Talphera, Inc. (TLPH) Q3 2026 Earnings Call Transcript

Operator: Welcome to the Talphera Third Quarter 2026 Financial Results Conference Call. This call is being webcast live via the Events page of the Investors section of Talphera's website at www.talphera.com. You may listen to a replay of this webcast by going to the Investors section of Talphera's website. I would now like to turn the call over to Raffi Asadorian, Talphera's Chief Financial Officer. Please go ahead.

Raffi Asadorian: Thank you for joining us on the call today. Today we announced our third quarter 2026 financial results and associated business updates in a press release. With me today are Vince Angotti, our Chief Executive Officer, and Dr. Shakil Aslam, Talphera's Chief Medical Officer. Before we begin, I want to remind listeners that during this call, we will make -- likely make forward-looking statements within the meaning of the federal securities laws. These forward-looking statements involve risks and uncertainties regarding the operations and future results of Talphera. Please refer to our press release in addition to the company's periodic, current, and annual reports filed with the Securities and Exchange Commission for a discussion of the risks associated with such forward-looking statements. These documents can also be found on our website within the Investors section. I'll now hand the call over to Vince.

Vincent Angotti: Thanks, Raffi. Good afternoon, and thank you to everyone joining our call today. I'll begin with an update on our NEPHRO CRRT registrational study evaluating Niyad, our investigational nafamostat-based regional anticoagulant for use in the extracorporeal circuit during continuous renal replacement therapy, or CRRT. This study is being conducted in U.S. hospital ICUs with nephrologists as principal investigators. We recently submitted a briefing document to the FDA requesting a Sprint Meeting to discuss our proposed approach to closure of the study by December 31, 2026. I'll explain the rationale for our request and then provide an update on Niyad's commercial opportunity. Over the past several quarters, we've made meaningful progress in advancing the NEPHRO study. Enrollment has now exceeded 75% of our planned target as we reported last quarter. In recent months, enrollment has been unexpectedly slow due to fewer qualifying patients. Other CRRT studies have recently faced similar enrollment challenges, reflecting the difficulties of conducting clinical trials involving critically ill patients in the intensive care unit. Importantly, as a result of these slower enrollment dynamics in the industry, there is precedent for CRRT studies closing enrollment early and subsequently obtaining regulatory approval. Given these dynamics, we've taken a proactive approach to pursue the most efficient path forward for the NEPHRO study. To that end, we recently submitted a Sprint Meeting request to the FDA seeking its agreement to conclude enrollment by December 31, 2026, with the number of available patients enrolled at that time. This would be instead of completing the originally planned target of 70 patients, should we not reach that number by the end of the year. Notably, based on our current enrollment, the study is over 80% powered for the primary endpoint. This is a meaningful consideration in evaluating the appropriate sample size for the study. It provides additional scientific support for our proposal to conclude enrollment early, particularly given the challenges associated with enrolling critically ill patients in the ICU. Above all, our objective is to maintain the study integrity while avoiding unnecessary delays and advancing Niyad toward a potential regulatory submission. We have requested a Sprint Meeting, submitted the supporting briefing document, and presented our proposed approach to the FDA. Based on Niyad's breakthrough device designation, our historical interactions with the FDA, and the statutory timing, we would anticipate feedback will be provided by the end of this year. Topline data are expected within four to six weeks after enrollment is completed. Now turning to the commercial opportunity, we're increasingly encouraged by the potential market for Niyad in the United States. Following further evaluation of the CRRT market, we have increased our estimate of Niyad's peak annual U.S. sales for use during CRRT to now exceed $200 million. This is based on formal feedback from physicians via quantitative and qualitative research. The research included expected anticoagulant treatment utilization and the unique characteristics of nafamostat. It also addressed the potential role of nafamostat in overcoming the limitations of existing anticoagulation approaches. We believe Niyad's differentiated profile, together with the significant unmet need in CRRT anticoagulation, positions it to address a substantial market opportunity if approved. Furthermore, a recent study published in the New England Journal of Medicine compared CRRT with intermittent hemodialysis in critically ill patients with acute kidney injury. The study was stopped early as it found higher mortality among patients receiving intermittent hemodialysis. This is the first study of its kind to provide clinical outcomes evidence favoring CRRT over intermittent hemodialysis in this patient population in the hospital. We believe the findings could support further growth of the overall CRRT market. In addition, as we discussed last quarter, the updated draft guidelines from KDIGO, which stands for Kidney Disease Improving Global Outcomes, elevated nafamostat as an alternative anticoagulant for CRRT when citrate cannot be used. We believe this recognition highlights nafamostat's potential role in addressing the limitations of existing anticoagulation options. Together, these developments provide additional support for the commercial opportunity we see for Niyad, if approved. With that, I'll hand the call over to Raffi to update you on the financial results for the third quarter.

