Good afternoon, everyone, and thank you for joining us on the fourth day of the Needham Healthcare Conference. My name is Gil Blum, and I'm a Senior Biotech Analyst here at Needham & Company. My coverage also spans the field of oncology. It is my pleasure to have with me today Anand Parikh from Faeth. Is that the right way to say it? Faeth Therapeutics? Faeth Therapeutics, yeah. Anand, you have the floor. Thank you, Gil, and thank you, Needham, for the platform. Faeth is a company focused on cancer metabolism and crucial multi-node pathways in cancer. Before I start, I just want to mention that today's presentation will contain forward-looking statements subject to risks and uncertainties detailed in our 10-K and other SEC filings. Faeth recently went public in a reverse merger transaction with Sensei Biotherapeutics. This was structured as a stock-for-stock transaction, and concurrent with the deal, we raised $200 million in a private placement from institutional investors. The Faeth leadership team has been merged with the Sensei leadership team, and we're very excited that the capital that we've raised is primarily dedicated to advancing Faeth's lead program, PIKTOR, which is expected to have phase II topline data in endometrial cancer, and initiate a phase Ib in HR-positive, HER2-negative breast cancer, both expected by year-end 2026. A little bit of an overview on Faeth. Faeth is a company focused on multi-node pathways, complex pathways in cancer, where multi-node inhibition is going to lead to not only hopefully better efficacy, but also less toxicity. We're beginning our work with the PI3K pathway, the most frequently mutated pathway in solid tumors, and we are engaging in vertical blockade with two oral small molecules. That vertical blockade inhibits PI3K alpha, TORC1, and TORC2. Compared to other pathway inhibitors, we believe that not only are we oral compared to intravenous, that we have similar rates of all grade hypoglycemia, we have lower rates of stomatitis with no prophylaxis, and that we have greater exposure above common efficacy thresholds like IC90, staying above those thresholds for longer than the competition, which should translate to greater efficacy. In terms of recent and anticipated readouts, we had a phase II recently read out at ESMO, which met its primary endpoint. That was with one half of the PIKTOR intervention, sapanisertib with paclitaxel. That's a randomized phase II. We also have a phase II with the entire PIKTOR intervention in endometrial cancer. That will read out in the second half of 2026. As I mentioned, the money we raised will also fund, in addition to the phase II in endometrial cancer, a phase Ib trial in HR-positive, HER2-negative advanced breast cancer. That trial will initiate in the first half of this year. We have a pipeline beyond PIKTOR, but PIKTOR is the focus of the company. One thing I would note about the origins of Faeth has really been, from the beginning, focused on multi-node inhibition of crucial cancer pathways. Our team and our scientific co-founders really reflect that with Lewis C. Cantley, in particular, being notable as the discoverer of the PI3K pathway. We're glad to have Lewis and our other esteemed scientific co-founders on our side as we attack this very important problem for patients worldwide. As I mentioned, the PI3K/AKT/mTOR pathway, also colloquially known as the PAM pathway, is the most frequently mutated genomic driver across all solid tumors. The way we are attacking this is with two oral small molecules that target what we believe to be the most crucial nodes in this pathway. Serabelisib, which inhibits PI3K-alpha, and sapanisertib, which inhibits mTORC1 and mTORC2. Together, we call this PIKTOR. One of the major benefits of targeting this pathway at multiple nodes is you're actually able to shut the entire pathway down. We believe that single node inhibitors which target components of this pathway are partial pathway inhibitors. When you actually inhibit this highly correlated and interdependent pathway, you are able to decrease the dose of any individual agent, which sets a firm lower bound to your therapeutic window and allows for much greater tolerability. Another benefit that arises from actually setting that firm lower bound on the therapeutic window is that evolved resistance is far less likely. Evolutionarily-derived mutations, resistance mutations that occur as a result of pressure being placed on an individual point of this pathway, escape mutations, can be avoided by multi-node inhibition. The other benefit of multi-node inhibition is it's a much larger addressable market. Of course, if you're focused on single point mutations in the pathway, then you're limited to that market. We, on the other hand, have shown the ability to target patients with mutations throughout the pathway and actually outside of the pathway as well, as our phase Ib shows. Finally, one of the benefits of Faeth's method of multi-node inhibition is that we are orally administered. While