Everyone, thanks for joining us here at the Goldman Sachs Global Healthcare Conference. Thrilled to have on stage with me today the Chief Executive Officer and President for Contineum Therapeutics, Carmine Stengone. Maybe I'll turn it first to you, if you could just high-level discuss the clinical catalyst you guys have ahead for the year and where investors should be focused for the remainder of 2026.
Yeah, absolutely. Corinne, nice to meet you, and thanks to the Goldman team for allowing us to join on the fireside. This is a catalyst-rich year for us. I think the main focus is going to be around LPA1. We have what we believe is the best-in-class LPA1 receptor antagonist. The big focus for this year is clinical execution on our phase II study in idiopathic pulmonary fibrosis. From a catalyst standpoint, BMS is looking to read out their LPA1 receptor antagonist, admilparant, in what we believe is Q4, based on what they said in their earnings release.
That is a big data point to further validate LPA1 receptor antagonism in pulmonary fibrosis, and there's already over 500 patients' worth of data over three different clinical studies in IPF and PPF to validate that, but having another 1,200 patients in an IPF is going to be a big readout, and we look forward to seeing their efficacy and safety and tolerability and being able to differentiate against that on multiple avenues.
Great. You started talking about it, Bristol has the phase III ALOFT data, like you said, probably in the fourth quarter. Both your agent, PIPE-791, and admilparant target LPA1R. Maybe we can start just by how you think your asset is differentiated relative to the admilparant profile and how that could translate across safety, efficacy, and dosing.
Yeah. A lot of this is thinking about the IPF patient population right now. There are three approved drugs all which seem to slow the decline of FVC, and that has been the bar for treatment. As we look to that patient population, on average, they are 65- 75 years old. From diagnosis to death is generally three to five years, so they are fighting against a terminal disease. There is some important measures here that we think that we can have that admilparant cannot. Again, with that patient population, convenience is important. Having a QD dose versus a BID dose we think is important, but equally important on that convenience and adherence standpoint is, from what we understand, BMS has a dose titration in their phase III to avoid hemodynamic issues. That dose titration can take anywhere from six to 17 days upon initiation of admilparant.
That is certainly cumbersome. There could be hemodynamic issues that occur during that dose titration. We know that they tested this in cohort 1 in their phase III study. We do not have that hemodynamic signal, this is a simple once-daily dose starting at the beginning of treatment. Dosing convenience, tolerability. As I said, we do not see the hemodynamic signal. If you look at even the original phase II study from admilparant, both IPF and PPF, outside of the hemodynamic signal, this mechanism is extraordinarily clean. The side effect profile in the phase II studies were generally consistent with what you see with pirfenidone and nintedanib, the historic standards of care. I think the most important thing here is we have a really unique PK profile with PIPE-791. This has a very slow association-dissociation rate, a very low peak to trough.
This allows us, with a QD oral non-titratable dose, to achieve greater than 90% receptor occupancy, which the way that we look at this is as close to an antibody profile that you can have with a small molecule against this target.
Great. You were just talking about the titration scheme that they have, 791 doesn't seem to require. If their Q4 data does show low incidence of syncope despite that titration, how would you think that informs, then, the commercial narrative for your opportunity set?
Well, I think that commercial narrative is already coming through. We've had a number of questions from investors as to whether we believe that the dose titration will be required in a commercial perspective, and I would assume yes. I'm not an expert in the space, but I would assume that given they did not have a dose titration in their phase II and they just introduced this into their phase III, that will play into the commercial narrative. Where we differentiate here is we don't have that. They're clearly taking it seriously, having done cohort 1 in their phase III study. This was a time period in the phase III study, a co-primary endpoint with FVC. FVC measured at 52 weeks. Episodes of syncope were in the first 60 patients through 28 days of the study.
We know that they see that hemodynamic signal very early in their dosing regimen, and they're hoping to wash that out.
At the recent ATS conference, you presented data comparing 791 to admilparant. I guess, could you elaborate on the distinct lung occupancy profiles that were demonstrated in that poster? Specifically, how does the potency or residence time allow for that safety profile?
