NMRA - NASDAQ

Ladies and gentlemen, thank you for standing by. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. Please be advised that today's conference is being recorded. I would now like to turn the conference over to Helen Rubinstein, Vice President of Investor Relations and Communications. Please go ahead.

Good afternoon, and thank you for joining Neumora Therapeutics' First Quarter 2025 Financial Results Conference Call. Before we begin, I encourage everyone to go to the Investors & Media section of our website at neumoratx.com, where you can find the press release related to today's call. With me from Neumora are Chief Executive Officer, Paul Berns; President, Josh Pinto; Chief Operating and Development Officer, Bill Aurora; and Chief Financial Officer, Mike Milligan. I'd like to point out that we will be making forward-looking statements, 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.

Thanks, Helen. Good afternoon, everyone, and thank you for joining us. At Neumora, we believe the greatest medical challenge of our generation is the global brain disease crisis. This affects upwards of 1.5 billion people and causes a severe impact on quality of life, not only for patients, but also their families and society at large. Despite a number of approved therapies, there is a significant outstanding unmet need for safe and effective treatment options to alleviate the burdens of these diseases. When we founded Neumora, it was with the intention to confront this challenge head on and focus on bringing novel mechanisms forward to redefine neuroscience drug development. We have made important progress towards that goal. We are advancing an industry-leading pipeline of programs, all targeting novel mechanisms of action with the potential to address some of the most prevalent brain diseases and are supported by a strong financial foundation. As we are poised to achieve a number of upcoming clinical catalysts across our pipeline, I believe we have the right science, people, and strategy in place to realize our vision of revolutionizing the treatment of brain diseases. I will now turn the call over to Josh Pinto, President of Neumora to review our business and pipeline updates. Josh?

Thanks, Paul. We are focused on clinical execution as we are advancing multiple programs towards key milestones over the next 12 months. We are on track to deliver top line data for NMRA-511, our vasopressin 1a receptor antagonist in Alzheimer's disease agitation around the end of the year. We are also progressing navacaprant in the Phase 3 KOASTAL program in MDD, where we have implemented important changes for the ongoing studies and plan to report top-line data from KOASTAL-3 in the first quarter of 2026 and KOASTAL-2 in the second quarter of 2026. In our M4 franchise, we are working with urgency to bring a best-in-class M4 PAM into the clinic in the middle of this year. Additionally, we announced this morning that we entered into a $125 million debt facility with K2 HealthVentures with up to $40 million available for draw this year. K2 HealthVentures has deep expertise in life sciences, and we are pleased with the opportunity to work with their team. Financial discipline has always been a core tenant of how we operate our business, and today, it is more important than ever to maintain diligent stewardship of capital. The non-dilutive capital from this facility combined with the cash already on our balance sheet further strengthens our financial position and will support our efforts to achieve value creating milestones across our pipeline. With this update, we now expect our cash, cash equivalents and marketable securities together with the $20 million funded at close under the K2 facility to support our operations into 2027, well beyond anticipated clinical data milestones. As you can see, we are well-positioned to generate value from a number of programs, and we are supported by a strong financial foundation. Each one of our programs evaluates a novel mechanism of action in their respective indications with the potential to bring new treatment options to patients and capitalize on significant market opportunities. Our pipeline is supported by very strong intellectual property portfolio with worldwide rights to all of our programs and composition of matter patents extending into the 2040s. As a multi-product company with multiple shots on goal, we are prepared to execute against our vision of maximizing all pathways for success and generating long-term company growth. With that overview, I will now turn the call over to Bill to provide additional details on our clinical programs. Bill?

