Neumora Therapeutics Q4 2025 Earnings Call - Catalyst-rich pipeline: navacaprant readouts in Q2 2026, NMRA-215 delayed to Q1 2027 after rat tox audit

Operator: Ladies and gentlemen, thank you for standing by. At this time, all participants are in a listen-only mode. After the speaker’s presentation, there’ll be a question and answer session. Please be advised that today’s conference is being recorded. I would now like to turn the call over to Helen Rubenstein, Vice President of Investor Relations and Corporate Strategy at Neumora. Please go ahead.

Helen Rubenstein, Vice President of Investor Relations and Corporate Strategy, Neumora Therapeutics: Good afternoon, and thank you for joining Neumora Therapeutics’ fourth quarter and full year 2025 financial results conference call. Before we begin, I encourage everyone to visit the Investors and Media section of our website at neumora tx.com, where you can find the press release related to today’s call. With me on the call today are Chief Executive Officer Paul Berns, President Joshua Pinto, Chief Operating and Development Officer Bill Aurora, Chief Scientific Officer Nicholas Brandon, and Chief Financial Officer Michael Milligan. I’d like to point out that we will be making forward-looking statements during today’s call, which are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. Please review the risk factors discussed in today’s press release and in our SEC filings for additional detail. With that, I’ll now turn the call over to Paul.

Brian Abrahams, Analyst, RBC Capital Markets0: Thanks, Helen. Good morning, everyone, and thank you for joining us. 2025 marked a year of important clinical progress and execution for Neumora. We made meaningful strides in advancing our diverse pipeline of novel mechanism therapies, reported compelling data for NMRA-511, our oral, highly potent, brain-penetrant, and selective vasopressin 1A receptor antagonist, progressed our phase III program for navacaprant with optimizations based on key learnings from prior studies, expanded our M4 PAM franchise with two new programs in clinical development, and prioritized obesity as the lead indication for our brain-penetrant NLRP3 inhibitor, NMRA-215, and reported class-leading DIO data, all while continuing to strengthen our financial foundation. Our mission at Neumora remains clear, to advance the next generation of novel therapies that offer improved treatment outcomes and quality of life for patients living with brain diseases.

We believe through our differentiated approach, centered on advancing programs with best-in-class pharmacology and brain-penetrant chemistry, targeting novel mechanisms of action, we have the potential to deliver transformative therapies to millions of patients in need of better options. Now, as we move into 2026, Neumora is well positioned to achieve multiple potentially value-creating milestones within the next 12 months. As we approach these near-term catalysts, I am confident in the strength of our science, the focus of our strategy, and the dedication of our distinguished Neumora team to deliver revolutionized therapies for patients living with brain diseases. I will now turn the call over to Josh to review our pipeline updates. Josh?

Joshua Pinto, President, Neumora Therapeutics: Thank you, Paul. We are poised to build on the strong momentum from 2025 as we enter a catalyst-rich period with multiple clinical data readouts expected this year. Leading with NMRA-511, our oral, highly potent, brain-penetrant, and selective antagonist of the vasopressin 1A receptor in Alzheimer’s disease agitation. In January, we announced positive results from the phase I-B signal-seeking study of NMRA-511. NMRA-511 demonstrated a clinically meaningful effect size in people with Alzheimer’s disease and a favorable safety and tolerability profile, with no reports of somnolence or sedation. Today, we built upon those positive findings with new data from a pre-specified analysis of the phase I-B study in patients with a neuropsychiatric inventory, agitation, aggression, or NPI-AA score of four or greater, which aligns with the enrollment criteria from the Rexulti and Eveli pivotal studies.

These data further reinforce the potential for an unsurpassed profile of NMRA-511 in AD agitation, an area with significant unmet need for new treatments. As a next step, we are exploring higher doses of NMRA-511 in a MAD extension cohort from which we expect to report data in the second half of 2026. From there, we plan to initiate a phase II study with NMRA-511 in the first quarter of 2027. Turning to navacaprant, our kappa-opioid receptor antagonist for the monotherapy treatment of major depressive disorder. The KOASTAL-2 and KOASTAL-3 studies are now fully enrolled with more than 400 patients enrolled in each study. We look forward to reporting data from these studies in the second quarter. Additionally, on our M4 PAM franchise, we announced today that we have selected NMRA-898 as our lead program.

