the the assets for a lot of the nutrients, metabolism, recycling of neurotransmitters And when there's a a stressful situation, like during a stroke or, you know, traumatic brain injury, things go haywire and the kids just go crazy. They just start, you know, firing the signals more they actually have recurring depolarizations. They tire themselves out. They exhaust themselves. And actually, the cells can basically end up lysine and dying because of it. So the astrocyte as the caretakers cells can calm things down. One of the things that the astroids are known for is they clear glutamate from the synaptic clef. So it stops that excitatory signal. But if your assays aren't functioning, they won't do that. And that causes the neurons to depolarize and tire themselves quicker. So the caretakers cells do have, you know, mechanisms to help. Like, is that clearing like glutamate, providing more glutathione into the substrates of neurons as well? There's things that they can be doing But eventually, they'd tire out and they kinda can give up. So what our drug is d zero zero four. It's an adenosine athere agonist adenosine ends up being a kind of distress signal in the brain. And so with our molecule, we're able to tell the acidized prolongnet distress signal. And tell them to kinda keep using their energy stores, alternate energy stores, to kinda keep fighting, you know, wait, keep caring for the neurons and we see that the cells are able to kind of recover their ion channels and start to repolarizing, control setting level dima. You're able to help the neurons greater, the atherosight survive, the neurons that area can survive. So there's lots of benefits we have through this mechanism, which really is kind of leveraging some of the intrinsic healing mechanisms that the brain does have.

Speaker 2: 12:36

And we know that with strength, you know, one of the key issues is being able to treat patients quickly, you know, there's a really narrow time frame after onset of the disease. I just wondered how AADT004 can potentially address that particular challenge will improve outcomes for patients.

Speaker 3: 12:52

Yeah. So in stroke, the mantra is time is brain. And the longer people have a let's stroke have a blockage to the more brain is lost. And so the current treatments, one is TPA, AltaPlace, or connected place. It's a thrombolytic that helps shoe up the clot, I guess, in a simple way. But it has safety liabilities has to begin within the first four and a half hours. And with strokes and strokes, you just don't know, you know, you know, that you you find someone that had a woke up of a stroke. You know, there's a lot's been going on. So they often will not administer that, because they're not sure how long it's been. And with surgery, it's interesting that time clock has really changed and stroke in the last decade, such as starting to not be defined by the hours on the clock and more so by the state of the tissue because some people have strokes that really evolve very fast. It is have much collateral circulation in the area, much blood flow at all. So the cells die pretty quickly, and the bleeding just grows. And really, in the first six to ten hours, this stroke can be over. Other people, maybe so fortunate the way their brain developed, they just have more collateral circulation in the area. The lesions grow slower. There's more stability and twenty hours into that stroke, they could still have a brain that has a number of area that's at risk, but it's still evolving, still salvageable. So with the second method of treatment, now the device thrown back to meat procedure, they look at the state of tissue. And if there is a tissue to be salvaged, they'll go in. By eight hours, there might be nothing left to salvage. But in some of people at twenty hours, there's still plenty of salvage, and they will go in and dupe surgery. So to your question about us, we think that as long as there's brain left to salvage, our drug can have a benefit. We've seen that even in a mouse experiment just later twenty four hours. If we start treating it twenty four hours, we freeze the damage at that point, and it doesn't go further. If you treat earlier, it's better. If you can stop it earlier, but there's kind of a late window here where you can still be treating. And then the other aspect that's an advantage of our drug is that we see benefit in both the ischemic side of stroke and the hemorrhagic. So there's two types of stroke, both the blockage of the clots or the rupture of a blood vessel. And those two treatments of thrombolytics TPA and surgery only work under the clot. So they cannot even be considered until the patient gets to the hospital, they get an image, and they know what's a clot and where it's at, then they can do it for us because we don't need to differentiate we could be administered earlier. So even emergency responders can be showing up, they can tell us a stroke, they see mop paralysis, and they can start administering our drug way earlier kind of in the ambulance with an IV versus waiting until they get to the So we see our approaches have that advantage of potentially starting earlier and still being a relevant later if a patient shows up late.

Speaker 2: 15:44

That's amazing that you've got the option. Yeah, you can treat those patients earlier. But if that doesn't happen, there's potential for benefit later as well. Very exciting. We talked about the emerging understanding of how astrocytes work and what they do. I wondered how the landscape for new protective clinical trials has evolved and they're singing particularly in terms of care control design and drug development.

Speaker 3: 16:05

Yeah. So this is probably been the biggest change. So in many other disease that you've seen kind of more personalized trials, more gratification of patients, you know, some ways to get more sophisticated in trial design. Cancer is the prime example where they shifted from breast cancer and prostate cancer to using different biomarkers, triple negative breast cancer. So you kind of know that define the underlying disease a lot better. And a stroke that wasn't available in the nineties and two thousands. And so when people are coming in with a stroke, they were enrolling people in clinical studies that may have been twenty four hours or forty eight hours into a stroke at the end, but the damage is done. There's nothing left to really do or save at that point. They're testing people that had very large vessel occlusions and people are very small. That's all of the locations where they're gonna very different outcomes. People add the clots in very different locations in the brain, which leads to different political outcomes as well. So it was really kind of a wild west type of patients that they were enrolling in these studies, and it makes sense that these people regardless of interventions. Some people looked like they were doing quite well and we're still a coherent. And then they would be dead in twenty four hours. And there's other people that were comatose almost and then we're fine twenty four hours later. So it's a challenging population or at least the way that was studied back then. That really changed throughout two thousand ten. And people started using the the standard imaging, which now everybody uses it, you know, you get a code stroke someone that's got a breath into the They always image these people now to see whether they have a quadrant. And you can use that imaging to see what's actually happening in the brain and pick people that are having a similar type of stroke. So the big advance was now using that imaging to say, hey, we're using this to do a study with people that have large vessel occlusions, strokes that are in that middle cerebral artery, and the lesion is only about a third at most of the at risk tissue. So there's a big mismatch between what could be saved and what's already dead. And if they have that mismatch, now we're going to try to do an intervention, which in the two thousand tens is really about thrombectomy devices and this endovascular treatment. But they're picking people that had, again, the same injury, the same location, at the same stage of progression, and they had more similar outcomes, so now you could finally tell if your intervention was having a benefit or not. So this is tremendous. It went from a lot of clinical trials that are very, very noisy, great spread of outcomes to now a much more homogeneous population, and we'd be able to see the benefit from those device trials. And so now the new generation of companies that are looking at neuroprotective treatments are leveraging this approach and are doing clinical trials now based on imaging based patient selection, so you can have that homogeneous population to do these initial studies. Now, basically, you kinda wanna work in almost all stroke patients are a broader population relation, but at least for these kind of critical phase two proof of concept type trials, you can get that more modest group and reduce end of the number of variables and reduce that risk so you can actually see whether or not the drug it is working or not.

