Welcome to the Talphera Fourth Quarter and Full Year 2024 Financial Results Conference Call. This call is being webcast live via the events page of the investor section of Talphera's website, www.talphera.com. You may listen to or replay to 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. Please go ahead. Thank you for joining us on the call today. Today we announced our fourth quarter and full year 2024 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 discussion of the risks associated with such forward-looking statements. These documents can also be found on our website within the investor section. I'll now hand the call over. Thanks, Raffi. Good afternoon, and thank you to everyone joining our call today. We made strong progress in 2024 and anticipate furthering that progress in 2025 with the expectation that our NEPHRO CRRT study should be completed by the end of the year. We have a number of important updates to share with you today, all of which support the timely development of Niyad and the planned submission of the PMA in the first quarter of next year. I'll first provide an overview and then hand it over to Dr. Aslam to provide additional details on all the improvements being made in the study and with the clinical sites. First, as announced earlier today, I'm pleased to highlight an agreement with existing and new investors for a private placement investment of up to $14.8 million in gross proceeds should all milestones be achieved. I want to thank Nantahala Capital and Rosalind Advisors, who remain committed investors supporting the company. This financing should provide us capital to a potential completion of the study by the end of the year. Raffi will provide additional details on the financing later in the call. I'll now provide key updates we've made to the NEPHRO CRRT study. As a reminder, nafamostat has been approved and used for multiple indications in Japan and South Korea, including as an anticoagulant for the extracorporeal circuit for well over 30 years. This extensive clinical use, demonstrating its safety and efficacy in those territories, as well as multiple studies performed outside the U.S., we believe will be corroborated by the data being produced from the NEPHRO CRRT clinical study. If approved, Niyad would become the only FDA-approved regional anticoagulant for use during continuous renal replacement therapy. We believe this profile would be impactful given the many disadvantages of the currently used products: heparin, which is systemic in nature, and citrate, which is being used off-label. Importantly, we announced that the FDA approved our request for a reduction in the size of the NEPHRO trial from 166 patients down to 70. Even with this significant study size reduction to 70 patients, the primary endpoint remains powered at 90%. This was a major step forward for the timely development of Niyad, and we're thankful the FDA continues to meet or exceed the statutory timelines in responding to our requests. The FDA's responsiveness has been a key benefit of Niyad's Breakthrough Designation. During the same meeting held with the FDA in January, where we discussed the study size reduction, we also requested and the FDA approved two major protocol changes to the inclusion/exclusion criteria. At a high level, one, we're now allowed to enroll patients that have been on CRRT for over 48 hours, and two, the inclusion criteria requiring documentation of heparin intolerance has been removed for institutions that do not use heparin as part of their protocol, which, importantly, is applicable to six of our seven current sites. All of these changes to the NEPHRO study are crucial modifications that support our projected timeline to complete the study by the end of the year. Dr. Aslam will provide more details on what these changes mean and how we believe they'll impact enrollment. In parallel to our work on the regulatory front, making changes to the study protocol, we've also been focused on adding new clinical study sites. Not only is the number of sites important, but also the site profile. Specifically, again, one, the type of intensive care unit where the study will be performed, for example, medical ICUs instead of surgical or cardiothoracic ICUs. 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. Three, the efficiency of the administration to initiate a new study at their institution. Dr. Aslam identified these site characteristics after his review and learnings from assessing the existing sites as critical to successful and timely enrollment. At the end of 2024, we had five enrollment-ready sites, four of which were inherited relationships from our acquisition of Lowell Therapeutics. Upon Dr. Aslam's review, these do not meet our ideal site profile moving forward. The fifth site identified by Talphera meets our target site profile and has enrolled five of the six patients who have completed the study. The principal investigator at this institution is a nephrologist and is enrolling patients from the medical ICU. We added three new sites in the first quarter, two of which are just now starting to screen patients for a total of eight sites that are now enrollment-ready. We expect to bring five additional sites on by mid-year. Before I turn the call over to Shakil, I want to reiterate our belief that the three critical risk elements, clinical, regulatory, and commercial, for the NEPHRO 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 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'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. In