Q2 2024 Aadi Bioscience Inc Earnings Call

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Operator: 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. To ask a question during this session, you will need to press star 11 on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star 1 1 again.

Speaker Change: To ask a question during the session you will need to press star one one on your telephone.

Speaker Change: Here, an automated message advising your hand is raised.

Speaker Change: To withdraw your question. Please press star one one again.

Operator: Please be advised that today's conference is being recorded. Now I will turn the call over to Audrey Gross, Head of Corporate Communications for Aadi Bioscience. Ms. Gross, please go ahead.

Speaker Change: Please be advised that today's conference is being recorded.

Audrey Gross: Now I will turn the call over to Audrey gross.

Audrey Gross: Head of corporate communications for <unk> Bioscience.

Gross: Gross please go ahead.

Gross: Yeah.

Audrey Gross: 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 and news page of the Aadi Bioscience website at aadibio.com following the call. A quick reminder that statements made on the call today will include forward-looking statements

Audrey Gross: Thank you.

Audrey Gross: Good morning, and welcome to the antibody is brands conference call to provide an operational update and review our results for the second quarter of 2024.

Audrey Gross: We will be presenting slides as part of a live webcast of this call. So that's why it will be posted on the investors and news page of the antibody science website at Alibaba Dot Com following the conference call.

Audrey Gross: Actual events or results could differ materially from those expressed or implied by any forward-looking statement 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 7, 2024, and should not be relied upon as representing our views on any subject.

Audrey Gross: A quick reminder, that statements made on the call today will include forward looking statements.

Audrey Gross: Cool 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 filings with the Securities and Exchange Commission, which can be found at www dot SEC Gov or on our website at <unk> dot.

Audrey Gross: Com.

Audrey Gross: In addition, any forward looking statements made on this call represent our views only as of today August seven 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.

Audrey Gross: We specifically disclaim any obligation to update or revise any forward-looking statements. On the call today are 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

Speaker Change: On the call is Dr. Dave Lennon, our president and CEO, Scott <unk>, our CFO and our Chief Medical Officer, Dr. Loretta Itchy.

David Lennon: 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.

David Lennon: On slide five, you'll see that at Aadi, we are focused on unlocking the full potential of mTOR inhibition by uniquely combining NAB technology and the potent mTOR inhibitors to your alignment. With more complete mTOR target inhibition, greater tumor suppression, and a wider therapeutic index, we believe Napsier-Wymeth has the potential to build on previous mTOR inhibitors to deliver better outcomes for people living with We've established the value of this approach with FIARO for the treatment of advanced malignant pacoma, an ultra-rare soft tissue sarcoma with poor outcomes and high biological evidence of the mTOR pathway activity. FIARO has cemented its position as the preferred treatment for malignant PECOMA after just two years on the market. Since its launch in February 2022, we have achieved $51.1 million in sales.

David Lennon: We're proud of the impact VRO has had and will continue to have for patients with this rare and aggressive cancer. Building on this commercial backbone, we're also exploring Napsir-Limus for larger indications across multiple types of mTOR-driven, The most advanced of these studies is PRECISION-1, a registration-intended tumor-agnostic trial in patients with solid tumors harboring TSC-1 or TSC-2 This trial is fully enrolled and expected to complete by the end of the year.

David Lennon: In a moment, I'll talk more about Precision One and the opportunity it represents for patients and providers. Meanwhile, we're also evaluating Napsirolimus in two mTOR-driven cancers with promising potential. The first is advanced or recurrent endometriotype endometrial cancer, or EEC, in combination with the aromatase inhibitor letrozole. Endometrial cancer is the most common cancer of the female reproductive tract and one of the few cancers with increasing mortality. There are an estimated 10,000 cases of EEC diagnosed annually in the U.S. alone

Moment, I will talk more about precision one and the opportunity it represents for patients and providers.

