Q4 2023 Aadi Bioscience Inc Earnings Call

Operator: Good day, and thank you for standing by. Welcome to Aadi Bioscience's fourth quarter 2023 earnings conference call. At this time, all participants are in a listen-only mode.

Yeah.

Good day, and thank you for standing by.

Welcome to add Bioscience fourth quarter 2023 earnings conference call.

At this time, all participants on a listen only mode.

Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 1 on your telephone. You will then hear an automatic message indicating that your hand is raised.

After the Speakers' presentation, there'll be a question and answer session.

A question during the session you will need to press star one on your telephone.

Got an automatic message and placing your hangar space leased.

Operator: Please note that this conference is being recorded. I will now turn the call over to Audrey Grose, Head of Corporate Communications for Aadi Bioscience. Ms. Grose, please go ahead.

Note that these compounds being quoted.

I will now turn the call on the two articles head of corporate communications.

Science.

Please go ahead.

Audrey Grose: Thank you. Good morning, and welcome to the Aadi Bioscience conference call to provide an operational update and review results for the fourth quarter and full year 2023. On the call is Dr. Dave Lennon, our President and CEO; Scott Giacobello, our CFO; and Chief Medical Officer, Dr. Loretta Itri. