Thanks, everyone, for joining us for our biotech conference this year. I'm Vamil Divan, one of the biotech analysts here at Guggenheim. Pleased for our next session here in this room, we have SCYNEXIS, and we have David Angulo, the CEO, Ivor Macleod, the CFO, joining us. So have some questions. Obviously, if any of you have questions in the audience, please feel free to raise your hand as well. But thank you both so much for joining us. I think the first maybe before we go right into the main questions, just if you want to give any sort of opening remarks or just kind of how things are going with the company overall, kind of where, where your focus is here for 2024, and then we'll get into more specifics. Thank you, Vamil. This is David Angulo. I'm the CEO of the organization, and thank you for really for joining us for this chat, and thank you for the invitation. So for the ones that are not familiar with SCYNEXIS, we are based in New Jersey. We are a biotech organization dedicated at this point in the development of new antifungal medications for systemic invasive fungal diseases, which is a very significant unmet medical need. We have been successful in develop the first new class of antifungals in more than 20 years, and we have already received approval for the first analog, which is called ibrexafungerp, in the United States, and we are working right now in the second-generation analogs from the same platform of antifungals. We have partnered our first analog with our first product approved with GSK, which is now responsible for the commercialization of that particular product. We are now focusing and really continue developing our platform of antifungals in very significant areas of unmet need, particularly in the fungal space, in the antifungal space. Okay, great. So before we get into all the pipeline work you're doing, maybe we could just talk a little bit about BREXAFEMME and the collaboration, obviously you mentioned with GSK and just the status of getting that product back in the market. Now GSK is sort of leading the effort, but if you can give an update to us, kind of where things stand on the manufacturing side and any sort of projected timelines on re-entry. Sure. Thank you. So we have two aspects to this question. One aspect is really that the reintroduction on the market for BREXAFEMME is a commercial name for ibrexafungerp, which is the antifungal medication that was approved for two indications already in the United States. It's for the treatment of vulvovaginal candidiasis. It's a single-day treatment. And then we got a second approval for the prevention of recurrence for recurrent vulvovaginal candidiasis, which is a once-a-month treatment for six months. Because of some manufacturing issues, we needed to really stop the commercialization of the product a few months ago, and GSK is working right now in really resolving all these manufacturing issues to try to relaunch the product. Really, the commercialization efforts are entirely on the hands of GSK at this point. However, we know that there is a lot of energy and a lot of work towards really putting the product back in the market. We are all highly motivated because it's a product that is a very substantial unmet medical need. There are very few treatment options for patients suffering from vulvovaginal candidiasis, and when they don't respond adequately to these oral treatment options, there are no other alternatives but BREXAFEMME. So we are all very highly motivated to really bring this product back into the market. The main efforts for that purpose are being through GSK. GSK is responsible for bringing the product back into the market. Okay. So maybe then let's shift to the trial side, and obviously, you have a number of trials looking at more in the hospital setting. So the few that I want to ask you about, FURI and CARES, I think, you've talked maybe some data coming this year, potentially, SCYNERGIA on the combination side and also VANQUISH. Maybe you can just talk about the kind of the concept behind those trials, which one is each going after in terms of the population of patients, and then just the status when we might see some data. Absolutely. Thank you. So the mechanism of action of the glucan synthase inhibitors, of the platform of products that we are developing, they are called glucan synthase inhibitors, and they are particularly effective against infections caused by Candida. Candida is a pathogen that can cause systemic infections in the blood, in the liver, in the spleen, and they have very high mortality. However, glucan synthase inhibitors as well have activity against other kind of mold infections that are rare, a little bit more rare, but also with a very high mortality, like Aspergillus, which is an infection of the lung that has a very, very high mortality as well. So the initial development program for ibrexafungerp, we focus in addressing many of those unmet medical needs, and those trials are addressing these areas. The FURI trial is a trial that it is intended to evaluate ibrexafungerp as a salvage therapy in patients that have systemic fungal infections. Could be Candida, could be Aspergillus, or other rare molds or other rare infections that are not responsive to current antifungal therapy. And I don't know if everyone is aware, but the options that are for treatment