Speaker Change: We're also evaluating napster alignments in <unk>, driven cancers with promising potential. The first is advanced or recurrent endometrial type endometrial cancer or EC in combination with aromatase inhibitor electrical.

Cancer is the most common cancer of the female reproductive tract and one of the few cancers with increasing mortality. There's an estimated 10000 cases of <unk> diagnosed annually in the U S alone prior clinical studies of <unk> inhibitors combined with lectures all have yielded promising results and recent changes in the recommended standard of care for early stage disease creates a potential opportunity for.

David Lennon: Prior clinical studies of mTOR inhibitors combined with letrozole have yielded promising results, and recent changes in the recommended standard of care for early-stage disease create a potential opportunity for this combination to be used in the first and second-line setting. The second trial is in neuroendocrine tumors of the lung, gastrointestinal tract, and pancreas. Neuroendocrine tumors, or NETs, are rare and have a historically low response rate to treatment with oral rapalogues and other agents, which are nonetheless used clinically and recommended in treatment guidelines.

Speaker Change: This combination to be used in the first and second line settings.

Speaker Change: The second trial is a neuroendocrine tumors of lung gastrointestinal tract, and pancreas, neuroendocrine tumors or <unk>, a rare and have historically low response rates to treatment with oral <unk> and other agents, which nonetheless are used clinically and recommended in treatment guidelines in preclinical animal models Napster alignments demonstrated improved targets pressure relative to other <unk>.

David Lennon: In Preclinical Animal Models, NAVSAR alignments demonstrated improved target suppression relative to other mTORs, warranting further exploration of NAVSAR alignments in this study. These Phase II open-label studies are both enrolling well, and we look forward to presenting initial data from these trials later this year. Aadi is led by an accomplished team with deep expertise and a track record of responsible capital management.

Speaker Change: Warranty further exploration of Napster alignments in this indication.

Speaker Change: These phase two open label studies are both enrolling well and we look forward to presenting initial data from these trials later this year.

Speaker Change: <unk> is led by an accomplished team with deep expertise and a track record of responsible capital management with sustained commercial success of <unk> cash runway is anticipated to extend into Q4 2025 with a catalyst heavy 2024 and 2025 ahead of US we believe <unk> is well positioned to achieve our goals.

David Lennon: With sustained commercial success of PRO, Cash Runaway is anticipated to extend into Q4 2025 with a catalyst-heavy 2024 and 2025 ahead of us. We believe Aadi is well positioned to achieve our goals. Now, turning to slide six, as mentioned, Precision-1 is a registration-intended tumor agnostic trial evaluating patients with solid tumors harboring either TSC-1 or TSC-2 in activating alterations. As of May, the trial has fully enrolled 120 patients across a broad array of tumor types. TSC-1 or TSC-2 driven cancers are found across a wide range of tumor types clustering in the lung, gastrointestinal, general urinary, breast, and gynecological regions, and are often difficult to treat.

David Lennon: Although Precision-1 is a single trial, the TSC-1 and TSC-2 arms are independently evaluated and can effectively be viewed as two separate studies, each with its own outcome. Importantly, by design, patients in Precision One have received all standard therapies appropriate for their tumor type and stage of disease, or, in the opinion of the investigator, the patient would be unlikely to tolerate or derive clinically meaningful benefit from the appropriate standard of care.

Speaker Change: Now turning to slide six as mentioned precision one as registration attended tumor agnostic trial evaluating patients with solid tumors harboring either <unk> or <unk> and activating alterations as of May. The trial is fully enrolled 120 patients across a broad array of tumor types GSE.

Speaker Change: <unk> driven cancers are found across a wide range of tumor types clustering in the lung gastrointestinal general urinary breast and gynecological locations and are often difficult to treat.

Although precision one as a single trial <unk> and TC two arms are independently evaluated.

Speaker Change: <unk> effectively be viewed as two separate studies each with its own outcome.

