Good day and thank you for standing by. Welcome to the Aadi Bioscience Inc. Second Quarter 2024 Earnings Call. At this time, all participants are in a listen-only-mode. After the speaker's presentation, there will be a question-and-answer session. [Operator Instructions] Please be advised that today's conference is being recorded. Now I will turn the call over to Audrey Gross [ph], Head of Corporate Communications for Aadi Bioscience. Ms. Gross, please go ahead.

Thank you. Good morning and welcome to the Aadi Bioscience conference call to provide an operational update and review results for the second quarter of 2024. We will be presenting slides as part of the live webcast of this call. Such slides will be posted on the Investors & News page of the Aadi Bioscience website at aadibio.com following the conference call. A quick reminder that statements made on the call today will include forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in the risk factors section of our annual and quarterly filing with the Securities and Exchange Commission, which can be found at www.sec.gov or on our website at aadibio.com. In addition, any forward-looking statements made on this call represent our views only as of today, August 07, 2024, and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements. On the call is Dr. Dave Lennon, our President and CEO; Scott Giacobello, our CFO; and our Chief Medical Officer, Dr. Loretta Itri. Today, we will provide an overview of operational activity and financial results for the second quarter of 2024. We will then open the line for questions at the end of the call following closing comments. I'll now turn the call over to Dave for his opening statement. Dave?

Good morning, everyone, and thank you for joining us today to review our financial and operational results for the second quarter of 2024. I'd also like to take this opportunity to refresh everyone on Aadi's story where we are today and where we're going in the weeks and months ahead. On Slide five, you'll see at Aadi, we are focused on unlocking the full potential of mTOR inhibition by uniquely combining nab technology and the potent mTOR inhibitor sirolimus. With more complete mTOR target inhibition, greater tumor suppression and a wider therapeutic index, we believe nab-sirolimus has the potential to build on previous mTOR inhibitors to deliver better outcomes for people living with cancers that are dependent on that pathway. We've established the value of this approach with FYARRO for the treatment of advanced malignant PEComa, an ultra-rare soft tissue sarcoma with poor outcomes and high biological evidence of the mTOR pathway activation. FYARRO has cemented its position as preferred treatment for malignant PEComa after just two years on the market. Since launch in February 2022, we have achieved $51.1 million in sales. We're proud of the impact FYARRO has had and will continue to have for patients with this rare and aggressive cancer. Building on this commercial backbone, we're also exploring nab-sirolimus for larger indications across multiple types of mTOR driven tumors. Most advanced of these studies is PRECISION1, a registration-intended tumor-agnostic trial in patients with solid tumors harboring TSC1 or TSC2 in activating alterations. This trial is fully enrolled and expected to complete by the end of the year. In a moment, I'll talk more about PRECISION1 and the opportunity it represents for patients and providers. We're also evaluating nab-sirolimus into mTOR driven cancers with promising potential. The first is advanced or recurrent endometrial type endometrial cancer or…

Thanks, Dave. Looking at Slide 11 and starting with FYARRO. FYARRO product sales were $6.2 million for the second quarter, in line with the prior year period and up 15% over Q1. In the quarter, we saw a 14% increase in the number of ordering accounts compared to the first quarter, and growth was observed across all segments, including large accounts. Since launch in February 2022, we've achieved $51.1 million in cumulative sales. FYARRO has a high demand and penetration across both academic and community settings, and we have seen the consistent addition of new accounts ordering FYARRO with more than 200 accounts ordering since launch. Turning to Slide 12. We ended the second quarter of 2024 with $78.6 million in cash, cash equivalents and short-term investments. Responsible capital management continues to support a healthy balance sheet and will fund operations into Q4 2025 based on current plans. Research and development expenses for the quarter amounted to $13.1 million compared to $13.3 million in the prior year quarter. R&D expenses were primarily related to the continued progress of the ongoing PRECISION1 trial in the programs in endometrial cancer and NET. Selling, general and administrative expenses for the second quarter was $7.9 million compared to $11.8 million in the same period in 2023. This decrease was driven mainly by reduced commercial, marketing and personnel expenses related to the rightsizing of our operations earlier in the year and reduced legal expenses versus the prior year quarter. Net loss for the second quarter was $14.6 million compared to $18 million in the second quarter of 2023. For more information on our financial performance in the second quarter, a detailed discussion of the results reported on this call will be provided in our Form 10-Q. I'll now hand the call back over to Dave.

