AcelRx Pharmaceuticals, Inc. Aktie

Thank you.

Welcome to the Telfero Second Quarter 2026 Financial Results Conference Call. This call is being broadcast live via the events page of the Investors Section of Telferra's website at www.telferra.com. listen to a replay of this webcast by going to the investor section of telpara's website would now like to turn a call over to Rafi Asfordian, El Perro's Chief Financial Officer.

Thank you for joining us on the call today. Today we announced our second quarter, 2026 financial results and associated business updates in a press release. With me today are Vince Angotti, our Chief Executive Officer, and Dr. Shaquille Aslam, Telferra's Chief Medical Officer. Before we begin, I want to remind listeners that during this call, we will 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 Telfera. Please refer to our press release in addition to the company's periodic, current, and annual reports filed with the SEC 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. Thanks, Rafi. Good afternoon, and thank you to everyone joining our call today. We remain on track to complete enrollment in the NEFRO CRRT study later this year. This registrational trial is designed to evaluate whether Nefamistat is a safe and effective anticoagulant for use during continuous renal replacement therapy, or CRRT. The study is being conducted in hospital ICUs with nephrologists leading as principal investigators. With all of our final clinical sites now activated, we have reached 75% enrollment in the NEFRO CRRT study. This progress allows us to increasingly turn our attention to the commercial aspects of the famostat.

We remain especially pleased with the high level of engagement from our principal investigators and study site personnel. Today, we'll share some details on these areas, along with some initial insights from our updated market research on the FAMISTAT and the CRRT space. On the commercial front, clinical guidelines are an important part of the treatment landscape and were encouraged by recent developments. Specifically, the KDGO 2026 Clinical Practice Guideline for Acute Kidney Injury and Acute Kidney Disease is current. pending final publication following the close of its public comment period in May. KDGO, which stands for Kidney Disease Improving Global Outcomes, is the global nonprofit organization that develops and implements evidence-based clinical practice guidelines in kidney disease. Of note, the guideline now references Nifamistat as an acceptable regional anticoagulant. The only available regional anticoagulant being used in the U.S. today is Citrate, yet regional Citrate is not FDA approved for CRRT, and it's also complex to use and has other As a result, most U.S. sites simply don't incorporate it into their CRRT protocols.

This is the first time the FAMISTAT has been recommended in the CADIGO guidelines, supported by historical studies and publications, a positive change from prior published recommendations. KDGO guidelines are widely referenced by healthcare providers internationally. We believe this guideline will provide momentum for the commercialization of Nefamistat if approved. This new guidance should further highlight to healthcare professionals that Nafamistat is already standard medical practice in Japan and South Korea, where it is is the most widely used method of anticoagulation during CRRT. A 2018 national survey in Japan found that Nefamistat was used in about 80% of cases, making it the most common method of circuit anticoagulation. In South Korea, the famistat was approved for this use in 2005 and remains one of the most widely used anticoagulation methods today. In addition, our updated market research on the CRRT space points to a larger market opportunity for the FAMSTAT than initially estimated.

This research puts the estimated annual CRRT procedures in 2027, the projected timing of an ephemostat launch, at approximately 200,000 in the United States. That's a 21% increase from a prior estimate of 165,000, driven by new data from this research. We also expect a number of CRRT procedures to continue growing annually. We believe the Famistat, if approved, can address an unmet need in the market given the disadvantages of systemic heparin and regional citrate. Addressing that unmet need provides the famostat with an opportunity to gain a meaningful share of the CRRT anticoagulant market. These market insights are consistent with what we're hearing directly from principal investigators and other physicians about the currently available CRRT anticoagulants. We'll share the complete findings later this year at another investor and analyst event as we get closer to completing enrollment.

Now I'll turn the call over to Dr. Aslam, our Chief Medical Officer, for some comments on the study. Thank you. Shaquille?.

Yes, thanks Vince and good afternoon everyone. I am very pleased with the progress we are seeing in the nephro CRRT study. as we move toward completing enrollment later this year. We have completed the realignment of sites to match our target profile. Now all sites have nephrologists as the principal investigators and are recruiting patients primarily from the medical ICUs. Finalizing our study sites coupled with protocol modifications granted by the FDA has us on track to complete enrollment later this year. As a reminder, nephroCRRT is a placebo-controlled study in which administration, titration, and monitoring of anticoagulation are identical in both treatment arms. With 75% of patients enrolled, our investigators have consistently reported that these procedures are straightforward to perform.

Investigators continue to express their excitement over having Nefamostat available for their use, if approved. and its inclusion in the public review draft of 2026 KDGO guideline as a regional anticoagulant alternative to citrate. The International Expert Panel's inclusion of nifamistat reflects decades of clinical experience and accumulated published evidence on the safety and efficacy of nifamistat as a regional anticoagulant during CRRT. and we look forward to sharing the results with you. With that, I'll hand the call over to Ravi to update you on the financial results for the second quarter.

Thanks, Shaquille. Our cash balance at June 30, 2026 was $17.1 million. We believe this cash, combined with future conditional financing tranches, will provide us sufficient capital through at least a potential NIAID 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 the completion of the study. Our cash operating expenses, or combined R&D and SG&A expenses, for the second quarter of 2026 totaled $3.9 million compared to $3.7 million for the second quarter of 2025. excluding non-cash stock-based compensation expense, these amounts were $3.7 million for the second quarter of 2026 compared to $3.5 million for the second quarter of 2025. The $0.2 million increase in cash operating expenses in the second quarter of 2026 is primarily due to higher NIAID development expenses reflecting increased enrollment and certain SG&A expenses relating to initial market research activities. I'll now hand the call over to Vince.

Thank you, Rafi. And thank you for joining our second quarter earnings call. With enrollment progressing well, we remain on track to complete enrollment in the NEPHRO Registrational Study later this year and to report top-line data soon thereafter. Our focus remains on bringing the Phamistat to the market as a new regional anticoagulant for CRRT, if approved. and I'd like to open the line up for any questions you might have. Operator?.

Ladies and gentlemen, we will now begin the question and answer session. If you have a question, please press the star followed by the one in the touchdown sound. Should you wish to cancel your request, please press the star followed by the two. using a speakerphone, please flip the answer before pressing any keys. Once again, that is star 1. Could you wish to ask a question? And your first question is from James Malloy from AGP Global Partners. Your line is now open.

Hey guys, thanks for taking our questions. It's Matt on for Jim today. So as you guys are gearing up toward potential commercial launch here, When would we start to see maybe some strategic hires? And could you take us through a little bit of what the strategy might look like for a rollout, like centers of excellence that you guys may target, high enrolling sites that might want to come right on board, anything like that?.

color would be helpful. Thanks. Sure. Thanks, Matt. Appreciate it. I think a couple of things that are important. I want to reiterate the fact that we do have a strategic potential with CoreMedix who has a right of first negotiation for 60 days post data readout. And as a reminder, the CEO of CoreMedix, Joe Tedisco, he is on our website. board and obviously knows everything going on with the company. So that's one consideration. With that as a backdrop, we are preparing for launch on our own, as well as any other strategic considerations that might happen. And more specific to the launch, we'll likely start the hiring once the PMA is submitted. We plan that for early next year.

First quarter is our goal. And with that PMA submission, we would likely start to hire and launch our pre-launch planning in our medical education. So it won't be significant number of hires, just right now as a preliminary plan, just a couple of hires really about education on the FAMAS status background, the KDGO guidelines, et cetera. As a strategy for rollout in general, as you mentioned, if you recall, this market is highly concentrated. At least that's what the data suggests to date, and we'll be doing some additional targeting and segmentation work moving forward. But those 200,000 procedures that we mentioned in today's call based off of the most recent data we have and will validate moving further, about 70 institutions in the country, as far as we can tell, represent over 50% of those procedures. So from a rollout standpoint, we believe it will be highly targeted and concentrated and likely, at least today, not your traditional CISO. sales representative rollout. It'd be more account managers and educators and trainers. and a lot of peer-to-peer education moving forward.

So again, we believe it will be highly concentrated. I think a big focus for us will be on the pre-launch activities in medical education. And that'll coincide once the PMA submitted next year. And Matt, just to correct you, just to...

be clear on the PMA filing, not first quarter, first half is what it's supposed to be. First half, yes. Yes. Got you. All right. Thanks, guys. Thanks for the callers. And thanks for taking our questions today.

Of course. Thank you and your next question is from Ed Arcee from West Park Capital. Your line is now open.

Hi guys, thanks for taking my questions and congrats on the continued progress with the trial. A couple of questions for me. I just wanted to ask as we are approaching full enrollment here. I wanted to ask if you could run through again, just to be clear on the timeline enrollment to the data collection to the extent that there is much after that and then top line readout and the interim between that and what's necessary to submit your PMA, as you mentioned, in the first half of next year. And then separately from the timeline, I also wanted to ask if you have heard any information know, anything of note, anything particularly interesting in terms of feedback from these nephrologist PIs? You mentioned that the... The feeling has been that the procedure remains quite straightforward. You know, that's one aspect of this that's been repeated, I think, before.

But are there any other aspects of this as, you know, as all the sites now are up and running? Thanks.

Thanks, Ed, for the question. Raf, I'll refer to you for the timelines, and then we'll move to Shaquille for the nephrology feedback.

relative to our PIs? Yes, so to get the data, it's going to be about four weeks after we complete enrollment. around that time, four or five weeks, something like that to get to the top line data. We're working to get that on the sooner end of that, but that's probably around the timing. And then to get to a PMA filing, we may be requesting an interim meeting just to make sure everything is clear and everything, but we're probably... probably talking another couple months or so, probably another three months or so to get to that PMA filing, which will put us inside the, should put us inside that first half of now. next year. Does that answer your question? Yes. I guess related to that. Obviously, there's the PMA approval.

that's expected sometime around the middle of the year. But is there any... necessary activities between approval and full launch. any color on the timeline there as well. Yes, I would suggest. Okay.

I would suggest likely not, Ed. If you're asking between approval and launch, our goal would be to launch at approval. And part of that would be what I'll call market conditioning and sensitization to nifamistatin, its availability in the medical education. I don't suggest there be much of a delay between approval and a launch, at least how we're planning it today. I think the second portion of your question was feedback from the nephrology PIs. Shaquille, you want to comment on that? And I think one other aspect outside of what we said today, Shaquille, if you wouldn't mind mentioning how, at least based off of the early feedback as well, they're using other agents off in the second line. They might move the FAMISTAT the first line when and if it's approved.

Right. So, just remember that this is a blinded study, so there is no feedback that really pertains to one treatment arm versus the other. But overall, there have not been any surprises in the study. And their experience is exactly as they were expecting. Monitoring is extremely straightforward, simple, and very predictable. I think that's two important things in this patient population that your response should be consistent and predictable. And so far, that's the feedback we have gotten. We have had our first independent data safety monitoring meeting a couple of months ago, and we They did not identify any risks to the patient or any new findings.

So they essentially recommended to continue the study without any changes. So that's also very reassuring that everything is going as planned. I can tell you that people who have used citrate or clinicians who were looking into using citrate, many of them have informed us, gee, I should just wait for this to become available. Why invest all these resources? Because this is just going to be so much simpler and easier to use citrate. without any special training required, is essentially the use is just very, very similar to haprine, except that it's just more predictable and more consistent in terms of the way the anticoagulation goes in these patients. So I hope that answers your question. There have been no surprises and everybody remains. I talk to PIs almost on a weekly basis, and they all remain very excited.

And many of them have told me that they cannot wait to get their hands on it. So that's, I think, it's all very encouraging and quite as expected. Yes, that's great.

Thanks, Dr. Asim. I appreciate that. Uh, if I, if I may, I just want to ask one quick, uh, question about the investor event planned. Is there any further details at this point that you could share? Thanks.

No, not yet. I mean, it's going to be focused on the market, the market opportunity, and our commercial approach to the market. And we'll be providing more details on all the updated market research that we've been going through. that's going to be a little closer to the time where we're imminently completed with the study.

