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2026.09.28 | TB | Pharma | Latigo LTG-001 Non-Opioid Pain

原标题：Latigo Biotherapeutics – LTG-001 Deep Dive & Outlook for Non-opioid Pain Medications

#pharma

Third Bridge · 2026-09-28

Analyst-led • 17 Sep 2026

Companies: LTGO US, VRTX US

Sandra Sacks (SS) Pain physician at University of California Los Angeles (UCLA)

Will Coupe (WC) — Third Bridge Sector Analyst

Agenda

Key Insights

Introduction

WC [00:00:03]: Welcome to Third Bridge's Interview entitled Latigo Biotherapeutics – LTG-001 Deep Dive & Outlook for Non-opioid Pain Medications. I'm Will Coupe, and I'll be facilitating today's Interview with Dr Sandra Sacks, Pain Medicine Physician at UCLA Health, in addition to other roles and responsibilities.

Dr Sacks, before we start today's Interview, please state I agree or I disagree with the following statement: You understand the definition of material non-public information and agree not to disclose any such information, or any other information which is confidential, during this Interview.

SS [00:00:39]: I agree.

WC [00:00:41]: Could you please begin with a brief introduction to your background?

SS [00:00:46]: My background is in anaesthesiology and then I did a pain fellowship. I primarily see both inpatients and outpatients, occasionally still do OR, but not as much. My primary role is a pain management physician, seeing both acute patients on the inpatient side, but also manage the outpatient chronic pain patient population as well.

Questions

[00:01:20] How many patients with moderate-to-severe acute pain are you seeing in the inpatient setting today? How are you using the various approved options to treat them?

SS [00:01:37]: In a typical day, like today, I see about 20 patients. In general, as a pain specialist, everybody that I'm seeing is moderate-to-severe pain, very rarely, am I seeing patients with mild pain. If they have mild pain, they're usually not seeing a pain specialist. It's something that their primary doc can handle. In terms of medications that I'm using to manage these patients, all of these patients are on some sort of prescribed medication. I would say that the vast majority are usually on some sort of combination of NSAIDs, muscle relaxants, gabapentin or Lyrica, a handful of them are on opioids. Usually for acute pain setting, we really try to limit it for short-term use only. Ketamine, even fewer. There's a couple of different ways that ketamine is used, but it's all out of pocket and compounded, so it's cost-prohibitive in most of our patients. Then Journavx has been up and coming over this past year. It's usually used as a one-time thing. If I'm seeing patients in clinic and they were prescribed for postop by their surgeon already, then I'm not going to represcribe it. If I'm seeing them pretty short afterwards, shortly afterwards, if it's something that they haven't tried and they're still having a lot of pain, it might be something that I recommend that they try.

[00:03:17] How would you compare the inpatient and outpatient populations you're seeing? I understand the latter is a chronic population, but how much overlap is there with the various treatments? Could you quantify that patient population you're seeing?

SS [00:03:36]: Yes, so there is a lot of overlap with medications. I would say that my chronic pain patients often are… I try to clean up their medications because I don't want people long term to be on five or six different classes of medications, and definitely, if they're not getting better. The doses that they might be on might be higher because it's chronic medication for them. I would say that often, a lot of these chronic pain population patients are ones that I've inherited over the years, and they've been on opioid therapy for decades. There is a higher population of patients managed with opioids than acute pain.

[00:04:29] Thinking about patients that are on Journavx [suzetrigine], could you help me understand what the various lines of treatment look like leading up to a patient being prescribed Journavx? Is it a situation where maybe they've been on NSAIDs [nonsteroidal anti-inflammatory drugs], ketamine or other options and then they're prescribed Journavx? Is it more of a go-to off the bat? Where does it sit within the algorithm?

SS [00:05:09]: I would say when it first came out last year, it was more of a, "We don't really know how this is going to perform, let's use it if other things haven't worked." I've definitely seen it move up in the algorithm now. In my practice as well, they don't necessarily need to fail any medication class. We'll use it right off the bat, like if they're in surgery and they have moderate pain, severe pain, or patient even says they want to avoid opioid therapy, we'll use Journavx and prescribe it for them directly postop. Now it's pretty high up in the first medications that we're going to try for a patient. I mean, it can be combined with other medications as far as I know, so we often will just use Journavx alongside NSAIDs and muscle relaxants and use that as a combination therapy to just avoid the potential use of any opioids at all.