As discussed today, we're making tremendous progress against our clinical development plans with two sizable markets in TSC1 and TSC2 in activating alterations as well as other mTOR driven cancers. On Slide 14, what you'll see is the back half of the year will be an important time for Aadi, and we look forward to providing the anticipated two thirds interim analysis from PRECISION1 later this quarter, and if appropriate, sharing those data with the FDA thereafter. We expect to complete PRECISION1 by the end of the year. Additionally, we plan to provide an initial look at data coming out of the EEC and NET trials by the end of the year as well. Looking ahead to 2025, we expect to have full results of PRECISION1. And if the data continue to hold, we believe this would form the basis of a filing with the FDA in 2025 as well. With that, we can now open the line for questions. Operator?

[Operator Instructions] And our first question comes from Roger Song with Jefferies. Your line is now open.

Thanks for that Dave for taking our question. Maybe we first talk about the PRECEISION, Dave, if we may. Understanding you will have the second interim data in 3Q. First of all, given the first-interim data, what kind of the expectation you have for TSC1 and 2? And the second part of the question is, you say you will discuss with the FDA with the second interim data? And then just curious to what would be the key topic there and then what could be the potential outcome out of the FDA discussion after second interim? I have a follow-up. Thank you.

Sure. Thanks, Roger. I'll make a couple of comments and ask Loretta if she has anything she'd like to add. Our PRECISION1 outcome in Q3 will be -- will present -- obviously, just a reminder, this is the primary endpoint analysis on two thirds patients, so 80 patients or 40 patients in each arm. The primary endpoint of independently assessed overall response rate after six months, minimum six months of follow-up, will be reported out along with key demographic and select secondary data. We -- I wouldn't draw any anticipation in terms of the direction of which we see that data going at this point in time. We'll have to wait for that report to see that. But those are the -- that's the information. If you want more specifics, just let me know the follow-up there. And then presumably, since this is representative of the primary endpoint and a preplanned interim analysis, we do think this would be a good foundation for data discussion, data-driven discussion, with the FDA on a potential path to submission, and that would be the goal of that next discussion with the FDA. Loretta, anything you would add to that?

No, Dave, I think you covered it nicely. Thank you.

Got it. Yes. Thank you. And then since the enrollment for the EEC and NET studies going pretty well. And then just curious what should we expect from the later this year initial data update? Will that be focusing on the -- maybe some of the safety [indiscernible] or you expect to see some clinical activity from those initial data results? And how many patients we should expect to see for the data? Thank you.

Yes. I'll let Loretta start by commenting on where we are with those trials, and I can follow up if anything to add. So Loretta, why don't you comment on this?

Sure. Thanks, Dave, and thank you for the question. For the EEC trial, we have been recruiting very rapidly and which I think reflects the support in the community for this combination. Currently, although we're not giving exact numbers, we have completed enrollment of the entire first cohort and we're well into the second cohort at this point in time. My expectation is that by the end of the year, we will be able to give a fairly full summer report on the first cohort of patients and probably some partial information on the second cohort. So that's EEC. And for the NET program, again, we are accruing quite rapidly, and I would -- I have full expectation that by end of the year, we will be able to report on the first cohort of patients quite completely. Dave, I don't know if you want to add something else?

That's great, Loretta. Thank you. The only thing I might add is, right, that these are two indications where there is precedent data with mTOR inhibitors. And so, one of the opportunities we have here is to compare what we know from prior studies with mTOR inhibitors in these indications to the data we're seeing with nab-sirolimus, which will be something we'll bring forward as we look at that data, depending on the patients that we enroll in these early trials.

Dave, if I might add, I just want to remind everyone that these studies are open label unlike PRECISION. So there will be no problem statistically with reporting the information. Thank you.

Thanks, Roger. Let's -- can we move on to the next set of questions?

Thank you. Our next question comes from Joe Catanzaro with Piper Sandler. Your line is open.

Hey guys, thanks for taking my question. Maybe following up a bit on sort of what happens post the second 2/3 interim analysis here in the range of outcomes. I'm guessing it's-- I'm wondering if there's any scenario in which the design and execution of the remainder of PRECISION1 is altered or changed in any way. I do recall maybe some speculation that there's a possibility of maybe increasing the target enrollment of the trial, again, depending on sort of the outcome. So maybe you could just speak a little bit more to that on sort of the various scenarios that may play out.

