Contineum Therapeutics, Inc. (CTNM) May 19, 2026 Conference Transcript

joining us for this next session. My name is Nevin Varghese. I'm one of the analysts at RBC Capital Markets. Thank you for joining us today. We have with us Carmine Stengon, who's the president and CEO of Continuum Therapeutics. Carmine, thank you for being with us. All right. Thanks for the invite. So diving right into it, you know, we've seen we've seen some data recently. I think some of the data that we saw recently from pain was particularly intriguing. So I'm wondering if you could touch on that a little bit more, just given that, you know, some of the Phase 1B chronic pain data that we saw showed promising trends in pain reduction and responder rates. This was supposed to be exploratory, but it was a nice surprise, I guess, seeing this. To what degree do you think that this potential pain improvement that we saw was mediated by the central activity of 791? We're actually pretty confident about that.

And just to set the stage for the study that Nevin's talking about, this was a small exploratory phase 1D study. The goal was to enroll 40 patients in two different pain syndromes, so chronic osteoarthritic pain, as well as chronic lower back pain. Primary endpoint was safety and tolerability, but we had exploratory endpoints around the PINRS scale, both on an average basis, on a worse scale basis. um looking into 30 responder rates and then some pros associated with adl so activities of daily living specific to oa um we hit our primary endpoint on safety and tolerability and uh pipe 791 the lion's share of the value is in the ipf arena and a lot of the information that we got from safety and tolerability perspective we believe helps de-risk the ipf phase two that is currently ongoing but from a central versus peripheral sensitization here we believe that we have impacts on both so part of that reason is we have a peripherally restricted lpa1 receptor antagonist in our portfolio as well and we tested that not in not in humans but in animal models and what we saw was an outsized response with a centrally active compound as opposed to a peripheral. And if you think about this mechanistically with LPA activating LPA one on Schwann cells, that is the peripheral component that where you start to see an impact on the central side, it's driven through microglial activation. So LPA activating the microglia leading to a neuroinflammatory cascade that can be mitigated with a compound like 791. And it is, it's a unique attribute to type 791. We're the only company that we're aware of with a centrally active LPA1 receptor antagonist.

Got it. And then, you know, we had seen some kind of differential responses there between, excuse me, the osteoarthritic pain and the lower back pain as well. Just given, I guess, the centrally mediated effect here, what do you think kind of explains the differences that we saw there? Why was, I believe it's the osteoarthritic pain where we saw more kind of greater signals of efficacy than in the lower back pain? What do you think maybe explains that?

Yeah, we're not looking to over-interpret the data. If we look at it objectively, we have treatment period one. So the way that this was designed, it was a crossover design, patients on drug for four weeks, and then they cross over to placebo or vice versa. And there was no washout at that. at that crossover period. If we look at just treatment period one, which is more indicative of what we would do in a potential phase two study, that is a true parallel design. You see numeric improvements in both chronic lower back pain as well as osteoarthritis. The signal for osteoarthritis is objectively better over treatment period two as well, but there is there's reasoning for that as well. For osteoarthritis, it's a pretty homogeneous disease. Actually, all of the subjects who were in our study for OA had imaging to make sure that they did have true osteoarthritis. For chronic lower back pain, it's much more heterogeneous. You have patients who have musculoskeletal pain, that have joint pain, that have sciatica, that have LSR. So it's a much more difficult patient population to assess in a crossover design.

Okay, great. And then if you could touch a little bit more on the safety profile here. So I know that again, this was just exploratory, and finding the signals was good. But this was also one of the longer studies that have been conducted with 719. And how do you see that de-risking this opportunity in IPF, and then if you could also bake that into the, just given the pain signals that we saw here, how you think that might be a potential additional differentiator for 791 versus what Bristol's looking at with a no point.

Sure. Sorry, I missed the first part.

So essentially just on, if you could touch on the safety aspects of this again, and some of the de-risking that we've seen from the period of dosing that we've seen so far.

