Conference Transcript - CTNM 2026-06-09

Speaker 1

Hi, everyone, and thanks for joining us here at the Goldman Sachs Global Healthcare Conference. I'm thrilled to have on stage with me today the Chief Executive Officer and President for Continuum Therapeutics, Carmine Stengon. And maybe I'll turn it first to you, if you could just kind of high-level discuss the clinical catalyst you guys have ahead for the year and where investors should be kind of focused for the remainder of the 2026.

Speaker 2

Yeah, absolutely. Corinne, nice to meet you, and thanks to the Goldman team for allowing us to join on the fire side. This is a catalyst-rich year for us. So I think the main focus is going to be around LPA1. So we have what we believe is the best-in-class LPA1 receptor antagonist. The focus for this, 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 at Milperant in what we believe is Q4, based on what they said in their earnings release. So 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.

Speaker 1

So you started talking about it, but Bristol has the Phase III ALOF data, like you said, probably in fourth quarter. Both your agent, Pipe791, and Admiral Parent target LPA1R. So maybe we can start just by how you think your asset is differentiated relative to the AdMilfrant profile and how that could translate across safety, efficacy, and dosing.

Speaker 2

Yeah, so a lot of this is thinking about the IPF patient population right now. There's three approved drugs, all which seem to slow the decline of FPC, and that has been the bar for treatment. As we look to that patient population, though, on average, they're 65 to 75 years old. From diagnosis to death is generally three to five years, so they're fighting against a terminal disease. But there's some important measures here that we think that we can have that Milparan can't. So again, with that patient population, convenience is important. So 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 3 to avoid hemodynamic issues and that dose titration can take anywhere from 6 to 17 days upon the initiation of Edmil Paran that is certainly cumbersome there could be hemodynamic issues that occur during that dose titration we know that they tested this in cohort one in their phase 3 study. We don't have that hemodynamic signal, so this is a simple once-daily dose starting at the beginning of treatment. So dosing, convenience, tolerability, as I said, we do not see the hemodynamic signal. And if you look at even the original phase 2 study from Edmil-Pranton, both IPF and PPF, outside of the hemodynamic signal, this mechanism is extraordinarily clean. The side effect profile in the phase two studies were generally consistent with what you see with profenadone and intetanib, the historic standards of care. And 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, this is as close to an antibody profile that you can have with a small molecule against

Speaker 1

this target. Great. So you were just talking about the titration scheme that they have, and 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?

Speaker 2

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 two, and they just introduced this into their phase three, 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 one in their phase three study. So this was a time period in the phase three 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. So we know that they see that hemodynamic signal very early in their dosing

Speaker 1

regimen, and they're hoping to wash that out. At the recent ATS conference, you presented data comparing 791 to Ed Milperent. I guess, could you elaborate on the distinct lung occupancy profiles that were kind of demonstrated in that poster, and specifically, how does the potency

Speaker 2

or residence time allow for that safety profile? Yeah, so 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 EMSO2O, 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. So 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 they have a compound that has a very fast and what initiates the fibrotic cascade for IPF with this specific mechanism is when there's an injury, LPA floods into the system, right? And LPA activates the LPA1 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 to peak. And the peak to trough is very low. and you can think of this as an automatic stopping break with our pharmacokinetics, right? It is a built-in titration that allows us to not have that hemodynamic impact. Okay, great. And you

Speaker 1

mentioned the importance of receptor occupancy and 791 achieving about 90% receptor occupancy. I guess, what are the PK kind of properties that enabled that activity? Yeah, so when we first

Speaker 2

started this program, we did what a lot of companies do. We were patent busting around other LPA1 receptor antagonists. We couldn't get the properties that we wanted, both from a CNS perspective or from a PK perspective. So we moved into a completely novelist state. 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, we went as high as 10 milligrams, so one milligram. With all of those doses, we are able to achieve 90% receptor occupancy at steady state, and when we look at the 10 milligram dose, which is what we tested in our pain study, where I'm multiples above 90%. And as we look at that relative to BMS, when you start to analyze the data from their phase two, they had two doses. They had a 30-mig BID and they had a 60-mig BID for 26 weeks. It's pretty clear that the 30-mig BID really didn't have much receptor occupancy at all, and we can look at their PK to justify that. And with that, they did not have a signal of any significance in their study. The 60-MIG-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. So as we look to what they did in their phase three, the only rationale in doubling that dose, again, looking at 120 meg BID, knowing that there is a potential hemodynamic signal, is to increase receptor occupancy. And from our modeling, we still don't think that they are anywhere close to 80, 90 percent receptor occupancy with the new dose, whereas we're able to do that with every dose that we test.

