Good afternoon, everyone. My name is Sean Lerman. I am the head of U.S. Midcap Biotech Equity Research at Morgan Stanley. Welcome to Morgan Stanley's Global Healthcare Conference. Before we begin, just to make you aware of some important disclosures, please see those disclosures at the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you do have any questions on that, please reach out to your Morgan Stanley sales representative. For this session, we welcome Contineum Therapeutics with CEO Carmine Stengone. Welcome, Carmine. I hope I pronounced your surname correctly. Close enough. Close enough. Maybe just to begin with some introductory macro questions. How is the rise of China origin innovation changing the way that you think, either in a BD sense or an R&D sense, or if at all? Yeah. I think it changes the pace of innovation now. We have several compounds that are being developed across mechanisms that we see. in U.S. and European companies. For us, we see it as a potential advantage. There is the opportunity for additional BD, as you said. As we look to continue to expand our portfolio, we can look towards China and potentially more rational cost metrics around there as well. It also gives us an opportunity in the future to potentially find additional partners for the Asian regions. Sure. Thank you. Are you implementing AI across your business? If so, can you point to some specifics on whether it is a cost save, a decision made, or even sort of POS assumptions within your pipeline? We do. The main focus on this is cost efficiency and being able to generate data in a much more efficient manner. For instance, we can generate phase II data sets from our competitors and be able to evaluate that in a much more rapid fashion than had we were building spreadsheets for that, as well as around competitive intelligence and investor interactions and things like that. We see this as a tool for efficiency and ability to reduce costs. We are not using this to synthesize molecules or anything like that. We are very focused on the biology and the team that we have that has been able to generate our portfolio since our inception. Yeah, wonderful. Thank you. Last question in a macro sense. I am guessing it is the FDA, but which policy variable do you think about the most? Is it FDA? Is it Medicare negotiation tariffs? What do you think about the most? By and large, FDA. We're an early-stage company. We're in the clinic. Obviously, we lean on FDA for guidance for study conduct. It is really the key regulator that we focus on in getting the study up and running. Wonderful. Thank you. I'm going to focus this discussion on PIPE-791. Sure. Just to deal with, can you give us a summary of PIPE-307 and the recent disclosure before we move on? Sure. We recently put out data or a press release with our partner, Johnson & Johnson, for PIPE-307. This program or this compound was in a phase IIa study focused on MDD and really looking into the cholinergic thesis of depression. A well-controlled study, over 100 patients. Unfortunately, like a lot of MDD studies, we missed on the primary endpoint. J&J has been a fantastic partner through this, and as we communicated in the press release, they are investigating pre-specified exploratory endpoints. We don't have any data to speak about today, but we're looking forward to getting more information from J&J and seeing what the next steps, if any, in the development program of PIPE-307 will be. Okay. Thank you, Carmine Stengone. To move on to the real meat, which is PIPE-791 and PROPEL-IPF. It is a once daily LPA1R antagonist without the same titration burden as Bristol Myers Squibb's shot on goal in IPF. How meaningful is that in older symptomatic population already taking background anti-fibrotic therapy? Yeah. I think that it is more meaningful than it sounds like on paper. If you look at the patient population with IPF, generally 65- 85 years old patients, infirm, a lot of comorbidities, as well as additional treatments that are on their treatment schedule. So having a dose titration adds complexity to their treatment. It potentially leads to additional doctor's visits and things like that. To be able to identify in advance a compound that can be at its starting dose from the very beginning leads to convenience, and I think in this patient population, that is not lip service. That is something that is meaningful in their adherence and ability to address their disease with 791. Sure. Thank you. PROPEL-IPF, it is now active in more than 55 sites across Yeah eight countries. Where does enrollment stand against the 324-patient target, and when should enrollment complete, and when should investors expect top-line data? Yeah. As you mentioned, it's a 324-patient study. We actually have, as of ClinicalTrials.gov yesterday, we have 70 sites open. The goal here is to potentially go as high as 150+ sites. We don't give guidance on individual patient enrollment. Sure. We will continue to update ClinicalTrials.gov and we expect to have the study completed in the middle of 2028. From a runway perspective, we have about $240 million in cash based on our last earnings, and that funds the company for 12 months past the completion of the PROPEL-IPF study. Wonderful. Thank you. The primary endpoint is absolute change in FVC through week 26, while admilparant's phase III evaluates FVC at week 52. Why is 26 weeks sufficient, and what placebo-adjusted difference would be both stat C again and clinically meaningful? Yeah, there's a difference here with a phase II versus a phase III. The admilparant ALOFT-IPF study has over 1,200 patients in it, and obviously they're looking at this as their key component for the registration program. In contemporary studies, 26-week programs for proof of concept have been well accepted, and we're able to see that change in FVC decline. This is really establishing the proof of concept, evaluating the doses that we could potentially bring forward in a pivotal study. With admilparant, like I said, this is a 52-week study that they will be looking to include in their pivotal program. Sure. Thank you. What proportion of PROPEL patients