CorMedix Inc. (CRMD) Earnings Call Transcript & Summary

Hello, and welcome. My name is Matt David, Executive Vice President and Chief Business Officer of CorMedix. Thank you for joining us today. Both here in person and virtually. We appreciate the time and interest of our analysts and investor community, and we are pleased to have you with us for today's Analyst Day. Today's session is intended to provide a deeper look into our company our strategy, our portfolio and the long-term opportunities we see ahead. Over the course of the afternoon, you will hear directly from members of our leadership team, who will share updates on our commercial execution, pipeline progress and key operational priorities. We are also pleased to be joined by external experts who will provide additional perspective on the evolving market landscape and unmet needs within our therapeutic focus areas. As a public company, transparency and disciplined execution are central to how we operate. Our objective today is to give you a clear view of where we are, how we think about value creation and how we are positioning the business for sustainable growth. We also look forward to engaging in a thoughtful dialogue during the Q&A sessions later this afternoon. Before we begin, I would like to remind everyone that today's presentations will include forward-looking statements, which are subject to risks and uncertainties. Please refer to our SEC filings for a discussion of the factors that could cause actual results to differ materially. We do not undertake any obligation to update forward-looking statements beyond what is required by law. On behalf of our Board of Directors and our leadership team, I want to extend our sincere thanks for your continued engagement and support. Now it is my pleasure to turn things over to our Chairman and CEO, Joe Todisco, who will kick off this exciting event.

Everybody hear me okay? Okay. Well, thank you. And I am Joe Todisco, I'm the Chairman and CEO of CorMedix, and welcome to our 2026 Analyst and Investor Day. We do have a pretty ambitious agenda. We're going to try to move as quickly as possible through some of the background sections to leave a lot of time for the thought leader panels as well as Q&A at the end. Happy to be joined here today by my talented leadership team. In addition to myself, Liz Hurlburt, our Chief Operating Officer, will be presenting. I'd like to welcome 2 new additions to the CorMedix leadership team. Susan Blum joined us late last year as Chief Financial Officer; and Mike Sechler joined us a few weeks ago as Chief Commercial Officer. You've met Dr. Matt David, our Chief Business Officer and also happy to welcome Beth Segno Kauffman, our Chief Legal and Compliance Officer as well today. So 2025 was a record year for CorMedix. And during the heart of our TDAPA reimbursement for defend [indiscernible] in hemodialysis, we achieved just under $260 million in net sales and drove really strong cash flow throughout the year. We parlayed that success into the acquisition of Melinta Therapeutics, which in addition to providing about $140 million of revenue on a pro forma basis, really transformed us into a diversified specialty pharmaceutical company with a portfolio of commercial stage drugs and a pipeline that is now positioned to create long-term sustainable value. So 2026 is now a transitional year for CorMedix. We focus on promoting our existing commercial stage assets, but we are also preparing for upcoming potential future launches from the pipeline. Just a quick look at our overall commercial portfolio post acquisition of Melinta. As you can see, almost all of the products are injectable drugs used in institutional setting of care which is really core to our business development strategy and where we are looking now to find synergy. Institutional settings would be areas such as hospitals, clinics, infusion centers, places where products are administered to a patient by a health care professional. Most of our current products are anti-infectives. But from an expansion standpoint, we are more focused on the setting of care than in a particular therapeutic area. So for the purpose of today, our goal is to provide significant depth education into 3 areas. The first is the opportunity for REZZAYO in its current treatment indication, but also for our pipeline, which I do believe is an overlooked future value driver. For REZZAYO specifically, there's an ongoing Phase III study in prophylaxis of invasive fungal disease in patients that are immune compromised. But there are also 2 ongoing Phase II studies in treatment, one for Pneumocystis, the other for [indiscernible]. For REZZAYO, I think it's important to understand that these studies are being run by our global development partner, Mundipharma, who is the current sponsor of those studies and currently is the NDA holder for REZZAYO in the U.S. We're also excited to provide more information in detail around our Phase III study for DefenCath in prevention of collapsing patients undergoing total parental nutrition. So just a quick look at our overall financial picture, which I do believe is stronger than perhaps the investment community currently appreciates. So we are sitting here today with approximately 0 net debt, about $150 million in cash, $150 million debt. We've guided 2026 EBITDA in the $100 million to $125 million range. And today, we sit here with a market cap that's approximately 5x that EBITDA guidance. As I mentioned, '26 is a transition year because of the change in our defensive reimbursement that will occur in July. But we do expect a meaningful rebound in defend cat in hemodialysis in 2027 compared to the back part of as more dollars are expected to be added into the dialysis bundle by CMS in '27. For that reason, we took the unusual step to provide longer-term financial guidance, specifically for DefenCath into 2027. Now I think if you look at this chart on the left, it visualizes a couple of things really well. First, the general durability of the momentum-based business, which is highly important to provide financial stability and I think really underscores kind of the rationale when we talk about the stability of the base business and the Melinta transaction. But what I also think you can kind of see is the atypical revenue curve that the TDAPA reimbursement structure, right, causes during a product launch, where you have this bolus of revenue coming during a 24-month period. Now over the last couple of weeks, I think we've spent quite a lot of time working to educate investors on how we plan to manage our post TDAPA customer contracts, why we believe we can maintain patient momentum from the back part of '26 into 2027 as well as our thoughts on the pending to TDAPA legislation that is before Congress. For the purposes of today, we're really here to focus on providing education for our other growth drivers. So to the extent there are TDAPA questions, I think I'd kindly ask that either you hold them for the very end of Q&A or perhaps even we can address one-on-one post meeting. Because we have 3 excellent panels of thought leaders here today, each to talk about these 3 different market opportunities REZZAYO for treatment, REZZAYO or the prophylaxis segment and DefenCath TPN, as you say, each of which has a sizable total addressable population. And with that, I'm happy to welcome Liz Hurlburt to come up and give a brief background on the market opportunity and overview for REZZAYO for its treatment indication.

Thanks, Joe. So it's my pleasure today to discuss our first lead asset, REZZAYO, or rezafungin. It's a next-generation echinocandin antifungal, which is FDA approved to treat candidemia and the more severe invasive candidiasis, or IC. Rezafungin has broad spectrum activity against [indiscernible], Aspergillus and Pneumocystis. REZZAYO is dosed weekly with a long-acting PK and front-loaded plasma drug concentration that provides treatment for 7 days versus daily dosing with the first-generation echinocandins. In STRIVE and restore the 2 NDA-enabling studies a favorable safety profile is consistently demonstrated. Unlike AZOLS, rezafungin has demonstrated no hepatotoxicity or clinically relevant drug-drug interactions.p Candidemia is simply the presence of Candida in the blood. Invasive candidiasis or IC is a deep-seated infection that may or may not be in the blood, but occurs when Candida impacts otherwise sterile organs like the heart, brain, abdomen or bones. The Centers for Disease Control recommend intravenous echinocandin therapy as the first line treatment for IC for at least 14 days after negative blood cultures and REZZAYO has unique properties that other [indiscernible] don't. In addition to once weekly dosing, utilizing REZZAYO eliminates the need for a patient to get a [ pICline ]. It could potentially allow for earlier discharge and demonstrates activity against azole-resistant Candida species. While REZZAYO launched in 2023, CorMedix sees significant opportunity now and in the future with the current indication for growth. Over the past 2 years, Melinta has made solid progress in hospital systems with formulary adoption and driving clinical interest, which is now translating into broader adoption and utilization. We see substantial growth drivers in the outpatient infusion center space, where more favorable reimbursement exists and the logistical challenges are minimized. In the past years, the emergence of Corus creates numerous challenges in treatment due to increasing azole resistance and the organisms ability to travel quickly in a health care setting. When we think about additional patient populations, those such as patients with intra-abdominal candidiasis a severe and often fatal type of infection without candidemia or those with the need for long-term therapy due to deep-seated infections, are perfect potentially for rezafungin. These opportunities combine the total addressable market of $250 million to $350 million. To share deeper insights on the treatment of candidemia and invasive candidiasis, it is my pleasure to introduce our first panel. Dr. Neil Clancy, Professor of Medicine at the University of Pittsburgh. Dr. Clancy has been funded by the National Institutes of Health for over 25 years for research on pathogenesis, antifungal resistance and the clinical aspects of invasive fungal infections. Dr. Michael Mansour serves as an associate professor of medicine in transplant and infectious diseases at Harvard Medical School and is the head of his own laboratory at Massachusetts General Hospital, where they focused on developing novel cellular diagnostics and therapies for invasive fungal infections and Dr. Travis King, earned his doctor a pharmacy degree from the University of Mississippi School of Pharmacy. He completed his PGY1 pharmacy practice residency at Methodist University Hospital in Memphis, Tennessee, and went on to complete a PGY2 infectious disease residency at the University of Mississippi Center in Jackson, Mississippi. Dr. King specializes in transplant infectious diseases and antimicrobial stewardship as well as clinical microbiology. Welcome.

Thank you.

So thank you again for being here with us. When we talk about rezafungin and it's placed in the market and how you're utilizing it in clinical practice, it would help our audience, I think, to talk about what factors most influence your choice of antifungal therapies. Pathogens, host factors, drug toxicity, resistance, institutional protocols. Let's start with you, Dr. Clancy.

Well, probably all of the above -- but I think the key is understanding your local epidemiology. So what types of infections do you see at your center among your various patient populations? And then with that, understanding the microbiology, what species are you seeing and what the general resistance patterns are. And from there, you can devise rational diagnostic and treatment strategies and then place different agents based on their unique properties appropriately into sort of the treatment algorithms that you put together.

Great. Dr. Mandsor?

Let me add to Dr. Clancy's great comments and say one concern that I have is the really rapidly growing patient population that's composed of those undergoing solid organ transplants and stem cell transplants as well as the growing oncology population. And I focus on those patients that I care for because they happen to have a large burden of other drugs required for all those diseases and processes. So the drug-drug interactions for me become front and foremost when I'm considering how to treat their candidemia or invasive candidiasis. The azols happen to carry a lot of drug-drug interactions that can be quite detrimental and hinder treatment. And so the kind of candins and having rezafungin as a as a week long agent becomes really attractive. So those are the factors I'm considering when I'm designing an antifungal regimen.

Okay. Great. Thank you. So Dr. King you're often in the position of overseeing surveillance of these infections and opining on the best course of treatment for patients. What outcomes matter most to you when you are assessing the success in candidemia management? Are you looking at survival, infection clearance, quality of life for the patient? What are you most focused on?

