NASDAQ:NMRA Neumora Therapeutics Q2 2025 Earnings Report $1.62 -0.02 (-1.22%) Closing price 08/22/2025 04:00 PM EasternExtended Trading$1.64 +0.02 (+1.23%) As of 08/22/2025 07:57 PM Eastern Extended trading is trading that happens on electronic markets outside of regular trading hours. This is a fair market value extended hours price provided by Polygon.io. Learn more. ProfileEarnings HistoryForecast Neumora Therapeutics EPS ResultsActual EPS-$0.33Consensus EPS -$0.38Beat/MissBeat by +$0.05One Year Ago EPSN/ANeumora Therapeutics Revenue ResultsActual RevenueN/AExpected RevenueN/ABeat/MissN/AYoY Revenue GrowthN/ANeumora Therapeutics Announcement DetailsQuarterQ2 2025Date8/6/2025TimeAfter Market ClosesConference Call DateWednesday, August 6, 2025Conference Call Time4:30PM ETUpcoming EarningsNeumora Therapeutics' Q3 2025 earnings is scheduled for Tuesday, November 11, 2025, with a conference call scheduled at 8:00 AM ET. Check back for transcripts, audio, and key financial metrics as they become available.Conference Call ResourcesConference Call AudioConference Call TranscriptPress Release (8-K)Quarterly Report (10-Q)Earnings HistoryCompany ProfilePowered by Neumora Therapeutics Q2 2025 Earnings Call TranscriptProvided by QuartrAugust 6, 2025 ShareLink copied to clipboard.Key Takeaways Positive Sentiment: Nomura has prioritized obesity as the lead indication for NMRA215, its brain-penetrant NLRP3 inhibitor, with preclinical DIO model data expected this fall and Phase I studies planned for 2026 targeting a global market of up to 4 billion people. Positive Sentiment: NMRA861, a highly selective M4 PAM for schizophrenia, has entered Phase I trials to assess safety, tolerability, once-daily dosing and CNS penetration, with data anticipated in 2026. Positive Sentiment: The company expects up to six key clinical data readouts over the next 18 months, including Phase 1b results for NMRA511 in Alzheimer’s agitation by year-end and Phase III topline data for nabacoprant in major depressive disorder in 2026. Positive Sentiment: Nomura ended Q2 with $217.6 million in cash and equivalents, projecting a cash runway into 2027 and reporting a reduced net loss of $52.7 million versus $58.7 million a year ago due to lower clinical and personnel expenses. Neutral Sentiment: The company will not advance its NMDA program this year in order to focus resources on higher-priority neuroscience and obesity assets. AI Generated. May Contain Errors.Conference Call Audio Live Call not available Earnings Conference CallNeumora Therapeutics Q2 202500:00 / 00:00Speed:1x1.25x1.5x2xTranscript SectionsPresentationParticipantsPresentationSkip to Participants Operator00:00:00Ladies and gentlemen, thank you for standing by. This is RG, your conference operator today. 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. Operator00:00:17I would like now to turn the conference over to Helen Robenstein, Vice President of Investor Relations and Communications. Please go ahead. Helen RubinsteinVP-IR and Corporate Communications at Neumora Therapeutics00:00:27Good afternoon and thank you for joining Nomura Therapeutics second quarter twenty twenty five financial results conference call. Before we begin, I encourage everyone to go to the Investors and Media section of our website at pneumoratx.com, where you can find the press release related to today's call. With me today from Nomura are Chief Executive Officer, Paul Burns President, Josh Pinto Chief Operating and Development Officer, Bill Arora Chief Scientific Officer, Nick Brandon 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. Helen RubinsteinVP-IR and Corporate Communications at Neumora Therapeutics00:01:11Please 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. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:01:21Thanks, Helen. Good afternoon, everyone, and thank you for joining us. At Nomura, we are on a mission to address the largest population health challenges of our generation and to do so at scale. To achieve that goal, we know that we need to generate better medicines, therapies that enable better outcomes, that meaningfully improve the treatment of prevalent diseases, and ultimately that positively impact quality of life for patients and their families. With that aim in mind, we built an industry leading pipeline targeting some of the most prevalent and burdensome brain diseases. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:02:02Our approach is centered on advancing programs with best in class pharmacology, targeting novel mechanisms of action with the potential to improve upon the current standard of care for hundreds of millions of people. We are proud to be making important progress toward that goal. Today we announced that we prioritized obesity as the lead indication for NMRA two fifteen, our highly brain penetrant NLRP3 inhibitor. An increasing body of evidence supports the need for the role of centrally acting drugs to drive weight loss and obesity and NLRP3 inhibition in particular has shown promise across multiple studies. Importantly, recent data suggests that molecules with high CNS penetration and activity are required for efficacy with this target. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:03:01Currently, obesity and overweight affect more than two point five billion people globally, and by 2035 that number is expected to increase to up to four billion people. The need here is immense. Obesity is associated with significant negative outcomes and lower quality of life, and there is room to improve upon the efficacy and tolerability of the current generation of incretin therapies. In fact, up to a third of patients are non responders for current therapies and do not experience clinically meaningful weight loss. Additionally, patients experience numerous on target GI adverse effects, and weight regain is common after patients stop taking these drugs. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:03:52These challenges are highlighted by the real world use data on GLP-1s. A recent real world study found that sixty eight percent of people taking a GLP-one for obesity discontinued use of their medication within one year, and research from the Blue Cross Blue Shield Association found that fifty eight percent of patients discontinued use before reaching a clinically meaningful health benefit. We believe that NLRP3 inhibition may offer an efficacious, well tolerated treatment option for obesity, potentially as a monotherapy, in combination with GLP-one medications, or the maintenance treatment option. Our deep expertise in neuroscience and specifically in developing highly brain penetrant chemistry makes Nomura uniquely positioned to bring a potential new mechanism to this large and growing public health challenge. The breadth of our pipeline and its potential impact is immense, and we are in a strong position to translate that science into real world therapeutic breakthroughs. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:05:06We expect to have up to six clinical data readouts in patients over the next eighteen months, and I'm excited to continue to build on this momentum. I will now turn the call over to Josh Pinto, President of Nomura to review our pipeline updates. Josh? Joshua PintoPresident at Neumora Therapeutics00:05:25Thanks, Paul. We continue to make important progress across our pipeline, which is a direct reflection of our highly productive team, differentiated approach to neuroscience drug development, and rigorous prioritization of our pipeline. With the initiation of our phase one study of NMRA eight sixty one, we now have three clinical stage assets advancing through development, each with near term catalysts on the horizon, including data from our Phase 1b study of NMRA five eleven in Alzheimer's disease agitation, which is expected around year end top line data from the optimized phase three coastal program with Nevakoprant in major depressive disorder with the first top line data expected in the 2026, and Phase I SADMAD data for our recently announced M4 PAM NMRA eight sixty one, which is anticipated in the 2026. Additionally, we expect to bring another M4 PAM, NMRA898 into the clinic in 2025, and we are currently running a preclinical diet induced obesity or DIO model with NMRA two fifteen in mice, a model that we believe is highly translatable to the clinical setting. Joshua PintoPresident at Neumora Therapeutics00:06:55We are excited to provide more detail on the DIO data this fall, which we believe has the potential to be highly compelling. Looking forward, we expect to initiate clinical studies with NMR-two 15 in the 2026. As we continue to prioritise our pipeline, we are focused on allocating resources to the programmes we believe will make the biggest difference for patients. Given that focus, we will not be advancing our NMDA program this year. As you've heard, we have a wealth of opportunities at Newborough and are entering a catalyst rich period. Joshua PintoPresident at Neumora Therapeutics00:07:36With that in mind, we plan to host an R and D event in the fourth quarter of this year to discuss our programs in more detail. Each of our programs targets a substantial unmet need and represents a meaningful market opportunity. Our development strategy has multiple pathways for success and the potential to deliver multiple breakthrough and blockbuster therapies to patients in need of better treatment options. And we look forward to sharing more detail later this year. With that overview, I will now turn the call over to Bill to provide an overview of our clinical programs. Bill? Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:08:18Thanks, Josh. We designed our clinical programs to target mechanisms of action that we believe have the potential to fundamentally change how diseases are treated. Our approach is grounded in strong scientific rationale and a commitment to improving patient outcomes. This is clearly seen in our newly initiated Phase one study of NMRA861. NMRA861 is a highly potent and selective M4 positive allosteric modulator or PAM, which we believe offers best in class pharmacology. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:08:50Schizophrenia is a complex disorder and the effectiveness of current treatments is often limited by suboptimal efficacy, side effects, and high rates of non adherence. We believe M4 PAMs represent a promising new class with the potential to deliver a more favorable therapeutic profile, including efficacy, improved tolerability, and once daily dosing. NMRA eight sixty one demonstrated robust activity in preclinical efficacy models. It was also well tolerated in preclinical safety studies with no convulsions observed in rabbits, dogs, or rats. NMRA861 is currently being evaluated in a phase one single ascending dose and multiple ascending dose study in healthy adult participants and adults with stable schizophrenia. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:09:40We look forward to reporting data from that study including safety and tolerability, human pharmacokinetic data confirming the potential for once daily dosing and central nervous system penetration in the 2026. Additionally, we expect to bring another pan into the clinic this year as we continue to advance our broader M4 franchise. We also have upcoming clinical milestones for Nabacoprant and NMRA five eleven. Enrollment is ongoing in the COSTAL program and we continue to expect top line data from COSTAL-three in the 2026 and COSTAL-two in the 2026. Additionally, we expect top line results from our Phase 1b signal seeking study of NMRA-five eleven in Alzheimer's disease agitation around the end of this year. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:10:29We have made meaningful progress across our robust and growing pipeline with multiple programs advancing towards near term clinical milestones. With our robust pipeline and R and D efforts, we believe we are poised to bring forward novel therapeutics and deliver transformative treatments to millions of patients around the world. With that, I'll now turn the call over to Mike for a review of the financials. Mike. Michael MilliganCFO at Neumora Therapeutics00:10:55Thanks, Bill, and good afternoon, everyone. Our financial results for the 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. We ended the quarter with $217,600,000 in cash, cash equivalents and marketable securities as of 06/30/2025. We anticipate our cash runway to support operations into 2027 well beyond all of our upcoming clinical milestones. Michael MilliganCFO at Neumora Therapeutics00:11:27Our total net loss for the second quarter was $52,700,000 compared to $58,700,000 for the same period in 2024. This decrease was primarily due to a reduction in stock based compensation and personnel related expense and a reduction in clinical trial costs. With that, I'll now hand the call over to Helen to manage Q and A with the operator. Helen? Helen RubinsteinVP-IR and Corporate Communications at Neumora Therapeutics00:11:53Thanks, 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 and A. Operator? Operator00:12:10At this time, I would like to remind everyone, in order to ask a question, press star then the number one on your telephone keypad. Your first question comes from the line of Brian Abrahams of RBC Capital Markets. Please go ahead. Analyst00:12:32Hi, this is Joe on for Brian. Thanks for taking our question. Can you talk about the preclinical study design in obesity, the type of diet, whether if you're looking to combine with GLP-1s and whether what sort of comparator arms you're looking to implement in the study. Are there any certain aspect of weight loss that you're looking to demonstrate such as better quality weight loss or maintenance of weight loss post GLP-one withdrawal? Thank you. Joshua PintoPresident at Neumora Therapeutics00:13:05Thanks, Joe. This is Josh here. I'll take that question. For our program NMRA215, which is our NLRP3 inhibitor that we're moving forward and we've announced it and we've prioritized in obesity, The next step, as you've highlighted, will be to run a diet induced obesity study in mouse. Part of the reason we're so excited about this study is we know that this model really translates between the animal setting and the human setting. And we think it'll give us a prediction in terms of how this molecule could ultimately perform in a clinical trial setting. In this study, we are going to look to run a set of studies and across them, there's really going to be three key goals. First, we're going to assess the potential of NMRA two fifteen as a monotherapy treatment for obesity. And in this, it'll just be NMRA two fifteen dosed in the mice. Joshua PintoPresident at Neumora Therapeutics00:13:56We really think that this could provide a value proposition as you relate to what's out there today in terms of the GLP-one as well as the GIP therapies, we think that this molecule could offer the potential for incretin like weight loss with better tolerability, convenience as a small molecule, which could also result in a lower cost of goods as well. And so from a monotherapy perspective, we absolutely will be looking to show benefit there. We'll also be testing the product in combination as an add on to a GLP-one product. In this particular model, we will use semaglutide. It is known to be the standard GLP-one used in the mouse DIO model, and so we will look at two fifteen as an add on to SEMA in this study, and ultimately to see can we, with two fifteen, reduce the level of SEMA that is given and ultimately increase the weight loss and the tolerability? Joshua PintoPresident at Neumora Therapeutics00:14:58We know in this population there's been a range of studies out there, but we've seen anywhere from sixty to seventy percent of people taking the GLP-1s right now do not respond or ultimately discontinued due to lack of maximal weight loss. So we think that there's absolutely room to add new therapeutics on top of this. And then finally, one of the key questions is just the long term durability of the existing therapies, and we will be looking to test NMR-two fifteen as a maintenance treatment. And so you can think about this paradigm, Joe, as dosing both two fifteen and semaglutide in combination to reach a level of weight loss, and then removing the semaglutide dose ultimately to demonstrate that NMRA two fifteen can maintain the weight loss over a long term period. What this could really provide the market is a long term cost effective and tolerable option beyond the GLP-one therapy today. Joshua PintoPresident at Neumora Therapeutics00:15:55So we're really excited to bring this program forward, Joe, and really looking forward to providing the data from our DIO model as we move through the rest of 2025. Operator00:16:05Your next question comes from the line of Paul Matteis of Stifel. Please go ahead. Analyst00:16:13Hi. This is Matthew on for Paul. My question is on eight sixty one. Could you perhaps provide more description on what gives you confidence that this would be safer than the two sixty six molecule, which was also from the Vanderbilt deal? Joshua PintoPresident at Neumora Therapeutics00:16:32Yes, absolutely. So Joe, is Josh here. I'll take the question first and I'll pass it over to Nick to provide some specifics. I think Joe, one of the things to really remember about our M4 franchise is that all of our compounds are structurally distinct. And so as we think about the convulsions that happened with February, August and August, which is our third M4 PAM that we announced today, are all structurally distinct from one another. Joshua PintoPresident at Neumora Therapeutics00:16:59But Nick, maybe you can provide some added details just on what gives us confidence on the safety of eight six one, you know, as it Nicholas BrandonChief Scientific Officer at Neumora Therapeutics00:17:06relates to what we saw in two six six. Thanks, Josh. It's Nick here. Matthew, a good question. So just stepping back, if you remember, with two