Raffi Asadorian: Thank you, Vince. Our cash balance at September 30, 2026 was $14.2 million. We believe this cash, combined with future conditional financing tranches, will provide us sufficient capital through at least a potential Niyad PMA approval expected in 2027. Two conditional financing tranches remain, totaling approximately $16 million of additional capital. If the conditions are met, we expect these to close around the time we release our top line data and announce completion of the study. Our operating expenses, or combined R&D and SG&A expenses, excluding non-cash stock-based compensation expense, for the third quarter of 2026 totaled $3.8 million, compared to $3.3 million for the third quarter of 2025. The $0.5 million increase in cash operating expenses in the third quarter of 2026 was primarily due to higher Niyad development expenses and certain SG&A expenses related to pre-launch commercial preparation activities. As a note, we plan to file a Form S-3 shelf registration statement to replace our existing Form S-3 that expires on November 30, 2026. I'll now turn the call back to Vince.

Vincent Angotti: Thank you, Raffi. We're enthusiastic about the potential of nafamostat and the progress made with the NEPHRO CRRT program. A recent submission requesting an FDA Sprint Meeting under the Breakthrough Devices Program reflects our proactive approach to determining the most appropriate regulatory path forward. Supported by the study's current statistical power and relevant regulatory precedent, we believe our proposal provides a sound basis for discussion with the agency. We value our ongoing collaboration with the FDA and look forward to the agency's feedback on our proposed approach. Our updated market research has increased our estimate of peak annual U.S. sales from nafamostat in CRRT to more than $200 million, reinforcing our confidence in Niyad's commercial potential. We look forward to discussing this opportunity in greater detail at our Investor and Analyst event planned for the first quarter of 2027. We appreciate the continued support of our investors and look forward to keeping you updated on our progress. And I'd like to open the line for any questions you may have. Operator?

Operator: [Operator Instructions] Your first question comes from Ed Arce with WestPark Capital.

Antonio Arce: I have a few questions as you might have gathered. First, just to start, just, I'm wondering why are there fewer qualifying patients? In particular, I'm wondering, about the prior trial protocol amendments that were designed to basically resolve that. And secondly, you mentioned precedence with other companies, specifically in the CRRT space. I'm wondering if you could expand on that. Which companies? When? And what were the circumstances?

Vincent Angotti: Sure, Ed. I'll turn it over to Shakil as he runs first line with our PIs on the study as it relates to just the past, it's really just the past two to three months where we've seen some lower enrollment. And then we'll answer the question after that on the precedent.

Shakil Aslam: Yes, thanks for your question. So there isn't really any single reason that we can point out that. Just compared with the same period in 2025, our number of patients consented and enrolled dropped by 85% to 90%. And we visited all the sites and tried to understand what's happening, but there was really no clear reason. I hate to call it just bad luck, you know, patients just happen to have some -- meet some exclusionary criteria and end up not qualifying or patients, you know, not able to get the consents from the patients. So there isn't really any clear reason that we can understand. It's just a combination of a number of things. You know, that -- we really feel that led to this overall significant drop in enrollment. So I wish I could give you a little bit clearer answer, but there isn't really any single reason. You're right. Our protocol amendments that we have done over time, they have facilitated enrollment and qualification of the patients for this study, and that still holds true. It's just that we had [ a loss ] to explain what exactly happened over the past two, three months.