fact, we recently attended the 30th annual AKI and CRRT meeting in San Diego, where a number of physicians asked us if they could have access to nafamostat through a compassionate use program where neither heparin nor citrate meet their needs. I'll turn the call over to Dr. Aslam, who was named as Talphera's Chief Medical Officer in October last year. He's been critical in instituting the major changes to the protocol as well as the site selection process. Dr. Aslam? Thank you, Vince. We have been busy making changes to the study protocol as well as evaluating the characteristics of clinical sites to improve the study enrollment. I'm happy to say, as Vince highlighted, we have had success on both fronts as the FDA has approved the changes we requested. We now better understand the profile of an ideal clinical site for our registration trial. The three newest sites have our target profile with the highest CRRT volumes, and two of these sites are just beginning to screen patients. This brings our current total enrollment-ready sites to eight, seven of which are screening today. Before providing more information on the study sites, I would like to elaborate on the reasons we believe the FDA agreed with our request to significantly reduce the study size from 166 patients to 70. With 166 patients, the study was overpowered with over 99% power to meet the primary endpoint. Despite a significant size reduction, it's important to note that even with 70 patients, the study has at least 90% power to meet the primary endpoint. You are probably wondering why this study was so overpowered in the first place. It is our understanding that Lowell Therapeutics proposed a study size of 166 patients to assure the FDA that a sufficient number of patients would be exposed to Niyad from a safety perspective. In our meeting with the FDA in January, we presented the safety data from the existing large safety data sets and the published literature on the real-world use of nafamostat across multiple indications in Japan and South Korea for over 30 years. We were able to assure the FDA that nafamostat had a well-characterized safety and a favorable benefit-risk profile based on over three decades of use across multiple indications, including CRRT. Based on the screening data from our active study sites and input from our PIs, we identified two eligibility criteria which were responsible for several screen failures and could be modified without affecting the study outcome. The first was an exclusion criterion, which excluded patients from the study if they had been on CRRT for more than 48 hours. The sites informed us that many patients who were started on CRRT late Friday or over the weekend were no longer eligible by the time the study team returned on Monday. The FDA allowed us to remove this exclusion criterion, agreeing with our rationale that time on CRRT before study enrollment had no impact on the primary endpoint. Fifteen patients were excluded from the study because of this criterion. We believe this protocol change will be impactful to the enrollment speed going forward. The second change we requested was the inclusion criterion that required the sites to document either intolerance or contraindication to heparin. We found this requirement irrelevant and restrictive because many institutions, including most of our study sites, do not use heparin during CRRT. The FDA agreed to remove this requirement for these sites. Ten patients were excluded from the study because of this criterion. As a note, only one of our current sites uses heparin for anticoagulation during CRRT, and this dissatisfaction with heparin is universal amongst the physicians we speak with. In addition to these protocol changes, we analyzed the screening data to understand the study site profile that would predict better patient enrollment. We identified an ideal site profile based on the type of ICU, the specialty of the principal investigator, and the time to complete the startup paperwork. The startup activities were the main bottleneck in site activation previously. As part of our strategic review, we identified that nephrologist-led sites were an important differentiator since nephrologists effectively decide on CRRT use and study enrollment. The other key factor was the type of ICU. We determined that medical ICUs were the most appropriate type of ICU for study enrollment. In contrast, our initial less productive sites relied on the cardiothoracic and general surgical ICUs, where most patients on CRRT received systemic heparin for other indications or had active bleeding. Exclusion criteria for NEPHRO enrollment. The one initial site that has been the most productive has a nephrologist as the PI, with all enrolled patients coming from the medical ICU. As a result, our new and future sites target a nephrologist as the PI and draw patients primarily from the medical ICU. This includes the two new sites that just began screening and the six additional sites expected to be activated in the first half of 2025, all of which are similar in profile to our current highest enrolling site, but with higher CRRT volumes. Our most productive current site has about 20 CRRT patients per month, while the three new enrollment-ready sites range historically between 90-100 CRRT patients per month, with many of the additional sites planned by mid-year having even higher monthly CRRT volumes. Because of our selection of sites with a quick administrative