six six, you know, we had an unfortunate and unexpected convulsions in rabbit. Nicholas BrandonChief Scientific Officer at Neumora Therapeutics00:17:20And, really, as we brought these structurally distinct compounds forward, that was really the main barrier for us to achieve. When you look at the basic pharmacology, you know, have a look at our, you know, our our current corporate deck. The molecules are really good, in particular, a c one eight nine eight. Critically, we've taken both those compounds into rabbit. We've, you know, pushed doses and exposures, which have exceeded what where we saw convulsions of two sixty six. Nicholas BrandonChief Scientific Officer at Neumora Therapeutics00:17:44So moving forward, we truly derisked the two sixty six of both of these molecules. So we feel like we're in a really good position now to push both of these forward and obviously very excited as we announced we've started our Phase I study with eight sixty one and more news to follow on August. Operator00:18:04Thank you. Your next question comes from the line of Yatin Suneja of Guggenheim. Please go ahead. Yatin SunejaSenior MD & Biotechnology Analyst at Guggenheim Partners00:18:12Hey, guys. Thank you for taking my question. Exciting announcements today. Maybe just a couple on the COASTal program first, if I may. Any color on screen failure rate you can provide on the two studies or any parameters that might give you confidence that the site quality is good here? Yatin SunejaSenior MD & Biotechnology Analyst at Guggenheim Partners00:18:36Then if you can also comment on the male to female ratio that you might be targeting or you might have enrolled so far. And then just a quick one on the five eleven, obviously those data are gonna come relatively soon, so if you can maybe help us set expectation, what we should be expecting, and what will be considered good for you to move forward. Thank you so much. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:19:01Hi, Yatin, this is Phil. Good to speak with you again. We are really pleased with some of the benefits we're seeing from the added measures we put into place with two and three. As you'll recall, we took three steps when we paused the COSTAL one study. Number one, we enhanced the medical monitoring second, we added in verified clinical trials and third, we reduced the overall number of sites that were participating to focus on those that had more experience in MEG. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:19:28So the first of these steps, which was enhancing the medical monitoring, included partnering with MGH, so RITIO, FAVA, the SAFR Group, CTNI. And we are seeing that that independent verification of the diagnosis is helping to ensure that appropriate patients are being randomized. The VCT approach, or Verified Clinical Trials, is a screening database that's helped us to ensure that the subjects being considered for the study aren't enrolled at a different site, or in a trial that would serve as exclusionary, for example, in a TRD study. So that is also providing some added benefits. So we're pleased with what we are seeing with the measures we've put into place, and the trial is progressing in that regard. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:20:12With respect to male to female ratio, I'll just simply state that we are seeing more females already enrolled relative to males in cohort two and three. I won't get into specifics today, but we are pleased to see that that is in fact more consistent with the prevalence of MDD and historically what's been enrolled with sex distribution across the studies. Lastly, with five eleven, as you'll recall this is a signal seeking study that's not powered to demonstrate statistical significance between active and placebo. Part A of the phase 1b study was designed to evaluate the safety, tolerability, and the PK in healthy elderly participants. We completed Part A in 2024, and MRA five eleven was well tolerated in those participants. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:20:59We've subsequently moved on to Part B and expect to have results towards the end of this year. Part B is designed to evaluate the safety, tolerability, efficacy in people with AD agitation. The primary endpoint is the change from baseline to weak data on CMAI. Although the study is not powered to show statistical significance, we believe the data will help us better understand the drug's effect in AD agitation, including the domains of agitation that it affects, and then we'll proceed with further steps around clinical development based on what we learn. Operator00:21:34Your next question comes from the line of Douglas Tsao of H. C. Wainwright. Please go ahead. Douglas TsaoManaging Director at H.C. Wainwright & Co.00:21:42Hi. Good morning. I'm just curious in terms of two fifteen and your thoughts in terms of development in obesity. Obviously, this is a very competitive space. And once you get past the preclinical stage and even Phase I, things start to become more expensive in terms of the studies. Douglas TsaoManaging Director at H.C. Wainwright & Co.00:22:02And obviously, as a sort of DNS focused company, you know, sort of obesity is maybe a little bit out of your primary focus. I'm just curious, is this something that you would want to take to a certain stage of development and accrue a certain amount of clinical data before potentially finding a partnership? Joshua PintoPresident at Neumora Therapeutics00:22:23Yes, Doug, this is Josh, and thanks for the question. I think in terms of how we view the obesity indication for us at Nomura, we're really committed to following the science as we advance our pipeline. And there's been this increasing body of evidence that really supports the role of centrally acting drugs for treating obesity. We've even seen it with some of the GLP-one therapies. It's clear that some of the appetite suppression is working through central mechanisms. Joshua PintoPresident at Neumora Therapeutics00:22:51What we think NLRP3 offers is really a distinct approach for the treatment of patients with obesity, different than the incretins or some of the other mechanisms that are in clinical development. And we've seen that through multiple sponsors having generated preclinical data in the DIO model supporting the role for NLRP3 inhibition in obesity. And so as we looked at this opportunity, we really felt like this fit within the scope of what Newmar was set up to do, which is tackle large population health challenges at scale that require expertise in developing chemistry that can act centrally. And that's what we've done. And I think you've seen through some of the data we've put out today, Doug, that we absolutely believe we have the best in class NLRP3 inhibitor in terms of CNS penetration. Joshua PintoPresident at Neumora Therapeutics00:23:42From a development perspective, we're not going to comment right now in terms of whether we're going to partner and or move the program forward on our own at various stages. What I can say is that progression of NMRA two fifteen through the DIO model and into phase one is contemplated in our spend that's associated with cash runway into 2027. And so it is currently in our operating plan to move forward under our own steam. So Doug, we're really excited about this announcement today, and really looking forward to kind of what we're going to bring forward over the rest of this year in terms of some of the preclinical data for NMRA two fifteen in obesity. Operator00:24:26Your next question comes from the line of Miles Minter of William Blair. Please go ahead. Myles MinterResearch Analyst - Healthcare at William Blair00:24:33Hi, guys. Thanks for the questions. The first one's on two fifteen. One of your peers that you listed as a molecule on Slide 28 in your presentation did have a diet induced obesity model showing 15% body weight decreased as a monotherapy. Just curious as your comment that efficacy is related to increasing brain exposure in your greater than twofold that compound according to your data. Myles MinterResearch Analyst - Healthcare at William Blair00:25:03Are you expecting efficacy in that preclinical model to be greater than 15% weight loss in a monotherapy setting? That's the first question. Second question is, has your confidence in COSTAL two or three changed at all since we've seen the Ventura one and two trial data at ACNP? I believe those showed a 0.9 and a 0.5 improvement versus placebo on the MADRS, respectively. So just wondering whether views have changed since you've actually seen that data. Joshua PintoPresident at Neumora Therapeutics00:25:33Hey, Miles, this is Josh. In terms of two fifteen, we've obviously looked at the weight loss that has been generated by competitors across the DIO model quite substantially. I think as you look at the weight loss that's been achieved by LRP3 inhibitors to date, I think it's showing in general about 10% to 15% weight loss as a monotherapy. From our perspective, that is quite compelling weight loss, particularly as we think about the translation from mouse models to humans. If you look at it in comparison, semaglutide, is a very well known molecule that's typically used as a control GLP-one in these studies, tends to generate in and around 20% weight loss. Joshua PintoPresident at Neumora Therapeutics00:26:17And so as we sit here today, I'm not going to provide a specific numerical guide in terms of what we would expect for NMR-two fifteen in the DIO model, but we absolutely think that the potential of these molecules is based on their activity centrally. And so we believe based on the data that we put out today showing that NMR215 has best in class brand exposure, that we have a chance to show some really compelling data within the DIO model. In terms of your second question on confidence around K2 or K3 post ACNP, I don't think our confidence or conviction of the study has really changed since we announced the changes that we're making to the study in the March timeframe. And maybe I'll turn it over to Bill right now just to comment on how some of those changes have really come into play and what we're seeing out of it. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:27:08Sure. Hi Miles, this is Bill. As you'll recall, the bacoprant is far more selective for kappa over mu opioid receptors, so there's a difference in pharmacology between the bacoprant and atincloprant. And then of course ours is a monotherapy development program in contrast to the adjunctive setting. And so with those fundamental differences between the molecules and the program to remain confident in our program, the steps we've taken post K-one also are proving to be quite helpful with enhancing the medical monitoring and the application of the verified clinical trials database, as well as having gone to the sites that are most experienced in MDD and having stopped those sites that have just less experience. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:27:49And so things are progressing per plan, and we're on track for K3 in the first quarter and K2 in the second quarter of next year. Operator00:28:07Your next question comes from the line of Amy Fadia of Needham. Please go ahead. Ami FadiaSenior Analyst at Needham & Company00:28:15Hi, good evening. Thanks for taking my question and apologies if this was already asked. My question is regarding the eight sixty one molecule. You mentioned earlier that it's obviously different from your earlier M4 PAM. But could you give us any color on any preclinical work that you may have done that gives you confidence around its safety profile? Thank you. Joshua PintoPresident at Neumora Therapeutics00:28:43Thanks, Ami. This is Josh. What I'll start off by mentioning is that, just a reminder, all of our M4 PAMs are structurally distinct from one another, including two six six, eight six one, and eight nine eight. But I'll turn turn this over to Nick right now to provide some more specifics on your question on eight six one safety profile. Nicholas BrandonChief Scientific Officer at Neumora Therapeutics00:29:00Yeah. Hi, Amy. Nick here. I think the, you the critical preclinical information we have is what we did in vivo in the rabbit. As you recall, it was unexpected feast in a rabbit which put us on clinical hold with that molecule. Nicholas BrandonChief Scientific Officer at Neumora Therapeutics00:29:13We've done a lot of work in the last twelve months with eight six one and eight nine eight in the rabbit where we've taken and we've dosed those compounds and achieved exposures, which surpassed where we were with two six six, and we've not seen any evidence of any convulsions. You know, we feel very confident we have have derisked both molecules as we move forward alongside that, you know, really encouraging, you know, overall pharmacological profile and other data we have. You know, we're really encouraged about moving both of them forward. Yeah. And as I mentioned earlier, really excited about having eight sixty one back in phase one clinical development. Operator00:29:57J. P. Morgan. Please go ahead. Analyst00:30:02Hi, team. This is Mariam on for Tess. Thank you for taking our question. What synergies do you see between your existing neuro focused pipeline and obesity? And along these lines, how did you come about deciding that this is the right next indication for Nomura? Analyst00:30:15And can you help us reconcile what your cash runway does and does not include in terms of R and D initiatives? Thank you. Joshua PintoPresident at Neumora Therapeutics00:30:23Great. This is Josh, and I'll take the question. I think as I mentioned previously, we were looking at indications to take 02/15 into, we are really committed, as I highlighted before, to following the science and the growing body of evidence highlighting that the drugs that are being developed and brought forward to treat obesity really are working through central mechanisms. We feel like obesity is an indication that fits squarely within our mandate of bringing novel mechanisms and novel approaches forward to patients suffering from a range of large population health disorders that are driven through a central mechanism. And so we really feel like NMRA215 into obesity is an opportunity for us to develop a new therapeutic that we believe could be best in class for that area. Joshua PintoPresident at Neumora Therapeutics00:31:15So we think there are a lot of synergies in terms of the team's expertise in designing and developing molecules that are highly brain penetrant as really the critical step to unlock the potential of this class and target. In terms of cash runway and what's included, what I will highlight is we have a strong cash balance as we sit here today. Mike highlighted about $217,000,000 on the balance sheet as we ended the second quarter. This gives us runway into 2027. That fully funds all of our critical programs where we provided public guidance through the clinical stage gates. Joshua PintoPresident at Neumora Therapeutics00:31:55And so we think that with each of the four most advanced programs, we will be able to deliver meaningful clinical milestones for each of them within the current cash runway period. So we're really excited about what we have moving forward, and frankly, the opportunity we have to bring forward six potential clinical catalysts in patients over the next eighteen months. Operator00:32:18That ends our Q and A session, and we appreciate your participation. I will now turn the call back over to Paul Burns, Chief Executive Officer, for closing remarks. Please go ahead. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:32:31Thanks, operator, and thank you again to everyone for joining us this afternoon. So as you can see, this is an exciting time at Nomura with up to six distinct catalysts anticipated over the next eighteen months, each serving as a critical inflection point with the potential to create significant value across our portfolio. These include preclinical data with NMRA two fifteen in obesity and the initiation of clinical studies with this program, initial clinical data from NMRA eight sixty one in schizophrenia, the Phase Ib data in Alzheimer's disease agitation, and Phase III data from nabacoprant in the coastal program. We are well positioned to achieve all upcoming milestones, which reflect the strength of our pipeline and caliber of our execution. But most importantly, it reflects our commitment to the millions of people who are in need of better treatment options. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:33:24We are working with urgency to bring forward the next generation of novel therapies and ultimately redefine drug development in neuroscience. So thank you again for your continued support, and that concludes our call this afternoon. Operator00:33:37Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.Read moreParticipantsExecutivesHelen RubinsteinVP-IR and Corporate CommunicationsPaul BernsCo-Founder, Executive Chairman & CEOJoshua PintoPresidentBill AuroraChief Operating & Development OfficerMichael MilliganCFONicholas BrandonChief Scientific OfficerAnalystsAnalystYatin SunejaSenior MD & Biotechnology Analyst at Guggenheim PartnersDouglas TsaoManaging Director at H.C. Wainwright & Co.Myles MinterResearch Analyst - Healthcare at William BlairAmi FadiaSenior Analyst at Needham & CompanyPowered by Earnings DocumentsPress Release(8-K)Quarterly report(10-Q) Neumora Therapeutics Earnings HeadlinesNeumora Therapeutics Initiates Phase 1 Study for Schizophrenia Drug NMRA-861August 20 at 2:27 AM | msn.comNeumora Therapeutics, Inc. (NASDAQ:NMRA) Receives $7.14 Average PT from BrokeragesAugust 18, 2025 | americanbankingnews.comMarket Panic: Trump Just Dropped a Bomb on Your Stockstock Market Panic: Trump Just Dropped a Bomb on Your Stocks The market is in freefall—and Trump's new tariffs just lit the fuse. Millions of investors are blindsided as stocks plunge… but this is only Phase 1. If you're still holding the wrong assets, you could lose 