Vincent Angotti: I think, Ed, what I'll add to that is that we've always said that the enrollment is erratic. You get heavy strong months, you get heavier light months, you get months in between. It just happened in this most recent stretch of call it really 2.5 to 3 months. The pace that we had before hit one of the low stretches. And with our goal to complete by the end of this year, and wanted to stay track on that goal, and having now exceeded the 75% powering to now be -- I'm sorry, 75% enrollment rate and exceeding over 80% powering, we want to stay in firm control of our timelines and that's why we approached the FDA. I think your second question, Ed, was on the precedent. Dr. Aslam, do you want to handle that?

Shakil Aslam: Sure. So there have been at least three studies attempted in this space, and those are all based on citrate, regional anticoagulant. There was one study started by Vantive spun off from Baxter, and that started in around 2016. The original goal was 160 patients. And across 12 to 14 sites in the U.S., after about 3 years, they were only able to get 34 patients, and they decided to terminate the study because of low enrollment. They went back to the FDA and renegotiated the study and they resumed the study with a smaller number of only 40 subjects. That started close to 2 years ago, I think in mid-2024, and the study is still ongoing, so we don't really know how the enrollment is going in that study. More importantly, there was a study conducted by Fresenius Medical also using their citrate system. And that study was expected to enroll 50 patients, and after about 2.5 years, they were able to get only 31 patients. And they reached back to the FDA and got their agreement to submit both their 510(k) as well as NDA because citrate is being regulated as a drug. So they were able to submit that data from those 31 subjects and they got approval of all of their products about 2 weeks ago, 19th of October around that time, so a little bit less than a month ago. So there are at least 3 studies using regional anticoagulant within this exact same patient population, essentially having a very, very tough time enrolling.

Antonio Arce: Okay. Just a clarification on the prior question and then a follow up if I may before jumping back in the queue. So just to clarify on the number of patients, 3 months ago you had reported 75% enrollment and today, 3 months later you're saying it's over 75%. So, am I to understand that over the last 3 months you've maybe enrolled 2 or 3 patients. And then just the final follow up question is regarding the feedback that you expect from the FDA by year end. What contingency plan do you have in place if the FDA says no, or if there's some back-and-forth negotiation that might take some degree of time?

Vincent Angotti: Yes. So I'll handle those. So, Ed, I think the first part of your question was on the number of patients. Yes, we have enrolled patients since our last update and our communication is we're over 75% enrolled now without giving a specific number. We're staying on the historical updates where we gave an update at 25%, 50%, 75% and our next final update would either be with the closure of the study, with the FDA agreement or at the 100% mark. But yes, we have enrolled patients since that time. As it relates to your question on the FDA, what if they say no? Well, we would continue on as is until we achieve the 70 patients. Now this is with our experienced sites and they do remain highly engaged. We'll evaluate that based on what the FDA comes back with, and we'll decide on the appropriate course based on that feedback. But our request to the FDA is that we terminate, I'm sorry, end or early closure of the enrollment at the close of the year. So between now and then, we'll continue to enroll. Just as a note, if we had the same enrollment statistics as the third quarter last year, we'd have already reached our enrollment target by -- or pretty close to it by now. So it's clearly an anomaly at this particular period of the year versus the same time last year. But again, we want to control our own fate with the timing and based off of the greater than 80% powering with our current enrollment, thought that this was the course to do. If they say no, we'll stay on course as is. And our internal forecasts just push it into the first quarter. Now you might ask, well look, if the additional forecast right now in your early forecast or based off your enrollment rate is only one additional quarter, why would you go with this approach? And it's because we have such strong power in the study already and we could wrap it up really tomorrow if we wanted to, but we're telling the FDA we'll enroll to the end of the year. And just the unpredictability of the CRRT enrollment for any of the studies in this particular marketplace, we'd rather have control of that with the power we've got and bring it to conclusion, and we feel confident in the filing of the data with that potential early enrollment closure.

Operator: The next question comes from James Molloy with Alliance Global Partners.

James Molloy: Maybe some more on Ed's question. The answer, what if the FDA says no? But how would you handicap the outcome at 80% here? And what -- how does that impact your ability to hit this endpoint here at 80%? Obviously, you feel it must be good enough, you'll be asking to stop it. And when exactly will you hear back from the FDA?

