Conference Transcript - FTH 2026-09-16

Jason Russell, Moderator

Okay. Good morning. Thank you, everyone, for joining here for the third day of the Morgan Stanley Healthcare Conference. My name is Jason Russell. I'm Managing Director with the team. And it is a pleasure to be joined by CEO Anand Parikh, CEO of Fythe Therapeutics. First time joining the conference. First time being Fythe, I think, at this time of the year. So it's exciting. you've got a big, big kind of period in front of you moving quickly. So I think it would be great to get oriented. Let's jump right in. Maybe at the 10,000-foot level, you're a new public company under this name. Maybe give us perspectives around the two- or three-minute overview of FITE and what you're trying to do.

Anand Parikh, CEO

Yeah, so FITE's a company focused on multi-node innovation, of crucial cancer pathways. We're starting with the PI3K-AKT-MTOR pathway, which is the most frequently mutated pathway in all solid tumors. It's actually a pathway that was discovered by my co-founder, Lou Cantley. And we have two drugs, sapinacertib and cerebulisib, which inhibit PI3K-alpha and mTORC1 and 2. And those drugs have shown a 47% overall response rate in a phase 1b, and we're excited about some data that's coming up here at the end of the year in endometrial cancer. You know, we believe that multi-node inhibition of the PAM pathway has been de-risked, but that there are some important challenges still to be addressed, including oral administration, lower rates of stomatitis with no prophylaxis, and also greater target coverage. And so that's really what we think we can bring, is really unlocking the promise of the PAM pathway and hopefully other pathways in the future as well. We're well-funded with about $186 million is at the end of Q2, which is more than enough capital to get us through the endometrial phase 2 readout at the end of this year, and then a phase 1B phase 2 in breast cancer at the end of next year.

Jason Russell, Moderator

Great. That's a great summary. Maybe to dive in on the pathway, so the PAM pathway, to your point, It's been something to study for decades at this point. Your approach is pretty unique in trying to inhibit across the PI3K, AKT, mTOR pathway all at once. Why is that going to potentially produce a different outcome here? and maybe underline my question is, you know, what's the value of being across all the nodes versus single node?

Anand Parikh, CEO

Yeah, I think the way we look at it is that single node inhibitors are really partial pathway inhibitors. They don't fully shut the pathway down. And when you do that, you don't have a solid low bound to your therapeutic window. So it means that the only way you can drive any efficacy is by continually dosing up. And when you do that, you see challenges in terms of toxicity. And that's really what's bedeviled the PAM pathway for a long time, is the toxicity associated with single-node inhibitors. And we believe, paradoxically, that multi-node inhibition, hitting the pathway at more points but at lower dose, is actually going to provide better efficacy and better tolerability. And I think we've borne that out, and some of our competitors have borne that out in clinical data.

Jason Russell, Moderator

Got it. So, better tolerability, better pathway inhibition don't have to be as high a dose because you're across the pathway. So, this is quite simply just finding a way to prevent the tumor from having a workaround being across all nodes.

Anand Parikh, CEO

And it's something that we've seen in other pathways, right? Even if we look at KRAS inhibition, instead of inhibiting just G12D, being pan-KRAS, BRAF-MEC, this is a story that's been told many times in cancer, and we see that with these evolutionarily conserved pathways like PI3K that inhibiting these pathways up and downstream often leads to better results from an efficacy and a toxicity perspective.

Jason Russell, Moderator

Well, let's get deeper. So on the dosing strategy, the PK strategy, it's somewhat unique. You talk about maximizing your time above the IC90, you know, avoiding the peaks, rather than kind of in most oncology development, we're always just kind of trying to take it to the MTD. you know there's the intermittent dosing concept uh as well uh so so walk us through that uh and and again what what you hope to see out of that yeah so maybe i'll start with intermittent dosing the pan pathway is such a central regulator of homeostatic metabolism that really inhibiting it 100% seven days a week, 365, is going to cause tremendous toxicity.