30% or more in the coming weeks. | American Alternative (Ad)Q3 EPS Forecast for Neumora Therapeutics Lifted by AnalystAugust 12, 2025 | americanbankingnews.comNeumora Therapeutics, Inc.: Promising Potential in Obesity Therapeutics with NMRA-215August 7, 2025 | tipranks.comNeumora outlines six upcoming clinical catalysts and prioritizes obesity program with NMRA-215August 7, 2025 | msn.comSee More Neumora Therapeutics Headlines Get Earnings Announcements in your inboxWant to stay updated on the latest earnings announcements and upcoming reports for companies like Neumora Therapeutics? Sign up for Earnings360's daily newsletter to receive timely earnings updates on Neumora Therapeutics and other key companies, straight to your email. Email Address About Neumora TherapeuticsNeumora Therapeutics (NASDAQ:NMRA), a clinical-stage biopharmaceutical company, engages in developing therapeutic treatments for brain diseases, neuropsychiatric disorders, and neurodegenerative diseases. The company develops navacaprant (NMRA-140), a novel once-daily oral kappa opioid receptor antagonist, which is in phase 3 clinical trials for the treatment of major depressive disorder. It also develops NMRA-511 that is in phase 1 clinical trials in patients with agitation associated with dementia due to Alzheimer's disease; and NMRA-266, which is in the phase 1 clinical trial for the treatment of schizophrenia and other neuropsychiatric disorders. In addition, its preclinical phase product includes NMRA-NMDA for the treatment of schizophrenia; NMRA-CK1d, a CK1d inhibitor program for the treatment of amyotrophic lateral sclerosis; NMRA-NLRP3 for the treatment of certain neurodegenerative conditions; and NMRA-GCase for the treatment of Parkinson's disease. The company was formerly known as RBNC Therapeutics, Inc. and changed its name to Neumora Therapeutics, Inc. in October 2021. Neumora Therapeutics, Inc. was incorporated in 2019 and is headquartered in Watertown, Massachusetts.View Neumora Therapeutics ProfileRead more More Earnings Resources from MarketBeat Earnings Tools Today's Earnings Tomorrow's Earnings Next Week's Earnings Upcoming Earnings Calls Earnings Newsletter Earnings Call Transcripts Earnings Beats & Misses Corporate Guidance Earnings Screener Earnings By Country U.S. Earnings Reports Canadian Earnings Reports U.K. Earnings Reports Latest Articles After Earnings Miss, Walmart Is Still a Top Consumer Staples PlayRoyal Caribbean Earnings Beat Fuels Strong 2025 OutlookDLocal Stock Soars 43% After Earnings Beat and Raised GuidanceGreen Dot's 30% Rally: Turnaround Takes Off on Explosive EarningsElbit Systems Jumps on Record Earnings and a $1.6B ContractBrinker Serves Up Earnings Beat, Sidesteps Cost PressuresWhy BigBear.ai Stock's Dip on Earnings Can Be an Opportunity Upcoming Earnings PDD (8/25/2025)BHP Group (8/25/2025)Bank Of Montreal (8/26/2025)Bank of Nova Scotia (8/26/2025)CrowdStrike (8/27/2025)NVIDIA (8/27/2025)Royal Bank Of Canada (8/27/2025)Snowflake (8/27/2025)Autodesk (8/28/2025)Marvell Technology (8/28/2025) Get 30 Days of MarketBeat All Access for Free Sign up for MarketBeat All Access to gain access to MarketBeat's full suite of research tools. 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PresentationSkip to Participants Operator00:00:00Ladies and gentlemen, thank you for standing by. This is RG, your conference operator today. 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. Operator00:00:17I would like now to turn the conference over to Helen Robenstein, Vice President of Investor Relations and Communications. Please go ahead. Helen RubinsteinVP-IR and Corporate Communications at Neumora Therapeutics00:00:27Good afternoon and thank you for joining Nomura Therapeutics second quarter twenty twenty five financial results conference call. Before we begin, I encourage everyone to go to the Investors and Media section of our website at pneumoratx.com, where you can find the press release related to today's call. With me today from Nomura are Chief Executive Officer, Paul Burns President, Josh Pinto Chief Operating and Development Officer, Bill Arora Chief Scientific Officer, Nick Brandon 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. Helen RubinsteinVP-IR and Corporate Communications at Neumora Therapeutics00:01:11Please 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. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:01:21Thanks, Helen. Good afternoon, everyone, and thank you for joining us. At Nomura, we are on a mission to address the largest population health challenges of our generation and to do so at scale. To achieve that goal, we know that we need to generate better medicines, therapies that enable better outcomes, that meaningfully improve the treatment of prevalent diseases, and ultimately that positively impact quality of life for patients and their families. With that aim in mind, we built an industry leading pipeline targeting some of the most prevalent and burdensome brain diseases. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:02:02Our approach is centered on advancing programs with best in class pharmacology, targeting novel mechanisms of action with the potential to improve upon the current standard of care for hundreds of millions of people. We are proud to be making important progress toward that goal. Today we announced that we prioritized obesity as the lead indication for NMRA two fifteen, our highly brain penetrant NLRP3 inhibitor. An increasing body of evidence supports the need for the role of centrally acting drugs to drive weight loss and obesity and NLRP3 inhibition in particular has shown promise across multiple studies. Importantly, recent data suggests that molecules with high CNS penetration and activity are required for efficacy with this target. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:03:01Currently, obesity and overweight affect more than two point five billion people globally, and by 2035 that number is expected to increase to up to four billion people. The need here is immense. Obesity is associated with significant negative outcomes and lower quality of life, and there is room to improve upon the efficacy and tolerability of the current generation of incretin therapies. In fact, up to a third of patients are non responders for current therapies and do not experience clinically meaningful weight loss. Additionally, patients experience numerous on target GI adverse effects, and weight regain is common after patients stop taking these drugs. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:03:52These challenges are highlighted by the real world use data on GLP-1s. A recent real world study found that sixty eight percent of people taking a GLP-one for obesity discontinued use of their medication within one year, and research from the Blue Cross Blue Shield Association found that fifty eight percent of patients discontinued use before reaching a clinically meaningful health benefit. We believe that NLRP3 inhibition may offer an efficacious, well tolerated treatment option for obesity, potentially as a monotherapy, in combination with GLP-one medications, or the maintenance treatment option. Our deep expertise in neuroscience and specifically in developing highly brain penetrant chemistry makes Nomura uniquely positioned to bring a potential new mechanism to this large and growing public health challenge. The breadth of our pipeline and its potential impact is immense, and we are in a strong position to translate that science into real world therapeutic breakthroughs. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:05:06We expect to have up to six clinical data readouts in patients over the next eighteen months, and I'm excited to continue to build on this momentum. I will now turn the call over to Josh Pinto, President of Nomura to review our pipeline updates. Josh? Joshua PintoPresident at Neumora Therapeutics00:05:25Thanks, Paul. We continue to make important progress across our pipeline, which is a direct reflection of our highly productive team, differentiated approach to neuroscience drug development, and rigorous prioritization of our pipeline. With the initiation of our phase one study of NMRA eight sixty one, we now have three clinical stage assets advancing through development, each with near term catalysts on the horizon, including data from our Phase 1b study of NMRA five eleven in Alzheimer's disease agitation, which is expected around year end top line data from the optimized phase three coastal program with Nevakoprant in major depressive disorder with the first top line data expected in the 2026, and Phase I SADMAD data for our recently announced M4 PAM NMRA eight sixty one, which is anticipated in the 2026. Additionally, we expect to bring another M4 PAM, NMRA898 into the clinic in 2025, and we are currently running a preclinical diet induced obesity or DIO model with NMRA two fifteen in mice, a model that we believe is highly translatable to the clinical setting. Joshua PintoPresident at Neumora Therapeutics00:06:55We are excited to provide more detail on the DIO data this fall, which we believe has the potential to be highly compelling. Looking forward, we expect to initiate clinical studies with NMR-two 15 in the 2026. As we continue to prioritise our pipeline, we are focused on allocating resources to the programmes we believe will make the biggest difference for patients. Given that focus, we will not be advancing our NMDA program this year. As you've heard, we have a wealth of opportunities at Newborough and are entering a catalyst rich period. Joshua PintoPresident at Neumora Therapeutics00:07:36With that in mind, we plan to host an R and D event in the fourth quarter of this year to discuss our programs in more detail. Each of our programs targets a substantial unmet need and represents a meaningful market opportunity. Our development strategy has multiple pathways for success and the potential to deliver multiple breakthrough and blockbuster therapies to patients in need of better treatment options. And we look forward to sharing more detail later this year. With that overview, I will now turn the call over to Bill to provide an overview of our clinical programs. Bill? Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:08:18Thanks, Josh. We designed our clinical programs to target mechanisms of action that we believe have the potential to fundamentally change how diseases are treated. Our approach is grounded in strong scientific rationale and a commitment to improving patient outcomes. This is clearly seen in our newly initiated Phase one study of NMRA861. NMRA861 is a highly potent and selective M4 positive allosteric modulator or PAM, which we believe offers best in class pharmacology. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:08:50Schizophrenia is a complex disorder and the effectiveness of current treatments is often limited by suboptimal efficacy, side effects, and high rates of non adherence. We believe M4 PAMs represent a promising new class with the potential to deliver a more favorable therapeutic profile, including efficacy, improved tolerability, and once daily dosing. NMRA eight sixty one demonstrated robust activity in preclinical efficacy models. It was also well tolerated in preclinical safety studies with no convulsions observed in rabbits, dogs, or rats. NMRA861 is currently being evaluated in a phase one single ascending dose and multiple ascending dose study in healthy adult participants and adults with stable schizophrenia. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:09:40We look forward to reporting data from that study including safety and tolerability, human pharmacokinetic data confirming the potential for once daily dosing and central nervous system penetration in the 2026. Additionally, we expect to bring another pan into the clinic this year as we continue to advance our broader M4 franchise. We also have upcoming clinical milestones for Nabacoprant and NMRA five eleven. Enrollment is ongoing in the COSTAL program and we continue to expect top line data from COSTAL-three in the 2026 and COSTAL-two in the 2026. Additionally, we expect top line results from our Phase 1b signal seeking study of NMRA-five eleven in Alzheimer's disease agitation around the end of this year. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:10:29We have made meaningful progress across our robust and growing pipeline with multiple programs advancing towards near term clinical milestones. With our robust pipeline and R and D efforts, we believe we are poised to bring forward novel therapeutics and deliver transformative treatments to millions of patients around the world. With that, I'll now turn the call over to Mike for a review of the financials. Mike. Michael MilliganCFO at Neumora Therapeutics00:10:55Thanks, Bill, and good afternoon, everyone. Our financial results for the 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. We ended the quarter with $217,600,000 in cash, cash equivalents and marketable securities as of 06/30/2025. We anticipate our cash runway to support operations into 2027 well beyond all of our upcoming clinical milestones. Michael MilliganCFO at Neumora Therapeutics00:11:27Our total net loss for the second quarter was $52,700,000 compared to $58,700,000 for the same period in 2024. This decrease was primarily due to a reduction in stock based compensation and personnel related expense and a reduction in clinical trial costs. With that, I'll now hand the call over to Helen to manage Q and A with the operator. Helen? Helen RubinsteinVP-IR and Corporate Communications at Neumora Therapeutics00:11:53Thanks, 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 and A. Operator? Operator00:12:10At this time, I would like to remind everyone, in order to ask a question, press star then the number one on your telephone keypad. Your first question comes from the line of Brian Abrahams of RBC Capital Markets. Please go ahead. Analyst00:12:32Hi, this is Joe on for Brian. Thanks for taking our question. Can you talk about the preclinical study design in obesity, the type of diet, whether if you're looking to combine with GLP-1s and whether what sort of comparator arms you're looking to implement in the study. Are there any certain aspect of weight loss that you're looking to demonstrate such as better quality weight loss or maintenance of weight loss post GLP-one withdrawal? Thank you. Joshua PintoPresident at Neumora Therapeutics00:13:05Thanks, Joe. This is Josh here. I'll take that question. For our program NMRA215, which is our NLRP3 inhibitor that we're moving forward and we've announced it and we've prioritized in obesity, The next step, as you've highlighted, will be to run a diet induced obesity study in mouse. Part of the reason we're so excited about this study is we know that this model really translates between the animal setting and the human setting. And we think it'll give us a prediction in terms of how this molecule could ultimately perform in a clinical trial setting. In this study, we are going to look to run a set of studies and across them, there's really going to be three key goals. First, we're going to assess the potential of NMRA two fifteen as a monotherapy treatment for obesity. And in this, it'll just be NMRA two fifteen dosed in the mice. Joshua PintoPresident at Neumora Therapeutics00:13:56We really think that this could provide a value proposition as you relate to what's out there today in terms of the GLP-one as well as the GIP therapies, we think that this molecule could offer the potential for incretin like weight loss with better tolerability, convenience as a small molecule, which could also result in a lower cost of goods as well. And so from a monotherapy perspective, we absolutely will be looking to show benefit there. We'll also be testing the product in combination as an add on to a GLP-one product. In this particular model, we will use semaglutide. It is known to be the standard GLP-one used in the mouse DIO model, and so we will look at two fifteen as an add on to SEMA in this study, and ultimately to see can we, with two fifteen, reduce the level of SEMA that is given and ultimately increase the weight loss and the tolerability? Joshua PintoPresident at Neumora Therapeutics00:14:58We know in this population there's been a range of studies out there, but we've seen anywhere from sixty to seventy percent of people taking the GLP-1s right now do not respond or ultimately discontinued due to lack of maximal weight loss. So we think that there's absolutely room to add new therapeutics on top of this. And then finally, one of the key questions is just the long term durability of the existing therapies, and we will be looking to test NMR-two fifteen as a maintenance treatment. And so you can think about this paradigm, Joe, as dosing both two fifteen and semaglutide in combination to reach a level of weight loss, and then removing the semaglutide dose ultimately to demonstrate that NMRA two fifteen can maintain the weight loss over a long term period. What this could really provide the market is a long term cost effective and tolerable option beyond the GLP-one therapy today. Joshua PintoPresident at Neumora Therapeutics00:15:55So we're really excited to bring this program forward, Joe, and really looking forward to providing the data from our DIO model as we move through the rest of 2025. Operator00:16:05Your next question comes from the line of Paul Matteis of Stifel. Please go ahead. Analyst00:16:13Hi. This is Matthew on for Paul. My question is on eight sixty one. Could you perhaps provide more description on what gives you confidence that this would be safer than the two sixty six molecule, which was also from the Vanderbilt deal? Joshua PintoPresident at Neumora Therapeutics00:16:32Yes, absolutely. So Joe, is Josh here. I'll take the question first and I'll pass it over to Nick to provide some specifics. I think Joe, one of the things to really remember about our M4 franchise is that all of our compounds are