Speaker 1

You mentioned this at the top, but you've got a Phase II Propel IPF study that's currently 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?

Speaker 2

Yeah, the receptivity has been really good. So 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. So we're running 324 patients, 108 patients per arm. two different doses, and a placebo arm. We have not updated trial enrollment, but the clinicaltrials.gov listing was recently updated, so 20 sites are online. New territories are coming online very rapidly, so we're looking forward to getting that into steady state.

Speaker 1

And patients are allowed to be on background therapy like OFEV and Esbriate, but how do you think the recent approval of JOSCAID kind of changes the market dynamics, and particularly the enrollment dynamics in IEPF?

Speaker 2

Yeah, I think it's too early to tell. So obviously, profanadone and intentative 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 JASCADE. 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. But as we see that continue, currently in our IPF study, in the Propel IPF study, we have only nintentative and profenadone as background therapy, but we'll continue to monitor JASCADE, and in all likelihood, we'll be adding that into the background therapy over the course of this study.

Speaker 1

And then in terms of the additional drugs that could come to market, things like TPIP, Do you anticipate any changes, like further changes there as you progress through clinical development?

Speaker 2

No, I think we're in a pretty good situation right now in terms of recruiting. There are no major big pharma phase threes ongoing. EMS is essentially done. BI is out of the market. Tyvaso is out of the market now as well. So there are a few phase twos. 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 it's about 350 patients, but it's focused on PHILD and not IPF or PPF generally. So I think even with the smaller programs, the Avalon programs, Endeavor, from what I understand, is fully enrolled as is VICOR. So this is really a good opportunity for us to pick up recruitment in the Propel IPF study.

Speaker 1

Great. And I think you've previously shown benefit on pain. So how would you think about incorporating that as a secondary endpoint in Propel-IPF, and what role could that play in

Speaker 2

kind of capturing the total patient benefit? Yeah, we'll have some patient-reported outcomes that were already contemplated in the Propel-IPF study, but as we think about how a brain penetrant LPA1 receptor antagonist can change the treatment paradigm for these patients, we find this really interesting. So we have a compound that we believe will have the best benefit on FVC, just given the target coverage. It's a safe compound. But when you look at what patients are being treated on right now, whether it's ntetanib, profenadone, nirondomalast, eventually Tyvaso, this is slowing the rate of decline. So 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. So if we can have a drug that allows for, even if it's a reduction in decline of FVC, but we can also have a quality of life measure. So 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, you know, 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

Speaker 1

required for that reduction in pain. What portion of IPF patients currently suffer from comorbid pain? You just talked about a couple of sources of it. And how is that

Speaker 2

symptom currently managed? Right now, they're currently managed. So, again, focusing on the patient population, 65 to 75. 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, over 50% of patients have have chronic pain, whether it's chronic lower back pain or OA. So 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? And 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

Speaker 1

pain. Okay, great. And could you just speak to the properties, particularly the brain penetrants, the 791 that enable that benefit you've seen previously on pain and contrast that with

Speaker 2

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 Continuum. Great, great. So you've mentioned the PROPEL-IPF study a couple

Speaker 1

times, but it's a 26-week trial. Can you talk about the rationale for measuring FEC at 26 weeks for, I think, registrational programs or 52? Yeah, for us, we need to think about this as

Speaker 2

a proof-of-concept study, and as we think about the potential approval procedure, a 26-week study can qualify as one of two well-controlled clinical studies, so that can be part of the registration package. We chose this because we saw the BMS020 data, we saw the BMS278 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, like even in looking at the BI data showing a profibrotic 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. And what do you think about as defining a sufficient

Speaker 1

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 end point?

Speaker 2

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 O2O data, it was pretty spectacular. You look at the 278 data, what it was about, 40 to 60 mil decline, something like that.

Speaker 1

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 triprostanols. There's privates. CINDEX has their program. So 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?

Speaker 2

Yeah, so this comes down to polypharmacy in the long run. There will be multiple agents used in parallel. Right now, we don't have that benefit because profanidone and intendinib can't be used together or not used together. And similarly, near-endomolaf has a DDI with profanidone and exacerbates GI issues when on top of OFEV. we think that LPA1 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. And 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 FBC and can be combinable with all other agents. So 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 nirondolamolast or Avalyn's nintetanib.