Yeah, and as you mentioned, so four weeks of dosing is the longest any patient has been on, type 791. It's also at the highest dose that we have tested in our MAD study, in our healthy volunteer. And we were confident in this, but we were really pleased with what we saw. There was a very benign AE profile, generally mild to moderate. The important thing here, and again, as it relates to IPF, is EMS has a hypotension signal that they've been pretty upfront about across all of their studies, and they seem to have used the dose titration in the phase three to try and wash that out. We monitored blood pressure throughout this study. we didn't see any hemodynamic effects, no major AEs, no cardiac issues. And again, this is at a dose that is orders of magnitude above, I'm not orders of magnitude, it is above the 90% receptor occupancy. So this is a very potent dose of 791.

How confident are you that the four-week endpoint at that point, if we're not seeing these hemodynamic effects, that likely that we may not see those effects later on?

You know, I never say never, but based on what we've seen in our healthy volunteer study, in our PET work, and now in a study where we've had over 40 patients on drug for a four-week period, it definitely raises our confidence that we will not see what BMS has seen. And there's other reasons for that that we can certainly discuss on IPF. Got it.

Yeah, and then last question on pain, I guess, how are you assessing, just given that you've had a little bit more time with the data at this point, how are you thinking about next steps and what that might look like, what pain indications you might potentially go Is it osteoarthritis and lower back pain, or are there, you know, plundionectomy, abdominoplasty studies that have been more traditional? Definitely not acute.

Just the pharmacokinetics of this molecule, it's not, it would not be an acute treatment. method. We need to be upfront that the lion's share of the value in the company and the focus of the company clinically right now is in IPF and pulmonary fibrosis. That doesn't mean that we don't want to bring this into a phase two, but we want to spend a little bit more time with the data, talk with KOLs, engage with pharma and with investors, and really decide on the next steps in a more conservative fashion at this point. So we believe that the data warrants movement into additional clinical studies. We want to make sure that we choose the right indication right now. Objectively, OA looks better than chronic lower back pain, but we also want to look at this on how do we improve quality of life in patients with pulmonary fibrosis with pain. You have progressive pulmonary fibrosis. 62% of patients have chronic pain. And if you look at OA simply is you have the majority of the population with osteoarthritis is approaching elderly. You have IPF 90% of patients are greater than 65. So at this point, when you look at the current treatments for IPF, they are reducing the decline in FVC, but they're not changing the patient's life, right? So they will never feel better than the day before because they continue to lose function.

With the profile that we have with 791, we hope that we can improve not only on the function, the lung function, but potentially add a quality of life metric in there, whether it's thoracic pain, knee pain, that improves um that improves their life okay um and then i guess looking out across the broader lpa one receptor landscape what are you looking for from the adnobirant data in ipf later this year if bms is able to show robust efficacy there is that something that could potentially accelerate 719's development um and you know how do you think the potential clinical differentiation of 791 might be, like, how well defined do you think the differentiators might be based on that data set? Sure.

Yeah, we've spent a lot of time with the BMS data. We expect that it'll work in IPF and PPF, but that still remains to be seen. In terms of accelerating our clinical trial, right now the focus of the company is on running a robust and well-controlled phase two. because we know that that is one of the components of getting an approval is two well-controlled studies. We're rooting for them, honestly, but we feel like even if they hit on most of the endpoints that we've got key differentiators. And I think that there are four that we like to discuss. The easiest one is the PK of our molecule allows for QD dosing, right, which is generally not the biggest differentiator, but again, you're dealing with patients that in the Taivasso study were 75 years old on average. Where it gets really interesting is given, again, the PK of our molecule with the slow on and off rate, we have not seen any BP issues that we're concerned with. So nothing clinically relevant there, which is a departure from where BMS is. So we think that we can avoid safety and tolerability challenges. And then, given the properties of the molecule, we have extended coverage above 90% receptor occupancy. If you look at the animal models, as well as the BMS020 data, and to some extent even the BMS278 data, higher coverage means a bigger improvement in that FVC decline. and given we've tested in humans one milligram, three milligrams, 10 milligrams, each of those allows for 90% receptor occupancy or multiples of that beyond it. So we think that we can differentiate hopefully on efficacy, on safety and tolerability, on dosing. And then the last one is the surprise that we saw out of our phase 1b study. Can we improve quality of life? Can we potentially alleviate pain in PPF patients or ILD patients to make this a better patient journey.