We believe that NMRA-898 is well suited for continued development in schizophrenia based on promising clinical results from an ongoing phase I study. We are currently conducting a multiple ascending dose study of NMRA-898 in healthy volunteers and patients with stable schizophrenia, and we expect to report data in the second half of 2026. Turning to our metabolic franchise, we announced two key updates today regarding NMRA-215, our highly brain-penetrant oral NLRP3 inhibitor for the treatment of obesity. The first update, and a very exciting one for us, is new positive data from a 12-week diet-induced obesity or DIO mouse study that reinforces the potential of NMRA-215 for the treatment of obesity in both the mechanism of action switch and the weight loss maintenance paradigm. These encouraging results further validate what we reported previously.

Class-leading weight loss as a monotherapy, additive weight loss in combination settings, potential for an incretin-sparing and/or switch treatment paradigm, and weight loss maintenance that matches semaglutide. We are eager to advance next steps for NMRA-215. However, as we shared this morning, there were unexpected adverse findings from a separate 13-week rat tox study in a small number of animals. We have opened a for-cause audit of this study and expect to bring NMRA-215 into the clinic in the first quarter of 2027. Nick will go into more detail on both of these updates shortly. First, I will turn the call over to Bill to provide additional detail on our clinical programs. Bill?

Bill Aurora, Chief Operating and Development Officer, Neumora Therapeutics: Thank you, Josh. We are excited about the data from NMRA-511, which demonstrated a differentiated profile for the treatment of agitation in Alzheimer’s disease. In January, we shared top-line results from our phase 1b signal-seeking study of NMRA-511. This was a two-part signal-seeking study that was not powered to detect statistical significance. Instead, we evaluated the effect size of NMRA-511 on a variety of clinical measures to inform additional development in AD agitation. In the phase 1b study, NMRA-511 demonstrated an unsurpassed clinical effect size on CMAI total score and a range of other endpoints in a pre-specified population with elevated anxiety at baseline. Today, we announced new data from a pre-specified analysis from the phase 1b in 53 patients with an NPI-AA score of greater than or equal to 4 at baseline.

This population is similar to the group studied in pivotal trials with Rexulti and Auvelity. 511 treated patients demonstrated a clinical benefit and had a Cohen’s d effect size of 0.32-0.34 on CMAI total score, a similar magnitude to Rexulti. Additionally, in this population, 511 showed an unsurpassed effect size across the CMAI Aggressive Behaviors subfactor score and CGI-S agitation score. Notably, 511 demonstrated a favorable tolerability and safety profile in phase Ib, which we believe provides an opportunity for us to test higher doses. We are advancing a MAD extension study this year, with data expected in the second half of the year, before moving to a phase II study in the first quarter of 2027.

Transitioning to navacaprant, we are pleased with the significant progress we have made with the navacaprant KOASTAL program for the treatment of major depressive disorder. Today, we announced that KOASTAL-2 and KOASTAL-3 studies are fully enrolled with more than 400 patients enrolled in each study. We expect to report a joint top-line data readout for KOASTAL-2 and KOASTAL-3 in the second quarter of 2026. As a reminder, KOASTAL-2 and KOASTAL-3 are phase III studies being run both in the U.S. and in ex-U.S. territories. The design for these studies incorporated key learnings that we implemented in early 2025 following the KOASTAL-1 readout. This included enhanced medical monitoring to verify inclusion of appropriate patients, screening tools to rule out professional patients, and site selection that focused on sites with expertise in conducting MDD studies.

We believe that these optimizations facilitated appropriate patient enrollment in these trials. For example, we saw an approximately 10% higher screen fail rate in the KOASTAL-2 and KOASTAL-3 studies compared to KOASTAL-1. Overall, we are confident that these changes will result in a stronger dataset and look forward to the results. In the joint top-line readout, we expect to include top-line results for each individual study, as well as pre-specified analyses with more than 450 patients enrolled after study optimizations occurred in early 2025. We believe this approach will provide a comprehensive view of the data and help us better assess navacaprant’s clinical profile. We will assess next steps regarding regulatory submission once we have the data in hand, but we believe that with the FDA’s recent commentary, one positive study plus supportive evidence may be sufficient for approval.

With one positive study, we would request a pre-NDA meeting with the FDA. Lastly, on our M4 positive allosteric modulator franchise, today we announced that we have designated NMRA-898 as the lead program in the franchise and plan to advance it for development in schizophrenia. This decision is supported by the encouraging data we have seen to date from our ongoing phase I study. In that study, NMRA-898 demonstrated an approximately 80-100-hour half-life in humans, which confirms the potential for once-daily dosing, and is within a similar range to the half-lives of highly successful neuropsychiatry medications like Vraylar, Abilify, and Rexulti. We also observed dose proportional exposures with low variability, as well as predicted free brain exposure significantly above the in vitro M4 EC50 levels.

In addition, we saw on-target changes in heart rate that were similar to those demonstrated by Cobenfy, which we believe provide pharmacodynamic evidence of target engagement. Taken together, these findings strengthen our confidence in NMRA 898 and support our view that it has a potential best-in-class pharmacologic profile. We are conducting a multiple ascending dose study of 898 in healthy volunteers and patients with stable schizophrenia. The goals of this study are to identify a maximum tolerated dose and to confirm CNS penetration through CSF exposure. We expect to report data from this MAD study in the second half of 2026. While we have paused development of our other M4 PAM, NMRA 861, we believe it has a profile that could support development in the future. We are pleased to have this optionality in our portfolio.

As you can see, we are making significant progress across our clinical pipeline that I believe has the potential to translate to meaningful medicines for patients. With that, I’ll now turn it over to Nick to walk through our NLRP3 update in more detail. Nick?

Nicholas Brandon, Chief Scientific Officer, Neumora Therapeutics: Thanks, Bill. I’ll begin with our 12-week DIO data with our NLRP3 inhibitor, NMRA-215. As Josh noted, the results from this study further highlight our CNS penetrant pharmacology that translated to class-leading weight loss in these models. In earlier DIO studies, NMRA-215 drove dose-dependent class-leading weight loss as a monotherapy and in a combination setting with semaglutide. The 12-week DIO data we announced today provides supportive evidence for potential use of NMRA-215 in both the mechanism of action switch and maintenance treatment paradigms. DIO mice that were switched from a combination of NMRA-215 plus semaglutide to NMRA-215 monotherapy at week 8 maintained weight loss similar to mice who received semaglutide monotherapy for the entire study duration.

NMRA-215 also demonstrated sustained semaglutide-like weight loss at 12 weeks following the switch from semaglutide monotherapy to NMRA-215 monotherapy at week 8. These findings, along with our previously reported data, are very encouraging and support our view that central NLRP3 inhibition may offer an important new mechanism for weight loss. Additionally, with data from multiple sponsors in the space showing reductions in hsCRP, it’s become clear that NLRP3 inhibitors offer potentially compelling cardioprotective benefits. We believe that this is a class effect, and we are likely to see hsCRP reductions with NMRA-215 when it enters the clinic. Now, as Josh mentioned, we also shared that unexpected adverse findings were observed in a very small number of animals in a 13-week rat toxicology study. A few details to highlight.

The observations were not dose-dependent and not associated with a known molecule-related or on-target effect, but did occur in conjunction with documented study conduct issues. We have opened a for-cause audit into the study. We have also completed 28-day rat and dog and 13-week dog toxicology studies with no similar findings and sufficient margins to achieve IC90 concentrations in the brain, which we believe are needed for weight loss. We remain confident in the potential of NLRP3 inhibition for the treatment of obesity and have started dosing in a repeat 13-week rat toxicology study. We now expect to bring NMRA-215 into the clinic in the first quarter of 2027. From here, I will turn it over to Mike to review the financials. Mike?

