In this episode we are joined by Trevor Klee. Trevor is the founder of Highway Pharmaceuticals is a biotech startup creating drugs for autoimmune diseases. Right now, they're running a pilot trial of our drug in feline stomatitis.
Feline stomatitis is a serious autoimmune disease that affects 1 million cats per year in the US. The only treatment for it currently is a $1k+ surgery. By the end of the trial, we expect to have evidence that our drug can safely and effectively suppress the feline immune system. This positions our drug to become the only alternative to an expensive and traumatizing surgery.
Trevor is currently raising funds to cover the rest of the costs of the trial, as well as position us for our next milestones, which you can check out here: https://wefunder.com/highway.pharmaceuticals/
William Jarvis 0:05
Hey folks, welcome to narratives. narratives is a podcast exploring the ways in which the world is better than in the past, the ways it is worse in the past, where it's a better, more definite vision of the future. I'm your host, William Jarvis. And I want to thank you for taking the time out of your day to listen to this episode. I hope you enjoy it. You can find show notes, transcripts and videos at narratives podcast.com. Well, Trevor, how are you doing this afternoon?
Trevor Klee 0:39
I am doing great. Thanks. How are you?
Unknown Speaker 0:42
Doing? Great. Thanks again, for coming back on the show. I think you're our first repeat guest, which is which is super cool. I'm excited about the effort you're working on and the problems you're admiring. And you've got a new initiative there. I've kind of wanted to highlight on the show and get a little more eyes on it, if that makes sense. Because I really believe in kind of the mission you're working on. Just for someone who you know, perhaps didn't listen to the last episode. Do you mind giving us like a brief bio and you know, some of the big problems you're interested in?
Trevor Klee 1:12
Yeah. Okay, cool. So hi, Trevor. In terms of a bio, I have a really weird non traditional background. So done, like a bootstrapped and tech slash tutoring business and then veered into doing a biotech startup after spending several years posting essays on Reddit and arguing about them in the comment, like biotech essays and biology essays. So, you know, what we're working on essentially is with this biotech startup highway Pharmaceuticals is immunosuppressants, and specifically, what we're working on right now is creating safer better versions of immunosuppressants for animal autoimmune diseases, human autoimmune diseases, and eventually human note or degenerative diseases like dementia and Parkinson's and that kind of thing.
Will Jarvis 2:16
I love that. I love that. How did you first come up with the drug cyclosporine as the the one to use, if that makes sense?
Trevor Klee 2:23
Yeah, yeah. So you know, when I got interested in this problem, I was looking for sort of ways to tackle it. And I came across this drugs cyclosporine, which is, you know, used to be a really widely used immunosuppressant. And humans sort of fallen out of fashion. Still pretty widely used in animals. And what I thought was interesting about it is it's, you know, this really powerful drug, it has great effects in a ton of different diseases, everything from, you know, psoriasis, to IBD, to, you know, there are even some early studies done on like ALS and stuff where it showed some promise. But it always been, you know, sort of relegated or useless because it has a bunch of bad side effects. And it's, it's pretty hard to dose it's a it's a very tricky drug. So, you know, I was focusing a lot on how can we make this drug which is so powerful, but so hard to use? How can we make it easier to use safer better, and so, you know, doing research on that eventually came up with this idea that if we combine it with a, you know, certain other drug, which is a metabolic inhibitor, we could solve a lot of the issues while keeping the potency. So that's, you know, it started off by looking at some human case studies where they had done this accidentally and then move on to in vitro studies. And, you know, now like, we're really testing the this and well, cats.
Unknown Speaker 3:58
Why cats? Yeah, you always hear about mice. You know, you hear about, you know, perhaps these rhesus monkeys, perhaps dogs, beagles or something, but like, you don't often hear cats.
