Chief Medical Officer Dr. Chris Galloway previews Diffusion’s Altitude Trial, the second in a trio of Oxygenation Trials that will collectively inform late phase programs and the clinical development plan for lead drug candidate TSC.
Lauren Ashburn: Welcome to Fueling Life, a podcast brought to you by, and all about, Diffusion Pharmaceuticals, an innovative biopharmaceutical company developing novel therapies that enhance the body’s ability to deliver oxygen where it is needed most. I’m your host, Lauren Ashburn.
Joining me is Dr. Chris Galloway, the Chief Medical Officer of Diffusion Pharmaceuticals. Dr. Galloway is an executive physician with diverse clinical and pharmaceutical industry experience. He joined the company in October 2020 and is overseeing the development strategy for Trans sodium crocetinate, or TSC. That’s Diffusion’s lead product.
TSC is being developed to enhance the diffusion of oxygen to tissue with low oxygen levels. This is commonly known as hypoxia, and it’s a serious complication of many intractable and difficult-to-treat medical conditions.
We’ve been talking with Dr. Galloway about three foundational, short-term clinical TSC studies. Collectively, they’re known as the oxygenation trials, and they use experimental models to evaluate dose-response, and the effects of TSC on oxygenation through several different lenses.
In this episode, we’re focusing on the second oxygenation trial known as the Altitude Trial.
Hi Chris, it’s a pleasure to speak with you again.
Dr. Chris Galloway: Thank you, Lauren. Thanks for having me.
Lauren Ashburn: In our last episode, we explored the TCOM trial, the first of three oxygenation trials. And today we’re going to talk about the Altitude Trial. When I hear “Altitude,” I think of mountain climbing. That’s not a coincidence, is it? Tell me about the design of this trial and what you’ll be studying.
Dr. Chris Galloway: This is a really interesting trial. Just as we leaned on the experts in the hyperbaric therapy community for TCOM, this area of hypoxia, or extreme exposures, we have engaged thought leaders nationally and internationally that do these studies in healthy volunteers. The unique challenge with TSC is to dissect this oxygenation enhancement while the other factors of oxygen delivery are somewhat controlled, meaning each patient in the trial has a healthy functioning heart, lungs, and are not anemic.
Lauren Ashburn: So you’ll actually be exposing people to simulated altitude conditions that induce hypoxia?
Dr. Chris Galloway: We will. Or I should say the investigational site will. These are extreme-exposure environments that have been tried over and over again for decades where basically healthy volunteers will be in a chamber, just like a hyperbaric, high pressure, but these have the capability of hypobaric, or decreasing pressure, not unlike when you scale up a mountain. And when you scale up a mountain, the partial pressure of oxygen also is less.
So at this simulated altitude, the healthy volunteers will hop on a bike that’s called an ergometer, or an exercise bike, and we’ll see how long they can ride while we measure their arterial oxygen content, which will be seeing how effective TSC is at improving oxygen uptake in the lungs. But then also how their performance is improved, which is measured by the VO2, or maximal oxygen consumption.
And this will be in a placebo-controlled trial where each volunteer acts as their own control. So on the same day, they’re going to do one simulated altitude exposure and exercise with a placebo given, and then have a rest and wash out, and then have another exposure the same day in a randomized sequence, and then have TSC. And what we’re going to do is compare the placebo exposures to the active, or TSC exposures, and see how TSC has enhanced oxygenation and also performance.
Lauren Ashburn: When are you going to start this trial and when will Diffusion be reporting results?
Dr. Chris Galloway: This trial startup is ongoing with our partners. This is a next-level-of complexity trial, which will be performed in an academic center. So academic clinical trials take longer to start up, but we’re on track to start this in quarter four of this year. And hopefully, with a robust enrollment, we’ll be able to have top-line data within one to two months after the last patient has been enrolled.
This is a randomized and blinded trial. So it means all along the way, the volunteer, the clinical investigator, and the site don’t know what each subject is getting. So you have to wait until all are enrolled before that database can be locked and then you can unblind the data.
Lauren Ashburn: What is the clinical relevance of the Altitude Trial? Are there specific diseases or medical conditions that relate to this study?
Dr. Chris Galloway: Well, the clinical relevance is a good question because, hey, you’re doing this in healthy volunteers. But VO2, or what is maximum oxygen consumption, is highly relevant clinically, particularly in complex cardiopulmonary surgeries. If you go into a surgery with an optimized VO2, or essentially your aerobic threshold, or intraoperative or even postoperative, your morbidity and mortality or your clinical outcome is improved. So potentially TSC, if it can optimize or improve VO2, that will translate clinically.
Now, the other aspect we’re going to look at in the Altitude Trial is also the arterial oxygen concentration. So when these volunteers are at an altitude, low oxygen environment and exercising, obviously every minute amount of oxygen is paramount to enhancing your performance. And if TSC can also demonstrate increased uptake of that low oxygen content in the environment, that will also be an endpoint we’re looking at in this trial.
Lauren Ashburn: How and why is the Altitude Trial important in framing the development strategy for TSC?
Dr. Chris Galloway: As part of this trilogy of studies, the Altitude [Trial] really encompasses this, again, oxygen continuum I speak of. If we can streamline more efficient uptake of oxygen in the lungs by TSC’s mechanism of action, and also at the end organ delivery by enhancing diffusion, you really are kind of removing some of the speed bumps, or areas of resistance, from oxygen uptake to delivery.
And so we believe we’re going to see this translate into an enhanced VO2, or increased ability for our mitochondria to use oxygen, but also increase in that uptake in the lungs when we’re in a stressed environment. And we’ll see that through the improvement in the arterial oxygen concentrations.
Lauren Ashburn: This has been so informative. Thank you so much and I look forward to talking to you in the future.
Dr. Chris Galloway: Thank you so much, Lauren.
Lauren Ashburn: Thanks for listening. Fueling Life is a podcast from Diffusion Pharmaceuticals. Stay tuned for our next episodes and follow us on Spotify or wherever you get your podcasts.