All right, thank you everybody again for joining us at Citizens Life Science Conference here. Next company we have is Cidara Therapeutics, and we have Jeff Stein, he's President and CEO and a co-founder. Frank Karbe, CFO, was going to be here, had some travel-related issues, but we're happy to have Jeff here to walk us through the Cidara story. Pretty exciting few weeks coming up, definitely with a phase 2B readout at the end of June. Jeff, maybe people that aren't quite familiar with Cidara yet, give us a quick background on the company. Sure, yeah, I can illustrate that on this slide here, provides a good overview. Cidara was actually formed back in early 2014 on the premise of application of bispecific immunotherapy to infectious disease. We had several iterations of that along the way. We actually had advanced an antifungal drug, which was not an immunotherapy, from preclinical to approval. Then in 2018 is when we discovered this drug-Fc conjugate format, unique application, and it's really a combination of small molecules and monoclonal antibodies. In the case of CD388, it's the small molecule inhibitors, a very potent inhibitor of viral neuraminidase, which is an essential enzyme that mediates the exit of the flu virus from an infected cell. You can see in the history that we had formed a partnership with J&J while this molecule was still at the preclinical stage. Under that partnership, Cidara was responsible for advancing CD388 through two phase 1s and a phase 2A study. We started that in 2022, delivered the data in the first quarter of 2023. J&J was preparing to deliver to us their notice to proceed, which would have been the formal handover of that program to J&J. They had the global license to CD388 and intended to take this into a large phase 2B study and then subsequently into a pivotal phase 3 study. In the summer of 2023, they had a change in leadership, a new head of R&D that came in. At the end of that evaluation process, they elected to exit the infectious disease space broadly. They then embarked on a series of divestitures, starting with their latest stage program, which was an E. coli vaccine that had completed phase three, that was divested to Sanofi. They then had another program, a Hep B program, which they divested to GSK. The third most advanced program in their ID portfolio was CD388. They started a competitive divestiture process, really, you know, with other big pharmas. That's when we had the opportunity to participate through the help of RA Capital, Bain, BVF, and Canaan. We put together a $240 million financing that enabled us to reacquire global rights to CD388. Last year, we started a 5,000 subject phase two B study. It was almost exactly a year ago when we closed that deal, the financing and the license agreement on the same day. From a standing start, enrolled a 5,000 subject study, phase two B study, starting the end of September, completed enrollment beginning of December. That happened to coincide with a historically severe flu season, which has some advantages if you're running a flu trial. You can see some of the details on that trial. We're testing three dosing arms versus placebo. Okay, great. And then maybe, along with the $240 million pipe, you totally divested. Our antifungal drug. Antifungal, right? It's all about CD388, really. You have some other drugs. Okay, great. The great image of CD388 here, but I just want to emphasize maybe again and again that it's definitely not a vaccine. That's right. It doesn't depend on the immune system, correct? And the Fc domain's really just there to extend half-life. You've knocked out the Fc effector function, is that correct? Exactly right. Often it gets confused with a vaccine because it is dosed once a flu season. The reason we can do that is that, as you rightly pointed out, Roy, that Fc provides a long half-life. Half-life is about six to eight weeks. The three dosing arms of the study, those doses are administered once at the beginning of the flu season, and we follow the subjects out for the entire flu season. On April 30, we stopped collecting the efficacy data. That coincided with the end of the flu season. That puts us on a track to announce top-line data around the end of June. Yep, great. Okay. Sorry to stick to the mechanism more, another aspect that maybe this gets confused with is ADCs and that the linkers are stable, right? This does not release a payload into the cell. That's exactly right. A big advantage of this platform. The active small molecule zanamivir is in the form of a dimer. That linker cannot be cleaved. The linker that connects the dimer to the Fc is a PEG linker that is covalently linked to a lysine on the Fc. The Fc has no immune effector function, so it's strictly there as a PK enhancer, provides that once a flu season dosing. Okay, great. The multivalency results in high potency, and theoretically it makes sense that should reduce the chance of resistance. That's right, yeah. Obviously you have multiple copies of those dimers. On average, it's about 4.5 of those dimers, so on