Michael Milligan, Chief Financial Officer, Neumora Therapeutics: Thanks, Nick, and good afternoon, everyone. As of December 31, 2025, we ended the year with $182.5 million in cash equivalents, and marketable securities. We expect our current cash position to support operations into the third quarter of 2027. Additional financial results are available for review in the press release that we issued this morning, including detailed information on our fourth quarter and full year 2025 operating expenses. Our total net loss for 2025 was comparable to the same period in 2024. With that, I’ll now hand the call over to Helen to manage the Q&A with the operator. Helen?

Helen Rubenstein, Vice President of Investor Relations and Corporate Strategy, Neumora Therapeutics: Thanks, Mike. Before I turn it over to the operator, I’ll ask that you limit yourself to one question. If you have an additional question, please feel free to return to the queue. With that, I’ll turn it over to the operator to handle Q&A. Operator?

Operator: Thank you. To ask a question, you will need to press star one and one on your telephone and wait for your name to be announced. To withdraw your question, please press star one and one again. We will now go to our first question. One moment, please. Our first question today comes from the line of Myles Minter from William Blair. Please go ahead.

Myles Minter, Analyst, William Blair: Hey everyone. Congrats on the progress. I’ll keep it to one. Just wanted to follow up on comments that potentially one study and supportive evidence would be sufficient for the navacaprant filing in MDD. Did wanna confirm that just means that a positive KOASTAL-2 or 3 would be that one study, and then the source of supportive evidence, maybe that comes from the combined trial analysis of those more than 450 patients enrolled post-protocol amendment?

Brian Abrahams, Analyst, RBC Capital Markets2: Is that coming from something like the phase II you’ve already got in hand or even external data like from the FAST-MAS that supports the kappa antagonist mechanism here? Thanks very much.

Bill Aurora, Chief Operating and Development Officer, Neumora Therapeutics: Good morning, Myles. This is Bill. Thank you for your question. Yes, we do believe that with one positive study, either KOASTAL-2 or KOASTAL-3 plus supportive data, we’d be in a strong position to proceed in requesting a pre-NDA meeting. Supportive data can take a variety of forms, whether that’s an improvement on anhedonia as measured by SHAPS, whether it is tolerability safety profile that’s quite compelling in an untreated large population. There are a variety of ways by which we believe supportive data could play an important role, but one of the two studies being positive puts us in that position to have a meeting.

Operator: Thank you. We will now go to the next question. The next question comes from the line of Brian Abrahams from RBC Capital Markets. Please go ahead.

Brian Abrahams, Analyst, RBC Capital Markets: Hey, good morning, guys. Thanks for taking my question and, congrats on the continued progress. Maybe just on two one five, can you give us any color around these conduct issues that you mentioned, like what these were, why you suspect them, and how these might relate to the toxicity findings? I guess I’m curious, would the onus be on you to prove that the findings here were spurious or historically has the FDA been fine with progressing a program if a redo of a 13-week tox study comes up clean? Thanks.

Joshua Pinto, President, Neumora Therapeutics: Hi, Brian. It’s Nick here. Because we do have an ongoing audit into the initial 13-week tox study, we can’t really provide too many more details. Clearly, we have stated today that, you know, we do believe they are procedure related. We’ve now started a second repeat study with a different CRO and that’s, you know, in that second study, we have made some changes. I think importantly, these types of findings in tox studies are very common in the industry. They’re well documented in the literature. We know that other sponsors have, you know, repeated studies and have been able to, you know, move their programs forward. We’re obviously looking forward to completing this second study and progressing 215.

Brian Abrahams, Analyst, RBC Capital Markets: Thanks, Nick. Really helpful.

Operator: Thank you. Your next question today comes from the line of Douglas Tsao from H.C. Wainwright. Please go ahead.

Douglas Tsao, Analyst, H.C. Wainwright: Hi. Good morning. Thanks for taking the questions. Just on the M4 program, I’m curious if you could provide a little bit more in terms of what sort of put NMRA-898 in the lead. Also, I think, you know, Bill mentioned that you continue to see opportunity potentially for NMRA-861. I’m just curious, do you see that largely as a backup molecule right now, or do you potentially envision development in alternative indications? Thank you.