Just to give you a little more color, Ed, on Rob's comment, so we completed this in-depth market research with a data analysis provider on market sizing, growth rates. and stratification within it, meaning what are some of the most related to CRT. An example would be sepsis and then some others. Beyond that, what I'll call secondary market research, we have just recently completed primary market research with over 30 physicians on both the quant and qual subjects. format. It was fully chaperoned as opposed to more of a survey, really getting insightful. readouts from them on their feeling about today's current products, the target product profile of a new entrant, for instance, the FAMISTAT, how that might affect their use of products moving forward. Does it shift them from second-line therapies as rescue with coronary anticoagulants to potentially a proactive first-line therapy use with a new entrant like nifamistat based off that TPP, etc.? We've also done some recent research with some nurses to add some more qualitative feedback on just the burden that they have in the ICU. in the often one-to-one ratios of workload once a patient goes on CRRT, especially involved with citrate. So we're looking to finish the synthesis of all that data, package it properly, and that'll allow us to think about the proper mechanisms for launch moving forward, all of which we'll communicate with you Kate to you in that investor event. Fantastic. Thank you so much.

You're welcome. Thank you. And your next question is from Brad and folks from H.C. Wainwright. The line is now open.

Hi, thanks for taking my questions and congrats on all the progress. from me, I apologize if I've been answered, just hopping between a few calls here. But firstly, do you have any blinded insight into the titration that's happening in the nephroclinical trial? Even if this is just through way of drug supply, and if so, is there anything you can say whether that is tracking in line with expectations? Secondly, maybe just on the, I guess, Kadeo side, guidelines. I'm assuming this is based on ex-US usage and history. Is there anything in those draft guidance that is different to the way the FAMISTAT would be used in the US? I guess, are they recommending it in any different way than you envision it being used in the US? That's it for me. Thank you.

Shaquille, I think that's right down your alley. So any insights on, in particular, the titration or anything you can comment on, realizing it's a blinded study?.

Absolutely. So the titration has been, again, it's a blinded study. and with only limited information available. But overall, it's behaving actually quite well. exactly as we were expecting. So we had a maximum dose that we can give. There's a ceiling on that dose. So most of patients in this study never really get even anywhere close to that dose. So most are titrated below half of the dose of the maximally allowed dose. So that's very, very good news.

So it's exactly in the window where we wanted it. So that's very important that we only use the minimum amount of agent to nifamustat to get a therapeutic effect. So from that point of view, it's quite aligned with it. And second thing that investigators point out is that there's hardly any need to make multiple adjustments. So when patients feel it gets titrated, they remain at the same level. For some of these patients, the study had gone up to one week, and they did not need to go back up and down to retitrate to stay in the therapeutic range. So I think that's a huge, huge advantage when you compare it to haptrin, for example, where titration can be all over the place.

And it's actually so frustrating that many physicians actually just, you know, do not even titrate with haptrin when they use for CRRT.

Can you also remind them on the titration, how quickly it occurs as it relates to the protocol in the study?.

So roughly about 80% of the patients, they are within therapeutic range at the starting dose, that infusion rate that we have in our protocol. So within half an hour. almost 100% of the patients are within therapeutic range.

And that titration schedule if they're not happens in the first hour, correct?.

Right, right. So we titrate every 15 minutes and that's guided by bedside blood test of ACT. so every 15 minutes you can change the dose, go up or go down. As I said, 80-85% of the patients are already therapeutic at the starting dose and another 15% may need one up titration which is relatively small. As opposed to 50 mg which would be the highest dose, most patients.

are therapeutic around 20 to 25 milligram per hour. I just want to reiterate that this is a blinded study. These are observations, but we'll see the final results when obviously it's unblinded. Shaquille, can you comment on the second question Brandon had relative to the KDGO guidelines and if those recommendations are of any treatment patterns or different use than how we're seeing at XUS?.

Right, so the guidelines, the way they are phrased right now is that this is an alternative to citrate, so if there is contractual indication to use of citrate or if the citrate is not available, then this would be agents that could be used in that scenario. So in the U.S., Citrate use is around 25% of the patients or clinicians use citrate or the hospitals use citrate. So approximately 75% of the institutions do not have citrate available. And even within institutions where citrate is available, there are complexity to its use. So it's contraindicated in patients with liver disease, for example, and some other metabolic issues that can result from its use. And so there is a chunk of those patient institutions which do have access to citrate, they are not able to use citrate on every patient. Now, in Japan and South Korea, there's barely any use of citrate, so in those countries, this is the first-line agent.

So the way it's worded for the rest of the world right now, the KDU guideline is that you should use citrate first, but if it's not available or contraindicated, then you go to to Nefamostat as a use. But again, I think just because 75% of the U.S. facilities do not have access to Citroën, I think there's a pretty big chunk of market which will be a candidate for Nefamostat right now. out the gate and within even the 25 percent segment that does use it there's a lot of and a lot of labor-intense method that CITRUT uses, so there is a definite desire to move away from CITRUT if a better and easier to use agent becomes available.

All right, thank you very much. Sure. Thank you. And your next question is from Naz Rahman from Maxon Group. Here, Linus, I will open.

Hi, everyone. Congrats on the progress and thanks for taking my questions. Just a few. So, on the Cave-Deagle guidelines, could you comment on basically how long it takes or what are the next steps for this to become, I guess, confirmed or permanently approved guidelines? And following that, How quickly does this guideline get adopted by American institutions? And also, how closely is it followed by American institutions? And I guess not just in terms of anticoagulants for CRRT, but just in general.

We're going to move to Shaquille again. So on confirmation, you know, once the commentary is done, Shaquille? Yes. So I unfortunately do not know the exact timeframe. They closed their public review comments on the in May of this year. So my guess would be somewhere between three to six months, they will have the final draft. More like three months, I would say. And in terms of its adoption within U.S. institutions, it's quite variable.

So these guidelines are well known and they are recognized by most health care professionals today. But there is institutional variability within the U.S. like any other place. Some clinicians follow them very closely. Others would have their own kind of versions of guidelines. So from our point of view, what the inclusion of Nufamistat does is, number one, it validates that this is actually an acceptable, safe, and efficacious alternative to other therapies and which has been used in other countries and they are recommending obviously wider use of nifamistat. And secondly, many institutions and clinicians when they want to develop their own protocols for anti-coagulation CRRT in their own institutions, having an international body of experts, basically giving you rationale and recommendation, I think it really makes things much easier for them to adopt those recommendations. recommendations at their own institutions. So I think it just supports that, okay, well, this data has been reviewed by international group of panels and therefore, You know, you can go to the pharmacy and other stakeholders in the hospital and tell them that this is what you want to do.

And so from that point of view, I think it's also positive news for us.

Got it. Thank you. Sure. Thank you. There are no further questions at this time. Please proceed with the closing remarks.

Thank you, Operator. I just want to say thanks again to everyone on the call for your time with us today and your interest in Telferra. We're excited about the prospects moving forward and look forward to updating you on our progress.

Operator, that concludes our call. Thank you, ladies and gentlemen. The conference has now ended. Thank you all for joining. We now disconnect our lines.

This live transcript is auto-generated without human intervention or review.

[Call has ended.]

Welcome to the Talphera First 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.

Thank you, and thank you for joining us on the call today.

Today, we announced our first 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 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 SEC for a discussion of the risks associated with such forward-looking statements. These documents can also be found on the website within the Investors section.

I'll now hand the call over to Vince.

Thanks, Raffi. Good afternoon, and thank you to everyone joining our call today. It's been less than 2 months since our last update, and we're excited about the progress we've made this year in the NEPHRO study with our ongoing enrollment at current clinical study sites, activation of additional sites, achievement of the 50% enrollment milestone and consequently, the closure of an additional financing tranche.

With this continued progress, we believe we are well positioned to complete enrollment in the NEPHRO CRRT Study this year and file the PMA for a targeted potential approval of Niyad in 2027.

As mentioned, in early March, we announced the attainment of the 50% enrollment milestone in the NEPHRO study. With continued enrollment since that date, I'm pleased to report that we have well exceeded this level. The protocol changes we adopted last year, supported by bringing on new target profile clinical study sites have positioned us to achieve our goal of completing the study this year.

Building on our virtual investor and analyst event in March, we continue to be genuinely excited about completing the study and submitting our PMA for potential approval of Niyad.

The KOLs who participated in our March event highlighted the disadvantages with the currently available anticoagulants they're using and their belief that nafamostat will fill an unmet need in this market. These insights as well as our ongoing discussions with other nephrologists further reinforce our belief that Niyad could have an important role in anticoagulation for CRRT, if approved by the FDA.

9 of our 12 activated sites aligned with the new target site profile that we set last year. And with nephrologists as the lead, these sites have enrolled over 90% of the patients in the study. The quality of our study sites and the principal investigators and their teams is excellent. Dr. Aslam and I have been actively visiting many of the sites over the past several weeks, and all of them are highly engaged and have expressed their desire to have a new CRRT anticoagulant approved for use.

In addition, we look forward to welcoming a couple of additional institutions who have been enthusiastic to participate in the study, allowing us to maximize the 14 sites granted by the FDA. While these new sites will find us further along in enrollment, they've been drawn to the NEPHRO study by a deep appreciation for nafamostat's nearly 4 decades of use outside the U.S. and a strong interest in contributing to the U.S. research with their peers on a potentially new approved CRRT anticoagulant. Adding these final sites helps lay the groundwork for broader clinical awareness of nafamostat, which will serve us well, if the FDA approves it next year.

With that, I'll now hand the call over to Raffi to update you on the financial results for the first quarter.

Thank you, Vince. Our cash balance at March 31, 2026, was $21.1 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 next year.

During the quarter, we closed a $4.1 million financing tranche from the March 2025 private placement. There are 2 remaining conditional financing tranches totaling approximately $16 million of additional capital, which if the conditions are met, are expected to close around the date we release our top line data and announce completion of the study later this year.

Our cash operating expenses or combined R&D and SG&A expenses for the first quarter of 2026 totaled $3.9 million compared to $2.9 million for the first quarter of 2025. Excluding non-cash stock-based compensation expense, these amounts were $3.7 million for the first quarter of 2026 compared to $2.7 million for the first quarter of 2025. The increase in cash operating expenses in the first quarter of 2026 was primarily due to higher Niyad development expenses, reflecting increased enrollment and an increase in certain G&A expenses.

I'll now turn the call back over to Vince.

Thank you, Raffi. I'd now like to open the line for any questions you might have. Operator?

[Operator Instructions] Your first question comes from the line of James Molloy from Alliance Global Partners.

Matt on for Jim today. I was just wondering, if you guys are going to announce enrollment and any other milestone, maybe 75%? Or is the next update going to be full enrollment and then where to expect data quickly after?

Yes, Raffi, I'll start it, and then you can give them an idea of kind of the data communication we're planning. So we're not planning on any additional enrollment updates, in particular, realizing that the balance of the study isn't tied to any tranches until the closure of the study until the study is being completed.

With that said, I think Raffi can communicate to you what our expectation is upon study completion, or enrollment completion being last patient out and how we plan to communicate data thereafter.

Yes, sure. Yes, I think we'll announce last patient out. But the most important is the top line data, which should come within a month after that last patient out. Remember, it's a very quick study, 72 hours at the secondary endpoint, 24-hour primary endpoint. So it's a quick study, and we're cleansing the data along the way. So it will be a quick announcement for that top line data.

Got it. And is there any guidance you can give as to where you might be now or timing going forward, second half '26 still looking like the most likely for a top line read?

Yes, the second half of '26. The study goes in ebbs and flows. And so we're going to remain in our guidance for the second half of 2026, depending on the flow of those qualifying patients moving forward, but we're confident in being completed this year and announcing those results this year.

Your next question comes from the line of Ed Arce from West Capital.

Congrats on the continued progress. Just a couple of quick questions for me as we anxiously await full enrollment and top line data later this year. The first one is these 2 new sites that you expect to come online pretty soon here and basically cap out the full complement of sites. Would you be able to disclose which sites those are or perhaps give a qualitative description of the type of site and the type of patients that they see? And then the other question is, have you received any commentary from site administrators that are treating the patients, anyone that is conducting the study? Any commentary that you could share with us about how things are progressing?

Yes. I'll start with the new sites, Ed, and then I'll turn it over to Shakil to give a little more insight on those sites and the site administrators feedback. The 2 new sites, we don't expect to be significant contributors to the study, but they have significant CRRT populations. I say not to be significant contributors to the study because they're coming in so late to the study, but they wanted to be involved moving forward. These are study sites that match our new profile with nephrologists being the lead.

