Neumora Therapeutics Q1 2025 Earnings Call Transcript

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May 12, 2025

There are 12 speakers on the call.

Operator

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.

Operator

Please go ahead.

Speaker 1

Good afternoon, and thank you for joining Numora Therapeutics first 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 from Nomura are Chief Executive Officer, Paul Burns President, Josh Pinto Chief Operating and Development Officer, Bill Arora 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.

Speaker 1

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.

Speaker 2

Thanks, Helen. Good afternoon, everyone, and thank you for joining us. At Nomura, we believe the greatest medical challenge of our generation is the global brain disease crisis. This affects upwards of one point five 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.

Speaker 2

When we founded Nomura, 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 Nomura to review our business and pipeline updates.

Speaker 2

Josh.

Speaker 3

Thanks, Paul. We are focused on clinical execution as we are advancing multiple programs towards key milestones over the next twelve months. We are on track to deliver top line data for NMRA five eleven, our vasopressin 1a receptor antagonist in Alzheimer's disease agitation around the end of the year. We are also progressing the Avacoprant in the phase three COASTal program in MDD, where we have implemented important changes for the ongoing studies and plan to report top line data from COSTAL-three in the first quarter of twenty twenty six and COSTAL-two in the second quarter of twenty twenty six. 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.

Speaker 3

Additionally, we announced this morning that we entered into a $125,000,000 debt facility with K2 Health Ventures with up to $40,000,000 available for draw this year. K2 Health Ventures 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 tenet 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.

Speaker 3

With this update, we now expect our cash, cash equivalents and marketable securities together with the $20,000,000 funded at close under the K-two 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 02/1940. 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.

Speaker 3

With that overview, I will now turn the call over to Bill to provide additional details on our clinical programs. Bill?

Speaker 4

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 nivacoprant, we are confident in the potential for nivacoprant 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 and J Phase II study of eticaprant, and importantly, our own Phase II study of Nevakoprant, which was recently published in the Journal of Clinical Psychopharmacology.

Speaker 4

This publication highlights that Nevakoprant demonstrated statistically significant and clinically meaningful reductions in symptoms of depression and andhedonia in participants with moderate to severe MDD. So when trying to understand how Coastal-one 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 Postal 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 Coastal 2 And 3 to help ensure that appropriate patients are enrolled.

Speaker 4

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 SAFR 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 COSTAL-two and three studies.

Speaker 4

This is an additive step to the clinical trial subject database we used in COSTAL-one, 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 COASTal II and COASTal III 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 III studies but ultimately succeeded in multiple studies and become important treatments.

Speaker 4

We designed the COASTal 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 COASTal III in the first quarter of twenty twenty six and COSTAL-two in the second quarter of twenty twenty six. 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.

Speaker 4

We look forward to sharing more on the pharmacology of our M4 programs when they enter the clinic in mid-twenty twenty five. In phase 1b is our vasopressin 1a receptor antagonist, NMRA511, 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 five eleven reduced measures of anxiety, agitation, aggression, and was very well tolerated in a Phase I SADMAD 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 five eleven in AD agitation, an area of significant unmet need with only one approved agent that carries a black box warning.

Speaker 4

We look forward to delivering top line data from Phase Ib 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 Nomura, 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.

Speaker 4

Mike?

Speaker 5

Thanks, Bill, and good afternoon, everyone. Our financial results for the first quarter of twenty twenty five 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 $68,000,000 compared to $53,700,000 for the same period in 2024. And we ended the quarter with $249,400,000 in cash, cash equivalents and marketable securities as of 03/31/2025.

Speaker 5

As Josh noted, we are focused on disciplined capital allocation and expect our cash on hand and the $20,000,000 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 and A with the operator. Helen?

Speaker 1

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 and A. Operator?

Operator

Our first question comes from Douglas Zhao with H. C. Wainwright.

Speaker 6

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

Speaker 4

Thanks, Doug. This is Bill. Appreciate your question. We've already seen benefits from steps that we've taken with both SAFR 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.

Speaker 4

So we do have confidence that the steps we're taking are helping to get appropriate patients randomized to indicate to indicate three.

Speaker 6

And I guess, Bill, to follow-up, 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 the rate of that is occurring at a rate consistent with what you were expecting.

Speaker 4

Yes, Doug, 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.

Speaker 6

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? Thank you.

Speaker 3

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 were looking to achieve in this financing was extending our cash runway into 2027. And so with the 20,000,000 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.

Speaker 3

In terms of the milestones, you can think about progression of Nevakaprant through some of the clinical stages as well as some regulatory stages as ways to ungate additional capital. But as we noted in the press release beyond the first twenty million that was funded at close, there will be another $20,000,000 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.

Speaker 6

And Josh, just to confirm though, only need the $20,000,000 to get you into 2027?

Speaker 3

Correct. Our existing cash balance sheet as of the March, plus the 20,000,000 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.

Speaker 6

Okay, great. Thank you so much.

Operator

Our next question comes from Jan Suneja with Guggenheim.

Speaker 7

Hey, guys. Thank you for taking my question. A couple of questions on coastal 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 COSTOL one, there was a lot of patient that had never taken antidepressant therapy in the past.

Speaker 7

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, you know, the other question is also on the K2 and three. Are there any possibility of some form of an interim analysis in the study? Thank you.

Speaker 4

Hi, Haetan, this is Bill. Thanks for your question. With respect to how we are ensuring we've got the proper patients being included in K2 and K3 after the pause, the steps that we've taken include having safer clinical team involved in providing the assessment for patients, taking a look at their history, both of depression treatment. Our own clinical team is partnering closely with the MGH SAFR 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 K-one as part of that.