WC [00:06:24]: It's used in tandem with everything else to maximise the patient's response before you have to resort to opioids in a worst-case scenario. Is that a fair summary?

SS [00:06:37]: Yes. Exactly.

[00:06:41] How would you quantify the number of patients that have been on Journavx? You mentioned that sometimes it's prescribed by the surgeon and in those cases, you won't represcribe, but of that total inpatient population that you're seeing, what percentage is either on Journavx or has received it in the past?

SS [00:07:11]: Do you want percentage, or do you want specific quantities?

WC [00:07:19]: I think percentages would be helpful. I think you mentioned, for example, 20 inpatient individuals.

SS [00:07:31]: Yes. I would say that, it depends on the kind of surgeries. I'd say probably about now because it's on formulary in a hospital, 60-70% of patients that we're seeing, we're using Journavx pretty early on. A lot of the patients that I'm seeing today, they've already been on a course of Journavx or they're right in the middle of their course of Journavx.

WC [00:07:31]: It's interesting to hear that it's on formulary for you. I know that it still hasn't been approved for that long in the grand scheme of things. When it comes to peers in the space, is this something that is typically on formulary elsewhere, or would you say this is more of an exception at this point in time?

SS [00:08:43]: I believe it's an exception. Even within our multiple hospitals at UCLA, I think one of our hospitals has that on formulary and then the other one doesn't because sometimes we round on the weekends, we cover both hospitals. If we want to recommend Journavx at one of the other hospitals, it's not something we can do. I do think there was a lot of work that was put in early last year and there were a lot of meetings that I was not a part of, big stakeholders that really pushed this through to get it approved on formulary at one of our hospitals.

[00:09:31] You mentioned how some patients will be vocal about not wanting opioids, but generally speaking, who's primarily driving the transition towards integrating non-opioid pain meds such as Journavx into the treatment paradigm? Would you say it's primarily physicians, or is it more patient-driven?

SS [00:09:53]: Physicians. I mean I think that Journavx… I remember there was a time, even now, I mean, there's ads everywhere, so patients are seeing it, but… It's hard to say because I feel like in the pain world, we were very much aware that this was coming out, and we are very excited about it. I feel like on the surgical side, at least when I've spoken to some of my colleagues, it's because patients have brought it up to them first and they said, "Hey, I'm having this minor surgery. I know I'll be in some pain. I really want to avoid opioids." Now it's been adopted, and now it's mostly physician-driven, but I think in the beginning, a lot of people who were not in the pain world who are surgeons or other kinds of doctors were not aware that this was out, and it was brought to their attention by their patients.

WC [00:10:46]: Is it fair to say that there is a push by pain medicine physicians to use it, but for the surgeons, perhaps it's a bit more patient-driven?

SS [00:11:02]: Yes, that was my kind of like feeling on how it all played out over this past year.

[00:11:15] You mentioned that Journavx isn't represcribed. Could you help me understand the likely rationale for that? Why wouldn't you represcribe Journavx to a patient, in the event that the surgeon has done it in the past?

SS [00:11:37]: My understanding is that it's not covered by insurance within a certain time period. I don't know maybe it's changed recently, but usually… I don't know where this came from, I really didn't look into the details, but I had heard from maybe one of my colleagues that insurance only cover it maybe three times a year, so try to spread it out like by at least four months before you try it again. That's just what I've been going off of. If I see a patient, they recently finished a course of Journavx, it was two weeks ago, they're still having a lot of pain. I'm going to try everything else. If it's somebody who had a flare of their pain, I think in these cases, it's not surgical pain, but they have maybe a flare of their chronic pain, acute on chronic, then I might try Journavx if it's been a few months.

[00:12:36] Latigo Biotherapeutics' lead candidate onzotrigine – LTG-001 – is a NaV1.8 inhibitor. It shares the same mechanism of action as Journavx. What are your thoughts on the mechanism of action broadly and its potential to address acute pain? How good have the patient responses to Journavx been so far?