Anand Parikh, CEO

And so what we've seen with gadatilisib and capovacertib to an extent is that you can have intermittent dosing. You know, gadatilisib is dosed once weekly and falls below IC90 relatively quickly. Capovacertib is dosed four days on, three days off. We dose three days on, four days off. So it's been proven time and time again in breast cancer so that this pulsatile dosing can work for this pathway. So we're really excited about bringing that to bear in our oral package. You mentioned the unique PK profile that we have, even within the context of pulsatile dosing. We have, since we're not intravenous, unlike gadatomacid, it has a very high CMEX, actually about 50X IC90. We are never more than 2 to 3X IC90. and that means that we avoid some of the toxicity seen with that drug, particularly stomatitis, where they have a prophylactic regimen and still see significant stomatitis, well above 50% and 20% grade 3. And we, on the other hand, have very low-grade stomatitis, sub-20%, with no grade 3 at this point. And so that's one of those things that I think is a very meaningful differentiator differentiated for patients. And then the other nice thing about our PK profile is we have much greater coverage above those critical thresholds like IC9-T. So I always say internally, cut the peaks, but not the coverage. So we have two to three X greater duration above IC9-T, which typically, as you know, in oncology translates to greater efficacy.

Jason Russell, Moderator

Right, right, right. Okay. I do have to compliment you by the way whoever came up with the decision to name it Pictor it's impossible to forget so kudos to you for that the oral just to pull the thread just a little bit more I mean how important is that I mean we're going to get to you know endometrial and breast in a second and there are other places this could go but just from a combinability perspective where the landscape is going you know how important do you see that attribute Yeah, particularly in breast cancer, we think oral is crucial.

Anand Parikh, CEO

You know, duration on therapy for these patients is significant. And if you also get in the mindset of a patient for a second, maybe you've been on adjuvant therapy, you know, for a number of years. You had a recurrence several years after you finished adjuvant therapy, usually. And then in first line, you've been on CDK4-6 plus AI. Again, oral therapies. you're not sitting in an infusion chair three days on with a port potentially, right? So the treatment burden feels very different for an oral therapy than it does for an intravenous therapy. And we think that's important to these breast cancer patients. You know, we've seen it in our own trials in breast cancer. These patients don't feel the same treatment burden as they might in other diseases where they're kind of willing to sit in an infusion chair. And so that's something that we think is going to be increasingly important, not only in second line, but in first line even more so. If you want to combine with CDK-466 and AI, which are both oral therapies, having another oral that you're adding on to that is a lot easier than adding an intravenous or infused therapy into that mix.

Jason Russell, Moderator

Yep, makes sense. Okay, let's switch to the clinic and what's on the come here. So first opportunity to see or next opportunity to see real data is endometrial cancer. You're running a phase two there. Public guidance is top line for the phase two by the end of the year. when that data set comes to the public what are the two or three things that you're focused on you encourage investors to focus on to decide if the profile that we're seeing from PICTOR is clinically meaningful in a very difficult cancer I think it's a great question first of all you want to look at what the treatment landscape looks like and what a likely comparator in a Phase 3 would be.

Anand Parikh, CEO

So that is going to be Paclitaxel re-challenge, which gets you 10% to 15% ORR with 3 to 4 months PFS. If we're meaningfully above that, I think that really is going to give you a good signal that we are active and capable of winning a Phase 3. In terms of a comparator which has done so So recently, SAC-TMT in an all-China Phase II showed with a 30% ORR in about 5.6 months PFS in only a third of those patients that had prior IO, and they won in a Phase III. They've announced that. At the first interim OS look, they won. So again, if we are showing something in that neighborhood, I think you're going to have high confidence that in a Phase III, we're going to be successful. I think that's one thing. The second thing I think is going to be very important is tolerability. So endometrial provides significant read-through to breast cancer in terms of both efficacy and tolerability. So endometrial cancer, 90% of the patients are obese, pre-diabetic, or diabetic. We have an HbA1c inclusion requirement or permission that is up to eight. that is higher than any of the other PI3K agents thus far. And we're doing it in the sickest population. If we show really good tolerability along the dimensions of hyperglycemia and stomatitis, again, with no prophylaxis, then I think you're going to have real confidence when it comes to breast cancer that that tolerability profile is going to hold. So I think those are the major things that investors are going to look to from that readout. One, are you active? Can you win in a phase three? And two, what can I learn from the tolerability profile that's going to allow me to make that jump into breast? I think the final thing I would add, because I like making points in threes, is, you know, endometrial cancer, as you mentioned, is a really tough disease. Average mortality at a five-year point is about 85% death. It's only 50% in breast. I mean, both statistics are horrible, but clearly endometrial is a higher rate of mortality. You also have the sicker, more insulin-resistant patients, and our combination partner is paclopaxil. So I think what you can see from the tolerability and efficacy perspective in endometrial, you should be able to improve upon that in breast.