Thanks, Josh. We are excited about the industry-leading pipeline we have constructed and the potential of these novel mechanisms to revolutionize the treatment of brain diseases. Starting with navacaprant, we are confident in the potential for navacaprant to become a differentiated treatment option for patients with MDD. There is a strong body of clinical evidence validating the potential of kappa opioid receptor antagonists to show benefit in MDD and anhedonia. Supporting studies include the National Institute of Health or NIH run FAST-MAS Study, the J&J Phase 2 study of aticaprant, and importantly, our own Phase 2 study of navacaprant, which was recently published in the Journal of Clinical Psychopharmacology. This publication highlights that navacaprant demonstrated statistically significant and clinically meaningful reductions in symptoms of depression and anhedonia in participants with moderate to severe MDD. So, when trying to understand how KOASTAL-1 results compared to other studies, we identified a few factors that were different from what you would expect to see in a typical MDD population. For example, approximately two-thirds of the patients had never taken a prior antidepressant, despite experiencing an average of five prior episodes of MDD in their lifetimes. Prior trials and publications suggest that a substantially higher percentage of people with chronic MDD would have received prior antidepressant treatment. As we've looked at the data, we concluded that the total population in KOASTAL-1 was not necessarily representative of the MDD population and that's why we've made modifications in site selection, patient screening and medical monitoring in KOASTAL-2 and KOASTAL-3 to help ensure that appropriate patients are enrolled. The studies resumed enrolling in March with the following changes. We enhanced engagement with sites around medical monitoring to confirm the patients enrolled in the studies have an independently verified diagnosis of MDD that helps to ensure they appropriately meet eligibility criteria for these studies. We added the clinician rated Massachusetts General Hospital clinical trials network and institute SAFER approach, which is an independent review conducted by clinicians to verify the diagnosis and appropriateness of the patient population. Our internal medical team is partnering with the SAFER clinical team to confirm eligibility prior to randomization. We also added an additional tool called the Verified Clinical Trial screening database aimed at better identifying patients, who are participating in multiple clinical trials and excluding them from enrolling in the KOASTAL-2 and KOASTAL-3 studies. This is an additive step to the clinical trial subject database we used in KOASTAL-1 and we believe it will help to ensure the appropriate patients are enrolled in our ongoing studies. And finally, we've reduced the number of clinical sites and selected those sites that we believe have the greatest level of expertise in conducting MDD studies. We have already seen benefits from these added measures in the KOASTAL-2 and KOASTAL-3 studies. For example, the Verified Clinical Trial screening database has identified multiple potential participants who are not appropriate for inclusion, enabling us to exclude them from the studies. More broadly, it's important to remember that many approved medicines in MDD and psychiatry broadly have failed individual Phase 3 studies, but ultimately succeeded in multiple studies and become important treatments. We designed the KOASTAL program with the historical challenges in mind knowing that we would need two of the three trials to be successful, in order to file an NDA. We anticipate data from KOASTAL-3 in the first quarter of 2026 and KOASTAL-2 in the second quarter of 2026. I also want to highlight our franchise of M4 PAMs that we are advancing, where we plan to move a candidate into the clinic in the middle of this year. Based on available data, it is clear that M4 is the driver of antipsychotic activity seen with muscarinic drugs to date. We believe we are well-positioned to become a leader in M4 PAMs that can potentially offer improved safety and tolerability profile and once a day dosing. We look forward to sharing more on the pharmacology of our M4 programs when they enter the clinic in mid-2025 In Phase 1b is our vasopressin 1a receptor antagonist, NMRA-511, which is a highly potent and highly selective antagonist being evaluated for Alzheimer's disease agitation. The V1a target is a proven pathway as it is known to play a role in the regulation of aggression, affiliation, stress and anxiety response. In preclinical data, NMRA-511 reduced measures of anxiety, agitation, aggression and was very well tolerated in a Phase 1 SAD/MAD study, as well as in healthy elderly volunteers. We believe that based on these data combined with findings from other sponsors, there's a strong rationale for NMRA-511 in AD agitation, an area of significant unmet-need with only one approved agent that carries a black box warning. We look forward to delivering top-line data from Phase 1b signal seeking study around the end of this year. In parallel, we continue to progress our four preclinical programs, which have opportunity to make impacts in serious and common diseases, such as Parkinson's disease, Alzheimer's disease and ALS. Those programs are advancing and we look forward to sharing more information on those studies in the near future. In short, it has been a productive start to 2025 for Neumora and we're well-positioned to achieve our multiple upcoming clinical catalysts in the second half of this year and beyond. With that, I'll now turn it over to Mike for a review of the financials. Mike?

