Welcome to the Talphera Second Quarter 2025 Financial Results Conference Call. This call is being webcast live via the events page of the Investor section of Talphera's website at www.talphera.com. You may listen to a replay of this webcast by going to the Investor section of Talphera's website. I would now like to turn the call over to Raffi Asadorian, Talphera's Chief Financial Officer. Thanks, Andrew, and thank you for joining us on the call today. Today, we announced our Second Quarter 2025 Financial Results and Associated Business Updates in a press release. With me today are Vincent 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 be found on our website within the Investors section. I'll now hand the call 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 acceleration of the NEPHRO study enrollment. At the end of last year, upon the announcement of Dr. Shakil Aslam becoming the Chief Medical Officer of Talphera, we embarked on a restructuring of the NEPHRO clinical study, which included changing the target profile of our clinical sites, approaching the FDA with various study protocol changes, including the reduction of the study size from 166- 70 patients, and adjusting internal processes to ensure acceleration of study enrollment with the goal of completing the study by the end of 2025. I'm very pleased to inform you that we now have evidence that all of these changes were indeed the appropriate adjustments, and we're confident that we're on the right path to achieve our goals. We have seen a strong acceleration of the enrollment rate over the last six weeks from the first three sites with our new target profile. This target profile includes a nephrologist principal investigator and the institution screening patients at medical ICUs. As a result, the number of total enrolled patients has more than doubled since May. These sites, combined with six additional new target profile sites that are expected to begin enrolling over the rest of this quarter, should keep us on plan to complete the study by the end of this year. Dr. Aslam and I have recently returned from a visit with many of the new study teams at their respective locations. In addition to observing their study engagement, I'm also highly encouraged by the eagerness of these institutions to have Nafamostat available if approved. In their words, Nafamostat, based on its profile and use in other countries, will be a preferred anticoagulant for CRRT. While we still 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. The addition of more of the right clinical study sites and principal investigators has been critical to achieving the increased enrollment rates. As a reminder, the new site profile concentrates specifically on one, the type of intensive care unit where the study will be performed, for example, medical ICUs instead of surgical or cardiothoracic ICUs where many of the legacy sites were focused. Two, the specialty of the Principal Investigator, specifically a nephrologist as a primary lead for selecting patients to enroll compared to an intensivist or other specialist, which were the specialties of the legacy site PIs. And three, the efficiency of the administration to initiate a new study at their institution. Dr. Aslam identified these characteristics after his review and learnings from assessing the initial sites as critical to successful and timely enrollment. In addition to the acceleration in enrollment at existing new profile sites and the institutional interest in joining the study as we add new sites, we believe there are other tailwinds supporting the market potential of Nafamostat. These include, one, advancing a compassionate use IDE. As stated on our last call, we have been approached by multiple institutions and are discussing using Nafamostat under a compassionate use IDE for a specific patient population that does not do well with other available anticoagulants for continuous renal replacement therapy. Two, continued shortages of citrate and potential supply chain issues with heparin. Healthcare providers are inquiring about the timely availability of Nafamostat given the recurrent heparin and citrate shortages. 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 in 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, and good afternoon to all. The acceleration in enrollment rate is exciting, and the new site engagement has been excellent as we shift away from the legacy sites to the new target profile sites previously described. We now have a total of seven sites that are actively screening. We have four legacy or old profile sites and three new target profile sites. These new sites have enrolled over 90% of the 15 patients to date. Importantly, the enrollment rate from these three new sites has been impressive and has validated our strategy of changing the target site profile. These sites have enrolled nine patients over the last six weeks, which was in line with our enrollment forecast. We terminated one legacy site because of its low screening numbers and failure to enroll any subjects. We expect to add six new sites over the course of the third quarter, all with the new profile. A couple of them were recently activated and will begin enrolling shortly. This gives me confidence that the relaunch of the NEPHRO study with significant protocol changes and a pivot to the sites with a different profile has been successful. We expect the study enrollment rate to accelerate further with the addition of the