Sure, Joe. Thanks for the question. It's a good one. We have talked in the past about that ability to adjust the trial at this point in time. We will say that the trial has been fully enrolled at this point in time. And so we anticipate being able to report out on the full 120 patient data set in early 2025 once those patients have completed their follow-up period. And so we do feel we're in a good position on the full trial enrollment. In terms of -- so at this point, we don't anticipate any adjustments to the trial given the trajectory that we've seen so far. And we wouldn't anticipate that, that would be an outcome in the short term. That's -- of course, we still would be waiting for our data monitoring committee's recommendation on that as well as kind of internal deliberations. And any changes we do would be part of our disclosure when we report out that data later this quarter.

Okay. Got it. That's helpful. And then maybe one quick one on FYARRO. I know you've maybe previously have spoken to expectations to continue to see some incremental growth there. Just wondering if that's still your expectations and what would be sort of the driver of that? Thanks.

Yes. I want -- I mean, I would -- do want to highlight that we did have a low Q1, which we discussed had -- likely was being impacted by potentially some cannibalization we were seeing at some of our large centers. Importantly, in Q2, we saw a really strong rebound in demand across all of our key segments of business. And we do believe that that's being sustained as we go into the next quarter. And that we're seeing from a demand perspective, our demand numbers in Q2 actually outperformed what we saw net sales as we had some deductions on a gross-to-net basis related to inventory movements still in Q2. And so we remain very positive on the outlook for continued incremental growth in the business in Q3 and Q4 of this year.

Okay, great. That's helpful. Thanks for taking my questions.

Yes. Thanks, Joe. Next question, Operator?

Thank you. Our next question comes from Tara Bancroft with TD Cowen. Your line is open.

This is Greg Weasner [ph] on behalf of Tara Bancroft. Is there any particular tumor type that you're favoring at this point for future trials? Or will this continue to be a pan-tumor approach? And if it's the latter, what guidance does the FDA give for registrational trial requirements? Thank you.

Sure, Greg. Thanks for the question. We -- this is, as I pointed out, I think, and we tried to discuss deeper in the slides, this is truly a tumor-agnostic trial. And therefore, the FDA has no guidance on biasing the trial for any particular indications. And we certainly enroll any and all patients who qualify regardless of tumor type into the trial based on their TSC1/TSC2 status and a few other of the inclusion criteria. So we do believe that this will be conducted and reviewed as a tumor-agnostic trial. Our indication will not be tumor-specific. It will be for that tumor-agnostic label, assuming we submit and gain approval around that. And we don't -- just to reiterate, we don't anticipate or guide this trial PRECISION1 towards any specific tumor types. Obviously, we are very interested in thinking about our endometrial and neuroendocrine specific tumor indications where we know mTOR plays a role regardless of TSC1 and 2 status. And actually, those trials exclude patients with those mutations. And therefore, we are -- or we haven't had any -- I should say we haven't had any patients with those mutations in that trial. And so that's looking at the impact of the mTOR pathway in those specific indications where we know they are potentially more mTOR sensitive.

Okay. Wonderful. That's very helpful. And if I can just ask one quick follow-on question. Is there a particular conference that you're targeting for the second interim? Or would this be something that we can expect from a PR?

Yes, we would imagine this will be a company presentation at this point.

Thanks guys.

Our next question comes from Ahu Demir with Ladenburg Thalmann. Your line is open.

Thanks very much for taking my question. I appreciate the additional information with the results today. Two questions from us perhaps one more after the second question would be -- my initial question is, you mentioned the earlier lines of treatment, having a better impact as we have seen in many targeted therapies. Curious if you are planning to maybe disclose this data with the next data release? Are we going to see distinct populations where patients are treated more than three lines of treatment versus earlier lines of treatment? Are you planning to disclose that information?

We'll certainly disclose the response rate overall. I think the question, once we get the data, will be, did we see a difference between lines of treatment, is that meaningful given the data set that we have. So I think, Ahu, that would be a decision that's highly data dependent in terms of what we actually see from the patient population. I can say in the early line -- in the early interim we did in December, we didn't see any -- it was a very small data set, so it's hard to extrapolate, but we didn't see any particular pattern and we had responses spread across different lines of treatment.