Joshua Pinto, President, Neumora Therapeutics: Yeah. Hey, Doug, it’s Josh here. As we mentioned, we’re prioritizing NMRA-898 this morning as our lead in schizophrenia. Really, you know, it’s not because of anything that we saw with 861. It’s because 898 looks so compelling based on the data that we’ve put out today, and both compounds are structurally distinct. With our focus being on schizophrenia, we’re gonna progress 898 as the lead in that indication. We do view 861 as a viable compound for future indications. As we think about indication expansion in LCM within this franchise, we could look to bring another compound like 861 forward in that. For the time being, Doug, 898 is-- will be the lead for schizophrenia.

Based on the data that we’ve you know published today, the compound’s behaving you know exceedingly well in early clinical studies.

Douglas Tsao, Analyst, H.C. Wainwright: Okay, great. Thank you.

Operator: Thank you. Your next question today, one moment, please, comes from the line of Marc Goodman from Leerink. Please go ahead.

Brian Abrahams, Analyst, RBC Capital Markets2: Good morning, everyone. Thanks for taking the question. This is Alyssa. I’m for Mark. I was just wondering if you could give a little bit more details on the pre-specified analysis for the KOASTAL-2 and KOASTAL-3 readouts. What exactly are we gonna see? And, how do you imagine interpreting those results compared to kind of the entire top line analysis? Thank you.

Joshua Pinto, President, Neumora Therapeutics: Yeah. Hey, Alyssa, it’s Josh here. In terms of the KOASTAL studies for the pre-specified analysis, you know, what you can really expect is that we will be putting out top line data for the KOASTAL-2 study, top line data for the KOASTAL-3 study, and then we will be looking at those patients that were in a post-pause pooled population, so those that have gone through the SAFER process since the KOASTAL-1 study read out. Bill, maybe you want to just add a bit more in terms of what we’ll see from the pre-specified top line and what we’re really going to be looking for in the KOASTAL results in the second quarter.

Bill Aurora, Chief Operating and Development Officer, Neumora Therapeutics: Sure. Thanks for the question, Alyssa. With respect to the KOASTAL-2 and KOASTAL-3 study, just as a quick reminder, when we paused those studies, we did implement a series of measures that were designed to enhance the quality of the patients coming in, and those included things such as working with MGH and implementing the SAFER process. It included implementing BCT as a screening database and paring back the number of sites overall. We’re pleased with the measures that we had taken, and we’ve seen higher rates of screen failure as a consequence, for example, approximately 10% higher than in KOASTAL-1.

Joshua Pinto, President, Neumora Therapeutics: These would have otherwise been patients that would have been randomized into the study. It gives us confidence that in fact, we’ve done a better job in making sure that we get the quality of patients consistent with what the protocol and our expectations were. With respect to the post-pause population, we’ll have an opportunity in each of the individual studies to take a look at how those patients perform, as well as taking a look at the pooled population post-pause. Those will be added measures on top of looking, of course, at the individual study results for K2 and K3. Excellent. Thank you very much.

Operator: Thank you. We will now go to the next question, and the next question comes from the line of Paul Matteis from Stifel. Please go ahead.

Brian Abrahams, Analyst, RBC Capital Markets4: Hey, thanks for taking our question and congrats on the progress. This is Julian on for Paul. Do you mind just walking us through really quickly the update that you shared with respect to the maintenance data for NMRA-215? I guess was this your expectation and you know how did you get to sort of modeling that target dose where you’re showing you know an estimated 23% reduction in weight loss in the DIO model? Then really quickly, if I may, just how does the delay on the sort of tox-related issue for the program factor into your capital allocation strategy? Thanks so much.