six new sites with a similar profile over the current quarter, as these are large academic institutions with CRRT volumes higher than the legacy sites. As we mentioned on our last call, we continue to advance our compassionate use IDE with a large institution. Physicians at this institution see an immediate and compelling need for a subset of patients with contraindications to currently available anticoagulants and need an alternative. We are in the process of submitting a compassionate use IDE to the FDA. This is an opportunity to provide an alternative to these patients who cannot receive the currently available anticoagulants and, as a result, clot their CRRT circuits frequently. We do not have a timeline finalized, but we wanted to share this information as this was not the first such request we have had. It is evident that the current anticoagulants for CRRT are not ideal products, and there is no FDA-approved regional anticoagulant on the market. We will provide more information on the progress of this compassionate use IDE submission. 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 three 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 help minimize study execution risk. 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. Lastly, while we know there is 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. As you heard from Dr. Aslam, there is a clear need for an FDA-approved regional anticoagulant. I'll now hand the call over to Raffi for a financial update. Thank you, Vince. We continue to focus on our efficiency while accelerating the enrollment in our clinical study. Accordingly, we are reducing the previously communicated 2025 expected cash operating expense guidance to now be in the range of $16 million- $17 million, which includes the estimated expenses related to executing and targeting completion of the NEPHRO CRRT registrational trial by the end of the year. This is a reduction from the $17 million- $19 million range provided last quarter. Our cash operating expenses, or combined R&D and SG&A expenses for the second quarter of 2025, totaled $3.7 million compared to $4.3 million for the second quarter of 2024. Excluding non-cash stock-based compensation expense, these amounts were $3.5 million for the second quarter of 2025 compared to $4 million for the second quarter of 2024. The decrease in cash operating expenses in the second quarter of 2025 was primarily due to reductions in personnel expense and other general and administrative expenses. Our cash balance at June 30, 2025, was $6.8 million, including the proceeds from the first tranche of financing that closed on April 2. As a reminder, the financing was structured in three equal tranches, with the first tranche received at the initial closing and the two additional tranches committed upon achieving an enrollment of 17 patients and 35 patients, and with the stock trading above $0.73 per share following the announcement of each milestone. The expected proceeds from the closing of the two additional tranches, combined with the $6.8 million in cash at June 30, 2025, should support the company through the completion of the study anticipated by the end of the year. I'll now turn the call back to Vince. Thank you, Raffi. I'd like to open the line for any questions you might have. Operator? Thank you. Ladies and gentlemen, we'll now begin the question and answer session. Should you have a question, please press the star followed by the number one on your touch-tone phone. You will hear a prompt that your hand has been raised. Should you wish to decline from the polling process, please press the star followed by the number two. If you are using a speakerphone, please lift the handset before pressing any keys. One moment, please, for your first question. Your first question is from Ed Arce from WestPark Capital. Please go ahead. Hi, guys. Hope all is well and congrats on the progress with NEPHRO enrollment as well as the expense run rate. One major question and perhaps a follow-up. Just trying to get a better sense for, you know, given all the detail that you've provided now on the acceleration with these new profile sites, I just wanted to get a better sense for the acceleration that you expect to get to the 70 enrollment target by year-end, given that the last six weeks saw nine patients enrolled. Maybe just talk through the kind of arc that you're expecting through the remainder of the third quarter and into the fourth quarter. Thanks. Yeah, hey, this is Vince. Congratulations to you on your new position and welcome to the call. Thank you. I can help answer that. The rates of enrollment are significantly increasing, obviously, with the new sites enrolling at the same rate. Besides the fact that they are bigger in many cases, the newest sites, if you do the math, you look at the nine sites that are going to come on board within the next, call it, month and a half with our target profile. For an average of four months, September through December, we need a total of 55 patients. That's about one and a half patients per site per month. Our current run rate in just the last six weeks is higher than that. We're not seeing an arc or change to the run rate. As a matter of fact, it'll be a little bit lower on a per-site basis. The key is just getting these sites up and running. We've had two, as Dr. Aslam mentioned, of the next six with the new profile just come on board as of really yesterday, and their enrollment should start here