Cidara Therapeutics, Inc. (CDTX) Earnings Call Transcript & Summary

Sure. I'll start, and then see if Kieren have any comments, too. She's very familiar with this data. So the data that we have is thorough nonclinical data. So I also note that the echinocandin, which obviously rezafungin is a member of, do have activity and work clinically against both of these pathogens. So the question is what about rezafungin. So rezafungin we've seen in comparison to the other echinocandins has a better distribution, improved distribution to the lungs, to the respiratory tract. And we think those higher levels are going to improve the anti-mold activity that we're going to see compared to, say, micafungin, which does have anti-mold activity, but does fall down certainly compared to, say, azoles. The -- for PCP, we've done a number of different studies with Melanie Cushion at University of Cincinnati, really top-notch researcher, NIH funded all that kind of stuff, who looked at comparison to Bactrim, which is the standard of care, really, the trimethoprim-sulfamethoxazole and it was demonstrated even at very low levels, like 15 milligrams or so of equivalent of rezafungin for prophylaxing for Pneumocystis, it was equivalent to the primary standard of care. So we think at our levels of 400, 200 should be no problem for Pneumocystis prophylaxis in our patients in these populations. Kieren, I don't know if you have anything to add?

I'll just add a little bit about the importance of the potential anti-pneumocystis activity of a drug like this. One is, it reminds me of history and that the first echinocandin was being developed as a pneumocandin. It was developed to prevent PCP, but that was later abandoned because it was thought to have no need. To that effect, Bactrim works great in preventing PCP, it just is not well tolerated by people. And this is -- for a long period of time, we get cytopenias, we get rashes, we get other toxicities with the drug, either that or perceived, and it's the first drug to come off of the prevention list. And for that reason, people like Catherine Cardona in Europe has shown that a great deal of pneumocystis breakthrough infection in various different populations is because people are not tolerating trimethoprim sulfamethoxazole. So we do have a real strong unmet need there regardless of the availability of a good drug. It's just not a tolerated drug.

Yes. And the alternate that I use most commonly is atovaquone and that, I ask the patient, did you take your [ yellow pints ] today? It literally looks like yellow paint that you drink. And the patients wrinkled the nose and yes, I took it. Maybe they did and maybe they didn't, not a good option to go to back to Bactrim.

GI toxicities we see.

Okay. So I see there are no further questions. And to the audience, we will have an opportunity to address other questions at the end of the next section, which is the Cloudbreak section. So let me launch into that program here. So clearly, the prevention and treatment of severe respiratory viral infections is in the news recently. You can see on the left, Moderna recently had their R&D Day where they announced a program on making a combination COVID-19 and flu vaccine and also will try to add RSV onto that as well. I can tell you, I'm a grateful recipient of the Moderna COVID-19 vaccine. Should these others become available, I would certainly look to receive that as well. And if by chance I were to get a severe breakthrough infection, I certainly would raise my hand to get the Regeneron monoclonal antibody cocktail. However, despite the fact that both of these companies have had a profound impact on society, there are really severe limitations to both vaccines as well as to currently available treatments. Les Tari, who is in this next section will highlight that unmet need. And why certainly, we at Cidara are very excited to advance our Cloudbreak platform a fundamentally new approach for the treatment and prevention of viral infections. So let me turn it over now to Les Tari, our Chief Scientific Officer, to walk you through some of the data that shows why we are excited about this program. Les?