timeline, we have experienced a much shorter time for their activation. For example, our most recent site took us less than four months to activate compared to over a year for some of the initial sites. In summary, we expect to have 13 sites enrollment-ready for mid-year, and we continue to pursue additional sites up to the limit of 14. With that, I'll turn the call over to Vince. Thank you, Dr. Aslam. I'd like to highlight Dr. Aslam's expertise in CRRT and experience in both drug and device trials during his accomplished career that have facilitated these enhancements to the program. I'll hand the call over to Raffi for a financial update. Thanks, Vince. As mentioned, we have been highly focused on delivering a completed nephrology study by the end of this year. Accordingly, we have reduced our operating expenses to reflect this objective. Also, as announced earlier today, we signed agreements with investors regarding private placement financing with existing and new fundamental investors led by Nantahala Capital and Rosalind Advisors, who remain committed and supportive shareholders. The amount of the financing is expected to provide capital to support the targeted completion of the study by the end of 2025. The financing was structured in three equal tranches of $4.925 million, with the first tranche received at the initial closing expected shortly here in April, and the two additional tranches based on achieving an enrollment of 17 patients and 35 patients, and with the stock trading above $0.73 per share. In total, the $14.8 million commitment is expected to be achieved later this year, as we expect acceleration in enrollment rates given all the changes made to the nephrology CRRT study and the new sites that are coming online. As mentioned, this financing, combined with the $8.9 million in cash at December 31, 2024, supports the completion of the study anticipated by the end of the year. Our combined R&D and SG&A expenses for the fourth quarter of 2024 totaled $3 million, compared to $4.6 million for the fourth quarter of 2023. Excluding non-cash stock-based compensation expense, these amounts were $2.8 million for the fourth quarter of 2024, compared to $4.3 million for the fourth quarter of 2023. The decrease in combined R&D and SG&A expenses in the fourth quarter of 2024 was primarily due to reductions in personnel expense and other general and administrative expenses. We expect cash operating expenses, or SG&A and R&D excluding stock-based compensation, to be in the range of $18-$19 million in 2025. I'll now turn the call back to you, Vince. Thank you, Raffi. Before we open the line for questions, I reiterate that we've made significant improvements in the study design in concert with the FDA. We now have an improved trial design with the right types of ICUs as operating sites. I look forward to sharing our progress on the Niyad registrational trial over the course of the year. I would like to open the line up 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 HC Wainwright. Please go ahead. Hi, good afternoon, everyone. This is Thomas. We have asking a couple of questions for Ed. Thank you so much for the kind of questions. First, regarding the changes in the inclusion criteria that was formally approved now by the FDA, it sounds like it makes a lot of sense, but can you discuss what was the original line of thoughts for excluding these patients in the previous protocol? We'll have that over to Shakil. Again, the question is changes in the inclusion criteria. What were the original thoughts on—I just want to be sure, Thomas—why that protocol was written originally as it was with Lowell? Yes. Yes. That's what I meant. Thank you. Okay. Shakil, you want to answer that? That's relative to the heparin and relative to the 48 hours on CRRT and why they were originally included that way. Sure. Since I was not part of the initial protocol development, I can only guess the reason that makes medical sense from my point of view. Forty-eight hours restriction perhaps was done if you were to look at some important clinical endpoint. My thinking on this was since we are not really looking at the clinical endpoint as a primary efficacy endpoint, time on CRRT had no impact on how somebody's going to respond to Niyad. That is why we changed it. My understanding is that because of impact, that longer duration on CRRT, for example, could have patients who are longer on CRRT, they may take longer time to recover their kidney function, or they may have higher mortality because they are not recovering their kidney quick enough. That is my guess that that was the reason. The second, in terms of contraindication to use of heparin, FDA's position has been that heparin is FDA-approved for this indication, and it is and perhaps should be used or at least offered to every patient who starts on CRRT. As we approached many of these sites and activated these sites, we did not find that to be the case. What we found was most of the sites were not offering heparin at all to their patients. As a result, it did not really make any sense for us to require these sites to document contraindication to use of heparin. FDA, as Vince mentioned, also agreed to remove that restriction. Does that answer your questions? Yes. Thank you so much for the clarification. Both updated endpoints make a lot of sense. Shakil, can I ask you also to quickly elaborate on why have these institutions decided not to use heparin for the most part? In your clinical experience and discussion