Finding a better, longer-lasting fix in opioid overdose

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The BioWorld Insider podcast

 

Lynn

This is the BioWorld Insider podcast. I’m Lynn Yoffee, BioWorld’s publisher.

The opioid crisis may not be making as many headlines these days, but it’s still very much a crisis. One company, Elysium Therapeutics, has come up with a longer lasting rescue agent for opioid overdoses that’s designed to evade the problem of rebound that current users face.

This happens when the standard reverser wears off and the opioid stays active in the body, often with fatal results. With us today is Elysium CEO Greg Sturmer, who will tell us about what his company calls the Synthetic Opioid Overdose Prevention and Reversal Program. It’s an improvement over Narcan, the approved opioid antagonist, and another nasal spray for overdose called OPVE.

Welcome, Greg.

 

Greg Sturmer

Thank you, Lynn. It’s great to be here and I appreciate BioWorld continuing to shine light on the overdose crisis. Even if the headlines have cooled down, the reality on the ground hasn’t. Opioid overdose deaths are still about six times what they were in 1999 despite recent declines.

 

Lynn

And we’re so glad that you’re working on this new solution. Greg is here today to chat with Randy Osborne, a staff writer who’s been tracking the company’s progress. Randy, over to you.

 

Randy

Hey, Greg, and thank you again for talking with us. It’s pleasure to touch base with you again, as we did for the story that I did in BioWorld. But certainly the story was, I think, pretty comprehensive. But I know that at Elysium, you’re dealing in an especially innovative way with the fentanyl overdose problem. Can you just run through the technology, which I know you call SOOPAR, using the acronym?

 

for us its origin and how it’s better than what’s available now.

 

Greg Sturmer (02:49.198)

Sure. Thank you, Randy. So, SOOPAR came from recognizing, you know, a simple but devastating truth, and that is fentanyl and nitazines, which can be even more potent than fentanyl, have changed the game. And current rescue tools like Narcan and OV just aren’t enough.

 

Narcan was built for heroin and Oxycontin era overdoses and fentanyl and nitazines are far more potent and when taken orally, far longer acting than current rescue agents. Statistics show that upwards of 45 % of individuals who overdose on oral fentanyl and are rescued with existing rescue agents experience that rebound that Lin referred to, also referred to as re-narcotization. And that essentially represents a reassertion of respiratory depressive effects. And that increases the risk of fatality and hypoxic brain injury.

 

So what’s SOOPAR or the synthetic opioid overdose prevention and reversal program is all about, it’s a next generation, single dose, long acting, intramuscular naloxone, think like an EpiPen and it’s built for this synthetic opioid era.

 

It not only works quickly, but crucially maintains protective levels for many hours, preventing the re-narcotization we see so often today.

 

Randy

Yeah, and there seem to be a lot of not only medical, pharmaceutical, chemical type solutions to be sought here, but there’s also social and legal issues tangled up in the whole crisis. You and I talked about this once before, how addicts simply want to keep using, and the family members want them to stop.

 

Greg Sturmer

Yup.

 

Randy

And paramedics want to help but can’t in certain states. They can’t force the patient to go to the hospital. So they stay at home and then the reverser wears off and then they die. And you and I also talked about how what the SOOPAR technology does might help with actually getting these people to recover over time.

 

Greg Sturmer

Yeah, no, absolutely. I mean, what our product does is not only provide a SOOPARior rescue, but it provides a window of opportunity for friends, family, to clinicians to gather around that individual and help them on a road to recovery. Because the reality is, and studies have shown, that if you can intervene after an opioid-dependent person has overdosed, if you can intervene at that rescue point, that’s going to be their best chance at survival.

 

Randy

Well, another thing that you and I have discussed in the past a little bit is that in this illegal drug world, it seems like the cartels are constantly reformulating and changing the appearance of drugs, coming up with an oral versus an injected fentanyl, all that complicated the overdose situation a lot. Is there a way that the SOOPAR approach deals with that with like the pharmacokinetics of oral versions versus the injected? Or is that, are we pretty much talking about the same solution?