Jason Russell, Moderator

Great. So we do not, from the Phase I-B dataset, need to replicate what were pretty fascinating results. I think you had four responses in five patients and endometrial and three CRs. So if we see that in the Phase II, then we're off to the races.

Anand Parikh, CEO

Look, I would love to see that, but I think it's an apples to oranges patient population just because out of those five patients, only two had received prior IO, three had not. 100% of the patients in our upcoming phase two will have received IO. One of the patients was taxane naive in the phase 1B.

Jason Russell, Moderator

100% of the patients will have received taxane carbotaxel in the phase three.

Anand Parikh, CEO

So we're taking a little bit later line, a little bit more homogenous patients in that phase three. But I think as we look to earlier lines, you know, I would hope to see that type of response rate in patient population potentially in earlier lines.

Jason Russell, Moderator

Maybe just to wrap up in an endometrial, and then I'm going to get to breast. You recently got a fast-track designation. You know, these data are coming. saying, you know, talk to us about what the, you know, the next step would be post these data in endo, you know, thoughts around what a pivotal strategy might look like to the extent you're willing to share.

Anand Parikh, CEO

Yeah, so, you know, after this data, we've been in discussions with the FDA, and we'll have an interaction at some point this year, and then we hope to announce our registrational strategy from there, and that would be a randomized phase three and likely putting PICTOR plus Paclitaxel up against Paclitaxel. We also hope within the context of that study to answer a contribution of components, potentially cerebilis and plus Paclitaxel in a third arm. It would be randomized and have an inbuilt futility analysis, we believe, and then could drop out. So, you know, it wouldn't be a long, arduous endeavor, but a small number of patients in a futility analysis. Now, we have to align on that strategy with the FDA, but in prior discussions, they've been receptive.

Jason Russell, Moderator

Okay, yeah, no, I think that's an important point of clarification is people, you know, contribution of components and this being two drugs. So thanks for that. Okay, maybe to switch gears to what is, you know, a huge commercial opportunity, but let's bridge it. So endometrial data, you know, assume that study is successful, defined across kind of the parameters I've discussed. How does that de-risk press, which is on the come, and, you know, what risks are still out there independent of the endo outcome?

Anand Parikh, CEO

Yeah, it's a good question. So I think when I try to break that down, I think of it through two lenses, disease and combination partner. So when we look at endometrial, again, as we talked about, higher mortality, more metabolically sick patients, I think those things are worse in endometrial than in breast. So we would expect improvement in terms of tolerability there. And then when we look to, or in terms of safety, and then when we look to the combination partner, again, you know, we're pairing with paclitaxel in endometrial cancer. In breast, our likely combination partner is CDK4-6 and fulvestrin to oral SIRDS. Targeted therapies generally are much more tolerable than chemo, right? So, again, we expect hopefully better efficacy and also better tolerability in breast than will show in endometrial just because of the disease and the likely combination part.

Jason Russell, Moderator

Makes sense. Okay, so development for breast. I think you're on the record that you've now enrolled the PICTOR plus fulvestrant dose escalation cohorts. You're working through the triplet with palpocycliib. Public guidance is interim efficacy data, I believe, in the second half of 27. So what does that mean, and what do you hope that package will tell you?

Anand Parikh, CEO

Yeah, so we said year-end 27.

Jason Russell, Moderator

Okay, year-end 27.

Anand Parikh, CEO

And what we hope that it will show is really that we're active across both PI3K mutant and wild-type patients in combination with CDK4-6 and Fulvestrin, and that people can underwrite a phase three and that we'll have the necessary data set to be able to take to the agency and then begin phase three work. I think there's also important de-risking. You know, we talk about the read-through from endometrial to breast, but I think investors and others want to make sure they see it in breast. You know, they want to make sure they see that same tolerability profile that we can combine with CDK4-6 and fulvestrant or oral SIRDS, which are the backbones of breast cancer. You know, when I think about breast cancer, I think about three buckets. You have CDK, you have hormone therapy, be it fulvestrant or ulcerd, and now you have multinode PAM. Those are the only three things with labels all the way across breast, and so we need to make sure that we can combine with the other players in breast cancer, those other two buckets that I mentioned.