with these sites, what has been their main rationale for those on the phone today to understand why they're not using the heparin even though it's indicated for this condition? Right. There are many reasons. I think overall, most institutions do not feel that the risks from heparin justify the use of heparin routinely in all patients. Heparin is kind of difficult to use in this patient population. Number one, it has a long half-life, approximately two to three hours, and the half-life can change within the same patient. That makes it very difficult to use. Titration of heparin is quite difficult. It takes a while before you titrate to the target therapeutic activated prothrombin time, which is the marker that we use in the clinic. I think the most important thing perhaps is that it is a systemic anticoagulant. You are trying to prevent clotting in a circuit which is outside the body. There really is no justification to expose the whole patient to anticoagulation because these patients are very high risk of bleeding from many organs. This increases their risk of systemic bleeding. Those are, I think, my top few reasons why I never liked heparin and most physicians don't. Thanks, Shakil. Got it. Thank you so much. Perhaps a couple of questions regarding the private placement that was announced today. Just wonder the second and third milestones tied to the patient enrollment, 17 and 35 patients respectively. Is there any time limit tied to these achievements of the milestones? No, there are not. Okay. Just to be clear, the funding will trigger as soon as both the number of patients being enrolled and also the share price hitting the five-day average. That's correct. And some normal closing conditions. Yes, that is correct. Okay. Okay. And then one final question also on the private placement. Just wonder if you have disclosed which member of the management team participated and then also what's the amount. Yeah. I mean, we didn't, but it's Vince. That would be me, Thomas. The member of management. You will see the amounts, I suspect, with the filing, Mark. Right. Thank you so much for taking our questions again. Looking forward to hearing progress for the study throughout the year. Thanks, Thomas. The next question is from Jim Molloy from Alliance Global Partners. Please go ahead. Hey, guys. It's Matt on for Jim. Congrats on the quarter and the private placement this morning. First question, I wanted to follow up on the private placement for those milestones at 17 and 35 patients. Have you guided at all to when you might see that come in, 17, maybe next quarter? Is that a fair assumption? Yeah, we haven't, but yeah, we're expecting kind of mid-year for the first one and the third quarter or so for the second one. Okay. Gotcha. As far as the existing sites, do you have any plans to shift the PIs to nephrologists and maybe make those sites look a little bit more like the highest enrolling? Is that a possibility? Yeah. I'm going to turn that one over to Shakil and just preface it by Shakil. Can you also include in your answer, as we continue to find highly productive sites that really meet our criteria with a high number of CRRT patients, one, would you ever consider deactivating the unproductive sites? Two, especially with the demand that we're starting to see to get into the trial, and two, for those sites that we have been very close with, which is all of them, the work you're doing to potentially shift those PIs over to the specialty that most fit our needs? Absolutely. Yes, that is the case. We are in discussions with these PIs to see if either they can shift the primary responsibility to a nephrologist or they can broaden their patient population by including medical ICUs. In terms of closing any of the sites that are not being productive, I think that's possible. Once we recognize or are close to getting the 14 sites up and running, and by then, if any of these sites have not performed, we would like to swap them for better-performing sites. Right now, we have a lot of interest in joining this study, and we are activating those sites as quickly as we can. I think an important additional color I'll add on that is these sites were the ones that really brought to our attention the challenges that they were experiencing with the protocol and the two particular exclusion criteria. Kudos to them, even though they haven't been as productive on their engagement enthusiasm for the study. I think you have to remember these are very prominent sites around the country related to the reputation of the institutions. The PIs are extraordinary, but these are the same PIs that worked with the founding company Lowell prior to that La Jolla on Giapreza, which is a vasopressor. It starts to make a lot of sense, the comfort level that was with these PIs as intensivists in the ICUs they were pulling from being cardiothoracic and/or surgical. I think that Lowell/La Jolla leaned on those relationships, extraordinary talents, but might not be the best fit, as Dr. Aslam has explained for many reasons, for this particular study. Got it. Okay. Thank you for the color. I appreciate that. Lastly, do you have any clues yet to the enrollment rate with this new revised criteria? Or should we assume those six patients that have completed the study are the six patients fully that have been enrolled as of right now? Yeah. Yeah. Those are the original six. Again, I'll reiterate what we said in the script, that five of those six are coming from one of the institutions that