Thanks, Bill, and good afternoon, everyone. Our financial results for the first quarter of 2025 are detailed in the press release that we issued this morning. I'd like to take a moment to provide some context and highlight a few key points. Net loss for the first quarter was $68 million, compared to $53.7 million for the same period in 2024. And we ended the quarter with $249.4 million in cash, cash equivalents and marketable securities as of March 31, 2025. As Josh noted, we are focused on disciplined capital allocation and expect our cash on hand and the $20 million drawn at the close of the K2 facility to support operations into 2027. We expect that this runway will allow us to realize multiple catalysts across our programs. With that, I'll now hand the call over to Helen to manage Q&A with the operator. Helen?

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. Now, I'll turn it over to the operator to handle Q&A. Operator?

[Operator Instructions] Our first question comes from Douglas Tsao with H.C. Wainwright.

Hi, good afternoon. Thanks for taking the questions. I guess two for me. First, starting with navacaprant, I understand the operational changes that were put in place. I'm just curious, have you had any sort of sense of how it has affected, sort of the pace of enrollment early going, just sort of early experiences it and sort of what gives you that confidence in terms of the achieving the readouts in next year?

Thanks, Doug. This is Bill. Appreciate your question. We've already seen benefits from steps that we've taken with both SAFER and the Verified Clinical Trial screening database that we've implemented in the K2 and the K3 studies. Both have identified multiple potential participants who really aren't appropriate for inclusion in the study, enabling us to exclude these patients from being put in. So, we do have confidence that the steps we're taking are helping to get appropriate patients randomized into K2 and K3.

And I guess, Bill, as a follow-up, just, is that, is it having a negative impact, in terms of the pace of enrollment? Or obviously, you're sort of disqualifying some patients. And I guess, it sounds like though that is the rate of that is occurring at a rate consistent with what you were expecting?

Yes. It is consistent. The rate of those patients being excluded is consistent with our expectation. It doesn't impact our timing guidance that we provided with respect to the enrollment. So, things are progressing as planned.

Okay. Great. That's great to hear. And then, just on the K2 financing, I'm just curious if you can provide any details, in terms of sort of limitations on prepayment or so just to the extent that as you hit other milestones, are you able to perhaps pay down that debt as sort of your cost of equity comes down?

Hey, Doug, it's Josh here. I'll take that one. And the details of the facility are disclosed in our 10-Q, so I would point you towards that. But really, with this facility, what we're looking to achieve in this financing was extending our cash runway into 2027. And so with the $20 million that we're able to draw close, plus our existing cash balance, we were able to achieve that goal and we've extended our cash runway now into 2027. In terms of the milestones, you can think about progression of navacaprant through some of the clinical stages, as well as some regulatory stages as ways to un-date additional capital. But as we noted in the press release, beyond the first $20 million that we, that was funded to close, there will be another $20 million that we can bring in at our discretion before the end of this year. So, there is flexibility, in terms of bringing more capital onto our balance sheet this year through the facility.

And Josh, just to confirm though that you only need the $20 million to get you into 2027?

Correct. Our existing cash balance sheet as of the March, plus the $20 million funded at close gets our runway into 2027. So, any additional drawdowns beyond that would provide funding for additional investments or extension of the cash runway beyond that.

Our next question comes from Yatin Suneja with Guggenheim.

