Okay. Good morning. Thank you everyone for joining here for the third day of the Morgan Stanley Healthcare Conference. My name's Jason Russell. I'm managing director with the team. It is a pleasure to be joined by CEO Anand Parikh, CEO of Faeth Therapeutics. First time joining the conference, first time being Faeth, I think, at this time of the year, so it's exciting. You've got a big 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 Faeth and what you're trying to do. Yeah. Faeth'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, Lew Cantley. We have two drugs, sapanisertib and serabelisib, which inhibit PI3K alpha and mTORC1 and mTORC2. Those drugs have shown a 47% overall response rate in a phase Ib. We're excited about some data that's coming up here at the end of the year in endometrial cancer. 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. 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 end of this year, and then a phase Ib/phase II in breast cancer at the end 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? Maybe underlying my question is what's the value of being across all the nodes versus a 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. When you do that, you don't have a solid lower bound to your therapeutic window. It means that the only way you can drive any efficacy is by continually dosing up. When you do that, you see challenges in terms of toxicity. That's really what's bedeviled the PAM pathway for a long time, is the toxicity associated with single node inhibitors. 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. I think we've borne that out, and some of our competitors have borne that 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. This is quite simply just finding a way to prevent the tumor from having a workaround, being across all nodes. 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. Yeah. BRAF-MEK. This is a story that's been told many times in cancer. 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. Let's get deeper. On the dosing strategy, the PK strategy, it is somewhat unique. You talk about maximizing your time above the IC90, avoiding the peaks, rather than in most oncology development we are always just trying to take it to the MTD. There is the intermittent dosing concept as well. Walk us through that and again, what you hope to see out of that. Yeah. Maybe I will 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. What we have seen with gedatolisib and capivasertib to an extent, is that you can have intermittent dosing. Gedatolisib is dosed once weekly and falls below IC90 relatively quickly. Capivasertib is dosed four days on, three days off. We dose three days on, four days off. It has been proven time and time again in breast cancer that this pulsatile dosing can work for this pathway. We are 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. Since we are not intravenous, unlike gedatolisib, it has a very high Cmax, actually about 50x IC90. We are never more than 2x- 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 three. We, on the other hand, have very low-grade stomatitis, some 20%, with no grade three at this point. That is one of those things that I think is a very meaningful differentiator for patients. The other nice thing about our PK profile is we have much greater coverage above those critical thresholds like IC90. I always say internally, cut the peaks but not the coverage. We have 2x- 3x greater duration above IC90, which typically, as you know in oncology, translates to greater efficacy. Right. Okay. I do have to compliment you, by the way, whoever came up with the decision to name it PIKTOR, it is impossible to forget. Kudos to you for that. The oral, just to pull the thread just a little bit more, how important is that? We are going to get to 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, how important do you see that attribute? Yeah, particularly in breast cancer, we think oral is crucial. 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 for a number of years. You had a recurrence several years after you finished adjuvant therapy, usually. 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. We think that's important for these breast cancer patients. 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 willing to sit in an infusion chair. 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 CDK4/6 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 see 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 PIKTOR is clinically meaningful in a very difficult cancer? Yeah, 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 III would be. That is going to be paclitaxel re-challenge, which gets you 10%-15% ORR with three to four months PFS. If we are 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 III. In terms of a comparator, which is done so recently, sac-TMT in an all-China phase II showed with a 30% ORR and about 5.6 months PFS in only 1/3 of those patients that had prior IO, and they won in a phase III. They have announced that. At the first interim OS look, they won. Again, if we are showing something in that neighborhood, I think you are going to have high confidence that in a phase III, we are going to be successful. I think that is one thing. The second thing I think is going to be very important is tolerability. Endometrial provides significant read-through to breast cancer in terms of both efficacy and tolerability. Endometrial cancer, 90% of the patients are obese, pre-diabetic, or diabetic. We have an HbA1c inclusion requirement or permission that is up to 8%. That is higher than any of the other PI3K agents thus far, and we are doing it in the sickest population. If we show really good tolerability along the dimensions of hypoglycemia and stomatitis, again, with no prophylaxis, then I think you are going to have real confidence when it comes to breast cancer that that tolerability profile is going to hold. Okay. 