Innovation Conference. I'm Vamil Divan, one of the biopharm analysts here at Guggenheim. Pleased to join us now next in this room, we have the team from SCYNEXIS, David Angulo up here, the CEO of the company. We do have a few slides we're going to kind of show throughout the course of the discussion. David, maybe I'll just have you start by just, for people less familiar with SCYNEXIS and the story, a little bit of an overview. It's been a sort of transformative year for you, so where things stand now, and then we'll look forward from there.
Thank you. Thank you for the invitation, Vamil and SIA. Certainly, to tell you a little bit about the company, the ones that you are not familiar with. We're focusing really advancing innovative solutions for rare disease spaces. What you, Vamil, mentioned about really the developments over the past year, what we did is that in the past, we were focusing development of antifungal products for many years.
We have a long platform of antifungal products that we were developing in invasive fungal disease infections. We recently acquired an asset that we are developing in the ADPKD space. Primary reason for really expanding our indications into the ADPKD space was obviously, this is an area, it's still in the rare disease space that we were quite interested on, has an area of significant attractive market, a lot of development opportunities.
It's an area that is substantially underserved by current therapeutic options, and obviously was a way to really provide a potential shareholder value creation opportunity within the space. At this point, really, we have evolved the company right now in having two programs, one in ADPKD and one in invasive fungal disease infections. We have already developed a product in the past that we partnered with GSK, which is called BREXAFEMME. At this point, it's fully out-licensed to them, for which we are eligible to receive some sales milestones about it.
Okay, great. Maybe we can talk more about SCY-770 and the potential there in ADPKD. Just maybe you can give a little more background on the product itself, this mechanism, and why you think this has a potential in ADPKD.
Yeah, thank you. Yes, we selected this particular product for acquisition really because we were very much attracted by the mechanism of action in this particular disease. I don't know if you're familiar, but in the ADPKD space, there is only one therapeutic alternative right now, that it is, I would say, not very much used because the fact that it has a very significant safety connotations and lack of tolerability.
Beside of that, it's a very substantial market opportunity. This particular product that we're licensing has a novel mechanism of action that is very well validated by the scientific community to have the opportunity to really deliver a clinically meaningful effect in ADPKD patients. It's a product that has already been administered in around 300 individuals in different stages of clinical trials.
It's ready for really initiation of phase II that we're planning to initiate by the end of this year, and really has a very clear path for regulatory approval. It has a good IP protection. Those were kind of elements that really drove too much into our decision to really bring this product into the company. More specifically, addressing your question regarding the mechanism of action.
ADPKD is a disease that it is generated by the mutation of one or two genes that are responsible for the production of certain proteins, polycystin-1 proteins, that are needed or essential for the adequate functioning of the tubular epithelial cells. When these two proteins are not present, there is a cascade of events in which they start really forming cysts, and those cysts start taking over the entire kidney architecture, and they ended up causing kidney dysfunction.
It is well-known that AMPK activation is reduced during this physiopathological pathway, and by reactivating this enzyme that is responsible for multiple metabolic aspects in the cells, by reactivating this enzyme via a direct AMPK activator, we are able to modify critical pathways like the mTOR, cyclic AMP, that are responsible for the cyst proliferation.
We are also able to really reduce the fluid secretion into the cells by the chloride channels, and also reduce inflammation, which I would say that three of the key hallmarks of this particular disease. What we are also very excited about this AMPK activator is that it has a very high selectivity. So it binds preferentially into the versions of this enzyme that are more common in the kidney space, rather than binding into other versions of that enzyme that may be more common in other type of organs. With that type of selectivity, really allows you to have a better safety profile.
Okay, great. You did have some phase I data, I think, that you've shared also. Maybe you can review that.
That's right. We actually conducted a phase I study in order to evaluate additional doses that had not been evaluated with this particular molecule in the past. We recently announced the completion of that particular study, and with that data from that study, the doses that we evaluated were higher than doses previously evaluated, had allowed us to really conduct a population PK modeling in order to inform us properly about the doses that we are proposing for the phase II study that we are planning to initiate by the end of this year.
The positive data is that all those doses were well tolerated. We were able to further characterize the pharmacokinetic profile of those doses. We're in the process of discussing with the FDA our final study design for phase II and really trying to move it into initiation towards the end of the year.