One of the sites in particular is one of the top 5 as far as our data suggests CRRT administering hospitals in the country. And we'll end up communicating those sites when we update federalgov.com on the study sites. So you'll be able to see who those sites are specifically in conjunction with all the balance of the sites we have to round out the 14.

As it relates to the site administrators and how it's going, I think Shakil is best positioned to communicate that while he and I have been making a rounds over the last several weeks. Remember, it's a blinded study, but I think what's important about this is the placebo and the product are treated similar in the protocol and the simplicity that comes with it. So Shakil?

Sure. Thanks, Ed. Absolutely. So when we talk to the PIs and the investigators and then as well as the nurses who are running this study and who are doing testing and looking at some of the test results, they are all very, very impressed with the ease of administering this intervention, as Vince said, both placebo as well as Niyad, they are administered exactly the same way.

And sure for first 24 hours, we have a little bit more intense monitoring of blood test to see how patients are responding to it. But after 24 hours, that intensity goes down. And they basically all are very, very impressed that how little variability they are seeing in the test results. So that's quite a pleasant surprise to them that they don't have to chase their tails trying to keep some -- the parameters within a target range. Once they have somebody stable at a parameter lab parameter, they basically stay at the same value. So overall, I think everybody is...

Shakil, can you comment on the reach or the conclusion of that stability to get to the proper dose in that first hour and why that protocol works for them and how we're basically controlling that primary endpoint on that first hour.

Right. So as you know, this study, we start at a starting dose, which is predefined. And 15 minutes later, we check the activated clotting time by a handheld device by the bedside, which we provide and we provide the cartridges as well. So it's pretty standardized test across all sites. And within 15 minutes, they check the value, and we have a certain range in which we want that value to be. So about 70% of the cases, you see the ACT going in that range right at the first starting dose.

Occasionally, a patient rest 25% may need 1 and a couple of them may have needed even more than 1 titration, 2 titrations, which is by the end of first hour, everybody is in the range in which they are expected to be. Obviously, I'm not going to disclose the different groups because there's one placebo in which we don't expect the value to change much. But as expected, the value doesn't change, in active treatment the value changes. But they remain within that range. So it's a very, very stable response. And which is not a total surprise to us because nafamostat metabolism is really not dependent on any specific organ. So there are other drugs which either depend on liver or kidneys or any other organ for metabolism. And every time the function of those organs deteriorates or changes, you can see different response in whatever parameter you're following.

Whereas the beauty about nafamostat, it really is not dependent on any organ. And most of these patients, they can have fluctuating organ function, which can affect other medications such as heparin being one example. Citrate is another example. If you have liver failure, citrate will not be metabolize as quickly. Nafamostat doesn't have those issues. So that's the reason why once you hit the target level, it essentially remains stable. Does that answer your question?

Shakil, just a little bit more color. So on the administrative side, can you comment to the people on the line, how many of the sites are typically using citrate as a primary intervention for anticoagulation in CRRT and/or heparin as a primary intervention for anticoagulation in CRRT?

Sure. So of the 12 sites that we have, we don't have any site that uses citrate as a standard of care. So there are 2 or 3 sites that will use citrate only if a patient continues to clot. And these sites do not use heparin at all. So the sites that are using citrate, they don't believe in heparin. So they, 2 or 3 sites that have access to citrate. They are not citrate-first users, only use citrate as a rescue as citrate is the only rescue they have.

We have 2 sites -- only 1 site that uses heparin as standard of care of all the sites that we have. Then we have 2 or 3 sites that use heparin as a rescue therapy. So they don't use either citrate or heparin when the CRRT started. But if they see clotting, they don't have access to citrate, so then they go back to rescue heparin. Majority of our sites right now, I would say, 10 out of 12 or 13 that we have, they don't really have any first-line anticoagulant that they use for every single patient. They are really using either heparin or citrate as a rescue. And we don't have any site that uses citrate for everybody.

And I think importantly, Ed, when they execute the protocol in the NEPHRO study and the titration schedule, they see the ease of use, whether it's placebo or controlled doesn't matter, placebo or active doesn't matter. It's just the ease of that titration schedule compared to what their historic challenges have been with heparin and citrate and that seems to be the additional feedback. Simplicity is the main comment.

Right. And the nurses, even we spoke visiting a site today and the nurses, they were like shocked, okay, we don't have to do anything else? No, that's it. That's all the monitoring that's required. Yes.

There are no further questions at this time. I will now turn the call over to Vince. Please continue.

Thank you, operator. And I'll just clarify my comment I said earlier about the site names, the additional 2 that will be coming on, that will be on clintrials.gov -- clinicaltrials.gov, excuse me, and our next update of those sites.

So again, thank you all for joining us on our first quarter earnings call. We're really very high on what's happening at the start of 2026 and the enrollment that's continuing to move forward. The NEPHRO study progress has been excellent. Our commitment enthusiasm to bring the potentially new regional anticoagulant for CRRT to the market next year is unwavering. So we appreciate your attendance today, and we're very excited about the future for the NEPHRO study as well as Talphera moving forward.

We'll provide you additional updates on our progress, and thank you for joining us on the call today. Operator, that concludes our call.

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

Good morning, everyone, and welcome to the Talphera Virtual Analyst and Investor event. [Operator Instructions]. As a reminder, this call is being recorded, and a replay will be made available on the Talphera website following the conclusion of the event. I'd now like to turn the call over to Vince Angotti, Chief Executive Officer at Talphera. Please go ahead.

Thank you, Tara. And good morning, everyone, and thank you for joining our event today. I'm excited to be joined by Dr. Shakil Aslam, Talphera's Chief Medical Officer; and 2 key experts in continuous renal replacement therapy who are also principal investigators in our NEPHRO CRRT registrational study. To their experience and expertise, we hope to provide you with a better understanding of CRRT, the anticoagulants currently being used during CRRT and how these experts see nafamostat potentially filling an unmet need for anticoagulation of the CRRT circuit.

Our agenda will specifically include, first, a very brief business update, so we can move quickly to our key expert discussion, followed by Q&A and closing remarks. Before we begin, I want to remind listeners that during this call, we'll 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 SEC 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.

Now for the business update. Earlier today, we announced our Q4 and full year financial results. The NEPHRO CRRT study is progressing nicely. And as announced a few weeks ago, we reached the 50% enrollment milestone. This achievement, along with the achievement of some other conditions triggered the closing of the third tranche of our March 2025 financing, generating gross proceeds to the company of $4.1 million.

In addition to the funds received back in October 2025, when 2 investors waived all their conditions and closed on the second and third tranches of this investment. As of December 31, we had cash and investments of $20.4 million, which, along with the remaining tranches, if closed, should provide runway through a potential FDA approval of Niyad next year.

We expect to complete enrollment of the NEPHRO CRRT study later this year and file the PMA within about 3 months after study completion. As a reminder, the primary endpoint of the study is measured at 24 hours. So a quick turnaround of data is expected once patients have been enrolled. I'd now like to move on to why we're all here today.

As a reminder, continuous renal replacement therapy or CRRT is a specific type of dialysis that runs for 24 hours on a slow flow and continues on average between 5 and 7 days while the patient is in the intensive care unit, the ICU. Because the blood clots when it comes in contact with an outside material, the filters used in CRRT machines frequently clog. Therefore, to make sure the patient is receiving continuous therapy that is not interrupted by clotting, international guidelines specify using an anticoagulant to make sure the filters remain functional for as long as possible.

As you'll hear today, each hospital currently has a different protocol to achieve the best uninterrupted therapy for the patient, sometimes not using an anticoagulant at all, because many physicians don't trust the current options being heparin or citrate. Other times, physicians select 1 of the 2 available options despite their limitations.

I'll now hand the call over to Dr. Aslam to introduce our key experts, so you can hear directly from them how each of their institutions manage CRRT for their patients and their broad experience with CRRT in currently available anticoagulants. Dr. Aslam?

Yes. Thanks, Vince. So good morning, and welcome to an exciting session with our 2 experts in acute kidney injury and continuous renal replacement therapies. My name is Shakil Aslam. I'm the Chief Medical Officer at Talphera. As a nephrologist, I have had special interest in acute kidney injury dialysis, continuous renal replacement therapy for over 30 years. First as a clinician and then as a device and drug developer in these areas.

It's my privilege to have doctors McMahon and Dr. Teixeira join us on this call. In addition to being key thought leaders in AKI and CRRT, Dr. McMahon and Teixeira are also principal investigators on our Niyad registrational trial. In fact, their sites are the highest enrolling sites for our study. So we are very excited to have them.

I would like to briefly introduce them. However, I would not be going through their entire list of accomplishments and contribution to this field for the sake of time. So first, Dr. McMahon. Dr. McMahon is an Associate Professor of Medicine at the Medical University of South Carolina in Charleston. Her key interests are in the areas of acute kidney injury and renal replacement therapies and intensive care setting. She has published over 50 papers in leading peer-reviewed journals and has written numerous expert opinions, review papers and book chapters.

She is Director of nephrology clinical trials at MSU (sic) [ MUSC ] and is involved in several ongoing studies in acute kidney injury and continuous kidney replacement therapy. Dr. McMahon is also the Director of CRRT program at (sic) [ MUSC ] and is responsible for managing prescription protocols for CRRT and dialysis in the intensive care unit. She has won multiple teaching awards at Johns Hopkins MUSC and University College, Dublin.

Dr. Teixeira is an associate professor in the Divisions of Nephrology and Pulmonary Critical Care and Sleep Medicine at the University of Mexico in Albuquerque. In addition to other clinical responsibilities, Dr. Teixeira serves as the director of acute dialysis and continuous renal replacement therapy programs at UNMH. As a critical care nephrologist, his research interest lie in acute kidney injury, CRRT and septic shock, among others.

He has enrolled over 300 critically ill or hospitalized patients into more than a dozen clinical trials. He has coauthored over 100 peer-reviewed publications, book chapters and conference abstracts. He's on the editorial board of 3 journals as a Director of the CRRT program and UNMH, Dr. Teixeira is responsible for overseeing the development of CRRT protocols and quality assurance programs.

So welcome to our call, Dr. McMahon and Teixeira. So nice to have you.

Thank you. Good morning.

Thank you. Thank you for having us.

Absolutely. So let's just start off with some basics. So as I'm sure you have the same experience, there are just so many different names, acronyms when it comes to acute kidney injury and the different modes of dialysis. Our audience, could you just break it down to -- Dr. McMahon, this question is for you. what exactly are the key differences between CRRT, which I recognize increasingly as referred to as CKRT, which continuous kidney replacement therapy, although they mean same thing. So we use the CRRT and CKRT interchangeably. And then you have regular intermittent hemodialysis, which most people are aware of. So what are the key technical difference between these 2 modalities?

Yes. So when we consider...

And Tara, if you have that slide, I think that will highlight.

So when I -- when you think of outpatient dialysis. These are chronically -- chronic dialysis patients. Yes, they have organ failure and are attending an outpatient facility in the community. These are usually relatively stable patients. Most of them are relatively healthy other than the organ failure, and they often walk into the unit and attend 3 days a week for their dialysis therapy, either Monday, Wednesday, Friday for 3 to 4 hours or a Tuesday, Thursday, Saturday.

And then when you compare that to the chronic renal replacement therapy, dialysis in the intensive care unit, most often, these are critically ill patients. Most of these patients will have more than one organ failure in the ICU, some of them are mechanically intubated and they're really sick, some of them are unstable. In other words, they're hemodynamically unstable and require medications to keep their blood pressure up.

So the big difference between the 2 modes of dialysis is, one, is it's a higher dose of dialysis for stable patients, but the CRRT dialysis is a more gentle form of continuous dialysis run 24/7 in the ICU at the bed side, okay? So it's a more gentle form, lower blood flow. And you can see the setup here in this picture where you can actually see the filter on this continuous renal replacement therapy set up, the machine on the left-hand side. And I don't think this picture reflects -- sometimes you go into a room, there's a lot more machinery like the mechanical ventilator.

And you can see at the bottom of the machine, you have these bags, these replacement fluids and often the citrate anticoagulation is contained within those bags and they require infusions of calcium to run, to maintain that filter life span. So the filter is really everything. It's really important. These patients get really good quality dialysis in the ICU. You do not want to interrupt their dialysis. It's really important for the patient.