Trevor Klee 4:09
Okay? Yes. So there's a good reason why you don't often hear cats. It's actually funny. I have a friend who was like, thinking of testing drugs, and he was like, Do you think I should test my drug in cats? And I was like, probably not, unless you're really certain that you want to. And so, you know, cats in general are harder to deal with then dogs, which would be the other obvious option, you know, cats, they're, you know, they're tricky animals as anyone who's owned a cat, they're a little smaller than dogs. And, you know, they also you know, can have some bad reactions to certain drugs like Tylenol, for instance. Cats can't take Tylenol for sort of biological reason. Um, but you know, what we found when we were looking at like, really good uses for this safer version of cyclosporine is essentially that cats get this, you know, autoimmune disease called feline stomatitis. It affects about 1% of all cats. And like right now, it really doesn't have a good treatment. And we wanted to, you know, think like, Okay, could this be something that our immunosuppressant could be used for? So we were talking to vets, and you know, of all the diseases that we talked about, they were like, Oh, my God, yes. Like any treatment you can create for Feline stomatitis would be great right now. And the only option is, is surgery. So that's, that's really where we started our exploration of like, using using cats as as our first indication here.
Unknown Speaker 5:45
I love that. I love that. Can
Will Jarvis 5:46
you talk a little bit about the its feline stomatitis? correctly? You are correct. Awesome. Awesome. Can you talk a little bit about how it affects cats? And perhaps why and how, more say a safer cipher cyclosporine could really be useful in this
Unknown Speaker 6:01
context.
Trevor Klee 6:02
Yeah, sure. Um, so yeah, so Feline, stomatitis? It's sort of like a, you know, have you ever had like a canker sore? Yeah, yeah, stomatitis is close to that, except cats get really bad. So they get basically a bunch of sores all over their mouth and lips. And like, you know, it's, they can't eat, they can't drink. And they're really miserable. And if you know, they don't, if something's not done, you know, they, well can be as bad as you'd expect not eating and drinking to be. Um, so that's, that's basically, you know, the disease and it affects, you know, about a million cats per year in the US, and like the current treatment was or is pulling teeth. So they literally will sedate cat pull all its teeth. And this will happen to cats, they're like two, three years old. It's really sad. Oh, man, it's expensive, can be 1000 2000. And we've been here $3,000. And, you know, it only works like 70% of the time. So it's, it's ruffled altogether. So we were looking at the studies, and found that a couple of people had experimented with using cyclosporine instead of pulling teeth. So they were, you know, used it before pulling teeth, like instead of it, and they also used it after, and basically what we found, or what these these authors found is that cyclosporine does work. But again, it's difficult to use, it has a high rate of side effects. And so, you know, they, like the author's basically, in the papers themselves were like, you know, it would, this looks really good, but it's tricky enough that, you know, you should probably stick with like surgery first, and then cyclosporine only if you absolutely have you. So then reading this, you know, these are papers from like, 2006 2010 2013. You know, I was reading that, and I was like, huh, I have a better version of cyclosporine. So that's, that's sort of how, how it got started on the idea of feline stomatitis.
Unknown Speaker 8:15
That's great. That's great. You know,
Unknown Speaker 8:17
how expensive as our feline, you know, clinical trials? And what is the how's the regulatory environment difficult with different between humans and cats?
Unknown Speaker 8:27
If that makes sense?