of current antifungal-- the current treatment antifungal options are very, very limited, are only limited to three classes prior to the approval of ibrexafungerp. So there are very few treatment options. Once the patient develop resistance or not responsive to those limited treatment options, then it's where we were evaluating ibrexafungerp as a treatment alternative for them. The FURI clinical trial is for that purpose, to evaluate the activity in those patients that are not responsive, not responding or are resistant to other antifungal therapies. We already completed the enrollment for that particular trial. We are in the process of analyzing the data, and certainly, the plan is to really have the data analyzed and the study reports completed by the first half of this year. The second study that you mentioned, CARES. The CARES study is evaluating ibrexafungerp in patients who have infections due to Candida auris. Candida auris is a specific species of Candida that I'm not sure if you have been following the news sometime. It's multidrug-resistant. It typically does not respond to the azoles, which is one of the groups, limited groups of medications. It, half of the time, don't respond to amphotericin B, which is the most potent antifungal that we have right now on the market. We are evaluating ibrexafungerp, who has demonstrated very good activity in vitro and in vivo in animal models against this disease. We evaluated ibrexafungerp in patients with Candida auris infections. This is intended to really provide further information regarding the potential utility of this platform of products, and specifically ibrexafungerp, against Candida auris infections. We completed that trial as well, and we are doing the data analysis as well. These two trials were meant to be complementary to each other, to really try to seek potentially a regulatory approval in the future for the treatment of very difficult to treat and resistant Candida infections. The data analysis, as I mentioned, ongoing, and we're also planning to have that study report ready by the first half of this year. The other study that you mentioned, which is the VANQUISH, and I'm gonna go through the Candida, the Candida studies first. VANQUISH is a follow-up study that we did after the approval of BREXAFEMME for the treatment of vulvovaginal candidiasis. The VANQUISH study enrolled patients who were already failing fluconazole. Fluconazole is the only other oral available therapy for vulvovaginal candidiasis, and also has a very good response rate generally. There are many patients who fail, and those patients who fail, we wanted to evaluate how BREXAFEMME will be what the response will be with BREXAFEMME in patients who failed fluconazole. The VANQUISH study is fully enrolled, analysis is nearly complete, and we're also planning to really have that CSR ready, the study report ready by the first half of this year. The last study that you mentioned was a phase II study, which is called SCYNERGIA. SCYNERGIA is evaluated ibrexafungerp in patients with invasive pulmonary aspergillosis. Patients that are immunocompromised are at risk of really getting Aspergillus in their lungs. Aspergillus is a mold that is like a very commonly mold that is around us. But if you are not immunocompromised, you don't need to worry about it. But patients that are immunocompromised, they get that mold in the lung, and they cause very severe and fungal infections. Currently, the mortality of this particular fungal disease is still in the 30% range, and we evaluated... It's a phase II study in which we did a preliminary evaluation of the efficacy and pharmacokinetic profile of ibrexafungerp in combination with the current standard of care, which is voriconazole, in combination in patients with invasive pulmonary aspergillosis. This was a randomized, double-blind trial. We completed the enrollment as well, and the study's in data analysis as well. And really, the study report should also be ready, wrap up by the first half of this year. Within the GSK agreement, that just to mention, why we're still responsible for some of these trials. When we licensed the product to GSK, which was sometime in May last year, there were many trials that you can see were about to be completed. We were just wrapping up the trials. Our responsibilities as an organization to support our partner was to wrap up all those trials and to really deliver the study reports to them so that they can really continue progressing the approval process for them. So one, just follow up on that. I was gonna ask you is on, in terms of public data release. So you finish up all the analysis, the reports, do you then give it to GSK, and then they sort of decide how it's gonna be released publicly, or is there, is there any plans from your side to any, do any sort of press release or other data release of any of these trials? Yeah, that will need to be coordinated certainly with GSK. GSK will be primarily responsible for really deciding what is the forum that they really want to get these results publicly. We know there is great interest within the scientific community and our investors to learn the outcome of these trials. So we're really discussing with them what is the best way to really try to disclose the information to the public, but as well to the scientific community that