Hey, guys. Thank you for taking my question. A couple of questions on the KOASTAL program. Could you talk about the patient population who might have received an antidepressant in this? How you are tracking it? Because, as I recall, in the KOASTAL-1, there was a lot of patient that had never taken antidepressant therapy in the past. So, just curious to know, is there a particular percentage of patient that you're targeting who would have taken a prior antidepressant in this study and how that might be tracking? And then, the other question is also on the K2 and K3, are there any possibility of some form of an interim analysis in this study?

Hi, Yatin. This is Bill. Thanks for your question. With respect to how we are ensuring the proper patients being included in K2 and K3 after the pause, the steps that we've taken include having SAFER clinical team involved and providing the assessment for patients, taking a look through history, both of depression, treatment. Our own clinical team is partnering closely with the MGH SAFER team to ensure that we are providing the degree of oversight that is consistent with our expectations to ensure we have patients with the proper history being enrolled. So, we are in fact strengthening that quite a bit and avoiding some of the things that we saw in K1 as part of that. With respect to the interim analysis, we do not have plans for an interim analysis and we are moving ahead with the enrollment and the timelines for K3 being in Q1 and K2 in Q2 of 2026.

Our next question comes from Brian Abrahams with RBC Capital Markets.

Hi, everyone. Thank you for taking my question. This is Nevan on for Brian. Just kind of high level, I guess, what are kind of your latest views on how to reconcile the core mechanism, based on the Phase 2 data that you've shown, as well as J&J's. But then, also with respect to the KOASTAL-1 study readout and J&J's decision to discontinue aticaprant or pivot that into different indications? And then, I have a follow-up after as well.

Sure, Nevan, this is Bill. Let me start here. We were surprised by J&J's decision to terminate their program, given their January 2025 communication about submitting an NDA later this year. We're looking forward to the presentation of their pool data later this month. That being said, there are several important differences between navacaprant and aticaprant, as well as the development strategies that are employed with each of the agents. First off, from a pharmacology point of view, navacaprant is significantly more selective for kappa opioid receptors over new opioid receptors than aticaprant is. Secondly, the study design for each of the programs and molecules were different. We believe the KOASTAL program really reflects the most appropriate study design for this mechanism to be utilized in the monotherapy setting. The steps that we've taken for enhancing K2, K3 really, in our view, improve the probability of success with the changes that we're making. I would simply say that, it's difficult to think about the aticaprant program in read-throughs that are limitations due to the pharmacology and study design that limit that read-through. We remain confident in navacaprant, so believe KOASTAL-1 results may have been an anomalous finding. So, we're excited about K2, K3 progressing and the timing for those reading out.

Great. Thanks so much. And then, I also found the 10-Q that was released that you had triggered the second tranche of funding from PBT for selection of an NLRP3 candidate. So, I guess, what can you tell us about this early program when we could see more from this, and when you might be able to disclose more data during this quarter?

Yes, Nevan, this is Josh here. Thanks for the question. I appreciate that. NLRP3 has been a program that we've been very excited about and progressing for a while now. And really, it's focused around targeting the NLRP3 inflammasome, which we believe is a critical part of the innate immune system. It can have an impact on a range of CNS, as well as other conditions. We tend not to talk a lot about our programs until we move them into the clinic. And as you've noted, we have been making progress with our NLRP3 program. And so, looking forward to having more specific updates on that program as we move through the next few quarters and into early 2026.

Our next question comes from Graig Suvannavejh with Mizuho Securities.

Hey, good afternoon. Thanks for taking my questions. Appreciate the updates that you provided. Two questions each on pipeline candidates. Just with respect to 511 and the readout in Alzheimer's disease agitation, maybe could you put in perspective what you expect to see with that data set, especially relative to the data -- the Phase 3 data sets that exist for a competitor product, AXS-05 from Axsome Therapeutics? And then, secondly, on the M4 PAM, maybe if you could revisit kind of your thoughts on differentiation between your candidate and perhaps the other program, emraclidine, in which, unfortunately the Phase 2, 3 data weren't great. Any color as to the confidence that you have that you'll perhaps show a different set of outcomes?