shortly. Even without any enrollment through the balance of August, if we just assume everyone's on in September and starts enrolling, it'll be a flat run rate to what we've seen historically with these three new profile sites. We're not talking about an acceleration on a per-site basis, although that might happen. We're just talking about producing what they already are. Okay, great. That's helpful. Just wondering, you know, you mentioned this program where you're providing the product for sites that would like to try it, as you mentioned, given all the issues, especially now with the use and provisioning of heparin and citrate. Is there any opportunity, given their use, I would assume this is more than one site or facility, to leverage the data that they have, perhaps not for approval, but perhaps for future publication and to buttress commercial uptake? Yeah, I'll start with, it's an excellent question on the background of it. Dr. Aslam can certainly comment about why these sites, one in particular that we're moving down this path with fairly rapidly, is important and the requirements to actually capture data with compassionate use. While we've been at a number of different CRRT meetings over the course of last year and up to date this year, we continuously get approached by experts in the field at certain institutions whose patient profiles might be unique to their particular situation. While we can't satisfy everyone for compassionate use, there are one or two that we are heading down this path with in a fairly aggressive fashion based off of their ability to handle the requirements on their side because there are requirements on their side. The fact that their patient population is unique, meaning that it doesn't really overlap what we're doing in our current study. Dr. Aslam, I'll turn it over to you about what those types of patient profiles might look like at these institutions, why these people are requesting Nafamostat, and the requirements they might have regarding data capture, et cetera. Absolutely. Thanks, Vince. Congratulations, Ed. You're absolutely right. The data that we collect from these patients, although this will not be part of our efficacy data set, our larger data set that will contain safety data from every patient who ever got exposed to Nafamostat, this data set will be part of our submission for safety reasons. Obviously, this will be used as a publication to highlight that in patients who currently are not suitable or eligible to receive either heparin or citrate, they can actually safely and effectively receive Nafamostat for CRRT anticoagulation. These patients that we are providing compassionate use Nafamostat are patients who get chemotherapy, and as a result, their bone marrows are severely compromised. They have very low platelet counts, and that contraindicates the use of heparin. Because of low white blood cell count, these patients also get infected and go into sepsis and can end up having liver dysfunction, which contraindicates the use of citrate. These sites are really struggling with these patients because they cannot give them two of the commonly used agents on the market right now, one obviously citrate being of liver use. They clot very, very frequently because cancer increases your risk of blood clotting. This is a very specific patient population, which cannot be captured in our clinical study at this point, but it is a big unmet need in that population. The data that we use there will be very helpful for our commercial needs as we get through the approval of Nafamostat. Does that answer your question, Ed? Yeah, that's helpful color. I appreciate that. Again, congrats on the progress. Thank you. Your next question is from James Molloy from Alliance Global Partners. Please go ahead. Hey, guys. Thanks. I was wondering if you could walk through the heparin and citrate shortages you guys mentioned earlier in the call. What is the status on that? How long has that been going on for? What do you think? What is the expectation for that to resolve? On the second tranche, when you hit 17, does the fact that it looks like a long road to go to get to $0.73 from here preclude that cash coming in, or do you think investors will waive that requirement? Yeah, good questions, James. I'll start on the first one with the supply chain issues that we've continued to hear about or watch and observe with heparin and citrate. Heparin is episodic. There's been a well-documented set of historical challenges with the supply chain there, and they continue to happen each year at different periods of time. The dependency on it becomes difficult because that supply chain isn't always well supplied. Citrate, we often get, we've had a lot this year, sites telling us they're running low or running out. I can't tell you the reasons for that particular shortage. Maybe manufacturing issues at certain plants, as well as other maybe supply chain issues. We know citrate's used not just for CRRT – it's used in other areas like blood banks, et cetera. There's demand for the product in and outside of CRRT. When you combine the both, each year that we've been involved with this project or this disease state, this therapeutic area, we continue to hear challenges with both. Sometimes they are fixed faster than others. I think the takeaway is that the users of these products for CRRT are always on edge about the supply that they'll have and if it'll be predictable or not. I think the second question was