Speaker Change: Importantly by design patients in precision one have received all standard therapies appropriate for their tumor type and stage of disease or in the opinion of the investigator that patient would unlikely to tolerate or derive clinically meaningful benefit from the appropriate standard of care.

David Lennon: In essence, for most patients enrolled in this study, this means they have limited, if any, further treatment options and an extremely poor prognosis. By the design of this trial, NAPSER alignments is the last available line of systemic therapy for these patients and truly tests the ability of NAPSER alignments to address TSC1 and TSC2 mutated cancers in these sickest patients. We remain on track for our next planned interim readout, which is expected in Q3 2024.

Speaker Change: In essence for most patients enrolled in this study. This means they have limited if any further treatment options and an extremely poor prognosis by the design of this trial <unk> alignment is the last available line of systemic therapy for these patients and truly test the ability of napster alignments to address <unk> mutated cancers in the sickest.

Speaker Change: <unk>.

Speaker Change: We remain on track for our next plant interim readout, which is expected in Q3 2020 for this analysis will include a total of 80 patients who have been followed for a minimum of six months and we will evaluate the primary endpoint of the study independently assessed overall response rate.

David Lennon: This analysis will include a total of 80 patients who have been followed for a minimum of six months and will evaluate the primary endpoint of the study, independently assessed overall response. Now looking at slide 7, as a reminder, in Q4, we provided top-line results for the planned interim evaluation of the first 40 patients enrolled in Recision 1. These data demonstrated sustained tumor reductions in a heavily pre-treated population based upon investigator-assessed responses across both. For TSC1, we reported an investigator-assessed overall response rate of 26%, which was within the range of our expectations.

Speaker Change: Now looking to slide seven as a reminder, in Q4, we provided top line results for the planned interim evaluation of the first 40 patients enrolled in precision one.

Speaker Change: These data demonstrated sustained tumor reductions in a heavily pretreated population based upon investigator assess responses across both arms for Tsi. One we reported investigator assess overall response rate of 26%, which was within the range of our expectations. These responses appear to be early deepen durable, which is especially noteworthy.

David Lennon: These responses appear to be early, deep, and durable, which is especially noteworthy given this heavily pre-treated population with an average of three prior lines of therapy. These responses were seen across four different tumor types, potentially supporting a tumor agnostic indication. For the TFC2 arm, we reported a 11% overall response rate.

Speaker Change: This heavily pretreated population with the medium of three prior lines of therapy.

David Lennon: This arm had a median of 3.5 prior treatments, including 50% who had at least five prior lines of therapy. To put these early interim data in context, the overall response rate for the phase two trial of erythrolimus in a pan-cancer cohort of patients with mTOR pathway alterations was 8% for TSC1 and 6% for TSC2, both in slightly earlier lines of treatment. While this isn't a one-to-one comparison, and studies have important differences, these historical data are helpful as we think about the clinical significance of the responses we reported in the first interim analysis, especially in light of the late line. I also want to highlight that ongoing conversation with experts has reinforced this view.

David Lennon: We have heard from key opinion leaders that these data are compelling, especially for tumor types in late line for whom disease control is a meaningful outcome. Now turning to slide eight, it's important to note that Precision One closely follows the most up-to-date guidance from regulators on how they would like to see tumor agnostic studies for targeted therapies. As we've reiterated today, PRECISION-1 is a truly tumor-agnostic trial, enrolling any solid tumor type harboring a TSC-1 or TSC-2 activating alteration.

David Lennon: By design, PRECISION-1 will not have more than 25% of enrollment from any two tumor types combined. Additionally, patients in PRECISION-1 are heavily pretreated, with a median of three prior lines of therapy, as reported in our December interim data. By contrast, when we look at other targeted therapies that have gained approval in the past, they relied on a cohort approach with significant enrollment from just one or two tumor types, as much as 79% in one case. Patients also appeared to be less advanced, with these interventions often coming in earlier line settings, which impacts the overall response rate seen in these trials.