Hey, Graig, this is Bill. Thanks for your question. Let me start out here with the 511 question. And just as a reminder, this is a study that hasn't been powered to show statistical separation of active from placebo, but is rather a signal seeking study. Two parts, Part A, the Phase 1b, truly the randomized double-blind placebo-controlled cohort designed to evaluate safety, efficacy, tolerability, PK in healthy elderly volunteers. That portion has been completed. Part B of the Phase 1b is a multicenter randomized double-blind placebo-controlled study, where we're evaluating NMRA-511, 20 milligrams twice a day in about 88 patients, relative to placebo in agitation associated with Alzheimer's. The primary endpoint for the signal seeking study is the change from baseline to week eight on the CMAI or the Cohen-Mansfield Agitation Inventory. And so, looking at the total score change there and we're really looking at these data to help better understand which domains on the CMAI improved and it helped inform our thinking about the design for the next phase of study that we follow looking at these results.

With respect, Graig, to the M4 question. Yes, Greg. This is Josh. In terms of the M4 differentiation, one of the areas we've been very focused on engineering is ensuring that our compounds have high blood brain barrier penetration. We think, given the class and the cardiovascular related AEs being one of the key limiters for the M4 muscarinic, that really ensuring optimal blood brain barrier penetration is going to provide the biggest chance to show a great central effect. And so, in terms of areas where we think we could differentiate, we do think CNS penetration is one of them. We look forward to providing more specific details on our M4 PAM programs when we bring the next set into the clinic by middle of 2025.

Our next question comes from John Boyle with William Blair.

Hi, this is John on for Myles Minter. Thanks so much for taking our question. I was just wondering, if you could talk a little bit about maybe potential timing for when you might decide to increase enrollment in KOASTAL-2 or KOASTAL-3? And also just what aspects of the blinded data are you looking at and considering when making that decision?

Sure. Hi, John. This is Bill. I'll start here and basically communicate that with KOASTAL-2 and KOASTAL-3, those studies were designed to and scheduled to randomize up to 332 patients into the protocol. We've built in flexibility that allows us to go 25% higher than that 332. With respect to KOASTAL-1, you'll recall that we were just north of 380 patients enrolled. So, we did end up about 15% over enrolling, relative to the 332 base. K2 and K3 are progressing. We haven't made a decision on what that overall number will be, but we'll provide updates at the appropriate time point.

Our next question comes from Ami Fadia with Needham & Company.

Hi, this is [Pooyan] on for Ami. Thank you for taking our question. I'm just curious in KOASTAL-1, how does the MADRS baseline scores compare with the severity that was seen in the Phase 2 study where you saw the differentiation? And also, just wanted to understand how, what is the mix of females that you're seeing now in K2 and K3, and if you're managing the mix of patients?

Sure. So, looking at K1, relative to Phase 2, in Phase 2, we utilized the HAMD-17. And in that study, there were about 100 patients that had moderate to severe MDD. In KOASTAL-1, we're utilizing the MADRS and we are using a cutoff of 25 or higher on the MADRS consistent with the moderate to severe MDD population. So, once you think about those populations as being similar with respect to disease severity, in that manner. When we think about the mix of subjects in K2 and K3, relative to KOASTAL-1, it was a bit anomalous to see the high percentage of males in K1, relative to historically conducted studies. In K2, K3, we are seeing a mix that's more representative of what's historically been seen, roughly two-thirds female, one-third male, and we're pleased to see that being the demographic sex distribution for K2, K3.

That concludes today's question-and-answer session. I'd like to turn the call back to Paul Berns for closing remarks.

All right. Thank you, operator, and thank you for all of your questions to the participants in today's call. We very much appreciated the opportunity to give you the quarterly update. And I'd also like to thank my fellow Neumora team members for their commitment to excellence, as we advance the programs with the goal of bringing novel new therapeutics to treat patients with brain disease. With that, I bid you adieu and a good afternoon.