Thank you, Jeff. We've made some exciting progress in our Cloudbreak platform. Let me show you where we are and where we're going. Cloudbreak molecules have 3 basic components. The proprietary Fc domain derived from a human IgG1 antibody, shown on the left, that we can engineer to extend half light or modulate immune effector function. To that Fc, as shown in the middle, we can conjugate -- we can stably conjugate small molecule antivirals. And in some cases, as shown on the right, we can combine those small molecule conjugates with antiviral peptide fusions that target different viral proteins. So this platform can be thought of as a molecular version of a Mr. Potato head toy. It allows us to generate inhibitor cocktails on a single molecular scaffold. The product molecules are called drug Fc conjugates or vaccines. In our research programs, we've demonstrated several potential advantages for this platform compared with vaccines, small molecules or monoclonal antibody therapies. The ability to modulate and increase the drug to Fc ratio can have a profound impact on potency. And the ability to install different targeting groups on the same molecule when we're targeting one virus, can improve spectrum and reduce the resistance potential or alternatively, it allows us to target different viruses with a single molecule. The limitations of existing influenza vaccines was one of the primary catalysts that inspired us to pursue DFCs. The tri and tetravalent influenza vaccines that are currently in use are based on annually circulating strains. And even if those are correctly predicted, they provide only limited coverage from season to season and Eric Simoes will highlight some of this. Their protective value in high-risk and immune compromised populations is worse. And that's a 50 million person segment of the population in the U.S. The IND candidates that we've generated in our flu program have the potential to address these key limitations of the current flu vaccines, and I'll show you some of that data after this. Our influenza DFCs demonstrate potent universal influenza activity, and they retain their activity in immune compromised hosts highlighting their potential to cover all strains in all people. A bonus feature with DFCs are the rapid onset of action, which makes them suitable for treatment or post-exposure prophylaxis for pandemic preparedness. Our DFCs are so potent that we believe we'll have the potential to achieve seasonal protection with low single doses at attractive costs. DFCs share favorable attributes with monoclonal antibodies. They have a long circulating half-life, and they can recruit the immune system to the site of infection, but they also have several upgrades when compared to monoclonal antibody therapies. The ability to control the drug to Fc ratio and install multiple targeting groups on the same scaffold provide multiple paths to candidates with exceptional potency and viral coverage or, as I mentioned already, single molecule drug cocktails, which could inhibit different viruses. DFCs are only about 40% of the size of monoclonal antibodies. And in preclinical models, that size difference translated to improved kinetics and overall distribution of our molecules to the site of action in the lung. We anticipate that tissue penetration of DFCs will also be improved compared with monoclonal antibodies for applications outside of infectious disease. So any of you who have worked in small molecule drug discovery programs appreciate how difficult an art that is. You invariably get stuck up and having to trade away potency of your best molecules to address problems with metabolism, safety or oral bioavailability to name a few parameters. Since our DFCs don't enter cells to any significant extent, we don't have to throw away our most potent molecules due to these issues, and we can focus our optimization primarily on enhancing potency. As you can imagine, translation of that potency to in vivo activity may allow us to move away from requiring IV administration for long-term protection intramuscular shots, so that our molecules can be used outside of the hospital with lower costs. Next slide. We were able to exemplify many of the platform advantages that I just described in our influenza program, where we have advanced 2 development candidates for seasonal universal prevention of flu shown here. We shared a wealth of data on these programs, which can be accessed with the link at the bottom of the slide. The 2 molecules shown here are identical with the exception of the FC domain, which in CD388 was engineered for long halfway. The entire program has been licensed to Janssen Pharmaceuticals and CD388 is moving towards an IND submission by the end of this year. I'll share some of the data that we've generated with our influenza lead candidates that highlight some of the strengths of the platform. The data that you'll be seeing was derived with CD377. Note that comparative CD388 data has been generating using many of the same experiments and it's very similar to what you'll see here. Here, we're looking at a pharmacokinetic study in mice that were subcutaneously dosed with CD377, where the concentrations of the compound in plasma and lung epithelial lining fluid or ELF fluid were compared over 2 weeks. Within the first 30 minutes, the ELF concentrations start to track with the plasma concentrations and the levels reached are high, about 60% of the concentrations that you see in plasma are reached in the epithelia lining fluid. This is in stark contrast to monoclonal antibodies where distribution to the epithelial lining fluid lags by as much as 48 hours and relative distribution to the lungs is typically much lower. Translation of this behavior to humans would position these molecules well to be used for treatment and pre-exposure prophylaxis in addition to prevention. The exceptional in vitro potencies we observed with our lead candidates has translated well to animal efficacy. Both molecules demonstrated durable, robust efficacy and infection models against multiple flu strains with low single doses. Here, you're looking at the results of a representative prophylactic efficacy study with CD377. It was administered to mice subcutaneously 28 days prior to infection with a lethal H3N2 viral challenge. Single dose is down to 0.3 milligrams per kilogram, so very low doses, were sufficient to fully protect the animals. Using this same model, we evaluated the efficacy of CD377 against multiple influenza A and B strains. Due to the broad spectrum and high potency doses of 1 milligram per kilogram or lower were sufficient for full protection against all the strains we tested when dosed 28 days prior. Getting protection for that long with such low doses in mice, highlights the potential for achieving seasonal long protection in humans with single low doses. One thing we wanted to establish early in this program was whether our flu DFCs have the potential to protect high-risk groups. We evaluated that notion preclinically using several experiments, including what you're seeing here. We compared the efficacy of CD377 and lethal challenge models in mice where you're looking at the results for immune competent mice on the left and severe combined immunodeficient mice on the right. In both cases, the same low-dose threshold was required for full protection, 0.1 milligram per kilogram doses. So they were protected in both backgrounds, highlighting the potential for CD377 to protect normal and high-risk individuals with the same doses. For broad use, in fluid treatment and prevention, particularly in prevention, a clean safety profile is essential. Here, you're seeing a summary of a non-GLP dose range finder toxicology study with CD377 in cynomolgus monkey, where at the highest dose tested, which afforded us more than a 95x therapeutic margin or predictive therapeutic margin, there were no adverse findings in any of the parameters shown on the right. CD388 is in the latter stages of GLP toxicology studies now in rat and monkey, and we're not anticipating a different outcome. For those interested, as I mentioned before, there's a link on one of the earlier slides to a more complete data package that you can look at. I'll now pass it over to Dr. Eric Simoes, who's going to tell you about the unmet need in flu, RSV and other respiratory diseases that could potentially be addressed with assets from our platform. Eric?