Are there any specific modifications that you might make to the ongoing phase two in order to incorporate more aspects of quality of life, just given the pain signal that you've seen here?

We do have exploratory endpoints already in the study, and there is an opportunity to do more on that in a phase three or in subsequent studies. Got it. Okay.

Yeah, just I guess taking a step back, looking at the broader market, how are you thinking about what the broader IPF market looks like now and how 791 would fit into that treatment landscape?

Yeah, it feels like we're in a renaissance for pulmonary fibrosis treatment. It was a long time between OFEV and profenadone and now having near-endomalast, and I assume, like everybody else, that Tyvaso will get a label soon as well. From what we understand, BI's uptake of near-endomalast relative to OFEV is pretty interesting. So there is something that treating physicians and patients have in the quiver, again, as a treatment. But I think that there are still holes in a lot of these. So nirondomilast is an interesting drug. They certainly showed a robust move on FVC, but it also did exacerbate some of the GI challenges associated with OFEB, as well as a potential DDI with perfidodone. So we think anything that comes to market is fantastic, because it is an extra potential treatment for patients. Similarly with Tybaso, the data look pretty darn good. The 90% confidence intervals are actually pretty close to what your endomalask has, but there is a cough component to this and a compliance component doing four puffs a day, four times a day. So we see those as in the treatment regimen, but if we look at, we don't have a safety profile right now in patients, but BMS does from their phase two. And if you look at the data with that Milprand in the phase two, both in IPF and PPF, removing the hypotension, because that's a signal that we don't expect to see, and we are not going to have a titratable dose. This is going to be a very simple regimen. The AE profile for GI toxicity or other issues associated with profenadone were the only real adverse events that come through with the LPA1 mechanism. So we think that LPA1 receptor antagonism and, you know, pointing out 7-9-1 as a best-in-class can serve as the backbone therapy within an IPF and PPF landscape and then add on your endomalase, tyvasa, or whatever is on the horizon.

Okay. That makes a lot of sense. And then what's your latest thinking about looking at 791 in PPF? Are there any points along the current clinical development path for IPF that you will look to initiate these clinical studies in PPF, or are you waiting to see maybe data from?

No. So BMS ran their IPF-PPF in parallel in the phase two. If you look at BI with narindomal acid, they ran IPF alone. What we want to do is make sure that we run a well-controlled study right now in IPF. And again, to get a drug approved through the pulmonary franchise, it is two well-controlled studies. So we can get a phase three on IPF. And then in parallel, we would also run the phase three in PPF. And we're very confident in LPA1 receptor antagonism in PTF. Just looking at the BMS data, looks like the patients with progressive pulmonary fibrosis actually perform better than the idiopathic pulmonary fibrosis patients.

Just switching gears to 307, that's being studied for MDD by your partner, Jane Jay. Can you remind us about what the rationale for this is and how it might impact potential market use and positioning? And how do you think the mechanistic rationale here differs in depression as compared to multiple sclerosis where we didn't see as much of a strong syndrome?

Yeah, so jumping on that second part. So for 307 in MS, we were looking at the potential to remyelinate axon. And this is driven through M1 receptor antagonism on the oligodendrocyte. While it's mechanistically the same, the biological rationale in depression is very different. And this is through work done with scopolamine and some validation that came through BMS, I'm sorry, through Eli Lilly and Jane Jay, by inhibiting M1 receptors on GABA, inhibitory GABA neurons. That allows for an increase in glutamate burst and then a a synaptogenic response, so showing increases in dendritic spines.