Yeah. We spent a lot of time looking at receptor occupancy based on what we saw in animal models as well as the early data that came through BMS-986020, which was the first LPA1 receptor antagonist that they brought into the clinic. It was clear that the harder you can hit the receptor. The better impact that you have on the fibrotic cascade. That was important for us to see. At ATS, we also had a poster that demonstrated, and again, this is in animal models, it's not in humans, but demonstrated that we lack seeing signals that they have. They have a compound that has a very fast. What initiates the fibrotic cascade for IPF with this specific mechanism is when there's an injury, LPA floods into the system, right? LPA activates the LPA-1 receptor that starts recruitment of fibroblasts, collagen secretion, and subsequently fibrosis.
When you have a compound that is fast on, fast off, it competes with LPA, and the vasoconstriction that comes with LPA turns into vasodilation, and we believe that that may be a contributing factor in their orthostatic hypotension signals. We have a compound that takes hours, not minutes, to associate to the receptor, and then to dissociate afterwards, so we have a very measured curve to peak, and the peak to trough is very low, and you can think of this as an automatic stopping brake with our pharmacokinetics. It is a built-in titration that allows us to not have that hemodynamic impact.
Okay, great. You mentioned the importance of receptor occupancy in 791 achieving about 90% receptor occupancy. I guess, what are the PK properties that enabled that activity?
Yeah. When we first started this program, we did what a lot of companies do. We were patent busting around other LPA-1 receptor antagonists. We couldn't get the properties that we wanted, both from a CNS perspective or from a PK perspective. We moved into a completely novel estate. This allowed for consistent brain penetration, so whether we were looking at pain or other disorders, but it also came with this low peak to trough and steady signal of association dissociation. With that, once we achieved 90% receptor occupancy in that study, we went as high as 10 mg. So 1 mg. With all of those doses, we are able to achieve 90% receptor occupancy at steady state, and when we look at the 10-mg dose, which is what we tested in our pain study, we're at multiples above 90%.
As we look at that relative to BMS, when you start to analyze the data from their phase II, they had two doses. They had a 30 mg BID, and they had a 60 mg BID for 26 weeks. It's pretty clear that the 30 mg BID really didn't have much receptor occupancy at all, and we can look at their PK to justify that. With that, they did not have a signal of any significance in their study. The 60 mg BID, again, we believe is below the EC50, so less than 50% coverage, and the data kind of demonstrates that. It's a little bit muddy data. There are a lot of patients who are above the EC50. There's a lot who are scattered below.
As we look to what they did in their phase III, the only rationale in doubling that dose, again, looking at 120 mg BID, knowing that there is a potential hemodynamic signal, is to increase receptor occupancy. From our modeling, we still don't think that they are anywhere close to 80%-90% receptor occupancy with the new dose, whereas we're able to do that with every dose that we test.
Great. You mentioned this at the top, but you've got a phase II PROPEL-IPF study that's currently underway. Could you talk to us about the trial enrollment and sort of pace you're seeing in terms of receptivity of patients coming onto that study?
Yeah, the receptivity's been really good. We have a good clinical advisory board. ATS was really the coming out party for us at that point. This is a large phase II, we're running 324 patients, 108 patients per arm, two different doses in a placebo arm. We have not updated trial enrollment, but the clinicaltrials.gov listing was recently updated, 20 sites are online. New territories are coming online very rapidly, we're looking forward to getting that into steady state.
Great. Patients are allowed to be on background therapy like Ofev and Esbriet, but how do you think the recent approval of JASCAYD changes the market dynamics and particularly the enrollment dynamics in IPF?
I think it's too early to tell. Obviously pirfenidone and nintedanib have been the standards of care for an extended period of time, and BI has flashed out some very positive signals on the uptake for JASCAYD. We haven't seen the script data yet. It is something that anyone running a study in IPF right now is going to keep in the back of their mind. As we see that continue, currently in our IPF study, in the PROPEL-IPF study, we have only nintedanib and pirfenidone as background therapy, but we'll continue to monitor JASCAYD, and in all likelihood, we'll be adding that into the background therapy over the course of this study.