SS [00:13:06]: Yes. I would say that's a challenging question to answer because I've had… The side effect profile is fairly low. I think we use Journavx in almost everybody, but there's probably a 20% or less where I've seen it really do amazing things. For the most part, I think it maybe brings their pain down a little bit. I don't know if it's any better than… I think it prevents people from using opioids, but I haven't seen it treat acute pain consistently very well. The mechanism itself, I think, is very interesting because it's non-opioid and it's targeting a very specific sodium channel blocker. I like the mechanism. I think if it was more effective, that would be great, but that's just the general experience that I've had. Low side effect profile, so I'm willing to try it, but I haven't had like amazing results.

WC [00:14:26]: Some very good responders, but overall, definitely a wide spectrum in terms of how patients are doing?

SS [00:14:37]: Yes.

WC [00:14:41]: You mentioned that you think it's prevented people from using opioids who otherwise would have.

[00:14:41] How many patients who would have been receiving opioids previously do you think now aren't because of Journavx?

SS [00:15:12]: Probably like 20% of patients. Again, it just depends on how complicated these patients are at baseline because if they had a really big surgery, if they have other medical issues going on and if they're just overall very complicated, we're like a tertiary care centre, then there's sometimes no way to avoid it. For the straightforward patients who are not on a ton of medication, they have a surgery, the pain is just supposed to be like limited to one week or less, we've been pretty successful in avoiding opioids by using this.

[00:15:54] You mentioned that roughly 60-70% of your patients are either on Journavx right now or have been prescribed it in the past. How do you see your usage of Journavx trending over the next 3-5 years? Could you feasibly see yourself prescribing this to all your patients down the line?

SS [00:16:25]: Yes. I mean for most patients, there's very minimal side effects, and it's just nice to add on as an adjuvant for treating acute pain, as long as they don't have contraindications. I mean we do have patients who are on strong medications that are CYP inhibitors, but otherwise, I really feel like as long as those surgeons are on board, this is something that we're really going to try to just be a part of everyone's like recipe when they have acute pain, kind of like Tylenol is now, we'll just add on Journavx on everybody.

[00:17:11] It sounds as if Journavx hasn't necessarily been incredibly impressive in terms of efficacy, but ultimately, there's a low side effect burden for patients. For a physician, there doesn't seem to be a lot of risk in adding it on top of an NSAID or something else. Is that correct?

SS [00:17:39]: Correct. I have no idea what this costs to the health care system, but for right now, it hasn't really been a concern. It's almost like everybody that comes in with acute pain, we add on around the clock Tylenol. I have a feeling this is the way that it's trending with Journavx. They come in with acute pain, Tylenol doesn't have miraculous results, but it's mostly low risk, unless it's truly contraindicated. We just added on everybody and hope it at least plays its part in helping its little portion of bringing their acute pain down.

[00:18:21] Thinking about patients who might be seeing the advertisements and perhaps requesting Journavx, what is the primary reason for those requests? Are they primarily interested in the better side effect profile? I noticed that there are fewer gastrointestinal issues and perhaps less sedation. What do you think is motivating them to advocate for it?

SS [00:18:44]: Most of them, they see that it's a non-opioid, and I think they just don't even want to be on opioids. I think that the opioid epidemic and all the news about fentanyl and overdose, I mean a lot of patients are just… If they don't have to touch opioids, they want to avoid it at all costs. When they see these advertisements are like ask your doctor about Journavx, it's a non-opioid, that's usually the information they come to me with, "How can we use this medication in my care? Is this reasonable for me?" I saw all those in like a magazine or online.

WC [00:19:29]: Do you think patients have become increasingly aware of this over the last couple of years in terms of the issues with addiction and opioids?

SS [00:19:45]: Yes. Yes.

WC [00:19:49]: How well has Journavx been reimbursed in your clinic, perhaps delineating by insurance coverage, including commercial, Medicare, Medicare Advantage and anything else?

SS [00:20:21]: I read through the questions, this is a section that I literally have no idea how to answer.

WC [00:20:30]: Is it just these ones on reimbursement specifically?