Okay, got it. And then how are you thinking about, or I guess, has it been communicated yet when and where that data might be shared? Publicly?

Yes, sorry. Not when the data will be shared, but J&J has updated their clinicaltrials.gov listing for this.

Unfortunately, given well not unfortunately because we love our partners we're not going to divulge anything confidential but they are looking at study conclusion in June of this year and we anticipate data in the second half okay um and moving uh just taking a step back to the MS trial as well Um, have you, have you kind of done a, a, a postmortem of sorts on what went wrong with the phase two trial? Was this a target engagement issue? How was there a population, uh, mismatched there or any other limitations, uh, within kind of the M1 antagonism for remyelination?

No, we, again, the clinical validation for M1 antagonism in MS was thinner than what we see in depression, which is thinner than what we see with LPA1 and IPF. We ran a well-controlled study. The drug was safe and tolerable. We just, we missed on our primary endpoint.

There's potential maybe that primary endpoint wasn't ideal, looking at low contrast letter acuity in these patients. um but we have worked with j and j looking at some of the exploratory work and there's some interesting nuggets for them there as well well will we see any additional kind of color on that in in the near term or um tbd yeah it's uh it's discussions with our partner got it um and then going back to 791 just wondering how you're thinking about um what your appetite for additional partnerships is at this stage so assuming that admiral baranton looks good is this kind of one of those things where you want to wait to see before you you know potentially have these partnering discussions or these kind of in uh in in in active discussions now would

you look to take this yourself uh moving forward how are you coming yeah so so we signed the j and j deal back in 2023 and it made perfect sense then um we were a company of 35 people maybe There was no way for us to effectively run and then commercialize a product in MDG. So it made a lot of sense to do that deal. We think that we have validated our ability to identify compounds against top targets through that. And we've done the same thing with LPA1. But as we look at the landscape for IPF, it's different. This is something that a small company can bring forward. We also understand that this is the main value driver for the company at this point. And partnering a second asset and lead asset is not something that we would foresee in the near future. But we obviously will have partnering discussions on some of our earlier stage assets. We've got a couple of interesting targets coming through. Okay.

Is there any additional color you can provide on some of those earlier assets? or? No, I'm trying to keep it pretty tight at this point. Can you remind us about what the IP for 791 looks like?

So we have, I believe it's coverage through 2042 with potential patent term extensions pushing it to 2044. And I think with 307, it was 2040. And those are all pre-patent term extensions.

And then I guess in your recent interactions on the regulatory side, how have they been going? Have you had any recent updated conversations with the FDA? Have there been any changes with your regulatory interactions?

No, the team is trying to execute on getting as many territories and sites up and running. We're meeting our internal guidelines for the board. So we're pretty happy around the start of this. We only started enrolling patients last quarter.

Okay. And then if you could talk a little bit more about what the trial conduct has looked like, I know it's early days, but just what the trial conduct has looked like. Are there any potential learnings that you've taken from the trial that Bristol has run so far that you've kind of integrated within your own conduct?

Yeah. So we want to run as close to an apples-to-apples comparison if possible against Bristol Space 2. We've upsized it a little bit because we are powering it up appropriately. But being able to look at that apples-to-apples comparison, being able to look at their data, so based on what we see on clinicaltrials.gov, we don't believe that they have in their 30-mig and 60-meg BID target receptor occupancy that would drive a full effect with an LPA1 receptor antagonist. We're really excited to see their 120-meg BID and also learn more about the dose titration scheme that they implemented in that phase three. Okay, got it.

And then can you remind us about what the capital runway looks like?

Sure, yeah. We just reported Q1. We have about 250 million in the bank that funds the company through the middle of 2029 and that gives us buffer on the conclusion of our uh phase two propel ipf study excellent well carmine thank you so much appreciate it thank you everyone thanks david thanks again for seeing you