related to the financings. Raffi? Yeah, hey, James. We will clearly need capital to get to the PMA filing. The question about the two conditions that are obligations for the investors to fund are obviously the 17 and 35 patients, and then the stock price. We will see, right? We will see what happens after we attend or announce, I should say, the enrollment of the patients at 17, which should be coming here pretty shortly. What we do know is the investors do have the right to waive those. When we are in discussions with them, the overwhelming majority, we are really just focused on the 17-patient milestone and less so on the stock price. We will have to certainly have discussions with them if we do not achieve that $0.73. But they have the right to waive, and the interest really is focused on the milestone of the 17 patients because that was their most, that is what they really wanted us to see hit, to see if we can get that acceleration and the momentum that we now have. Understood. Kudos to Dr. Aslam for rejiggering the trial design and getting it back moving. Absolutely. This plan is coming to fruition. Thank you. Actually, while I get you, Raffi, just a quick question. What are the main components in the OpEx that drives down sort of the numbers? Looking at, if you just run the numbers that you had in the current quarter out, you're well below that $16 million, $17 million OpEx for the year. Do we anticipate a bump here in the second half? We do, yes. It'll bump up. Maybe we're being a little conservative, but it'll bump up because of the enrollment that's increasing now, has just recently increased, and is increasing as we head into the third and the fourth quarter. Got it. Thank you very much. Thanks, James. Your next question is from Nazibur Rahman from Maxim Group. Please go ahead. Hi, everyone. Glad we're in progress, and thanks for taking my questions. I only have a couple. The first one is on the new site initiations. Previously, you had quite a bit of logistical administrative issues on the site initiations. At this point, what kind of gives you confidence that you can have the new site up and running and rolling by the end of the third quarter to reach the end of 2025 completion? That's my first question. Yeah, no, I'll turn that over to Shakil because Shakil has done an outstanding job on vetting these institutions before moving into the contracting process. Shakil, maybe you can comment on that vetting process and what we've actually seen in performance of the administrative advancements. Absolutely. Thank you, Naz. Yes, when we were looking at new sites, one of the criteria we used was how quickly they can get their sites up and running. There is some historical data on those sites on their paperwork timelines. In addition to that, some of these sites, which were very, very comforting for us to know, had their internal benchmarks on how long it takes for them to actually, from start initiation of the paperwork to open for enrollment. Some of these sites had that benchmark at 90 days or 120 days. Three to four months was their own timeline, and they got reprimanded or penalized if they were foregoing outside of that timeline. That was very helpful for some of these sites. In addition, as Vince mentioned, we had improved some of our internal processes, how we managed the contracting process with them. We were very, very, very hands-on, and we turned things around very, very quickly. We got external resources groups to help us with all the paperwork. The reality is that we are very close to activating all sites by the end of this quarter. Every day, we are reaching out to start these initiation visits, get the dates for them. We have a very high level of confidence by the end of this quarter we will have all nine sites with our target profile up and running and enrolling. Some of these new sites are coming on board. They are really large volume sites. Yes, as Vince mentioned, the rate of enrollment may not accelerate in our current sites, although I think with the time as we get more comfortable with the patients and the clinical trials, it will likely accelerate a bit. Some of the new sites are coming in. Their rate is, I expect, to be much higher than the current new target profile sites. I think, Naz, what I'll add to that is it's important. None of these sites are starting from scratch right now. I want to emphasize what Shakil said. We're way down the path. As a matter of fact, of the next six sites with the new profile, two have already been activated as of last week and this week. They should start enrollment imminently here this month. That leaves us just with a balance of four more sites that we've already got CTA s agreed to, budgets agreed to. We get the SIV s scheduled, all here to get completed by the end of this quarter. We're not starting from scratch on any of these. If anything, we're on the, yeah, we're the last leg of the sprint. Got it. That was very helpful. My next question is kind of on patient enrollment. Once again, obviously, you've cross-corrected for some of the sites, but you have basically been running the study for just a little over a year at this point. I guess what has been the trepidation from the different sites, or patients from enrolling in the trial? Has it been the fact that a lot of these critical patients and either investigators have been concerned about enrolling them, or the patients, they didn't want to agree to enroll in the trial or the families? The