Great. So to summarize, intermittent hemodialysis is done mostly outpatient though can be done inpatients as well. Patients are typically more stable, walk in to dialysis, very high speed, quick 3, 4 hours dialysis and they go home, whereas CRRT is patients with life-threatening disease, many of them on ventilators, multiple comorbidities, they are in medical ICUs, critically ill, multiple machineries and interventions. And the dialysis is very gentle and slow, but it has -- since it's not as quick, it has to be done over an extended period of time, 24 hours a day and can go up to 5, 7 days as long as the patient needs it. Thank you. That was very helpful.

And Dr. Teixeira, you work as a director of an outpatient unit as well as you're the Director of the ICU. Are you seeing any interesting epidemiological trends and the incident rates of end-stage kidney disease, which is what most of these patients get dialysis for as an outpatient versus acute kidney injury, which you see in ICU in a patient like that shown in this picture?

Yes, absolutely. So the chronic dialysis population in United States is kind of historically over the first 20 years of the century has gone up and up and that's been kind of a big topic in nephrology. But it's starting to level off. If anything, during the pandemic, all those -- these are somewhat more stable patients, they are vulnerable to things like infection like with our dialysis population locally, and I think this reflects national data, too, dropped somewhat.

So to some degree, the chronic dialysis population may be stabilizing. And in theory, with some of the treatments that we've developed to help sort of prevent progression of chronic kidney disease to end-stage kidney disease that will continue. I think that trend, that chronic dialysis may become a smaller part of our practice.

The opposite is true of the acute kidney injury. ICU populations in general are just growing across the United States. And there are some kidney specific things that can happen to land someone in ICU. But most of the time, this is a complication of some other severe illness, like septic shock, for example, being a very obvious one. And the incidence rates of septic shock and acute kidney injury and acute kidney injury severe enough to require dialysis often continuous renal replacement therapy has only continued to go up and up and up.

And so this is becoming a bigger problem, a more frequent problem. And over time, I think, is going to be dominating the practice of your average nephrologist, not to mention someone like myself who's kind of a dedicated critical care nephrologist. And so I think the patient population that this issue is relevant to is only going to continue to grow.

And Dr. Teixeira, as fewer patients are progressing to end-stage kidney disease and going on dialysis, that means that the proportion of patients who have chronic kidney disease, but not on dialysis that portion of patient is going to expand, I presume. And those patients are very high risk of acute kidney injury. And so is that what you're seeing as well that there's actually more patient to develop acute kidney injury?

Yes. And so to some degree, I mean, these things relate. That's absolutely fair. So the patients with chronic kidney disease that not yet requiring dialysis that population is not going anywhere, and they are more at risk of acute kidney injury. And to some degree, the proportion of patients with what we call end-stage kidney disease or chronic kidney failure, they're requiring maintenance continuous dialysis outside the hospital.

The portion of those patients that originally developed their kidney failure due to acute kidney injury that usually gets better, but sometimes it does not, especially in those with underlying chronic kidney disease. In other words, those who previously had a kidney disease and have a superimposed kidney injury, the proportion of those patients that account for the total chronic dialysis patient population, I'd say, is going up over time, slowly starting to compete with things like diabetes and hypertension that are thought to be the most common causes of end-stage kidney disease in the United States.

But yes, absolutely. So the patient population, just like the United States population is aging and developing more chronic kidney disease, the patients at risk of acute kidney injury are increasing, which I think is part of the reason why we're seeing more of it along with, to be fair, I think just a gradual -- I'm going to say gradual explosion, it seems like to be an explosion. Over the course of my 20 years since I was a med student messing around in ICUs long ago, the expansion of critical care in the United States, it's only going up and up and up.

The complexity of the patients that we're supporting, the amount of devices that we are using to keep people with impaired circulation, whether it's mechanical circulatory support and ECMO, extracorporeal membrane oxygenation. So these complex life support devices are being used more and more and not just an academic medical centers, spreading to sort of community hospitals and more and more to sort of somewhat less subspecialized centers, the complexity of, I think, the life support that we're offering across the United States is only increasing.

And as a result of that, acute kidney injury to some degree is kind of the collateral damage that can happen with some of these really high levels of life support. Patients, to be blunt, may not have survived 10, 15, 20 years ago are being supported by some of this more complex level of critical care that we can provide. But a lot of them along the way, unfortunately, are suffering some degree of kidney injury, which is often a consequence of this underlying severe illness.

So I presume that you're seeing similar trends in utilization of CRRT for management of these patients seem to be growing pretty rapidly?

Yes. Absolutely. Look, I think the use of CRRT is only going to continue to rise over time. We're seeing it locally and across the country.

But Dr. McMahon, tell us about the risk of clotting into totally different modalities of treatment. So you have very fast, high flow acute dialysis and obviously, filter and clot. And then you have slow dialysis for a long period of time, low flow and patients who probably are much more sick and inflamed. So how do you compare the risk of clotting between these?

Yes. It's a good question. The risk of clotting by far is a lot higher in the intensive care unit patient. I think we can say that for sure. These are a different cohort of patients. The majority of the time we're starting CRRT, for example, for septic shock, and that means patients are really inflamed, they have these inflammatory markers. A lot of those markers will stick and adhere to the filter, reducing the efficiency of the filter predisposing them to clotting. And it's not just with sepsis or septic shock.

We're a big liver center. Our liver patients have bilirubin, these other proteins floating flow around that can affect the filter. There's a lot of risk factors that exist in the ICU patient that makes them vulnerable to clotting in the ICU on CRRT. So preventing that clotting is paramount and delivering good dialysis is really important. We do use some anticoagulation, it's typically heparin, a very low-dose heparin in a small proportion of outpatient chronic dialysis patients for some patients, but we don't see that level of clotting in the outpatient compared to the ICU.

And Dr. Teixeira, I've seen you even on national holidays running off to the ICU and putting those fires out. So what happens? So in general, I think many people take a very simplistic view, well, okay, the filter clots, you pop the filter out and put a new filter in and keep going. So could you just walk us through what exactly are the implications when a filter clots, implications for you as a clinician, for staff that's taking care of those patients and the patient themselves. What happens? What is life like when you get a call in middle of the night, hey, gee, Dr. Teixeira, this filter has clotted off?

Yes. I mean there's implications kind of in many levels and affect sort of both the patients as well as the health care system, I would say. Very simply, if you are not on the machine, you're not getting the therapy that's sort of life-saving kidney replacement therapy, whatever you're trying to fix with the machine, whether it's a buildup of potassium in the blood, which can be directly life-threatening, acid buildup in the blood, excess salt and water that you're trying to remove to say, let's get someone off of mechanical ventilation because they have too much fluid in their body.

None of that happens when the machine is down, takes at least, and I say at least because sure if the nurse has absolutely nothing else to do in this patient on multiple forms of life support, they drop everything that they do. It maybe takes just an hour but takes at least an hour, like I think on a practical level, it's often an hour or 2, sometimes 3 before they get -- the nurse has the kind of bandwidth and time to sort of reconnect everything and get everything going again. And so that's valuable sort of time that the patient is not receiving the therapy.

And that ends up reducing the effective delivered dose, which is not the goal of this sort of life support modality that is indeed meant to be continuous. And then like I already alluded to, the nursing time is extremely valuable that we're sort of kind of cutting into here. And there's all sorts of cost as well with each of these hemofilter sets, as we call them, cost hundreds of dollars. Just thinking from an equipment perspective, that's obviously extremely sort of counterproductive for kind of efficient patient care.

And then occasionally, it's usually not, the nurses are able to often identify that the filter is about to go down before it completely clots off, and rinse back the blood as we say, to prevent as much blood loss that would typically occur with one of these filter sets. But occasionally, they don't. And the net result of that is they lose all the blood and that too being in that filter. And these filters are pretty slick, but they still have about 150 milliliters or perhaps a more kind of intuitive way to think about it, basically, about half unit of blood is in these circuits at any given time to allow this therapy that cleans the blood to be going on continuously.

And so it's not infrequent. It's a minority, but still a substantial number of times they're unable, the issue, the clotting or whatever issue that causes it to stop all of a sudden is sudden enough and catches the nurse by surprise that they actually lose half of unit blood, which is obviously the exact opposite of what you want to do for critically ill patient, many of which already have active bleeding or because of their sepsis or some other disease process they're already very anemic. And so the implications of that are definitely not helpful to the patient or to the health care system.

So briefly, what exactly are you doing to prevent the clotting? So what is your anticoagulation of choice right now to prevent this filter clottings?

For me, I can answer. So I've been at the University of Mexico now about 7 years. And when I came in, we didn't have a specific protocol about how to approach it. And we haven't really evolved beyond that. And in part, like I -- to some degree, I think the guidelines suggest that we should. But there is no hard data suggesting that these other options available improves outcomes and none of them have sort of -- none them are free of major issues or complications.

So in other words, heparin we can talk about a lot, in short, I'm not a huge fan of heparin. And so as a -- definitely never had the thought that becoming a heparin first center made sense. So we haven't done that. And then citrate can work well if I'm sitting at the bedside, managing it. I joke that I love citrate because it gives me job security because I'm perhaps the only nephrologist in the state who understands it well. It's a little bit perhaps, arrogant of me to say, but it's complicated. The reality is that it's complicated.

Citrate nominally has been recommended as first-line for CRRT in the United States for -- or worldwide, I should say, for over a decade, and it still accounts for only a fraction of practice as -- in other words, only less than 50% centers across the United States are citrate first because of the complexities and issues related to that. So we are nothing first center, which is like arguably not adhering to the guidelines just because the options available are basically -- neither of them are fully satisfactory.

Okay. And Dr. McMahon, what is your strategy for anticoagulation?

Yes. So we're the same. We -- if you clot more than once in 24 hours, you automatically start citrate anticoagulate. We have ACD-A 2.2% citrate in our institution. But like my last institution, they didn't have citrate because the Director of CRRT there just didn't want to take it on board. Because like mentioned before, it's the complexity and the burden. It's quite fascinating too, when you talk to your colleagues in the division, some of them still aren't 100% familiar with the protocols, and we've seen these events occurring.

Safety is an issue, especially as the Director of CRRT. Your job is to keep things safe for the patient while delivering good dialysis and modifying these protocols as we go. But -- so yes, we do use ACD-A and it is not -- it is a job security.

Right. Right. So life expectancy of these or useful life of these filters is about 72 hours. So when you are not using anticoagulation, what kind of life span do you get for these filters?

Yes. So if you actually look at the data, the data has been published on this, 1/3 of filters that start to go down in the first 12 hours. And then another 1/3 will last 12 to 24. Most institutions are, therefore, not getting 24 hours with their filters. Remember, these filters are expensive. Dialysis is expensive. The filter alone is -- a connection fee at our institution is about $2,300 plus the nursing fee. So not cheap and then the cost of anticoagulation, the cost at the connection, the cost of blood, should it go down, and then the implications, obviously, for -- but yes, so it's not cheap.

And Dr. Teixeira what kind of filter life do you get at UNM?

Yes, I just like pull up some of our most recent data. This is actually skewed by pediatrics, which is a little bit different situation and filter life tends to be better than ours. But our filter life tends to be -- our median is 13 hours. I'm just looking at some data. This is a few months ago. And we have some that extend a little bit longer. So our median is a little bit longer than that, but still less than 24 hours. And so that is suboptimal.

But again, I think part of the issue with that is that the options available to us to improve that are limited. And so we haven't sort of implemented any major changes based on that other than trying to remind people to like consider heparin or citrate upon a premature filter loss. But yes, our data locally match the sort of more global data that Dr. McMahon just said.

And heparin has been used forever and it's FDA approved. And -- but there is a lot of, I would say, disagreement on when to use it, if to use it at all, does it really offer a favorable benefit to the risk profile to the patients. So Dr. McMahon, what is -- you tend to looks like world heparin altogether. So what is that your beef against heparin?

Well, I used at my last institution for 7 years, and I can tell you, it just is not as efficacious as citrate, okay? So the data on it is about 26 hours with heparin. It's not significant -- like these filters are supposed to last 72 hours. And if you're getting 26 hours with heparin, it's just -- that's just not really good enough. More importantly, it's not regional. It doesn't stay in the circuit, you're affecting the systemic pinning of the blood and your bleeding risk goes up for heparin.