Thanks very much, Les. So I will talk about -- can we have the next slide, please. So I'll talk about the major viral respiratory pathogens that affect us today and these are some of the major ones. The ones I will discuss are SARS-CoV-2 influenza and RSV. I think these are really the most important. The other viruses, Rhinovirus certainly are important, but 90-plus serotypes makes it difficult. The next slide, please. So we'll start with SARS-CoV-2 in the global situation. As you're all well aware, this is from the WHO website recently, last week. There are over 224 million cases confirmed. As you know, this is an underestimate because in many developing countries, cases are not really confirmed. Over 4 million deaths are certainly high numbers, if you account for the nonreporting in developing countries and 5.4 billion doses of vaccine administered. Unfortunately, not a lot of them in Sub-Saharan Africa and in the poorer countries in Asia. Next slide, please. Understanding that there are -- there really is an unmet need for SARS-CoV-2. There are over 442 clinical trials on 185 vaccine candidates ongoing as of this year. So there really are a lot of candidates that are being tried, but there are some problems with -- and you can see all the different platforms that have been used. The next slide, please. So I'm not going to go into great detail about any of the 3 topics that I'm going to discuss, but I will highlight some issues. So for prevention, we do have efficacious vaccines. There's no question that the Moderna, the Pfizer, Janssen, the J&J vaccine and the AstraZeneca which are very good. But Universal Global Distribution is a real issue. As you know, the places where there are the greatest unmet need are in Asia and Africa. Vaccines prevent against invasive disease. And this we do know, but it's less so against infection and even less so against transmission. And this is a very important factor that we have to take into account. So if one considers that people get infected after transmission, the only way to end this epidemic, despite what everyone else is saying is really to prevent transmission. And even places where mask usage is very good, you still have transmission of virus. For instance, in the Philippines, where I do some of my work, everyone has to wear a mask and a face shield, everyone, in public. But they haven't yet been able to control the epidemic. I was speaking to my colleagues yesterday. So that's one issue that preventing transmission is really a big issue. The second is there is an inevitably will evade the immune response. And I don't see an end in sight, unlike most of the other epidemiologists that are -- that seem to use or not to determine how long this epidemic is going to get over. The problem is very simple. The virus tends to evade the immune response. And as long as there's transmission, you're going to have new variants that will inevitably arise. It evolves and what everyone thinks that it will become a mild flu like illness. I don't think so. It will continue to be -- the pathogenesis is completely different from influenza and it's not going to evolve at least in our lifetime to become a mild illness. It's not going to develop the -- it's not going to become less and less pathogenic. Monoclonal antibodies, as you know, are available. Our Regeneron's antibodies certainly seem to work, but they are costly and of limited use. They have to be given -- they are certainly not used widely outside of the U.S. They are inconvenient. They have to set up specific centers to use them, but they certainly seem to work. Specific treatments are limited like remdesivir, corticosteroids seem to work, but there are dangers as you know, what's happening with fungal infections in India, it's because of the use of steroids. So there still is an unmet need. The virus is going to evolve. We are going to be -- to live with this virus for many years. And so there is certainly a role for limit as well as prevention. The next slide, please. Influenza has a large pipeline of candid vaccines, which are now available. These are from the CDC website. These are all the various trivalent and quadrivalent vaccines. In the U.S., it's mostly or almost all quadrivalent. In many other countries, it's trivalent or quadrivalent vaccines. But Universal protection is still elusive, it has to be given every year. The next slide, please. You can see that there is decreasing effectiveness over time. And this is quite well documented in -- the CDC has documented this by a series of studies. It is less effective for the elderly and the immune compromise precisely the group, but this seems to affect the most. The one vaccine that does seem to work better in children is a live attenuated vaccine, but it's not used very much. So there certainly is a big burden of disease, and there certainly is a big space for prevention. The next slide, please. So vaccines are available, there's no question about that. There are at least 40 different vaccines available. They're not very effective, as I just showed you. They have to be given annually. There is a reticence on parents to give