 

Greg Sturmer

Yeah, absolutely. This is the same solution. you know, as you pointed out, illicit drug markets evolve constantly.

New analogs, new routes, new pill forms. Right now what’s happening in the illicit market is a bit of a shift towards nitazines from fentanyl with a lot more, you know, focus of the enforcement on precursors to making fentanyl, you know, the illicit drug makers are kind of shifting over to a new and sadly more deadly version of opioids and nitazines. The strength of SOOPAR is that its protective duration isn’t tied to how these synthetic opioids are taken, you know, whether their exposure is fast or slow, short or long,

SOOPAR maintains that antagonist coverage long enough to neutralize the opioids activity and as I mentioned before, provide this bridge to medically assisted therapy, increasing that individual’s potential for long-term survival. Fentanyl, as we’ve talked about before, puts an individual at risk for six to eight hours, and that’s why these sad situations come up where a friend, family member will find a loved one who’s overdosed, they’ll give them a rescue agent. It appears everything is fine and everybody kind of goes back to bed or whatever and they wake up in the morning and find that loved one has passed. So you know our current rescue agents just aren’t matching up to what the illicit markets are delivering now.

 

Randy

It must be a challenge to stay ahead of that too. at least you have a chemical agent that works. Can you talk about its relationship to Narcan or OPVI? Is it a similar compound?

 

Greg Sturmer

It actually is, and Elysium’s co-founder, Dr. Tom Jenkins, who’s a PhD, synthetic organic chemist at a Stanford, just has a brilliant mind and has a way of taking an existing drug. And in this case, we took naloxone and just made some molecular tweaks to it. One tweak actually improved the onset of action, actually increasing the speed at which the rescue can occur.

 

And a second tweak extended the duration of action dramatically. So we’ve seen in our in vivo work, 24 hours, even up to 48 hours in a version of this product that could be used by saving military and first responders prophylactically to protect them from ever overdosing if they’re in some sort of theater of war where weaponized synthetic opioids are an issue.

 

Randy

Mm-hmm. And we talked about this too, and it was kind of scary. I remember you mentioning that you were surprised that this hasn’t been used as a military weapon because it’s so easy to aerosolize.

 

Greg Sturmer

Yeah, sadly the case, I mean it has been weaponized. There was a case back, I think it was somewhere around 2012, 2013. There was a takeover of a theater with a bunch of civilians and they tried to use a synthetic opioid to actually rescue the people by using it to knock out those that were holding them hostage. But unfortunately, they just overestimated the power of these synthetic opioids and many lives were lost. And what SOOPAR offers is something that the military just doesn’t have currently.

The longest protection available to them is about three hours by taking a significantly high dose of Naloxone. And what we’ve done is, you know, modified Naloxone. So at the end, what’s being delivered to the individual and what’s providing the protection is known. It’s Naloxone. It’s just that the way Tom’s made this elegant change to the molecular structure provides that difference in onset time and duration of action.

 

Randy

Hmm, yeah. and let’s just say apart from the military, I touched on this a little bit earlier, but I’d like you to go into it somewhat more. The social aspect of this where a paramedic comes to the house and it’s got an overdose in front of him, administers an arcane and then leaves and then sometimes there is a tragedy later. Well, I mean, let’s say he comes to the house with a SOOPAR product and gives it to the person. What happens after that? Is there a follow-up? don’t know how big of a hitch might that be with the compound that you would introduce.

 

Greg Sturmer

Yeah, what I mean, what you’re talking about is that this crisis is complex. It’s not just a biochemical matter. There are social, emotional, legal aspects to it. paramedics can’t force transport. So family members that are there, if they’re there with their loved one, feel a bit powerless and kind of like, It’s all up to them.