are receiving background antifibrotics, and do you expect PIPE-791's treatment effect to be consistent across the background regimens? Yeah. In most contemporary studies now that include background therapy, typically it's 2/3-3/4 on background. For our current study, we include nintedanib and pirfenidone as background therapy. Nerandomilast had not been approved by the time we Right initiated this study. We will continue to evaluate their script numbers, and there's a high probability that we will include nerandomilast as a background therapy as well. Sean, I'm sorry, I missed the second part of the Oh, yeah. Just that do you expect the treatment effect to be consistent across whether background therapy or no background therapy? We do. We've seen this through the original admilparant data in their phase II as well as nerandomilast and others. Sure. Thanks, Carmine. At ATS, you highlighted differences in lung occupancy and vascular pharmacology versus BMS-986278. What does the PD PET dataset establish about the depth and duration of LPA1 coverage, and how did it inform dose selection? Yeah. So this is really a critical component of our differentiation strategy versus admilparant. From the non-clinical work as well as looking at BMS-986020, which was the first-generation molecule, it appears that having higher receptor occupancy drives a benefit in the bleomycin model, but potentially in FVC as well. BMS has added a new dose into their phase III at 120 mgs BID. We believe that they are doing this to attempt to improve target coverage and have an FVC benefit there as well. We ran a positron emission tomography study to set the 50% and 90% receptor occupancy with our molecule. What we were able to demonstrate through the PK that we generated in our multiple ascending dose healthy volunteer study is at all of the doses in the MAD, so 1mg, 3mg, and 10mg as a QD dose, we achieve, at steady state, 90% coverage at the 1mg, and then multiples beyond that at both three and 10. So we think that this is an opportunity to really max out the viability of this receptor and having a positive outcome in this patient population. Yeah. Well, wonderful. Moving on to the evolving IPF landscape, so on a pretty important data point coming up with BMS' phase III ALOFT-IPF for admilparant. Expected to read out by year-end, so well before PROPEL. How would you interpret a positive result versus a negative one, and how should investors gauge that data as it relates to the class and to your program and its differentiation? Yeah. I would tell you that the Contineum team is the biggest cheerleaders out there for the BMS data. We are very bullish on this. I think unlike other mechanisms that have failed in phase IIs, there is a high degree of clinical validation that BMS has generated. 500 patients, two different studies, three different cohorts, all demonstrating an improvement in FVC decline. We think that the clinical validation there is pretty indisputable at this point. For their phase III, again, if this is positive, this is further validation for the class and will make us even more bullish on our differentiation story. If they miss, one, we would have to know what that was. Was it insufficient target coverage? Is it a tox profile? Is it actually mechanism related, or is it drug related? That is something that we would have to dig through and see if it is drug related. We believe that we have a best-in-class, if not best-in-disease approach to IPF. Sure. Can you make some commentary around the potential differences in hemodynamic profile between your drug and admilparant? Yeah. A credit to BMS, they have been very upfront that they have seen hemodynamic signals across their studies. Starting at the healthy volunteer into the phase II, and they were looking to mitigate this in the phase III in a dose titration. It looks like this has worked because from what we understand, the 120 mg dose got through that cohort one. But they did implement a dose titration from what we understand can take anywhere from seven- 16 days to get to the 120mg dose. That dose titration was not evaluated in the phase II. We are questioning whether a dose titration will be required in a commercial setting or not. We have not seen the hemodynamic signature that BMS has, so we are confident in not having to do a dose titration. We actually generated data and presented it at ATS, non-clinical data obviously, demonstrating why a compound with a fast on and off rate and a high peak to trough may have a hemodynamic signature, whereas the pharmacokinetic profile of PIPE-791 prevents that. Right. Sure. You've kind of made a case already for the next question, but I'll ask it anyway. Assuming admilparant reaches the market first, what's the commercial case for a second LPA1 antagonist? I think that their commercial case right now is that they're first in class. I don't think it's a bad position for a smaller biotech to have pharma start to build the market. What we believe is that a more safe, tolerable QD dose, potentially with a benefit in FVC and a potential benefit in quality of life around CNS penetrance, will overtake a first-in-class approach. We truly believe that the LPA class will serve as the backbone for combination therapy. We also truly believe with what we have seen so far with our compound, that we have the potential to be best in class and the backbone of therapy across IPF. Sure. Thank you. Still on the evolving competitive landscape. United Therapeutics are advancing their drug through a non-antifibrotic mechanism. If successful, does it change the standard of care PIPE-791 would be added to or the efficacy bar it must clear? I don't know that it changes the efficacy bar that must be cleared. I didn't answer your question before. We think that a 50% reduction in FVC decline is the barrier here. With TYVASO, I think it's a different mechanism. It is certainly something that we would look to combine with, but I don't think that it changes the landscape. Even if you look at the data between nerandomilast and TYVASO, the 95% confidence intervals overlap. In speaking with KOL, something that we have heard is