Vincent Angotti: Yes, so I'll turn the first portion of the question over to Shakil based off of our confidence in the statistical analysis and the statistical analysis plan even with just the patients we have enrolled today. Shakil?

Shakil Aslam: Right, yes, thanks. So the study was already overpowered with our originally planned 70 subjects. It had over 90% power to hit the primary endpoint. With the number of subjects that have gone through the trial, our power is keeping the assumptions unchanged. So we're using the same assumption that we used for the original sample size calculation, our power is still over 80%. Given the unique trial size and the fact that we're looking at a very objective numerical endpoint based off a lab test value, we are very confident that we have more than enough patients to hit the primary endpoint. Yes. And Vince, do you want to answer the second part or...

Vincent Angotti: Yes, I think I'll expand a little bit more on the powering. Beyond the primary, you clearly hear Shakil's confidence based off of execution of the study at the sites and the powering based on those assumptions. The secondary endpoints are interesting because 2 studies recently published within the last, call it 10 years or so. The same 2 studies that supported the elevation of nafamostat's recommendation in the KDIGO guidelines as an anticoagulant for CRRT had similar N's to the range that we're talking about. Well, our N is -- goal is 70. Choi et al. published a study in 2015 with an N of 55. And in that study, the mean filter lifespan was significantly longer in the nafamostat group than in the no anticoagulant group with a p-value of 0.03. I think importantly the filter survival rate in that particular study compared with the no anticoagulant group was 0.001. My point being is that in same range of N, there has been evidence of the filter life being affected as well. A second study was actually published a year before that by Lee et al. in 2014 with only 60 in the N. And in that study they found fewer clotting events and required use of fewer filters and again, highly statistically significant. So we've got two other studies in this area looking at similar outputs, at least on the secondaries. And while there's no guarantee, it just tells you the size of these studies are in the neighborhood of where we are. The second point, I think, to your question, James, could you reiterate the second part your question again please?

James Molloy: I think you covered it nicely. When exactly do you anticipate hearing back from the FDA?

Vincent Angotti: Oh that was it. Yes. So it'll be before. So look this is a sprint request. If you guys are familiar with sprint requests, they are a specialized time-bound interactive feedback mechanism and they're available to developers enrolled in Breakthrough Devices Program, i.e., Talphera, and they're a 45-day clock. And so we've already submitted, it would be before the end of the year, December.

Shakil Aslam: And Vince, just one other comment about the secondary that I would like to make very quickly is that the studies that you pointed out, Vince, they were not -- the dose of nafamostat was not titrated to an effect. So everybody just got some weight-based dose and then they looked at the filter life and whatever happened to it. Whereas our study is very unique that we are actually targeting to a therapeutic window where we think the blood is optimally thinned. So therefore, that's what gives us a lot of confidence as well that it's a very high likelihood that we will hit those secondary endpoints as well.

James Molloy: Maybe a quick follow up question for Shakil. I know that when you came in, you made some nice, some excellent changes to get the things going. And it looks like a bit of a stumbling block is coming here. What have you found most, sort of, surprising as you've come in on getting this trial, which historically had its challenges getting fulfilled? What have you found most surprising that seems to be the challenge to getting this trial done?

Shakil Aslam: Right. I think the biggest challenge really is the unpredictability. So some of the earlier challenges we had were with the protocol and some of the sites didn't have the appropriate patient population and we fixed those and that's what led to kind of pick up in enrollment. It really is unpredictability in these studies. These patients are extremely sick. Because they are so sick, protocols tend to be overly cautious and conservative. And then every site has -- as is in most clinical trials, different sites have different performance. Some sites are high performing, some sites are low performing, all you need is a couple of high performing sites, couple of people change, or a couple of people go on vacation, or something else happens along those lines. It really has been so hard for us to predict how the enrollment would go. Looking at our performance data up to 2, 3 months ago, we were very, very happy that we are on target and just out of nowhere, we saw this very, very slowdown over the past couple of months and threw everything off. And that I think is the biggest challenge. These patient population is just very, very unpredictable.

James Molloy: Understood. Have you noticed any change in enthusiasm from the doctors?