So if you've got someone in with a bad brain bleed, post-op, the surgeons don't want you to start it. And it's a huge problem. So it's lack of efficacy, it will reduce efficacy and then the risk of bleeding with it. And yes, it's cheaper, but that the cost doesn't come into it at that point. So yes, even though it is approved, we actually don't have a heparin protocol at our institution for that reason. And we actually did bring one in for research because it was a requirement for a protocol, but we don't use it. We don't use that at all.

And do you see any issues with -- at least I felt that titration with heparin was never a straightforward thing.

No, I think with regular patients too, right? We get super therapeutic, and you have to hold it and it's a mess.

Yes, Shakil, I can add to that, too. Just more globally, thinking of my practices as a intensivist, just use of heparin is no longer -- it is the only thing that's FDA approved for CRRT. I hope that changes soon for obvious reasons. It's no longer considered a first line for anything. It's no longer -- regular and fractionated heparin is no longer consider first line for acute PE, it's no longer for clotting in the lung, it's no longer considered first line for heart attacks. It's because in addition to the fact that, like Dr. McMahon just pointed out nicely, it doesn't really work that well, like the benefit you get in terms of prolonging the filter, it's pretty marginal.

You have the risk of bleeding that comes with it. But also, it has, to try to phrase this in a nonmedical term, it like both overshoots a lot in terms of its blood thinning effect. And then sometimes it don't work, it doesn't adequately thin the blood when it's supposed to. The technical term has got unpredictable pharmokinetic. So basically, like, it's hard to get it on and off, and then some patients, it's hard to get -- prevent it from overshooting.

It's just a pain in the a**. It's like a drug that I think even outside, if you set aside CRRT, I think it's eventually going to fall away to newer agents that are just kind of easier to use, but it's not either very good at doing what it's supposed to do, which is get the blood thin quickly nor is it good at preventing overshoots and bleeding risk associated with blood too much. So it's really just like an inferior agent.

Yes. And if a new overshot, so it's not like you just turn it off and it just goes away in many patients, it can linger on for hours. And sometimes you have to reverse it with using fresh plasma and all that. But it's very cheap. So do your hospitals incentivize you to, hey, use it, it cost us pennies and why not. So you don't buy into that incentivization?

No.

Right. Okay, great. So -- and you talk to other people, and this obviously is your experience with heparin and is that the general consensus you get? I know you guys goes to all these meetings as we are going to the one at the end of this month, you meet all the main people in CRRT world. When you talk to them, is this experience with heparin universal across all or do you have some real strong supporters of heparin out there?

No, it's not -- I mean, citrate still is superior as a higher incidence of use across the United States. So compared to heparin, it's definitely not used despite the cost advantage. You wouldn't sacrifice patient safety or efficacy over -- it's just not used. It's not used as much.

I've never met anyone who is a strong proponent of heparin. Heparin hasn't been recommended as first-line for the last 10 to 15 years, right? Despite the fact that it's the only thing that's approved technically for this use, nobody is pushing for heparin to be the first line.

And Dr. McMahon, you do use citrate in select patients. And so tell us what is life like?

Well, how long have you gone? Because I can -- if I can tell you, it's an absolutely -- as the Director of CRRT at MUSC, it is an absolute pain in the a** for me because it's constant. I mean I'm not going to bash citrate, okay. It does its job, but there's issues with its use. We talked about complex protocols and it has a huge burden on nursing staff and also on the medical staff.

These monitoring of labs, the iCas, the post-filter calcium, the lactates, the CNPs and then these titration of this calcium infusion that you have to give the patient. There are certain cohorts of patients that you can't even use citrate in. Well, you've got to watch them really closely.

Deliver patients, for example, they can accumulate it and get some degree of toxicity related to it and then you're stopping the citrate. And then because you're starting a calcium infusion, my protocol starts at 60 ccs in hours, and if you have decompensated heart failure, you can't even pull off that 60 ccs. So you're going in there with your machine and then you're overloading them with this infusion.

And then don't even mention now because the REGIOCIT, the 0.5% got pulled by the FDA because they didn't have an emergency use authorization. And then we moved to ACD-A, this higher percentage, I'm seeing a lot more metabolic disturbances with it while they're not therapeutics.

For some of us who may not know what exactly is ACD-A.

It's just -- it's just a higher -- it's a higher percentage of citrate that we use.

So highly concentrated citrate.

Highly concentrated citrate 2.2%. So it's like this alkylating drug, and it changes the PH of the blood and you have to monitor for that. So we see a lot -- I get a lot of the safety events that come back when its used and it's all the time to the point now that I actually have to do -- we have to do citrate rounds when we start citrate.

I have highly skilled nurses who actually do their round -- one nurse actually goes around on anyone who starts so that we can start monitoring it because what we're seeing is a lot of these metabolic disturbances and then at the same time, we're not getting therapeutic. So we have our methods of monitoring events and sometimes they're still clotting. So it's been a thorn in my side since we moved to ACD-A, and that just has to be a better option.

Right, right, right. And what kind of other logistical challenges that you face? So ACD-A is now, you have it injected into your substitution dialysis fluid and so that offers -- that you see some challenges for you?

And then storage, right? So we live in Charleston and the pharmacy are screaming at me going we don't have room because every time you order another bag with the citrate, it's another pallet. You can -- Tara, you can see on the next slide, you can see the fluids that we have in storage. We had to actually store out of warehouse in North Charleston, and every 2 days, they send a pallet of this stuff down for use.

So there's a storage problem with this as well. And that's a big deal for my -- we have to pull back on other bags to allow for the citrate anticoagulation. We had to drop one of the phosphate containing bags because they're just saying, you have too many bags. You need to find options for storage. And that's not my job as a physician. I want a simpler option. I want a smaller bag.

Yes. And I'm sure that you win some popularity points from your nurses every time you prescribe citrate. How does that...

It's a heart sinker. The nurses go, really, are you kidding me? And then they just sit there and they're like, yes. So you can see here with this slide on the right-hand side, these are the citrate bags -- well, these are the CRRT bags, but to order citrate, you need another shipment of citrate bag. So they're big -- these are 5-liter bags. Patient might go through probably 6 of these, 6 to 9 depending on the blood flow per day.

So it's a lot, and if the patient is on CRRT from 2 days to a month, you're going to turn over these bags. In comparison to the nafamostat on the left-hand side, this is the -- see where the circle is, that's the bag. It's just like a saline bag. So this is a 1-liter bag -- actually, no, sorry, this is a 500 cc bag or 250 cc, much smaller. Yes, easy storage. That's what we want.

And Dr. Teixeira, you actually trained at one of the premier citrate using institutions, but you have not been able to implement a citrate program at UNM. So tell us about what are the challenges or pushbacks that you experienced?

I think Dr. McMahon sort of hit upon it. Like it's a drag on kind of nursing kind of bandwidth, it's complex. It's hard enough for me. I think most of the fellows -- I'm involved with the nephrology fellowship quite intimately here. I think most of the fellows graduate from our program and understanding how to use it well.

And then we did have citrate available where I trained at the University of Colorado. But to be honest, actually, I wouldn't have actually probably call it a center of CRRT excellence. I know that a little bit better now in retrospect to be honest. But like certainly, I had faculty there, and these are like world famous nephrologists in their field, but who don't -- didn't understand citrate and I only started to learn it somewhat after training because it's hard to sort of learn.

We actually -- when I was fellow, there was a disruption in the supply of calcium infusions related to one of the hurricanes in Puerto Rico and we lost our ability to prescribe citrate, for like a year of my training, to be honest. At UNM, and again, I think we've already hit this up, like it is complicated. One of this -- we'll just say, I won't name him, brilliant nephrologists who sometimes even within my own field, even though he's not specifically a critical care nephrologists, I'll ask him questions because he knows so much about everything.

Like even some of the most experienced nephrologists in my group who are brilliant, kind of general nephrologist who know everything about everything to some degree, don't know how to manage citrate properly, like the fellows sometimes texts me on a Saturday afternoon and be like, Dr. Teixeira, I can't understand what's going on with this patient, like why are we doing this? I'm like I don't know either. But what ends up happening half the time is that we end up stopping because people are confused. They don't understand what's going on.

Sometimes they develop real accumulation of citrate or toxicity like Dr. McMahon alluded to, that can occasionally be life threatening. But most of the time, the nurses, the intensivist, even the nephrologist is confused and we end up stopping it anyway. And so it ends up being kind of this like dance that like burns up sort of my bandwidth to be honest. And I'm not there at the bedside all the time, able to manage things and that's a difference between sort of a clinical trial that shows citrate is better than heparin than real life.

Like if you're running a clinical trial where everything is sort of carefully controlled with a complex therapy like citrate. It's going to look great. It's going to look great, but we know it. There's actually good data from the United Kingdom that like it doesn't actually perform that much better than heparin. We've already talked about how much I think heparin is basically garbage. Citrate in real-life settings, when it was implemented on a national basis in the United Kingdom had no benefit basically. And so I think I see that on a day-to-day basis when I try to sort of provide this therapy to my patients. And so that's part of the reason why, we have citrate available, but it's -- we're not a citrate first center.

Yes. So it's very clear that 2 options that we have, they have their own unique challenges. So heparin, yes, it's easy to administer and far less complicated, but very unpredictable, doesn't always work the way it should and then cause systemic anticoagulation and adds too much risk to the patient safety.

And then you have citrate with no uniform protocol, intensive, intensive monitoring, extremely high workloads and a benefit, which could be there, to some degree, it could not be there based on where you use it, what setting you use it in and how experienced your staff is. And also the nurses that are well trained in it, they're always there. They're not really rotating through other jobs, and you're not always having to find new staff to train. What would be your ideal -- the profile of an ideal anticoagulant that you would see -- feel comfortable using? Obviously, it has to be safe and...

Yes, it has to work.

Yes, it has to work.

The kind of drug that work and that's worked and is safe even in our high-risk patients like our younger patients who are vulnerable to clotting and have had clotting coag, like these clotting disorders. We want to be able to use it in our surgical patients. And I want that drug to remain in this circuit and not to overflow into the patient's blood. So having a drug that remains in the circuit is important. Having a drug that does not require these complex protocols that we talked about, that I don't have to send half a dozen labs to monitor, okay, I'll do the 1 lab or the 2 labs to monitor its safety but it's really straightforward and simple.

Simple in the ICU is really important for the nursing, especially with the nursing shortage -- like you don't want to overwhelm the nurses and then also having not requiring these calcium infusions and titrations of calcium. And also like the storage thing, I mean, you might not think it's important, but it is. For me, it is. And so yes, I wanted to tick all of the boxes.

Right, right. Yes. So I think -- and both of you have been involved with Niyad trial, and I recognize this is a blinded trial, but their administration of the placebo and the active drug are very similar, exactly the same. They have to be in trial design and the titration. What is your and your nursing experience so far who've been exposed to citrate and they say, okay, we don't know what it is, but gee, it is very simple to use, or is it like...

Actually, it's quite fascinating. The nurses are really excited. They're coming down, they’re going, is this the new drug? Is this the -- and they're popping their heads in and they're going, is that it? And they're excited at this setup, and they're like, oh, please come on, hurry up, finish the trial, make our lives easier. It's all over. We get a lot of excitement when we set up.

Okay. Good to know. And your titration, again, as we mentioned that one of the challenges that, at least I felt, titration with the heparin to hit the -- your target window of aPTT is always challenged. And many times, you have to give a bolus of heparin at the beginning, which many of these patients don't get because of the high risk of bleeding. So do you find this easier to kind of get into your therapeutic range when you want it? The steps to get there are easier and more convenient than you would say with heparin, Dr. Teixeira?

So no, it's straightforward. It's straightforward. Within a few titration steps, it levels out like the amount of adjustments is a fraction that's required for heparin, which is like the easier thing to, in general, titrate. And so usually within the first hour of therapy, we have a steady rate and then maybe it will need to be adjusted once more over the next 24 hours, even then not always. And so and it's been very straightforward. I think just like Dr. McMahon described like the nurses are like, that's it. That's all we have to do. And it's been pretty straightforward.