In terms of the additional drugs that could come to market, things like TPIP, do you anticipate any further changes there as you progress through clinical development?
I think we're in a pretty good situation right now in terms of recruiting. There are no major big pharma phase III's ongoing. BMS is essentially done. BI's out of the market. TYVASO is out of the market now as well. There are a few phase II's. I don't really think about the TPIP program just because from what I understand, the only study that they're running right now is about 350 patients, but it's focused on PH-ILD and not IPF or PPF generally. I think even with the smaller programs, the Avalyn programs, ENDEAVOR, from what I understand, is fully enrolled, as is Vicore. This is really a good opportunity for us to pick up recruitment in the PROPEL-IPF study.
Great. I think you've previously shown benefit on pain. How would you think about incorporating that as a secondary endpoint in PROPEL-IPF, and what role could that play in kind of capturing the total patient benefit?
Yeah. We'll have some patient-reported outcomes that were already contemplated in the PROPEL-IPF study. As we think about how a brain-penetrant LPA1 receptor antagonist can change the treatment paradigm for these patients, we find this really interesting. We have a compound that we believe will have the best benefit on FVC just given the target coverage. It's a safe compound. When you look at what patients are being treated on right now, whether it's nintedanib, pirfenidone, nerandomilast, eventually TYVASO, this is slowing the rate of decline. If you think about that conceptually, it means that that patient never feels better as they did the day before, and they know that they have a terminal illness. If we can have a drug that allows for, even if it's a reduction in decline of FVC, we can also have a quality-of-life measure.
We're extending their lives, but for that additional period that we give them, that also allows for them to have a better quality of life, whether it's around osteoarthritic pain, whether it's PPF pain. These are areas that we want to be able to investigate as we continue bringing this forward to really have a game changer here, and where this makes us unique is having that CNS penetrance that's required for that reduction in pain.
What portion of IPF patients currently suffer from comorbid pain? I think you just talked about a couple of sources of it. How is that symptom currently managed?
Right now they're currently managed. Again, focusing on the patient population 65-75 years. It's NSAIDs, which in that patient population, kidney issues are obviously a concern, and there's opioids who have pulmonary issues associated with them. If you look at the general patient population, once over 75 years, over 50% of patients have chronic pain, whether it's chronic lower back pain or OA. There is a way to help them on typical musculoskeletal pain, but there's also, we want to see can we have an impact on thoracic pain? Even as we move on from IPF and think about progressive pulmonary fibrosis or ILDs, the most recent data I saw is 62% of patients within that category suffer with comorbid pain.
Okay, great. Could you just speak to the properties, particularly the brain penetrance of 791 that enable that benefit you've seen previously on pain and contrast that with the rest of the agents in the category?
Yeah. Like I said, there's no other LPA1 receptor antagonist that can access the CNS. Our compound was specifically designed for that because we had interest not only in the pulmonary fibrosis space but also in the CNS. This is something that will be completely unique to Contineum.
Okay, great. You've mentioned the PROPEL-IPF study a couple of times, but it's a 26-week trial. Can you talk about the rationale for measuring FVC at 26 weeks versus, I think, registrational programs are 52?
Yeah, for us, we need to think about this as a proof-of-concept study. As we think about the potential approval procedure, a 26-week study can qualify as one of two well-controlled clinical studies. That can be part of the registration package. We chose this because we saw the BMS-020 data, we saw the BMS-278 data. We believe that we have a higher-powered molecule, and we can demonstrate a significant change over the course of 26 weeks. There's always concerns about running a 12-week study. I think even in looking at the BI data, showing a pro-fibrotic signal at four to eight weeks is pretty unrealistic. We wanted to make sure that we gave these patients enough time to really get the full benefit of this mechanism, knowing that the next study will be 52 weeks.
What do you think about as defining a sufficient or proof-of-concept type response at the 26-week time point?
What do we think is important?
What would be clinically meaningful at the 26-week endpoint?
