What is Elysium Therapeutics' O2P?

ACT: Could you tell our audience a bit about O2P and its development journey?

Greg Sturmer: O2P, another acronym. We're an acronym rich industry. O2P stands for oral overdose protection. Since you asked to talk about the development journey, I'll go back towards the beginning and early on in our journey. We took, what essentially at the time was our ideas, we didn't have much data. We had ideas, we understood what the underlying drivers of the opioid crisis were. It's just far too easy to abuse existing opioids, by simply swallowing too many pills. That's what's happening most of the time. And there just aren't barriers to abuse. There are far too many pills out there. A lot of diversion occurs, 80% of abusers get their pills from friends or family. So we understood what these underlying drivers were. And later in the company's life, of course, the fentanyl crisis began. And we immediately spotted the weaknesses of the existing rescue agents. So early in our journey, we took our ideas to the National Institutes of Health, specifically the National Institute of Drug Abuse and we presented our ideas to combat the opioid crisis. And they were quite impressed. And we were successful over the years and received about $16 million in grant support. To develop our technologies, we also received $3 million from the state of Ohio, through its Ohio Third Frontier program, because Ohio is a state that's been hit hard by the opioid crisis. As I mentioned before, we're developing smart products that are safer medicines that alleviate risks and trauma, to fulfill a mission that we set for Elysium. And that's to reduce suffering. From opioid use disorder, pain, and fatal overdose. There's just far too much suffering. I could show you graphics that show all the fatalities and a number of people suffering from opioid use disorder. And the statistics don't tell the whole story. But our SMART opioids for pain, led by O2P, again, oral overdose protection, or protected hydrocodone and this OTP hydrocodone is designed to mitigate the major risks associated with existing prescription opioids. And importantly, to do so without sacrificing the superior analgesic efficacy of existing opioids, especially when you compare those to currently marketed non-opioid alternatives and those in development.

So just to put things in perspective, because I think there's been a lot of history in the opioid space and other companies who have tried to make what they refer to as abuse deterrent formulations. ADFs, that's the acronym that they would use. And most of these past efforts were ADF efforts. And they're primarily designed to thwart tampering, and non-oral routes of abuse. And as I mentioned before, 90% of the time, it's just swallowing too many pills. Well, because ADF approaches rely on physics, rather than chemistry there's limitations to what you can do with that formulation. You're basically using formulation techniques. And I guess Tom (Tom Jenkins, co-founder & CSO, Elysium Therapeutics) and I affectionately refer to these sometimes as “gums” and “goos;” putting the opioid in some sort of matrix that makes it difficult to inhale or inject. Well, unfortunately, these physics approaches are easily defeated. For example, when Tom got his hands on the new version of OxyContin when it came out years ago I think that took all of minutes to separate oxycodone from their formulation matrix. So, they didn't have a high barrier to tampering. And important: they had no way using physics to protect against the overdose, which is the biggest problem.

In stark contrast, bringing it around back to our smart opioids. What we're doing is leveraging a technology that Dr. Tom Jenkins invented using chemistry. Tom's a PhD, synthetic organic chemist at Stanford, and has this knack for coming up with elegant solutions to just crushing problems with existing medications. And Tom decided earlier, when he looked at the problem, he said, you know what? We can leverage the body's natural digestive process, and create a new class of opioids, using existing opioids as the active and we can control exposure. Because what's important to understand is when you're fighting an epidemic, whether that epidemic is obesity, or it's some bacterial effect, infection spreading, or virus, what's the number one thing you need to do? You need to control exposure. And so Tom set out to create this O2P technology that can control exposure, without taking away the super efficacy that opioids have. So he created this bifunctional prodrug. And the way it works is we basically fool the body into thinking this new opioid is food. And that's important because we rely on a digestive enzyme in the upper GI to activate the opioid. Okay, so that what does that mean? That means if somebody were to inject it, or to inhale it, they're going to get no joy, because there's nothing circulating. It’s the digestive enzymes just in the upper GI, so there's nothing to activate the opioid. What he also did in the same molecular construct is added a trypsin inhibitor subunit. So trypsin is this digestive enzyme that I referred to. And if you're good and you're only taking one to two pills, this trypsin inhibitor is not going to affect the release of hydrocodone that's going to provide you pain relief, but if you take too much, then there's going to be enough trypsin inhibitor to start shutting down that process to progressively shut it down. And so what we have here is really a balanced solution to reduce exposure on the one hand without compromising patient care.