Sure. That's -- I think to take a job there over Clansy answer all of them. Certainly, [indiscernible] first and foremost, for your patient. I spent a lot of time on the transplant side. So certainly, graph success is huge. You had someone go to the length of donating an organ, whether living or deceased, you would like that graft to survive. And so thinking about those long-term outcomes for our patients is obviously very important. Other things that we always think about for our patients is also maximizing the quality of life. And so certainly thinking about once weekly options such as rezafungin may fit better with their work life balance, with certain things that are going on from a social side of things. So that's -- those are the kind of the big ones. But again, all of them are very important and they're on right.

Excellent. So we know there are a number of operational barriers within institutions that you see. What are those that most impact timely antifungal care, right? Are we looking at diagnostic access, stewardship oversight, care transitions, what are most impactful when you're managing a patient with IC or candidemia.

I'll say, I think the major challenge facing the field that if you compare candidiasis to say a disease like aspergillosis, what's really lacking, I think, our diagnostics and early interventions. So we're still largely dependent upon cultures, cultivating an organism that we're taking either from the blood or appetitive site of infection and growing it in the lab. The sensitivity of that for canadisis is only about 50%. So in this half the cases to begin with, and then it takes typically 2 to 3 days for the organism to grow. During which time, we're either not treating the patient or we're treating the patient empirically. The advances in survival with aspergillosis have been combining a diagnostic test, galactomanin systematically employed in high-risk patients and then treating early based on that result. And we don't do that in Canadiasis. We largely wait for cultures. We're reactive. We're treating too late and mortality rates since the time I was in training, despite the introduction of new drugs, really have not changed. So I think diagnostic and treatment algorithms based on early diagnosis and treatment, sometimes empirically is what the field really needs.

Great. So Dr. Manser, you have a lab where they're focusing on cellular diagnostics and therapies for IFIs. Would you like to expand on that?

Our lab focus is really on trying to promote immune health and having that immune system recognize and clear those invasive fungal infections. That goes hand-in-hand with the appropriate timely diagnosis as Dr. Clancy just said, and really trying to use the best antifungal drugs in conjunction with the best immune health immune response. Often these patients who are undergoing transplant really just won't have a deficient immune response because they're on antirejection medications or chemotherapy agents for their disease. So it's a fine balance to really assemble together that appropriate response. And I think overall, for me, getting the patient out of the hospital as just one big driver, removing them from all the exposures to nosocomial infections and drug-resistant bacteria, et cetera, really begin to touch on a critical variable of lifestyle, getting them home to be in a better, healthier environment, having them move around and having physical activity returns. So having them tied down with requiring IV therapies and other things that could be moved to the home become a better, more attractive scenario. So long-acting agents, and we have some in the gram-positive bacteria area. And now with rezafungin in the Candida area, really gives additional opportunities administratively to get them out of the hospital and get back home.

I'll follow up on something Dr. Manser just said. He's talking about the long-acting aspect of rezafungin which is a very favorable pharmacokinetic profile. But the other thing it does and it ties into the inadequacy of diagnostics is it gets a very early peak concentration, which is the reason that you can give them once a week. And if you look at the major driver of response in animal models and other models, it's getting that early peak of drug at the site of infection. And the theoretical advantage that rezafungin may have is by doing this, if your diagnostics are suboptimal and you're diagnosing late, getting that early peak may give you a greater chance of clearing infection. And I think that's part of the reason the clinical trial, there was a signal that you had earlier clearance of blood cultures becoming sterile with rezafungin compared to the comparator or cinacandins.

So I think something that might be helpful for people to understand is the management of these DDIs. So we throw out terms like hepatotoxicity, neurotoxicity and those concerns. But what does that look like from a clinician standpoint, what does that look like for the patient and what they're dealing with. Dr. King maybe you want to...

It's obviously, the pharmacists and the drug interactions are very give hard and more importantly avoiding them. And unfortunately, the population that we see more commonly in to the Dr. Manser was pointing that is rapidly growing is that immunocompromised population who doesn't really have options. We can't really negotiate our shoe size when we think about having the prophylaxis against certain fungal infections, be it candida molds, aspergillis, what have you. And so we run into issues of trying to negotiate different dosing regimens, which kind of makes the treatment regimens oftentimes very confusing for the patients because again, patients first in everything that we do. And so having options that are clean, certainly the kind of [indiscernible] as a class are that, but then also having ones that we can, again, avoid simple line catheters for patients that are already immunocompromised and even those that aren't, but getting plastic out of a vein is really the best case scenario. So it does give us a lot of laterality, both on the drug direct negotiation range and also just the ease of treatment management and avoiding unnecessary things like central lines, pieces of plastic that can lead to secondary infections.

That's helpful. Dr. Manser.

Maybe we're all saying a very harmonized, we're trying to paint a really clear picture. I mean there's like real cases that I remember. Patients who could not receive specific chemotherapy agents. Oncology has taken on a different sphere, a different era where you now have such a wealth of agents and biologics. And there's really a lot of amazing medications in oncology where like a drug-drug interactions may mean you don't get that option. When -- specifically when using an azole. So many patients that I've cared for were unable to continue or we have to make a decision on switching antifungal agents because that DDI was very severe. In the [indiscernible] organ transplant world using azols often requires adjusting agents like tacrolimus or other antirejection medications. We've had many times where liver numbers go up, and so now we wonder is that the azole? Is that rejection? And these lead to very serious decisions where we have to collect the biopsy to make sure that graft is not being rejected because we would have to intensify treatment regimen. So these decisions have very real consequences. Someone's going to biopsy you. Someone's going to really increase your steroids or other antirejection medications, leading at risk for more infection. So they're not benign blips in liver numbers. They lead to very serious consequences.

Yes, I think the thing you have to bear in mind with DDI's toxicity side effects in these patient populations is how sick they are to begin with. I mean, these are profoundly immunosuppressed patients that transplant [indiscernible] malignancy patients, but also other critically ill patients in the intensive care. The patients undergone complicated abdominal surgeries, liver and gall bladder surgeries. So under the best of circumstances, tolerating your other drugs is very challenging, getting reliable drug exposure in these patients is very challenging. So then when you have an agent you're adding on, that's interacting with these and further confounding it, it becomes incredibly difficult. So these are your sickest of your hospitalized patients who are at risk for developing these diseases and in whom you're using these antifungal drugs and the fastest-growing population. Atleast in my hospital, that is the fastest-growing population. Are these immune-compromised individuals.

Yes. And again, to go back to understanding your local lymphology, at the University of Pittsburgh, we have very big liver transplant program, but we also have probably the largest liver surgery program in the country. So you wouldn't think of these necessarily as classically immunosuppressed patients are not taking chemotherapy agents, but they're functionally immunosuppressed. Can do the lives in your gut. That's where the infection comes from. So anything you do to disturb the gut potentially causes leakage of Candida and either bloodstream infection or otherwise sterile site infections such as within the abdominal cavity. So my patient population overlaps but has unique aspects of it compared to Dr. Manser and I have to understand that if I'm going to use a drug properly at my center and the considerations might be different than at his center.

And one thing that I will add, too, just thinking of my population in New Orleans. Outside of the immunocompromised population outside of the transplant, the BMT, certainly, we have a large volume of perimeter volume patients. And the fastest way to get my cardiology clinical pharma stuff in arms is to throw an azole on someone who is being treated for Afib with a non-orphan regimen. So it becomes very difficult to manage and that we don't necessarily have the gray anti-coag parameters to follow when I have to introduce an azole to that very complex regimen. That's just one small example. If you think about patients that come in with arhythmias, we have issues with QT prolongation obviously, that is something we don't have to worry about here, which is fantastic. So I think that the opportunity to avoid drug interactions in these patients is huge, and it expands certainly in those that are near and dear to our heart with immunocompromised but also far reaching outside of just that group.

So we've talked a lot about, and thank you for bringing up the severely immunosuppressed patient population. What are the other patient groups that we're not thinking about that could potentially benefit from treatment with the long-term echinocandin like [indiscernible]

So speaking to people, colleagues of mine throughout the country. I think largely nonblood-borne noncandidemia candida infections are often overlooked.

The invasive [indiscernible].

[indiscernible] and what you spoke about, I say in your introduction. It's a lot harder to diagnose these, drawing blood, it's invasive, but it's accessible. If you've got a deep tissue infection, you've got to go into the site of infection in order to draw fluid out and potentially culture and organism. So I think we miss a lot of these because we're not diagnosing them to begin with. The yield on culture is not great from these sites because the bugs are not uniformly distributed. So even if you go away, you've got a 50-50 chance that you're going to miss it. And people are not conditioned because the clinical trials are largely done in patients with candidemia because they're easier to identify. And oftentimes, within the abdominal cavity or other sites of infection, you also have bacteria mixed in there. So people will focus on the bacteria and pay less attention to the candidate. So at the University of Pittsburgh, we actually see more non bloodstream infections per year than we see candidemia. That's not true at every center. But I would guess that nationwide, probably the population we're most missing are diseases like intra-abdominal candidiasis osteomyelitis some of the other end-organ infections that often will not have a positive blood culture.

That makes a lot of sense. CDC says we're seeing 40,000 to 60,000 invasive candidiasis instances a year. I think people know how to really put in context what candidemia is, but I think it's a little harder sometimes to say, what does an IC patient look like? So...

And they're a lot tougher to treat because oftentimes, you've got to go in and do an intervention to remove the focus of infection. So if I'm treating the intra-abdominal abscess, the antifungal drug, I'll typically give for several weeks until the [ abscess ] is gone. But hand in glove with that, you've generally got to go in and drain the abscess, which requires an intervention. If you've got a leak of your hepatic or global bladder drainage system, they have had a biliary system, you'll get biofluid that goes into the abdomen. You've got to repair that leak in order to prevent the infection from recurring over and over again, which is very, very difficult to do. So as a general rule, these non bloodstream infections require longer courses of treatment, oftentimes on the order of several weeks -- they require a surgical or intervention component, oftentimes as part of it, and they're just more difficult to manage over time. And I think they're underrecognized and underdiagnosed to begin with. I think to add another variable to that and not thinking with a focus only on immune compromised patients is the Candida species itself, right? So I think that's the other elephant in the room, which is [indiscernible], as a group, are one of the most common fungal infections we experience, but really Candida's composed of many different types of species, Candida albicans, Canara, [indiscernible], you mentioned those and the [indiscernible] Joe mentioned those in the introduction. But some of those species are rapid risers and making lots of headlines as being drug-resistant candor is being sometimes multidrug-resistant. So there where you need to treat for a long period of time, you may have lost the azols completely. And now you may be stuck with a patient who's attempting to recover and rehab and improve but they require long-term echinocandin treatment. And you get kind of stuck and put into a corner where you need to either use a PICC line or some sort of central catheter. And as we were mentioning, not the most ideal scenario because now you've got risk for secondary bacterial infections. So again, that's a great area that we worry about and where we can use long-term pharmacokinetics like rezafungin to maybe avoid those catheters and get through a very prolonged treatment depending on what drug resistant species we're trying to deal with.