annual vaccines to children because they know that those children need to leave to get it throughout life. And you can see there is a trend towards decreasing efficacy certainly with the current quadrivalent vaccines. The next slide, please. RSV is the next major challenge. At least for me, as a pediatrician, I think it's the most important virus that causes problems, not only in infants, but in -- certainly a major cause of mortality. Next to now coronavirus, I think it has a higher mortality in developing countries than influenza does, certainly in the pediatric population. There are several -- this is a snapshot from past that has been looking at all of the vaccines and monoclonal antibodies for the last few years. And you can see that the only marketed and approved product is palivizumab or Synagis, marketed by AstraZeneca. It's been around for 21 years. It was licensed in 1999. There are key candidates, AstraZeneca has now being marketed by Sanofi Pasteur, has a monoclonal antibody nirsevimab. Merck has monoclonal antibodies that are in trials. So does -- the Gates Foundation has a monoclonal antibody that is coming up. The next major one, maternal immunization. So to protect babies less than 6 months of age, the tactic of maternal immunization is certainly important. You will notice that the -- of disease for infants is in the first 6 months of life and the only way to protect them. A shot of a vaccine at birth is really monoclonal antibodies of passive protection from maternal immunization. So there are several candidate maternal immunizations in Phase III trials. They look very good, but there are problems with both of these. The next slide, please. So for instance, the greatest burden of disease is before 3 to 6 months of age. So if you look at the ICU admissions, the most severe disease, the most mortality and the Gates Foundation has a large program on reducing infant mortality due to RSV. We just had a big series of publications in terms of infectious diseases, just about that issue of mortality. And most of the mortality globally occurs in the first 3 to 6 months of life. And likewise, in industrialized countries, most ICU states are in children less than 3 months of age, infants. Long-acting monoclonal antibodies show promise, but there is one issue that -- because the monoclonal antibodies are targeted to a very specific epitope on the surface of the prefusion F protein, there are -- there is the possibility of escape mutants. Now this may occur with immune pressure or it may occur spontaneously. There was a Regeneron monoclonal antibody mortal that I work with very closely, that did not work against RSVB, and that was a pure spontaneous mutation that occurred, it started in China and went around the world in a year, right when we were doing the trial. And unfortunately, it worked against RSV, but not in RSVB. And that is a real possibility with monoclonal antibodies. Maternal immunization certainly shows promise, but our studies in South Africa, for instance, with influenza, immunization randomized controlled trial, 1 of only 3 that were done recently, shows a protection last about 3 to 4 months. The other issue is going to be maternal uptake for maternal immunization, but they do show promise, just because of the prefusion F that has been developed. There is still a major unmet need that is not yet being addressed with these 2 strategies, which is older children. They go to the outpatient, they go to the emergency room visits. And in fact, the emergency room visits in children 6 months to 2 years, is far more than the rate in younger children. And it probably equals the burden of disease of hospitalization. And it's not really been targeted at the moment. There's certainly vaccines being developed. Several vaccine manufacturers are developing vaccines for that group, but it's going to be a difficult one to address. Older adults, the burden, even though there are my colleagues in Rochester show a burden of disease, it's difficult to really replicate that -- those studies globally and most studies require 40,000 to 60,000 participants to show efficacy. So smaller studies probably won't do that. Vaccine immunogenicity is an issue in these populations in the old adults. For treatment, fusion inhibitors all seem to target the same pocket in the RSV prefusion F structure, which is fine. It seems to be a very specific confirmation, very specific pocket and all of the fusion inhibitors target that. Escape mutants are a possibility, but may not be. It may be one of the strengths because that pocket may be so important for the structure that if mutations occur, it may disrupt the structure. So -- I'm sure, treatment is best when disease is early. So for infants, diagnosing the disease very early before the immune response kicks in is really critical. In the older adult, it's difficult to actually show a role for treatment in the older adult. And an immune compromised, certainly, it's important. Certainly, it's easy to show it, show that it's RSV is a problem, but to treat RSV is -- that population. So I'll stop there with my -- with my unmet need for RSV.