Trevor Klee 8:28
Yes, that's a great question. Um, yeah. So there's, there's a big difference there. So basically, you know, human clinical trials you've got, you get your sort of preclinical work. And then you talk to the FDA, and you say, I would like to test my drug and humans and the FDA says, Okay, make sure you have all your ducks in a row, make sure you know, the drug is safe, that, you know, safe, and you can manufacture it and whatever, whatever. So that can be super expensive. And then they allow you to test your dog and healthy humans, then they allow you to test your drug for safety and healthy humans. And at last, they allow you to test your drug and sick humans. And there's a lot of paperwork around this because you know, you don't want to be hurting anyone. For animals, it's really different. So for animals, the FDA is basically basic position is, you know, we don't care what you do to lab animals, like you have to abide by minimal ethical standards. And for the record, we abide by way more than that we're working with people who are, you know, very careful about, you know, the well being of their animals. But from the FDA standard, they actually don't need to talk to you until you want to work on basically pets. So, you know, we don't have to talk to the FDA when we work on our lab cats, which we're going to be doing for our healthy lab cuts and for our safety trial. And then we're going to talk to the FDA once we want to you know recruit some people whose pets actually have feline stomatitis. And so the cost of this like initial trial where we're testing our drug combination on healthy cats and saying, Okay, it's reasonably safe, it works better than the original version of cyclosporine, it can be dosed less often and, you know, can stay around in the blood longer. So that cost is about 300,000. All and so that's actually, you know, we're currently fundraising right now to basically cover that gap, which is, you know, we have about 200,000 in the bank, and we're need to cover the extra 100,000 For to finish out our pilot trials.
Unknown Speaker 10:42
That's great. That's great. And can you give like context for your listeners who might not know how much human trials cost? What is the cost delta between, you know, your, your study and doing an equivalent trial in humans?
Trevor Klee 10:55
Yeah, so we started off doing it. Thinking about this in humans, we had a human autoimmune disease that we wanted to test this combination on. And so the cost for that would have been around 1.4 million for basically doing probably would have ended up being more than that, probably around 1.6 million for doing like a good high quality, you know, trial and healthy humans. And, you know, meanwhile, we're going to be about 300,000 for a good high quality trial on healthy cats. So you know, it's a big difference, cats, there's less regulation, you can pay cats and cat food, you know, rather than money. Cats are very happy to stay overnight in the facility, because, you know, they don't have a home that they're waiting to get back to. So yeah, it's it's much cheaper.
Unknown Speaker 11:53
That's great. That's great. Why don't more people use, you know, cat as subjects for these trials.
Trevor Klee 12:01
Uh, so, you know, if you think of cats specifically, the basic reason why you would use dogs instead of cats is because cats are tricky, like, you know, you, the cats that we're working with, have actually been trained to take drugs and trained to be okay with having their blood drawn. And if they're not, then, you know, giving drugs to a cat is, I mean, difficult. They've got Yeah, they will, they will bite you. Meanwhile, dogs, you know, you put it in peanut butter, and they're happy to take it. So that's, that's why people don't use cats instead of dogs. The reason why people don't often do what we do, and do you know, sort of the animal trial instead of the human trial, or switch from human to animal is really economics. So for your average disease, it's going to be way more lucrative in humans than it is in animals. So for instance, you know, a really big example is not a lot of people know, there's actually a drug for doggy dementia, for basically, Alzheimer's. It probably doesn't work. But more to the point, it's, it's not that widely prescribed, because the only real concern people have with doggy dementia is like, you know, you want to make sure your dog doesn't, you know, pee inside the house. But other than that, like people don't really care. Meanwhile, of course, you know, human Alzheimer's is something people care a lot about. And it's like, you know, a drug for human Alzheimer's would bring in like 100 billion a year. So, you know, there's not that many diseases that people care enough about and animals to be willing to pay for them. And, you know, feline stomatitis is, is one of them. They're a couple auto, other autoimmune diseases like atopic dermatitis, like the itchy skin rash that people pay for, and that's like a billion dollars a year. But, you know, there's really not that many drugs that are worth developing an animal's from an economic perspective.
Unknown Speaker 14:07
That's great. That's great. What do you see, we expect to see from this trial, specifically, what kind of outcome do you expect to see?