oral administration is, of course, a convenience advantage for patients and physicians alike, it also provides important PK advantages, which I'll detail throughout the course of this presentation. I want to walk through some science here that I think is crucial to understanding the benefits of multi-node inhibition. While targeted therapies focus on shutting down the genomic drivers of cancer, the actual translational readouts at the bottom of these pathways are the key to shutting down the activity of these pathways in cancer cells. For the PI3K/AKT/mTOR pathway, the key translational readouts are phosphorylated S6 and phosphorylated 4E-BP1. As you can see from these western blots, single-node inhibitors do a good job of shutting down phospho-S6, but not such a good job shutting down phospho-4E-BP1. Our agents in combination, however, are able to shut down both S6 and 4E-BP1. As has been demonstrated in the literature, it's 4E-BP1 that correlates far more closely with drug potency. This is true not only of the approved therapeutics in the class, but also the investigational therapeutics, including mutant-specific inhibitors, as detailed on the western blots to the right. We shut down phospho-AKT, phospho-S6, and phospho-4E-BP1 in a far more complete way than any single node inhibitor. As it relates to the multi-node inhibitors, we think we have some crucial and important advantages. The historical development of multi-node and pan PI3K inhibitors has shown that alpha selectivity is important. Pan PI3K inhibitors have traditionally been dogged with less tolerability and also potential immunological toxicities due to the fact that PI3K gamma and PI3K delta are largely expressed in immune cells. In solid tumors, it is PI3K alpha that predominates, and any limited signaling that may occur through beta or other PI3K isoforms is largely inhibited by the fact that we are also shutting down downstream mTORC1 and mTORC2. The initial clinical data for our combination was really demonstrated in this phase Ib study. This was the first time that PIKTOR was put together with another mechanism of action, paclitaxel. In this case, although we also believe and are undertaking trials with other cytotoxic agents, including CDK4/6 and potentially hormone therapy, in this trial, however, paclitaxel was the partner of choice. Within these advanced solid tumors, you can see that the doses tested for sapanisertib and serabelisib were significantly lower than the monotherapy RP2D of these agents. These agents, when given in monotherapy, the RP2Ds were determined to be 900 mg and 9 mg. Our recommended phase II dose was 3 mg of sapanisertib, so threefold lower than the RP2D, and 200 mg of serabelisib, so over fourfold lower of its RP2D. That's an important fact because when we see the activity that we've seen, and which I will further demonstrate, this explains why the tolerability is also so beneficial for patients and physicians. In that phase Ib, we saw a 47% overall response rate with three complete responses, four partial responses, and four patients with stable disease. When we look at those patients who had stable disease on the swimmer plot, we can see that that stable disease was sufficient to qualify also for clinical benefit. These patients had endometrial, ovarian, and breast malignancies, and on average, had four prior lines of therapy. It's notable that all of these patients, except for one, had prior taxane. This was taxane rechallenge. In that setting, taxane rechallenge in advanced solid tumors, we would expect a 10%-20% overall response rate with about four months PFS. This data appears to be outpacing that significantly. I also want to discuss the mutational landscape. When we look at the mutational landscape here, you can see classical PIK3CA mutations in green, PI3K pathway mutations without PI3K PIK3CA mutations in red. mTOR, AKT, PIK3R1, those kinds of mutations, those are in red. Patients without any pathway mutation in black. It's notable to see that we had activity across all three different mutational subtypes. Also, if we look to the VIKTORIA-1 study, which was undertaken by Celcuity, the data that got a positive market response was actually in wild-type patients. That means patients who had an absence of a PIK3CA mutation. In this study, that would be all patients denoted in the red or the black. All those patients would be considered PIK3CA wild-type under the VIKTORIA-1 stratification. Importantly, none of these patients would be eligible for a mutant-specific inhibitor because they have co-occurring mutations in PTEN. Given that fact, we thought the safety profile was very favorable with grade 3 AEs in 58% of patients, which compares favorably with other comparable therapies, and discontinuation in about 5%. Common AEs were GI and low-grade. We did see some neutropenia and anemia, but we think that was potentially due to paclitaxel, given that that's a signal that hasn't really historically been seen with these agents. When we move to the