Shakil Aslam: No, as a matter of fact, actually we see people even more enthusiastic and we hold monthly PI calls, we invite all the PI's, investigators and their teams. And there's a lot of energy and a lot of desire to actually help us finish this study because they understand that there's a need and they want to have access to this. And we are so close that -- that's always a question. Do we see any fatigue in these sites? No. So no, we do not see any fatigue. People are still trying to enroll patients and they're very excited to get it over the finish line so they can have this product for their use.

Vincent Angotti: Yes, Jim, it's a unique environment with this particular study product disease state. I say that on their enthusiasm because, being under the device designation right now in order to break through, it's only a 6-month review. So the sooner we can get the PMA filed, the sooner they get it in their hands, and they're not going to be waiting like you do in many studies for maybe 6 months, 1 year to see the data. We're going to have the data 4 to 6 weeks post-enrollment closure, and then we're going to file the PMA as quickly as we can. And there's a shot they could have. I mean, there's a shot that they could have it in their hands by the end of next year, actually using it on their patients. And to them, that's something tangible. And they actually comment on that to us. So fingers crossed.

James Molloy: Outstanding. It would be great to be ahead of schedule. Now, I know you guys are trying your best, working the hardest.

Vincent Angotti: Thanks, Jim.

Operator: The next question comes from Brandon Folkes with H.C. Wainwright.

Brandon Folkes: Maybe just 2 for me. Do you unblind the results before or during the Sprint request? And if so, do you take a statistical penalty? And then secondly, is the feedback from the agency here as simple as yes, submit on those numbers or do not submit on that number? Is there any other scenario or feedback in between those 2 scenarios? And what goes into the FDA making a decision here whether it's appropriate to submit with the patients you have?

Vincent Angotti: Yes. I'm going to turn that over to Shakil. So the blinding, the simplicity of the answer and kind of what goes into the briefing book, et cetera.

Shakil Aslam: Right. So no, we are not unblinding the study and it will remain blinded and our submission to the FDA is based on blinded data. But again, we shared with them the sample size calculation, what the power is at each sample size, original, what we agreed upon and then the number of patients we already have enrolled in the study and recognizing that between now and the end of the year, we may have a few more patients to that list. So it lays out the statistical power for a different number of patients. In terms of briefing document, that's -- part of it is providing them with the rationale that we -- based on our same assumptions, our study that currently is already -- has over 80% power to meet the primary endpoint. So therefore, there is no risk to the study. And also the remaining subjects that we are short also provide them statistical analysis that enrollment of those subjects will not change what the power of the study at this point. So that's also the other thing that regulators will also want to know that if you're shortening a study, what is the risk if you had completed the study would your primary endpoint basically not remain significant. So that's part of our statistical package, little package that we gave with the briefing document. And then all the safety, I think their number -- again, there was no reason for us to power the study over 90%. And this was their feedback with us that they wanted to see more -- as much safety data as possible. So there's a rationale that this is not a new intervention. It's been used in other countries for 40 years, and there is actually earlier this year in 2026, there was a publication on nafamostat safety from over 20 years, 2004 until 2024 from Japan. And it basically outlines all the safety of the compound, and there is nothing -- no surprises there. So this is something that's already been well characterized in terms of safety and efficacy. So just enrolling a few more patients is not going to uncover new thing that we have not seen in the literature and all these large safety databases over the past 40 years now. So that's the second part of the argument. And the third part of the argument really is that given this KDIGO recognition that nafamostat is actually a viable option as an anticoagulant in CRRT and the huge unmet need and the difficulty that everybody experiences conducting clinical trials in this space that it just doesn't -- it's not warranted to delay this study any further. We have enough power to show an efficacy. We have enough data to show you safety and the patients need it, and there is legitimate unmet medical need that will be met with nafamostat. So that's what goes in the briefing document. In terms of what response FDA might give, I can imagine it's anybody's guess. It could be a straight no. In that case, as Vince said, we'll continue to -- we're already continuing to enroll, and we will go to our original target. Best outcome would be they say, okay, well, you made your point, you can submit PMA. And then there is a whole bunch of 'in between'. And that could require some additional data as a post-marketing commitment or there are some pathways as well where you can file for PMA. But at the same time, you keep the study open and get a few more patients just to satisfy their needs. So those, I think, are the 3 main scenarios that I can foresee. Brandon, does that answer your question?

