SCYNEXIS, Inc. (SCYX) Earnings Call Transcript & Summary

Greetings, and welcome to the SCYNEXIS Inc. Corporate Update Call. [Operator Instructions] As a reminder, this conference is being recorded. I would now like to turn this conference over to your host, Ms. Debbie Etchison, Investor Relations. Thank you, ma'am. You may begin.

Hello, everyone, and welcome to today's conference call to discuss results from our CANDLE trial in recurrent vulvovaginal candidiasis, or RVVC. Before we start, let me remind you that today's call will include forward-looking statements based on current expectations, including statements concerning our financial outlook for the future, leadership's expectations for our clinical results, future financial and operational performance as well as our business strategy. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Please refer to our filings in the Securities and Exchange Commission, including our most recent annual report on Form 10-K and quarterly report on Form 10-Q, including in each case under the caption Risk Factors, and in other documents subsequently filed or furnished to the Securities and Exchange Commission. All forward-looking statements speak only as of today, February 10, 2022. SCYNEXIS undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. The information on today's call is not intended for promotional purposes and not sufficient for prescribing decisions. Joining us today on the call are SCYNEXIS' President and CEO, Dr. Marco Taglietti, and Chief Medical Officer, Dr. David Angulo. Following our prepared remarks, we'll open the call to your questions. Now I will return -- I will turn the call over to Dr. Taglietti, President and CEO.

Thank you, Debbie. Good morning, everyone. [Foreign Language] Thank you for joining us today to discuss the positive results of our pivotal Phase III trial called CANDLE in recurrent vulvovaginal candidiasis, or RVVC. But before David will walk you through the details of the study design and the results, I want to take a moment to provide a high-level overview of what this trial means to our overall ibrexafungerp franchise, as we pursue brand growth and expanded utilization both in the U.S. and abroad in a variety of indications and clinical settings. As you know, we received FDA approval for BREXAFEMME last June. And we have been actively promoting the drug to U.S. health care providers for the treatment of yeast infections. Our execution from both the commercial and research teams remain strong despite the headwinds of the pandemic, and we are still forecasting over $400 million in peak sales for the VVC franchise alone. This latest CANDLE trial mirrors the prior findings from our VANISH program. And we believe that with positive data will support approval of our label expansion for prevention of recurrent yeast infections, an indication for which no product has been approved to date in the U.S. Our plan is in line with our prior guidance, and we are executing our plans methodically, effectively and most importantly, successfully. We intend to file our supplemental NDA by June, and to potentially receive approval by late 2022 for this second indication for ibrexafungerp, the prevention of recurrent VVC. But we never rest on our laurels. In parallel, our team is working to launch the MARIO trial in the hospital setting to evaluate efficacy of ibrexafungerp as an oral step-down therapy in patients with invasive candidiasis. We have also finished the Phase I with our liposomal intravenous formulation, and we continue to advance the FURI, CARES and SCYNERGIA studies in the hospital setting. Taken together, we remain extremely focused on building a large global antifungal brand for the first novel oral antifungal approved in over 20 years. So back now to today's conference call on the positive results of CANDLE, you will hear from David Angulo, our Chief Medical Officer, who will walk you through the design of the CANDLE trial, its safety and the efficacy results. After David's presentation, we will open up the call to your questions. And now let me turn it over to David. David?

