Good afternoon, everybody. I'm Seamus Fernandez, one of the biopharma analysts here at Guggenheim Securities. This is Guggenheim's annual SMID Cap Biotech Conference, and I'm really pleased to be joined by Cidara Therapeutics CEO Jeff Stein here to my left. We don't have a ton of time with Jeff, but I think it's important that we introduce everybody to the story because it's a bit of a transformation. So Jeff has a few slides that he's going to share, and I'll turn it over to you, Jeff, and then we'll jmp into Q&A. Yeah, so Cidara is a publicly traded company based in San Diego. Our sole focus is on one molecule, CD388, which is a version of what we call a drug-Fc conjugate, and it's really comprised of two main elements that are clinically validated. This is being developed for the pre-exposure prophylaxis of influenza and, importantly, universal prevention and universal in the broadest sense, meaning active against all strains and in all people, regardless of immune status, so as mentioned, two clinically validated components. There's zanamivir, an approved drug called Relenza. We have a version of that, and actually, as you can see on this slide, multiple versions. We have, on average, four to five dimers of zanamivir. So on this picture, we actually have eight copies of zanamivir, an exquisitely potent enzyme inhibitor, but really poor drug properties. We've improved those drug properties by stably conjugating it to the Fc fragment of a human antibody, and this is a YTE mutant, extended half-life Fc, and that's a component of other approved drugs as well, so very low clinical risk, but very high potential in this unique format. I mentioned it's a stable conjugate, so the linkers do not disassociate from the Fc, and this has a long half-life, and if there's one challenge that we have is emphasizing that this is not a vaccine. It is a long-acting drug. It's not a monoclonal antibody. It's a small molecule that can access cryptic binding pockets, so we invented this drug- Fc conjugate format back in 2018. CD388 was the first molecule developed in that platform, and we partnered that at an early stage, pre-clinical stage, with J&J, and that was in November 2021. Under that partnership agreement, J&J paid for all non-clinical and clinical development. We executed on all of the non-clinical and clinical work through two phase I studies and a phase IIa study. Based on the results of those studies, J&J was preparing to deliver to us the notice to proceed, which under our contract represents the formal handover of the program from Cidara to J&J. They were to have taken it into a phase IIb in the fall 2023 flu season. However, right at that period of time, they had a change in leadership in R&D. John Reed came in and headed R&D. Coming out of his evaluation of their portfolio, they made the decision to exit the infectious disease space. They started a series of divestitures, starting with their most advanced program, which was an E. coli vaccine that they divested to Sanofi. That was followed by a Hep B program, which they divested to GSK. The third in line was CD388. They started a similar process with Big Pharma. That's when we got together with RA Capital, Bain, and other investors and put together a $240 million PIPE financing at the end of April of last year, and managed, from a standing start in May, designed a phase IIb study, put it into the clinic, enrolled our first subject the last week of September, and our last subject was the first week of December, 5,000 subjects in all. Great timing because that was right before the flu season took off, so now we're in the midst of a phase IIb study. You can see some of the bullet points on your lower right there about the study, and I have some more details subsequently. Great. So Jeff, it's obviously an interesting journey for CD388, but at its core, I think we have to understand the unmet need for influenza. I think people understand it sort of peripherally, but maybe not as directly as being demonstrated in this flu season. So maybe you can talk a little bit about that. Yeah. One thing that you never know about the flu season is how severe it is. One of the members of our scientific advisory board, Fred Hayden, said, "If you've seen one flu season, you've seen one flu season." You can never predict what it's like. But we can look historically and say, you know, a lot of the influenza A historically trends around a 3%, influenza A and B slightly higher than that. So we had a conservative assumption in going into this flu season, assuming a 2% breakthrough infection rate. As it turns out, and as you indicated, this flu season is very different. It is very severe. The CDC puts out data on a weekly basis. The cumulative breakthrough infection rate from the 1st of October until last week is about 11% breakthrough infection rate. This last week, it's 29%. I doubt there's anybody in this room that doesn't know somebody who has had the flu. The reason for that is