A reduction in FVC. I think at 26 weeks, it's hard to really gauge whether you're talking about a 50% reduction in FVC decline or something else, but it's something that when you look at the 020 data, it was pretty spectacular. You look at the 278 data, what it was about 40-60 mil decline, something like that.
Okay. The IPF landscape is expanding pretty quickly right now. Besides the approved agents, you also have the ones we've talked about in LPA1, you've got treprostinil, there's Private, Syndax has their program. There's just a number of things here. I guess, where do you think the treatment paradigm is evolving to, and how do you think about 791, where that could fit relative to a relatively crowded therapeutic landscape?
Yeah. This comes down to polypharmacy in the long run, and there will be multiple agents used in parallel. Right now we don't have that benefit because pirfenidone and nintedanib can't be used together or are not used together. Similarly, nerandomilast has a DDI with pirfenidone and exacerbates GI issues when on top of Ofev. We think that LPA-1 is a really important mechanism, and we think that it's also a de-risk mechanism, because with the other agents that you had mentioned, there's really no clinical validation out there.
We have over 500 patients of full data with 2,400 more coming with the ALOFT studies in IPF and PPF. Safety, tolerability, efficacy, that should define what the backbone should be. As I look at this mechanism and our compound in particular, we think that that is a best-in-class approach. It's a safe molecule, tolerability issues are minimal, if any, and then a bigger benefit in FVC, and can be combinable with all other agents. We see this as not only best in class, but potentially best in disease that serves as the foundation of polypharmacy, upon which we add nerandomilast or Avalyn's, nintedanib, inhaled n intedanib.
You mentioned that this could be a backbone with combination across all of these different categories. Are there any that have particular mechanistic rationale or that you think would be particularly interesting combinations?
There's a number of ways. This is clearly a fibrotic pathway. Even drugs with Tyvaso, I think a lot of this is driven through bronchodilation. There's that potential. With treprostinil, I have some questions around it, just given BMS gets some heat for having a hemodynamic signal, but if you look at Tyvaso's current label for PH, 6% of patients have syncope. You have 6% of patients who pass out. They also have 40% of patients who dropped out of their study, some of which is probably due to cough or adherence of doing a dose titration up to 12 puffs a day in an elderly patient population.
Maybe switching gears here a little bit, you recently reported positive data from a phase I-B study in pain. I guess, could you recap that data and your primary takeaways as it relates to advancing that program?
Yeah. We started this study probably about a year and a half ago, and enrolled quickly. Small study, just all the caveats. This was a phase I-B exploratory trend-seeking. What really had us starting to consider this is there's a lot of literature precedent that's similar to IPF, LPA being the bad actor that activates the ascending pain pathway, both centrally and peripherally. We chose chronic lower back pain and OA somewhat because of that as well. There's literature out there that if you take synovial fluid from patients with chronic osteoarthritic pain, the levels of LPA correlate with the pain severity. That was the first step, and then we did a non-human primate study, a chronic constriction injury, functional MRI, a very objective measure in anesthetized animals. What we saw is a blunting of that signal in the brain.
That started the process for us. The takeaways from our study, again, it was 43 patients, crossover design, four weeks on drug, then four weeks off, and vice versa. The biggest takeaway for me is this is the longest we've ever had patients on PIPE-791 at the highest dose that we can test, or that has been tested. We saw no issues with safety and tolerability, no hemodynamic effects, a very clean safety profile. The cherry on top for us was we were hoping to see a signal, and that's exactly what we saw.
In chronic osteoarthritic pain, we saw numerical improvements versus placebo over four different measures. On the NRS scale, on average daily pain, there was improvement. The worst daily pain by NRS, the 30% responder rate, and then really important, the KOOS score as well, which is specific to osteoarthritis. We saw a similar improvement on chronic lower back pain in treatment period one. There's always vagaries associated with crossovers, especially carryover effect. What we saw was the trend that we had hoped to see.
Right. You mentioned tolerability profile with this, like longest dosing, I guess. How much can we read through from a tolerability and safety perspective to the PROPEL-IPF trial?