average about nine inhibitors, the zanamivir inhibitor per molecule. That enables a single DFC to make multiple binding interactions with the target, which enhances the binding. It also enables that single molecule to bind the target on adjacent viral particles, which results in aggregation and rapid elimination from the system. Okay, interesting. Really unique construct. Maybe let's talk a bit about the clinical data that you've seen so far for CD388. You did a challenge trial in flu. What has that told you about the construct and the? Yeah, let me touch upon some of the phase one studies first. On the lower right, you can see from one of those phase one studies, the first in human study, that's the PK in humans of two of the three doses we're testing in our phase 2B study. That horizontal line is the target exposure line. That target exposure was determined based on the outcome of lethal mouse challenge models. Basically, you asked the question, what is the exposure that provides 100% protection against a lethal dose of influenza? That exposure is about 1 microgram per milliliter. That translates to the 150 milligram dose in humans. As you can see, if you look at the timeframe on the horizontal axis, that's pretty much the flu season. You can see that all three doses, if you interpolate between those two lines, the 300 mg dose should provide exposure, ample exposure above that target for the entire flu season. I will not read all the other safety observations and so forth. The real advantage of this modality is it does not enter cells. There is no opportunity for intracellular off-target toxicities. There are no cytochrome P450 interactions. There is no liver toxicity signals that we have seen in phase 1, no hERG activity. A real advantage of this modality versus the ADC, which you mentioned previously. Getting to your question on the phase 2A, this is pretty typical in developing influenza preventatives and treatments, is you run a study in healthy volunteers, and it is called a human challenge study. The way that these studies are run is you administer the drug, and five days later you challenge them with an attenuated strain of H3N2 virus that limits the infection to the upper respiratory tract. The primary endpoint is RT-PCR confirmed influenza. Now, what's interesting about this is that, as I mentioned, neuraminidase inhibitors like zanamivir prevent viral exit from an infected cell. They don't prevent viral entry. You expect to see PCR positive in these types of studies. What these studies are, what neuraminidase inhibitors are really good at is limiting severe infection. If you look at the results of the phase 2A study, you can see on the right, you can see the placebo-adjusted efficacy, so clear evidence of efficacy. These results are the basis by which J&J was delivering to us the notice to proceed before they elected to exit the infectious disease space. We had the opportunity to have positive phase 2A data plus results of two phase 1 studies in order to give us an opportunity to get global rights back. What I mentioned previously about how neuraminidase inhibitors work, we do have precedence of, we can look at other trials. A better known neuraminidase inhibitor is Tamiflu or oseltamivir, orally available neuraminidase inhibitor. In the challenge study that was run on Tamiflu, you can see the placebo-adjusted response rate of about 24%. Again, not surprising given that you do not expect these to prevent viral entry, but you do expect to prevent viral exit and the subsequent proliferation of severe influenza. When you look at their phase 3, however, of Tamiflu, you see this dramatic jump in efficacy. Why is that? Because in phase 2B or phase 3 studies, the endpoint is signs and symptoms of fever along with PCR confirmation. You first look at PCR confirmation, but then the primary endpoint requires fever and respiratory and systemic signs and symptoms. That is what these neuraminidase inhibitors are really good at. You can see the subsequent leap in efficacy. What does that mean for the phase 2B study that we are running? We had a 57% placebo-adjusted response rate in the phase 2A. The phase 2B will report out at the end of June. We often get asked, what does success look like? In my view, success looks like anything at or above 57%. Why is that? Number one, we fully expect it to be higher than 57% based on precedence. Number two, neuraminidase inhibitors work regardless of immune status. We've shown that in our animal efficacy studies, the response rate we see in immune compromise is the same as in immune competence. There is no contribution of the immune system. In the general population, the vaccine is about 40% effective because CD388 and other neuraminidase inhibitors hit neuraminidase, which is a different target than what vaccines are targeting. Vaccines target hemagglutinin, which is the other target on the surface of the virus. Hemagglutinin mediates viral entry. We expect to see complementarity or additive benefit of inhibiting neuraminidase on top of vaccines. If the average