Jason Russell, Moderator

Okay. There's, from a competitive backdrop perspective, you mentioned it in your opening remarks, but, you know, Salkuity's RepTorPic just got approved. And so how do you view that? Obviously, there's the formulation difference, which matters, and I think you've explained, but is, I assume you view that as a validation of this approach. Where can we get better?

Anand Parikh, CEO

Yeah, so I think ultimately it is an incredible validation of the multinode hypothesis, and I think it's a great advance for patients and physicians. There are three buckets that matter, right? It's efficacy, tolerability, particularly with regards to stomatitis and hyperglycemia, and route of administration. We clearly win on route of administration, and I think if we can win on two out of those three buckets and we're close on the third, with the larger struggle in the space. That's really what we're hearing from KOLs, and it also gives us the undeniable front-line opportunity, which is the bigger market. So out of those three buckets, we need to win on two, be close on a third. I think we can win on all three. I see no reason why we cannot, but I don't even think we need to.

Jason Russell, Moderator

Going back to a comment earlier, desire, and then this relates to the comments related to ReptorPIC. So the space is trying to move to an all-oral regimen. Obviously, if you're a patient, that would certainly be preferred. You know, you're running cohorts with Fulvestrin and Paolo. How do you see that regimen, that landscape evolving? You know, is that more phase three work that you'll have to do as those become more established to, you know, just help walk us through the journey there?

Anand Parikh, CEO

Yeah. So if we go back to the framework that I sort of discussed around CDK, hormone, multi-node PAM, I think we've seen evolution in the CDK4-6 landscape, but we're also seeing CDK4s come to the fore in first line potentially. actually. And so...

Jason Russell, Moderator

And does that, sorry to interrupt you, maybe as part of your comments, does that interject a potential risk? Because that landscape is changing quickly. And so, yeah, they keep going.

Anand Parikh, CEO

Yeah, I think, look, the first line, at the time we're probably thinking about a first line study, I think that landscape will be more settled. And so I think that actually puts us in a really great position. This is one of those few times where being second to a market, I think it's actually going to allow us to be the more novel regimen, right? We're going to be able to pair with the latest stuff. If you look at Relay, Salkuity, because of the timing of their trials, they were pairing with Fulvestrin. I don't think if you ask any KOL or physician today, they really want to be giving patients intramuscular injections. If we can pair with an oral SIRD and a 4.6 or a four in second line or an AI in a four in first line, I think that's a really exciting opportunity for patients and physicians. And that's the world we want to bring to the four for patients, right, is give them the benefit of that all-oral, more tolerable, potentially more efficacious regimen. It's a win-win for everyone.

Jason Russell, Moderator

Yeah, no, it makes a lot of sense. So in this case, having a little bit of time is your friend. and so you're not spending a lot of money for something that's going to be antiquated.

Anand Parikh, CEO

Yeah, you don't have to do a phase four afterwards to get up to speed on the latest regimen.

Jason Russell, Moderator

Yeah, yeah. Talk to me, so back to the formulation of Big Tor. So obviously it's two drugs to be able to have this multinode inhibition. Is there a concern or is it an opportunity, the fact that you can individually titrate these two doses and how sure can you be that you've got the right ratio in the work that we're doing and what does that all mean?

Anand Parikh, CEO

I think it's a great opportunity because from disease state to disease state, we can align on different doses. So in endometrial, we've aligned on the 200-meg, 3-meg dose. But for many of the reasons that I cited earlier, you know, the breast cancer population being a little more robust, disease being a little more indolent, potentially better combination partners, maybe there's a universe where we can push dose in breast. That's one of the things that this ability to titrate dose gives us. And then once we do that dose escalation work, we can lock in and move that forward for patients. So I absolutely think of it as an opportunity and something where we can go disease area by disease area and really think about what's the right dose for the biology of that disease area.

Jason Russell, Moderator

Okay, great. A couple more minutes here, so let's step back and think, okay, beyond endometrial breast, the PAM pathway is obviously relevant across a whole host of solid tumors. And so we've got to get ourselves through the gates of these next kind of key catalysts. But as you start to think more broadly about where you might go, any perspective or guidance you want to give on places that seem to make sense for you?