And there are countless cases where people are rescued. They may even be transported to the emergency room. But then they decide they want to get out of the hospital. And then they’re found the next morning on some street corner in the past. So what SOOPAR does is it changes the dynamic. Someone stays stable for many hours, what you’re doing is you’re disrupting that revive, renarchetize, collapse cycle. That stability creates opportunity. That’s that critical window where families and clinicians can talk to the overdose victim about treatment or just simply getting the person into a safer environment. SOOPAR doesn’t treat the addiction, but it provides that window in which treatment can begin, kind of a bridge to that medically assisted therapy.

 

Randy

Sort of like an intervention with an alcoholic. Well, I know that the NIH became interested in the Elysium approach almost immediately after the company was founded. Is the government still helping you along or are you pretty much on your way now without such help?

 

Greg Sturmer

Yeah, absolutely. Yeah, we’re pretty much, you know, at this point without the NIH funding, what the NIH became interested in our work early on was our work in our O2P program. That’s our oral overdose protection program. And that program focused on protecting against overdose by redesigning prescription opioids. And what we’ve shown in our human studies is we can dramatically reduce the risk of oral overdose without removing needed pain relief options.

What SOOPAR does is addresses the other side of the crisis. So those who progressed to elicit opioids use or inadvertently take illicit fentanyl.

O2P, while it helps protect against overdoses from happening with a pharmaceutical grade prescription opioid, SOOPAR is designed really to rescue an individual from any opioid, whether the opioid came from a prescription or illicit source.

And we think the way we look at it, it’s kind of a unified strategy, protect on the front end hopefully reducing the next generation of opioid use disorder sufferers that kind of begin after say a know high school sports injury or something like that and then provide back-end support where we could not only rescue but protect and provide this bridge to you know long-term therapy.

 

Randy

It does seem like there are two really distinct problems here where, as you said, someone with a sports injury or some other kind of pain situation that they need medication for, they find that they like the opioid and want to keep taking it when they don’t need it anymore. But then there was also these subjects that you mentioned once before who don’t even know they’re getting fentanyl. They’re buying street drugs and there’s fentanyl…throughout this, what they thought was an amphetamine and all of a sudden they’re in an overdose state. How common is that?

 

Greg Sturmer

I mean, I think that anybody who is buying an illicit drug needs to assume that there’s fentanyl laced in it. So whether you think you’re buying a knockoff ADHD drug or you’re buying cocaine, whatever it happens to be, the likelihood of it having fentanyl and nowadays, know, nitazines, which are even more potent and longer acting, is very high. When the cartels shifted to, you know, oral fentanyl they made very colorful tablets, you know, that would attract younger individuals into taking these colorful pills at parties or whatever, but sadly, you know when the DEA tested these tablets about 60 % of the time they had a fatal amount a lethal dose, you know, in those tablets.

 

Randy

That’s just stunning. think it’s so sad for so many people. Let’s talk about something else that’s really important to all of our drug developers, which is the regulatory path. seems like, given that Narcan is out there and you’ve kind of got an active ingredient that’s proven, that it should be somewhat smoother than maybe others find. Could you discuss the regulatory situation a little bit?

 

Greg Sturmer

Yeah, I truly feel, you know, blessed here. We had a meeting with the FDA in August and we really felt supported. The FDA recognizes the urgency around fentanyl and nitazines and recognize that current rescue agents have shortcomings.

 

So we’ve confirmed that SOOPAR will follow what’s called a 505b2 development path, which basically means that, as you pointed out, Lot is already known about Naloxone, which ultimately is the delivered active from our approach. So they clearly recognize the need. They conveyed their commitment to support us through the development process.

 

Their feedback was really quite helpful for guiding not only the efficient development of SOOPAR for, you know, as a rescue agent for emergency use, but also this idea of having a preventative agent or a protective agent for prophylactic use. So, you know, if you’re in the military, a first responder or God forbid, you know, there is a mass casualty – in the event that civilians could have access to something that would protect them for a day or two.