I'm sorry, I was going to say the other one that I always think about and certainly identifying the patients that are drug-resistant the deep-sea infections. We have a large population of oil and gas workers and agriculture workers in Southeast Louisiana. And if I had to ask them if they would like to go to the refinery with a pink line in, so a central line answers, right? And that's actually the best case for the patient because there's a high risk of severe complications. And so we try to at least identify those patients. Sometimes they fit, sometimes they prefer to sit it on the pig. That's up to them. But it is kind of an untapped market thinking about that patient's work life balance and what they're actually doing to minimize secondary complications. The other that I'd like to kind of position a once-weekly medication such as rezafungin in is our transplant population or depending on how your clinic functions, a lot of our patients travel from very long distances come in and so we'll set up around Robin clinics for them. So they're rapid fire with their cardiologists, endocrinologists, transplant surgeon infectious disease if they need us. And so we can streamline that care all in 1 day to minimize the burden on their actual just day-to-day life, that also, again, just kind of helps coordination of care and streamlining servers on the same page. So certainly, the infectious complications, infections issues are worried, but I think there's the social side of things that plays a very large factor for us.

So speaking of the social side, I know we talked about this a little bit earlier. There are social determinants of health that certainly weigh into patients that may benefit from a long-term echinocandin a bit more. And we've talked a little bit about the geographic disparities as it comes to like Dr. Clancy as said, knowing your local epidemiology but from a social determinants health standpoint. Can you expand a little bit on that?

Sure. So just from my personal experience, what we end up running into more times than not is a patient's ability to physically show up to our infusion suite. Or do they have the support structure at home to be able to help facilitate deal in [indiscernible] on daily, whatever your medication may be. But -- because again, you think about all the secondary complications that are not benign when we introduce a foreign object into a patient. So certainly, transportation coverage is always an issue -- but we haven't thought that too much, which has been good. And again, thinking about just where our patients are coming from and again, where they're living, what their actual support structure is, tends to be the biggest one. again, thinking about patient comorbidities, things to avoid. I think we hit on the drug-drug actions very well. So yes, I always like to bring up the social side of [indiscernible] because having a 1-week option like rezafungin very, very nicely dovetails into making life a lot easier for someone than having a daily infusion again, but also making sure that we can actually get them to our infusion suites. So...

Yes. I mean I think if you look at our health care system, Dr. Kennedy University Kripa, because it's typical of a lot of modern large health care systems now and that we've got the urban core, where the primary university-based hospital is. And then we service a vast underserved largely rural hinterland, in our case, Western Pennsylvania, West Virginia, where there's extremely poor access to care. And the other issue that we face increasingly in Western PA is the fentanyl and injection drug scourge. And this is a population where for both bacterial and fungal infections, which we increasingly see in that population having a once weekly treatment option where you don't have to have a permanent indwelling access device is very, very important and allows care in these patients. Previously, these were people that we would have to keep in a facility for 6 to 8 weeks to complete a course of treatment for endocarditis, for example. So having the ability to come in once a week, get treatment, not have a permanent and dwelling line has made a real difference in that population.

I echo the same. We've definitely seen wonderful advances where you can get someone to appropriate care by not being tethered to a central line, especially if -- they have barriers to access to care, other issues that they're dealing with, such as substance abuse. They really have more options if they can leave the main hospital and really begin to engage with care without those anchors. And the once weekly agents have really made an impact there.

I did want to follow up on 1 thing Dr. Manser mentioned about resistance. Just to point out, the 3 top priority resistant candida that have been highlighted at CDC and WHO are all potentially azole-resistant. And that includes Candida Aris, 95% fluconazole resistant, azol-resistant cantaperopsalosis, which we've seen now over the past 5, 10 years, previously did not exist and then [indiscernible] with 15% to 30% as resistance. So azole-resistance is going to be an increasing challenge, already a big challenge, but it's just going to get bigger.

Great. Well, I'd like to thank you all so much for your continued commitment to patients and educating us today. With that, I'd like to welcome Dr. Pete Sullivan, Senior Vice President of Market Access and Board certified oncology pharmacist.

Thank you, [indiscernible] Thank you. As we look beyond the current market with REZZAYO, we are most enthusiastic about the opportunity of prophylaxis in patients undergoing immunosuppressive therapies. These patients are profoundly immunocompromised and highly susceptible to opportunistic infections, patients battling hematologic malignancies like leukemia and lymphoma and those undergoing highly immunosuppressive therapies are the 2 key patient populations at risk and require long-term prophylaxis, including antifungal therapy. The treatments for these malignancies, while potent against cancer leave the patients with limited natural immunity ahead here. One critical patient population requiring long-term prophylaxis is those patients undergoing stem cell transplant. Similar to the treatment of fungal infections, there are a number of different agents used to prevent infections based on patients' risk. Today, azoles are the standard of care for allogeneic stem cell transplants with alternative agents such as the first-generation short-acting kind of candens. In addition, hematological malignancies like AML and ALL are also most likely to receive prophylaxis due to the treatment and disease burden these patients have. Based on recent market research that we conducted with stem cell transplant physicians and ID physicians, there is a wide variety of antifungal agents use in prophylaxis. This prophylaxis is dictated by risk factors and protocols. Although the majority of the top 10 transplant centers in the United States, prefer posaconazole, we see a large opportunity for rezafungin REZZAYO in this patient population based on the variety of products and agents used for prophylaxis. In the same market research, we found a strong signal for the willingness of prescribers to prescriber REZZAYO in patients receiving stem cell transplants and undergoing treatment for hematologic [indiscernible] as prophylaxis and well within our target goal to penetrate the TAM. Looking beyond our current indication, we believe the convergence of the unmet clinical need, growing economic pressures within the health care system and evolving standards of care, it's creating a meaningful and durable opportunity for REZZAYO expansion. We determine the opportunity as expanding into a broad patient population at risk for invasive opportunities infections, including those caused by Candida, Aspergillus and PJP. We estimate the total addressable market is over $2 billion. And we'd be happy to speak more about the granularity of how that addressable market is comprised and certainly, the Phase III trial data and the FDA label will impact that addressable market and market potential. In terms of why we are so excited about the potential for REZZAYO in prophylaxis as an indication despite the current available options, as was previously discussed in the previous panel, patients that experience -- patients currently experience unacceptably high rates of hepatotoxicity and drug-drug interactions, potentially compromising their treatment and exposing them to serious adverse events that we'll talk about here momentarily. Supporting the prophylactic indication is our ongoing Phase III study run by our global partner, Mundipharma, Respect is a global Phase III randomized double-blind trial evaluating the efficacy and safety of once-weekly rezafungin or REZZAYO, compared to the standard antimicrobial regimen for the prevention of invasive fungal disease in adult patients undergoing allogeneic blood and marrow transplant. Enrollment was completed in late 2025, and the top line results are expected later in Q2 of this year. In addition to the primary efficacy endpoint, respect evaluates the discontinuation of rezafungin compared to the standard anti-infective regimen, secondary to toxicity and intolerance as we heard by the panel. We've also heard from the clinical community that this still remains a serious concern. It is now my pleasure to introduce our panel today to talk about infection prophylaxis in high-risk BMT in hematologic patients. Dr. Jay [indiscernible] is an assistant professor of leukemia, an affiliate faculty member in clinical cancer genetics at MD Anderson Cancer Center, Houston. He focuses on the management of patients with acute and chronic leukemias along with drug development and translational research in high-risk myeloid leukemias. Dr. Melinda Cook is a Board-certified oncology pharmacist. She practices in both the inpatient and outpatient setting as a bone marrow transplant clinical pharmacy specialist at Memorial Sun Center and Cancer Center. And Dr. Doris Ponce is a hematologist oncologist specialized in bone marrow transplantation. She is an Associate Professor of Medicine and Memorial Son Kettering Cancer Center, where she is the Director of the graft versus host disease research and translational program and the co-chair of the Center for hematologic Malignancies Research Council. Thank you very much for being here. All right. So the previous panel talked about treatment, and we're going to shift to talk about prophylaxis and how that impacts your patients. So Dr. [indiscernible], how do you -- how do you approach infection risk across the transplant continuum from induction to early transplant to prolong neutropenia and GPH. How does that shape your prophylaxis strategy across the patients?

Okay. So we need to take into account that we have a very unique patient population. So these patients with hematostrpelic disease or advanced nonligand hematology condition, typically will undergo through song treatment before transplant most of them and they already will comment to us with some level of immunity compromised. So they already got exposed to some chemotherapy agents, they might have some experience with infections in the past when they come to us. So then when they come to transplant, they go to this spirit of conditioning treatment where we basically remove their immunity with this very aggressive therapy to allay out the new stem cells to grow and thrive in the new environment. So with that, we advise for patients at that period is very sensitive for infection. And then on top of that, they will lose their accounts and they will have neutrophils or other cells from the immune system, sophisticated upfront cells, the core battle any infection. So they are in a quite sensitive period of time through their transplant. Now after account recovery that can take 2 to 3 weeks from the time they get their stem cells. They're still quite immunocompromised because even though they recover their neutrophils just like the upfront of the soldiers in the battle, the more sophisticated immune system hasn't recovered yet, which is why or prophylaxis for like, for example, antifungal and others last longer than just the neutropenia recovery because that sophisticated immune system has to kick back in. So these patients are quite sensitive for any source of infection. And that's why all of that universally will receive prophylaxis.

Okay. So those patients are on long-term prophylaxis, whether it be fungal or PJP or anything else. What are the biggest limitations? And maybe this is a question for the full panel. What are the biggest limitations to the current antifungal prophylaxis options when it comes to safety, tolerability, maybe long-term use? And do you see any development of resistance in those current therapies? Maybe Dr. Cook...