there's a mismatch against one of the two influenza A strains, which is driving a lot of these breakthrough infections, and you can see on this slide on the left part, that's data from last year, really, the burden of illness in the U.S. just from last year, and last year was a mild to moderate flu season. This season is eclipsing last year's, and on the right, you can see the most recent data through the end of last month. The way the CDC reports this is they report there's influenza-like illness, and then they do PCR confirmation, and there's three respiratory viruses that are circulating, obviously flu, COVID, and RSV. COVID and RSV is actually going down while flu is still trending upwards. Interesting. And when we look at sort of the timing of when you sort of finalized the recruitment of your study and then where you would hope to evaluate the individual doses of CD388, can you just help us understand how much of the flu season is it your expectation that you'll cover? Yeah. And the strong point of this drug is really, obviously, the potency is one thing, but is the PK. And a lot of people focus on potency, but the efficacy of a drug is based on exposure. And that's what this drug does. It provides high exposure, single dose, beginning of the flu season, covers for the entire flu season. So we're testing three doses in the clinic right now, 150 milligrams, 300 milligrams, and 450 milligrams dosed once at the beginning of the flu season. We follow the subjects for the entire flu season, and then at the end, we unblind and we will look at the efficacy. Great. Talk a little bit about the choice of zanamivir specifically as your neuraminidase inhibitor, just the evidence that supports neuraminidase in general in the prevention landscape, but also this particular neuraminidase inhibitor. Yeah, so there are two targets on the surface of the flu virus, hemagglutinin and neuraminidase, and that's why you get the designation H5N1 or H1N1, H3N2. It's the variant of hemagglutinin and neuraminidase. Our bodies generate antibodies in response to a flu infection against hemagglutinin. Monoclonal antibodies are directed against hemagglutinin. The other target, however, neuraminidase is a very attractive target, and it's harder to direct a drug against it unless you can bind an active site of neuraminidase, and you think about these targets kind of as a cauliflower with a stalk and a head. Your immune system is directed against the head of that cauliflower. Of course, the virus has evolved evasion mechanisms to mutate that head to evade the immune system, which enables it to evade vaccines and monoclonal antibodies. By contrast, the neuraminidase, the binding pocket is on that stalk, and it's a cryptic binding pocket. There are other neuraminidase inhibitors, the most broadly known of which is Tamiflu, but zanamivir is by far the most potent of the inhibitors. So raise the question, why isn't that more broadly used? The problem is that it is an exquisitely potent enzyme inhibitor, but it is a very poor drug. It has basically no systemic exposure. It has to be formulated as an inhaled nebulized drug. You have to take it through inhalation, no systemic exposure. Flu infections tend to be systemic as well as in the respiratory mucosa. It's never been a very successful drug. Basically what we did with CD388, we took this exquisitely potent enzyme inhibitor, the best neuraminidase inhibitor available, and turned it from a poor drug into a great drug by extending the exposure and half-life. Great. You've conducted, or you were J&J, or you and J&J have conducted clinical studies so far, includes a human challenge study. Maybe you can just talk about some of the preclinical data and the challenge study data that you've generated so far. Yeah. So two phase I studies, a first in human study and then a Japan bridging study. J&J wanted to do the latter because they intended to commercialize for the Japanese market. Flu is a big deal there, as well as in the U.S. and in Europe. And they also wanted to conduct, obviously, the first in human study to confirm safety and exposure. From a non-clinical perspective, we had the full supportive package, which suggested that CD388 could, in fact, be dosed once a flu season and very safe. This molecule does not penetrate cells. That's another strength is safety. Because it doesn't penetrate cells, it doesn't have cytochrome P450 interactions, no hERG activity. So it can be dosed at very high exposure. And we've dosed this up to 900 milligrams in humans, multiples above that in animals, and so far, incredibly safe drug. So it was great that across the three clinical studies, we corroborated safety, corroborated efficacy in a phase IIa study, and corroborated the PK. Great, and now let's talk a little bit about your NAVIGATE phase IIb, healthy unvaccinated individuals. Maybe just walk us through the goals of the study as a starting point and how you've designed it, and is there a sort