SS [00:20:35]: Yes, because I have no idea. I just have no clue. I put in the prescription, it either gets filled or it doesn't. Sometimes I have to do a prior auth by my team, but aside from that, I don't actually have any clue.

WC [00:20:51]: I suppose you're not even overly aware of what insurance your patients are covered by?

SS [00:21:06]: I know most of my patients are Medicare. I know that there was a time where it was very hard for them to get Journavx. For the first part of last year, they had a manufacturer coupon with codes, and it will only apply to commercial insurances. It was really frustrating because I would say over 50% of my patients are our Medicare and I wanted to use this medication, and there's no way for them to get it affordably.

[00:21:41] I've read that Medicare coverage for Journavx is very limited, with only about 10.7% of Medicare Part D and Medicare Advantage enrollees having plan coverage, so perhaps that ties back to your point about how, universally, this isn't super well-reimbursed at this point. Is that fair?

SS [00:22:13]: Yes, that's what it seems like. I don't know the details.

[00:22:19] We've talked about the typical prescription length of Journavx so far. My understanding is that it's about two weeks. Is that consistent with your experience?

SS [00:22:37]: Yes.

WC [00:22:37]: Do you find that to be sufficient for most patients?

SS [00:22:44]: Depending on their pain, if their pain gets better, they'll stop before the two weeks. If their pain doesn't get better, I have actually been recommending that they finish the two weeks anyways, but I really don't know if that's the right recommendation. Yes, I think I do not know if a longer course would be more helpful. I think by the two-week mark, we usually know… It's hard to say because for a lot of more chronic pain medications we use, like gabapentin or any of the nerve medications, patients usually have to be on a medication for about like 4-8 weeks to really notice a difference in chronic pain symptoms. If we're using it for acute pain only, then I think the two-week mark, if it hasn't helped by then, it probably isn't going to miraculously help. I think given the indication for treatment of acute pain, two weeks is fine.

[00:23:46] What percentage of patients are getting to the two-week mark and not feeling that their pain has been sufficiently relieved?

SS [00:24:10]: If we're truly treating only acute pain and at the two-week mark, it's not getting better, we're usually looking for what else might be going on because even with just time, usually acute pain is getting better by the two-week mark.

WC [00:24:29]: Perhaps better put, how many of your patients are getting better before the two-week mark and stopping, as you mentioned?

SS [00:24:40]: I would say about 20%.

[00:24:48] Journavx requires a 100mg loading dose, taken on an empty stomach, followed by 50mg daily. It carries a CYP3A interaction warning. Has that language been restrictive for patient uptake?

SS [00:25:08]: Has it been restrictive? No, this is something I… I definitely tell every single patient that I prescribe this to about the 100mg loading dose, but it is confusing for some patients because typically for other pain medications, they don't have a loading dose. I do explain it to them. I actually have no idea how many of them maybe did not do the loading dose. Then I have patients that came to me maybe at the five-day mark, and they're like, "Oh, I forgot to do the loading dose. Do I just double my next dose?" I was like, "No." Yes, I would say it has been restricted, but I don't know about the CYP interaction. I mean if patients are on a strong CYP inhibitor, then we let them know and they just don't use this drug. I mean there's contraindications to every medication that's FDA approved. That one is not as restrictive. It just means they can't use it or they should use it very cautiously, and in those patients, I don't put this medication.

[00:26:14] The CYP3A label perhaps isn't particularly restrictive, but the language around when you should be taking it is, and could be leading to some problems with patient adherence. Would you agree with that?

SS [00:26:28]: Yes.

[00:26:32] An expert in a previous Third Bridge Interview [see Vertex Pharmaceuticals – Journavx Clinical Uptake Barriers & Competitive Threats – 27 June 2025] raised the argument that patients with kidney disease, heart conduction issues and muscle spasticity are at a higher risk of Journavx's side effects. Is that consistent with your experience?

SS [00:26:46]: I mean, that's a lot of different types of patients, kidney disease, heart conduction. I mean, anybody with those kinds of issues are all very ill already. I have used Journavx in patients with those but less than side effects, I would just say it didn't work well for them. I wouldn't say that they stopped, I would say that they still completed their two weeks, but it just didn't help their pain because they have a lot of other things going on.

[00:27:36] Could you talk about the general FDA approval process for non-opioid pain meds? My understanding is that the FDA requires demonstrated success in a soft and hard tissue model for approval with abdominoplasty and bunionectomy, respectively, representing the typical benchmarks. What are the benefits and limitations of using abdominoplasty and bunionectomy for seeking approval of a novel candidate?

SS [00:28:06]: I think this is the problem that we had with Journavx too. Those procedures, I would say, are overall less painful than a lot of the patients that we see in our hospital system and the patients that we're really hoping that Journavx or these kinds of novel medications would be helpful for. I think the data can still be extrapolated and patients… I think most importantly is just looking at side effect profile and making sure that these medications are well-tolerated. I would say that we have to take this data with a grain of salt because our patient population that we hope to use these medications are not usually just patients going in for a simple bunionectomy or abdominoplasty because those are fairly simple, straightforward, not a ton of pain.

WC [00:28:06]: A physician in a previous Third Bridge Interview [see Vertex Pharmaceuticals – Journavx Check-up – Clinical Impressions & Chronic Pain Expansion Outlook – 3 November 2025] noted something similar, in that the abdominoplasties and bunionectomies aren't particularly painful, which limits what you can draw from the clinical trial results, but it's interesting to hear that this enrolled patient population is ultimately not representative of what you're seeing in the clinic.

[00:29:10] Looking at the Phase II abdominoplasty trial that Latigo ran, a high-dose onzotrigine achieved a statistically significant 62.1-point reduction in SPID48 vs the placebo group, and had a 50% greater analgesic effect than Vicodin [hydrocodone with paracetamol]. What was your initial reaction to those results?

SS [00:30:10]: I mean I think that's great. 50% better analgesic effect than a strong opioid is very significant. Yes, it seems like it could be a very effective pain medication to use in this patient population. Again, I do think that it can be extrapolated to other more complicated patients because if you have a simple patient and it works very well, it may not work as well in a more complicated case, but I think you can still make some inferences that it is hitting on certain pain receptors, post surgical pain receptors for acute pain. While there may be other things going on in more complicated patients, there can still be improvement. I don't know if it's going to be as significant, but there can still be some positive impact from using this medication.

[00:31:18] Do you think there's a case to be made that, if you're showing benefits in a less severe population, that might actually imply that you're going to see an even more powerful effect in patients with more severe pain – those that you're seeing in the clinic, for example? What might be wrong with that reasoning?

SS [00:31:58]: I think I wouldn't agree with that because if the surgical case is bigger, if the patient has more medical underlying issues that they're on multiple medications that may potentially interfere, maybe not contraindicated with something that's like a NaV1.8, but may just somehow interact with the pharmacokinetics. I think there's just so many different layers of a more complex patient where you can't… It's not just a straightforward pain pathway. In an otherwise healthy patient who's just getting an abdominoplasty and not on a lot of medications, you're just dealing with the incisional pain. You're not dealing with all the other systems and medications at play. I would say that when you layer on more complexity, the significance of the pain relief, at least the way I'm thinking of it, is actually going to be less strong than more strong because now you have to weave through all the different layers of this patient's whole body and all the different things and disease process states and medications that they're on.

[00:33:17] Unlike Vertex, I don't think Latigo is planning to run a larger abdominoplasty Phase III moving forwards. Vertex's Phase III study for Journavx demonstrated a 48.4-point reduction compared to placebo in that trial. Acknowledging that it's a cross-trial comparison, thinking about what we saw with onzotrigine in the Phase II, which was a 62.1-point reduction compared to placebo and Journavx's Phase III, how confident would you be in onzotrigine's probability of success here, based on the data that we've seen?

SS [00:34:15]: Do you know the number of patients that was in this Phase II trial for onzotrigine vs like how big the abdominoplasty Phase II trial was for Vertex?

WC [00:34:35]: That's a fair question. My understanding is that the onzotrigine abdominoplasty trial was fairly large for Phase II standards. It was 343 patients. I'd have to look up what Vertex's Phase III Journavx abdominoplasty trial sample size was, but 343 for onzotrigine Phase II and then 1,118 for Vertex's Journavx abdominoplasty.