that a compound that has a slightly smaller FVC decline but is tolerable is more ideal than a compound like we have with OFEV. Sure 50% of patients don't take the drug, and the majority of patients roll off the drug because of tolerability. If we can have, with this class or any other class of compound, a sizable reduction in FVC decline, but also have a side effect profile that makes patients adherent to it, is really the benefit that we want to show so patients can actually extend their life. Sure. How should investors compare the data that we have seen so far from Insilico Medicine and their program? To be frank, I haven't seen any data. Okay. Yeah. Yeah. Okay. I'm sorry. I haven't. Yeah, fair enough. Longer term, do you view LPA1 antagonists as replacements for existing antifibrotics or combination partners or treatments for patients unable to tolerate current therapy? Our hope is that this. We've had a kind of renaissance in IPF, right? There was dark days a few years back, but now we have not only pirfenidone and nintedanib, but we have nerandomilast, which it looks like a very good drug. From what we understand, the scripts have been pretty impressive, and we'll have TYVASO coming. I think we need to think about IPF like we thought about the antivirals in HCV and HIV. It really changed the treatment paradigm in patients and the lifespan of patients when combination therapies came around, similarly with drugs in oncology. We look forward to the opportunity to combine with nerandomilast, with Ablynx drugs. I think we're all in this to extend the lives of patients and give them a healthier existence. To do that, it's not going to be a one drug treats all. Sure. Maybe a bit of a market sizing question. Yeah. How do you think about the market size in the U.S., how many patients are annualized, that are diagnosed with IPF? The existing prevalent base, how do you frame that, and how do you assess the addressable population? Yeah. From an IPF side, you have about 130,000- 140,000 prevalent patients. The incidence rate, I believe, on an annual basis is around 30,000, and that kind of fits with the current lifespan of patients. From diagnosis, generally, the lifespan is about three- five years. Really, as you think about this disease, it's comparable in terms of lifespan with some of the more virulent cancers, and I think people need to understand that is a big component of this is patients are refusing therapy right now despite the fact that it may be able to extend their life given the tolerability and safety issues. This is where we believe that LPA1 really excels. If you look at the BMS phase II data, the major side effects were primarily around the background therapies of OFEV and pirfenidone. Sure. How is it typically diagnosed, and what is the diagnostic algorithm? Yeah. It is usually diagnosed very late in the disease progression. It is generally people going to their primary care, and then to a pulmonologist to see if they have a UIP signature, and then that starts leading to the treatment regimen. Right. Is it better to diagnose early? Do we know that data? I do not know that there is prophylactic treatment, but yes, I would assume that it is much better to diagnose this early. Okay. How do you think about pricing and reimbursement? It might be a bit early in the day for- Oh, it's early for us- Yeah but it's certainly something that we think about. Yeah, maybe give us some context around that. Yeah. Medicare versus private, et cetera. Well, from what I understand, the average price in the U.S. for OFEV is about $135,000. Nintedanib, I think, is closer to $200,000, and TYVASO's already on the market for PH. That is a little bit more than $ 0.25 million. So, yeah. Yeah. What would you think about the pricing for your drug against those? Oh, I don't think that I'm ready to- Yeah. make an estimate there. No problem. Yeah. Thankfully, we do have a big pharma coming ahead of us. Yeah. You will know. Okay, fantastic. Moving on to capital and portfolio strategy. With PROPEL, the principal value driver, how are you balancing investment in that study against preserving optionality in chronic pain and CTX-343? Yeah. We have a nice balance sheet right now. As we look at resources, the number one resource that is going to be pushed is into the IPF franchise, and specifically on the phase II. That being said, we are excited about CTX-343. This is a peripherally restricted LPA1 receptor antagonist that could potentially move into additional indications, and as you mentioned, we have a pain portfolio or a pain program here as well where we tested PIPE-791. Right now, we are laser focused on PROPEL-IPF, getting that study completed, well, fully enrolled and then completed. But we will opportunistically use resources to advance other programs as well as we have bulked up our translational division at Contineum. Looking at the LPA1 mechanism, not only in pulmonary fibrosis- Right potentially other fibrotic disorders. Interesting. What milestones does the current balance sheet fund, and is the next major capital decision expected before or after PROPEL-IPF? I am sorry, Sean, I missed that. Oh, sorry. What milestones does the current balance sheet fund? Yeah. Is the next major capital decision expected before or after PROPEL data? We are funded through the middle of 2029. Okay. Which that means about 12 months after conclusion of the PROPEL-IPF study. From a capital perspective, obviously there is BMS data coming up. We are going to be opportunistic in terms of capital raises moving forward. We want to make sure that the company has the appropriate capital to not only complete this phase II, but run the ancillary DDI studies and everything else, and then start to think about a phase III program. Sure. Great. I have run through all my questions, so is there anything that I did not ask that I should have? No. No. We have covered it? Yeah, I think we are good. All right. We might call a close to proceedings here, but thank you- Okay for participating, and appreciate talking to you next time, Carmine. All right, Sean Lerman. Okay. I appreciate it. Thank you, everyone. Thank you.