Cidara Therapeutics, Inc. (CDTX) Earnings Call Transcript

Greetings. Welcome to Cidara Therapeutics announced it's positive top line results from its Phase IIb NAVIGATE trial evaluating CD388, a non-vaccine preventative of seasonal influenza. [Operator Instructions] As a reminder, this conference is being recorded. At this time, I'll hand the conference over to Brian Ritchie with Investor Relations. Brian, you may now begin.

Thank you, operator, and good morning, everyone. With me today on the phone from Cidara Therapeutics are Dr. Jeff Stein, President and Chief Executive Officer; Dr. Nicole Davarpanah, Chief Medical Officer. Following Dr. Stein and Dr. Davarpanah's prepared remarks, they will be joined by Mr. Frank Karbe, Chief Financial Officer; Dr. Les Tari, Chief Scientific Officer; and Mr. Jim Beitel, Chief Business Officer, to participate in a Q&A session. Earlier this morning, Cidara released top line results from its Phase IIb NAVIGATE trial evaluating CD388 for prevention of seasonal influenza. A copy of the press release and slides that will be shared during this call are available on the company's website. Please note that certain information discussed on the call today is covered under the safe harbor provision of the Private Securities Litigation Reform Act. We caution listeners that during this call, Cidara management will be making forward-looking statements. Actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with the company's business. These forward-looking statements are qualified by the cautionary statements contained in Cidara's press release issued today and the company's SEC filings, including in the company's annual report on Form 10-K for the fiscal year ended December 31, 2024, and subsequent filings. This conference call also contains time-sensitive information that is accurate only as of the date of this live broadcast, June 23, 2025. Cidara undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call. With that, I'd like to turn the call over to Jeff Stein. Jeff?

Thank you, Brian, and thank you all for joining us on this call. We could not be more excited to share and discuss the positive top line results from our Phase IIb NAVIGATE trial. For your convenience, the slides from today's discussion are available on our website. Before we begin, let me remind everyone that Cidara's proprietary Cloudbreak platform is designed to enable the development of novel drug Fc conjugates or DFCs, a fundamentally new class of drug that combines the strength of small molecules with those of monoclonal antibodies. Our lead asset, CD388 is a long-acting antiviral drug that was designed to provide once-per-season protection against all strains of influenza in all people, regardless of immune status. Its unique properties have been shown to substantially enhance its antiviral activity, making it a potentially best-in-class neuraminidase inhibitor that overcomes the limitations of existing vaccines and antivirals. Before I hand it over to Dr. Davarpanah to discuss the details of the NAVIGATE Phase IIb top line results, I would like to provide a brief summary of the data. Also, as a reminder, today, we are sharing the top line results comprised of key efficacy and safety cables needed to determine the success of the study. Additional results on pharmacokinetics, virology and longer-term safety from the NAVIGATE trial needed to inform final dose selection for Phase III are expected to be disclosed at upcoming scientific conferences in 2025. With that said, we are delighted to share that the NAVIGATE study met its primary end point prevention efficacy, or PE, a protocol-defined influenza-like illness events at 24 weeks and was statistically significant at each dose group, single doses of 450 milligrams, 300 milligrams and 150 milligrams of CD388 confirmed 76%, 61% and 58% protection, respectively, from symptomatic influenza over 24 weeks compared to placebo. The placebo attack rate was 2.8% for the primary endpoint, which means that 2.8% of subjects in the placebo group contracted an influenza infection that met the criteria for the primary end point. Moreover, all secondary endpoints were also met with statistical significance in each dose group. The safety and tolerability data were consistent with prior studies of CD388 and similar in all arms of the study with no safety signals observed. While we observed a clear dose response relationship for efficacy, there were no meaningful changes in safety across the dose groups and placebo. Loss to follow-up rates were low and similar in all arms. We believe these results are groundbreaking for the field of influenza and support our confidence in the potential of CD388 to offer robust once-per-season protection against influenza A and B. I would like to now turn the call over to Nicole, who will further discuss the NAVIGATE Phase IIb study and top line results. Nicole?