Anand Parikh, CEO

Yeah, I think gynecologic malignancies generally are a very interesting space to us. I think it's a space where when you look at the ADC portfolio that's coming, all of them are topo-1 payloads, and you cannot re-challenge topo-1 after topo-1. So we think as we look to move to earlier lines, our toxicity profile appears to be meaningfully differentiated from the ADCs, where a rational mind would think that a combination with ADCs for a first-line strategy makes a lot of sense. Whether it's in ovarian, endometrial, there's diseases generally where ADCs are becoming quite pervasive. So that's definitely something we're thinking about. And we've already shown sapinacertib plus paclitaxel, shown a really nice hazard ratio. It's a late-breaking oral presentation in asthma, low hazard ratio in terms of PFS. So we've shown activity in ovarian already in a randomized phase two. We'd love to bring the PICTOR regimen to bear rather than just saponassertive alone in ovarian, as I mentioned, potentially in combination with an ADC. And then when we look at lung cancer, saponassertive monotherapy has already shown in Nrf2, KEEP1 mutated lung cancer, 25% ORR, 8.9 months PFS, which is really meaningful in that subset of patients in second line who had docetaxel reign supreme. So we'll hopefully have an announcement upcoming here about a lung map study that's going to be PICTOR plus Paclitaxel in that cohort of lung cancer. So look out for that. But I think there's a lot of opportunities for PICTOR. Really, as we said, it's the most frequently mutated pathway in all of solid tumors. We want to bring this to patients in need across a variety of different tumors. I have a conversation with my co-founder, Lou Cantley, who discovered the pathway, and he said to me, I didn't give my life for 5.5 months PFS in one disease, right, in 40% of one disease.

Jason Russell, Moderator

That's a good point.

Anand Parikh, CEO

And so, you know, we want to bring that promise to bear. Like, we think PICTOR is the right vehicle, the right package, in terms of it's oral, it's combinable, it's tolerable. How do we now, you know, we have to earn the right to get there, as you said, with breast and endometrial, lower that cost of capital, show people that we're active, and then really spread the development of these.

Jason Russell, Moderator

That's great. That's a really helpful framing. Maybe in the couple minutes we have left, IP, exclusivity runway, maybe tie in with some history around where these drugs are from, but spell that out for us.

Anand Parikh, CEO

Yeah, so the drugs were initially developed by Kayvon Chokot at UCSF, And then Kayvon and Troy Wilson put them into their company, Intellikine. Intellikine was acquired by Takeda. Takeda never got development of these drugs quite right, a story that we've seen with gadatlasib, ironically enough. And they then out-licensed them. We acquired Cerebulis have been 21, Sapinacert have been 23 with the idea of putting together multi-node inhibition, something that we worked on with Lou Canley quite extensively.

Jason Russell, Moderator

And, you know, we have IP out until 2037 for composition of matter and then method patents beyond that reach well into the 2040s, which we believe are quite strong.

Anand Parikh, CEO

But we have two oral small molecules, and so combining them into a fixed dose provides the opportunity for further IP extension. And that's something we're working on and, again, hope to have an announcement there in the next 12 months or so. So that would give us exclusivity well into the 2040s.

Jason Russell, Moderator

We'll be on the lookout for that. Last question. 12 months from now, you're back in New York at the Morgan Stanley Conference. What would you be hoping to tell investors you've accomplished? And clearly, you'll be on the doorsteps of something big as well. But, yeah, final comments.

Anand Parikh, CEO

Yeah, if I'm lucky enough to get the invite again, Jason, I would love to be able to show investors that we have built or are in the process of building a premier oncology company, something that really has the ability to touch tens or hundreds of thousands of lives in the near future, both with endometrial and breast, hopefully de-risked or on the precipice of being de-risked, and really able to widen the aperture to other disease states potentially as well, including rare disease. So that's what I'm excited about. That's what we're really focused on at Fythe is building the next premier oncology company.

Jason Russell, Moderator

Listen, thank you for being here. We appreciate it. Good luck here as you run into the end of the year, and I think we'll wrap it there.

Anand Parikh, CEO

Thank you very much.