Trevor Klee 14:16
Yeah, so you know, what we're going to see at the end of this trial is basically that our drug is reasonably safe, that it works better than the original form of cyclosporine. And that, you know, we can dose it basically once per week, or roughly once or twice per week instead of the current cyclosporine, which is once per day. And so that's, that's pretty exciting, because, you know, cyclosporine right now, is a pretty commonly used drug in animals. I mean, it's used in dogs. It's used in cats. You know, it used to be used really commonly for atopic dermatitis, which, you know, as I mentioned, is billion dollar a year. disease in dogs. So, you know, essentially at the end of this trial, if we can say, you know, we are, I don't know, 80% Sure, 90% sure that our drug is better than the original form of cyclosporine. You know, that means at the end of this trial, we're going to be pretty sure that we can, at the very least take on the, you know, X hundreds of millions per dollars that, you know, per year that people spend on animal cyclosporine. And that's not even counting, expanding the market, like we planned to do with feline stomatitis.
Unknown Speaker 15:40
That's great. That's great. I, I'm curious, what are the steps after the trial? Like, what do you need to do next to commercialize, let's say, just in pets?
Trevor Klee 15:48
Yeah. So you know, if we want to go totally on our own, we have to do safety trial, which is basically recruit a bunch of cats, and follow them for a long time, as they're given this to make sure that they, you know, no safety issues crop up and like, say, month for, you know, because the trial we're doing right now is only two weeks, so we would only see very immediate safety effects. So, and then after that, we would talk to the FDA, you know, say, here's what we have so far, here's what we want to do next, they give us okay, and then we basically go to a bunch of vets all around the country and say, Do you have owners with feline stomatitis? You know, what cats with feline stomatitis? If so, can we, you know, recruit them for our trial, and you know, they'll take this experimental drug and see if it works better than surgery. So that would be you know, basically, and then we would, you know, of course, market and sell the drug. So that's if we go totally on our own. Another option is, you know, we've already been approached by a couple of different big pharmaceutical companies who are interested in licensing the drug. And what's neat about that is they would license it only in animals. So you know, they basically give us upfront payments, and then milestone payments, and then some sort of royalty fee. And they would do basically everything that I had talked about, you know, the safety trial, the FDA, you know, the pivotal trial and with pets. So they would do all that, and then we could focus just going back to the human auto immune and human neurodegenerative stuff. So I think, you know, once we finish this pilot trial, we're going to, you know, get in some serious talks with a couple of these big pharmaceutical companies that have approached us see, see what their thoughts are, and then you know, more, or basically how our option, you know, we can either go out on our own or, you know, license it out and go specifically for human autoimmune disease. It's, yeah, some good, good times, and some good choices to make.
Unknown Speaker 18:03
That's great. All right.
Unknown Speaker 18:03
Do you have any sense on which way you want to go? Do
Unknown Speaker 18:05
you want to keep it in house? Do you want to, you know, license things out.
Trevor Klee 18:08
Um, so if I could get a, so I would love to license it out specifically for animals, because I think that's a less I am sorry, human biased, I think it's a less important problem than, you know, the autoimmune diseases that exist for humans that, you know, are really can be pretty devastating, and, you know, don't have great treatments. So, you know, if I can find a partner who's, you know, an animal health company, that's, I think, is responsible, that will, you know, do the trials correctly, that will, you know, actually bring the drug to market and not just shelve it, then I would love to partner with one of them. But, you know, something that I've literally already told, like the pharmaceutical companies we've been talking to, is, you know, part of my conditions for licensing would be, you know, you have to take this, as far as possible, like, I really would not be interested in anyone, you know, paying us money to basically put this on a shelf forever, which is something that, you know, depending on their incentives, they might do because, you know, for instance, the Lanco is still selling, you know, the original form of cyclosporine and their incentives, if they license it might just be let's take out this competitor.
Unknown Speaker 19:40
That makes sense. That makes sense. Speaking of humans, can you talk a little bit about application, your drug in humans, specifically for human autoimmune diseases?