David Lennon: Based on these precedents, we feel confident in the design of PRECISION-1 to meet the standard established for this type of study. We continue to believe that should these results reported in the one-third interim hold or improve in a larger group of patients, we have a path to submission and potential approval for TSC. Now looking at the market opportunity on slide nine.

Speaker Change: And the design of precision wanted to meet the standard established for this type of study. We continue to believe that should these results were reported in the <unk> interim hold or improve and a larger group of patients we have a path to submission and potential approval for <unk> mutations.

Speaker Change: Now looking at the market opportunity on slide nine TLC.

David Lennon: TSC-1 and TSC-2 mutations define a large mutation-driven oncology population, with broad distribution amongst tumor indications and special... Our latest internal analysis indicates there are approximately 16,000 patients with TSC1 and 2 mutations across a variety of tumor types, and these mutations are roughly evenly split between genes. Notably, we are seeing an increasing utilization of NGS testing by oncologists to help inform treatment. There are some populations in particular for whom NGS testing is more common, so-called high NGS testing.

<unk>, one and <unk> two mutations to find a large mutation driven oncology population with broad distribution amongst tumor indications and specialties. Our latest internal analysis indicates there is approximately 16000 patients with PSC, one and two mutations across a variety of tumor types and these mutations are roughly evenly split between genes.

Speaker Change: Notably we are seeing an increasing utilization of NGF testing by oncologist to help inform treatment decisions. There are some populations in particular for whom Ngf's testing is more common so called high ngf's testing specialties nearly half of <unk> and <unk> tumors present in these high Ngf's testing specialties, which include tumors of.

David Lennon: Nearly half of TSC1 and TSC2 tumors present in these high NGS testing specialties, which include tumors of gynecological and thoracic origin, as well as melanomas and sarcomas. These physicians see roughly half of all TSC1 and TSC2 positive patients. According to our research for the product profile, similar to our interim results to date, high NGS testing specialties indicate they would be likely to use nabsirolimus after second and third line preferred treatments, which aligns with what we observed in Precision 1.

Speaker Change: <unk> and thoracic origin, as well as Melanomas and Sarcomas. These physicians see roughly half of <unk> in <unk> positive cancers.

Speaker Change: According to our research for the product profile similar to our interim results to date high Ngf's testing specialties indicate they would likely they would be likely to use napster alignment after second and third line preferred treatment, which aligns with what we've observed in position one we anticipate that market adoption would be led by the specialties with initial updates occurring in later line settings.

David Lennon: We anticipate that market adoption will be led by these specialties, with initial uptakes occurring in later line settings, where patients are often thoroughly tested for mutations, and physicians are looking for unique treatments. Even if we limit the majority of NAPSR alignments utilization to be in the third line with these high NGS testing segments, TSC1 and TSC2 mutated cancers would represent a significant $300 to $600 million projected market opportunity in the U.S. alone.

David Lennon: So if precision One delivers similar results to our prior interim analysis, we know there's a significant unmet need that we're addressing. We remain confident that we've designed and conducted the appropriate tumor agnostic trial for the FDA, and we remain bullish on the significant commercial potential for napsirolimus B. With that, I'll now turn it over to Scott for updates on our Q2 financial progress. Scott.

Scott Giacobello: Looking at slide 11, and starting with FIARA, BioNet product sales were $6.2 million in 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 orders 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. FIARO has high demand and penetration across both academic and community settings, and we have seen the consistent addition of new accounts ordering FIARO, with more than 200 accounts ordering since launch.

Scott Giacobello: Turning to slide 12, the end of the second quarter 2024 is $78.6 million in cash, cash equivalents, and short-term investments. Responsible Capital Management continues to support a healthy balance sheet that will fund operations into Q4 2025 based on current funds. 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 Precision One trial and the programs in endometrial cancer.