of obvious SAP yet, or are there any things that need to be sort of confirmed as you advance towards the sort of definitive conclusion of the study? Yeah. So all three doses, 150, 300, and 450 milligrams, provide exposure based on the phase I studies above the efficacious target for the entire flu season. Now, the original objective of the study was to pick a dose to take into phase III. So the study is being conducted in approximately 5,000 healthy unvaccinated individuals. And so you might ask, well, why unvaccinated? It's because we wanted to be able to get a signal without a very large study. So in healthy normal individuals, on average, the seasonal vaccine is about 40% effective. If we included vaccinated individuals, we would have to have sized the study much larger. And the objective was to select a dose. So we will be now, the flu season this year has afforded us an opportunity. Because the breakthrough infection rate is about roughly five times higher than what we had planned for, we now have an opportunity to do two things. One is get data sooner than later. When you typically think about going to your top-line data efficacy and safety tables, you tend to report those at the same time. Safety in a long-acting drug is driven by this long half-life. You have to follow the drug out for five half-lives. That kind of sets when the top-line listings, tables, and figures are available. With this more severe flu season, we determined, hey, let's separate efficacy from safety. And so now we're planning on this week, we will be submitting a modification to the statistical analysis plan to do an earlier read of efficacy such that we now believe that we can get efficacy in the second quarter of this year instead of the third quarter of this year. So that's a big deal because then we could potentially start phase III in the fall of 2025 instead of the spring of 2026. Got it. And the likelihood that that proposal is actually accepted, is it high because the events will be very, very close or in fact even fully represented from your original plan in terms of the number of efficacy evaluable events? Yeah. I think it'll be acceptable for two main reasons. Number one is a phase II study. It's not a registrational study. And so the FDA tends to be very flexible on proposals like this. Second reason is that it is a very severe flu season. We've seen failures of the Vir monoclonal. We saw failures of the Moderna mRNA flu vaccine. There's simply nothing out there now. And I think the FDA is going to be very motivated. And similarly, BARDA, the government funding agency, should be interested as well. Great. Let's drill into the study itself and maybe just helping us level set what the study is, maybe not necessarily specifically powered to show yet or at this point, but what you would expect each of the dose ranges to show and kind of what your sort of numerical expectation for efficacy would be at each of those doses. Yeah. So our a priori assumption is that the low dose, 150 milligram, would be 50% efficacious. The 300 milligram dose would be 70%, and then the 450 would be 90%. Based on those kind of pre-specified assumptions with the 5,000 subject study, it should be powered to enable us to determine a difference between placebo and each of those three doses and select a dose. So not powered for inferential statistics, no pre-specified p-value. But that was based on the 2% breakthrough infection assumption. Now that it's five times higher, we are now evaluating the opportunity to introduce a pre-specified p-value because we believe this study is going to be powered to determine a statistically significant difference in each of those three doses. Got it. And if we were to see, what would you say is the sort of flu equivalent bar in a good season in normal uncompromised patients? And maybe you can just sort of compare and contrast that for us to an immunocompromised patient population or even an immunosuppressed population? Yeah. I think the thing to keep in mind is that, again, even though this is being dosed like a vaccine, once a flu season, it is definitely not a vaccine. So it doesn't rely on the immune system for any aspect of its efficacy. We've determined that from numerous animal efficacy studies, parallel immunocompromised and immunocompetent animal models, other antiviral drugs like baloxavir and Tamiflu have demonstrated that clinically. So technically, there should be no difference in the efficacy in healthy individuals versus immunocompromised individuals. The other important thing to keep in mind here is because CD388 targets neuraminidase, whereas vaccines target hemagglutinin, we fully expect its activity to be additive on top of vaccines, and I think that's what the FDA is going to be really focused on. This is definitely not being developed as a substitute for the seasonal influenza vaccine, which on average is about 40% effective, one of the reasons why not everybody feels a need to get the