SS [00:35:21]: I mean, I think given how significant the results, still 1,000 compared to 300 is still a pretty big difference. Given how significant the pain relief was in the Phase II trial, I would anticipate that it would show fairly similar results in a bigger trial and that we could just extrapolate that it would do pretty well even if the trial wasn't run at a bigger… In a Phase III trial, I think that onzotrigine… It can be said that. It is at least comparable, if not better to suzetrigine for those types of patients.

WC [00:36:12]: Perhaps that's kind of the bet that the company is making by not running the larger Phase III for abdominoplasty. Do you think those abdominoplasty results are strong enough to support approval of onzotrigine, assuming a positive bunionectomy readout?

SS [00:36:31]: Yes, I think so. I think it should be good enough to show some good data.

[00:36:44] I think the plan is to initiate the Phase III bunionectomy trial in late 2026. What do you think is onzotrigine's bar to beat in the bunionectomy trial in terms of SPID48 reduction compared to placebo? For reference, I believe Journavx demonstrated a 29.3-point reduction vs placebo in its Phase III bunionectomy trial.

SS [00:37:15]: I think it needs to be at least as good as suzetrigine, with faster onset and improved improvement in pain more than Journavx. I mean, I don't have specific numbers, but I would just think that it would need to be… Journavx had some really good data. I think that in order for something else to come to the market, it would have to show significant improvement over the Journavx.

[00:37:59] How much better would onzotrigine need to be, percentage-wise, in terms of SPID48 reduction specifically or any other endpoints that you think are most relevant?

SS [00:38:38]: I don't have specific… If it was better by even, I don't know, 10-15%, but also side effect-wise that it's just as well-tolerated, if not better, I think that's important, too, especially since Journavx had great numbers for abdominoplasty and bunionectomy. Again, when we extrapolate it to real-world data, I would say maybe 20% of my patients are doing well on it, which is still like it's okay. It's not amazing. I think more importantly than just significant pain level changes is, is this something that we can integrate into everyone's like pain regimen, and that can only happen if it's really well-tolerated with minimal side effects. I think more importantly than just significant levels in pain improvement is tolerability.

WC [00:39:46]: Ultimately, is tolerability going to be the most important factor that will determine how successful this candidate is?

SS [00:39:55]: For me, yes, as someone who prescribes it regularly, that's what I would worry about.

[00:40:02] I believe that 85% of the enrolled patients in Journavx' Phase III bunionectomy trial were female, and 98% of the enrolled patients in the Phase III abdominoplasty trial were female. Does that potentially change how we should be thinking about these cross-trial comparisons and the relative efficacy that onzotrigine might need to show to be comparable to Journavx?

SS [00:40:40]: I think with just those types of surgeries, there are often just more female patients. I mean, I don't know. I mean, I feel like if it could be more even, that, of course, is always going to be a good thing, but then it might not be as well-comparative to suzetrigine. I think if we're looking at similar age ranges with similar medical complexities, I think it's okay if the genders don't exactly match up.

WC [00:41:13]: That was just something I noticed and wasn't sure how important it was. Why do you think there are often more female patients available for enrolment in these trials?

SS [00:41:41]: I think in general, a lot more women… I mean, I don't know. I'm not like a podiatrist, but I feel like more women… I always hear people complain about having bunions and getting like an abdominoplasty. It's like a tummy tuck, so how many men are really getting that?

[00:42:04] Sticking with the clinical trial analysis, the onzotrigine results indicate rapid absorption of the candidate molecule, with a Tmax of roughly 1.5 hours. How do you think this compares to Journavx? Ultimately, how important is the onset of action with these non-opioid pain meds for physicians and patients?

SS [00:42:36]: I think onset of action is really important. Patients are in moderate-to-severe pain, they are miserable and they want something that works not in two days, but something that works today, preferably within like hours, minutes to hours. In general, I feel like Journavx, I haven't had any patients tell me that it's worked within hours, but some people usually say they feel better within the first day. I don't know specifically Journavx what that Tmax is, but is that time to…

WC [00:43:25]: Sorry, you're asking…

SS [00:43:29]: Yes, I'm asking about Tmax at 1.5…

WC [00:43:34]: Tmax is just the time that it takes for the substance to reach its maximum concentration in the body after being administered.

