Newsfilter article unlocker

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 the Managing Director with the team, and it is a pleasure to be joined by CEO Anand Parikh, CEO of Fife Therapeutics. First time joining the conference, first time being Fife, 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 Fife and what you're trying to do. Yeah, so FITE's a company focused on multi-node inhibition 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, sapinoceratib and cerabilisib, which inhibit PI3KAlpha 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 multinode 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 as of the end of Q2, which is more than enough capital to get us through the endometrial Phase II readout at the endof this year and then a Phase Ib Phase II in breast cancer at the ending of next year. Great. That's a great summary. maybe to dive in on the pathway, so the PAM pathway to your point it's been something that's studied 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? 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-nodal 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 it out in clinical data. Got it. So better tolerability, better pathway inhibition don't have to be as at 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. And it's something that we've seen in other pathways, right? Like even if we look at KRAS inhibition, instead of inhibiting just G12D, being pan-K-RAS, B-RAF-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. Got it. 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. as well. So walk us through that and again, what you hope to see out of that. Yeah, so maybe I'll start with intermittent dosing. The PAM 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. And so what we've seen with gadaxalysib and cap of the serotip to an extent is that you can have intermittent dosing. You know, Gvatalicid is dosed once weekly and falls below IC90 relatively quickly. Cap of the Serotip is doused 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 that this pulsatile dosing can work for this pathway. So we're really excited about bringing that to bear in an 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 Gidathamacib, it has a very high CMEX, actually about 50x IC9T. We are never more than 2 to 3x IC 9T, 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 stomatitus, well above 50% and 20% grade 3. And we, on the other hand, have very low-grade stomatritis, sub-20%, with no grade 3 at this point. And so that's one of those things that I think is very meaningful differentiator for patients. And then the other nice thing about our PK profile, is we have much greater coverage above those critical thresholds like IC9T. So I always say internally, cut the peaks, but not the coverage. So we have 2 to 3x greater duration above IC9C, which typically, as you know, in oncology translates to greater efficacy. 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 uh it's impossible to forget so uh kudos to you for that um 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 and how important do you see that attribute yeah particularly in breast cancer we think oral is crucial 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 adjunant 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 care. 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 CDK466 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. 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 view real data is endometrial cancer or you're running a Phase II there. Public guidance is top line for the Phase II 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? Yeah, I think it's a great question. And so, first of all, you want to look at what the treatment landscape looks like and what a likely comparator in a phase three would be. So that is going to be Paclitaxel re-challenge, which gets you 10% to 15% ORR with three to four months PFS. If we're meaningfully above that, I think that really is going 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 recently, The SAC-TMT in an old 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 endometrio 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 the 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 paclitaxel. So I think what you can see from the tolerability and efficacy perspective in endometrio, you should be able to improve upon that in breast. Great. So we do not, from the Phase 1b data set, 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 two, then we're off to the races. 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. A hundred percent of the patients in our upcoming phase two will have received IO. So one of the patients with taxane naive in the phase 1B, 100% of the patient will have received taxane carbotaxel in the phase 3. So we're taking a little bit later line, a little more homogenous patients in that phase 3, 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 the earlier line. Okay. Okay, great. 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. You know? Talk to us about what 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. 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, you know, putting PICTOR plus paclitaxel up against paclotaxel. We also hope within the context of that study to answer a contribution of components, potentially cerebellus plus pacletaxel 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. 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 known, a huge commercial opportunity, but let's bridge it so endometrial data um you know assume that study's successful defined across kind of the parameters as discussed um how does that de-risk breast uh uh which is on the come and uh you know what risks are still out there independent of of the endoalkyl? 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 endometrio 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 at a combination partner, again, you know, we're pairing with paclitaxel and endometrial cancer. In breast, our likely combination partner is CDK4-6 and fulvestrantor 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, then we'll show an endometrial just because of the disease and the likely combination of polymers. Yeah, 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 Palbocyclib. public guidance is interim efficacy data, I believe, in the second half of 27. So what does that mean? And, you know, what do you hope that package will tell you? Yeah, so we said year-end 27. Okay, year-ending. 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 full vestrant 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 that 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 fulvescent or oral CIRD, 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. Okay. There's, from a competitive backdrop perspective, you mentioned it in your opening remarks, but, you know, Selkuity'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 I assume you view that as a validation of this approach, where can we get better? 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, we're the largest drug 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 these three buckets, we need to win on two, be close on a third. I think we can win I see no reason why we can't all, but I don't even think we need to. Okay. Going back to a comment earlier, desire, and 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 Palo. 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? Yeah, so if we go back to the framework that I sort of discussed around CDK hormone, multinode PAM, I think we've seen evolution in the CDK4-6 landscape, but we're also seeing CDK-4s come to the fore in first line, potentially. 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, but keep going. 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 it's going to be a good idea and I think I think we're going to have a good time. I think the landscape will 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, Salcutie, 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 CERD and a 4-6 or a 4 in second line or an AI and a 4 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 4 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. Yeah, no, it makes a lot of sense. So in this case, having a little bit of time is your friend, so you're not spending a lot of money for something that's going to be antiquated. Yeah, you don't have to do a phase four afterwards to get up to speed on the latest regimen. Yeah, yeah. Talk to me, so back to the formulation of Pigtor, so obviously it's two drugs, to be able to have this multinode inhibition. And is there a concern in the, you know, 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? 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 mg, 3 mg 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 culmination partners, maybe there's a universe where we can push dose and 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. 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? 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 topo1. 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, those diseases generally where ADCs are becoming quite pervasive. So that's definitely something we're thinking about, and we've already shown sapinocertib 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 ovorian already in a randomized phase two. We'd love to bring the PICTOR regimen to bear rather than just saponocertib alone in ovarian, as I mentioned, potentially in combination with an ADC. And then when we look at lung cancer, saponicertib monotherapy has already shown in NERF to keep one mutated lung cancer 25% ORR, 8.9 months PFS, which is really meaningful in that subset of patients in second line who had dose attacks or reign supreme. So we'll hopefully have an announcement, you know, 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, you knows, 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, Luke 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. That's a good point. 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. That's great. That is a really helpful framing. Maybe in the couple of 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. Yes. The drugs were initially developed by Kayvan Chokat at UCSF, and then Kayvan and Troy Wilson put them into their company, Intellikind. Intellikkind was acquired by Takeda. Takedo never got development of these drugs quite right, a story that we've seen with Gidatlizib, ironically enough, and they then out-licensed them. We acquired Cerebilisib in 21, Fapnasertib in 23, with the idea of putting together multi-node inhibition, something that we worked on with Luke Hanley quite extensively. 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. 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. that would give us exclusivity well into the 2040s 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 final comments 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 FITE is building the next premier oncology company. Amazing. 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. Thank you very much. Thank you.