Scott Giacobello: Selling general and administrative expenses for the second quarter were $7.9 million compared to $11.8 million in the same period last year. This decrease was driven mainly by reduced commercial, marketing, and personnel expenses related to the right sizing of our operations earlier in the year and reduced legal expenses versus the prior year. The net loss for the second quarter was $14.6 million compared to $18 million in the second quarter of 2020. 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 10-2. I'll now hand the call back over to David.

Speaker Change: This decrease was driven mainly by reduced commercial marketing and personnel expenses related to the right sizing of our operations earlier in the year and reduced legal expenses versus the prior year quarter.

Speaker Change: Net loss for the second quarter was $14 6 million compared.

Speaker Change: Compared to $18 million in the second quarter of 2023.

Speaker Change: 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.

Speaker Change: I'll now hand, the call back over to Dave.

David Lennon: As discussed today, we're making tremendous progress against our clinical development plans with two sizable markets for TSC-1 and TSC-2 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 ADDIE, and we look forward to providing the anticipated two-thirds interim analysis from Precision I later this quarter and, if appropriate, sharing those data with the FDA thereafter.

Dave: As discussed today, we're making tremendous progress against our clinical development plans with two sizable markets in tier one and tier two inactivating alterations as well as other M Tor driven cancers.

Dave: On slide 14, but youll see as the back half of the year will be important time for Eddie and we look forward to providing the anticipated two thirds interim analysis from precision. One later this quarter and if appropriate sharing those data with the FDA thereafter, we expect to complete precision one by the end of the year.

Dave: Additionally, we plan to provide an initial look at data coming out of the EC a net trials by the end of the year as well looking ahead to 2025, we expect our full results precision one and if the data continue to hold we believe this would form the basis of a filing with the FDA in 2025 as well.

David Lennon: We expect to complete Precision I 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 from Precision I, 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? As a reminder,

Speaker Change: With that we can now open the line for questions operator.

Operator: As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. And our first question comes from Roger Song with Jeffreys. Your line is now open.

Roger Song: Great, thanks for the update and taking our questions. Maybe we first talk about the position, Dave, if we may. You know, understanding you will have the second interim data in 3Q, first of all, you know, given the first interim data, what kind of expectation do you have for TSC 1 and 2? And the second part of the question is, you say you will discuss with the FDA the second interim data, and then just curious about what will be the key topics there and then what will be the potential outcome of the FDA discussion of the second interim data as a follow-up. Thank you.

David Lennon: Sure. Thanks, Roger. I'll make a couple of comments and ask Loretta if she has anything she'd like to add. Our precision one outcome in Q3 will be, will present, obviously, just a reminder, this is a primary endpoint analysis on two-thirds of 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. I wouldn't draw any anticipation in terms of the direction of what we see that data going in at this point in time. We'll have to wait for that report to see that, but that's the information.

Loretta Itri: If you want more specifics, just let me know the follow-up there. And then, you know, presumably, since this is representative of the primary endpoint and a pre-planned interim analysis, we do think this would be a good foundation for data discussion and 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. If you had anything you would add to that, No, Dave, I think you've covered it.

Loretta Itri: No, Dave, I think you covered it nicely. Thank you.

Roger Song: Got it. Yeah, thank you.

Roger Song: And then, you know, since the enrollment for the EEC and the NET phase, the studies are going pretty well. And then, just curious, what should we expect from the later this year's initial data update? Will that be focusing on, you know, maybe some of the safety, turbidity, or do you expect to see some clinical activity from this, those initial data results? And how many patients should we expect to see?

Speaker Change: We expect to see clinical activity.

Speaker Change: From this.

Speaker Change: Initial data readout and how many patients we should expect to see.

Speaker Change: For the data thank you.

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

Speaker Change: Yeah, I'll, let loretta start by commenting on where we are.

Loretta: With those trials and I can follow up if anything to add so the right I wanted to comment on that sure. Thanks, David. Thank you for the question.

Loretta Itri: Sure. Thanks, Dave.

