Good afternoon, everyone. Welcome to the first day of the Jefferies Healthcare Conference. In this session, we have Aadi Bioscience with us, and CEO Dave Lennon. Welcome. Thanks, Ming. And thank you to Jefferies for hosting the conference. So, Dave, could you start with a brief elevator speech, maybe updated version, to give us a picture about Aadi Bioscience? For sure. So Aadi Bioscience is a commercial stage biotech company focused on the development of a technology that allows us to more potently inhibit mTORs in the treatment of cancer. We currently have an approved product, which is FYARRO or nab-sirolimus, for a rare soft tissue sarcoma called PEComa, that affects about 100-300 patients in the U.S. every year. We currently sell about $25 million a year in that product. We then have a number of additional indications we're developing that product for, including TSC1 and TSC2 mutated cancers, as well as endometrial cancer, and potentially for a treatment in neuroendocrine tumors. We are a single-asset company, and today we are looking forward to our next interim readout of that TSC1 and TSC2 trial, which will come in Q3 of this year, and really an important catalyst for us as a company. Got it. Thank you. So, you know, apparently, Aadi has a approved product, FYARRO, since last year being on the market. So could you give us a brief, you know, description about the sales trajectory and, you know, how it has been recently been seen in the market? Sure. So Aadi, as we mentioned, Aadi got approval for FYARRO in soft tissue sarcoma called PEComa, which is an ultra-rare soft tissue sarcoma. We have great adoption of FYARRO in that indication among sarcoma centers across the U.S., which we cover today. Product has seen rapid adoption in the first-line setting for PEComa, with about 70% first-line share amongst sarcoma treaters for that indication, and ramped up really quickly into going into the first half of last year. We've seen sales stabilize around $6 million or a little more a quarter, and we continue to project that that is the appropriate run rate with some opportunity for incremental growth in that product. But we're very highly penetrated, it's really high adopted, and the product is well-liked in the marketplace. Yeah. So that's very impressive that with, you know, around $25 million a year in such a, like, a small, rare indication. So, and you mentioned—as you mentioned, the sales has been stabilizing recently. I guess, you know, we note that in Q1, the sales has been down a little bit, so maybe provide us some additional colors on that. Sure. I think when you look at, you know, our sales, quarter to quarter, there may be some fluctuations that we see as this is an ultra-rare indication, and every patient matters when we think about each quarterly sales. And so fluctuations around the $6 million mark, we don't get too concerned about. In particular, in Q1, we did see a decline in some of our top centers. We did actually see that this correlated with some of the places where we were rapidly enrolling our TSC1 and TSC2 trial. So some of the largest centers in the country are also our main clinical trial sites, and we do believe there might have been some cannibalization that was occurring over the first quarter. It's important to note that trial is now closed, and we anticipate a return to growth, for the product, in Q2 of this year. Yeah, totally. So, Q1 typically is slower for pharma, and we've seen some fluctuations, maybe some impact from the ongoing precision trial. But as you mentioned, the trial has been closed for enrollment, so we probably expect more stabilized sales trajectory. Yeah, we're looking forward to a much improved Q2, for sure. Yeah. So I guess, you know, currently, the key is your PRECISION1, TSC1 and TSC2 tumor-agnostic trial. So maybe let's get on to that. But before we get into the clinical details, maybe, you know, give us a brief introduction for TSC1 and TSC2 as a tumor-agnostic target. Sure. So TSC1 and TSC2 mutated cancers are a particular genetic mutation that accumulates in either one of these genes. TSC1 and TSC2 are part of a heterodimer complex in the cell that forms a tumor-suppressive function on the mTOR pathway, and when it's mutated or lost, we actually see activation of mTOR, and therefore, we want to use our mTOR inhibitor to combat the cell growth signals that are being generated through that pathway. The TSC1 and TSC2 mutated cancers are found across a wide range of different cancer types. We've enrolled over 20 different cancer types in the trial, as an example. But occurs at about a 2% rate across all cancers, and we anticipate that that means there are about 16,000 new cases of TSC1 or TSC2 mutated cancers in the U.S. each year. When you compare that to the 100-300 in PEComa, it's really a considerable, sizable market step-up for us, potentially, if we were to secure this indication. Yep, 2% of the tumors across the tumors, so definitely a very sizable market. Mm-hmm. So maybe, you know, TSC1 and TSC2. So how should we think about them? Should we think about them as a more together... or like more separate- Yeah -targets? So, in general, they act as a heterodimeric pair. We see pretty even distribution and mutation rates across different tumor types. They're rarely mutated together, so usually loss of one is sufficient to, you know, induce tumorigenic potential within a cancer. And, and so we, we tend to think about them acting together, but the mutations as separate, and they roughly split evenly, 50/50, between the two mutation types across these cancers, about 1% in