Good morning, everyone. The CANDLE trial for recurrent vulvovaginal candidiasis was a randomized double-blind placebo-controlled trial. We ran this study across both U.S. and European sites as we did with VANISH. As a reminder, this trial was designed under a special protocol assessment with the FDA, which is an agreement between the agency and the company indicating concurrent by FDA with the adequacy and acceptability of a specific clinical elements of the overall total design for the study for the study intended to support the marketing authorization. Recurrent VVC is a condition in which patients have multiple symptomatic episodes of VVC during a year. It is a chronic condition caused by multiple factors, including persistence of Candida in the vaginal environment and the individual immunological response to the pathogen. This chronic condition can be very distressing. And in the U.S., there are no approved treatment options to date. Also continued suppressive therapy with oral fluconazole for 6 months is recommended. The overall goal of a treatment and strategy is to present or decrease the occurrence of symptomatic episodes. The CANDLE trial enrolled 260 female patients with a recurrent VVC, which was defined as 3 or more episodes in a 12-month period. Patients needed to have a symptomatic episode of VVC at the time of enrollment, and initially receive a 3-day regimen of oral fluconazole for their VVC episode as recommended in current guidance. Those who had resolution of their signs and symptoms were then advanced to the prevention of recurrent phase of the study and were randomized to either ibrexafungerp or placebo, which were administered at a dose of 300 milligrams BID for 1 day once a month for 6 months. The test-of-cure visit occur at week 24, which is 4 weeks after the last dose. This study was designed to evaluate the efficacy of this dose regimen in preventing VVC recurrences. The primary endpoint was clinical success, and we use a rigorous definition. For a patient to be considered a clinical success, they should not have any suspected or proven recurrence of VVC regardless of culture results. We need to remember that the culture results are not available immediately, and this is a very symptomatic condition that typically requires and receive treatment even without culture results on hand. In other words, patients are often treated based on suspected recurrences. Therefore, we believe that the definition of this endpoint in our study considering suspected recurrences [ of a failure ], closely reflects the way that recurrent VVC cases are being approached in real-world clinical settings, making these results meaningful to most clinical practices. In the randomized portion of the trial to access the activity of ibrexafungerp preventing recurrences of VVC, we had 130 patients treated with ibrexafungerp and 130 patients treated with placebo. There were no imbalances in baseline characteristics between the 2 groups. 65.4% of ibrexafungerp-treated patients achieved clinical success, the primary endpoint compared to 53.1% of placebo-treated patients. The results were statistically significant with a p-value of 0.02. The advantage of ibrexafungerp over placebo was sustained over the 3-month follow-up period, and remained statistically significant, with a p-value of 0.034. Considering the importance of understanding how new treatment options work in VVC patients, who are failing fluconazole treatment, we took advantage of this study to investigate how patients failing the initial 3-day regimen of fluconazole that could not be enrolled into the maintenance study will respond to 1 day oral ibrexafungerp. For this study, we have 24 patients who failed to respond fluconazole and were given a single day open-label ibrexafungerp treatment. After receiving ibrexafungerp, 71% of these patients achieved meaningful reduction of their signs and symptoms at their test-of-cure visit, which occur around 11 days after treatment. This is a testament to the efficacy of ibrexafungerp in a more challenging patient population that may not respond to azoles. Safety was generally was -- generally considerable to what we have seen in the VANISH trials with no treatment-related serious adverse events or no discontinuations due to adverse events in the ibrexafungerp group. The most commonly reported events were headaches and gastrointestinal events, which were mostly mild in nature. Only top line data is available at this point. We will be presenting additional details and results from this study in scientific meetings in the future. With these results on hand, we are now studiously working in preparing our supplemental NDA submission and seeking approval for this new indication by end of this year. Operator, we will now take questions.

[Operator Instructions] Our first question comes from the line of Michael Higgins with Ladenburg Thalmann.

Congrats on the positive results. First question is just trying to better understand the response rates, 65-ish versus 53. What were your powering assumptions coming into the trial?

David?

Sure. So what we were estimating -- the sample size estimate was estimated responses. When we initiated the trial, we were estimating response rates for the active arm, about 65%. And however, we were estimating lower response rates for the placebo that was in the 43%, 45%. That's the numbers that we were considering when we powered the study.

Okay. That's helpful. And walk us through again, the decision to secure an SPA agreement. It should certainly help with the review, but any comments there would be hopeful. But again, why you chose to go that SPA route?