have been extraordinarily supportive of the development of this particular product. As you know, there are two studies that were open label, FURI and CARES, that we have been disclosing data because we have been analyzing the data on an interim basis, and we have been disclosing data. So really, there is. We know that there is eagerness from the investor and scientific community to try to see what are the final results from these two studies. We will be discussing with GSK regarding the publication of those results. But to be frank and honest here, is really ibrexafungerp is now a GSK product. Yeah. So they will have. It will be their publication and their disclosure policy is the one that will mostly dictate when the results will be available. Okay, so one last question there before we move on to 247. Just in terms of... You mentioned Candida and then aspergillosis. So maybe just a little bit more background from your experience on sort of what drives your level of confidence on the impact it could have on candidiasis or Candida infections, and then also on aspergillosis, kind of where is your level of comfort across the two different programs? Yeah, no, thanks for the question, because that's, that's really what I have... Well, I have been doing drug development, particularly in antifungals, for the past 20 years. So that's really the area that, that we're very, very passionate and most passionate about. And the mechanism of action, which is glucan synthesis inhibition, is a similar mechanism of action than the echinocandins, another group of medications that exists right now have. The limitation with the echinocandins is that they can only be given intravenously. They cannot be given orally.... Ibrexafungerp and our platform of antifungals have very similar mechanism of action that has already been demonstrated to be the most efficacious mechanism of action against Candida today, that exists today, in any approved product. So we have the same mechanism of action that has what we call fungicidal activity, so it's able to actually kill the Candida, not only decrease the reproduction of the Candida, but actually kill the Candida, which many of the other agents don't do. And this mechanism of action is the most effective and is the one that is among in all the guidelines as the first treatment option for invasive Candida disease. With the same mechanism of action and already data in preclinical models and already data in our previous analysis from the FURI study that I did, that we have seen very good response rate. We're very confident at this point, really, of the ability of ibrexafungerp in the platform of products that we have to have extraordinarily good response rates for Candida infections. So the FURI, the CARES data that we have disclosed in the past, plus all the animal models supporting that efficacy associated with a well-known mechanism of action, that the echinocandins are very efficacious in treating these conditions, is what really give us the confidence that really, the product really works and is expected to work very well against invasive Candida disease. For Aspergillus, this is slightly different. For Aspergillus, the mechanism of action that is most effective in Aspergillus is actually the mechanism of action of the azoles, like posaconazole, voriconazole, or isavuconazole. That mechanism of action is cidal against Aspergillus, where inhibition of the glucan synthase is not cidal, it's considered static. That is the reason why we are evaluating or we thought about evaluating ibrexafungerp in combination with... Because even with the current antifungal standard-of-care treatment options, the mortality is still very high. We consider that in this particular case, combination therapy, that is very common in the antibacterial space and antiviral space, is not so commonly in the antifungal space because it has not been systematically evaluated. That is what we believe, that really, this particular group of compounds, the glucan synthase inhibition, has demonstrated synergy in vivo models, very substantial synergy in vivo models, and that was the purpose of really evaluating this first from the pharmacokinetic point of view in the synergy study, and try to understand how this product will play with some of the standard of care agents like voriconazole. Okay. All right, great. So let's move on maybe to 247, and maybe just as a starting point, before we get too much in the details, just the history of this product, how it's, how it's sort of coming to be at this point, and then we can talk about some of the work you're doing preclinically and, and the progress we expect. But, but just kind of the background of this asset and, and your level of enthusiasm. Yeah. Absolutely. No, thank you. You know, as I was mentioning at the beginning, there are very few therapeutic options for systemic fungal diseases, and the importance of developing new therapeutic options in this field has been restated and even more, made it more clear and more public in the past year. The WHO recently announced really the list of priority pathogens, fungal priority pathogens, that they were incentivizing the companies and governments to really try to develop products for, because we're seeing an increased incidence of resistance among those fungal pathogens, an increased incidence or