Yes, so I think as the other panel kind of talked about drug interactions, of course, is a major issue. And it's especially a problem in the transplant population with them being on immunosuppressants as was mentioned. So any time we're having to start 1 of the azole antifungals, we're having to take into account their immunosuppression dose adjusting it. We probably are going to have to bring the patient back in to monitor them and their levels more frequently. And so that's definitely a challenge. And then just drug interactions with all medications in general, it takes looking at the patient's medication list very closely to ensure that there is no adjustments or like that is even safe to give the azole for that patient. So that is a major challenge, and we may have to make adjustments to the antifungal we use based off of those drug interactions. We do run into issues where the -- it's rising at the level of the immunosuppression, it's so high that they'd be at risk for toxicities from that immunosuppression. So we may have to switch to an antifungal that has fewer drug interaction concerns. And then in terms of side effects, that's probably another major issue to talk about hepatotoxic hepatotoxicity we've talked about is probably the biggest issue. We -- it's especially important in the BMT population, just because the transplant itself has its own liver complications associated with it. And so if a patient is showing signs of hepatotoxicity, it can be hard to distinguish if it's drug toxicity from the azole or if it's a true complication from the transplant. And so the azole tends to be kind of the first one that needs to go just to rule it out as a cause for this potential hepatotoxicity and so that's a big challenge. And then trying to find switching them to an antifungal. That's going to be a bit more tolerable as an issue.

Dr. [indiscernible], how does that impact your leukemia patients receiving high-dose chemotherapy as well?

Right. So I'm going to give a little bit of background. In the last 30 years, the survival of leukemia has doubled. Let's call them acute myeloid leukemia, acute lymphoblastic leukemia. And we cannot put our backs by saying it has only been because of leukemia medication. So a lot of it has been because we were able to deliver better leukemia therapy, while we are able to cover patients with better antifungals, antibacterials during the peak neutropenic periods. And the efficacy of any antifungal drug at the end is determined by the compliance to that medication. When we are trying to develop new acute myeloid leukemia therapies or acute lymphoblastic leukemia therapies, the aim is now more combination trials in the last year itself, FDA has approved 3 new drugs in acute myeloid leukemia for relapsed/refractory. And if you go deeper into the way the journey of these drug approvals, all of them started with Phase I drugs that did not allow us antifungals. Because of drug-drug interaction potential for liver toxicity, being the primary veins to drug development when you're trying to combine them with good antifungal drugs. As a result of which, developing drugs with limited drug-drug interactions so that you can take the leukemia field forward with the respect to drug development is supremely important, that's point A. Point B, a lot of these patients when I'm as a leukemia physician, trying to put them on an agent, which is supposedly going to work very well for the leukemia. I'm worried to add on an asuntifungal low and behold, the liver and sensor to go up and then have to come down on the leukemia directed therapy, which in no way leads to better outcomes. So then we are talking about hepatotoxicity. And the third part of it is the compliance to treatment, which I started with. When you are not giving patients as all antifungals, you are worried whether price a week caspofungin or available drugs would be able to provide them adequate candida or even more prophylaxis compared to a drug like rezafungin where there is strong pharmacokinetic evidence of the drug having persistent efficacy with the peak and that was shown in both the [ restore ] as well as the STRIVE trial with 5-day early fungal clearance, which is extremely important in these patients with profound and deep neutropenia with not only one axis of the immune system being affected, but multiple access and low neutrophil counts, mucocell injury from the chemotherapy as well as other arms of the innate immune system being affected secondary to the therapy. So reduced rub brag interaction is important, reduced toxicity to other organ systems are important and improving compliance. And I think that's where rezafungin hits all the boxes.

I want to add something to the challenge that we got in transplant. If a patient is very high risk for mall infection and they go -- as they start their transplant conditioning, we compromise of not giving any coverage for mall infection because the drug-drug interaction is so severe that we will not be able to achieve a therapeutic dose of the anti-rejection treatment of the immune suppressant and therefore, they spend a good period of time about 2 weeks or longer with our proper coverage with the trade war that, okay, I will at least get a therapeutic level of immunosuppression, but at the cost of adding the risk for [indiscernible]

I'm going to add a point to that if you have time. Inotuzumab it's a drug which we used very commonly in acute lymphoblastic leukemia. We led the development of this drug. It's now bread-and-butter and acute lymphoblastic like management approved both in pediatric and adults. And this drug is known to cause hepatotoxicity. So I'm going to cite some important data from clinical trials. When the initial trial of this drug was approved, 27% of patients end up having significant inhibitor toxicity, especially if the renter transplant. So these patients end up not getting azole antifungals, and we develop this protocol, but a lot of these patients end up developing other fungal infections. And we are not able to cover them adequately, as Doris mentioned, as a trade-off giving them good leukemia therapy, preventing them hepatotoxicity so that they go to transplant. But on the other hand, compromising on the antifungal drugs because we haven't got any good, which patients can get adequately in the outpatient settings with good coverage. So getting long-acting drugs, which does not affect the liver with low drug-drug and correction is a strong need at this point.

Okay. So making that choice, right, making that balance of achieving therapeutic doses but also protecting the patient from high-risk infection. How often are you making that choice? And does REZZAYO into that category, assuming the data supports it.

Well, as mentioned, we do have a compromise where at least for us is actually is not negotiable where we need to make that trade off. Even with a strong history of mall infection, like patients as previous -- since they received treatment in the past, they're already immunocompromisin they can come to us with history as forges infection. And our trade-off is that we will expose them through the transplant process of beginning with our coverage, which is quite concerning. And now that we are adopting a new prophylaxis regimen for represents disease that is cyclophosphamide, that actually makes adding the main drug draconian drop which is immunosuppressant medication actually later. So now we are -- the problem is getting worse because we're pushing the clock when to be able to add more coverage to later. And I think now that this is widely adopted, we see this problem even more.

And I will say that we do run into like the scenarios I kind of talked about where patients are developed being signs of potential hepatotoxicity and we have to hold the azoles. It could be significant enough that we don't want to use any azole, and we might have to compromise coverage again and like go to like micafungin and not have that aspergillus coverage that we would want.

Yes. Thank you. We talked to...

Some minor thing, too. it might also need to say in the hospital longer for treatment, that's another issue. And when they go in the outpatient setting, sometimes we only option we have because of hepatotoxicity, for example, is giving a drug 3x a week like micafungin, which is not -- we don't reach the adequate PK throughout that week treatment. And obviously, we -- again, we compromise that coverage.

So great point leads to my next question. From a feasibility standpoint, that long-term prophylaxis is hard to manage, right? So whether it be different treatment cycles or patient tolerability or patient compliance, what are the main challenges in maintaining adequate long-term prophylaxis in BMT patients or even long-term leukemia patients.

I'll start. So the main challenge with maintaining long-term prophylaxis is toxicity. There is an additive toxicity there was a class effect to azole toxicity hepatic particularly. But especially in high-risk leukemia where the depth of remissions are not good, and we are looking forward to new drugs -- most of the Phase I trials, which we envisage high-risk leukemia patients who have relapsed frontline therapy, we should be able to be treating them on clinical trials as per NCCN guidelines. We're not able to do that on azole antifungals, given significant amount of toxicity risks. As well as drug-drug interactions because any clinical trial would want to do PK analysis of their own drug and we don't know how azole antifungals are affecting A. B, Venetoclax, which is a drug now most ubiquitously used in leukemia and it needs a ramp-up for both acute myeloid leukemia, chronic lymphocytic leukemia is strongly influenced by azole antifungals, there was so much of drug interaction. So during the ramp-up phase, especially if you're doing it outpatient, you are basing your judgment of the best antifungal prophylaxis to be 3 times a week, as Doris was mentioning, which is not ideal and providing them some form of antifungal drug for a long duration with adequate levels, while you're ramping up the dose of venetoclax as per the label provides you good coverage without compromise.

So -- the challenges remain in being able to optimize leukemia therapy, while continuing good coverage for antifungal drugs.

So we mentioned the challenges. We mentioned the new therapies evolving, whether it be post transplant Si or the new therapies in leukemia. Looking ahead for antifungal prophylaxis evolving in a couple of years what would meaningfully improve patient care in both the transplant setting and the leukemia setting.

I think like a steady treatment with compliance will be really important -- if you take a look at any of our transplant patients, you will see that they have -- they need to take like 20 medications a day, is quite a heavy list, and I have patients complaining with 12 medications like, "Oh, actually, it's not a lot. So the -- it's almost like you need to make a mathematical algorithm of the drug-drug interaction to really allow to be safe in their journey of treatment during the transplant period. So it's really difficult, like if they take I don't know, great fruit or something that they bought in [indiscernible] . You can already -- you can start seeing some shift in the interactions and that can really modify immunosuppression levels or other drugs. So for us, achieving a cell therapeutic immunosuppression level can be detrimental in the patient like have on control offers a host disease and some time -- it's just you have to tell what happened? Like you had a steady level what happened, what do you do? And then you start seeing that all these interactions, even outside of our medications can employee. So that can really affect the safety of the transplant journey. And some patients might be a little bit careless when they get out of the hospital things are better, I'm feeling better and then maybe they not be so consistent with their treatment regimen, even the timing of your drug matters. So that -- those are small issues that they add on into a bigger problem.

I want to take a page from the previous panel and from the societal view, right? So as a pharmacist, you're managing the patient's medications both while they're being treated in the hospital, discharge planning and then the outpatient follow-ups, which are pretty recurrent. -- how challenging is the pill burden, right, in a transplant or leukemia setting of how many pills are taking, how often they're having to take it and just removing some of those challenges change the -- maybe the outcome or the lifestyle of the patient.

Yes. It's definitely a big issue for patients. I go in and talk to every patient before they leave the hospital after transplant. And just like bringing in that giant bag of medications is like immediately very shocking for the patient and they get -- many of them are very scared to take all of these pills and just being able to handle it, we have to give them a pillbox to make sure that they can actually manage taking all these medications at the right time. The can be on medications up to 4 times a day. We try to limit that the best we can. But yes, any reduction in their pill burden always helps. And right now with like the azole antifungals, it's one of the medications that it's on for a little bit longer. So there's not as much hope to give the patient like, oh, you're going to be on this for a couple of more months. So yes, it's definitely a challenge. And the longer they're out of the hospital, yes, the less -- they feel like they need to take some of these oral medications. So yes.

Yes. I had patients where I see a huge swing in their immunosuppression level. And then I found out that they forgot to take our antifungal. So always taking those con didn't take a escape today, but tomorrow took it then I have a side effect that caught the pill in half and like those patients tend to have super and subtherapeutic levels throughout the week on and off, which really compromise or transplant. So -- and really having a treatment that you could -- you force the patient to be compliant on a medication and doesn't cause a drug darker accident. It will be really relevant for us as a tool to offer to our patients, too.