each mutation type. Yep. So I guess that, you know, gives you the rationale to do a tumor-agnostic trial for TSC1 and TSC2. So, you know, talking about tumor-agnostic, what's our current understanding for FDA, on FDA side, so for the regulation passed for tumor-agnostic? Yeah. So tumor-agnostic studies came up with precision medicine as people started to classify tumors by their genetic mutation as opposed to by indication. Initially, a lot of tumor-agnostic labels were given based on companies conducting multiple cohort studies and then assembling that data into a submission package for the FDA. Since that time, the FDA has come forward with guidance on a tumor-agnostic, true tumor-agnostic study, which is the design of the PRECISION-1 trial, which is our TSC1 and TSC2 mutated cancer trial. In this case, the design of the trial allows us to look at each mutation independently, over 120 patients, with 60 patients roughly in each of the mutations. The trial design is really, truly tumor agnostic, so we take all comers into the trial from any of the accompanying histologies. The one caveat to all of that is that the patients in those trials who enroll in the trial must have gone through all standard of care for the particular indication in which they enroll, which means that we're essentially enrolling last-line patients into our trial, so a very tough patient group to treat with very minimal expectations for potential efficacy that you might see from these patients and in any traditional therapy. This gives us the bar we're trying to come over, which is to demonstrate that we can have effect in these very difficult-to-treat patients. Yep. So based on your interaction with FDA, you designed as a PRECISION1 trial, TSC1/2. So, n equals 120 patients- Mm-hmm ... across different tumor types, and then, basically, those patients went through everything that they could. Right. So very heavily pre-treated patients. Heavily pre-treated patients. Yeah. Yep. Yeah. So could you comment on the current status of the TSC PRECISION1 study? Yeah. As I mentioned, we finished enrollment in the study in April of this year. We have now 120 patients enrolled in the study who are continuing to mature on study. We anticipate an interim readout on the 80 patients that were completed earlier in Q3 of this year, and finalization of the study for all patients by the end of the year, with full data on the primary endpoint in Q1 of next year. Yeah. So, you know, we, I guess, you know, as tumor-agnostic trial, we're probably most interested in what kind of tumors you have enrolled in the study. Mm-hmm. I know you provided your first interim, you know, early this year. Mm-hmm. What have you seen since then for your enrollment regarding the tumor types? Yeah. So, as I mentioned, we've enrolled over 20 different tumor types into the trial in each arm. The tumor distribution is very indicative of what you might expect for TSC1 and TSC2 mutated cancers, meaning that we've seen thoracic-based tumors, GI-based tumors, GU-based tumors, and gynecological-based tumors that are all indicative of the types of patterns we see in large analysis we've done around TSC1 and TSC2 mutations. So we do think we have a representative population of tumor types within the trial. And, you know, they have enrolled in kind of that last line setting. You know, just curious, do you have any, you know, inclusion, exclusion criteria for the tumor types you, like, that you enrolled? Just sarcoma. So patients cannot have sarcoma enroll in the trial. Got it. Got it. So, do you see any enrichment in certain tumor types? At this point, I wouldn't comment on enrichment or non-enrichment. I think what we would say is we did have a cap on the maximum number of patients we can recruit in any one tumor type, and we did not reach the cap for any. So we haven't over-enrolled any particular tumor type. We actually have a pretty even distribution across different tumor types. Yep. So you probably won't be able to give us a cap number, but you know, you said that you enrolled about 20 different tumor types. Yeah. The total number is 120. Yeah. So- You can get an idea. Yep. Yeah. The average, for sure. Yep. So, you know, we mentioned that early this year. So the study design is that you have two interim. Mm-hmm. First interim was already reported early this year. Yeah. Could you quickly remind us, what, what did you see in your first interim analysis? Yeah. So, we looked at both arms of the interim analysis. In the first instance, TSC1, we saw five of 19 responses for an overall response rate of about 26%, and then we saw two of 18 responses in the other arm for about 11% response rate. Both of those were in heavily pretreated populations, so the populations we saw were across a number of different tumor types, but in particular, had at least three lines of prior therapy at median. And in the case of TSC2, we actually had 50% of the population in 5th line or greater or exposed to five prior lines of therapy or greater, just indicating how heavily pretreated- Yep ... this population was. The 25%-26% response rate we saw in TSC1 is, you know, we, we think really a clinically meaningful and important demonstration of response that patients could potentially get here. Given that these are last-line patients and one in four are generating a response, clinicians and experts have given us the feedback that these are really important-... responses for these types of patients. And we've seen a good degree of durability, although the data is immature, in terms of duration of response in many patients experiencing