Okay. Great. I know you're still in discussions and finalizing, but maybe you can give us a sense of what you're hoping or what you're expecting to show in terms of the design for the phase II program.
Yeah. The outline of the design for the specifics of the design, as I mentioned to you, we'll probably share them once we do have a reached agreement with the agency. But the outline is a full one-year treatment period. We're aiming to really have three groups of patients, two of them receiving two different doses of SCY-770, and one receiving placebo.
It's going to be a full year treatment duration. We are aiming to have an interim readout towards the end of next year, and that particular interim readout will give us an indication of the progression or the impact in the progression of total kidney volume, which is one key relevant, I would say, endpoint to really understand the potential efficacy of a product in this particular condition. Sorry.
We are aiming to enroll patients that are rapid progressors, that are defined as rapid progressors based on certain categories, and that will allow us to really see the magnitude of effect in much more shorter period of time. The design is not so different to what is typically evaluated and seen in this particular type of studies. We will be happy to disclose soon what are the doses that we're going to be integrating into that particular study.
Maybe just on that total kidney volume-
Sorry
measures, or what would you be hoping to see when you look at sort of the interim data next year?
Sure. Really the best benchmark information that we have about how TKV evolves when you do have an effective therapy on board is really the data that exists for the current product that is approved, which is tolvaptan, because it's the only product that has been evaluated in a long term that has shown efficacy.
What has been observed is that patients not receiving therapy, let's say patients receiving placebo over a year period of time, they typically have a progression of their total kidney volume of about 5%. That subgroup of patients that are typically enrolled in these studies, about 5% increase in total kidney volume in a year. Tolvaptan showed that it was able to reduce that 5% by half, so it had a 50% relative reduction.
We believe that that particular trend that demonstrated to be, I would say, a good signal to obtain tolvaptan approval, but also to really prevent or delay the progression to end-stage kidney disease, could be a good target for us. If we are able to really show a 50% relative reduction in TKV, will definitely be a good signal of evidence of efficacy for this particular product.
Okay. What else would you need to do beyond that if you show that sort of benefited in the interim to kind of move into phase III, or what's the path to market essentially?
Yeah. TKV, total kidney volume, has been recognized as a reasonable surrogate or likely surrogate marker of the disease itself. At the end, in order to get approval for an indication like this one, you also need to demonstrate evidence of activity in reducing the decline of GFR, which is actually the reflection of the function of the kidneys. You need to be tracking both, but TKV has been identified as a surrogate endpoint because you're able to really see the changes in TKV typically sooner than you're able to really identify the changes in GFR.
Both programs, phase II and phase III, will be evaluating both, but certainly there is the opportunity to get an accelerated approval based on TKV data only initially at one year in your phase III program, and then eventually you will need to also show the evidence of efficacy in the GFR endpoint as well.
The outline of the development program at this point is thinking about one phase II study and one single phase III study, and both studies will be evaluating these two endpoints in the way that the phase II study will give us a good indicator about what is the magnitude of effect in both of these endpoints to properly plan the phase III.
Okay. And maybe you can talk about, you talked a little bit about ADPKD as a condition and obviously limited options available right now in the market. Maybe just the commercial sort of landscape as you see it. It seems like there is a lot more activity now, companies looking at ADPKD as a potential space to move into. Just how do you view the landscape would be helpful.
Yeah. It is certainly an area that has attracted a lot of attention, for sure. And number one, because there is a very significant unmet medical need. Number two, because the biology and many of the pathophysiological aspects of the disease probably are better understood now at this point. So, it has really allowed many other therapies to be progressed to. I was mentioning that there is only one product in the market, tolvaptan, at this point.
Despite the fact of the limitations in terms of safety and tolerability, they reported sales of $1.5 billion in 2024. So it is clearly an important commercial opportunity. And right now, there are different treatment modalities. To the best of our knowledge, we are the only ones exploring an AMPK activator as a treatment modality for ADPKD in the clinical stages. There are other treatment modalities that are being explored.
There is a product being developed, farabursen being developed by Novartis that really has another mechanism of action, which is inhibiting microRNA inhibitor that is intended to really increase the production of polycystin-1. There are others that really trying to really modify the genetic mechanisms to which some of the mutations are resulting in lack of production of polycystin-1 as well.