structurally distinct. And so as we think about the convulsions that happened with February, August and August, which is our third M4 PAM that we announced today, are all structurally distinct from one another. Joshua PintoPresident at Neumora Therapeutics00:16:59But Nick, maybe you can provide some added details just on what gives us confidence on the safety of eight six one, you know, as it Nicholas BrandonChief Scientific Officer at Neumora Therapeutics00:17:06relates to what we saw in two six six. Thanks, Josh. It's Nick here. Matthew, a good question. So just stepping back, if you remember, with two six six, you know, we had an unfortunate and unexpected convulsions in rabbit. Nicholas BrandonChief Scientific Officer at Neumora Therapeutics00:17:20And, really, as we brought these structurally distinct compounds forward, that was really the main barrier for us to achieve. When you look at the basic pharmacology, you know, have a look at our, you know, our our current corporate deck. The molecules are really good, in particular, a c one eight nine eight. Critically, we've taken both those compounds into rabbit. We've, you know, pushed doses and exposures, which have exceeded what where we saw convulsions of two sixty six. Nicholas BrandonChief Scientific Officer at Neumora Therapeutics00:17:44So moving forward, we truly derisked the two sixty six of both of these molecules. So we feel like we're in a really good position now to push both of these forward and obviously very excited as we announced we've started our Phase I study with eight sixty one and more news to follow on August. Operator00:18:04Thank you. Your next question comes from the line of Yatin Suneja of Guggenheim. Please go ahead. Yatin SunejaSenior MD & Biotechnology Analyst at Guggenheim Partners00:18:12Hey, guys. Thank you for taking my question. Exciting announcements today. Maybe just a couple on the COASTal program first, if I may. Any color on screen failure rate you can provide on the two studies or any parameters that might give you confidence that the site quality is good here? Yatin SunejaSenior MD & Biotechnology Analyst at Guggenheim Partners00:18:36Then if you can also comment on the male to female ratio that you might be targeting or you might have enrolled so far. And then just a quick one on the five eleven, obviously those data are gonna come relatively soon, so if you can maybe help us set expectation, what we should be expecting, and what will be considered good for you to move forward. Thank you so much. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:19:01Hi, Yatin, this is Phil. Good to speak with you again. We are really pleased with some of the benefits we're seeing from the added measures we put into place with two and three. As you'll recall, we took three steps when we paused the COSTAL one study. Number one, we enhanced the medical monitoring second, we added in verified clinical trials and third, we reduced the overall number of sites that were participating to focus on those that had more experience in MEG. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:19:28So the first of these steps, which was enhancing the medical monitoring, included partnering with MGH, so RITIO, FAVA, the SAFR Group, CTNI. And we are seeing that that independent verification of the diagnosis is helping to ensure that appropriate patients are being randomized. The VCT approach, or Verified Clinical Trials, is a screening database that's helped us to ensure that the subjects being considered for the study aren't enrolled at a different site, or in a trial that would serve as exclusionary, for example, in a TRD study. So that is also providing some added benefits. So we're pleased with what we are seeing with the measures we've put into place, and the trial is progressing in that regard. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:20:12With respect to male to female ratio, I'll just simply state that we are seeing more females already enrolled relative to males in cohort two and three. I won't get into specifics today, but we are pleased to see that that is in fact more consistent with the prevalence of MDD and historically what's been enrolled with sex distribution across the studies. Lastly, with five eleven, as you'll recall this is a signal seeking study that's not powered to demonstrate statistical significance between active and placebo. Part A of the phase 1b study was designed to evaluate the safety, tolerability, and the PK in healthy elderly participants. We completed Part A in 2024, and MRA five eleven was well tolerated in those participants. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:20:59We've subsequently moved on to Part B and expect to have results towards the end of this year. Part B is designed to evaluate the safety, tolerability, efficacy in people with AD agitation. The primary endpoint is the change from baseline to weak data on CMAI. Although the study is not powered to show statistical significance, we believe the data will help us better understand the drug's effect in AD agitation, including the domains of agitation that it affects, and then we'll proceed with further steps around clinical development based on what we learn. Operator00:21:34Your next question comes from the line of Douglas Tsao of H. C. Wainwright. Please go ahead. Douglas TsaoManaging Director at H.C. Wainwright & Co.00:21:42Hi. Good morning. I'm just curious in terms of two fifteen and your thoughts in terms of development in obesity. Obviously, this is a very competitive space. And once you get past the preclinical stage and even Phase I, things start to become more expensive in terms of the studies. Douglas TsaoManaging Director at H.C. Wainwright & Co.00:22:02And obviously, as a sort of DNS focused company, you know, sort of obesity is maybe a little bit out of your primary focus. I'm just curious, is this something that you would want to take to a certain stage of development and accrue a certain amount of clinical data before potentially finding a partnership? Joshua PintoPresident at Neumora Therapeutics00:22:23Yes, Doug, this is Josh, and thanks for the question. I think in terms of how we view the obesity indication for us at Nomura, we're really committed to following the science as we advance our pipeline. And there's been this increasing body of evidence that really supports the role of centrally acting drugs for treating obesity. We've even seen it with some of the GLP-one therapies. It's clear that some of the appetite suppression is working through central mechanisms. Joshua PintoPresident at Neumora Therapeutics00:22:51What we think NLRP3 offers is really a distinct approach for the treatment of patients with obesity, different than the incretins or some of the other mechanisms that are in clinical development. And we've seen that through multiple sponsors having generated preclinical data in the DIO model supporting the role for NLRP3 inhibition in obesity. And so as we looked at this opportunity, we really felt like this fit within the scope of what Newmar was set up to do, which is tackle large population health challenges at scale that require expertise in developing chemistry that can act centrally. And that's what we've done. And I think you've seen through some of the data we've put out today, Doug, that we absolutely believe we have the best in class NLRP3 inhibitor in terms of CNS penetration. Joshua PintoPresident at Neumora Therapeutics00:23:42From a development perspective, we're not going to comment right now in terms of whether we're going to partner and or move the program forward on our own at various stages. What I can say is that progression of NMRA two fifteen through the DIO model and into phase one is contemplated in our spend that's associated with cash runway into 2027. And so it is currently in our operating plan to move forward under our own steam. So Doug, we're really excited about this announcement today, and really looking forward to kind of what we're going to bring forward over the rest of this year in terms of some of the preclinical data for NMRA two fifteen in obesity. Operator00:24:26Your next question comes from the line of Miles Minter of William Blair. Please go ahead. Myles MinterResearch Analyst - Healthcare at William Blair00:24:33Hi, guys. Thanks for the questions. The first one's on two fifteen. One of your peers that you listed as a molecule on Slide 28 in your presentation did have a diet induced obesity model showing 15% body weight decreased as a monotherapy. Just curious as your comment that efficacy is related to increasing brain exposure in your greater than twofold that compound according to your data. Myles MinterResearch Analyst - Healthcare at William Blair00:25:03Are you expecting efficacy in that preclinical model to be greater than 15% weight loss in a monotherapy setting? That's the first question. Second question is, has your confidence in COSTAL two or three changed at all since we've seen the Ventura one and two trial data at ACNP? I