six more months of response. Yep, definitely. So for TSC1 patients, very impressive, 26% ORR. You know, small number and 18 patients, but this is the first interim, so we're gonna expect more data. So for TSC2, you know, I know you mentioned, commented that those patients tend to be more heavily pretreated. So any other reason at this point that you can, you know, you think you would hypothesize as why the OR is lower? Yeah. So I mean, I think two things I would point out. I think one is we saw some patients, who were really very late-line patients, so half of the patients had five prior lines of therapy or, or greater at the time of the analysis. And that, just may be skewing some of the initial overall response rate we saw in this first third of the patients that we recruited, into the trial. We would anticipate if we get a different mix, that might improve, over the course of the trial. The second thing I would point out is that we did have a couple, stable disease patients who actually, were on therapy nine and 12 months post, treatment, so very durable responses overall. They didn't reach the threshold for a partial response, but really important clinical benefit that those patients were receiving. And given the mix of trial, of tumors that we enroll in the trial, we may have some mix of patients who have more indolent type disease, where less might be less expectation for response rate, but still important clinical benefits are being derived from some of those patients who are having very long, stable disease. Yep, and as you mentioned, now you closed the enrollment for the whole study- Mm-hmm. And you probably have seen very consistent patient populations that enrolled into the study? Yeah, I think the patient populations we've enrolled in the study are very similar to what we saw in the first part. There's a different mix, for sure, but nothing that we think we would call out as being materially different- Mm-hmm ... at this point in time. The other thing I would say about enrollment is we did... You know, we published the results in December of the interim analysis, and in fact, some of our largest recruiting months were immediately following in January and February of this year, where we saw a continued acceleration of recruitment and were able to close the trial in April. And so we do think there's excitement amongst the investigator community about the results we did share, and continued interest in this molecule for treatment of TSC1 and TSC2 disease. Yep. So and then, for the second interim, obviously, you're going to report two-thirds of the total enrollment. Mm-hmm. So that's 80 patients. Mm-hmm. And, you know, with that consistent patient population enrolled into your study, so what would be some of your, you know, expectation on the data, compared to the first interim? So we know that, you know, the study, well, those patients will be followed for at least six months- Right ... follow-up. So. Yeah, so it's important to point out that our two-thirds interim is a slightly different endpoint than our initial interim. So our initial interim was investigator-assessed response. In the two-thirds interim or second interim we're doing, we will have independently reviewed radiological response, essentially reviewed. And we only had four and a half months of minimum follow-up in the first interim. We have six months of minimum follow-up in this interim. It's really actually an early interim assessment of the primary endpoint. Mm-hmm. I think from an expectation perspective, our expectation is that the data will show hopefully similar things that we saw within the initial interim data, with hopefully improvement in that TSC2 arm as the patient population gets bigger, that we've looked at in that overall. And as we, you know, are encouraged by what we've seen so far in terms of- Mm ... enrollment into the trial. I think importantly, that data set being the primary and with a significant number of patients, also allows us to think about discussions with the FDA more formally, to have a discussion on what the paths of submission might be. So our, you know, immediate, action coming out of that is to, you know, start to talk to the FDA about that data that we do see and, and how we might approach, that for submission for approval. Yep, and the second interim should be 3Q this year. Second interim is in 3Q this year. Yep. I can say that. Yep. Thank you for reminding me. Glad to confirm that. Yep. So, And we're all, we're on track for all of that. We anticipated- Yep ... to be delivered well. You know, very importantly, this is a little bit different with longer follow-up, with a, you know, very consistent population. And then you have a central review versus independent review. That's right. Yep. So, you know, I think one of the important thing that people, you know, investor being, care about this asset, for TSC1 and TSC2, so those as tumor-agnostic targets, you could, you know, independently file down the way, right? Mm-hmm. That's very good to know. It's a good note, Ming, and I think important that people understand we've separated these into two arms. Even though there wasn't necessarily a biological rationale to think they might be different, it was important to the FDA, who guided us to that separation, that we understand each of these mutations independently. We do think there are opportunities, obviously, to submit them independently, but there's also opportunities to talk about them together, especially when we talk about effects across indication types or other things. And so ultimately, you know, we do