vaccine. So let's take our low dose, 150 milligrams, a priori assumption, 50% efficacy, hitting a different target, average vaccine efficacy for the seasonal vaccine, roughly 40%. So 40 + 50% efficacy, that's a darn good combination. So that's what we're hoping for in individuals that in our phase III program, these people will be likely universally vaccinated, but the vaccine effectiveness in that population is substantially lower than 40%. Got it. Okay. And when we think about the sort of opportunity for the individual doses to differentiate on duration, the a priori is 50%. Is that predominantly because you're sort of scaling across the treatment duration, or is it because the time from dose to potential infection really requires sort of a higher PK to achieve that higher efficacy? No, that's an important question. When we look at our phase I data, looking at the exposure of those three doses, for the first two-thirds, three-quarters of the flu season, any of the subjects getting the flu during that first part of the flu season, we don't expect to see any difference in efficacy because the exposure from all three doses is well above the target exposure. It's only towards the end of the flu season. So let's say if we cut off the data at the end of the flu season, end of April, then individuals who get a flu infection in March and April, we may start seeing some separation. And that's actually a good thing because we want to base our dose selection based on data. Got it. Let's talk about the opportunity outside of sort of standard flu, bird flu, obviously. We're seeing a lot of news in the media about it spreading in animals very aggressively, lots of sort of costs associated with that. But in terms of the opportunity in humans and the need, how would you kind of characterize the opportunity for 388? We've tested CD388 against multiple strains of H5N1. Actually, we have to do it at a CRO that has BSL level III facilities. In vitro, it is equally potent against H5N1 as any other strain. What we're doing right now is we are working with a CRO that is obtaining the latest circulating strains of H5N1 for in vivo studies. We hope to be able to report on the results of those within the next one to two months. Okay. Great. And in terms of getting funding and how you would like to see the phase III funded going forward, whether it be post your phase II data, strategic decisions that need to be made, what's the focus there? Yeah. So we plan to conduct a study in one of three populations, all high unmet need populations, the over-65 population, the 18+ comorbid population. So these are individuals that have a very high risk of hospitalization if they get influenza, and also the over-18 immunocompromised populations. The middle and the last two, these are relatively heterogeneous populations. So in parallel, we're doing an assessment of clinical feasibility in testing these CD388 in these subjects. But the opportunity is you're talking well over 10 million potential subjects in just the immunocompromised population. So these are high unmet need and very large populations. Just one question that we get a lot of is related to pricing. How should we think about pricing? You've said we're not trying to go head to head with flu vaccine per se, but we may be a replacement in some of these populations. How should we think about pricing? Yeah. I think we can think about it in terms of monoclonal antibody pricing. I mentioned the YTE mutant of the FC. That is essentially the same FC that Beyfortus is using. And Beyfortus is approved in infants and children up to 24 months of age. Pricing is $500-$1,000 per course of therapy. The other end of the spectrum, you have COVID pre-exposure prophylaxis drug, Pemgarda. That is upwards of $6,000 per course of therapy. So I'm not saying we're going to get one or the other, but this is definitely kind of the pricing corridor that we're focused on. Great, and maybe just remind us what you see as kind of that peak market opportunity within the individual sort of landscape target opportunity. Yeah. So immunocompromised population, that's going to be the highest reimbursement population. That's where Pemgarda has gone. Beyfortus in infants and children is kind of more in that middle population. Going into the over 65 population, we think there's a high chance of ACIP designation for that population, but hard to imagine that Medicare would reimburse at the same level that it does for these other drugs. Great. All right. Well, unfortunately, we have to wrap up, Jeff. This was a really great discussion. I know you have a car to catch as well. So really pleased to have Cidara here, excited for the data coming up. And it sounds like there's a decent chance that rather than the third quarter of this year, we may be having a dialogue in the second quarter of this year, probably late second quarter, it sounds like. Absolutely. That'd be great. All right. Fantastic. Thanks so much. Thanks, Seamus.