Trevor Klee 19:50
Yeah, yeah. So most human autoimmune diseases used to be treated with cyclosporine. So you know, back In like the 80s, if you had psoriasis, if you had Crohn's, basically anything you would have been given cyclosporine. And that's become less and less common as biologics have become more common. Because cyclosporine, as I mentioned, is physically tough drug to administer. And biologics are generally safer. So, the the thing that still exists in hump human autoimmune diseases is basically a combination of two things, some people just can't afford biologics. I mean, you're paying a minimum of 1000 a month. So you know, anyone who you know, who has Crohn's or ulcerative colitis is paying a minimum of 1000 a month, and probably more. And then there's also drugs that, you know, diseases that don't have really clear physiology, we don't really understand, you know, how the disease starts, how it progresses. And so we can't develop biologics for those. And so that's a big place where, you know, cyclosporine can be really useful. So right now, actually, the two, well, the absolute biggest use case for cyclosporine is selling organ transplants, because, I mean, you can't have a biologic, because it's every part of your immune system attacks an organ transplant to pass to be a general immunosuppression. But there's also other stuff that's, you know, could be really useful, like, you know, lupus nephritis, which is a side effect of lupus where, you know, people can get some serious kidney disease. There is actually literally just an improved version of cyclosporine developed for that. And that's, that's approved, and that's being sold right now. And we think that our drug would be better than that. It's called vocalist foreign. So that would be for instance, one one really appealing target for us is, you know, creating better treatments for something like lupus nephritis.
Unknown Speaker 22:09
Makes sense? Makes sense. What about neuro degeneration? What applications do you see there?
Trevor Klee 22:15
Yeah, yeah. So yeah, so as as you as you noticed, you know, I, some people, you know, doctors mostly are surprised when I say, you know, oh, let's we're doing neurodegeneration after autoimmune disease, because, you know, they think of cyclosporine as this immunosuppressant. But, you know, I read a, I wrote a whole blog post about this actually, cyclosporine is this really interesting drug that has sort of this completely different side effect that it protects the mitochondria from, from apoptosis. So like, you know, mitochondria, as you may or may not know, started off as a completely different, like, you know, bacteria or think it was actually technically prokaryotes, but started off as a different cell that billions of years ago, our cells sort of subsumed and adopted, as, you know, the powerhouse of the cell. And one interesting thing about that, as the mitochondria has retained some of its, you know, characteristics back when it used to be a, you know, organism on its own, and one of those is in times of a lot of stress. It can get tough, which maybe it was didn't originally kill itself, maybe there was a different sort of evolutionary adaptation. But, you know, for us now, the practical results of that is, in times of high stress, mitochondria will die in large numbers. And that can be really bad if it happens in your brain or nervous system. So for instance, you know, one thing that cyclosporine has actually been studied in is like traumatic brain injury, if you a really common thing is people get hit in the head really hard. And they seem, you know, okay, ish for like, 24 hours, 48 hours, and then all of a sudden, they go downhill really rapidly. And what happens basically is, you know, that causes stress to the, like neurons, and the mitochondria start dying. And as they die, they create more stress on the other mitochondria. And you get this cascade, where, you know, from the doctor's perspective, it looks like the person with traumatic brain injury was fine for like 24 hours after the injury, and then all of a sudden, you know, they're experienced, like really significant brain trauma. And so cyclists foreign as calcineurin inhibitor is something that can prevent that. So there have been a bunch of experiments around that. There have been experiments around using cyclosporine and also So a similar drug called tacrolimus, and dementia, you know, with the same idea that some forms of dementia can be caused by that sort of like cascading mitochondria death, you know, all the powerhouses of the cell and the brain, you know, started going out at the same time. So those are the sorts of neurodegenerative diseases, that that's going to be a lot trickier to run a trial, and then autoimmune disease, because it's less well understood. But I think that could be you know, something that'd be really, really helpful, you know, and when I think of, like, maximum impact sort of stuff, you know, something like, I mean, almost none of the narrative degenerative diseases have good treatments. And so, you know, there's, there's so many of them that are mitochondria related, and that we could do some really interesting trials to try to try to fix
Unknown Speaker 26:00
and that feels like the ultimate goal. To me, it's like a, a real treatment for dementia. And a bonus practice of American football as well.