Brandon Folkes: It does. Thank you very much.

Vincent Angotti: I think the important one, just for clarification and emphasis, we said kind of anywhere in between was one where you have the opportunity to file the PMA to keep the IDE open and maybe collect some additional data that you supplement the PMA with later.

Operator: The next question comes from Naz Rahman with Maxim Group.

Nazibur Rahman: I just have 2 questions I'll ask upfront. My first one is on the filing of final PMA filing, how many patients do you need for the safety database? And can you also include the safety data generated from overseas studies? And two, on your $200 million sales estimate, considering how difficult it has been to enroll patients in this study, what kind of gives you confidence that that's nafamostat's peak sales potential and it's not a lot lower just due to difficulty in enrolling patients or enrollment criteria, et cetera?

Vincent Angotti: Yes. Thanks, Naz. For the filing of the PMA and the safety database, we'll have Shakil answer that.

Shakil Aslam: Yes, sure. Yes. So we have shared the safety data with our previous meeting with the FDA, especially when we reduced the size from 166 down to 70 patients. We had shared the safety data from Japan. And yes, so the safety data is from ex U.S. use is -- will be submitted to the FDA. And again, I think the point that we were discussing earlier that when you have over clinical real-world experience over 40 years and well-characterized molecule and that data exists in public domain and so widely published, our comment to the FDA has always been that this is not a safety study. This is not the population where you would do a safety study. These patients are very sick. They have very high background adverse event rate, a very high mortality, over 50%, 60% mortality. So getting 20 patients, 30 patients is not going to uncover a safety signal that somehow has been missed for decades. So therefore, there isn't really any fixed number of subjects needed for safety. First they thought 166 was the patient that they wanted to see. And then when we talked to them, they agreed that, okay, maybe we don't need that and the 70 would be okay. I think it's -- there isn't any fixed number. I think as long as we don't go to them with far fewer patients, I think they'll be more than happy to accept it, especially when supplemented by ex U.S. experience.

Vincent Angotti: And I think, Naz, the second question was on the $200 million sales estimate, the feedback that comes from that formal market research, market growth rates, the positioning of nafamostat by the participants in the research on their use of it and their protocols moving forward. How does that align with a challenge in enrollment? And I think the key there is that it doesn't. And it doesn't because clinical trial environment really can't be translated into the real world due to the qualifying protocols, the consents required, et cetera. I think importantly, if you refer back to a call we had, I think it was earlier this year with 2 of our PIs, one from MUSC and the PI from University of New Mexico, they made that same point on the same question that the clinical trials in this particular area are just so difficult. They don't at all resemble real-world use. And I think -- interesting evidence of that is just the market as it stands today and the use of citrate. So currently, citrate has a greater than 20% market share as an off-label anticoagulant for CRRT. Yet, as Dr. Aslam communicated in this call, 3 citrate studies that have been unable to achieve their enrollment N's, at least to date on one of them and 2 that were early closures, one in particular terminated. So there doesn't seem to be a real-world translation or a clinical trial translation of enrollment into real market penetration.

Shakil Aslam: Right. And that's a great point, Vince. So yes, citrate used according to our own surveys is somewhere between -- published literature is somewhere between 25% to 30%. And despite that, these huge sites, which are primarily citrate user sites, they could not enroll more than 35 patients. So it's just the correlation between difficulty in enrolling these patients and the market opportunity, that doesn't seem to be a strong correlation.

Operator: There are no further questions at this time. I will now turn the call back to Vincent Angotti for closing remarks. Please go ahead.

Vincent Angotti: Well, again, thank you for your interest in Talphera. We look forward to updating you on our progress. We're working hard to stay on the timelines as best as we can in everyone's best interest and manage our cash and resources moving forward. And again, above all, keeping the integrity of the study and wrapping it up as quickly as possible. Thank you for your attention to Talphera, and we look forward to updating you in the future. And that concludes our call.

Operator: Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.