Makes sense. And my second question is on the endometrial cancer program. You did mention the biggest idea of this trial is to compare it to the other mTOR inhibitors and the patient baseline demographics can impact the trial readouts significantly. So what was the other trial patient demographics look like? Are you planning to focus on those? Any particular populations that you would be targeting? Anything we should pay attention because sometimes it's very challenging when we are comparing apples to oranges and based on demographics that impacts a lot.

Yes. Understood. I probably oversimplified the comparison or a statement in that. So I'm going to allow Loretta to comment on kind of our strategy with the endometrial trial and where we think the real benefit is here for patients. Loretta?

Sure, Dave. Good morning. And thank you for that question. As usual, it's a good one. So the -- the design of the EEC study was largely based on an earlier study that was performed by GOG, the Gynecologic Oncology Group. This is a study GOG-209. And this is actually an older study that established platinum and paclitaxel as the standard-of-care for patients who had advanced endometrial cancer. And in that study, there was a cohort of patients who were chemo-naive. And in that group, they saw a response rate of about 51%. Now this was compared to a later study of the combination of Everolimus and letrozole in which the response rate in the chemo-naive patients was 47%. So not very different than what was seen with platinum and paclitaxel. But what was really riveting was the fact that the PFS reported for the platinum paclitaxel combination was 14 months, which is healthy. But for the Everolimus letrozole combination, it was 28 months, a doubling. And PFS in this population where quality of life is extremely important, really was what was the driver behind the design of our [Indiscernible] advanced stage endometrial cancer. We had an opening a chance to put this combination in frontline or in second line, in some cases, to take a look at how well it would work and to see if we could repeat or improve on the original Everolimus letrozole combination data in a chemo-naive patient population. So that was the basis of the study design and the community has been extremely supportive of this idea and has enrolled very rapidly because of their wish to replace, or try and replace, chemotherapy as frontline treatment for this population. I hope that helped.

Yes. Definitely. Thank you, Loretta.

Okay. As I mentioned, Ahu, I do it too simply Loretta does it wonderfully. So, thank you for the question. Do you have a follow-up?

Well, one last question I have, Dave, if I may. You have two distinct approaches to assess nab-sirolimus. So curious, when you talk to the KOL community. So where do you see the most excitement? Is it for more of the TSC1/2 approach, is agnostic approach? Or do you see more of an excitement for the endometrial and NET where there is an indication-specific approach?

I'll let Loretta comment first and then...

So first of all, they are totally different populations. Remember that your PRECISION, we are dealing with sort of a pan-representation of specialties. So they don't necessarily talk to each other. But the ones who do talk to each other remain really very bullish on the fact that we are seeing responses in some of these very sick, late-stage patients, as Dave mentioned in his commentary. It's perhaps easier to see the enthusiasm in the community for EEC, where these tend to be a group of specialists who are together all of the time. And they talk about this disease all of the time, and they treat the same kind of patients all of the time. So their excitement is palpable, and they are looking for the next big thing. So immunotherapy was, of course, big and changed the standard-of-care. And now they are looking for a way to replace chemotherapy. And they are hopeful and actually quite vocal that we will fill that gap. So that's as best as I can represent it, I think. Dave, you wanted to say something else?

I think that's a great summary of it, Loretta from first-hand experience. I would say we also went out with the TSC1 and 2 interim analysis, I mentioned and talked to a large number of physicians to get reactions to that profile and understand across different specialties what that reaction would be. And consistently, physicians are quite interested in finding solutions for late-line patients, particularly through targeted mutations where there's identifiable mutation and where often not just overall response rate, but even stable disease is a meaningful outcome for those patients who progress through multiple lines of therapy. And we had excellent reactions to the profile of nab-sirolimus especially amongst folks who are familiar with the mTOR pathway and/or doctors who have seen this product in the PEComa setting. So thank you, Ahu, for the questions. So, Operator, next question?

Thank you. Our next question comes from Robert Burns with HC Wainwright. Your line is now open.

Good morning. This is Dan on for Rob. Thanks for taking our questions. We wanted to ask, given the data demonstrating preferential tumor uptake for nab-sirolimus versus --sirolimus and Everolimus. Are you thinking of any drug combinations and subsequent target indications for the future? Or to rephrase: any ideas on future directions or expansions? And would you be able to give a little more color around when in this upcoming quarter you expect to report the interim analysis? And I'd like to have some follow-ups, if I could.