most recent initiations or the most recent enrollments, have they more been a function of just the new sites have been more effective at understanding Nafamostat, or has it been more of a function of the fact that there's been these shortages? These investigators decided, okay, why not enroll into this effort study? Shakil, I'll start with the first part of this, and then maybe talk about the characteristics of the new sites. Supply really hasn't been an issue. Look, the original sites that we inherited when we assumed this program from the previous owner of the company, those original sites were sites that that company had a relationship with based off of their previous development program in the ICU. That product was a vasopressor. That product utilized PIs that were typically intensivists. That study typically with those intensivists pulled patients from surgical ICUs, which aren't really the patient populations we'll see for CRRT. These were very good sites, very good investigators, very good people for that disease state of vasopressor. I believe they felt because they were intensivists in an ICU, they would be an easy cross to a CRRT study. That was basically every site that we inherited. Dr. Aslam, when he came in, evaluated the sites and quickly, based off his experience as a nephrologist and involvement with CRRT, diagnosed the fact that while these are great institutions and very talented PIs in medical centers, for a study in CRRT, it would need to shift the specialties with nephrology who were pulling patients from the medical ICU. The original sites, while they were inherited, really weren't the right mass for this study moving forward. With Dr. Aslam's expertise intervening, he changed that profile. Now, Dr. Aslam, you can comment on why this acceleration lately. Maybe you can talk about other metrics you're seeing and why you feel the patient enrollment is occurring. Absolutely. Thanks, Vince. As Vince mentioned, our previous sites were great sites, but they were really not very productive for this particular indication, primarily because the patient population they were screening had a lot of cardiac failure, heart failure, and they were post-operative cardiac surgery patients. Most of those patients who had kidney failure also had heart failure and were being treated with heparin for ECMO and other extracorporeal therapies. They had systemic heparin for other indications. That was our biggest challenge, that there were really very few patients consenting per month. Very early, you look at those patients and they were not qualifying. Secondly, with my bias, perhaps, nephrologists feel very close to CRRT as opposed to intensivists because intensivists are generally pulmonary critical care people and they have a focus on lungs and oxygenation and ventilator. Even when they run CRRT, the CRRT is like a little bit of, you know, perhaps side business for them. CRRT is not their main focus. Whereas nephrologists, that's the only reason they're seeing those patients, just to manage CRRT. They're very close to this lack of any proper anticoagulants in CRRT use, and they deal with the complications of CRRT anticoagulation all the time. Either patients are bleeding or the circuits are clotting and they have to send their nurses to swap those circuits three to four times a day. That's my bias, that if we have these nephrologists, they will take more ownership of the study and enroll these patients because they are really, really desperate to get some new agent and choices in anticoagulant therapy. Both of them have worked out. We are looking at, over the last six weeks or so, our consent rates, looking at patients who are passing the first screening, has really significantly increased, almost skyrocketed. Many of these patients are now being enrolled in the study. I think it really comes down to how passionate the PIs are to get into this indication and get their hands and access to Nafamostat, and also if they have the right patient to choose from. I think that's what's happening with our new sites and new PIs. I do not believe that this is really due to, although there is, if you go to the FDA's website, they are listing heparin as still one of the drugs which are in short supply because there's always problems with the raw materials, manufacturing, and short half-life and shelf life and all that. That's still ongoing. I don't think that's what's causing a spike or acceleration in our enrollment. I think it really is the interest and enthusiasm by the PIs and the sites. Got it. That was very helpful. Thank you, and congrats on the part. Sure. Thanks, Naz. Ladies and gentlemen, as a reminder, should you have any questions, please press the star key followed by the number one. We will pause a moment for further questions. There are no further questions at this time. Please proceed with closing remarks. Thanks, Andrew. Again, thank you for joining our second quarter earnings call. As you can tell, we're very excited about the progress we've made, all with the goal of completing the NEPHRO trial this year and in 2025 with an FDA approval of Niyad in 2026. We'll continue to manage our cash prudently, and we look forward to providing additional updates on our progress. That concludes our call, and thank you for your interest in our company. Have a great day. Ladies and gentlemen, this concludes your conference call for today. We thank you for participating and ask that you please disconnect your lines.