increased number of people affected by. Fungal infections, systemic fungal infections, are typically associated with patients who have another underlying conditions. They are immunocompromised, or they have been in a hospital for in an ICU unit for a long period of time. Because of the increase in the technology, increase in the efficacy of anticancer treatments, et cetera, the vulnerable population is growing. It's growing tremendously because now we have people surviving cancer for many more years, and all these years, they need to be in immunosuppressive therapy. All these patients are susceptible and are vulnerable to invasive fungal diseases. So there is a very substantial unmet need for more alternative treatment options. There are only three main groups, and the fungerps, as we call this particular group, is the fourth group. So we develop first ibrexafungerp, focused in certain conditions. However, we identify areas that we can optimize the molecule, and then we have a large platform of other antifungal agents that follow the same mechanism of action. 247 comes from an initial screening, initially 100 analogs, then we narrowed it to 30 analogs, then we narrowed it to 12 analogs, and now we finally selected the analog that we wanted to move forward because of specific characteristics into the development program. And we have been very, very pleased through the preliminary results that we have right now. We're extraordinarily pleased what we are seeing. SCY-247, which is the second generation fungerp that we are developing right now, is in preclinical stages, and we're planning to be in first in humans by the end of the year. So at this point is when we are creating all the characterization of the molecule, understanding adequately in vitro and in vivo models, their activity against the specific unmet medical needs and the pathogens that we want to cover, and as well as understanding the drug-drug interaction profile and the safety profile of the drug. So far, very excited, and this analog as well is really allowing us a better opportunity to really have both intravenous and oral formulations. And that's an important key differentiating factor and one of the reasons why we selected this analog as well, because we saw better opportunity to have an easier intravenous formulation. ... Okay, great. So I know you just presented some preclinical data last month. Can you just go over what the findings were on that? Sure. As I mentioned, we are really evaluating where this particular product may fit within the unmet medical needs, current unmet medical needs. And one area that we are very, very interested in exploring is mucormycosis. Mucormycosis is a very severe, deadly, and devastating fungal infection. In many places, what's called black fungi, because what it causes, it causes necrosis. It causes the tissue to die, and so the tissue becomes black. And you can really see that the tissue may die on the face because it causes infection on the sinuses, it destroys the lung, etc. So it's a very devastating condition with a very high mortality. It often affects patients with diabetes. It really got into the news because it affected patients with COVID. So, with the COVID pandemic, you saw a lot of reports of people dying, not only for COVID, but dying for this other super infection of mucormycosis. Current treatment options are very limited because many of the azoles don't work, few of the azoles do work. Amphotericin B is the treatment of choice, but it is an intravenous medication that has very high toxicity into the kidneys, so it's difficult to keep the dose regimens that are needed to really treat this infection with amphotericin B by itself. We did a preliminary work, seeing that really this particular analog, 247, has very good activity against mucor, and actually has surprisingly good activity in combination with amphotericin B. We just presented data in the Advances Against Aspergillosis and Mucormycosis international meeting last month, in which we presented an animal model, a mice neutropenic or immunocompromised model, in which we evaluated three doses of SCY-247 plus in comparison with amphotericin B, which is the standard of care, and in combination with amphotericin B. We saw that really SCY-247 had in that particular animal model comparable efficacy than amphotericin B, which is the current standard of care with high toxicities. However, in combination with amphotericin B, we saw surprisingly good results, surprisingly good survival rate in this mice model, which is very highly lethal. That really obviously gave us a very good, a very good hint of really what could be one potential treatment opportunity or development opportunity for this particular molecule. As you know, we will continue. We'll continue evaluating many other models in other fungal diseases, and we're planning to really continue releasing some that data in the upcoming months. And then you mentioned you're going into clinic by year-end. That is correct. Can you just talk about what's the key work you're doing this year to- Sure. - to decide what to do? Obviously, before going into your first human study, you need to run all your toxicology program. So your toxicology program involves really giving the product into for a number of days in different doses, ideally doses substantially higher to