Patient Safety Through Overdose Protection With Elysium Therapeutics' Greg Sturmer

Drug overdoses can result both from knowingly risky behavior, such as opioid use disorder, and from unwitting patient acts of over-consumption. In this episode of Sit and Deliver, Greg Sturmer, co-founder and CEO of biopharmaceutical company Elysium Therapeutics, talks with Sit and Deliver host Tom von Gunden about ways to add overdose inhibitors to oral medications prone to abuse or misuse.

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Episode Transcript

Tom von Gunden, Chief Editor, Drug Delivery Leader:

Welcome to another episode of Sit and Deliver, the series that brings timely insights from leading thinkers in drug delivery. My name is Tom von Gunden, Chief Editor of Drug Delivery Leader and your host for this series. Today I am joined by Greg Sturmer, co-founder and CEO at Elysium Therapeutics, a biopharmaceutical company focused on patient safety, specifically in the area of opioid delivery.

Welcome, Greg.

Greg Sturmer, CEO, Elysium Therapeutics:

Thank you for having me, Tom. Glad to be here.

Let's start at a high level. We'll talk specifically about what you're working on at Elysium in the area of opioids. But first, I know you have a significant passion for and commitment to patient safety. Can you start by talking about why that's of importance?

Absolutely. I think that the FDA does an incredible job of requiring pharma companies to test the safety of their drugs through the approval process. But when it comes to safety standards associated with super therapeutic doses, there aren't really such standards. The question is, what happens if someone takes more than they're supposed to? There are numerous medications with warnings associated with overdose, but no one had developed a molecular delivery system or a technology to protect against oral overdose until Dr. Tom Jenkins, my co-founder and the Chief Scientific Officer of Elysium, invented the technology.

Thanks for that overview. Let’s get into the specifics of what you're working on at Elysium in terms of opioids. Can you talk about translating the patient safety focus into what you're working on there?

When you look at patient safety when it comes to the opioid space, you have to not only look at the patients themselves, but also others that can be impacted. Those are the people that suffer from opioid use disorder [OUD] or naive users that may progress to OUD. The concerns we had when we looked into this area were the significant number of lives lost as a result of overdose. Prescription opioids alone have a fatality rate of about 17,000 a year. Opioids are a gateway to illicit drugs. Now, with the devastation of illicit fentanyl killing some 70,000, we've seen a pendulum swing away from patient care, which results in the negative consequences of undertreated pain.

We set out to create a solution that balanced the needs of both groups. One that provided unmatched efficacy for acute, moderate-to-severe pain relief, but at the same time, significantly reduced the inherent risks of existing opioids, which are related to misuse, abuse, diversion, and fatal overdose. The result is O2P technology, which stands for Oral Overdose Protection.

Tell us about the route of administration and the mechanism of action and what it's meant to deliver to patients.

The best way to think about the O2P technology is as a molecular delivery system. In the past, most people, when they think about drug delivery, tend to think about formulations or devices that can be used. Tom is a PhD synthetic organic chemist. We’re leveraging chemistry because we can create bigger barriers to abuse. We can also create product profiles that you can't create with formulations, specifically to protect against oral overdose. Tom created this molecular delivery system that attaches to an existing drug.

We are first focused on the opioids in the pain space and OUD space because of the devastation of the opioid crisis. With this delivery system, we attach the drug, it's basically inactive, and we've fooled the body into thinking this molecular delivery system is food. That’s important because we needed a trigger in the body to activate the known drug. In the first use, we're using hydrocodone. When taken orally, the drug interacts with trypsin, a digestive enzyme. That interaction pulls a trigger at a molecular level that releases the opioid. What Tom embedded in this same construct is a trypsin inhibitor. If someone takes a higher dose or more tablets than they're supposed to, we can shut down that trigger mechanism so that not all of that opioid is delivered. In our human study, we went all the way up to a 16-pill dose, which would have been fatal for a generic hydrocodone, and we reduced exposure significantly, by 50% or more.

That’s great to hear. As you think ahead about other areas that your company might focus on with this technology, are there additional therapeutic areas or patient needs outside of the opioid space that this work might be applicable for?

Absolutely. There are numerous medications that have what's referred to as a narrow therapeutic index, which are very effective within this narrow range. If you stray outside of that range in a super therapeutic dose, it could lead to an adverse event. There are certainly opportunities to extend the technology with an oral medication. An obvious one would be drugs for ADHD, because it’s also an area of abuse and they're amphetamines essentially. We can apply that same technology. There are other drugs, outside of drugs of abuse, where somebody, if they accidentally took too many, could get themselves in trouble.

Is there anything on the horizon as far as additional advancements or innovations that could alleviate challenges or barriers around addressing these therapeutic needs and/or the patient safety component?

There are several opportunities in the drug delivery approaches that we're following. I previously mentioned the fentanyl crisis resulting in over 70,000 fatalities a year. We currently don't have a rescue agent that is designed to tackle the problem of oral fentanyl overdose. When someone takes fentanyl orally, it changes from an IV situation where it would be fast onset, fast offset to a slow onset, very slow offset drug. This means an individual could be in the state of respiratory depression or at risk for respiratory depression for hours, and existing agents like Narcan® or Opvee® weren't designed for this long duration.

We've developed a drug delivery approach in this case that would be delivered like an EpiPen®, basically a single injection to outlast that danger zone that fentanyl has. The headline news for fentanyl overdoses are the devastating fatalities, but for many that survive, they're left with traumatic brain injuries. By having a rescue agent specifically designed to address oral fentanyl overdose or other synthetic opioids, we're going to dramatically reduce the risk of traumatic brain injuries and fatalities.

Beyond the areas that we're already looking at, we see opportunities for molecular drug delivery systems that can address such issues as drug-drug interaction. Frequently, if you take a drug by itself, it's fine, safe, and effective. But if you mistakenly take it with something else, it can create this serious adverse event. We see opportunities for using these molecular delivery systems to sort that issue out as well.

That all sounds extremely promising. Greg, I want to thank you for your time and sharing your perspective with the audience here at Drug Delivery Leader for another episode of Sit and Deliver. That's a wrap.