Yes, definitely easier than heparin and citrate in my experience that the titration, not only once you get to titration, you constantly have to move back and forth and with all the other things that change in patient or the dialysis. So how -- I'll start with Dr. Teixeira, how do you see if Niyad is approved, becomes available to you? And how do you see it fit into your anticoagulation regimen? Right now, Dr. Teixeira, you don't have one, you use occasionally citrate, where would nafamostat fit?

Yes. I mean I think we would move to the front of the line of our options available for anticoagulation for sure. Like there'd be no -- I could never foresee a situation in which I would use heparin instead of nafamostat, like it wouldn't exist. And then occasionally, maybe rarely we would use citrate in an especially complicated patient, enrich the risk of bleeding is like extremely high or the risk of worsening bleeding is extremely high, but I think that would be few and far between, to be honest.

I think nafamostat would become sort of our first option. Whether we were nafamostat upfront on all patients versus having been the first option if we clot, like again, that's sort of kind of a cultural thing like our institution, we're a nothing first center. And so I would think that, that might be something we should consider honestly because it would probably improve our outcomes overall in terms of filter life. But at the very minimum, I would think that if we encounter anything that requires initiation of anticoagulation, I think this would be our first option because it's just straightforward and effective.

Same here. I haven't had experience in the trial and as a CRRT Director, I would move it to frontline, I would actually replace my current protocol with it. And also because MUSC has bought up all these other community hospitals in South Carolina, and some of those programs don't have anticoagulation and they're not getting the filter lifespan and talking to some of the ICU staff there, they want simple, they won't take on the citrate protocol because it's too complex and they don't have the nurse.

They just don't have the bandwidth to deal with it. This is really simple, it's really simple. You just hang it in the prefilter and it runs and you might do a couple of titrations and then the nephrologists will monitor a couple of labs, but that's it. And it stays in the circuit allegedly. So it's nice. We're looking forward to finishing out the study where we are.

We are frequently asked, and we have been up -- have seen ups and downs in enrollment in this trial. And some of this was really had to do with the sites that we originally had which were not the right sites for this study, but we made those changes. We have sites like yours brought on and the study enrollment picked up, and we are way past the half point. And does that reflect any challenging -- challenges in acceptance of nafamostat? I think the people always ask us, gee, if you cannot enroll this trial, how are you going to find patients who need this? What are your thoughts on that?

I can answer this one. We've talked about this, Shakil. So the study was designed to be extremely cautious, right, like with anyone basically with increased risk of bleeding, including to be blunt, a bunch of patients who I think would be ideal candidates for nafamostat like because the whole concept of the nafamostat is that it produces regional anticoagulation, there's a bunch of patients that end up being excluded, I think would be perfect candidates for this therapy.

And CRRT studies are hard. CRRT studies are hard. These are sick, sick patients. You mentioned I have enrolled 300 patients in trials and prospective studies to be honest, not all trials. But nonetheless, like most of them are not CRRT patients. This is my one area of like most interest, to be honest is CRRT, but enrolling patients who are requiring CRRT into clinical trials, it's extremely hard in any setting.

And in this case, like the way the protocol is designed, which I understand, I don't I think it's reasonable to criticize per se, but like anyone with any sort of issue related to like possible increased risk of bleeding can't be in the study, they have to have like very specific dose of DVT prophylaxis, if their ACT is 151. And again, a patient who has a slightly high ACT that's excluded from the study, those patients would all be completely reasonable candidates for this actual therapy in real life.

So the study protocol, the way it's designed, assuming basically erring on the side of assuming that the bleeding risk associated with this drug is much higher than it actually is, in my opinion, the study protocol excludes a whole bunch of patients who would be very reasonable, if not even like ideal or preferential candidates for this therapy. And so I think that's the challenge of the studies, finding patients who meet all the criteria, including that baseline ACT.

That's been a major issue for our center. We identified more people who have had a baseline ACT out of range than in the range that the FDA asked for. And that's not something that we've been able to sort of negotiate to change the protocol. I understand that. But I don't think that's going to reflect the real view -- the real-world use of this whatsoever.

These are sick, sick patients just getting consent for any CRRT study to do anything is complicated. And so like the stars kind of all have to align to get someone into the study. We're making progress. We're doing the work. But all that said, I think the limitations of the study or the challenges enrolling a study will not translate whatsoever to the uses outside of study.

Good to know. Dr. McMahon, do you have any comment on that?

Yes. No, I mean, I enrolled 3 patients last week. Like I don't have an issue with it. And a lot of patients are coming in bleeding, actively bleeding and then we still manage to wait -- safely wait 24 hours, 48 hours and then we enroll them later once the bleeding had stabilized and they were treated and they were still on CRRT. So even in high-risk patients, we're still able to get them in, yes. No, I don't think it doesn't reflect it at all and drug will sell itself, to be honest with you, it's not going to change at all.

That's great. That's good to know. So coming to selling itself, how much challenge do you foresee selling it to your hospital formulary?

I don't think it's going to be an issue because we're the ones that request the purchase order on the drug as the Director of the CRRT in the hospital. And then we just have to go to a P&T committee and say, look, these are the adverse events I've had. These are the challenges. They already know the challenges with citrate. It's not going to an issue for me. And I can see that the other peripheral hospitals, they will probably end up starting the drug at the time of initiation. So it's just set up and then they walk away from it and use it and then see those longer -- like they will gain money because these filters are expensive. So if you're getting a longer lifespan of the filter, the drug will pay for itself.

Okay. And citrate is not cheap. I mean, there's...

No. Those bags are not cheap.

I mean there's even personal cost to it, but there are components and multiple testing and all that. So citrate -- nafamostat is not going to be more expensive than citrate actually.

And so like it's actually quite shocking. Those bags expire with the drugs really quickly. Those big bags, I got an audit last year back from the hospital, $45,000 of expired drug, I mean, it's massive money. It's huge money on the hospital. So we have to do better.

So that brings me to the end of my questions for you. And we have some little time left for any questions from the audience, from other people who are listening in. Tara, I'll hand it back to you before I do that, I really want to thank both Dr. Teixeira and Dr. McMahon for very exciting and enlightening discussion today. Thank you for joining.

Yes. Thank you for letting us be part of the study.

Absolutely. Tara, back to you.

Great. Thanks, Shakil. [Operator Instructions]. So our first question comes from Naz Rahman at Maxim Group.

Hi, everyone. Thanks for the discussion and the application on nafamostat and CRRT in general. So one thing that was mentioning or I guess a couple of points that were mentioned is that the rates of chronic kidney disease is increasing over time, and citrate is very labor intensive and I guess there's also the nurse charts is going on.

I guess with these factors combined, do you have any data on whether or not all of this is changing or increasing mortality risks per patients over time just due to how labor-intensive citrate is to use like, does this create like a backlog? Or is there like a backlog of patients that are being affected? And how does this all sort of fit in with nafamostat?

I can try to answer that. I don't think it's affected mortality rates. I guess I would start by saying that this patient population like we started off saying, that Dr. McMahon was saying like is extremely ill. So the typical survival rate of a patient who is sick enough to be in the ICU, with particularly in acute kidney injury requiring continuous renal replacement therapies like 50%, 60%, depending on the study.

So in other words, half of these patients won't survive because of their underlying severity of illness. I don't think that's improved a lot over the last 20 years, which is like actually in the context of critical care, where to some degree, our supportive care, all these devices have improved survival rates in many populations like slowly but surely improved overall, let's say, survival rates from septic shock, one of the most common reasons to be in the ICU.

But I don't think the issues that we described have led to increase in mortality. But I think to some degree, it may -- this is hard to prove, I suppose, but it may be part of the reason why we've made minimal impact on that survival rate in patients with AKI, acute kidney injury, severe enough to require renal replacement therapy. It's not like we haven't seen improvements in mortality for the last 10, 15, 20-plus years. And I think some of these challenges may be part of that. But yes, I don't know, Dr. McMahon if you have other thoughts.

Yes. And if you look at how medicine has gone now, dialysis isn't just the only form of extracorporeal treatment. They're developing new membranes, new devices for new indications, we were part of another clinical trial for another device that requires anticoagulation. So the application of nafamostat into extracorporeal treatments in patients with AKI and other illnesses on AKI, you're going to see it exploding. And we can tell you because these trials are listed on clinical govs. And they're all requiring anticoagulation.

So I think and we're going to take ownership of those devices in our ICUs as well as for dialysis and these devices once they get FDA approved, will bring down the mortality rate and have shown in one previous study to reduce mortality. So I think you're going to see the application of nafamostat outside of AKI as these devices come in.

Got it. That was helpful. And one more question, if I may. Seeing how this study has an extremely strict criterion for excluding patients with bleeding risk, do you think that could create like regulatory headwind in terms of getting potential approval or potential adoption risk by other institutions based on your conversations with other experts?

I think it's unethical to enroll a patient who's bleeding because you just couldn't get away with doing that clinically. And I've enrolled several patients who came in bleeding and then were stabilized and then enrolled them. They're high-risk patients, but they also need good dialysis, and we still manage to get them in. So no, I don't think it's going to have any implications.

You just got to -- and just for the sake of the study, and it really depends on -- once the pharmacokinetic data that comes out about the nature of the drug, we'll have a better idea. But it's certainly not an issue in my experience. Obviously, we don't give the drug to someone who's actively bleeding. You just -- you couldn't find a trial to do that.

Yes. I agree. I mean, like this issue of like dealing with patients who are at risk of bleeding, clotting is just like a daily issue in the ICU. And again, like the only sort of kind of like major issue here is that the bleed risk associated with nafamostat is going to be so much less than any other traditional anticoagulant that if anything, that balance is going to be easier to strike in real life clinical practice and ICU with nafamostat and then certainly heparin or anything else that we routinely use as an anticoagulant.

Our next question comes from Yuan Zhi at B. Riley.

Maybe first to the company, to Vince or Dr. Aslam. For the trial, you have an anticipated enrollment completion in first half 2026 and we have a 28-day safety follow-up. So I wonder what's the time line for the top line readout, should we anticipate in 3Q 2026.

I can answer that, Shakil, and you're going to add any additional color. So right now, we anticipate again second half 2026, and our operating plan includes a PMA submission in the second half of 2026 as well. So the data is being cleansed all along. It's because it's a 24-hour endpoints, so we're doing everything we can to have that PMA submission ready as quickly as possible.

The reason it slipped, honestly, past first half of the year was because 2 sites that we're planning on having just continued to delay. It was anything to do with us or the contracts and it was their own internal issues and one in particular, had all research studies on hold as they were revamping their research protocols throughout their facility. And they just recently released the ability to initiate studies again, and we were one of the first couple that was reinitiated and they lifted the hold immediately, activated the study with a training refresh.

So outside of that, we felt like we were on track for the midyear, except for those 2 institutions that caused the slip, and we believe we'll be in a strong position to have this completed and ready for submission before the close of the year. Shakil, did you have any additional commentary?

No, Vince. I think you've covered it all. Those were unexpected delays, but I think we are way past that and we'll continue to execute quite nicely actually from this on. As you heard from Dr. McMahon, as she enrolled 3 patients last week. So I think the pace is good now.

Got it. To the 2 doctors, when a new nurse is on board, how long does it take for them to get used to citrate for this ICU setting versus how long does it take for them to get used to Niyad if it's approved.

So yes, I can take that one. The nurses go through certain levels of experience when it comes to CRRT, they have to go through their basic CRRT training and they can do another more advanced training and it's the advanced training nurses that actually have to do the citrate training. So we have our basic nurses that not all of the ICU nurses do CRRT training. And of those who do the initial CRRT training, they don't deal with citrate.

It's actually the super users that deal with the citrate protocol. So it's like the cream of the crop of the CRRT nurses that do it because it is complex. So they don't overwhelm them initially when they're getting trained on CRRT and they reserve that for a more skilled CRRT nurse. With this, if we manage to bring this on board, we would actually train everyone upfront because it's so simple.

You hang a bag, you run a pre-filter, you're checking a lab and you're titrating based on a simple box. And that's it. It's so easy to use compared to our current protocols. So yes, I can see the nurses changing that for the initial all-comers upfront.

So Dr. McMahon, in the citrate training, what would you consider typically it takes to train nurses? Do you kind of...