what you're expecting to achieve, to do in humans, you need to give it to in some animal models. So we're going through all the toxicology program as we speak, and we're going into the scaling up of the manufacturing process in order to enable the, what is called GMP manufacturing, that is allowing you to really be first in human. All that has been progressing nicely as planned. So right now, we are at. We consider we're on target to really being first in human with this particular analog by the end of the year. The first study is typically just evaluating the pharmacokinetics of your product. You evaluate how well your product is tolerated, you start escalating the doses, then you start escalating single dose, then multiple doses, and you understand what are the levels that you're able to achieve, and you compare those levels versus the levels that have shown efficacy in the animal models, and you see if there is good parity there, that you're able to achieve efficacious, efficacious levels in humans. That is what we're going to do by the end of the year. You mentioned you have both oral and an IV option here. How are you gonna choose between them? Yeah. That is— It's an interesting question. So for ibrexa— for BREXAFEMME, we attempted to develop intravenous formulation, and actually, we were successful in running up to phase I. However, we identified that that particular product was, it's slightly tricky to formulate in an intravenous formulation. This product, we already started, all the toxicology assessments with the oral formulation, and we are in the process of really doing the intravenous formulation development. The oral formulation is gonna be slightly ahead than the intravenous formulation first in human, so the first in human is expected to be with the oral formulation, with the first in human for the intravenous formulation expected the next year. Okay. Maybe just last couple questions here. We have a few more minutes on more on the corporate side. Mm-hmm. Maybe you can just talk, maybe, or if you want to jump in on this one, just current cash position, how you see your cash runway. I know there's still some economics between you and GSK, obviously, on the collaboration, how that sort of fits in here. Yeah, thank you. Yeah. So we haven't, of course, published our year-end cash, but at the end of Q3, we had $105 million in cash and cash equivalents, which is a cash runway of more than two years. This year, we do expect to start receiving some of the nearer-term development milestones from GSK. There's $10 million tied to the delivery of the CSRs of the studies that David was mentioning, and then there's a further $30 million tied to the restart of the MARIO study and the progression of the MARIO study, and then $7.35 million upon hitting the primary endpoint in the MARIO study. But it's important to point out that even without assuming any receipt of future milestones, we're in a very strong cash position. ... Okay, and maybe just, around the expense side or burn the expense- Around, yeah, around the expense side, what we've been guiding is, unfortunately, our trailing twelve months never predicts the future twelve months. And what you really need to do is go back to 2020 pre-commercialization, and those levels will be pretty close to what we're expecting prospectively. So on the R&D side, on an annual basis, we're anticipating somewhere between $25 million and $30 million, and then for SG&A, somewhere in the $12 million-$15 million range- Okay. for 2024. Okay. All right, so maybe in the last question, I just want to touch on, I know there was some work being done in China to get ibrexafungerp there as well. Maybe you can just give a, an update on, on where that stands. Sure. We have a partner. We have licensed the product to a partner in China, Hansoh, and they actually submitted it. They conducted a phase II trial over there in order to get the product approved for vulvovaginal candidiasis, and they submitted a market authorization there last year. We announced that, I think that sometime in the middle of last year. And the timelines for approval there, so the review process is ongoing. The timelines for approval there is, are a little bit less clear and fixed- Yeah than it is in the United States. Yeah. But typically, we have learned that really, approval or decision, let's say, decision is given within, typically within 12-18 months. So we are approaching the 12-month clock- Mm So to speak, and we have not heard anything else regarding if there is any other anticipation of when the time for the decision from the regulatory agencies will be achieved or when it's expected. However, the review process is ongoing, and we have been collaborating with them to really support them through some of the questions that they have been receiving, et cetera. So at this point, we are optimistic, thinking that since the data that we generated here in the United States was very, very solid, two large clinical trials in acute VVC, et cetera, and they just replicated the same trial in China as well, we are optimistic in terms of really the outcome for that review process. Okay. All right, great. I think in the interest of time, we'll have to leave it there. Thanks so much again for joining us. Thank you, Vamil. Thank you. Thank you, everyone, for joining us. Thank you. Thanks.