Well, great. Thanks so much, Eric. Really and grateful that you had the opportunity to share your perspectives on this. So we'll wrap up the Cloudbreak section. And this is a great segue to less providing an overview of our advances in RSV, HIV, SARS as well as our new program. So Les, do you want to take it from here?

Yes. Thanks, Eric. Now I'll share some information on our platform expansion programs. The learnings and the experience and infrastructure we've built to advance the influenza program has allowed us to quickly progress new discovery programs in other viral indications. We've generated some exciting early data in RSV and HIV programs that I'll share, and we're starting a new SARS-2 program and programs outside of infectious disease that we're confident we can progress quickly. So let me share some of the progress highlights from our RSV program. As Eric pointed out, RSV presents a significant unmet need. In a recent -- in an alarming recent trend, as COVID-19 restrictions have been eased, there's been a large rebound in RSV infections with many children being hospitalized with RSV SARS-2 co-infections. If that outbreak translates to adult populations, we're in a typical year, almost 200,000 people over 65 are hospitalized with RSV in the U.S. Again, just reiterate that new options for the treatment and prevention of RSV are desperately needed. Here, you're looking at 3 different molecules. At the top, a peptide fusion that inhibits a late stage in RSV fusion with the host. In the middle, a small molecule conjugate where we've used a novel prefusion confirmation of the F protein inhibitor to the Fc. And at the bottom, a third molecule that combines both modalities. So it's an RSV cocktail, if you will. We are excited to see what would happen when we combine the 2 modalities on a single molecule, and the results didn't disappoint. If you look at the column on the right, where we're looking at EC50s, in cell-based assays, we didn't see viral replication with a combination molecule at the lowest concentration we tested with one picomolar, so it was exquisitely potent. The potent synergy we observed with the combination molecule translated to more than 4,000 full improvement in potency compared with Synagis shown on the right, which is the only agent on the market right now for prevention of RSV and high-risk inputs. Next slide. On a separate track, we leverage the additional degrees of freedom available to us with this platform that I talked about earlier, to focus our optimization efforts on the potency of our targeting groups. That allowed us to generate new single mechanism candidates, which target the F protein with significantly improved potency compared with our first-generation molecules that also demonstrated broad spectrum activity. Next slide. When we evaluated these molecules against a representative panel of RSV strains, we retained exceptional potency across the board. For most of the strains, it was less than one picomolar for all the compounds that we tested here. If you go to the next slide, we're in the process of installing these new optimized small molecule targeting groups to our peptide fusion Fc to generate what we expect to be some exceptionally potent new RSV drug cocktails. In addition, we are advancing the molecules shown there into animal pharmacokinetic studies and mouse efficacy models to validate this. While promising second-generation monoclonal antibody followers to Synagis, as described by Eric, are in mid- and late-stage clinical trials for RSV prevention in children, to translate this to the prevention to adults, large dosing volumes would likely be required for seasonal prevention, making them less practical for broad use in that population. Translation of the potency we're seeing with our RFC -- sorry, our RSV DFCs to efficacy in humans would reduce dosing volumes to levels where intramuscular dosing would be feasible, allowing DFCs to be used in an outpatient setting, and it could open the door for early treatment applications in adults as well. Let's move to our HIV program, where we're testing some interesting new candidates for long-term -- long-acting therapy and prevention. Given the high mutational frequency with HIV when it replicates, there is a perpetual need for novel treatments and maintenance therapies to stay ahead of resistance. There's a big push in the space towards long-acting regimens, using implants or subcu or IM injections to provide options to counter the fatigue of routine daily oral intake. From the standpoint of duration of coverage, our goal in the HIV program would be very similar to what we want to achieve with our influenza program, 4- to 6-month coverage with a single IM shot. Next slide. Using a similar philosophy to the one we used in our RSV program, we have generated single and combined mechanism conjugates with exceptional potency. On the left, you're looking at a schematic of a GP120 inhibitor conjugate that demonstrates similar potency to temp severe shown on the right, which is the first marketed drug with the same mechanism of action. We also have a viral envelope binding peptide fusion shown in the middle, which we've tested by itself and in combination with the GP120 inhibitor on the left, that's the molecule shown on the right. So it's another cocktail with 2 different mechanisms. Our combination molecule demonstrates superior potency, and if we go to the next slide, you can see that it has better coverage as well. When we evaluated our combination molecule, against the diverse panel of HIV strains, including strains with resistance to different classes of HIV therapies, you can see that there are 2 strains there that don't respond to temsavir. It stands out with superior coverage and potencies that are anywhere from 50 to more than 300,000 full better than temsavir. The viral clades and the co-receptor specificities of the strains represented in the panel in the last slide cover HIV strains found in the developed and the developing world. Work is now ongoing to evaluate our combination molecule and some other analogs against larger viral panels as well as pharmacokinetic