Joshua Pinto, President, Neumora Therapeutics: Yeah. Thanks, Julian. You know, this is Josh here. Maybe I’ll answer the second part of your question first. Obviously, you know, our spend this year for 215 will be reduced as we’re not gonna be moving the program into the clinic until the first quarter of 2027. It’ll free up capital as we think about allocation to other areas. In terms of the maintenance data, I think the data is exactly what we would expect, and it built on what we think was the best-in-class monotherapy and combination DIO data that we presented in October at our R&D Day. In terms of what we showed in this DIO study, it was completely focused on longer-term combination paradigms.

we demonstrated that you could switch from being on a GLP-1 to NMRA-215 and maintain the same level of weight loss, which commercially could be very important. We also looked at a paradigm where if you were on a combination of the two products and you took one off, could you maintain weight loss? We absolutely validated there that yes, if you’re on a combo and you take away semaglutide, you can maintain monotherapy level weight loss with 215. In terms of how we selected the target dose, it was really around achieving IC90 concentrations in the brain, as we’ve highlighted previously.

Julian, as you look at what we achieved in the 12-week DIO study, the combination of semaglutide and 215 alone, highly consistent with the 28-day data we previously put out, where you saw about a, you know, 20%-25% reduction in combination therapy over the study. Julian, I would say very validating, hits exactly what we’d expect to see out of the study and exceedingly consistent with what we have shown previously for 215 in DIO studies.

Brian Abrahams, Analyst, RBC Capital Markets4: Great. Thanks for the color.

Operator: Thank you. Your next question today comes from the line of Yatin Suneja from Guggenheim. Please go ahead.

Brian Abrahams, Analyst, RBC Capital Markets1: Good morning, everybody. This is Thelma for Yatin. Thanks for the update. A clarification on the 215 tox study. Have you received any specific guidance from the FDA on what would be required to clear the IND? Or are you proactively rerunning the studies based on your own assessment? Thank you.

Nicholas Brandon, Chief Scientific Officer, Neumora Therapeutics: Yeah. Hey, Nick here again. Yes. We haven’t discussed the studies with the FDA, but we have consulted multiple consultants and KOLs around what was the appropriate path forward. Repeating the study was clearly the clear guidance we were given. I would say based on the experience of our internal team, including myself and our consultants, you know, we’re confident that this repeat study will allow us to get the FDA to approve the IND. Yeah. There’s a lot of precedent for it. You know, personally, I can look back on my own prior experiences, other companies where we’ve done similar things. Yeah, we’re confident that this repeat study would allow us to get the IND cleared.

Brian Abrahams, Analyst, RBC Capital Markets1: Got it. Thank you.

Operator: Thank you. Your next question today comes from the line of Ami Fadia from Needham & Company. Please go ahead.

Brian Abrahams, Analyst, RBC Capital Markets3: Hi, this is Purna on for Ami. Thank you for taking our question. On NMRA-511, could you help us understand how the effect size changed at the different time points, week 4 and 6, in the subpopulation? How are you envisioning the phase II study design in terms of the patient population, trial duration? Thank you.

Joshua Pinto, President, Neumora Therapeutics: Sure. Good morning. With respect to the effect size that we have seen in the trial overall, we’re really pleased with the consistency of the results in looking at the effect size. The effect size, whether it be at week 4 or 8, depending on the various measures, is quite consistent, and we’re pleased with what we’ve been seeing here. With respect to the next steps with the program, we’ve communicated that we’ll be moving forward with another MAD cohort where we believe we’ve got room to push the dose given the favorable tolerability seen. Then from there, we’ll describe in further detail what our plans are for phase II, including the design, inclusion criteria and the like.

Suffice it to say, the data that we put out today showing the NPIAA of four or greater is consistent with what other sponsors have used as a part of their inclusion criteria and been able to maintain a broad label. That is one where one could expect

Bill Aurora, Chief Operating and Development Officer, Neumora Therapeutics: To follow the path of other sponsors and where there’s a regulatory path that’s been well-defined.

Joshua Pinto, President, Neumora Therapeutics: Yeah. Yeah, Bill, I would just add, I think the data today that we put out is really quite compelling for NMRA-511. I think it shows that in the total population, our data is consistent and just as compelling as what we’ve seen in patients with elevated anxiety. Bill, to your point, this new data that we’ve highlighted today shows that we can develop NMRA-511 down a well-established regulatory pathway while still preserving the ability for a broad label in patients with AD agitation. We actually view this data as the most compelling data set we’ve put out thus far for 511 and are really excited about this being the launching point of the program going forward. Got it. Thank you.