Sure. Happy to address that as well. So we need to keep in mind that as of now, there has not been product approved for this particular indication. So there is no particular regulatory path or benchmark that has been already defined in regards to how to get a product approved for -- intended to -- a product that is intended for the prevention of recurrence of VVC. So that was the primary reason. Since there are no specific guidelines regarding what endpoint the agency wants to see, regarding what exactly the design that the agency will be agree on in order to get approval for a program for this indication. We decided to go with that, and to discuss with the agency or propose protocol and to ensure that the endpoint that we were selecting as primary was in agreement to their expectation that the design of the study, the amount of follow-up, et cetera, all these elements are in agreement to the expectations of the agency for -- that if the results are positive, this will be a design that they will support -- that it will support their approval of a marketed product. So that was primarily the reason was that this is -- there are not studies in the past that have been used to support the marketed application in this indication. So it's prudent to ensure that the agency is in agreement with your proposal before, embarking into a large clinical trial at this time.

And Michael, if I can add that this actually makes us confident that we have -- at this point, we have package of data, which should be acceptable to FDA. Let me also add that we consulted also with the European Medical Agency as we did with the VANISH trial to ensure that all our protocols are acceptable on both sides of the ocean.

Appreciate that. One last one before I jump back in the queue. Can you share with us how many patients had failed oral fluconazole before being randomized into the study?

I don't have the total number in front of me. But as I mentioned, when they fail -- when they were not able to be randomized into the study, they were offered if they wanted to participate in another subset of the study, which was given then really the opportunity to receive 1 single date oral ibrexafungerp. Not all of them went into the substudy. However, the ones that went, which were the 24 patients, we were obviously very pleased to see really that single day of oral ibrexafungerp was able to really substantially decrease their signs and symptoms in a great proportion of them, 71% of them. So that certainly, we will provide a subsequent much more mapping of what was the flow of the patients that went from the screening to randomized to completed later on.

Our next question comes from the line of Louise Chen with Cantor Fitzgerald.

Congratulations on the data this morning. So my first question is, is this 65.4% versus the 53.1%, and I know you had a higher-than-anticipated placebo rate. Do you think that's enough of a therapeutic advantage for doctors to prescribe a ibrexafungerp? Any thoughts there would be helpful. And I may have missed this, but how does the side effect profile look in the study? And then last question is on pricing. How are you thinking about this is going to be in line with what you price currently? And do you think payers understand the value of your drug? Do you have any pharmacoeconomic studies to support this recurrent VVC sort of prophylactic use?

Well, Louise, that's a lot of questions, and thank you for the questions. So well, let's start, first of all, with the efficacy, and I will have also David jumping in. But at a high level, we truly believe that the doctors will be eager to have a new alternative for prevention of recurrence. Right now, there is nothing approved to date. And certainly, there is a need for a new class. Also the fact that we have been able to enroll the study so quickly, I think that meant that both doctors and patients were really eager to try something new because there is such an unmet need among the patients that don't have to respond to a standard treatment. So we believe that these are meaningful results -- clinically meaningful results, and the results that actually will help us to continue to expand the VVC franchise of BREXAFEMME. To answer your question about side effect, I will have actually David jumping in. David?

Yes. The safety profile was, I would say, that very comparable to what we observed in the VANISH trial. So the main adverse events that were reported possibly associated with the study drove with diarrhea, nausea and abdominal pain. The great majority were mild. We have also headaches -- some have headaches reported in this particular trial. And what was very positive to us, obviously, is to verify that none of these adverse events resulted in any discontinuation of the drug even when the drug was administered once a month for 6 months. So we saw that the safety profile was very, very positive in this particular trial.

And let me go to the pricing questions. For us, it's a little bit premature to talk about the pricing. We -- certainly it's something that we will let -- we will disclose later on. Right now, the pricing for the product for the treatment has not been an issue at all. We have been achieving great coverage with many payers covering the ibrexafungerp family. And the reason is because the payers, they have seen the value of the product, they have seen the value for the patients. Also, they are also always driven or, let's say, driven a lot from a pharmacoeconomic aspect, also the fact of having patients who can receive an alternative treatment to fluconazole, but do not need to go back multiple times to the doctor with the visit and so on. That, of course, provide us an incentive, an economic incentive to payers to cover our drug. And in fact, that has not been an issue. Clearly, the fact that we have something new after 25 years, that is something that has been appreciated also by the payers.