believe those showed a 0.9 and a 0.5 improvement versus placebo on the MADRS, respectively. So just wondering whether views have changed since you've actually seen that data. Joshua PintoPresident at Neumora Therapeutics00:25:33Hey, Miles, this is Josh. In terms of two fifteen, we've obviously looked at the weight loss that has been generated by competitors across the DIO model quite substantially. I think as you look at the weight loss that's been achieved by LRP3 inhibitors to date, I think it's showing in general about 10% to 15% weight loss as a monotherapy. From our perspective, that is quite compelling weight loss, particularly as we think about the translation from mouse models to humans. If you look at it in comparison, semaglutide, is a very well known molecule that's typically used as a control GLP-one in these studies, tends to generate in and around 20% weight loss. Joshua PintoPresident at Neumora Therapeutics00:26:17And so as we sit here today, I'm not going to provide a specific numerical guide in terms of what we would expect for NMR-two fifteen in the DIO model, but we absolutely think that the potential of these molecules is based on their activity centrally. And so we believe based on the data that we put out today showing that NMR215 has best in class brand exposure, that we have a chance to show some really compelling data within the DIO model. In terms of your second question on confidence around K2 or K3 post ACNP, I don't think our confidence or conviction of the study has really changed since we announced the changes that we're making to the study in the March timeframe. And maybe I'll turn it over to Bill right now just to comment on how some of those changes have really come into play and what we're seeing out of it. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:27:08Sure. Hi Miles, this is Bill. As you'll recall, the bacoprant is far more selective for kappa over mu opioid receptors, so there's a difference in pharmacology between the bacoprant and atincloprant. And then of course ours is a monotherapy development program in contrast to the adjunctive setting. And so with those fundamental differences between the molecules and the program to remain confident in our program, the steps we've taken post K-one also are proving to be quite helpful with enhancing the medical monitoring and the application of the verified clinical trials database, as well as having gone to the sites that are most experienced in MDD and having stopped those sites that have just less experience. Bill AuroraChief Operating & Development Officer at Neumora Therapeutics00:27:49And so things are progressing per plan, and we're on track for K3 in the first quarter and K2 in the second quarter of next year. Operator00:28:07Your next question comes from the line of Amy Fadia of Needham. Please go ahead. Ami FadiaSenior Analyst at Needham & Company00:28:15Hi, good evening. Thanks for taking my question and apologies if this was already asked. My question is regarding the eight sixty one molecule. You mentioned earlier that it's obviously different from your earlier M4 PAM. But could you give us any color on any preclinical work that you may have done that gives you confidence around its safety profile? Thank you. Joshua PintoPresident at Neumora Therapeutics00:28:43Thanks, Ami. This is Josh. What I'll start off by mentioning is that, just a reminder, all of our M4 PAMs are structurally distinct from one another, including two six six, eight six one, and eight nine eight. But I'll turn turn this over to Nick right now to provide some more specifics on your question on eight six one safety profile. Nicholas BrandonChief Scientific Officer at Neumora Therapeutics00:29:00Yeah. Hi, Amy. Nick here. I think the, you the critical preclinical information we have is what we did in vivo in the rabbit. As you recall, it was unexpected feast in a rabbit which put us on clinical hold with that molecule. Nicholas BrandonChief Scientific Officer at Neumora Therapeutics00:29:13We've done a lot of work in the last twelve months with eight six one and eight nine eight in the rabbit where we've taken and we've dosed those compounds and achieved exposures, which surpassed where we were with two six six, and we've not seen any evidence of any convulsions. You know, we feel very confident we have have derisked both molecules as we move forward alongside that, you know, really encouraging, you know, overall pharmacological profile and other data we have. You know, we're really encouraged about moving both of them forward. Yeah. And as I mentioned earlier, really excited about having eight sixty one back in phase one clinical development. Operator00:29:57J. P. Morgan. Please go ahead. Analyst00:30:02Hi, team. This is Mariam on for Tess. Thank you for taking our question. What synergies do you see between your existing neuro focused pipeline and obesity? And along these lines, how did you come about deciding that this is the right next indication for Nomura? Analyst00:30:15And can you help us reconcile what your cash runway does and does not include in terms of R and D initiatives? Thank you. Joshua PintoPresident at Neumora Therapeutics00:30:23Great. This is Josh, and I'll take the question. I think as I mentioned previously, we were looking at indications to take 02/15 into, we are really committed, as I highlighted before, to following the science and the growing body of evidence highlighting that the drugs that are being developed and brought forward to treat obesity really are working through central mechanisms. We feel like obesity is an indication that fits squarely within our mandate of bringing novel mechanisms and novel approaches forward to patients suffering from a range of large population health disorders that are driven through a central mechanism. And so we really feel like NMRA215 into obesity is an opportunity for us to develop a new therapeutic that we believe could be best in class for that area. Joshua PintoPresident at Neumora Therapeutics00:31:15So we think there are a lot of synergies in terms of the team's expertise in designing and developing molecules that are highly brain penetrant as really the critical step to unlock the potential of this class and target. In terms of cash runway and what's included, what I will highlight is we have a strong cash balance as we sit here today. Mike highlighted about $217,000,000 on the balance sheet as we ended the second quarter. This gives us runway into 2027. That fully funds all of our critical programs where we provided public guidance through the clinical stage gates. Joshua PintoPresident at Neumora Therapeutics00:31:55And so we think that with each of the four most advanced programs, we will be able to deliver meaningful clinical milestones for each of them within the current cash runway period. So we're really excited about what we have moving forward, and frankly, the opportunity we have to bring forward six potential clinical catalysts in patients over the next eighteen months. Operator00:32:18That ends our Q and A session, and we appreciate your participation. I will now turn the call back over to Paul Burns, Chief Executive Officer, for closing remarks. Please go ahead. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:32:31Thanks, operator, and thank you again to everyone for joining us this afternoon. So as you can see, this is an exciting time at Nomura with up to six distinct catalysts anticipated over the next eighteen months, each serving as a critical inflection point with the potential to create significant value across our portfolio. These include preclinical data with NMRA two fifteen in obesity and the initiation of clinical studies with this program, initial clinical data from NMRA eight sixty one in schizophrenia, the Phase Ib data in Alzheimer's disease agitation, and Phase III data from nabacoprant in the coastal program. We are well positioned to achieve all upcoming milestones, which reflect the strength of our pipeline and caliber of our execution. But most importantly, it reflects our commitment to the millions of people who are in need of better treatment options. Paul BernsCo-Founder, Executive Chairman & CEO at Neumora Therapeutics00:33:24We are working with urgency to bring forward the next generation of novel therapies and ultimately redefine drug development in neuroscience. So thank you again for your continued support, and that concludes our call this afternoon. Operator00:33:37Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.Read moreParticipantsExecutivesHelen RubinsteinVP-IR and Corporate CommunicationsPaul BernsCo-Founder, Executive Chairman & CEOJoshua PintoPresidentBill AuroraChief Operating & Development OfficerMichael MilliganCFONicholas BrandonChief Scientific OfficerAnalystsAnalystYatin SunejaSenior MD & Biotechnology Analyst at Guggenheim PartnersDouglas TsaoManaging Director at H.C. Wainwright & Co.Myles MinterResearch Analyst - Healthcare at William BlairAmi FadiaSenior Analyst at Needham & CompanyPowered by