Speaker 1

So you mentioned that this could be a backbone with combination across all of these different Are there any that have like particular mechanistic rationale or that you think would be particularly interesting combinations?

Speaker 2

There's a number of ways. So this is clearly a fibrotic pathway. Even drugs with Tyvaso, I think a lot of this is driven through bronchodilation. So there's that potential. With triprostanil, 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. So 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

Speaker 1

puffs a day in an elderly patient population. Maybe switching gears here a little bit, you recently reported positive data from a phase 1B study in pain. I guess, could you recap that data and your kind of primary takeaways as it relates to advancing that program?

Speaker 2

Yeah, so 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 1b exploratory trend-seeking. What really had us starting to consider this is there's a lot of literature precedent that's similar to IPF, right? LPA being the bad actor that activates the ascending pain pathway, both centrally and peripherally. And 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. So that was the first step. And then we did a non-human primate study, a chronic constriction injury, functional MRI. So a very objective measure in anesthetized animals. And what we saw is a blunting of that signal in the brain. So that started the process for us. The takeaways from our study, again, it was 43 patients, crossover design, four weeks on drug, and then four weeks off, and vice versa. So the biggest takeaway for me is this is the longest we've ever had patients on Pipe791 at the highest dose that we can test or that has been tested. And we saw no issues with safety and tolerability, no hemodynamic effects, a very clean safety profile. And the cherry on top for us was we were hoping to see a signal, and that's exactly what we saw, especially in chronic osteoarthritic pain. We saw movement in 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 COOS score as well, which is specific to osteoarthritis. So we saw a similar improvement on chronic lower back pain in treatment period one. There's always vagaries associated with crossovers, especially carryover effect. But what we saw was the trend that we had hoped to see.

Speaker 1

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 ICF trial?

Speaker 2

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 really gives us a lot of confidence that this is a safe and tolerable, it's a compound that should be tested further due to the safety and tolerability that we've seen already.

Speaker 1

Great. And on the regulatory front, what does the path forward look like here?

Speaker 2

For pain?

Speaker 1

Like, what does Phase II look like?

Speaker 2

So we see this as complementary to what we're doing in IPF and PPF. So 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. But 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. But right now, it's a little too premature.

Speaker 1

Switching gears again, you have a phase two study in major depressive disorder. And I think that readout is expected in the middle of this year. These are obviously kind of like notoriously difficult indications. But could you speak to your level of confidence at the M1 receptor mechanism here for depression? And just remind us the clinical data that exists to support it.

Speaker 2

So this is a program that we have partnered with Johnson & Johnson. J&J is running the Phase II Moonlight I 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. So there are multiple studies that have been done with dirty anti-muscarinics, so specifically scopolamine, which is a broad pan-muscarinic antagonist, demonstrating a rapid and robust improvement in Madras across multiple different depression settings, MDD, TRD, bipolar. So J&J is running the proof-of-concept study right now in MDD. They're looking at three different dose regimens, so placebo and then two pulse-dose regimens, one at a higher dose and one with a step-down dose. the data from scopolamine looks very compelling and 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 antagonists the lack of a cognitive signal in our phase one 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. So I'm not going to handicap what we should see, just because this is J&J's program, and 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, and now that's looking to do 1.7, than $1.8 billion a year in sales.

Speaker 1

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?

Speaker 2

So, again, the MDD study is their study. We keep... They keep us informed on the status, and we will be putting out top-line data. So, but this collaboration started in the first half of 2023. So with this, we received $50 million up front, $25 million in equity. They also contributed into the IPO. We have about $1 billion left in milestones, a little bit more than that, and 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, and that would allow us to push that royalty even further.

Speaker 1

Okay, great. Any learnings that you take away from the VISTA failure you guys had in multiple sclerosis? And could you discuss any read-through to Moonlight 1 with respect to either safety or the dose selection?

Speaker 2

Other than same mechanism, the biologic rationale is very different. So 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. So 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. The biggest takeaway for me is that we had over 150 patients on drug for six months,

Speaker 1

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 in terms of cash runway?

Speaker 2

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 have at least four quarters of capital post-conclusion of the Propel IPF study.

Speaker 1

Great. Thanks. And with that, thanks so much for joining us, both here and online, and thank you so much for all the insights today.

Speaker 2

Great. Thanks, Grant.