So we’ll take advantage of all the well-understood mechanism of naloxone, and the agent seems to be focusing where they should on the innovation. having us prove the faster onset and the longer duration and the safety of the elegant modification that Tom made, which actually, interestingly enough, yields naloxone, which as we know is well known, and the other metabolite is endogenous. So we also know that that’ll be safe. So we think an efficient regulatory pathway.

 

Randy

Yeah, it sounds like it’s not going to be the conventional phase one, phase two, phase three, but what shape will it take or do you know that yet?

 

Greg Sturmer

I think we have a pretty good idea. mean, our expectation is, you know, we’ve already demonstrated in vivo proof of concept that shows, you know, not only that targeted longer duration of action, but you know, quite frankly, a bit of a bonus, which we hadn’t expected was a more rapid onset of action than Narcan and even intramuscular injected naloxone. So what we can do having that data is we’re right now manufacturing the material we need for IND enabling studies. We’ll conduct those animal and in vitro studies that are necessary before going into humans in 2026. And then in 2027, we believe we can complete all the necessary human studies, which when you’re dealing with a rescue agent, an acute use product for a life threatening situation, what we essentially need to do is just prove or show the agency what RPK profile, what is the exposure of naloxone using SOOPAR versus, you know, the existing naloxone that exists today. And the agency actually used computer models to kind of figure out what the real world effect of our product will be.

So we’re really excited. We think we have the potential for accelerated review, including the commissioners national priority voucher, which could dramatically decrease the time for review. And we hope to have this on the market in 2028.

 

Randy

That computer modeling setup that the FDA has is pretty well established, isn’t it? It’s been used to other drugs and other companies.

 

Greg Sturmer

Yeah, that’s what OPV used. So Opiant when they took OPV for approval just in 2023, basically provided data that showed what the PK or the exposure to nalmothene was with their product.

And the agency is able to use this computer model to look at things like, you know, how fast will the onset be? What is the duration of effect expected to be? And another important aspect that is not often talked about is the harm reduction aspect of these rescue agents.

So they look at, you know, the potential for triggering severe withdrawal, which can be problematic, not only for the individual rescued, but the rescuers as well. So yeah, this model is very effective.

 

Randy

Well, yeah, well, given that, given the computer modeling, and I would think some pretty thorny ethical issues about doing trials with an agent like this on actual patients, I mean, what do do? Give them an overdose and then hope you can fix it? What will the trials look like? Will it all be in test tubes or in computer modeling, or will you be dealing with actual patients?

 

Greg Sturmer

No, we’ll do actual testing in subjects, but here in the US, you know, what those studies would look like are traditional kind of PK studies. So think, you know, sad, mad, or single ascending dose, multiple ascending dose type studies. Because you know, we do need to show that this is a safe, you know, compound for human use. And, but then what the agency needs for that computer model, again, is that PK profile. They just need to know what is the exposure to naloxone, you know, how quickly does it reach a level that know can rescue somebody from whether it’s a heroin, oxycodone, fentanyl or a nitazine overdose and how long will it last? the studies will focus on safety and this PK profile.

We are considering doing some studies abroad. There’s a doctor who’s done studies in the Netherlands where they actually do induce like a fentanyl overdose in a very well controlled environment, so the patient or the subject is very well cared for. But what you can do in that environment is not only look at PK, but you can look at PD effects.

So, you know, in a real world situation, what is the onset time, the duration, and importantly, that harm reduction factor that hopefully reducing the risk of severe withdrawal. And we think we have a shot at reducing that risk because what SOOPAR does, it’s almost like…

you know, hooking up a person to an IV because we achieve an infusion like profile by a single injection. So if we can just target a level that, you know, can rescue somebody but not overshoot it so much that the severity of withdrawal is high, that’ll be well received.