Speaker 2: 19:05

Yeah. So you can sort of reduce the noise by using the imaging to really target your patient population

Speaker 3: 19:10

Exactly. And that's true in traumatic brain injury as well. This scenario where it says been for even less clinical trials, but you can be looking at know, the level of edema you could be looking at, whether there's clear contusion, etcetera. But imaging based patient selection now has been a revolution now in these areas.

Speaker 2: 19:27

And so I know you're developing other therapies. Beyond AST-four, are there any other areas that you're exploring in the field of neural protection?

Speaker 3: 19:36

So we have a look at multiple areas. We have some great data in Natalie's stroke and traumatic brain injury and spinal cord injury and the concussion model. In terms of the most exciting I have to put concussion. Conclusion is something that, you know, like the world's really learned about in the last kind of ten, fifteen years now. And have become aware of not only the acute symptoms and challenges, but the long term consequences of multiple concussions as well. The statistics are that there's about one point seven million traumatic brain injuries each year in the US that go and present to the emergency room. The majority of those are mild, traumatic brain injuries. But there's an estimate of about five to ten million more that are happening, that is concussions that people don't go to the because nothing's gonna happen there except a big medical bill, perhaps, because there's no treatments out there for concussion. And our drug fortunately has been very safe. We've gone through our regulatory toxicology studies, two different Phase one studies have a very safe profile. So in addition to treating the severe injuries of stroke and traumatic brain injury, we see our drug is having a lot of potential for treating concussion. And we've been fortunate that US Department of Defense has really looked at our data that we've done in the various animal models and been impressed with it and traumatic brain injury. They've actually given us grants for the progression of the drug and to help make an oral tablet version. So our our main hospital version is an IB that you get to the stroke page their TBI patients, but we now have oral tablets that can be in weather resistant blister packs that you can imagine in a soldier's backpack or on sidelines of a football or soccer game. And when someone gets a concussion, you can take these tablets and dissolve in the tongue in, like, less than four seconds without any water. And we see that as having a similar benefits to help with that near term acute treatments, to help with brain swelling, help with symptoms, And we would hope that if you're able to help in the acute phase and help people return to the sport, to return to work, or return sooner without symptoms, that's a win. And if it could help with immediate clean up so that there's less chance of long term inflammation, consequences, that would be tremendous as well. We've seen some evidence of that in kind of long term mouse studies, but that's a longer term tool for treating people. We see that as an area that is a tremendous need and we think we have a potential to help.

Speaker 2: 21:59

Yeah. I mean, concussion could be quite debilitating, cancer. I've had it several times and know, you can imagine there's quite a high economic impact that days off of work.

Speaker 3: 22:07

Exactly. Because right now, people just tell you, like, well, just go rest because the brain can kinda you itself, but twenty percent of people are still feeling symptoms thirty days later. And so there's a need. Absolutely.

Speaker 2: 22:19

So this is the last question and more of a sort of forward looking question. But I just wondered what excites you most about the future of neuroprotection therapies and where do you see the field heading in the next decade. Howard Bauchner:

Speaker 3: 22:29

Yeah. Suneera Science is probably I think one of the most exciting places to be. I think it was an area that was kind of behind the curve and really taking advantage of the genomics revolution that occurred. Oncology was ahead of it because they were taking biopsies in the nineties and understanding what's happening between pathogenic cells and normal cells and neuroscience was much later in understanding the cells involved, the genomics implications, And so I think that really has kind of started to play out in the twenty ten's where people really understood all the genes and cells that are really driving disease states and in a lot of the neuroscience indications. We're finally seeing some progress in Alzheimer's disease, some other areas. I really do think it's gonna be the next decade here is really about neuroscience. And in terms of nerve protection, I think we'll see some winds here in that acute space where people have concussions to my brain injury strokes, but If you're able to help the brain do better in those more severe situations, there's a lot of potential here to help it into the more mild situations as well. We start thinking about stress from Alzheimer's or repetitive concussions. I think there's gonna be a lot of potential here for that nerve protection, neuro restoration, over time. So as you think about Alzheimer's, CTE, even aging, there's lots of benefits that can come here from enhancing glioblastipungsten and brain health. So that gets me excited. I think it'll be much better brain health here in the the decades to come. And hopefully, our research will contribute to that.

Speaker 2: 23:53

Bill, thank you so much for talking with me. It's been absolutely fascinating, learning more about after slides. I really appreciate your time today. Thank you.

Speaker 3: 24:00

Bill, thank you again, Amy.

Speaker 2: 24:06

They

Speaker 1: 24:09

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