profiling in humanized mouse and monkey to evaluate the potential duration of coverage and get a PK preliminary safety. In the next section, I'll briefly talk about our nation works to leverage the strengths of the Cloudbreak platform to advance new agents for the treatment and prevention of coronavirus and SARS-2. As has been discussed, while remarkable progress has been made to rapidly advance and deploy highly effective vaccines for SARS-2 prevention, protection of high-risk groups is still an unmet need, and there are other issues that Eric discussed that are problematic. And monoclonal antibodies have the limitations that were discussed, particularly in the treatment setting, and development of new effective treatments has lagged. Next slide. Using the same approaches that have been successful in our other antiviral programs, where we combine antiviral mechanisms on the same Fc, we're seeking to generate new molecules with pan-SARS -- pan coronavirus and SARS-2 activity. Next slide. We're in the process of screening different peptide and small molecule inhibitors for activity against coronavirus and SARS-2. We've already identified a peptide fusion with activity against one of the common cold viruses, coronavirus-OC-43, which is closely related to SARS-2 in some of the specific regions that we're targeting. In this case, it's fivefold more potent than remdesivir, which is the only approved SARS-2 treatment. We're in the process of evaluating different strategies and different molecules that target several different regions on the virus to inhibit viral entry infusion, and we will report new data on these as the program progresses. Once we've settled on the strategies we'll be using to address RSV and SARS, our next goal will be to exploit the modularity of our platform to combine all of these different modalities on one molecule for treatment and long-acting prevention of the 3 major respiratory viruses. Next slide. I'd like to finish by highlighting something that we're really excited about and new immuno-oncology program, which we feel will play to the strengths of the Cloudbreak platform. Developing treatments for oncology involves many of the same challenges as developing novel antivirals. Tumors can develop resistance in response to therapy, and they can employ multiple mechanisms to evade immune detection. And unlike the other programs I described, in cancer, we're targeting the host and toxicity is an acute concern. So you have to be careful with -- especially with small molecule therapies about toxicity. Next slide. Many of the attributes that make DFCs effective as antivirals have the potential to translate to immuno-oncology. The smaller size of DFCs compared with monoclonal antibodies could improve tumor penetration and efficacy against solid malignancies. And operating in the extracellular space and specifically disabling immune evasion in the tumor microenvironment has been demonstrated to dramatically improve side effect profiles compared with conventional chemotherapies. And most importantly, as shown on the right, combination therapy is a cornerstone in cancer treatment, and DFCs are ideally suited to address that. Installation of inhibitors of multiple immune evasion mechanisms on a single molecule could improve outcomes in a larger patient cohort versus monotherapies in first-generation ICIs. Here, we're looking at a 3D tumor penetration model from the paper cited at the bottom. The investigators here are showing tumor penetration of a HER2-positive targeting monoclonal antibody, and they compared it to an Fc domain that targets the same cells. By transitioning to the smaller modified Fc fragment, you can see that the depth and robustness of tumor penetration of the smaller fragment is superior to that of the monoclonal antibody. Since DFCs are similar in size to the conjugated Fc fragment that was used in this study, we expect to see similar relative improvements in performance of our DSCs relative to NAVs. Next slide. Here, you're looking at a schematic, highlighting the potential conceptual advantages of DFCs over monoclonal antibodies and small molecule therapies. The size and the attributes of DFCs place them in a sweet spot where they could enjoy the safety profile and the long half-life of monoclonal antibodies with a tumor penetration profile that's much closer to that small molecules. Next slide. We're currently evaluating strategies to inhibit several different immune evasion mechanisms at various stages of clinical validation, but where they've at least demonstrated robust preclinical validation, and we're off to a quick start. We tried conjugates that inhibit one of our targeted immune evasion mechanisms with similar potencies to one of the most advanced small molecules that's in clinical testing, shown on the right. We are very quickly able to do, they were so familiar with our platform. Cell-based assays and animal models will follow to fully validate the approach. And once we lead optimize -- we discovered lead optimized targeting strategies for each of the different modalities we're going after, combination DFCs will be generated and advanced. Next slide. In summary, you've seen that our Cloudbreak platform has strong momentum in multiple indications and shows considerable potential because it combines the best attributes of small molecule therapies and monoclonal antibodies, yielding a new modality where the product is greater than the sum of its parts. Here's where we're going. By end of year, we're planning to file an IND for influenza and initiate Phase I studies early next year. The manufacturing infrastructure and the process development we've done as well as the inquired know-how from our influenza program and our new programs have fed into each other. And that's helped us to streamline and accelerate our platform expansion efforts. The data from the influenza program and the new programs highlight the potential for this platform to generate highly differentiated solutions for the treatment of viral diseases in oncology. I'd like to thank you for your attention. And Jeff will close, and we welcome your questions.