Operator: Thank you. Your next question comes from the line of Graig Suvannavejh from Mizuho. Please go ahead.

Graig Suvannavejh, Analyst, Mizuho: Good morning. Thank you for taking my question. I wanted to ask about NMRA-898 and the M4 PAM space. Could you just remind us how you’re thinking about its differentiation versus, say, the Neurocrine program? If you could provide what you think the latest is with the emraclidine, just as we think about the M4 PAM class, and again, vis-a-vis the broader muscarinic space and any kind of thoughts you have on the Cobenfy launch and what that means about how doctors are thinking about muscarinic in the schizophrenia landscape. Thanks.

Nicholas Brandon, Chief Scientific Officer, Neumora Therapeutics: Hey, Graig, it’s Nick here. Thanks for the question on the M4. You know, in terms of the differentiation of 898 in particular compared to some of the other competitors, even including emerging companies like Neurocrine, I think, you know, I’d point to a number of key bits of data which we’ve put out. You know, knowing that we don’t know a lot about a Neurocrine compound. 898 and 861 have a very, very potent and equipotent across assays, which is critical. Those compounds were also optimized for CNS penetration. We’ve put out some data around that which, you know, which is in our R&D Day. The more data comes out there, you know, really holds up.

Now critically, you know, we’ve got early clinical data and particularly with 898, it’s really sort of showed its hands in the initial cohort. Clearly the half-life allows us for once-a-day dosing, which is critical. I might hand over to Bill in a second to talk about some of the other elements that may drive. We see really nice dose-dependent exposures. Variability is really low, and that’s important. Other compounds in this class haven’t had that quality. We also see really nice pharmacodynamic effects, and this is by the surrogate heart rate increases we see. Overall now the profile of 898 just looks really good as we compare to what we know about other sponsors in the field. Maybe Bill to that.

Bill Aurora, Chief Operating and Development Officer, Neumora Therapeutics: Sure, Nick. I would just simply add, Greg, that the half-life for eight nine eight is within a similar range of half-lives of highly successful neuropsych meds like Vraylar, Abilify, and Rexulti. We conducted market research with community prescribers that also has underscored some of the potential advantages of the profile that they’ve seen. As an example, we know we have the ability to maintain steady state in the situations where a patient may miss a dose of the medication, which we know is a common phenomenon in schizophrenia. The half-life also has the potential to reduce withdrawal symptoms if patients discontinue medication. We’re really pleased with the profile, and the excitement is certainly one that’s been underscored through some of the work we’ve done with physicians treating schizophrenia patients in the profile they’ve seen with eight nine eight.

Joshua Pinto, President, Neumora Therapeutics: Graig, this is Joshua. I would just add, we’re really compelled by the data that’s been put out this morning. I think as we look at it in the SAD study, we have not hit an MTD yet, so continue to move forward. We’re already seeing, you know, across the pharmacodynamic measures activity, you know, elevated from what we’ve seen with emraclidine and even at levels relative to Cobenfy. If you look at what we’ve seen at the 15-milligram level in terms of heart rate, elevation, and beats per minute, that’s comparable to what we’ve seen from Cobenfy at its highest doses. We feel like we, you know, are absolutely getting into a really good pharmacodynamic range, while also, you know, having a compound that is behaving very well from a safety and tolerability perspective.

Graig Suvannavejh, Analyst, Mizuho: Thank you.

Operator: Thank you. Our next question today is from the line of Myles Minter from William Blair. Please go ahead.

Myles Minter, Analyst, William Blair: Great. Thanks for the quick follow-up. Follow-up on Graig Suvannavejh’s question as well. On 898, did you also see any sort of transient increases in blood pressure in that single ascending dose study? Thanks.