Loretta: For the E. C trial, we have been recruiting very rapidly and which I think reflects the.

Loretta: <unk> in the community.

Loretta: For this combination.

Loretta Itri: And thank you for the question. For the EEC trial, we have been recruiting very rapidly, which I think reflects the support in the community for this combination. Currently, although we're not giving exact numbers, we have completed enrollment in 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 report on the first cohort of patients and probably some partial information on the second cohort.

Loretta: So currently although we're not giving exact numbers, we have completed enrollment of the entire first cohort.

Loretta: And we're well into the second cohort at this point in time.

Loretta: My expectation is that by the end of the year, we will be able to give a fairly fulsome report on the the first cohort of patients and probably some partial information on the second cohort.

Loretta Itri: So that's EEC. And for the NET program, again, we are accruing quite rapidly, and I would have full expectation that by the 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 anything else.

David Lennon: That's great, Loretta. Thank you. The only thing I might add is 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 NAV serolimus, which will be something we'll bring forward as we look at that data, dependent on the patients that we enroll in these early trials.

Loretta Itri: 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.

Roger Song: Okay, got it. That's helpful. There may be one quick one on FIYARO.

Roger Song: I know you've maybe previously spoken to expectations to continue to see incremental growth there. Just wondering if that's still your expectation and, and what would be sort of the driver of that? Thanks.

David Lennon: Yeah, I want to, I mean, I would do want to highlight that, you know, we did have a low Q1, which, you know, we discussed had likely been impacted by potentially some cannibalization we were seeing at some of our large centers. Importantly, in QT, we saw a really strong rebound in demand across all of our key segments of business. And we do believe that this is, you know, being sustained as we go into the next quarter.

David Lennon: And that, you know, we're seeing from a demand perspective. Our demand numbers in Q2 actually outperformed what we saw in net sales as we had some deductions on a gross to net basis related to inventory movement still in Q2.

Loretta: And the outlook for continued incremental growth in the business in Q3 and Q4 of this year.

Roger Song: Okay, great. That's helpful. Thanks for taking my question.

Speaker Change: Okay great.

Speaker Change: Helpful. Thanks for taking my questions. Thanks, Joe next question operator.

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

Speaker Change: Hi, This is Greg <unk> on behalf of Tara Bancroft.

Speaker Change: So the I'm sorry.

Roger Song: 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.

Speaker Change: Is there any particular tumor types 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 F. D. A gift for Registrational Trail trial requirements. Thank you.

David Lennon: Sure, Greg. Thanks for the question. Just to reiterate, we don't anticipate or guide this trial, Precision 1, 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, I should say we haven't had any patients with those mutations in that trial. And so that's looking at, you know, the impact of the mTOR pathway in those specific indications where we know they are potentially more mTOR-dependent.

Speaker Change: Sure Greg. Thanks for the question. We are this is as I pointed out I think and we tried to.

Speaker Change: <unk> discussed deeper in the slides this is truly a tumor agnostic.

Speaker Change: Trial, and therefore, the FDA has no guidance on biasing the trial for any particular indications and we certainly enroll.

Speaker Change: Any and all patients who qualify regardless of tumor type.

Speaker Change: The trial based on their <unk> status and a few other of the inclusion criteria.

Roger Song: Wonderful. Thank you. That's very helpful.

David Lennon: And if I can just ask one quick follow-on question, is there, you know, a particular conference that you're targeting for the second interim? Or would this be something that we can expect from a PR? Yeah, we would imagine this will be

David Lennon: 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.

Roger Song: My second question is on the endometrial cancer program. You did mention the biggest idea of the trial is to compare it to other mTOR inhibitors, and patient baseline demographics can impact the trial results significantly. So what did the other trials patient demographics look like? Are you planning to focus on those? Any particular populations that you would be targeting? Anything we should pay attention to? Because sometimes it's very challenging when we are comparing apples to oranges, and those baseline demographics can impact things a lot.