Thank you, Jeff, and thank you to everyone joining our call today. As a reminder, our NAVIGATE Phase IIb study is a blinded, randomized controlled trial evaluating the efficacy and safety of CD388 as a single subcutaneous administration for the prevention of seasonal influenza in healthy unvaccinated adults aged 18 to 64, not at risk for influenza complications. The trial enrolled 5,041 participants from the last week of September 2024 through the first week of December 2024, with the majority of participants being dosed prior to the onset of the 2024-'25 Northern Hemisphere influenza season. Participants were equally randomized across 3 CD388 dose groups, 150 milligrams, 300 milligrams or 450 milligrams and 1 placebo group in 58 clinical sites in the United States and United Kingdom. The primary endpoint was prevention efficacy or PE of influenza-like illness event, which was defined by 3 criteria. PCR confirmed influenza, 2 respiratory or 1 respiratory and 1 systemic minor symptoms and body temperature greater than or equal to 38 degrees Celsius. PE tells us the percentage by which a prevention method reduces the chance of getting seasonal influenza compared to not using it. The primary analysis included all data available as of April 30, 2025. And today, we are sharing top line data as of that data cutoff. Before I review the results, I'd like to remind everyone that the NAVIGATE study was initially designed primarily to determine dose selection for Phase III study and was not powered for statistical significance. Prior to study start, we had predicted that 2% of participants in the placebo arm would develop influenza illness. However, as a result of the severity of the 2024-'25 flu season, our assumption was that the incidence of influenza and placebo arm might be somewhat higher in the 2% to 3% range. We discussed and reached agreement with the FDA on modifications to the study's statistical analysis plan to evaluate potential statistical significance of CD388 efficacy versus placebo. The top line data that we are sharing with you today reflects that revised statistical plan. Now on to the top line results. Let's start with efficacy. The study met its primary endpoint demonstrating highly statistically significant protection efficacy data for each of the 3 dose groups compared to placebo over 24 weeks. The number of subjects with protocol-defined influenza-like illnesses or ILI would lower each of the 3 dose groups, ranging from 0.7% to 1.2% when compared to a placebo attack rate of 2.8%. Importantly, as I mentioned, PE tells us the percentage by which a prevention method reduces the chance of getting seasonal influenza compared to not using it. As you can see, regardless of the CD388 dose, the protection against influenza illness was impressive with greater than 76% at the 450-milligram dose. This tells us that subjects who were dosed with 450 milligrams of CD388 have a 76% lower chance of getting seasonal influenza compared to those who received placebo. At the 150-milligram and 300-milligram doses, the chance of getting seasonal influenza was also substantially decreased in over half of the subjects. For perspective, the prevention efficacy data for each of the CD388 dose groups exceeds the average vaccine effectiveness of approximately 40% for the seasonal vaccine. These are promising data for the potential of CD388 to provide influenza protection. I would also highlight that the confidence interval or CI is narrow and the lower bound of the CI is well above 0, giving us statistical confidence in this data. Moreover, the p-value for the 450-milligram dose was highly significant at a level of less than 0.0001. All secondary endpoints were also achieved. This includes maintenance of statistically significant prevention efficacy data up to 28 weeks, approximately 7 months. The key secondary endpoints displayed here utilize the same definition of the primary endpoint, which is PCR confirmed influenza and respiratory or systemic signs or symptoms, but with different temperature thresholds. These temperatures are historical fever definitions utilized in previous vaccine and anti-biochemical trials. The CDC definition of an ILI utilizes a temperature of greater than or equal to 37.8 degrees Celsius. As we see in the top half of the table, at the 37.8 degree Celsius temperature thresholds, each dose group demonstrated statistical superiority to placebo with prevention efficacies of 76.1%, 55.3% and 54.7% for the 450-milligram, 300-milligram and 150-milligram doses, respectively. Prevention efficacy superiority was also statistically significant to placebo at temperatures greater than or equal to 37.2 degrees Celsius temperature threshold. It demonstrates that regardless of temperature cutoff, prevention of febrile influenza was statistically significant and impactful. We believe it is particularly impressive that the p-value for both the primary and secondary end points demonstrated clear statistical superiority. Now on to safety. The safety and tolerability data were similar in all arms with no safety signals observed and no drug-related serious adverse events observed. There were no unexpected dose-limiting treatment-emergent adverse events between CD388 and placebo groups. Importantly, treatment emergent adverse events showed no dose-dependent pattern between the CD388 and placebo arms. The majority of treatment-related AEs were unrelated to CD388 and were grade 1 or 2, meaning that they were mild or moderate in nature. While cross-study comparisons should not be considered definitive, the adverse events that frequently occur with other neuraminidase drugs such as oseltamivir and Zanamivir were seen in the NAVIGATE study with lower frequency. For example, in the U.S. prescribing information for Zanamivir reported for the 28-day prophylaxis studies, a common adverse event with headache reported in an incidence of 24%. In the NAVIGATE trial, headache was observed with an incidence of 2.3% and the CD388 450-milligram dose arm. Cost was observed in an incident of 17% in Zanamivir prophylaxis studies, while it was observed in an incident of 2% in the CD388 450-milligram dose arm. And nausea/vomiting and diarrhea were observed at incidences of 2% and 2%, respectively, with Zanamivir. In NAVIGATE, nausea, vomiting and diarrhea were observed at incidences of 0.6%, 0.2% and 0.4% and the CD388 450-milligram dose arm, respectively. Additionally, injection site reaction rates were similar across all CD388 dose groups and placebo, including erythema, induration, pain and tenderness. These were participant reported reactions with an 8 days of subcutaneous administration. This is another important distinction from vaccines, which are administered intramuscularly and for which injection site reactions are common. Finally, as you can see here, the enrollment of the study was well balanced in terms of age, gender and race across the treatment and placebo arms. I would like to add that we expect to present additional results from the NAVIGATE trial at upcoming scientific conferences later this year. With that, I would like to turn the call back over to Jeff for next steps and closing remarks. Jeff?