That is probably the biggest takeaway out of this study. To be able to have that high level of receptor coverage over that long of a period, without any of the tolerability issues that we've heard from other companies.
Sure.
Really gives us a lot of confidence that it's a compound that should be tested further due to the safety and tolerability that we've seen already.
Great. On the regulatory front, what does the path forward look like here?
For pain?
In pain. What does phase II look like and
We see this as complementary to what we're doing in IPF and PPF. We want to be able to measure that in that patient population. That said, given this signal, we think that this is worthy of bringing forward. Given the size and the importance of the IPF study, that's really where the main focus is right now. We continue to talk with pharma and KOLs. We'll work towards a path for 791 in pain. Right now, it's a little too premature.
All right, switching gears again, you have a phase II study in Major Depressive Disorder. I think that readout is expected in the middle of this year.
These are obviously notoriously difficult indications. Could you speak to your level of confidence that the M1 receptor mechanism here for depression, just remind us the clinical data that exists to support it?
Yeah. This is a program that we have partnered with Johnson & Johnson. J&J is running the phase II MOONLIGHT-1 study. That study should complete this month. We're hopeful for data in the second half of the year. Much like LPA1 in IPF, this is a story around clinical validation in MDD. There are multiple studies that have been done with dirty antimuscarinics, specifically scopolamine, which is a broad pan-muscarinic antagonist, demonstrating a rapid and robust improvement in MADRS across multiple different depression settings, MDD, TRD, bipolar. J&J is running the proof of concept study right now in MDD. They're looking at three different dose regimens, placebo, then two pulse dose regimens, one at a higher dose and one with a step-down dose. The data from scopolamine looks very compelling, it's been done over multiple studies.
That, along with the profile that we have with PIPE-307, very selective for M1 receptor antagonism, more than 30x over the other muscarinic receptor antagonist. The lack of a cognitive signal in our phase I study, which is always a concern with broader anticholinergics. It looks like inhibiting that M1 receptor mechanism is really important from a safety and tolerability perspective. I'm not going to handicap what we should see just because this is J&J's program.
there was a reason that we chose to partner with them. They took a drug with all of the liabilities of esketamine, got it through the clinic. Now that's looking to do $1.7 billion, $1.8 billion a year in sales.
Right. Can you remind us on that point what the financial structure of the partnership with J&J is and how the decision-making process works, particularly with that partner?
Sure. Again, the MDD study is their study. They keep us informed on the status. We will be putting out top-line data. This collaboration started in the first half of 2023. With this, we received $50 million up front, $25 million in equity. They also contributed into the IPO. We have about a billion dollars left in milestones, a little bit more than that, have royalties that start in the low teens ramp to the very high teens. We also have the ability to co-fund heading into the registration program. That would allow us to push that royalty even further.
Okay, great. Any learnings that you take away from the VISTA failure you guys had in multiple sclerosis? Could you discuss any read-through to MOONLIGHT-1 with respect to either safety or the dose selection?
Other than same mechanism, the biologic rationale's very different.
Right.
When we were looking at the relapse remitting study in VISTA, this was built around OPC different M1 receptor antagonism on the OPC, the oligodendrocyte precursor cell, driving fully functioning and remyelinating oligos. With MDD, this is a story around neuroplasticity. Increasing glutamate burst, having a change in dendritic spine architecture that leads to that benefit. Very similar to what you see with the psychedelics and at least the output, but without any of the dissociative or tripping effects around that. The biggest takeaway for me is that we had over 150 patients on drug for six months QD, and it was safe and tolerable.
Great. Maybe last question here. Can you just remind us where you stand from a balance sheet perspective and in terms of cash runway?
Yeah. I think our last disclosure was about $250 million in the bank, right around there. That funds us through the middle of 2029, and that means that we have at least four quarters of capital post conclusion of the PROPEL-IPF study.
Great. Thanks. With that, thanks so much for joining us both here and online, and thank you so much for all the insights today.
Okay, great. Thanks .