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 III? And two, what can I learn from the tolerability profile that is 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 endometrial cancer, as you mentioned, is a really tough disease. Average mortality at the five-year point is about 85% death. It is only 50% in breast [three]. Both statistics are horrible, but clearly endometrial is higher rate of mortality. You also have the sicker, more insulin-resistant patients, and our combination partner is paclitaxel. I think what you can see from the tolerability and efficacy perspective in endometrial, you should be able to improve upon that in breast. Great. We do not, from the phase Ib data set, need to replicate what were pretty fascinating results. I think you had four responses in five patients in endometrial and three CRs. If we see that in the phase II, then we are off to the races. That would be- Look, I would love to see that, but I think it's an apples to oranges-- Sure --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 II will have received IO. One of the patients was taxane- naive. In the phase Ib, 100% of the patients will have received taxane Carbo-Taxol in the phase III. We're taking a little bit later line, a little bit more homogenous patients in that phase III. But I think as we look to earlier lines, I would hope to see that type of response rate in patient population potentially in an earlier line. Okay. Great. Maybe just to wrap up in an endometrial and then I want to get to breast. You recently gotten a Fast Track designation. These data are coming. Talk to us about what the next step would be post these data in endo, thoughts around what a pivotal strategy might look like to the extent you're willing to share. Yeah. After this data, we've been in discussions with the FDA, and we'll have an interaction at some point this year. Then we hope to announce our registrational strategy from there, and that would be a randomized phase III, and likely, putting PIKTOR plus paclitaxel up against paclitaxel. We also hope within the context of that study to answer a contribution of components, potentially serabelisib plus paclitaxel in a third arm. It would be randomized and have an inbuilt futility analysis, we believe and then could drop out. It wouldn't be a long, arduous endeavor, but a small number of patients in a futility analysis. So- Now, we have to align on that strategy with the FDA, but in prior discussions, they've been receptive. Okay. Yeah, I think that's an important point of clarification is people, contribution of components and this being two drugs, so thanks for that. Okay. Maybe to switch gears to what is a huge commercial opportunity, but let's bridge it. So endometrial data, assume that study's successful, defined across the parameters discussed. How does that de-risk breast, which is on the come and, what risks are still out there independent of the endo outcome? Yeah. It's a good question. 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, or in terms of safety. And then when we look to the combination partner, again, we're pairing with paclitaxel in endometrial cancer. In breast, our likely combination partner is CDK4/6 and fulvestrant or oral SERDs. Targeted therapies generally are much more tolerable than chemo, right? So again, we expect hopefully better efficacy and also better tolerability in breast than we'll show in endometrial just because of the disease and the likely combination partners. Yeah. Makes sense. Okay. Development for breast. I think you're on the record that you've now enrolled the PIKTOR plus fulvestrant dose escalation cohorts. You're working through the triplet with palbociclib. Public guidance is interim efficacy data, I believe, in the second half of 2027. What does that mean, and what do you hope that package will tell you? Yeah. We said year-end 2027. Okay. Year-end 2027. 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 fulvestrant, and that people can underwrite a phase III, and that we'll have the necessary data set to be able to take to the agency and then begin phase III work. I think there's also important de-risking. 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. They want to make sure they see that same tolerability profile that we can combine with CDK4/6 and fulvestrant or oral SERDs, which are the backbones of breast cancer. When I think about breast cancer, I think about three buckets. You have CDK, you have hormone therapy, be it fulvestrant or oral SERD, and now you have multi-node PAM. Those are the only three things with labels all the way across breast. We need to make sure that we can combine with the other players in breast cancer, those other two buckets that I mentioned. Okay. From a competitive backdrop perspective, you mentioned it in your opening remarks, but Celcuity's REVTORPYK just got approved. 