SS [00:43:45]: Does that correlate to symptom relief in a patient?

WC [00:43:50]: I don't know.

SS [00:43:50]: I don't know either, but if it did, that would be great. If patients were able to feel better in 1.5 hours, that would be fantastic because that's not what I'm seeing with suzetrigine.

WC [00:43:50]: Yes, we're not sure how well that translates, but perhaps we'll get some more data points on that in the future.

[00:44:08] In a hypothetical world where onzotrigine is approved, what patients would you plan on rolling it out to?

SS [00:44:32]: Post-surgical patients that similar to how I'm using suzetrigine now, just using it as part of a cocktail with different other classes of medications in hopes of avoiding opioid prescriptions altogether.

[00:44:55] Are the ideal patients for onzotrigine the same as those for Journavx, or do you think there's a differentiated use case for one or the other? We're talking about the same mechanism of action at the end of the day.

SS [00:45:12]: From what I've learned about onzotrigine, I mean, this is just only from our discussion today, it sounds very similar. I feel like the space where I would use it would be very similar. If they were both on formulary at a hospital, I truly don't even know which one I would pick, unless there was data that was showing that onzotrigine did have a faster onset of symptom improvement and better tolerability in patients with less side effects, but the target population would be the same.

WC [00:45:46]: Interesting, so the same target population, but in terms of how you would potentially use these things, given that you can say that they'd be competing head-to-head, it would be tolerability, then onset of action, then whatever you've seen from the literature in terms of efficacy. Is that all fair to say?

SS [00:46:06]: Yes.

[00:46:11] It sounds as if there's definitely a trend around pain medicine physicians pushing opioid use to the very end of the treatment algorithm. Does it make sense to potentially use onzotrigine in patients who don't do well on Journavx, given that we're talking about the same mechanism of action? Wouldn't you expect more or less the same thing to happen?

SS [00:46:42]: Yes, if one didn't work well, I don't know that I would try the other one. I mean the mechanism is the same. It's kind of like how I think about gabapentin and pregabalin, they act on similar receptors. If one doesn't help at all, I'm not going to try the other one just for the sake of trying.

[00:47:15] You pointed out how you're giving Journavx to a significant percentage of the naive patient population in the first line. Let's say that we ultimately see onzotrigine demonstrate Journavx-like efficacy with a similar tolerability profile in the bunionectomy trial. If you had to think about the theoretical split between onzotrigine and Journavx 2-3 years post onzotrigine approval, what would that look like?

SS [00:48:02]: I think that would ultimately come down to cost of the drug and recommendations from the hospital on guidelines on which one they recommend us to use, so that's inpatient. Then outpatient, if I'm using it is just insurance coverage or co-pays and what's the most cost effective for the patients. Especially if the efficacy is similar, I think that was your question, Journavx efficacy. I think if it's pretty similar, let's see we can extrapolate that data to real-world patients, and they're also performing similarly, like 20% of my patients are getting relief, then it just ultimately comes down to cost.

[00:49:06] When it comes to getting Journavx on formulary, what do you think that process would look like? Do you think it could ultimately be harder, given that you already have something similar on formulary, or should it theoretically be easier because we're talking about something with the same mechanism of action that could be used as another option for patients?

SS [00:49:37]: I don't know. Those are good questions because they're both new medications. I feel like Journavx hasn't been out long enough, like it's still fairly costly but I don't know the hospital is going to easily agree upon another formulary when one already exists, and they do very similar things. I did see your question about like an IV formulation, I think if there was something different that was offered and then there was an IV and an oral form, then they might… Whoever decides these things might be more inclined to potentially take on this as a new formulary option for the hospital because it's something new and different and can also be used in a whole different patient population that can't take anything by mouth.

[00:50:42] Latigo is developing an IV formulation of onzotrigine. How materially do you think that would expand the addressable market? You said that it could ultimately be more favourable for securing formulary coverage, but outside of that, how many patients do you think would prefer an IV compared to taking a twice-daily oral, which is the case with Journavx, and I believe would be the case with onzotrigine?