Our next question comes from the line of Oren Livnat with H.C. Wainwright.

Congrats on the positive results. I have a couple of questions. First, I'm sorry if I missed it, but just regarding the cure rates overall, you mentioned a higher placebo response rate than expected. I know it wasn't prospectively studied here in the study, but can you just comment on how the ibrex, I guess, recurrence prevention rates compared to what you would expect, what you've seen in the literature with regards to recurrence rates for patients on fluconazole not placebo? And then also just on that 71% efficacy that you saw in the, I guess, refractory patients, what's the apples-to-apples, I guess, cure rate? I think that 71% is for elimination or significant reductions. So it seems like it's a slightly different end point. So any help you can give us there. And then I have a commercial follow-up.

David?

Sure. So for the third question, well, number one, there are very few studies that have been rigorously conducted. I would say probably it's just only one that is in the literature regarding response rates after fluconazole-suppressive therapy. With fluconazole suppressive and the endpoints that were used for definition of recurrence, et cetera, were different. So that is very difficult to really have an apple-to-apple comparison here. Weekly doses of fluconazole-suppressive therapy generally considered effective in preventing the recurrences of the patients, that's the general concept. Immediately upon discontinuation of the fluconazole-suppressive therapy, you start seeing recurrences very rapidly. That is what the literature has reported for those particular scenarios. So it's, as I mentioned, difficult to really compare exactly percentage-wise one versus the other and pretend that this meaningful comparison because they are studies that have been done in different -- using different definitions and different times, many, many years ago. Based on that, it will be difficult to conclude, but it's that. However, what we know is in this case, we were very happy to see that ibrexafungerp retain really the, I would say, the effective factor in regards to not occurrence of recurrence during the follow-up period that we followed these patients even without the drop. So that role is clearly differentiating versus what has been reported previously in the past with fluconazole. Then your second question that was related to the 24 patients with -- that failed the 3 doses of fluconazole and then we offer open-label like ibrexafungerp. Yes, in this case, we evaluated different endpoints that we will be presenting in the future. We have -- at this point, we only have kind of the top line data, but we evaluated different cuts in regards to what is traditional 0 signs and symptoms, no more than 0 to 1 signs and symptoms that has been considered a clinically meaningful resolution of signs and symptoms. And we will be presenting that information in the future. At this point, what refers to the resolution of signs and symptoms, it was what it was considered an investigated clinically -- investigating the ones to sign in the study as a clinical -- clinically meaningful improvement based on the baseline signs and symptoms that the patient was coming with. And that is what it will be reported -- that we will plan to report all the different cuts of the data in the near future once we have them available.

Okay. And actually, just maybe think of another question about the clinical endpoints. Just remind me if it's a design. Is the recurrence -- any recurrence within at any point in that 24-week follow-up such that the time to recurrence would probably be a very meaningful differentiator that we're not necessarily seeing in this results? If ibrex has -- most of these people who are having a recurrence it's happening -- at week 23, that's working really well versus placebo having a week 1. What do we know about that data?

Yes. We are analyzing that data. We don't have it available as part of top line data yet, but that is the data that you could expect in the future in regards to a difference in time to recurrence. We are also something interesting in the design of these studies. But actually, we follow the patients for the entire period of time, which is the entire 6 months that was intended as a treatment period of time plus 3 months of follow-up. And we will also know if the number of recurrence is actually decreased with patients that were with ibrexafungerp, even those who potentially had a recurrence, if the number was different versus the ones who were having placebo treatment, et cetera, all that information will come in the future.

