Dr. Chris Galloway, Chief Medical Officer of Diffusion, explains the TCOM Trial design, top-line results, and the relevancy of this first of three Oxygenation Trials that together will inform late-phase programs and clinical indications 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. Today, I’m speaking with Dr. Chris Galloway, the Chief Medical Officer of Diffusion Pharmaceuticals. An executive physician with diverse clinical and pharmaceutical industry experience, Dr. Galloway joined Diffusion Pharmaceuticals in October 2020. He oversees the development strategy for Trans sodium crocetinate, or TSC, the company’s lead product in development. It’s designed to enhance the diffusion of oxygen to hypoxic body tissue — that is, tissue with low oxygen levels. This is a serious complication of many intractable and difficult-to-treat medical conditions. In this podcast, we’ll begin exploring three short term clinical studies of TSC, known collectively as the oxygenation trials. These trials utilize experimental models to evaluate dose-response, and the effects of TSC on oxygenation through several different lenses. The first of these trials, called the TCOM trial, is our focus.
Welcome to the podcast, Chris.
Dr. Chris Galloway: Thanks for having me, Lauren.
Lauren Ashburn: Chris, let’s start with the basic question. The TCOM trial derives its name from the medical device used in the study. Tell us about this study.
Dr. Chris Galloway: Sure. So TCOM is a device we borrowed from the hyperbaric oxygen therapy world. Hyperbaric oxygen has been used for decades to enhance oxygen diffusion, by not only putting patients on supplemental oxygen, but putting them under high pressure to try and enhance diffusion to heal wounds, to heal amputations, heal after surgery — a multitude of indications. These oximeters measure how effective oxygen supplementation or oxygen therapy will be for those patients. So for the TCOM trial, we used those on healthy volunteers, enrolled 30 subjects, we had a placebo arm and we gave all of them a dose of TSC, which was randomized and blinded. And then, we basically used these transcutaneous oximeters to measure the change in oxygen at the tissue level on their leg, before and after they received TSC or their placebo.
Lauren Ashburn: The TCOM trial was completed ahead of schedule in March, 2021. And Diffusion reported a positive trend in the oxygenation, when the company announced results from the trial in June. Can you walk our listeners through what you learned?
Dr. Chris Galloway: Certainly. This trial was a huge success. We ran the trial at an outside commercial clinical research site. So I say that because that’s outside of an academic or an institution, where it often takes lots of time, lots of obstacles. And so, we brought in the national leaders in the hyperbaric oxygen therapy world, and these TCOM measuring devices. So we brought in thought leaders into the clinical research site that then had the expertise not only to enroll the patients, but then we had the experts in the field giving us these readings. And we were able to enroll it very quickly because of the high interest and demand for the study.
And what we learned from this, is not only is TSC effective at raising the oxygen tensions in the tissues, but it does so across a wide range of doses. The other information, which was paramount, which we learned from this study, not only did we add the builds to our safety database showing how safe TSC is, but we were also able to discretely map the pharmacokinetics, or the concentration of TSC in the bloodstream over time, after a dose, and how that correlates with the effect, or the oxygen change, or oxygen improvement. Those were huge gaps that we needed to fill in the clinical development program, and we feel this trial was very successful in demonstrating that.
Lauren Ashburn: How and why are the TCOM trial results important?
Dr. Chris Galloway: Not only are these TCOM results confirmatory to the robust safety of TSC, we are also able to align the pharmacokinetics or that concentration behavior in healthy volunteers, just like we did in our COVID trial, which we completed in Romania. TSC behaves very, very discreetly and linearly. It’s very reproducible. And what the results demonstrated, that if we could show a change in that TCOM measurement, and we determined a clinically relevant change is 10 millimeters of mercury, that’s the units these are measured in. If you can improve oxygenation in the tissues by greater than 10 millimeters of mercury, you have the potential to turn a non-healing wound into a healing wound, potentially a threatened limb of amputation to a non threatened limb, and a multitude of other clinical indications, which hyperbaric therapy is indicated for. And TSC now could potentially be an adjunct to enhance that oxygenation.
Lauren Ashburn: How does the TCOM trial relate to the other two oxygenation trials that Diffusion is running? Each is designed to investigate a different aspect of TSC’s mechanism of action. Is that correct?
Dr. Chris Galloway: Well, oxygen transport and delivery is a continuum. From uptake in our lungs, to distribution through our vasculature or circulatory system, to actually that end goal or end organ delivery at the cellular level, which then goes to the mitochondria. So each of these trials is designed to differentiate the effect of TSC at these different junctures of the journey: Uptake, distribution, and delivery. TCOM specifically more at the delivery endpoint, because that’s why we’re using the transcutaneous oximeters.
Lauren Ashburn: Can you speak to the clinical relevance of the TCOM trial? What light, if any, does the study shine on potential future indications for TSC?
Dr. Chris Galloway: Well, the TCOM trial, for sure, clarifies further our correct or optimal dosing, and how long that dose lasts. How long do we see that efficacy? This not only will inform our Altitude and ILD-DLCO dosing, as we get further down the line to learn and inform along these trials. But it’s paramount we get this right, because this is truly foundational for TSC as a whole in our clinical development program, because TSC is so unique [for] any therapeutic area where hypoxia is a problem, and that could be in adults, it could be in kids, it can be in the acute setting, the chronic outpatient setting, in-patient. This is why we have to get this right, because TSC has the potential for a large [number of] expansive indications, where it could be an add-on as part of multimodal therapy to improve patient outcomes.
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.