Well, you have to take them through the protocol, you have to talk to them about where to draw the calcium from the different circuit, just 2 different lines. You have to draw the calciums from there, the timing of it, the interpretation of it. How do you interpret, how do you titrate your calcium in response to that? How do you look for citrate accumulation? What you do with alarming because you're dropping the blood flow, you get increased alarming with the citrate. How do you handle that? Like, I mean, it's a cluster and so you can't just put people -- you can't just put the nurses on that straight away. They'll get too overwhelmed. It's our super users that use the citrate protocol.

And Niyad would be just like hanging a bag of heparin except that it's...

Yes. It's a high -- it's a small deal. Hang up and you let it run and then you set out a rate and then you check your ACT level within 15 minutes, and then you titrate based on that. It's a simple -- it's easy. It's uncomplicated. And yes, no, it's good. It's good.

I could second some of that. I'm not sure exactly how long it takes, probably like ends up being months before they're comfortable, I would say. But like Dr. McMahon saying, first of all, look, only a fraction of our ICU nurses are trained to do any CRRT. I think in our institution, they all get some initial training on citrate, but like only the most experienced nurses are comfortable with it.

And so to some degree, again, one more reason why like we are reluctant to just throw people on citrate willy-nilly is because certainly in the middle of the night, expertise from the nursing side in delivering this therapy may be limited. And just like Dr. McMahon described, like nafamostat is going to be far more equivalent to just like any other drug administration that the nurses are able -- capable of doing. So I don't think there'd be any sort of restriction. Basically, if you run CRRT, you would be able to run nafamostat without issue.

Yes. Got it. Got it. Maybe one last question to Vince. Since Niyad is approved and used in Japan and South Korea for over 30 years, how should we think about the market exclusivity in the U.S. for this drug device combination. And would any new patent application in this setting help to extend the market exclusivity here?

Yes. Good question. So put patents aside for a moment, just on data exclusivity from a regulatory standpoint, we will get 6 years post approval. And then beyond that, we've already filed international and domestic patents that are citing different mechanisms of use. It will be on method of use in the United States, the titration schedule, supply, et cetera. And we feel comfortable right now that we'll get those patents awarded. And that would take us into the 2040s, correct me if I'm wrong, Raff. So we feel confident in that moving forward and have been working on that really since the day we got the asset.

Our next question comes from Ed Arce at Westpark Capital.

Great. And thank you to both of the physicians who have joined here as KOLs, very helpful and insightful. Just a couple of questions for me. I think Dr. Teixeira earlier on mentioned how, despite citrate being the nominal recommended first line, at least in his facility, and I would imagine similar situations at others. It's used maybe 2% of the time, I think he said, in other words, the protocol is basically don't do -- won't do anything at first.

So as you think about all of the benefits and advantages over the 2 options today, I'm wondering if you would expect to see a significant increase in the use of this versus the 2 other options today. In other words, could the market as it is today, actually grow because of the use of Niyad as the first-line therapy going forward?

Yes. So I can try to address that. So let me back up. The recommendation, that citrate is dominantly first line is actually not specific to my institution. It's from what we call our KDIGO or Kidney Disease: Improving Global Outcomes recommendations in 2012, they recommended citrate as the first-line anticoagulants in patients who don't have a contraindication, which is a little bit vague, but basically suggested that should be first line.

So that's been like a global recommendation for almost 15 years and I would say like across the U.S., it's more than 2%, but a substantial minority of centers. It's definitely less than 50%, though of substantial minority of centers are citrate first right now and kind of follow that recommendation. So I guess the point is that like more than 50%, 2/3, 3/4 of centers in the U.S. don't follow that recommendation to be citrate first in patients who don't have an obvious contraindications.

And that kind of paradox or seeming contradiction, I think, just underlines the challenges and actually effectively delivering citrate. In our institution, maybe it's 2%, it's probably a little bit higher than that. So -- but it is a minority of patients who end up getting started on citrate. It maybe it's like 1/4 of the patients end up getting citrate.

And often, that's because they're clotting a lot and they're not a candidate for heparin or they're clotting despite heparin, which we've talked about how heparin is kind of, basically, in my opinion, inferior drug overall. But one of the issues with it is that it doesn't do that great of a job of preserving the filters. It doesn't even do what it's supposed to do.

It's kind of -- certainly, if you had to compare citrate versus heparin, heparin is simpler, but citrate is a more effective anticoagulant. So sometimes we'll try heparin first, and they'll fail that, so to speak, and then go to citrate. And so the second part of your statement or the question, I think you're saying is it will -- will CRRT use overall increase because of nafamostat...

Dr. Teixeira, I think it's -- I think when we're talking about the market is more the anticoagulation market, correct me if I'm wrong, Ed and the question will be, if you're hesitant today, to use anticoagulation because there's a large segment that uses no anticoagulation as a first line and might not even used this therapy for all the aforementioned reasons that Dr. McMahon and you have mentioned, do you think that a simpler agent would compel them to maybe start introducing it to the protocol, whereas historically they haven't. So the overall market of anticoagulation in this area would start to increase.

Yes, that's exactly my question.

[indiscernible] Citrate use is going to increase regardless. So actually, I don't think that nafamostat is going to change that. But the answer is yes. So overwhelmingly, like will more centers -- will a larger proportion of the nothing first centers like my own switch to using nafamostat first. I think absolutely. Those will be like centers in which a therapy like this will be attractive because like I think nothing first is going to become second-line approach or newer guidelines are going to sort of continue to sort of emphasize what's already been emphasized is that something is almost certainly better than nothing.

And with all the issues with heparin, and citrate having a therapy that is both effective but less complicated and less risk of severe complications like citrate gone wrong, which is unusual, but can happen, it can be severe. I think overwhelmingly, like the global use of anticoagulation with CRRT is going to go up.

Yes, 100%, it will go up. I agree with that statement. The only reason we don't start with citrate is because of the issues that we're having with citrate. If I had a friendlier drug, a better drug, with less complications. I would absolutely use it because I want to push those filter lifespans out to 72 hours, like the FDA says they should get and we're not reaching that. 67% of people across the United States are not getting 24 hours, getting up to 24 hours. That's not good enough. We're not getting the quality dialysis we should begin. And I think a nafamostat has the potential to change that.

Okay. So my next question is sort of the flip side to this, where the first one is thinking about the potential for a substantially better option to actually grow the market overall or CRRT. The second question is more related to what limitation can you see? What patient populations or specific protocol situations do you envision where Niyad perhaps would not be thought of as first line and you prefer just to do nothing?

Well, I mean, the only thing that comes to mind is the drug allergy. Someone has an established allergy with the drug. Outside of that I can't see another reason why. Can you?

Yes. I mean -- so I think we need to sort of -- we need some data and the study is going to help clarify that. And the question is, is nafamostat 100% regional? In other words, is the effect on systemic anticoagulation 0%?

it's possible, but I think there may be some slight, slight, slight bleeding risk associated with it. We already talked about how part of the challenge of the study is that a whole bunch of patients who have like a little bit higher risk of bleeding that are, to be blunt, like an average ICU patient, is that higher risk of bleeding. There's a whole bunch of kind of relatively average ICU patients that excluded from this protocol because they're like have slightly thin blood to begin with, based on their ACT.

So those are all a bunch of patients who I think would be extremely well served by nafamostat. It's possible that like the highest risk scenario, which I would think like someone comes in with a large intracranial hemorrhage, which is like not a common scenario where CRRT is needed but can occur, this would be like a fraction of our CRRT population, like I would think 5% or less.

Some of those patients with a large intracranial hemorrhage, any anticoagulant may be prohibitive risk in that situation, even one that wears off within 5 to 8 minutes may still not be a first-line approach or maybe a situation where you wouldn't necessarily start them on nafamostat at first. In that situation you would do nothing at first or if you still have citrate, like again, like I wonder if citrate protocols are going to slowly go away over time because the effort required to maintain them is so high. And if it becomes like rare that they're used, less than 5% of patients, maybe it's not worth maintaining them.

But nonetheless, the one maybe option is like the patients who are bleeding, which the bleeding is in and of itself extremely sort of life-threatening the most kind of extreme of the extreme, like a fraction of the bleeding patients that we deal with would be those with intracranial hemorrhage that any additional drop of blood, so to speak can be prohibitive risk, so to speak.

Those might be a patient population in which nafamostat wouldn't be a good idea to start upfront. You would only consider introducing it 3 or 4 days later around the time when they would be starting standard, what we call preventative therapy or prophylactic therapy against clotting in the legs, which develops a lot in ICU patients. So these patients with head bleeds eventually actually end up getting started on low doses of heparin injections to prevent clot in the legs like most ICU patients.

But I wouldn't necessarily do that on day 0, like ICU admission for someone who, let's say, is a chronic dialysis patient but develops a head bleed. Again, not super large chunk of our CRRT population, again, maybe 5% or less, but those might be 1 population, which nothing may be the most safe thing upfront. But I don't know. That's about it. Like I think most other situations, certainly like bleeding into your gut, that's a big deal, but it's not nearly as directly lethal, so to speak, as bleeding into your brain.

So our final question comes from Jim Molloy at AGP.

Sorry, I missed a couple of the Q&A here. What would -- do you want to get a confirm on the -- sorry if it's already been asked. I was over in another call. When will the trial expect to now finally enroll and the PMA will be filed? And then actually, the $4.1 million you guys got, I thought it was $4.9 million when you hit 50%. Was that explained earlier in the call and I missed it?

Yes. So I can help answer that. So that tranche was larger than $4.1 million in totality, but because an early investor waived and yielded some of those conditions, $1.6 million in proceeds had already been received of that tranche. So separate from that, then another $4.1 million came in when we achieved the 50%. Does that make sense on that portion?

It does. Does that in cash on hand, get you through to the PMA?

Yes. So with the cash on hand and the expected activation of the other tranches, we expect this to get through approval from our cash position.

So yes. Beyond that, I think your question was guidance on the study completion. We mentioned it earlier in the Q&A. It slipped a little bit, last 2 sites came on later due to their own internal processes. One of them in particular had a hold on all research studies at their facility had nothing to do with the Talphera study in particular. They just recently released that.

And so with those 2 sites, built into the forecast to complete by midyear. It will slip a little bit past that, but enrollment seems to be performing nicely. We'll have the study completed in the second half of the year. Our goal is to also have the submission of the PMA in the second half of the year.

Great. And then a quick follow-up. Could you walk through what an ideal candidate would look like? I know there's some talk on the -- with the KOLs about how there's exclusive criteria for the trial is a little more demanding than you might find in real life. What will be sort of the ideal candidate you'd be looking at? And then also, is the 2 trials are driving 90% of the enrollment to date, is this effectively sort of a 2-site trial at this point?

No. So the over 90% of the enrollment is coming from the new target sites, of which there are 9 since we inherited the study. Just to give you a quick background on that. If you recall, when we bought the company Lowell Therapeutics that had the asset. They had already engaged a number of institutions, good institutions that have been used for the previous study affiliated with that company/La Jolla Pharmaceutical because as they were a subsidiary then prior to that.

And the change to the new profile sites incorporated not just critical care physicians, but Dr. Aslam came in and moved it towards nephrology leads and he moved the study towards the MICU, the medical intensive care unit instead of some of the other ICUs involved. And with that, 2 element profile of institutions, he engaged 9 new institutions into the study. So those 9 new institutions are the ones that are enrolling more than 90%. It's not just a 2 trial site.

Refresh me, I think the question prior to that was the ideal profile for the patient to be used on nafamostat as an anticoagulant in CRRT. I think we've kind of mentioned it, but Dr. McMahon or Dr. Teixeira, can you just quickly again, it didn't sound like there was a lot of restrictions to patients that are going on CRRT, but maybe reiterate who you feel is ideal for the profile.

Yes, I can give it a shot. Again, like I think you're sort of -- Vince, you're basically like taking the words out of our mouth. I think it's easier to think of who this would be inappropriate for and list like a very few number of patients, like again, they have admission for a head bleed, perhaps not. Like obviously, we have to -- need to do no harm. But I think this will serve the average ICU patient needs CRRT extremely well.

Like including some -- not some, most of the patients that are excluded from the study due to kind of the extremely conservative inclusion criteria that we have for the study. And so I think it's harder to think of patients in whom we wouldn't use this therapy. But I don't know, Dr. McMahon if you have any other thoughts...