Okay. So that's an important piece we'll look forward to seeing. And then I'm sorry, to just take a lot of time, but just on the commercial side, just help us understand how important this -- assuming it's approved at the end of the year, how important this is? Are we talking about growing into a new patient population, primarily? Or is this really just about further solidifying or opening physicians' eyes to the, I guess, value of this product even just as a first line treatment of any episode? Clearly, assuming it's covered by insurance, if I'm a doctor, I'd rather give someone that's going to -- products and have less odds of recurrence regardless if they're a predefined RVVC patient, right? So help us understand if that's, I guess, an important thing to get paid doctors over the hump now? And where are doctor expectations or what's the feedback now in the field? Why are we seeing the volume we're seeing now? Is there a perception problem? Is it just a matter of insurance coverage? Is it COVID? Help us understand when we should see some acceleration in even just the existing indications.

Well, Oren. Yes, that's a lot of questions. First of all, we -- that's actually -- that's very good. So first of all, let me make very clear what we expect is that recurrent VVC will also provide a meaningful contribution to the overall growth of the product. It will provide more confidence for the doctors that we have a product that works also for these patients where there is sort of almost a chronic status of candidiasis. But you are making a very good point, and a very astute one is how many of these recurrent patients after all are simply patients that with fluconazole are never completely cleared of their infection given the fact that azoles, it's well known, but azoles have just a fungistatic effect. So probably in some patients leaving some Candida, later on can regrow. Our product is fungicidal. So we believe that at the end of the treatment of VVC, the treatment of the episodes of VVC with BREXAFEMME will remain the major use of this drug because it gives you the possibility to clear the infections once and for all with 1 day of treatment. However, we expect also that some patients are patients to bet for a variety of reasons, can be an atomical reason, some maybe immunological status of the patients or other factors that really becomes these chronic cases. And these are the patients where certainly the treatment of the CANDLE study will provide a solution for them. So we expect that -- by the way, the feedback we received from the doctor is very good. It's very enthusiastic, both doctors and patients, is -- they are delighted to have an alternative to the patients to whom they have been giving fluconazole, fluconazole and only fluconazole for so many years. So this is certainly something that we are seeing is the doctor changing behaviors, if I can say, changing behaviors. Keep in mind for 25 years, we have been given fluconazole. So we are really changing their habits, their automatic response of VVC fluconazole. We also start to see doctors that are becoming regular prescribers of BREXAFEMME. And you mentioned about the data, our sales data, I would not read too much into the month of December and January. We expect that, especially as the country will recover finally from this Omicron wave, offices are opening, but you will see the fact that concrete results in terms of expanding our sales. So overall, we are very pleased actually. What we have seen on the market, the reaction of the doctors, the response of the patient and most importantly, the coverage of the payers. So we -- I think we are doing well on all 3 fronts.

Our next question comes from the line of Kumar Raja with Brookline Capital Markets.

Congratulations on the data. And with regard to the discontinuation rate in the placebo arm, what are you seeing there? And how does that compare with active arm?

David?

Yes. You mean that discontinuation due to adverse events specifically. We had a couple of patients who discontinued due to adverse events in the placebo arm. In regards to discontinuation for therapeutic, for lack of efficacy, that's an information that we will be happy to share in subsequent presentations, et cetera. At this point, we don't have those numbers entirely reported to us. As I mentioned before, we just got all primary end points kind of reported right now is top line data. But certainly, it's an important aspect to keep an eye on and to be -- and to report in the future.

[Operator Instructions] Our next question comes from the line of Michael Higgins with Ladenburg Thalmann.

This morning, there's a paper on recurrent VVC treatments. It goes through all the azole options forecasted, et cetera. It's pretty timely, obviously. It's an obvious setting. So I'm wondering -- I guess twofold. How do you plan to tomorrow, today, et cetera, before the approval, plan to address the market opportunity? In that answer, if you could provide some feedback for us as to how many -- or what percent of the current Rxs are in this setting as well. And then the last piece of this would be, in the Phase IV world, we have a little more flexibility under the SPA. Would you consider running a trial in kind of a real-world population in this the setting of patients that I mentioned in this paper where they fail all these different things. Would you consider running a Phase IV there to really highlight that in this case, 29% of patients have a recurrence that have already failed oral fluconazole?