Yes. So it's a great point, and I think it's easy to not fully grasp that challenge there, right? And so we're thinking about drug-drug interactions and transplant patients. They're on immunosuppressive therapy, right? You say you kind of talked, they're going to be on maybe a micafungin in the beginning and then you want to transfer them to an azole. How much does that actually impact maybe their [indiscernible] levels, right? So if someone is on tacro for immune suppression and you start posaconsole, right? So as the pharmacists on the team, how much is that dose actually changing?

So yes, if it's like a Posco [indiscernible] , usually, we're reducing the dose by half or voriconazole half less with some of the other azoles, but yes, it's a pretty big dose reduction. And it's something we just have to watch really closely to because especially in that early transplant period, we want to make sure they have therapeutic levels, and we don't want it to go too low, and you can't always predict exactly how a patient is going to metabolize medication. So yes, the -- it's definitely an issue. And yes, we have to just watch them really closely.

Thank you for that. Any last questions or thoughts on antifungal prophylaxis in leukemia or transplant.

No, I just want to say that there are other instances beside the early [indiscernible] period like patients who have like [indiscernible] disease, which is a transplant complication where you need to actually add more new suppressions for medication Main drug is like corticosteroids, and those patients actually require to resume antifunal treatment. And many of them have hepatic involvement and it's quite difficult to manage. So those are small scenarios where not that small, that you call encounter later on after the initial transplant period that they are backlog.

Two things. One, I think a good anti-mold prophylaxis is supremely important at this point. I'm very eager to look at the data of the RESTORE trial whenever it's read out. It's a very well-designed trial with posaconazole on the competitor arm and with a very small inferiority margin. So it would really open a box of opportunities for these patients to get drugs that have less interactions and less toxicity. The second is to understand that these drug interactions that we try to put it in 1 box that, okay, drug game might increase the dose of venetoclax 4x, drug B could increase it by 2x. It is done in a very small group of populations, which are not ethnically diverse and the drug metabolization is very different in individuals, even based on the profile of the immune suppression that they are on the type of leukemia therapy they have received. There is one as a antifungal will not name it. Initially, it was supposed to increase the dose of venetoclax 3x. Now we know it increases it by 8x. So as a result of which, we are learning more and more. And even though we probably are getting better at modifying the dose of leukemia drugs with respect to infectious drugs. It can never be as refined as treating with a drug that does not cause drug-drug interaction. So that is extremely important. And now -- in the present generation of leukemia therapy, I'm talking essentially pretransplant or post-transplant unfortunate relapses. The aim is no more to try a single rug because it doesn't work. So we try to do combination anti-leukemia drugs, which certainly gets better control of the leukemia, but the immunosuppression is also more profound, deeper, longer and more arms of the immune system compromised. And the mix of it, when we try to add drugs, which have strong drug-drug interaction, toxicity potential, it prevents better leukemia drug development. And as a result of which, we need those kind of drugs, which would be able to give us a longer duration of good profile axes.

SP-42 I want to do a final comment on it. I don't know if I mentioned that, but at least on the BMD side, we're seeing more and more Superbox resistance and breakthrough tripophlaxis. So I think in this timely manner is too to have another tool because we are seeing these cases, and we have not too many tools to treat the patients that have a breakthrough.

I just want to add something we haven't really talked about yet is just like the financial and insurance barriers to using the oral as -- it's a major issue on that actually is the main decider in what antifungal I use for patients that we're going to use for patients for prophylaxis. If a patient does have toxicity or we're running into drug interactions issues. We might want to switch to another antifungal, but the antifungal with less drug interaction concerns or side effect concerns is also the one that's harder to get approved by insurance and also has higher co-pays. But really, all the azoles can have co-pay issues for patients, depending on their insurance and their deductibles can run in -- once January every year, we have patients coming and telling us they -- all of a sudden, their posaconazole co-pay went up by this much, and they can't afford their co-pay. And have to figure out as fast as we can, some way to get them that drug affordably. So that's a major challenge.

Yes. Just to put one last point on practical situation. There are these patients who have breakthrough frontal infections, both azolprophylaxis or otherwise -- and they are on triple antifungal therapy. We try to get them out of the hospital because we don't want to keep them in the hospital for weeks. They get out of the hospital now they're coming every other day, driving 4 hours. And often, the companies better off in the hospital. So on 1 hand, quality of life and resource utilization versus providing them better therapy, we have to start really now thinking from the patient's perspective and developing drugs, which really helps in improving quality of life, just improving survival in leukemia therapy, while they were spending the better part of their life in the hospital and in the clinic it's not good improvement in leukemia therapy.

I think that's -- it's easy to sometimes overlook, but that's why we're here, right? To improve the quality of life of our patients that whether we're developing drugs for them or treating them in clinic or managing to try to get them on the hospital. So -- thank you very much. I thought this was a very insightful panel and appreciate you being here with us today. Thank you. And with that, I want to welcome Dr. Jared Crandon, Executive Director of Clinical Portfolio Management.

All right. So as Joe had mentioned, we are transitioning indications with the fin cap into the total parenteral nutrition space. And while there are a variety of patient populations that utilize central venous catheters, you can see the total parenteral nutrition space actually uses them almost universally. And I think as Dr. King put it earlier, these are effectively pieces of plastic that we're sticking into the veins of our patients. And so TPN specifically is delivery of nutrition via the vein. So these patients are unable to tolerate nutrition [indiscernible], so we're putting directly into the vein. So all of that's going through that device that's either inserted peripherally. So we talked a little bit about PIC lines earlier, so those would be in the periphery or actual central venous catheters, which will go right in the neck or the chest directly into the heart. Having TP in and of itself creates a variety of complications. Most notably, the metabolic abnormalities noted here in the middle. But having that piece of plastic in the vein certainly puts patients at risk for things such as thrombolytic complications, so blood clots, specifically in that catheter as well as central line associated bloodstream infections is what we're going to talk about today. These infections can be caused by both intra or inside the lumen of the catheter sources as well as extra outside the lumen of the catheter. They can be caused by a variety of gram-positive gram-negative bacteria. As well as fungal pathogens. I mean we talked a lot about fungal pathogens, so you understand some of the concerns there. These infections are associated with significant morbidity as well as mortality. On the upper end of that mortality range, you can see things in the neighborhood of 15% or even 30%, particularly with those fungal organisms. In a given year, we estimate that roughly around 26% of patients, TPN patients will develop one of these [indiscernible]. So current prevention strategies are really focused on the extra luminal sources of these infections. So things like washing your hands, making sure that you're changing dressings commonly we even -- there's even use of these chlorhexidine or drug-containing dressings. Certainly, every time the site is accessed, they're scrubbing the hub to make sure you try to kill these many pathogens as you can. And so those are really focused on the sort of extra luminal cases. Guidelines do suggest the use of preventative lock solutions. And so if I can kind of just take you through, so a patient gets TPN. So you have this nutrition going through their vein. At the end of that time, they'll take a saline syringe, they'll just flush it out so sort of clear all that nutrition out. And then the patient will put something in that tube effectively to kind of keep it valuable. So most commonly, heparin is what's used and heparin is used to prevent blood clot. And so that will go inside of the vein and then inside of the catheter and then the patient will go about their day until they get TP in the next day. And so those don't have any antimicrobial components to them, but guidelines do recommend that you could use these antimicrobial containing lock solutions. However, there currently is no FDA-approved catheter lock solution that's antimicrobial in the TPM population. So our product [indiscernible] is a combination of heparin, which I mentioned, is there to reduce clotting as well as Taroladine, which is a non-antibiotic antimicrobial has a broad spectrum of activity against both gram-positive, gram-negative as well as fungal pathogens. So it pretty much covers the waterfront as far as the organisms that cause these types of infections. [indiscernible] currently has no known resistance, here's pretty high concentrations of the drug within the catheter. And even in a bacterial study trying to develop resistance in the laboratory, we're unable to actually do so after 20 passages of these types of studies. Given this unmet need, we think that this TPN market represents a significant opportunity for [indiscernible] there are approximately 40,000 patients in the U.S. each year that will have TPN, whether it be at home or in the hospital. And those equate to about 4.7 million infusions each year, we size that market to be addressable at $500 million to $750 million. So we've conducted a little bit of market research recently to kind of look at the -- sort of the defend cap market and TPN versus some of the other indications, and it's certainly different -- most notably, TPN patients, about half of them actually have commercial coverage. And we are -- we anticipate that the fin cat in this population will be covered as a separately billable Part B drug. Also through our discussions with these payers, we found that not only are they likely but also willing to cover anticipate coverage for TPN patients in the [indiscernible]. I think there's recognition of certainly this unmet need, which I sort of outlined before, but also the potential returns on the back end for prevention of these infections as well as hospitalizations and certainly mortality. To support our indication in the TPN population, we're currently enrolling in a Phase III program called NutraGard. This is a study looking at the efficacy of DefenCath versus the standard of care, which is heparin at the reduction of [indiscernible] in a 12-month period in TPN patients. So our target population is 90 subjects, and we are currently about 1/4 of the way through enrollment. So with that, I would like to call up our last panel for today. First, we have Dr. Michael Owen Machine, who is a physician nutrition specialist, and Assistant Professor of Medicine at the Institute of Human Nutrition at Columbia University, serves as a Director of Medical Nutrition at Columbia University Irvine Medical Center, where he oversees inpatient and home parenteral nutrition for adults with a wide range of complex medical conditions. Next, Dr. Alise Brett is a clinical endocrinologist and diabetes specialist and solo independent practice in Manhattan. She was trained in nutrition support during her endocrinology fellowship at Mount Sinai Hospital. Following her training, she has become a certified nutrition support clinician, for more than 20 years, she regularly consulted on patients at the Mount side hospital for the management of parenteral and inter nutrition and also manage patients receiving home parenteral nutrition. And lastly, Dr. Jason [indiscernible] is a Clinical Professor of Pharmacy at the University of Michigan College of Pharmacy. He's an infectious disease clinical pharmacist at Michigan medicine, recognize Esper and epidemiology and the management of infections due to antimicrobial resistant organisms and antimicrobial stewardship with over 150 peer-reviewed publications on these topics and has been an invited speaker at numerous national and international conferences. So thank you all for joining.

All right. So to start off, I thought perhaps Dr. Brett, you could kind of take us through and we talked a little bit about perhaps some of the vulnerabilities of this TPN population, the fact that they have these severe gastrointestinal disorders. Maybe take us through a little bit about what development of the labs might look like in this already sort of vulnerable population.