adverse events of special interest, we see among best-in-class hyperglycemia profile. This data is from our ongoing phase II in endometrial cancer, which is given all at that 200 mg, 300 mg dose that was determined in the phase Ib. Here, we see a 14% overall hyperglycemia rate, which compares very favorably to inavolisib, the Relay compounds, or the Scorpion compound, and quite favorably to gedatolisib as well, especially considering that we have among the most lenient HbA1c and fasting glucose criteria in the field today. When we look at stomatitis, we have low-grade stomatitis and low overall rates of stomatitis with no prophylaxis. This is unlike gedatolisib, which has prophylaxis and much higher rates of stomatitis. We have received questions around, "Well, why do you see that, given that it's an on-target mTOR effect?" This is something that has been seen with everolimus, and the reason is oral dosing. Oral dosing is not just a convenience advantage, but it confers some very particular PK benefits. In particular, our dosing regimen of three days per week, every week, with no weeks off, means that we achieve greater exposure above critical efficacy thresholds like IC90, compared to the competition, which are administered intravenously. We see about 150-190 hours per month, and that's above IC90. That's as a result of dosing in above that efficacy threshold three separate times per week, with no weeks off. If we compare that with the competition, we see 60-70 hours per month above that efficacious threshold. Additionally, as it relates to Cmax, because we are oral, we can continually dose into that efficacious range rather than intravenous, where the entire bolus of drug is given at the beginning of the week, and then it falls below that efficacious range. Additionally, with intravenous drugs, you must have a very high Cmax. Because we are able to continuously dose, we don't need such a high Cmax to IC90 differential. In fact, we never reach more than about 2X our IC90. This is crucial because it relates to stomatitis. We have indeed seen in earlier studies of sapanisertib, our TORC1/2 inhibitor, that when given in large single weekly boluses akin to an IV dosing schedule, we see increased stomatitis. It is indeed a class effect, but by breaking the dosing up into this three-day-per-week regimen, we see far lower rates of stomatitis. Moving on to clinical development. Endometrial cancer is where we've begun our development, and given the data from the endometrial patients in the phase Ib study that I outlined, we think that was a logical place to start. Three of those patients had complete responses. Four of those patients had responses with a median PFS of 11 months. Several of these patients had previously received IO as well. Given that paclitaxel or doxorubicin is the prevailing second-line therapy in endometrial cancer with PFS of about 4 months and a response rate of between 10% and 20%, we think that if we're able to carry on this level of efficacy, it would have a significant place in the armamentarium of our physicians. I will note that endometrial cancer is a disease and one of the few cancers that is growing in both incidence and prevalence with very few approved therapies. In terms of our phase II trial design, we have the single dose established in the phase Ib combined with paclitaxel, again, as established in the phase Ib. It'll be 40 patients, a single arm study, and we hope to read that out, at least response rate and some preliminary safety data, by the end of this year. It will be an endometrial/endometrioid cancer. All patients will be post-carboplatin, post-IO. Moving on to breast cancer. We, of course, monitored the Celcuity data with some attention, and we're very pleased to see that succeed for both patients and the field as we think it provides a really good validation of the multi-node hypothesis. We believe that our advantages due to oral administration and PI3K-alpha specificity, as well as increased tolerability, offer some unique advantages over the Celcuity regimen. Indeed, our agents have been developed in breast cancer previously. Sapanisertib plus fulvestrant was randomized against fulvestrant alone in HR-positive, HER2-negative breast cancer patients and showed an intriguing PFS and DCR rate when compared to the VIKTORIA-1 study. This was in all comers, similar to the VIKTORIA-1 study. Serabelisib itself, the other half of the PIKTOR regimen, has shown encouraging efficacy as monotherapy in breast cancer as well. We, of course, believe that putting the two agents together would be superior than either one alone. As we look at the landscape of breast cancer, we believe that not only has CDK4/6 or CDK generally and hormone therapy been established as the backbone of breast cancer, but with the VIKTORIA-1 data, that increasingly PI3K kinase agents, multi-node agents specifically, are creating a third pillar of breast cancer. As we see that come to bear, not only in second-line, but looking forward also potentially in