Sure. Thanks, Dan, for the questions. Yes. So I think as you point out, we do see that preferential accumulation of sirolimus in the nab-sirolimus combination driven by that nanoparticle-bound albumin technology, and we do think that's one of the key advantages that we have with this product. Obviously, the TSC1 and 2 trial is a monotherapy trial, so there's no combination there. But the EEC trial is in combination with letrozole and the NET trial is a monotherapy or in combination for functional tumors with standard-of-care. In terms of more exploratory combinations that would build on that, we're absolutely looking at those opportunities. But I wouldn't -- I think it's premature for us to comment about that. I think we're looking for these results from these initial trials over the second half to really set the path for the future. And then in terms of timing, all I can say is later in Q3.

Thanks. That makes sense. So regarding follow-ups, what are you looking for from the Phase II program in neuroendocrine tumors regarding efficacy and safety? And are there specific tumor types that you expect to see the greatest impact in? Do you have an update -- Sorry.

Go ahead. Finish.

Do you also have an updated view on what maximum sales and the PEComas could look like in the United States and around what that would be? And how did -- I'm curious on the paclitaxel versus Everolimus trial. How does those overall survivals compare -- back in the day.

I can.

Yes, I'll let Loretta take the first question. Go ahead.

Okay. So I'll take the last question first because I -- there were so many questions I kind of forgot what the earlier ones are, but I can tell you that the overall survival for the combination of paclitaxel and [Indiscernible], it was 32 months. So -- and it was not reported for the letrozole Everolimus combination. But if the PFS was 28 months, it isn't that far from 32 months overall survival. So you may assume that it was significantly better.

Loretta, thanks. The first question was in regards to the net trial expectations and any particular tumor types that we might see better responses.

Okay. He wants me to answer that. So...

Yes. Go ahead, thanks. If you could add.

So are you -- I wasn't clear with the question; whether you were talking about subtypes of NET because NET occur in different organ sites. We don't actually have enough information. If that is the question. We don't have enough information to know which of the subset NET is going to have a better response rate. You just don't have enough information at this point in time.

Yes. And Dan, if I can add on the NET trial. Historically, mTOR inhibitors have been utilized in the setting or in neuroendocrine tumors. The reality is that those -- I mean, those approvals were driven off of progression-free survival benefit that was demonstrated. NET can be quite indolent and long lasting. And -- but there is benefit that has been derived from mTOR inhibitors in terms of extending time on treatment for those patients relative to other approaches. The reality is though that those prior MTOR inhibitor trials show very low overall response rate, so often in the single-digit setting. And we think the -- an early indication of the potential of our MTOR inhibitor would be to show superior -- or not superior, but because it's not a direct comparison, but to show numbers that would be better in terms of initial response rates that could guide to kind of that longer-term better outcome for those patients. And then on the PEComa sales, we don't guide -- we haven't provided guidance to the ultimate potential in PEComa. What I would say is that PEComa is a very rare indication. We're talking 200 to 300 patients in the U.S. in total. That means we're finding one in a million kind of what we're looking for in terms of finding those patients and getting them to the right treatment setting. Many physicians will never see a PEComa patients. And so therefore, our goal is to continue to hunt and find these patients and make sure they're getting to the right treating physicians so they can get exposed to the potential for nab-sirolimus to support their disease journey. That ultimately is a -- it's hard to predict exactly where that can land over time. What we have said consistently is that we do believe we've penetrated most of the marketplace at this point and any further growth will be incremental.

That makes sense. And I apologize for the inundation of questions.

No worries. We take notes as we go. So, thank you, Dan.

I apologize for my short attention span.

Thank you. Operator, are there any other questions on the line?

I'm showing no further questions at this time. I would now like to turn it back to Dave Lennon for closing remarks.

Thank you, Audrey, Loretta, Scott, for your comments today. Thank you, everyone, on the call for joining us for today's call. We appreciate your time and look forward to the opportunity in the near future to provide additional updates on our progress. Otherwise, have a great wonderful rest of your day and week and look forward to speaking to you all soon. Thank you.

This concludes today's conference call. Thank you for participating. You may now disconnect.