 

Randy

Yeah. Well, I know it’s early days, but it seems like the development will move pretty quickly once you get going. And I would think, maybe this is incorrect, but I would think at least with this computer modeling, you could reduce the size of the trials in human subjects. have you, I know you have looked at that now, and what do think that will resemble once you get to that stage?

 

Greg Sturmer

Yeah, think, you know, while we haven’t, you know, the agency wasn’t prepared to give us a specific number, you know, of exposures that we’ll need to achieve in subjects based on, you know, other product approvals in this space and in other space like acute use products for, non-life threatening indications.

The exposures are typically around 500 total subjects and some with kind of a 505b2 path where a lot is known about the delivered product. That number could be as low as say 350 or so. So we think we’re somewhere in that range. you know, we believe we can efficiently get to those numbers in a short period of time..

 

Randy

Yeah. Well, it’s good that the agency recognizes the need. And I wanted to talk a little bit about that too, because it seems to have gone out of the public eye to a great degree. And I think there is some conception that we have a handle on it now. But I remember you telling me in the interview that we did not too long ago that, well, a lot of the people have died. So yeah, I guess it’s not a problem for them anymore. But could you just talk about what the landscape looks like now?

 

Greg Sturmer

Yeah, I mean, I mean, that’s the sad truth in the whole situation. I mean, if you look at the statistics, you know, it sounds great to say that between twenty twenty four, twenty twenty three, you know, there’s a decline of more than 20 percent in deaths caused by fentanyl.

But if you peel back the onion a bit, one, that’s still six times what the level of deaths, the fatalities were in 1999.

There’s no statistics that are really gathered on this hypoxic brain injury issue. Tom and I, you know, because of the…

you know, we want to make sure that we understand what’s going on on the front lines. We spent several months just on the road talking to stakeholders and, you know, so we’ve sat in the living room with a mother and father and their son who’s now, you know, a quadriplegic, you know, and requiring 24 seven healthcare because their son experienced an overdose and while quote rescued, you know, was left with hypoxic brain injury.

 

So the situation is still, you know, bleak and there are far too many people, you know, continue to die. You have this risk of synthetic opioids being weaponized. That’s a significant threat to not only our military, but to civilians. And the existing countermeasures that we have, whether it’s Narcan or OV, just aren’t up to that challenge. And so that’s why a new rescue agent that lasts at least as long as that danger lasts, that’s what we need and that’s what SOOPAR can provide.

 

Randy

Yeah. Well, let’s look way down the road a bit. just, and maybe you won’t be able to answer this, but I’m curious about since you have a Narcan-like product, would the goal eventually to have that be an over-the-counter product that’s available to people who probably recreationally use drugs and put their lives in danger? Is that, or is that a crazy thing to imagine?

 

Greg Sturmer

Yeah, well, I don’t think anything should be out of, you know, off the table. You know, illicit drugs are a reality. They will continue to be a reality no matter how much we’re able to do to try to curtail the flow of illicit drugs. So, our number one responsibility at Elysium right now is to get this product approved, show it’s safe, show it’s effective.

 

And then we’ll seek a commercial partner that could do the things that you’re talking about. And that is ensuring that this product gets in the right hands, you know, whether that’s first responders, military, or civilians, and what’s the most efficient way to get this product into civilians’ hands.

 

Randy

Well, the nitty-gritty I always have to ask about is funding and how well funded you are and how far you can get on what you have and how easy or difficult is it for you to go out to the markets and get some more money for a project like this?

 

Greg Sturmer

Yeah, well we again truly feel blessed in that respect. We just completed a significant round of financing, raising over five and a half million dollars which is more than sufficient to take us into getting our IND approved and starting down the road towards human proof of concept.

So, you know, blessed to have a number of investors, largely, you know, wealthy individuals, many of which have been touched in some way by this crisis. And their support has been tremendous.