vaccine effectiveness is 40%, if CD388 is at 50% or higher, we consider that a win because the population that we will take this into for phase three is going to be in high-risk comorbid or immune compromised subjects who have a substantially lower efficacy with respect to vaccines. Okay, great. I want to ask you about the flu season, but maybe since you just mentioned that the target population, maybe talk about what your plans are for the next study and the target population. Yeah, the target population is shown here. This is a population. The mortality rate when this population gets influenza is at or above the mortality rate in breast cancer, colorectal cancer, other types of diseases that you may be hearing of more commonly. The reason why they have such a high mortality rate is they're very vulnerable. They typically, if anybody in these populations, the moderate to severe immunocompromised or comorbid populations, they get the flu, they're typically hospitalized. This is where we think CD388 can make the biggest impact. Okay, great. Maybe to the flu season, one thing we didn't point out on the challenge study, that's the low dose that's being used in the. That's right. That's the low dose, right. High dose is three times higher. Maybe I think you have a slide in here with the timelines. You guys picked the perfect flu season in terms of severity and timing. You pretty much hit the very start of the season and enrolled through the peak of it. That's right. Yeah, we don't have the kind of the shape of the flu season that is reported by the CDC. But for those of you who had followed it, we had a bimodal flu season, the worst in the last 17 years. The first peak started to emerge at the end of December, started to wane through mid-January, but then we saw a second peak that emerged at the end of January and into mid-February. And probably none of us know anybody or are aware of individuals who did not get the flu. Coming out of the JP Morgan conference, I know a lot of people who had influenza that they contracted there. So that certainly is not good for the populace, but great for a flu trial. Okay, great. I do not think I have heard you get asked this before, but the one site in the U.K., you are enrolling 1,000 patients. Have they also had a similar flu? They did, yeah. The U.K. flu season started a bit earlier than in the U.S., but it was as severe and tailed off a little bit earlier than that in the U.S. We enrolled about 830-850 subjects in that one site in the U.K. Okay. On healthy unvaccinated adults who are not at risk or translatable to the at-risk population? Yeah, that's a great question. It should be highly translatable based on two lines of evidence. Number one is the animal efficacy that I mentioned previously, where the same exposure results in prevention of influenza, whether it's immune competent or immune compromised animal models. The other line of evidence is if you look at the label of Tamiflu or other neuraminidase inhibitors, zanamivir for example, or other antivirals, they have a label for healthy normal and for the immunocompromised. It's the same dose because there is no reliance on the immune system for efficacy. That's not the case for vaccines. Not the case for monoclonal antibodies either, because monoclonal antibodies hit the same target as vaccines. There is the concern of vaccine interactions with monoclonal antibodies, which should not be a concern with neuraminidase inhibitors. They're hitting a completely separate target. Okay, great. Any nuances you can discuss about the primary endpoint, the logic that went into your choices and maybe distinguish versus Vir what they used in their antibody trial? Yeah, the most recent phase two study that has been conducted was the VIR-2482 study that they conducted two years ago. In that study, their primary endpoint did not include fever. And they tested two doses, a 450 milligram dose and a 1,200 milligram dose. Unfortunately, did not meet the endpoint. The bar is pretty high for monoclonal antibodies for the reasons I indicated. Had they included fever in the endpoint, and they did capture it in a secondary endpoint, the CDC definition of fever is 37.8, it would have done better, but would not have met the pre-specified p-value. That, I think, is a good lesson learned that you want to include that endpoint in the primary efficacy outcome because that really favors the use of the drug versus placebo. Okay. They also got a bit vexed by a season that was very early, right? They kind of missed the. Yeah. When they conducted their study, it was the first flu season coming out of COVID. It was an aberrant flu season. There was an early peak in October. They got a bit of a late start to their trial in October, which means that they had a number of subjects in the study that were enrolled in the dosing arms that had already been exposed to influenza, which resulted in that exposure occurring before their drug, the monoclonal antibody, which takes about seven days to reach efficacious exposure in the respiratory mucosa. They