first-line, that it will be important for patients to have an all-oral regimen that has really good tolerability. That's what we hope to bring to first and second-line settings. We will also be examining future standards of care as the treatment options in breast cancer continue to evolve beyond CDK4/6 and aromatase inhibitors plus oral fulvestrant. We will be doing work with some of the novel mechanisms of action in this space to determine tolerability and safety in the first instance, and then efficacy as well. As we move on to other indications, ovarian cancer, we had a positive readout in a randomized phase II in platinum-resistant ovarian cancer. This was in patients who had greater than one line, on average about four lines. This randomized phase II, which had 124 patients across about 25 sites, the control arm was paclitaxel. The experimental arm was paclitaxel plus sapanisertib, which is our TORC1/2 inhibitor. It did read out positively in terms of PFS with a low hazard ratio. Grade 3/4 AEs across both arms were similar, and the intervention was well-tolerated. In terms of next steps, we await OS, ORR, and detailed safety data, and we look forward to an FDA interaction on this program in the future. As you can see from the Kaplan-Meier curves here, the PFS separates and does not come back together for the two regimens. We think this is encouraging and look forward in future development of this to add serabelisib to this intervention as well. In terms of our regulatory positioning, we have inherited a large safety database from Takeda, which we're very pleased with, and we've also seen a lot of prior dosing work with these agents. That sets us in good stead for future development, and we will need to round out some contribution of components. That contribution of components has been done with sapanisertib and paclitaxel and sapanisertib and fulvestrant, but we will likely need to round it out with serabelisib and fulvestrant and serabelisib and paclitaxel. It is our belief that those studies will be qualitative. They will not require statistical significance, and we will provide further updates after greater engagement with the FDA. In terms of CMC, we are well-positioned with ample drug supply and drug product for ongoing and proposed phase Ib and phase II studies, including extensions thereof. We have a healthy patent life stretching into the late 2030s and potentially into the 2040s, with also the ability for a fixed-dose combination for our two oral small molecule agents. We are very excited about the catalyst calendar we have coming up. We have the Celcuity mutant data in the first half of 2026. We have our own endometrial data in the back half of 2026. We will have the breast cancer data, safety initially, in the first half of 2027, and then interim efficacy data in the back half of 2027. That will be 20-40 patients on CDK4/6 plus or, and/or fulvestrant as well. We're very excited by that. We think that's the data set that is really going to allow us to benchmark our data to the other agents in the class as well. With that, I'll thank you very much for your time, and Gil, looking forward to the conversation. Thank you, Anand. The floor is open for questions from the audience, but maybe I'll start with a couple. For full disclosure, I do cover Celcuity, so I'm pretty familiar with the space. Maybe one point to start, this is regarding oral dosing and PK. Now, I know this is apples to oranges, so bear that in mind. If you remember, Celcuity had differences in activity between two different dosing regimens. One which involved very continuous dosing, and another one that was three on, one off. With an oral dosing, I'm assuming that's more close to the continuous version. Again, apples to oranges, but I'd wonder what your thoughts are as it relates to that piece of information. Yeah. With the 3 on, 1 off, it still is very similar to an on/off regimen because we have those 3 days when we're in range and then 4 days where we aren't. It is similar to a pulsatile dosing that's been seen with gedatolisib or even with Capivasertib, which was 4 on, 3 off as well. We do see it as similar. We're just spending longer above IC90 and other critical thresholds. We do believe that continuous dosing in this pathway can be a challenge, but we have a very similar pulsatile approach. Right. My other question is, you see quite a lot of investment in, quote-unquote, "next-gen selective PI3KAs," Relay comes to mind. What prevents them from taking everolimus and adding it to their regimen? It's a great question and one that I get a lot, and I think is fundamentally quite misunderstood. Everolimus is a rapalog and derived from a natural molecule. It actually doesn't interfere with the TORC1 complex directly, but binds to a protein, FKBP12, that interferes with the TORC1 complex, not TORC2. Sapanisertib, our TORC1/2 inhibitor, is a next-gen molecule that is ATP-competitive and inhibits both TORC1 and TORC2. If you remember my slides earlier, I showed that everolimus does