Trevor Klee 26:09
Yeah, yeah. Yeah, so football, there's also strokes. I mean, that's another one that like, you know, again, there's a lot of different stuff. It's, it's really interesting. And like, you know, there's been all this like hints about in the literature for years, but like, there's been no economic incentive to run these trials, because cyclosporine itself is generic. So no one else no one can make money off it, if, you know, these are no one can make money off it, you know, in sort of this monopolistic way, if they successfully, you know, fund a trial. So it's just like, random academics like cobbling together grants here and there to run these trials. But, you know, if, if we could do that, that could be huge.
Unknown Speaker 26:55
So that's your sense, why it really has not happened, it there has not really been an economic incentive to go out there and make this a reality.
Trevor Klee 27:05
Exactly. Yeah. Yeah. So you know, that's a lot of people don't know, this. But human trials, you know, as I mentioned, they're super expensive, you know, to run trial and healthy people, is, you know, at least a million and a half to run trial, and sick people can be way more expensive, you know, depending on what you're doing, you know, easily 20 30 million academics don't have access to that kind of money. It's the only the only groups that have access to that sort of money are really, you know, a couple of very well funded nonprofits, and then the, you know, for profit companies, you know, the pharmaceutical companies. So, you know, if there's no economic incentive for, you know, running this trial, if, if no one can patent the results, at the end of it, it's almost certainly not going to happen, unless, you know, you get that random, one really funded. Nonprofit, that's happy to do it. So you know, and that's, like, there's a list of like, three or four nonprofits that, that fund trials like that. And you know, it's not the ones you'd expect, either, you know, people sometimes are like, oh, you know, why don't you just contact like, you know, the, there's like, the allergic disease society or whatever, why don't you contact like the Lupus Foundation. And they don't give out money like that. And they don't have money like that, you know, they can give out like a grant of like, 50,000 to run a, like trial and petri dishes for a scientist, but, you know, they they don't remotely have the funding to do you know, you know, even like a million dollar trial, nevermind a $30 million trial,
Unknown Speaker 28:43
right? It's just just their capital constraint, and it's too difficult for them. But I really set up for that. Trevor, I really love the effort. I'm really inspired by your work. And it's been nice to see your, your progression over time. I think we talked about a year ago, and you've made a lot of progress, which I find really inspiring. Trevor,
Unknown Speaker 29:01
if people want to help, how can they do that? Like,
Unknown Speaker 29:04
what are your big needs right now.
Trevor Klee 29:06
So big needs right now are, you know, the biggest thing is capital. And then second biggest thing is, you know, if you're connected to, you know, any of like the sort of pharmaceutical companies who would be interested in specifically animal health, but more more importantly, probably for the listeners of this show. You know, if if you find this interesting, if you'd like to help, we're running a crowd investing campaign right now. And you can find a link to that on the top of my Twitter. So you know, just search for Trevor CLI on Twitter, and I've got the post pinned. Or if you're an accredited investor, and you want to invest like 25,000 or more. You can also reach out to me directly through my website, Trevor cli.com. I'm I'm very easy to find online. I'm super Google. So you know, feel free to reach out to me Twitter, Trevor play.com. Whatever. Yeah. And of course, if anyone has any questions, clarifications, that sort of thing before wanting to invest money? Yeah, more than happy to talk.
Unknown Speaker 30:18
That's great. That's great. Well, Trevor, thanks so much for coming on the show. I'll put some links down there in the show notes so people know where to find it.
Trevor Klee 30:24
All right. Thank you very much. Well, it was pleasure talking to you again. Absolutely.
Unknown Speaker 30:32
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Transcribed by https://otter.ai
114: Trevor Klee - Autoimmune Diseases, Drug Development and Cats