Most of them have either are in phase I, many of them are in phase I, completed phase I-B. One of them, the most potentially advanced in the development program is probably the farabursen product that is right now about to enter phase III to the best of our understanding.
There is great interest, great interest in the novel mechanism of actions, and that is fantastic to really see because there is a fantastic opportunity to really demonstrate a significant impact in patients through one or two modalities, treatment by themself or in a combination therapy, to really being able to potentially finally impact the life of these patients that are in substantial unmet medical need.
Is this, do you see SCY-770 as something that will be able to use on top of tolvaptan or on top of farabursen in combination approaches, or is there some reason that wouldn't?
In theory, yes. I think that everyone is going to be developing their product to demonstrate efficacy of the product by itself. However, the fact that, as you can see here in this particular cascade that is shown here, the SCY-770 is a product that would be agnostic of any type of genetic mutation. It will be agnostic if this is a product that it is following or the disease is following PKD1 or PKD2 type of mutations.
If this is a missense mutation, a truncated mutation, it will be agnostic to all that because it's downstream to that. So in theory, it could potentially be considered as a good partner to many of the other products that are being developed at this point.
It's not the primary intention that this product will be developed for being used in combination, but however, as it has evolved with many chronic diseases, at the end, you end up having potentially two different treatment modalities to really try to maximize the beneficial effects in the patients. That is foreseeable in this particular disease as well.
Okay. Why don't we switch gears to SCY-247 and just kind of talk about that program as well, since you've had some good progress and developments there as well. You had the BARDA contract recently. Maybe you can just, again, sort of highlight where that stands and how you're developing that program.
Yeah. Let me tell you a little bit about the BARDA program probably first. Let me tell you. It was, we recently announced, in our other development path that we have is an antifungal program that is intended to really address very significant unmet medical needs in the treatment of invasive candidiasis. Invasive candidiasis is a deadly fungal disease that is typically impacting patients that are immunocompromised because of many reasons.
For instance, patients that are receiving cancer therapies or that are receiving bone marrow transplants, solid organ transplants. Once you have these invasive fungal conditions, you have really a very high mortality rate. There are not too many treatment options, and there is increasing the rate of resistance pathogens that are not responding to the currently available therapy options.
Considering this particular significant unmet medical need, BARDA has a program in which they really incentivize or partner with companies in order to make sure that there is good products being developed in order to address this particular, I would say, the public health threat that will represent the risk of having infections by multidrug-resistant strains.
So we were lucky that they decided to partner with us, and that provides up to $214 million in potential, if all options are exercised by BARDA, in towards the development of SCY-247. In the initial tranche, which is the initial option that they opted in, they are committed to provide us $18.5 million for that particular tranche.
Subsequently, there are different stages according to what you are, if you're meeting certain milestones of development, then you can maybe keep unlocking different stages and different tranches of funding through this particular program. So this is a fantastic opportunity because obviously allow us to, in a non-diluted funding, allow us to really, non-diluted funding additional input into our development programs, allow us to really continue progressing this development with really a very limited impact in our actual cash outflows from our standpoint.
Okay. You've completed some phase I work with 247, I think looking to move into phase II. Could you maybe just walk through what you've seen so far in phase I and your plans going forward?
Absolutely. There is a quite interesting, we selected this particular molecule, SCY-247, among a broad selection of fungerps that we own the full platform of. This particular analog we selected because we wanted to demonstrate some characteristics in terms of potentially enhanced oral bioavailability versus our prior analog that we developed, ibrexafungerp. We also wanted to really see a very significant tissue penetration to those organs that are typically affected by invasive fungal diseases.
We also wanted to have an intravenous and oral formulation that for the previous analog, developing the IV formulation was a little bit more challenging. In this particular case, we have already completed all full phase I assessment activities enabled with the oral formulation, and we recently completed as well that with the IV formulation.
The next stage of development for this molecule is a phase II study in patients with invasive candidiasis. It has a broader spectrum of activity. It not only impacts Candida, it also may be appropriate to really treat other fungal diseases like Aspergillus, Pneumocystis, et cetera. The initial focus is going to be in the treatment of invasive candidiasis because there is a very substantial unmet medical need.
However, because of the properties of this molecule to have low risk for drug-drug interactions and favorable safety profile, it can also play very well in other indications like prophylaxis, prevention of invasive fungal diseases. This is the overall picture in regards to what we are planning for the overall development program.