Got it. So thinking about the home TPN population. So all these patients are told, as soon as you get a fever, as soon as you get chills, you call us. And they call us and they come to the hospital. And so this is a major impact on their quality of life and often the quality of life of their caregivers, and they come to the hospital, they get blood cultures, they get put on antibiotics and often they're looking at atleast a 7-day hospital admission and exposure to antibiotics, they're at risk for drug reactions. They are at risk for C. diff infections, just being in the hospital. They're at risk for other nosocomial infections. And then depending on the type of infection, the pathogen itself and whether or not there is a port access, whether or not there's a there's a tunnel infection, they may need their access removed so they may have to undergo surgery to have their access removed and another surgery to have a new device placed and depending on how many times this has happened, they may be looking at decreased loss of vascular access. So these infections are really a big deal for these patients.

Yes. So it sounds like even -- so when you're sending a patient home on TPN, you're probably already having a conversation with them about, hey, you're at some level of risk because you do have this catheter -- is that more.

They're all told, but this is the major risk of being on predilution. The metabolic complications we can handle. We can take care of that. But they're all told when they go home, they have nurses come to their homes, they're all taught aseptic technique, how to handle these, but we can't prevent all these infections. And they're all told that this is even when we start them in the hospital, they're all told that infection is the biggest risk of being on the parenteral nutrition.

Could you just highlight then maybe a few of the key characteristics. So what is it about being on TPN specifically that comes with an increased risk for these cloud Cs?

So I mean -- so specifically, the metabolic risks that increase the risk -- the main thing that I think of is hyperglycemia, specific to my field that increases the risk. So hypoglycemia does several things. hypoglycemia, it serves as a substrate for the bacteria itself, -- it's a carbon source for the bacteria, so it increases the bacterias virulent growth and adherence. It also decreases the acute hypoglycemia decreases the host immunity. So it decreases the host ability to trap and kill the bacteria. And it also increases the production of cytokines, so like TNF-alpha and IL-6 and therefore, hyperglycemia worsens the host response to a bloodstream infection and decreases that risk. So we're worried we're always worried about hypoglycemia. And it's not just people with diabetes that get hypoglycemia. It's also metabolically stressed patients in the hospital that are at risk for hypoglycemia and people on certain medications, in particular, like steroids, -- so that's 1 of the biggest things that we worry about, and we need to -- we have strategies have how to get on top of that and control it and start with insulin in the formula when we need to and start with low dextrose and then raise up the next dose and the insulin as needed. That's the main thing that.

From a metabolic perspective. Yes, excellent. And then some of the -- you had mentioned some of the ideas around even just the fact that you're delivering this nutrition specifically. Can you speak a little bit to that context or anybody.

Yes. So the other thing that comes to mind is the delivery of lipids in the GPN formula. So just giving lipids increases the risk for infection and in particular, with our older lipid formulas, the intralipid, which is primarily soybean-based formula, which is mostly Omega 6 that is proinflammatory and has been shown to increase the risk of infection. And that's actually compared to the newer lipid formulas which are mostly omega-3, which contain fish oil and MCT oil and olive oil and our soybean sparing was in a little bit of -- always need a little bit of soybean oil because that contains essential fatty acids but -- but using any amount of lipids in the TPN does increase infection risk, and we have to -- and we have to think about when to start the lipids and make sure that we're not overfeeding lipids. And some of the society guidelines actually recommend holding lipids or limiting the amount of lipids at least for the first 7 to 10 days of providing TPN, particularly in critically ill patients or [indiscernible] patients.

Darrin, I would just add on to that. I think it's a really key point. You're giving food, right? So you're giving food in the microorganisms like the food. And 1 thing I think that's notable about TPN associated cloud needs in particular, that we certainly are concerned with our normal bugs of interest like you worry about staff res and resistance that comes with that. But you do see a little bit more gram-negatives. Even fungal and we've talked a lot about candidemia already today. So you see kind of a broader array of microorganisms that can cause collabs in these patients because, again, you are putting food and it's not just us that likes the food.

That's right. Yes, please go on the topic of lipids. There are some in vitro studies actually looking at what we call 2-in-1 TPN of just extrosin amino acids that you can't really culture a lot of bacteria or fungi. But when you add the lipids, you can culture Canada in the lab. So we do see that increased risk. And at least our data at Colombia, we see increased in roci and candida infections for patients on TPN -- and I think just to add to some of the risk factors, we have to consider other host factors. So a lot of the patients there's a reason that they're on TPM. They can't eat. They have GI dysfunction, so they may have bioleac that we heard about other things that are putting them at higher risk for perhaps look for some might be a transient bacteremia, but when you have this central line, then you develop claps.

I think Dr. [indiscernible]. So when you -- so you have a patient, you're going to send them home. You say, "Hey, you're on TPN now we're going to have you do this at home. What sort of preventative strategies do you send them home with currently to help sort of prevent these things that we've been talking about.

The things that you mentioned, so you covered it, but hand hygiene, sterile technique when changing dressings, cleaning the hub and using chlorhexidine dressings. Those are kind of the main things the bundle that's come out from CDC to prevent cases both in the hospital and the home setting. But we've really -- when I there's a lot of fear and shame associated with this. And a lot of these patients -- doctors will say to them, "Why don't you just eat? Why don't you just see don't you know how dangerous this TPN is and there's a lack of understanding that I can't eat, I can't eat. Patients are desperate for some way to reduce this infectious risk because it is so disruptive to your life to be admitted to the hospital repeatedly. And then the medical complications of the risk of endocarditis and other metastatic infections.

Yes. I think that's an excellent point. And so I think we did touch on the -- there are some guidelines that sort of suggest that maybe you could use an antimicrobial in your practice, have you seen much antimicrobial catheter lock something actually in the lumen of the catheter. We have not found anything that's just practical to use that's commercially available covered by insurance. And there's ethanol locks or one possibility. Some pharmacies will compound an epical outlook a lot of insurance won't pay for it, and then there's the risk of actually damaging the catheter over time through exposure to ethanol. So while ideally, we would love to have some sort of antibiotic lock or way to prevent line infections, it just is not currently available. It's not something that we use. Sometimes we'll do gentamicin lock as like a catheter salvage after you've had a line infection, but routinely preventatively, we're not doing that now.

All right. So basically, we've got these populations at risk, they're at home. They ultimately then develop this infection. And I think as you said, Dr. Betten, they present to the hospital. And so -- they come to you, they're in the hospital. And so when you're thinking about that classic patient, you touched a little bit on resistance a little bit. Maybe just talk through what are you thinking about in the context of the course of treatment and any associated outcomes with these particular patients?

Yes. I think Dr. Brett did a nice job of kind of setting the stage for this. It's what brings them to the hospital, right? And they were worried about it to begin with, so they present sick, right? And that can be a wide variety of presentations, right? It can be redness, it can be pain spelling fever but you also have a chunk of those patients that are going to have septus, maybe even septic shock. And what's interesting, Jared, is that [indiscernible] is very well published and research in the hospital setting. But this type of patient, you often don't find a lot of good evidence to kind of how does that journey look and there's a really nice publication that came out -- just a couple of years ago out of Hopkins and University of Maryland Medical Center that really looked at that journey that you're talking about. And Again, it's significant. You talk about 20% of patients going to the ICU, average length of stay, 8 days, over 1/4 of patients needing to be in the hospital for 2 weeks. Mortality is 10% in these patients. So 1 out of 10 patients are dying well, they're in the hospital. And if you push that out to 30 days, you're now talking 1 in 6 patients. So huge burden of illness -- and that doesn't even get to some of the infectious complications that we heard a little bit about before, right? Patients have line infections, they can get metastatic complications. So you can get infective endocarditis, so heart infection can get bone and joint infections, you get septic thrombophlebitis, where you're essentially stirring off blood clots, so from the bacteremia or the fungemia. And so -- it's a huge burden of illness. There's a wide array of what it might look like. But as you can kind of tell, it impacts a lot of patients in significant ways. So when you think about this patient population, you're thinking about empiric, okay, so I think this patient might have a cabs or they've got a line, they're here. What -- do you think about resistance passengers? Like, what do you think about when you -- as you're starting empiric therapy, we talked a little bit about therapy today, but.

Yes. Resistance is a huge issue in this population, much like it is in most of our populations. But -- and I think we touched on this a little bit before. But when you talk about line infection, the first thing you think about is Grand Plaza board is on staff and in particular, MRSA, right? [indiscernible] safaris is associated with devastating outcomes in patients loves the metastasize. It's a sticky budget likes to go places. And even though we've had antibiotics that treat this for like 4 decades at this point, we still don't really know the best way and the outcomes are poor. Sometimes we get multiple antibiotics. We're trying to find that right cocktail. And so I think from a resistance standpoint, you're immediately thinking going to -- I'm going to start to 1 gram-positive therapy to cover from RSA. But as we talked about a little bit before, I really like what you said about the transient bacteremia and that can colonize the catheter. See a lot of gram negatives in this population as well. And so what I think you had a lovely list up there of [indiscernible].coli Club Sella and you have 15% to 20% of those isolates are resistant to our standard cephalosporin therapy that we would give patients. And so that leads to a couple of different complications. First off, it means that 1 out of every 5 times when we empirically treat those patients, we're going to miss, which put those patients at risk for worse outcomes. But then our drug of choice, which we have a really good 1 for those patients, which is the carbapenems you give a couple of weeks of carbopenems do you have a lot -- you're perpetuating the cycle of resistance in that scenario. So I think of that as well. And I think it was touched on a lot in the rezafungin discussions. But again, you see fungemia in these patients as well. And when you think about resistance, I thought Dr. Clancy did a nice job of summing it up. But certainly, you can see [indiscernible] in these patients. You can see [indiscernible]. You can see all of these and so really across the spectrum of these different bacteria or fungi that can cause this infection, they're worried about resistance that might compromise empiric therapy makes it more likely the way you start up front won't be active, and that's going to put your patient behind the 8 ball for worse outcomes.

Yes. So I think -- and we've been focused, I mean, obviously, these infections are severe. Resistance is a big issue. I mean, we're talking a lot about these patients being at home coming to hospital. But there's also another side of this coin, which is that these patients oftentimes have other things that bring them the hospital, not infection. So Dr. [indiscernible], I know you have recently had a publication, maybe you could briefly share with us kind of what you found specifically around that topic of inpatient risk.