David Lennon: Yeah, understood. I probably oversimplified the comparison or statement in that.

Loretta Itri: And 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 for patients. Good morning, Ahu, and thank you for that question. As usual, it's a good one.

Loretta Itri: Now, this was compared to a later study of the combination of everolimus and letrozole, in which the response rate in chemo-naive patients was 47%, so not very different from what was seen with platinum and paclitaxel. What was really riveting was the fact that the PFS reported for the platinum-paclitaxel combination was 14 months, which is good, but for the everolimus-letrozole And PFS in this population, where quality of life is extremely important, really was the driver behind the design of our study.

Loretta Itri: Now, because the standard of care has recently changed in recurrent or advanced stage endometrial cancer, we had an opening, a chance, to put this combination on front line 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 the front line treatment for this population. Yeah,

Speaker Change: Uh huh.

David Lennon: As I mentioned, you know, Loretta, I do it too simply; Loretta does it marvelously. So thank you for the question. Do you have a follow-up?

Speaker Change: As I mentioned.

Speaker Change: I do it to simply Loretta does it wonderfully. So thank you for the question do you have a follow up.

Speaker Change: Well one last question I have David if I may are you have two distinct approaches to what I said and that's traveling there. So curious when you talk to the Kols, who many of you so where do you see the most excitement is that for more of the PSC wants to approach agnostic.

Speaker Change: I can I'll stick approach or do you see more of an excitement for the endometrial in Knutsford. There was an indication specific approach.

Loretta Itri: I'll let Loretta comment first and then I'll go. So, first of all, Ahu, they're totally different populations. Remember that for 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.

David: I'll, let the read a comment first and then.

Chris: So first of all on who they are totally different populations remember that Chris.

David: Precision, we are dealing with them sort of a a pan a representation oh specialties. So they don't necessarily talk to each other but the ones who do talk to each other remain really very big.

David: Louis on the fact that we are seeing responses in some of these very sick late stage patients and as games I mentioned is in his commentary.

Loretta Itri: 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, So thank you all for the questions. Operator, next question.

David Lennon: Sure, thanks Dan for the questions. Yeah, so I think, as you point out, we do see that preferential accumulation of serolimus in the NAB serolimus 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 TSC 1 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 monotherapy or in combination for functional tumors with a standard of care.

Loretta Itri: Yeah, 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 I can tell you that the overall survival for the the Combination of Paclitaxel and Cisplatin it was 32 months So, and it was not reported for the Letrozole-Everolimus combination, but if the PFS was 28 months, it ain't that far from 32-month overall survival, so you may assume that it was significantly better.

Loretta Itri: Loretta, thanks. The first question was regarding net trial expectations and any particular tumor types that we might see a better response to.

Loretta Itri: Okay, you want me to answer that? So, yeah, go ahead. Thanks.

David: But to show numbers that would be better in terms of initial response rates.

David: That could guide to kind of that longer term a better outcome for those patients.

And then on the Tacoma sales.

Speaker Change: We don't guide, we haven't provided guidance to the ultimate.

Speaker Change: Potential into coma, what I would say is that Docomo is a very rare indication we're talking two to 300 patients in the U S. In total.

Speaker Change: That means we're finding one in a million.

Speaker Change: Kind of what.

Speaker Change: What we're looking for in terms of finding those patients and getting them to the right treatment setting.

Speaker Change: Many physicians will never see a sarcoma patients and so therefore.

Speaker Change: Our goal is to continue to hunt and find these patients and make sure they're getting to the right of treating physicians. So they can get expose to the potential for napster alignments to support their disease journey.

Speaker Change: 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.

Speaker Change: Thanks that makes sense and I apologize for the innovation requests that had nowhere.

Dan: We take notes as we go so thank you Dan transformation of attention.

Speaker Change: Thank you operator are there any other questions on the line.

Operator: 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.

David Lennon: This concludes today's conference call.