Thank you, Nicole. The statistically significant and clinically meaningful results shown with CD388 mark a potential breakthrough for patients and the future of influenza protection as well as further validation of our Cloudbreak DFC platform. Results such as these are unprecedented in influenza and support our confidence in the potential of CD388 to offer robust once-per-season protection against influenza A and B for high-risk individuals, such as those with compromised immune systems or those at a heightened risk of severe illness due to underlying health conditions. Based on these robust data, we submitted our end of Phase II meeting request to the FDA to review the data and discuss the details of a Phase III study, focusing on large populations with the highest unmet need, which includes high-risk comorbid and immune-compromised patients. We are focusing our efforts initially in these populations because they are disproportionately affected by influenza as evidenced by substantially higher rates of hospitalizations and death and are underserved by currently available vaccines and antiviral drugs. Drug supply is available for any of the 3 doses we select to start with Phase III. With that, and on behalf of everyone at Cidara, I would like to thank all of our collaborating partners for their dedication and hard work to reach this milestone, and the individuals whose participation helped us execute this important study and achieve these stellar results. I will now turn it back to the operator to take your questions. Operator?

[Operator Instructions] And the first question is from the line of Eric Schmidt with Cantor.

This is Michael Bell on for Eric Schmidt with Cantor. We'd like to extend our congratulations for this exceptional outcome. A quick question from us. Assuming FDA sign off in August, is there any reason why you could not start the Phase III trial in the fall this coming flu season?

Thank you, Michael. Our guidance still remains that we will start the Phase III study in the spring of [Technical Difficulty] Southern Hemisphere. That said, we will be meeting with the FDA in the next 1 to 2 months, and we will have that conversation. But as of this time, we have not changed our guidance.