Great. Well, thanks, Les. I think we can generally see a sense of momentum in our Cloudbreak platform. It started with influenza. And now it is being broadened to other viral diseases and now to oncology. And certainly, as you indicated, the learnings we got from the early influenza program is definitely being applied to our other program. So let me wrap up with where we started. What you heard today is a robust update on our clinical programs, including some new data from a drug-drug interaction study, which suggests that rezafungin would be an ideal prophylactic in the BMT area as well, potentially broader in other oncology settings. In Cloudbreak, we shared some data with you on the expansion into other viral respiratory diseases as well as in HIV, you heard from Eric Simoes, how there continues to be a substantial unmet need in respiratory viral infections. And then finally, we wrapped up with oncology, an exciting new area. And collectively, we think that Cloudbreak has the potential to be the long-term driver of value in Cidara. And so with a near-term Phase III readout coming up at the end of the year, IND filing for CD388 in influenza and the rapid expansion into these new areas, we're very excited about our near-term and long-term future. And with that, let me turn it back to Tara, and we can entertain some questions. Tara?

Thank you, Jeff. At this time, we'll be conducting our final question-and-answer session. [Operator Instructions] I'll hand it back to you, Jeff.

Okay. Good. We have several questions here. One, why has Cidara been able to create this Cloudbreak platform while others have tried and failed? So let me just start that at a high level, then I'll turn it over to Les for a more comment. So Cidara actually was founded in 2014 on this Cloudbreak immunotherapy platform, Asking the question, can this bispecific immunotherapy, which has really revolutionized oncology, could it be applied to infectious disease. So this has been under the radar since we have been advancing rezafungin forward now on the customer Phase III data. But in the background, we have been advancing the Cloudbreak platform. The current version where we are fusing potent antivirals or anticancer agents directly to an Fc was really developed about 3 years ago as we have been evaluating numerous approaches. So now it appears we've settled on something that really is quite effective. And Les, do you want to comment on why you think others haven't focused on this?