Thank you, Michael. Let me take the last question first, about the real world. First of all, we do believe that really the way we designed together with FDA, through FDA, the study, it has been a real world type of study. In fact, our end point, 1 point that -- and it's something that David stressed. But let me stress it again, our end point is a very rigorous end point. It's not a -- I can say academic definition of recurrence that requires symptoms and positive microbiology because -- we know that in practice, doctors are not doing microbiology that is -- most of the diagnosis -- actually almost all diagnosis in this area are done clinically. And so our definition of endpoint is about having demonstrated or suspected VVC recurrence. So we believe that this is a real-world-type end point, one that really reflects what the doctors will see. However, your point is very well taken. It is -- there is a lot of discussion in the scientific community about real-world studies, and certainly it's something that we will consider. And excuse me, remind me what was the first question?

Yes. The other portion of that, I guess, 2 other pieces of it was on marketing. How can you go out to market this today? And also as your current prescriptions, what percent are already in the setting? Because obviously, it's one where we really don't have any options.

Yes. Well, let me just say, of course, we follow -- we promote and we follow the drug for the approved indication. Certainly, we are not planning to have any kind of promotion or support of an indication that is not yet approved. Of course, now the drug is available. The data are there. So doctors, of course, they have always the freedom to use the drug as they see fit best with the need the patients for this or for any other indications, but -- where we may have a fungal infection.

The other portion of that question was of recurrent business, what percent would you calibrate in this population where they failed prior treatment?

Well, it's -- so you're asking how many patients are actually recurrent patients, out of the patients with VVC. Is that your question?

Yes. That are being dosed.

Yes. That have recurrent. Well, let me say, epidemiologically, most studies we report that recurrent infections, about 8% of all the cases of VVC. As I mentioned, it is -- the -- what we have seen with doctors, clearly our, let's call it, the low-hanging fruit in our launch as the patients that have been receiving fluconazole many, many times. And this is what we have seen. But these patients -- that probably someone may even consider patients recurrent, they responded to 1-day treatment. And in fact, the biggest proof of that is actually the result of our substudy in the CANDLE study. These patients, these 24 patients who received 3 doses of fluconazole, and that is 3x the approved dose for VVC. So 3 doses of fluconazole, and still did not respond. However, 70% of them responded to 1-day treatment of ibrexafungerp. And that goes back to the point I was making. The mechanism of action makes a difference, being fungicidal is what we -- is making the difference for this product. So as we continue to gain experience in treating VVC, we will be able also to learn more how to position the drug when it will be approved also for recurrent between recurrent and treatment.

That's very helpful. Just to clarify my question on real-world was more so to expand beyond oral fluconazole to the other drugs. But clearly, the design of this is pretty much set up for real-world. Just one last one here and my follow-up, if I could. Regarding the confirmation of recurrent VVC, what percent were tested versus symptomatically confirmed?

David, do you have the data of the top line?

We don't. But we will certainly present the difference how these patients were classified or what was the category of each one of these patients classified as a culture-proven KOH-presumed or only symptomatic VVC. We will present that in the near future for sure.

Ladies and gentlemen, we have reached the end of today's question-and-answer session. I would like to turn this call back over to Dr. Marco Taglietti for closing remarks.

Thank you, operator, and thank you, everyone, for joining us this morning. We are truly so proud of our high-potential young brand and our team's continued execution. We are working in parallel to maximize the value of BREXAFEMME in the vulvovaginal franchise, and at the same time, expand utilization as we continue development in the hospital setting as a step-down therapy and in difficult-to-treat infections. Positive results such as the [indiscernible] we reported today give us further conviction in the value of ibrexafungerp as an asset that provides really something critical to patients, and will bring value to our shareholders. Our launch continues to progress. And by the way, we will provide a detailed update on our progress at next month's earnings calls. Thank you very much for your attention.

Thank you for joining us today. This concludes today's conference. You may disconnect your lines at this time.