The next question is from the line of Seamus Fernandez with Guggenheim Partners.

So first off, just congratulations on the great data. Maybe, Jeff, can you confirm for us, I think the automatic assumption is that you'll be advancing the 450 dose into the Phase III program. Just hoping to get a better understanding of your advancement towards a commercial presentation and what that commercial presentation ultimately might look like. I think given the fact that currently, you're still in the sort of 150-milligram prefilled syringe presentation at this point. So just wanted to get a better -- a little bit of clarity on that. And then second question is on prospects for engaging with BARDA prior to sort of a turnover of the budget from September of this year. Is there -- and do you see an opportunity to engage with BARDA sooner rather than later as an opportunity to capitalize on potential nondilutive -- incremental nondilutive financing?

Sure, Seamus. Thanks for the questions. With respect to the first question on the dose presentation, at our recent R&D Day, we spoke at length of our development work that is ongoing with CD388, which includes the potential change from prefilled syringe to a single-use vial and the potential for a higher concentration dose. We are still undergoing that work. We expect to start our Phase III study with the same 150-milligram 1 mL prefilled syringe. That said, the ongoing development work is still advancing. And at some point, we will evaluate the opportunity to change that to a commercial presentation. With respect to the second question on BARDA, we had also announced at that R&D Day that we have already started engagement with BARDA. We have not had the opportunity yet to sit down with them and meet to review the Phase IIb results we just disclosed this morning, but you can certainly expect that we will be doing that in the near future. There's no reason to -- for me to expect that they would not be interested in the results, and we look forward to that engagement.

Great. And maybe just a couple of additional questions. First on the strains that we could learn going forward. What would be sort of the targets for additional data that you think will be important at subsequent medical meetings. I think there were 2 things that we've talked about in the past. One is just sort of the PK relationship relative to dose over time and the efficacy there? And then additionally, maybe a strain analysis of the different flu strains as a separate opportunity. But just interested to know which of those analyses and when we might see those analyses at future medical meetings?

Sure, Seamus. Yes, the PK data, which includes the time course for when infections occurred in each dose arm as well as the strain level information from the NAVIGATE Phase IIb study will be available by the September, and there are medical conferences that start in September, and we will be submitting those results in time for those conferences.

Great. Congrats again on the phenomenal results. I'll jump back in queue.

Our next question is from the line of Brian Abrahams with RBC Capital Markets.

My congratulations as well on the data. Realizing that this is pending FDA discussions, but I'm just curious, given the effect size you're seeing here, but also the potential for variability and severity of the flu season, any updated thoughts on how you might be thinking about the design and powering of pivotal studies here? And then does this -- do the data here change your view on, I guess, how rapidly you might go beyond the high-risk comorbid and immunocompromised population and potentially explore broader populations, including in combination with vaccination?

Sure, Brian. Both important questions. We will be at our end of Phase II meeting. We will be meeting with the FDA to discuss the Phase III design. And Nicole, perhaps you can address what we have previously disclosed about our interactions with the FDA with respect to the Phase III study expectations.

Thank you, Brian, for the question. And thank you, Jeff. Yes, as we relayed in our R&D Day, the assumptions for the Phase III trial that we shared with the FDA were in effect size of 60% with 90% powering a placebo background attack rate of 1.5% and 10% loss to follow up. So as you can see from the trial results today, that provides us an adequate margin and sort of a buffer essentially for the results of the Phase III and how Phase III would turn out in a different population. And moving forward, of course, we will be allowing vaccination that is the standard of care for the Phase III population, but vaccination will be optional. So we will be able to evaluate essentially 2 subgroups. Those who have received vaccine and those who have not in combination of CD388.

Got it. That's really helpful. And then maybe just a quick follow-up. And I'm not sure if the data -- all these data have been analyzed yet. But did you see any differences with regards to age or region in terms of preventative activity in the study?

And Nicole, maybe you could just highlight that, yes.