think this will be an evolving discussion with the FDA- Mm ... once we really have the data in hand- Mm-hmm ... about, you know, this approach around two tumor-agnostic study. It's one of the first true tumor-agnostic studies for a targeted therapy, that's really ever been run. Yep. And then the whole study enrollment was finished, you know, correct me if I'm wrong, so in April? In April, yeah. Yep, and then with probably six months follow-up, and then we are expecting the final readout later this year, or? Yeah, we anticipate being able to have the final patients have gone through their last visit in Q4, and we would plan on releasing data in Q1 of next year. Got it. Got it. Okay, so I think that's about TSC1 and TSC2 precision, you know- Mm-hmm ... agnostic study. So, maybe move on to the other indications that you're- Yeah ... exploring right now. So I know you have endometrial EEC- Mm-hmm ... and you have NETs. So maybe, you know, remind us what's rationale there- Sure ... pursuing these indications? Yeah, so there's a lot of experience with mTOR inhibitors in both of these indications, right? So many oral mTOR inhibitors are approved for the treatment of neuroendocrine tumors, and I'll start with those. There's about 3,000-3,500 neuroendocrine tumors eligible for mTOR therapy. Typically, mTORs have had very low response rates within neuroendocrine tumors, and those approvals were actually achieved based on PFS or progression-free survival improvements that those patients saw. What we're really looking to do in our phase 2 trial is try to demonstrate that our nab-sirolimus is a more potent mTOR inhibitor. Mm-hmm ... and can improve upon the response rates that have typically been seen within neuroendocrine tumors by oral mTORs. And that's, you know, what we hope to see in the first, you know, 10 patients and ultimately full enrollment of approximately 25-30 patients that we plan in that phase 2 trial. So really there we'll be looking for improved overall response rates, which typically are in the high single digit, low double-digit rates for oral mTORs, and we believe through our IV-delivered nab-sirolimus mTOR inhibitor, we can achieve better response rates. Yep, so kind of like, you know, two sizable targetable population, but also, you know, kind of validated with other mTOR inhibitors. Yeah, and endometrial is similar. There was never an approval for an oral mTOR in endometrial cancer, but there is existing data that they can be effective, especially in combination with estrogen receptor blocker, or path- Mm-hmm ... cascade blockers. And so we're doing that combination, that program in combination with the blockade of the estrogen receptor pathway. And that allows us to look at potential combination strategy for those patients, where there's currently no approved therapy for an oral mTOR. Importantly, in those patients, we're really or that patient population, we've really seen the evolution now of combination IO therapy plus chemotherapy moving into the first-line setting. We really think there's an opportunity in the second-line setting to give a non-chemo-based regimen, and endocrine-based regimen... that would allow patients who fail on that first-line, currently preferred first-line regimen. And really, that's a sizable opportunity. There's about 12,000 new endometrioid endometrial cancers- Mm-hmm ... which is what we're studying every year, and about 7,000 of those patients go to second-line treatment. Sure. So, 2, that's 2 phase 2 studies, right? Mm-hmm. Maybe remind us, where are you for those studies? Yeah. Those studies are both open and currently enrolling. We anticipate providing an update on part one. These are Simon two-stage studies. We have planned to give an update on part one for each of those trials by the end of this year. Got it. So, part one, I guess you mentioned before, that's about 10 patient each study? About 10 patients in each. Yeah, and the total study is about 100 patients. About 30 patients in each. Oh, 30 patients. Yeah. Got it. I guess, you know, we went through most of it right now. Anything else we haven't touched on you want to bring up? Well, I just think, you know, the team has done a great job enrolling one of the first targeted therapy tumor-agnostic trials. We activated more than 150 sites to enroll this 120 patients into this trial- Mm-hmm ... which just speaks to the scale that we were able to achieve to generate the kind of infrastructure we needed to do a truly tumor-agnostic study, with patients coming from multiple different histologies through multiple different pathways, identified through next-generation sequencing, and just-in-time site enrollment that allowed us to stand up sites very quickly to treat patients. We're really proud of the achievement of closing that trial in April this year- Mm-hmm ... which was two years after we said we would, and on time. And importantly, I wanted to highlight that the NGS component of this testing for TSC1 and TSC2 is available on the market today. Mm-hmm. We utilized it in our clinical trials, and these are standard parts of the test. So when we look forward to how we implement the identification and treatment of patients in the commercial setting, we do think there are a lot of learnings we can take from the clinical trials. We also know it's- Down the way, you do not need any companion- It's basis... Yeah. There's standard testing. It's already standard in practice in many of the institutions that we're working in today. And we look for rapid adoption of this once we get to launch. That's a very good point. Thank you very much.