SS [00:51:17]: I think the patients that prefer an IV are patients that are often very complicated, and they either are very nauseous or they can't take things by mouth because they've got other issues going on or they have a G-tube. Oftentimes, those are the patients that we're not seeing like these miraculous results with Journavx anyways. It is a great option because especially in big tertiary centres, quaternary centres, we do have a lot of these very complicated patients that often can't take anything oral and they're in severe pain with very limited options except for IV opioids. This would be a good alternative to at least try first and see if we can delay the opioids or at least decrease the amount of opioids that they have to get.

[00:52:13] In what percentage of your total inpatient population is taking an oral not even a choice?

SS [00:52:24]: Yes, I would say less than 5%.

[00:52:25] It sounds as if, if we had oral onzotrigine and Journavx as well, you probably wouldn't start a patient who's failed one on the other one. Let's say that somebody doesn't do well on Journavx, but now there's an IV formulation of onzotrigine available. Is that something that you would potentially entertain, given we're talking about a different formulation now, and perhaps the bioavailability is better there?

SS [00:53:12]: Possibly, yes. It's definitely something we can try because it's another route of administration. Also, just given the patient situation, maybe they have poor absorption for whatever reason because they have other medical issues going on in IV, not only bioavailability, but just a different formulation might just work better because they're not absorbing what they're taking by mouth. I would definitely try it if there was an IV formulation, even if they failed suzetrigine.

[00:53:44] How are you thinking about the potential for the NaV1.8 inhibitors outside of acute pain, perhaps in chronic pain, given that's your outpatient population?

SS [00:53:56]: A lot of my patients have asked me about this because a lot of my chronic pain patients on chronic opioids want to get off of it, but they're just in so much pain when they try, and I have to tell them that this hasn't really been studied. Yes, I feel like we need something like this for chronic pain patients. I think if there could be future studies or if Latigo is thinking of doing any chronic pain studies for onzotrigine, that would be fantastic because right now, all of these acute pain studies, they're only for two weeks at a time, and our chronic pain patients are just really struggling.

WC [00:54:57]: Why haven't the companies explored this? Do you have any thoughts on that? Is there an argument to be made that it's perhaps harder to enroll a relatively similar patient population when you're talking about chronic pain?

SS [00:55:27]: Totally. I think chronic pain is a whole different beast. I mean a lot of chronic pain patients are dealing with traumas and psychosocial stressors and chronic pain. They could have back pain, they could have had surgery that's causing pain, and so there's just so many different pieces. You can't really enrol a very uniform subset of patients. I mean, I guess if they looked at chronic pain patients on chronic opioids who have had back surgery, that could be a good place to start because that's a lot of our patients here. I think there's a lot of work that has to be done in the chronic pain population that just hasn't yet, and so they're left with very limited options.

[00:56:22] Do you think any other non-opioid pain candidates are being developed right now that look particularly promising?

SS [00:56:35]: Not that I'm aware of. I haven't heard of anything else. I feel like Journavx was really exciting last year because there really hasn't been anything that has come around that's been similar to that. I'm hoping that there'll be more things in the future.

[00:56:53] Can you envision any other settings outside of acute and chronic pain where Journavx could be effective for patients?

SS [00:57:20]: I mean there's acute and then there's chronic, but then there's also acute on chronic. There's patients who are chronically in pain and then they have intermittent flares, like sickle cell patients that come in and out sometimes with their sickle cell crisis. It would be interesting to see how medications like this could help shorten hospital stays when patients are admitted for acute on chronic pain flares.

WC [00:57:48]: That's very interesting to think about. Would you like to share any final thoughts?

SS [00:58:04]: No. I thought this was very comprehensive.

WC [00:58:09]: I will conclude the Interview there. Thank you for joining us. I really enjoyed the conversation, and thank you for everything that you do for your patients. Clients, thank you as well. Thank you for the time, I enjoyed this and would love to have another one of these in the future.

SS [00:58:34]: All right. Thank you so much. Take care.

WC [00:58:36]: Take care. Bye.

SS [00:58:37]: Bye.

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