Yes. So we did an observational retrospective study of a cohort of patients with central lines either on TPN or not on TPN in our medical center and then also compared it longitudinally to a couple of other time points over the past decade. And we did find an increased risk of central line infection in patients on TPN, which was not unexpected. There has been improvement in that risk over time, especially with implementation of some of the CDC guidelines. But that risk remains. I will say I think there is a perception, especially among physicians and other providers. The risk is much larger than maybe in reality of this. We usually quote patients 1 in 100 days. So 1 in 100 days on TPN, we could expect on caps. Patients will tell me Dr. Sons said, if you start this, I'm going to have mushrooms in my blood tomorrow and I. I'm like, well, no, it's not quite like that. But I think for me to explain to patients to patients and other providers, okay, we're doing the line maintenance. We're doing all the guideline-based clappevention, and now we have something else. We have an extra tool to prevent caps in this population, that would be like a dream.

Yes. Thank you. So basically, we've got this population now that potentially is in your hospital, thinking out for some other reason. And then they develop because they are at risk as we just described, so they may develop an infection. So can you just talk through some of the implications of that to you and your hospital and some of the things you think about there?

For sure. And before you even get to the implications for me or the hospital, I think let's talk about the implications for the patient, right? And so first and foremost, there's an attributable mortality for a hospital onset clouds of 12% to 15%. Again, you're talking 1 in 6, 18 patients. That's a huge mortality rate. So that's the first thing. And if you survive, you buy yourself another 10 to 14 days in the hospital. And as previous panel is nicely touched on before. Every day, you're in the hospital, you're risk for $8 billion other things occurring in that scenario. So I think first and foremost, there's that piece. Now from the hospital standpoint, there's a couple of pieces as well. hospital onset Club C is the most expensive HAI. So if you look at surgical site infections, you look at Coty, you look at VAP even Class is the most expensive of all those. It's about $40,000 to $50,000 per case is usually what's quoted if you look at the literature on this. So there's a big cost, which is going to push you over DRG and have reimbursement issues that you're going to have to deal with. But even in addition to that, it's publicly reportable and so [indiscernible] rate, you can go search it for any institution right now. And so the last thing our institution wants is more and more of these in that scenario. And so there's a prestige per that patients can go look at this and it might impact people coming to your institution for care. And even in addition to that, there's potential CMS penalties with reimbursement that come with that as well, too. And so there's a -- again, patient first, but both the patient and the hospital side, there are significant implications of that hospital-acquired infection.

Certainly detrimental on all aspects. And so in the last little bit of time we hear, Dr. [indiscernible], you're part of our NutriGard Phase III program, your principal investigator at your site. Maybe just tell us a little bit what was your interest in the study and kind of where you are as far as enrollment and patient population.

Yes, I think -- I've said that to have another tool to prevent Clopsy in this very vulnerable population, having that line if you can't eat a drink, sometimes since being an infant. That's your lifeline. And to lose that, it's devastating. We heard about each time there's a [indiscernible], trying to get a new line and the risk of not having vascular access. So to me, I think it's very important to my practice and for my patients to I really hope that this study works. And when I mention it to patients, there's a lot of interest. We haven't had people say, "Oh no, I don't -- they want this to, they want to get involved.

That's great. And so I guess -- and lastly, Dr. Brett, you had mentioned, obviously, you're sending patients out the door and you're telling them, hey, you're at risk for these infections. So what having an opportunity to talk about a drug like DefinKat? What might that mean for that conversation?

I think that would give me a lot of confidence and be very reassuring to patients. I think that's...

Yes. Thank you. So any other last comments or points or anybody.

I just wanted to add and that that choice of line and choice of sight and the ability to use a new mine with an untouched lumen and a single lumen catheter when available can also help make the difference as far as risk of line related infection. So we don't always get our choice of catheter, and we don't always get to use a fresh line, but that can make a big difference and just things about like mine site like, for example, if you've got a patient who's got a tracheostomy and they've got a whole bunch of secretions, you don't necessarily want neck line, you might be better off with the pikline. And then sometimes patient already has a Hickman and they've got a multiminute device and the risk with a multilumen device is much higher than with a single lumen so again, we don't always get our choice, but some of those factors play a role. And the risk of line-related infection.

Well, great. Well, I thank you all for joining and helping us understand a little bit more about [indiscernible] and the detrimental effects it has to these TPN patients. And so with that, I will turn it back over to our CEO, Joe Todisco.

Thanks, Jared. Before we get into Q&A, I just -- I really want to thank the thought leaders who came here today and the team that put this together. A lot of work went into today, and I really appreciate the efforts of everyone. But I also just want to touch on a couple of things before we go to questions. In less than 18 months, we've gone from a single product company with no commercial history, pigeon hold into the renal sector, to a multiproduct cash flow-generating, diversified specialty pharmaceutical company with multiple pipeline opportunities. in my view, we didn't just change ZIP codes we move countries, right? So I'd also like to highlight that we announced the Melinta acquisition in August -- closed it in August, and in less than 4 months, achieved over $35 million in operating synergies. And I really think that highlights the capabilities of this team to execute on our objectives. But going forward, we've got a great trajectory ahead of us. You heard a lot today from the -- about the value of our pipeline. We have 2 meaningful assets with REZZAYO and prophylaxis as well as defect in the TPM space. And we have the ability to do creative business development deals. We didn't present on it today, but it is worth highlighting the strategic investment we made in [indiscernible] gives us a tollhold in a highly complementary acute care asset with a near-term data readout hopefully later this year. And on the long term, we're an attractive durable platform with launch experience across multiple therapeutic areas and settings of care. And we have the ability to onboard additional new assets. So I'm excited about our capabilities and what we've built going forward. And I think lastly, just from a value creation for shareholder standpoint, I do want to highlight the recently announced share repurchase program where the Board authorized the repurchase up to $75 million of our common stock. I think this does underscore and kind of bellies our view that public markets are not currently appropriately valuing CorMedix and the value that we have here. We have started the repurchase process and expect to be active in repurchases throughout the year. So for Q&A, I'd like Liz, Pete and Jared to come join me, and we can start to take some questions from the audience. Sorry, Go ahead. right here. You need a mic. Sorry.

It's Leo from RBC Capital Markets. I just wanted to go back to the discussion around payers for a second. I think -- what we heard was physicians don't always have the choice of what drug they want to use. So can you talk a little bit more about how access is going to work if payers want only higher-risk patients, how easy it is to stratify patients who might need use prophylaxis by risk. And similarly for TPN, is there a way to stratify which patients might be highest risk or receiving TPN just to maybe make the role for payers easier.

Yes. I mean I'll let Liz comment on it in a minute. But I think for REZZAYO, certainly, I think you also want to draw a distinction between the azoles, which we expect -- which are Medicare Part D and REZZAYO prophylaxis, which we would expect, if approved, would be Part B, right? So you have a little bit different dynamic with economics. And certainly, we have the ability for both products, right, to engage in payer discussions and contracting, that's certainly a part of our launch strategy.

Yes. I would say for TPN in particular, we have done extensive market research with the payers themselves. -- unlike maybe some other therapeutic indications, I think there is broad agreement that all TPN patients are considered high risk because of the long-term indwelling device that they have. we saw very positive reception to covering and reimbursing defend cath for TPN patients at a number of different price points. I think from a payer perspective, when you're looking at total cost of care and understanding what it costs for these patients to become repeatedly hospitalized they're willing to make that strategic investment upfront. So I don't think from a -- we'll see when the data reads out and certainly when we get to contracting, but from what we've seen so far directionally, we're seeing very positive feedback from payers as it comes to TPN. I don't anticipate that it's going to be that different from a Roseoprofe standpoint, right? There's a significant investment made into these patients for the transplant journey. And so to think about not protecting the patient from something like a fungal infection after investing weeks, months, sometimes years of treatment and inpatient stay that could total millions of dollars to not protect them. I anticipate we will see something similar with the payers. We haven't started to engage and pay our research around periphylaxis. But anecdotally, what we're hearing certainly from the clinical community is there is a need, right, for a long-term antifungal regimen that does not have the DDIs that they're seeing now. And given those challenges that are being presented with the rehospitalizations and the constant titration of men's, I would anticipate that we would have some fairly positive feedback as well.

I just want to add to that. I think specifically for DefenCath, right, the real world in the in hemodialysis showed a 70% reduction in hospitalization.

Absolutely.

Right? And if we can read through that, obviously, it's not guaranteed. But into TPN, it's obviously a meaningful savings for the payer.

So it's Neil Clancy again. And this is really Pete, for your group. One thing that always struck me about from the earliest days of rezafungin is actually the potential for pneumocystis prophylaxis, which really didn't come up and if you want to talk about drugs that are difficult to use, the azoles are difficult to use, trametsulfur historic anti-neumocistis agent is among the most difficult drugs for patients to tolerate, particularly in these patients. So for the panel, do you see the pneumocystis activity playing and potentially now you could avoid both as walls and trimethromsulfhin in prophylaxis, which is a game changer, really.

I'll take just 20 seconds to answer that, but Yes, especially in CLL, which is the most common leukemia in this part of the world, when we are using our triplet combination and using CD20 monoclonal antibodies. They were at very high risk of pneumocystis prophylaxis. And you mentioned primeteprim, selfemetuxaola bacterium, extremely toxic drug, renal dysfunction and all of that. And in those patients who need prophylaxis for a long period. Again, a long-acting echinocandin would fit in very profoundly, not just to prevent immosistes, but also to protect them from Candida and malls during the period of neutropenia.

Jason? .

I guess this is another question for the panel, too. Could you maybe talk about -- when you think about the adoption of REZZAYO's clinical practice in prophy which of the patient segments that you would prioritize first? And then how do you think about the duration of prophylaxis versus today? Could it -- would it be the same? Could it be longer because the drug is easier to use? And then just 1 follow-up. How should we think about REZZAYO in this dynamic of increasing resistance to azoles?

I believe that question was for the panel. We need a microphone over here.

Everything that you said is correct. But 1 thing, again, I want to add to the entire dynamic of prophylaxis as CAR-T, which we didn't discuss today. A lot of patients will now be bridged after chemotherapy with CAR-T and not go to transplant. And these are patients who are profoundly immunosuppressed, not just low neutrophil counts but also need PGP prophylaxis, like Lance mentioned. And we do not have a good drug that would cover all of them. So good profile axis against PJP Candida, which is already kind of established with Rezafungin, looking forward to the more profile access activity, which could come in the next few months or so and with less toxicity. So I think -- as of now, with the MOL data are not active, even with Candida and PGP, there is a good case for rezafungin. And once the Phase III restore gets read out, we don't know maybe more profile access could also being optimistic about it.

Thank you. Did you cover everything, Jay?