Speaker 4

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 Q2 of twenty twenty six.

Operator

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

Speaker 8

Hi, everyone. Thank you for taking my question. This is Nevan on for Brian. Just to, you know, kind of high level, guess, what are kind of your latest views on how to reconcile the Korin mechanism based on Phase II data that you've shown, as well as JHAs? But then also with respect to the COSTAL-one study readout and J and J's decision to discontinue Atikaprant or pivot that into different indications.

Speaker 8

And then I have a follow-up after as well.

Speaker 4

Sure, Evan, this is Bill. Let me start here. We were surprised by J and J's decision to terminate their program given their January of twenty twenty five communication about submitting an NDA later this year. Looking forward to the presentation of their full data later this month. That being said, there are several important differences between the Avacoprant and Atacoprant, as well as the development strategies that are employed with each of the agents.

Speaker 4

First off, from a pharmacology point of view, the Avacoprant is significantly more selective for cap opioid receptors over mu opioid receptors than eticaprant is. Secondly, the study design for each of the programs and molecules were different. We believe the coastal 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 Atacoprant program read throughs.

Speaker 4

There are limitations due to the pharmacology and study design that limit that read through. We remain confident in abacoprant and still believe post hole one results may have been an anomalous finding. So we're excited about K2, K3 progressing and the timing for those reading out.

Speaker 8

Great, thanks so much. And then, I also saw in the 10 Q that was released that you had triggered the second tranche of funding from PVT for selection of an LRP3 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?

Speaker 3

Navin, 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.

Speaker 3

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 MLRP3 program. So looking forward to having more specific updates on that program as we move through the next few quarters and into early twenty twenty six.

Speaker 8

Great, thank you so much.

Operator

Our next question comes from Greg Suvanovich with Mizuho Securities.

Speaker 9

Hey, good afternoon. Thanks for taking my questions. I appreciate the updates that you provided. Two questions each on pipeline candidates. Just with respect to five eleven 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 III data sets that exist for a competitor product AXS-five from Axsome Therapeutics?

Speaker 9

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, enmiraclidine, in which, unfortunately the phase twothree data weren't great, any color as to, the confidence that you have that you'll perhaps show a different set of outcomes? Thanks.

Speaker 4

Greg, this is Bill. Thanks for your question. Let me start out here with the five eleven 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.

Speaker 4

That portion has been completed. Part B of the Phase 1B is a multi center randomized double blind placebo controlled study where we're evaluating an MRI five eleven twenty milligrams twice a day in about eighty eight patients relative to placebo in agitation associated with Alzheimer's. The primary endpoint for the signal seeking study is to change from baseline to week eight on the CMAI or the Cohen Mansfield Agitation Inventory. And so we're looking at the total score change there and we're really looking at these data to help better understand which domains on the CMAI improve and help inform our thinking about the design for the next phase of study that would follow looking at these results. With respect, Greg, to the M4.

Speaker 4

Greg.

Speaker 3

Yeah, 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 twenty twenty five.

Speaker 9

Okay, thank you very much.

Operator

Our next question comes from John Boyle with William Blair.

Speaker 10

Hi, this is John on for Myles Nitzer. 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 coastal two or coastal three and also just what aspects of the blinded data are you looking at and considering when making that decision? Thanks.

Speaker 4

Sure. Hi, John, this is Bill. I'll start here and basically communicate that with Postal two and three, those studies were designed to end scheduled to randomize up to three thirty two patients into the protocol. We've built in flexibility that allows us to go twenty five percent higher than that three thirty two. With respect to Coastal one, you'll recall that we were just north of three eighty patients enrolled.

Speaker 4

So we did end up fifteen percent over enrolling relative to the March 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.

Operator

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

Speaker 11

Hi. This is Pooner on for Ami. Thank you for taking our question. I'm just curious, in COSTAL-one, how does the MADRS baseline scores compare with the severity that was seen in the Phase II 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?

Speaker 11

Thank you.

Speaker 4

Sure. So looking at K1 relative to phase two, in phase two, we utilized the HAM D17. And in that study, there were about one hundred patients that had moderate to severe MDD. In Coastal I, we're utilizing the MADRS and we are using a cutoff of twenty five 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.

Speaker 4

When we think about the mix of subjects in K2 and K3 relative to coastal one, 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.

Speaker 11

Got it. Thank you.

Operator

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

Speaker 2

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 Nomura 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.

Operator

This concludes today's conference call. Thank you for participating. You may now disconnect.

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Key Takeaways

  • Nomura secured a $125 million debt facility with K2 Health Ventures, drawing $20 million at close, extending its cash runway into 2027 to fund pipeline milestones.
  • Top-line data for NMRA-511, a vasopressin 1a receptor antagonist in Alzheimer’s disease agitation, are expected by year-end from a Phase 1b signal-seeking study.
  • The COASTAL Phase 3 program for Avacoprant in major depressive disorder has resumed enrollment with enhanced site selection, patient screening and independent diagnostic verification, targeting data readouts in Q1 and Q2 2026.
  • Nomura plans to advance a best-in-class M4 positive allosteric modulator into clinical trials by mid-2025, aiming for once-daily dosing and improved safety/tolerability in antipsychotic indications.
  • Published Phase II results for Nevacoprant showed statistically significant and clinically meaningful reductions in symptoms of moderate-to-severe MDD and anhedonia, supporting the kappa opioid receptor antagonist mechanism.
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Earnings Conference Call
Neumora Therapeutics Q1 2025
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