A phase II study in invasive candidiasis and potentially two phase III studies, one in invasive candidiasis and one in prophylaxis of invasive fungal diseases, in the way that we can get a very broad label at the end that really is able to really support the treatment and prevention of these diseases in patients in need. That's really, we're very happy that we were able to progress it right now with the aim to initiate the phase II study by next year.
How are you looking just in terms of developing that further then, the phase II? It'd be both the IV and the oral, and then it'd be, like you're saying, sort of an easy step down for patients if you can get both of them available.
That is right. Among the antifungal for systemic invasive fungal disease offerings that exist right now in the market, there is only one family of compounds that you can start with IV therapy and step down to the same family of compounds oral therapy. Everything else, echinocandins, for instance, they are only available intravenously.
Polyenes, they are only available intravenously. Having a product that has a very highly potent compound that you are able to really initiate intravenously and being able to move orally once the time is right is really a great advancement into the current treatment armamentarium. We need to keep in mind that invasive fungal diseases typically require several weeks of therapy, sometimes months of therapy.
Having the option to really start IV when those patients are in a very, I would say that critical condition, and being able to step them down to oral and continue therapy to oral is a critical success factor, in our opinion, for a product in this case, and also is one of the significant unmet needs.
Okay. All right, great. In the last few minutes, a couple other things to touch on. One, BREXAFEMME, obviously you mentioned that is out-licensed now to GSK. Just the latest that you can share in terms of the progress on getting that back to the market.
Sure. We developed BREXAFEMME. We obtained two indications for that particular molecule for the treatment of vulvovaginal candidiasis and also for reduction of the incidence in patients with recurrent VVC. We had at that time other products under development. There were some other studies conducted in terms of treatment of refractory fungal diseases.
GSK indicated to us that they were planning to really focus their commercialization efforts in the VVC indications, and they are in the process of relaunching the product. They have not indicated publicly when is their time to really through the relaunch. We know that they are progressing in that particular process, and we are all very eagerly awaiting to the news from GSK announcing that BREXAFEMME will be available to the patients in need.
BREXAFEMME really fulfills a very significant need in the market because as an oral available medications to treat VVC, only fluconazole is available. Those patients that are not responding to fluconazole because they are either resistant or cannot tolerate the drug, there is no other treatment available for them.
So BREXAFEMME was really aiming to really fill that particular significant need. It's still extraordinarily relevant in the market. There is nothing else that come out that really has, I would say, that is supplying to those patients in that sense. We are eagerly awaiting for GSK to bring it back to the market. We believe that soon we know that they're making progress towards that, but they have not disclosed a specific timing for that.
Okay. Maybe now you mentioned the BARDA funding as a nice way to bring in some resources. What's your now the cash position for the company and your runway looking forward?
Yeah, our cash position, we reported $63.2 million by the end of September, and that really provide us a cash runway until into 2029. So that is sufficient cash for us to be able to really complete our phase II study that we are planning with the SCY-770, which is the ADPKD program. Certainly adding the development program for SCY-247, we don't anticipate that that will impact in any way our cash runway because most of that program is somehow subsidized through the BARDA contract. So we right now have cash into 2029, allowing us really past really the completion of the phase II study for SCY-770.
Okay. Maybe just to wrap it up here, the kind of lay out the catalyst events here coming up, so obviously-
Sure
starting the phase IIs, but maybe just talk through the details on.
Really some news flows that we're anticipating in the near future. Certainly, we just released, as you mentioned, the phase I data for SCY-770 that really provide us additional information to put together the design for the phase II study. We are anticipating to really start the phase II study before the year ends with an interim analysis by Q4 of 2027 for that particular program, and the completion should be in 2028.
For the antifungal, we just released the phase I data, and we certainly are planning for the initiation of the phase II study sometime mid-2027. At this point, for that particular program, we're in the process of discussing with the regulators what's going to be the design of the study, part of also with our BARDA partners, manufacturing clinical trial material, and being ready to really start that particular program. Those are, I would say, the key milestones in the progression of our programs in terms of development.
Okay, great. Thanks again for joining us. Congrats on the transformation of the company over the last 12 months, and look forward to-
Thank you.
seeing the progress over the next 12.
Thank you, Vamil. Thank you for the continued support. Thank you.