I would just say on the antifungal end. What I like about this is that you're going to get activity against azole resistance and that front loading with the peak gives you a real margin and a greater likelihood of PK target attainment for efficacy of the drug. Moreover, because you get this massive peak and you have this upfront loading, there's potential to even treat some makinicamdin resistant infections that have what we call FKS mutations, a target mutation that the other canacandidates can't get, but because you're getting so far above your PK target early on, -- and there's animal in vitro data to support that as well. So you may be able to even use it against some echinocandin-resistant candidate.

Thank you. We're going to do [indiscernible].

A couple of questions on REZZAYO. The first one, Joe, we're going to see results from the RESPECT study next quarter. Just wondering what you we consider a success from those results? And then secondly, does this respect study open up the entire I think there's 130,000 patients or the $2 billion TAM that you talked about -- or does Mondi need to conduct additional studies to open that up? And then lastly, just regarding capital allocation and regarding the share buyback program, how should we think about BD going forward? Does that mean more of a bolt-on or SP-63 Something as big as Melinta again.

Okay. I'm going to try to remember all those questions. I may have okay. So look, with the second question, obviously, we cut the TAM and moved away from 130,000 patients to more of a dollarized base system that really kind of takes into account the duration of therapy that is needed for the various underlying conditions. In terms of what will be available to REZZAYO, if approved, it's really going to depend upon the Phase III data results as well as the final label from the FDA, Right? So there may be potential to pursue investigator-initiated studies, maybe opportunity to pursue additional Phase III studies that's something we'll have to review once that Phase III data comes out. Now in terms of, obviously, what are we looking to see? Yes, we want to hit the primary endpoint, I want to hit the secondary endpoints. I think in terms of what will be available with top line, I don't anticipate that pathogen data will be available immediately. It will likely take a few weeks or months, right, for that data to be calculated and ultimately published. But right, we want to meet the endpoints of the study. Right? In terms of capital allocation, certainly, we wouldn't have announced the share repurchase program if we weren't comfortable in our cash flow forecast and our ability to do both of those things to pursue additional kind of tuck-in BD as well as the ability to repurchase shares. In terms of the types of opportunities that we're focused on, last year, we were pretty clear we were out looking to do something transformational, right? That's what we're looking to do. Melinta was #1 on our target list. We went out and we got that deal done. Where we sit today, I don't necessarily think we need to do anything transformational. I think our focus from a business development standpoint is really on finding assets that are synergistic that can be kind of tucked into 1 of our existing field deployments or where we may need to be with REZZAYO and prophylaxis right? Doesn't mean I'll never close the door on something larger than that, but that's not where we're spending a lot of our time today.

So I have a couple of questions. One, there is part of the discussion talking about top 10 transplant centers, having certain preferences for agents like posaconazole. I was curious what would it take or what types of metrics or data would you need to show these centers or other centers of excellence to prefer REZZAYO over time? And then the second question, I think, might be for more of the panelists just thinking about who would be the best candidates to start REZZAYO on and out of the gate? Like who would you want to give REZZAYO initially if you had it available?

And just to clarify your second question, you're speaking prophylactically.

Prophylactically, Yes.

Great. I guess for the first question, -- so I think from our interviews with key opinion leaders and some of those here today, the data in the microbes that come out in the study, right? So if it does cover mold and aspergilspecifically, Candida and PJP, I think it has a very good chance of competing across the spectrum of activity. And so where that starts and when it starts, I think it all starts the data, right? And effectively, if we can compete with those 3 categories of microbes, I think REZZAYO has a very strong chance of competing starting therapy at those centers and across the country. Where and what type of patients Dr. Cook or Dr. Panza.

No. So we got -- that's one. We will consider a patient like high risk for in the get-go. So for example, patient with history of mall infection coming into transplant, where that trade-off is quite concerning that they will have a gap of normal coverage. Those will be the ones that I will particularly be interested Also, there are certain regimens for conditioning that put the patient on higher risk like that wants to cause more epithelial damage, like high-dose radiation. Those will be other and even like meta base, regimens that are more GI disrupted. Those will be the 1 that I would probably consider. And also in that scenario, we'll give me a peace of mind that I will not have this fluctuating immunosuppressant levels for those patients to.

I'll have 2 settings, nontransplant, of course. One is certainly CAR T, and this is something that I feel like the urge to explain. We are doing so many more CAR-Ts nowadays as definitive therapy to reduce the duration of treatment, especially in ALL. Hopefully, in AML in the future, and these patients are at high risk of PJP candidates well as malls and all these patients need prophylaxis. As of now, they get PGP profile axis with pentamidine, which is not a good drug. Nobody likes back prime or at vac. So there is a huge need for a long-acting PGP profile axis. And for all patients who are going on clinical trials, even in frontline settings, we face a lot of challenge putting them on azole antifungals because of DDI, which was discussed at great length. So there is a huge scope of patients, CAR-T, frontline, relapsed/refractory are going on Phase I trials as well as post transplant.

And I'll just add in the saga transplant patient population. Liver and even above the diagram lung transplant, where Candida can be a very large problem. Following a complex surgery, we often put these patients on prophylactic regimens of azoles and that can be really a major burden. So again, in that patient population, I'd say, right out of the gate would be they're low-hanging fruit.

And prophylaxis and solid order transplant is highly heterogeneous and center dependent. There's 1 transplant problems, for example, a lot of people on 4 to 6 months of post-transplant azoles. So that's a lot of consumption of Azoles.

Maybe just following on from that question. We've heard a lot of places where Baseoprophylaxics can be used. Can you just help us contextualize how long do you think it takes to establish a consensus sort of guideline or protocol within these different centers in terms of where you are going to use it longer term?

So I'll start off that REZZAYO in treatment guidelines today in NCC and for treatment, right? And so effectively, when the data is available, we'll be looking to go after those nationally recognized and understood guidelines based on the data, right? And I think I won't speak for the panel, but from prior personal experience, those guidelines nationally really drive adoption at the large nationally recognized clinical practice sites, right, a number of these panelists are after. So I think understanding where that data is. We have the benefit of that data being read out several months before the FDA decision and the FDA label, but we will be working with the market access team doing preinformation exchange at the appropriate time to drive that information while the FDA is evaluating the application.

Maybe just want to follow up on TPN. As we think about maximizing the DefenCath TPN opportunity, anything which you have to consider or balance from the potential contracting of DefenCath under the current indication?

Yes. I think -- I mean, I think what your question is more related to is reimbursement and pricing across channels, right? So what I'd say is that we have a right now, call it, a regulatory and development strategy to pursue a separate J-code, right, in TPM, Presumably, if we are successful in doing that, that's 1 pathway and a little bit easier to differentiate. If we are not successful in obtaining a separate J-code, we have a different strategy around, call it, channel pricing, it gets a little bit tougher, right? We could be -- and we'll have to be mindful of ASP management and how we're going to go about contracting across the therapeutic areas.

A couple of questions. First on REZZAYO and just to build up on the previous question. If you have this dynamic, I love to hear, what proportion of the prophylactic addressable 130 patient pool, whether it's AML or nachos actually prophylax today versus eligible clinically eligible but not treated. And then you stated prophylactic has a lower barrier due to less formulary dependence and you expect -- would you expect materially faster uptake curve versus the treatment indication I have a follow-up on TPN.

All right. As I said before, in terms of the 130,000 patients, that was an older kind of market research, we've kind of recut how we're looking at the total addressable market, and we can provide a little more detail less in some one-on-ones as we move forward around how we think about the subset of patients with multiple underlying conditions that are currently getting prophylaxis for Candida, Aspergillus and PJP. And then there's another subset of patients that are getting PJP only therapy after, right after they complete the Candida and Aspergillus. So we'll come back to you on a percentage. In terms of our analysis on the TAM, all of those patients are currently getting prophy. So that -- so we recut it a little bit differently, have only included patients that would currently be getting some type of prophylaxis. But what was the second question.

Faster uptake versus treatment like...

Look, I don't think we're ready to guide yet on the ramp to peak for Prof. Obviously, it's going to depend to a large extent on the pathogen data on the strength of the Phase III results. And once we have our top line results, maybe we can comment on it a little bit more.

That's helpful. And maybe on TPN front. Is the 200-patient NUTRI-LAC study sufficiently powered to capture the 1 to 4 infection episodes per 1,000 catheter days. And then what clinical endpoints do you think will drive the PTN adoption or P&T adoption and payer coverage? And then just lastly, you mentioned the 50% commercial coverage on that subgroup. What's the other half of the payer landscape look like? And what kind of dynamics around formulary versus inpatient versus at home.

I'll address the third question first, and then you can get to it. So we have the breakdown on that chart. If you look at the slides, it will say about 50% is commercial -- there's another percentage that's Medicare, Medicaid right and government. So we do have that breakdown. That's from our most recent market research.

Do you want to talk a little bit about the power of the study and then we can go into clinical endpoints?

Sure. Yes. So the way the study was designed is actually -- it's an adaptive design. So it initially sort of teed up to have 90 patients that would be in the trial. And then after those 90 patients, and once we saw 14 infections, then it would actually go to a data safety monitoring board that want to evaluate effectively those 2 treatment arms, they would then be able to do a number of things. So 1 of which would be we didn't see the infection rate that we thought. And so that's how that allowed for us to increase up to the $200 million they could also say that there seems to be a discrepancy between the 2 treatment arms, and they may then have a conversation through FDA to say, and maybe might consider ethically stopping the study early. So I think we sort of...

No, I don't know where that came from. To get excited.

So nevertheless, the study effectively was powered at 90%, with the option to increase if the infection rate was not quite as high as we have seen in the literature because there is a pretty large range in literature around infection rates.

Yes. And I think the last part of your question was what clinical endpoints did the community need to see. And I think right? We've talked about before. It's in the guidelines to have an antimicrobial catheter lock solution. To date, there isn't 1 that's FDA approved. So I think if we are able to demonstrate a meaningful reduction in infections as well as hospitalizations are related to infections I don't anticipate that we would have a high burden on top of the data that's coming out of Nutriguard, right? I think just as we've heard to our panelists and from the market, there is nothing right now. Our drive to go into TPN was it was our #1 place that we were getting requests because patients were getting referred to hospice because they had no other options. So I think that both inpatient and outpatient, right, the avoidance of colabsy is such a driver for a number of reasons that I don't anticipate that we'll have a lot of clinical hurdles to jump through, provided the data reads out as we hope.

Got about 3 or 4 minutes left. Any last questions? Did I ask, are there any TDAPA questions in the last. All right. Well, thank you, everybody, for attending. Really appreciate it. Thank you.

Thank you very much.