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. I think ultimately it is an incredible validation of the multi-node 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 hypoglycemia, 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. It also gives us the undeniable frontline opportunity, which is the bigger market. 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 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 REVTORPYK. The space is trying to move to an all-oral regimen. Obviously, if you are a patient, that would certainly be preferred. You are running cohorts with fulvestrant and palbociclib. How do you see that regimen, that landscape evolving? Is that more phase III work that you will have to do as those become more established to just help walk us through the journey there? Yeah. If we go back to the framework that I sort of discussed around CDK hormone multi-node PAM, I think we have seen evolution in the CDK4/6 landscape, but we are also seeing CDK4s come to the fore in first line potentially. Does tha- sorry to interrupt you. Okay. Maybe as part of your comments, does that interject a potential risk? Because that landscape is changing quickly, and so, yeah. Keep going. Yeah, I think, look, for first line, at the time we're probably thinking about a first-line study, I think that landscape will be more settled. Yeah. 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 is 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, Celcuity, because of the timing of their trials, they were pairing with fulvestrant. 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 SERD 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. That's the world we want to bring to the fore 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, makes a lot of sense. 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 IV afterwards to get up to speed on the latest regimen. Yeah. Talk to me, back to the formulation of PIKTOR. Obviously, it's two drugs to be able to have this multi-node inhibition. Is there a concern or is it an opportunity, the fact that you can individually titrate these two doses? 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, 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. 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, beyond endometrial and breast, the PAM pathway is obviously relevant across a whole host of solid tumors. We've got to get ourselves through the gates of these next kind of key catalysts. 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 TOPO1 payloads, and you cannot re-challenge TOPO1 off of TOPO1. 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. That's definitely something we're thinking about, and we've already shown sapanisertib plus paclitaxel showed a really nice hazard ratio as a late-breaking oral presentation at ESMO, low hazard ratio in terms of PFS. We've shown activity in ovarian already in a randomized phase II. We'd love to bring the PIKTOR regimen to bear rather than just sapanisertib alone in ovarian, as I mentioned, potentially in combination with an ADC. When we look at lung cancer, sapanisertib monotherapy has already shown in NRF2/KEAP1 mutated lung cancer 25% ORR, 8.9 months PFS, which is really meaningful in that subset of patients in second line where docetaxel reigns supreme. We'll hopefully have an announcement upcoming here about a Lung-MAP study that's going to be PIKTOR plus paclitaxel in that cohort of lung cancer. Look out for that. I think there's a lot of opportunities for PIKTOR. Really, as we said, it's the most frequently mutated pathway in all of solid tumors. Yeah. We want to bring this to patients in need across a variety of different tumors. I have a conversation with my co-founder, Lew 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. We want to bring that promise to bear. We think PIKTOR is the right vehicle, the right package in terms of it's oral, it's combinable, it's tolerable. How do we now-- 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's 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. Yeah. So the drugs were initially developed by Kevan Shokat at UCSF, and then Kevan and Troy Wilson put them into their company, Intellikine. Intellikine was acquired by Takeda. Takeda never got development of these drugs quite right. Story that we've seen with gedatolisib ironically enough. They then out-licensed them. We acquired serabelisib in 2021, sapanisertib in 2023 with the idea of putting together multi-node inhibition, something that we worked on with Lew Cantley quite extensively. We have IP out till 2037 for composition of matter, and then method patents beyond that reach well into the 2040s, which we believe are quite strong. We have two oral small molecules, and so combining them into a fixed dose provides the opportunity for further IP extension. 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. Yeah. Okay. 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? Clearly, you'll be on the doorsteps of something big as well. Yeah, final comments. Yeah. If I am 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. That is what I am excited about. That is what we are really focused on at Faeth, 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 will wrap it there. Thank you very much. Thank you.