Well, I can comment on what I like about the concept. In influenza, it's been very difficult to generate monoclonal antibodies that cover influenza A and B. And we saw the opportunity with some great -- with a great target influenza viral neuraminidase where we could hit something, the only conserved part of the virus with a small molecule modality. And by fusing that to an FC, we have all of the benefits of a monoclonal antibody, but we can target something that is conserved across all of the different viruses. So it was -- and we see this opportunity in the other respiratory diseases as well.

Okay. Well, thanks, Les. Another question, is your arrangement with J&J exclusive? Or could you partner with other companies as well? J&J is a great partner. We have announced the partnership with them on influenza and that's a global partnership. They do have right of first negotiation, not first refusal, but first negotiation that expires at the end of this year on the RSV program. And so we have initiated those discussions with them, and we will see how those advance. And so great company to work with, and we've really had the benefit of that collaboration on influenza. Another question here, do you think more efficacious flu vaccines would increase vaccination rates? Let me throw that over to Dr. Eric Simoes since he is an expert in this field. Eric?

And so that's a very good question. I think that's exactly what would happen. At the moment, when people look at the vaccine efficacy and if you look at people getting tired of getting annual vaccines, it's because the efficacy is so low. And it's not just academic issue, I think it's quite well known amongst the public that the vaccines don't seem to work very well. So if you had a very efficacious vaccine, even if it had to be given every season, you would certainly have a better uptake. Now the pediatric issue is a different story. As long as -- so there is a difference, right, with the DFC -- with immune evasion and changing of the immunity, the need for an annual vaccine is a little different. So there'll have to be a change in the mindset. But certainly, a more efficacious vaccine to answer that question simply, yes, a more efficacious vaccine that were in the range of 80%, 90% will certainly improve uptake.

Well, thank you, Eric. Another question, can you comment on how Cidara is prioritizing the Cloudbreak platform to treat respiratory viral infections? And let me take a first pass at that, and Les you can certainly supplement. The order in which we discussed the Cloudbreak platform today is basically the same -- coincides with how advanced they are. So influenza, obviously, most advanced, expect to file IND by the end of the year, followed by the RSV program and then HIV and SARS and then finally, oncology. So how we're prioritizing them according to their stage of advancement. And Les, do you have anything else to say on that?

No, you answered the question well. There's a whole matrix of things that we choose, technical feasibility, availability of good targets and -- the 2 -- the RSV and influenza programs stand out there. And also the oncology program stands out as something that we'll prioritize.

Great. We have a question for Taylor. Will Cidara conduct an interim analysis of the rezafungin prophylaxis trial? If so, when will that happen? And also when will U.S. sites open for prophylaxis trial?

So we're -- I think we're not conducting an interim analysis. I think as the questioner is envisioning. We do have the DSMB meeting routinely to make sure in assessing unblinded data to make sure the benefit risk remains the same for all the patients that are in the trial. And we do have a blinded look at the overall outcome rates when we're halfway through the trial, and those 50% have exited to see if we need to upsize to increase from 460 to 600 to make sure we hit our mark. So it's a blinded look though. So it's not a true like unblinded interim analysis. And in terms of U.S. sites, so we expect the first U.S. sites to be open for prophylaxis by December, but the majority will be open in the first quarter of next year.

Okay. Great. Thanks, Taylor. Another question, would you commercialize your DFCs for immuno-oncology or seek partnerships there? So certainly, we have the full internal capability to take this program to the development candidate stage and also even into Phase I. So our goal at the moment is to advance that. That said, Cloudbreak clearly is a broad-based platform, which does lend itself for partnering different programs. So right now, our sole focus is to accelerate the oncology program and take that as far into development as feasible. So let me check for new questions. I think that is our last question. So Tara, I'll turn it back over to you.

Thank you, Jeff. This concludes today's webinar. You may now disconnect.