Bill Aurora, Chief Operating and Development Officer, Neumora Therapeutics: The changes that we’ve seen in blood pressure are consistent with what we have expected. Nothing that is different from what’s been seen with the class. It underscores that in the phase I B, we plan to move forward as other muscarinics have with routine monitoring. We do anticipate as the molecule progresses in development, like other muscarinics have done, we would look to do an ambulatory blood pressure monitoring study as others have in the space.

Joshua Pinto, President, Neumora Therapeutics: Yeah. Just to be clear, Myles, in the single ascending dose study, we have not seen blood pressure changes thus far. We are seeing the positive, you know, changes in heart rate, as we believe the pharmacodynamic measure is as it’s related to, you know, a measure of target engagement for M4 in the class. In these doses, we have not seen the elevated blood pressure yet, so we’ll continue to monitor as it moves forward. To Bill’s point, our assumption is that blood pressure could be a class effect. You know, we bake into our plans having to run an ambulatory blood pressure monitoring study if needed.

Myles Minter, Analyst, William Blair: Thanks.

Operator: Thank you. We will now take our final question for today, and our final question comes from the line of Douglas Tsao from H.C. Wainwright. Please go ahead. Douglas, are you on mute?

Douglas Tsao, Analyst, H.C. Wainwright: Hi. Thank you. Sorry about that. I was just curious, in terms of the combination, or for NMRA-215, sorry. For the combination to NMRA-215 maintenance study. I’m just curious about the dosing that was utilized and are things that you think you might be able to do to sort of further optimize the maintaining of the weight loss that was seen when it was used in combination with semaglutide.

Joshua Pinto, President, Neumora Therapeutics: Yeah. Hey, Doug, this is Josh here. As I mentioned before, I think in the 12-week DIO study, it validated the hypothesis that we absolutely wanted. The combo data, I think is consistent, where we saw over 12 weeks about a 23% reduction in weight loss on the combo. That’s consistent with the roughly 25-ish% we’ve seen in the earlier studies. As we know in these DIO studies, as you continue to feed mice high-fat diets over time, the weight does tend to rebound, whereas that’s not necessarily the case in the clinic. I think as we’re looking at ways to optimize the molecule, Doug, moving forward, really the next step is to get it into the clinic, start to understand how it’s behaving in humans from a PK perspective, and then we can look to move it forward there.

What I would say is the data we put out today continues to validate that NMRA-215 does have a best-in-class weight loss potential, at least as it relates to the DIO data we’ve put out between the R&D Day and today.

Douglas Tsao, Analyst, H.C. Wainwright: If I can, Josh, just as a follow-up. I mean, obviously you’ve sort of outlined in these DIO models a number of different use cases. How many do you anticipate ultimately bringing forward? Or do you think that this is more of a situation where you’ll just sort of validate the you know, 215’s ability to drive weight loss and maintain weight loss, and then kind of leave it up to clinicians to figure out their own particular dosing regimens and sort of ways of using the molecule. Thank you.

Joshua Pinto, President, Neumora Therapeutics: Yeah, Doug. Our view is there’s gonna be a lot of different things and paradigms that can be tested out with this molecule in combination potential. I think in terms of what you can expect from us moving forward, what you can expect from us is consistent with what we’ve highlighted before, which is we’re going to now be moving the program into the clinic in the first quarter of 2027. Initially at weight loss, you can expect data to come out from us in a standard monotherapy as well as combination approach. We’ll talk about future paradigms downstream, you know, after we validated the hypothesis of weight loss clinically.

Douglas Tsao, Analyst, H.C. Wainwright: Great. Thank you very much.

Operator: Thank you, everyone. That will conclude the Q&A portion of today’s call. I will now hand the call back to Paul Berns, CEO, for closing remarks.

Brian Abrahams, Analyst, RBC Capital Markets0: Okay, thank you, operator, and thanks to all who joined us for this morning’s call. We appreciate your interest and support. Have a lovely day.

Operator: Thank you.

Douglas Tsao, Analyst, H.C. Wainwright: Goodbye.

Operator: Thank you. This concludes today’s conference call. Thank you for participating. You may now disconnect.