Yes, I mean septic shock is the most common indication cause of AKI in hospitalized patients and including those in the ICU. And so they're relatively straightforward. And I can even see use for this in liver patients because they clot all the time because citrate is -- you've got to be really careful with citrate use, and we use half the dose of citrate in our liver patients, and they clot all the time. They're so vulnerable to clotting.

And we obviously have to wait and see what the data shows from the trial, but I can envisage it being used even in those patients and they're currently a cohort that we're not using in the study. But actually, we have used a couple of patients for liver failure, but yes, I can see the inclusion use of this drug expanding across the entire cohort of patients.

I agree with that. Liver patients would be pretty routinely excluded from this study based on the current inclusion criteria, but those are patients in whom this therapy, I think, would be perfectly appropriate for, absolutely.

So we've run a bit over. So we're out of time for questions. I'll turn it back to you, Vince, for closing remarks.

Yes. Rich discussion, I can't thank enough our experts, Dr. McMahon and Dr. Teixeira, 2 very busy professionals in patient care, in particular, ICU patient care. So you can imagine what their days and nights are like, for their time today, and I really hope that gave you an appreciation for the opportunity for Niyad and CRRT and our excitement once the study is completed, assuming all is as expected to get this in the hands of the physicians dealing with these complicated ICU patients.

We'll keep you updated on the progress of the trial and the FDA PMA submission planned for later this year. Thank you all for joining the call and listening. Dr. Aslam, thank you for conducting the questions in the engagement with the key experts and that concludes our call for the day.

Thank you, Vince, and thank you again to Dr. Teixeira and Dr. McMahon.

Thank you. Have a good day.

Thank you, guys.

Welcome to the Talphera Third Quarter 2025 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.

Thank you for joining us on the call today. Today, we announced our third quarter 2025 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 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.

Thanks, Raffi. Good afternoon, and thank you to everyone joining our call today. We're excited about the progress made this past quarter, specifically in the continued NEPHRO study enrollment at our current clinical study sites and completing a financing that, with the additional tranches provides us sufficient capital to a planned approval of the Niyad PMA later next year.

In September, we completed the first closing of $17 million of a 2-tranche financing, which included CorMedix with a $5 million strategic minority investment that provides them a 60-day exclusive negotiation period to enter into a definitive acquisition agreement following the release of our top-line data from the NEPHRO study. CorMedix was also provided the right to a Talphera Board seat to which Joe Todisco, CorMedix's CEO, was recently appointed.

In addition to the CorMedix strategic investment in the first tranche, existing financial investors, Nantahala, Rosalind, and Rock Springs Capital, along with some new institutional investors, invested $12 million to complete the $17 million financing. Importantly, these institutional investors committed an additional $12 million in a second tranche upon announcement of achieving the NPR study primary endpoint and a stock price trading above $0.69 per share for 5 consecutive days post the announcement. This latest financing, combined with existing cash and the remaining conditional tranches, is expected to provide sufficient capital through at least an anticipated PMA approval in late 2026.

These investments further validate the Niyad opportunity in the market and put us in a solid financial position to execute on the study and prepare for the launch. Beyond the Niyad opportunity, the recent investments were catalyzed by our efforts at the end of last year to restructure the NEPHRO clinical study, which included changing the target profile for clinical sites and investigators and approaching the FDA with various study protocol changes, including the reduction of the study size from 166 to 70 patients with a goal of accelerating the completion of the study.

The results of this restructuring were evident last quarter with the acceleration in the enrollment rate from our existing sites, which continued into the third quarter. The 3 new profile institutions that were brought on board earlier this year have demonstrated the speed of enrollment that is possible when focusing on medical ICUs and having nephrologists as the principal investigators. We expect continued positive enrollment rates from these institutions, and we'll provide an update once we achieve 35 patients or 50% study enrollment.

While the enrollment rate from our 3 existing target profile sites has remained robust, the initiation of the 6 additional target profile sites expected by the end of the third quarter has been slower than anticipated. As of today, we've successfully activated 2 of the 6 new target sites, each of which is expected to be high enrolling. The remaining 4 target sites, including one of the highest volume CRRT institutions in the country, are under contract, but for a variety of unique reasons to their respective institutions have not yet started their enrollment. Because of the delays on the new site's activation, we've pushed the estimated timing of study enrollment completion to the first half of next year. Dr. Aslam will provide some details on the specific reasons for the delayed activation, as well as his thoughts and assumptions on the timing of study completion.

In addition, Dr. Aslam and I have continued to visit with many of the new study teams at their respective sites. While observing their study engagement, I'm also highly encouraged by the eagerness of these institutions to have nafamostat available. In their words, nafamostat, based on its profile and use in other countries, would be a preferred anticoagulant for CRRT. And while we need to complete the study, this feedback from these investigators continues to strengthen my belief that nafamostat, if approved, will become a primary product in the market for CRRT anticoagulation.

Now before I turn the call over to Dr. Aslam to provide some additional details, let me remind you that if approved, Niyad would become the only FDA-approved regional anticoagulant for use during continuous renal replacement therapy. This is important and that there are many disadvantages to the currently used products, heparin, which is systemic in nature, and citrate, which is being used off-label.

I'll now hand the call over to Dr. Aslam.

Thank you, Vince. Similar to what we discussed last quarter, the enrollment rate at our existing target profile sites continues to impress and validate that the changes we made to the NEPHRO study were the right moves to accelerate enrollment. We are confident these sites will achieve enrollment to complete the study in a timely manner once the remaining 4 sites with our target profile begin enrolling.

Because of the short duration of the study, we have been successful in real-time data cleaning to minimize any delays in locking the database once the enrollment is completed. The guidance previously provided for study completion by the end of 2025 was contingent upon adding 6 new target profile sites by September 30 to the existing 3 target profile sites that were already exceeding the historical enrollment rate. Importantly, these 6 new sites are all large academic institutions, and most have higher CRRT volumes than the legacy sites. As of today, we have activated 2 of these 6 sites, with the remaining 4 sites to be activated during this quarter.

We knew 2 of these 4 sites were going to be slow to activate. However, due to their large CRT volumes and their status as prominent institutions, we welcomed their participation. These 2 sites have already completed contracting. One is waiting for the final internal approval, expected any day now. The other is in the process of scheduling its site initiation visit with activation expected next month. The remaining 2 sites changed their approval processes after contracting was completed, resulting in delays past their original timelines for activation. One had an institution-wide restructuring resulting in unexpected delays in the final approval. They have assured us the final approval next month.

The final institution is having their site initiation visit next week, followed by activation, as no additional approvals are required. Due to the delays in the activation of these new sites, we now anticipate study completion in the first half of 2026. While we are disappointed by the delays in the activation of these sites, we remain confident that these high-quality sites will significantly contribute to the study as well as the potential future utilization of Niyad. All of these institutions are anticipated to have similar or even higher enrollment rates than our initial 3 target profile sites. The PIs are excited to start enrolling and are expected to make a significant contribution to the study.

In our continuous efforts to improve study enrollment, we reviewed the emerging screening data to optimize the study design. Based on this review, we have submitted further changes to the study eligibility criteria, which we expect will accelerate the enrollment rate and broaden the target patient population for Niyad. We expect to hear from the FDA in a couple of weeks. As we mentioned on our last call, we continue to advance our compassionate use IDE with a large institute in the Southeast for a subset of specific patients with contraindications to currently available anticoagulants. This opportunity to provide -- this is an opportunity to provide an alternative to these patients who cannot receive the currently available anticoagulants and, as a result, clock their CRT circuits frequently. This is the first compassionate use submission by this institution, and we are helping them work through the process as quickly as possible. We will provide more information on the compassionate use IDE when submitted.

And with that, I'll turn the call back over to Vince.

Thank you, Dr. Aslam. Before I hand the call over to Raffi, I want to reiterate our belief that the 3 critical risk elements, clinical, regulatory, and commercial for the nafamostat program are low for a number of reasons. First, with over 30 years of use as an anticoagulant during CRRT in Japan and South Korea, we know nafamostat's track record of efficacy and safety, minimizing the clinical risk. The trial design has been agreed with the FDA, including broader inclusion criteria and a reduced number of patients, all of which have helped minimize study execution risk and proven to increase enrollment rates.

Second, we have a clear regulatory path, including breakthrough designation from the FDA, which has provided us with efficient access to the agency, leading to quick review and response times. And lastly, while we know there's always commercial risk, we believe this is mitigated given the disadvantages of the products currently being used for anticoagulation of the CRRT circuit, namely heparin and citrate.

Based on all our discussions we're having with healthcare providers, there's a clear need for an FDA-approved regional anticoagulant.

I'll now hand the call over to Raffi for a financial update.

Thanks, Vince. Our cash balance at September 30, 2025, was $21.3 million. We believe this cash, combined with the future conditional financing tranches will provide us sufficient capital through at least a Niyad PMA approval expected next year. Our cash operating expenses, or combined R&D and SG&A expenses for the third quarter of 2025, totaled $3.4 million compared to $3.7 million for the third quarter of 2024. Excluding noncash stock-based compensation expense, these amounts were $3.3 million for the third quarter of 2025 compared to $3.5 million for the third quarter of 2024. The decrease in cash operating expenses in the third quarter of 2025 was primarily due to reductions in personnel expense and other SG&A expenses.

As mentioned, due to delays on the activation of the new clinical sites, we've revised the estimated timing of NEPHRO study completion to the first half of next year. Accordingly, we are reducing the previously communicated 2025 expected cash operating expense guidance to now be in the range of $14 million to $15 million. This is a reduction from the $16 million to $17 million range provided last quarter. with the difference expected to be realized in the first half of 2026.

I'll now turn the call back to Vince.

Thank you, Raffi. Now I'd like to open the line for any questions you might have. Operator?

[Operator Instructions] And your first question comes from the line of Naz Rahman from Maxim Group.

I just have a couple. First, I just want to start on the enrollment. The new sites -- the new target sites that have already been activated, are you finding that they're enrolling patients faster? Or I guess, have the rates of patient enrollment increased? Because the last time -- when you last communicated the 17 patients, that was in August, and you still don't have the 35 patients. So it seems like mathematically, you're enrolling less than 2 patients a week. So I'm kind of left wondering why aren't the sites enrolling faster, the ones that have already been activated.

Yes. No, the original sites that we communicated last time, there were 3 of them, 3 of them only. And they hadn't enrolled the original 5 patients, right? Only when you put those 3 additional sites on did you see the movement from the 5 patients to the 17, and we're beyond the 17 now. So we're seeing a fairly similar rate of enrollment that we had seen before, similar rate of consents, enrollment, screening, et cetera. So we're well beyond that 17. But in order for us to achieve an accelerated enrollment, we need to layer on these additional sites.

No, what I'm asking is the new target sites, are you finding that they're enrolling patients faster now that they have some experience? Or are they still enrolling around the same rate?

Yes, they're enrolling about the same rate.

And one more question, if I may. So I know you're talking about these new target sites and they're seeing delays. But I was also curious, obviously, there's been a lot of volatility in the federal government, and that affected funding for a bunch of medical and academic institutions. Has that kind of played in or had any factor in any of these organizations and their ability to conduct clinical study, whether it's staffing or other leadership or structural issues? Has that affected anything?

Yes. I have not received that feedback from any of the sites, but I'll turn it to Dr. Aslam to see if he's gotten any additional insight as he speaks to these sites often weekly, if not daily.

Sure. Yes. So one of the sites, which is the Veterans Affairs Medical Center, they did have some issues earlier on after some cuts into their personnel. They are over that, but that did unfortunately add approximately, I would say, 3 to 4 months to their timeline. But rest of the sites have not been affected by that.

And that VA site, Naz, is not one that is currently enrolling. Dr. Aslam, when he says add the 4 months to it, that's until enrollment occurs. So we expect them before the end of the year now.

[Operator Instructions] And there are no further questions at this time. I will now hand the call back to Vincent Angotti for any closing remarks.

Thank you, operator. And again, thank you for joining our third-quarter earnings call. We're excited about the progress we've made with the recent financing, increased enrollment, and continued quality of the additional new sites to allow us to complete the NEPHRO study in the first half of '26 and achieve a potential FDA approval of Niyad in late 2026. We hope you appreciate our transparency and site activation, and continuous efforts to improve the study execution. We look forward to providing additional updates on our progress, and thank you for your interest in Talphera. That concludes our call.

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