not actually shut down one of the critical pathway readouts for 4E-BP1. It only shuts down S6. Pairing a next-gen molecule with everolimus would not give you full pathway shutdown. You would get reactivation through TORC2 and then AKT. We think that there is no product on the market that has our unique target profile, and nor can you piece together the target profile through other approved agents or investigational agents that we're aware of. Maybe a different way of asking this question, why do you think pharma and others are investing so much in having the most selective PIK3CA? Because we know it's a safety story. Everyone understands that, but at what point does that stop being differentiated? Yeah. I think when you look at the mutant specifics, the initial raison d'être was that we're going to be safer on hyperglycemia. That's why they were developed. I just showed you hyperglycemia data that is in the most inclusive patient population, i.e., higher HbA1c cutoffs, higher fasting blood glucose with much lower hyperglycemia. A quarter of Relay, a third of Scorpion, approximately, there or thereabout. I'm not really sure what you're buying. Of course, you can drive hyperglycemia very, very low with some of these next-gen agents potentially. I already think that we are at a lower bound in terms of hyperglycemia. What we hear from physicians is that what they're looking for is greater efficacy and greater survival with convenience in dosing regimen, not really continually pushing hyperglycemia to zero. We're already at 14% with an HbA1c of 8. If you drive that to zero, I'm not sure how much additional benefit or uptake you're going to get from the physicians. I think if we had a trial with hemoglobin A1c criteria of 6.4, like the others, we would similarly see decreases in hyperglycemia, where that would be TBD, but I would guess sub 14%. Yeah. Just to put that in context, because it's important, right? You have quite a few of these patients are diabetic. How much leeway does this give you as it relates to dosing of patients? Yeah. In our endometrial trial, many of these patients are medication-dependent diabetics. We are still seeing that these patients are able to tolerate the full dose. One of the things that I think is important, and one of the reasons why I think only hitting PI3K-alpha is a mistake, is that hyperglycemia is largely driven through PI3K-alpha. What we are able to do is to spread the hit across PI3K-alpha, TORC1, and TORC2. We're not leaning so heavily on PI3K-alpha. As the mutant-specifics in others, they must lean on that single node. Not only do you have a smaller market, but that's why you're seeing the elevated hyperglycemia that even the mutant-specifics are showing as compared to the multi-node inhibitors. I do have one question from the audience. How do you think that the endometrial data could potentially de-risk safety and tolerability as it relates to breast? Yeah, I think it's a great question. The way I would say it is PI3K inhibitors and the pathway inhibitors have only been approved in breast. Many of them have tried but failed in endometrial. In many ways, we believe that endometrial might be the tougher disease. If we are able to show a data set that looks promising in endometrial, we think that the read-through to breast is significant, particularly on the efficacy side and even on the tolerability side. Again, many of these patients are medication-dependent diabetics. 90% have metabolic syndrome. That is not a phenotype that is as common in breast. If you are efficacious and tolerable in endometrial, I believe that you will be efficacious and tolerable potentially to a greater degree even in breast. That's very helpful. Again, we think that gedatolisib is a great advancement for the space, especially in wild-type. Really, we haven't seen much work. I do want maybe a little of your perspective as it relates to oral versus IV in frontline, just given the fact that we're seeing more and more of these oral agents, right? Coming on. It's one of the reasons why we really feel like we want to get this to patients quickly, is that if you consider that we've seen all of this amazing patient benefit derived in the last few months in breast cancer, be it oral SERDs, be it the VIKTORIA-1 study. The bar is increasing in breast cancer. I think that's a great thing for patients. As that happens, the bar is going to increase not only in second line, but in first line as well. For patients to be tied to an IV, I think is increasingly challenging, particularly as we see greater emphasis on oral regimens in first line. We really want to get this out there so that the young working women who comprise the vast majority of the breast cancer population have the ability to go about their lives, without being tied to an infusion chair. Great. I think this is all we got as it relates to Q&A today. As always, I appreciate your time, Anand. Well, thank you very much, Gil. It's fun chatting and I look forward to talking more in the future.