we had identified to add into the study that really met the criteria that Dr. Aslam has framed out moving forward. Got it. Any clues to the enrollment rate going forward based on these new criteria that have been agreed upon by the FDA, or is it too early to tell? No, I think it's too early to tell. Again, I'll reiterate what we said, that we had 25 patients excluded since the enrollment started in the trial for these two criteria, 10 on one and 15 on another. I think it was 15 on the 48 hours, 10 on the heparin exclusion. You can see a number of patients were screened out from these original sites based off of those two criteria. We expect those original sites to have some production moving forward, but we really expect that change in the criteria to more heavily affect these higher potential sites. Remember, as Dr. Aslam said, our most productive site to date is averaging about 20 CRRT patients per month. With the sites that Dr. Aslam just activated and just started screening, they're averaging historically—now, there's peaks and troughs—but on average, between 90-100 CRRT patients per month. You see the magnitude of potential penetration of that population. The additional sites Dr. Aslam has engaged that we planned on having by mid-year, some of those are even larger than those sites that are averaging 90-100 CRRT patients per month. It starts exponentially rising, the pool of patients we can pull from. That should work in concert with the inclusion/exclusion criteria the FDA just granted us. All right. Great. Thanks for the color, guys. Congrats on the progress. Thanks for taking my questions. Thanks, Matt. The next question is from Naz Rahman from Maxim Group. Please go ahead. Hi everyone. Thanks for taking my question. Congrats on the progress. I guess in context of everything that's happened, what ultimately gives you confidence that you could have the phase three completed and the data by the end of the year? You're saying that it still takes four months, give or take, to initiate a site, which is faster than before, but that still seems like it would take a while to initiate additional screening and initiate an additional site, which kind of takes us into mid-year. All that considered, what gives you confidence you could have the data by the end of the year? Yeah. I can start on the answer to that question. Shakil, maybe you can add some additional color. Of our original seven sites you mentioned, we have two more we plan on adding here actually in April. It is very early on. It is not an additional four months from here. The balance of the sites to get us to the 13 that we are currently engaged with will be by mid-year. It is not four months starting from now. We are already well into it with two of the sites and then fairly far along with the additional sites to get us to the 13 by mid-year. When you just do the math on that, Naz, I mean, you are looking at 13 sites with a balance of 64 patients left to enroll. One to one and a half patients per month with exponentially larger populations, as I just outlined. I think from an engagement standpoint or other, maybe Shakil, you can add some color on the new sites, the engagement, the teams, and the profile that we have kind of already reiterated. Oh, did we lose Shakil? Shakil, you might be muted. There you are. There you are. No. Thank you. Yeah. The biggest change that we are seeing is the level of engagement that we have from the nephrologists. Nephrologists deal with this issue of anticoagulating these patients and how do you anticoagulate just the circuit and not the patient. They deal with this issue every single time they start a patient on CRRT. This is an issue which really is very, very close to them. The biggest difference that I see is these nephrologists, they are helping us with the paperwork. They want nafamostat available for their patients. Most of them do not use heparin. Most of them do not use citrate. They want an option so that they do not have to throw away these circuits every six to eight hours in some of these patients. That level of engagement is what gives me a lot of confidence that they are actually going to go and look for those patients. They know that this is not a big study. If they can help us, we can actually get this product in their hand next year. I think that is the most confidence-inspiring part of these new sites that I'm seeing. Vince, you've been talking to some of those people as well. I don't know how you felt about their degree of involvement and how enthusiastic they are. Yeah. I think it's very similar to Dr. Aslam. The engagement, not that the engagement from the previous ones wasn't high, but the nephrologists make a big difference because this is their world every day that they're in the hospital doing the CRRT. Got it. Thank you. That was very helpful. Thanks, Naz. There are no further questions at this time. Please proceed with closing remarks. Okay. Again, thank you for joining our 4Q earnings call. We are excited about the study modifications to address enrollment and the continued alignment with the FDA in particular, with a goal of completing the NEPHRO trial in 2025 and an FDA approval of Niyad in 2026. We will remain disciplined on our cash management, and we look forward to providing additional updates on our progress. Thank you for all your interest, and that concludes our call. Ladies and gentlemen, this concludes your conference call for today. We thank you for participating. I ask that you please disconnect your lines.