 

Randy

Yeah, so it sounds like your budget is nothing like what we’re used to hearing from regular biotech and pharma companies in terms of how much it’s going to take for them to get to market, even if they have an active ingredient that’s already been sort of blessed regulatorily.

 

Greg Sturmer

Yeah, no, mean this product, I mean for two indications, know, we believe it could be in the range of, you know.

$25, $30 million in total, you know, with all the CMC device and clinical and non-clinical work to get it to the marketplace. So it is unusual. It has a new molecular entity into a market that is, you know, has great need.

So we’re also seeing interest from potential strategic partners as well, and we’re grateful for that interest. So again, it’s up to us to prove safety and efficacy, and we want to be on the market in about that 2028 timeframe. We can save a lot of lives.

 

Randy

Well, I’m glad you mentioned the device again. Earlier you compared it to an EpiPen type of situation. How will this be given and how complicated is the device aspect of this?

 

Greg Sturmer

Yeah, we’re, mean, our goal is to have a very simple to use will be an intramuscular injection. So very much like an EpiPen, which is, you know, administered by a lay person. When someone has anaphylactic response to whatever they might be highly allergic to, whether that’s a peanut allergy or I know a someone who’s an allergy to garlic.

 

Randy

That would be tragic, it?

 

Greg Sturmer

And yeah, so yes, that would be tragic! Anyhow….

We want something very, very simple to use. And there are devices out there that are approved for emergency use, like the EpiPen. That’s very, very straightforward. importantly, what people don’t realize is that while Narcan has become kind of the standard of care currently, that when you take a drug like naloxone and you deliver it intranasally instead of intramuscularly, you change its PK profile. So it actually slows down the onset of action. you know, there’s investigators out there who’ve done studies head to head that show, you know, you try to rescue somebody with, say a product like Zimhi, which is intramuscular delivery of naloxone, you get a much faster onset of action, much more rapid rescue.

Whereas with Narcan, you know, even after three doses of Narcan, takes several minutes longer for a person to return to that baseline respiration. you know, in a world where, as Tom likes to say, my co-founder, brilliance behind our technology, he likes to say, time is, time is brain and, you know, you got to get the oxygen back to the brain as quickly as possible.

 

Randy

Yeah. Well, we’ve ranged pretty widely in our discussion so far and touched on a lot of different aspects of this. Is there anything important that we haven’t probed that you’d like to talk about? Something that’s an elephant in the room that I’ve missed?

 

Greg Sturmer

Gosh, I think you’ve done an outstanding job, Randy, but I think I, you know, just a couple thoughts maybe. You know, first, fentanyl and nitazines have changed the rules, and you know, but what they haven’t done is they haven’t erased hope.

 

And we shouldn’t accept re-narcotization as unavoidable, given the significant increased risk of fatality and hypoxic brain injury. And we think that SOOPAR is the answer. And a lot of people on the front lines believe that to be the case as well.

 

You know, second, you know, a single long acting rescue dose not only can keep somebody alive, but give that window of time to reconnect with the family, consider treatment, you know, simply make it to tomorrow. You know, after all, you know, survival is the first step and it’s essential step before recovery.

 

And then finally, just thank you, thank you, thank you. We’re truly grateful for BioWorld continuing to shine light on this devastating crisis. And we are also grateful, as I mentioned before, to our investors who support our life-saving mission.

 

Randy

Yeah, sure a lot of people thankful for the work that you’re doing too. There’s a of ways to make money in the world, but they don’t all do the good that looks like you’re on the road to doing. And I think that’s all I had to ask you about unless Lynn, do you have any questions you’d like to put in?

 

Lynn

That was an extremely thorough overview and we certainly look forward to tracking progress over the next year or two. Greg, thank you so much for joining us today.

 

Greg Sturmer

Thank you. Thank you, Lynn.

 

Lynn

That’s our show for today. As always, BioWorld will continue to keep you informed of all the most important scientific, clinical, regulatory, business updates.

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