had breakthrough infections, which then made it more challenging to achieve the primary outcome. Okay, great. I think you guys have planned an R&D day, May 22nd, if I recall correctly. What are we going to see there? It looks like plenty of details. Are we going to get infection rates and what do you guys plan to announce? Yeah, we'll have two KOLs, Fred Hayden and Rick Bright, that will speak to some details on the nature of the flu season, why it was as severe as we noted, what is the prospect for future flu seasons, what is the prospect for H5N1 pandemic influenza. These are two of the world's experts on that. We will still be blinded on May 22nd. However, we will have locked the database. What we will speak to is the statistical analysis plan by which we will evaluate the phase 2B data. When we initially embarked on this study, we did not have a pre-specified p-value because we assumed that it would be a relatively modest flu season with about a 2% attack rate. Attack rate is the rate of infection you expect in the placebo arm of the study. With a 5,000 subject study, randomized one to one to one to one, you expect 1,250 per arm. If you have a 2% breakthrough infection rate or attack rate in the placebo arm, that's 25 infections in the placebo arm. We assumed about a 50% efficacy in the low dose, the 150 milligram dose, and that's based on what I just showed you on the phase 2A study, which would mean 12.5 breakthrough infections in that low dose and subsequently lower infection rates in the higher doses. With those relatively small numbers, even though it's a 5,000 subject study, we didn't believe it would be powered for a pre-specified p-value. The original intent of our phase 2B study, as with many phase 2 studies, is to select a dose. We're just simply going to look at the breakthrough infections in each of the doses compared to placebo, but not compare it in a pre-specified manner. We were rewarded with a very severe flu season. We now believe that the breakthrough or attack rate in the placebo arm is a lot higher than we initially expected, which enables us now to revise the statistical analysis plan. We've had those meetings with the FDA, and we look forward to talking about the details of that analysis on May 22nd. Okay, great. Assuming that phase 2B hits, obviously you continue on with CD388, but where else do you take the DFC platform? Do you look at other infectious diseases, focus back on oncology? What do you think about? There is an opportunity in RSV that we had a nascent program there that we would look to resurrect. In oncology, as I mentioned, we've got a cleared IND to start a phase 1A, 1B study with our CD73 inhibitor. We expect to take that forward on top of chemotherapy in triple negative breast cancer. We have our earlier molecules, which are really exciting because one thing that this platform lends itself to is combination therapy in a single molecule. As you can note, we can actually, instead of a zanamivir dimer, we can make heterodimers. We can have different small molecules in that dimer pair. One of our molecules we have is a combination of CCR5 and a PD-1 inhibitor or CCR5 and CD73 inhibitor. We can have this combinatorial approach where a single molecule can attack multiple targets. As many of you know, in oncology, the game there is what is the therapeutic window? Small molecules, especially in the chemokine receptor pathway, are very potent, but can have substantial off-target toxicities. We can attenuate those toxicities by attaching those molecules to an Fc fragment as we have done with CD388. Okay, great. Maybe last question, just cash. I know you report very soon, but where does cash get you today? How do you take CD388 forward? Do you partner it again or how are you thinking about that? Yeah, at the end of the year, we reported $196 million in cash. In the absence of starting phase three, that cash would take us into the second half of 2027. Obviously, if we're going to embark on a large phase three study, we would look to raise additional cash, but we'll see what the phase 2B results look like. We are in partnering discussions as well. We think that positive data will provide some opportunities there. Okay, great. Another last thing, another thing I think gets overlooked in addition to CD388 not being a vaccine. You guys' market cap, if you look it up on Thomson or whatever, it's $250 million, but it's not. Yes. I mentioned that we did two pipe financings last year. One, and I do not know if it is in this, there we go. $240 million pipe financing at the end of April of last year. Then in December, we did $105 million pipe financing. All of those were in preferred shares. So the preponderance of the share count is in preferred. The Bloomberg market cap is based on the common. If you look at the fully diluted market cap, it is $700 million at least when we last looked at that share price. Who knows what it is today? No idea. All right. Thank you very much, Jeff. Very interesting. Looking forward to the data coming up in a few weeks. Great. Thank you.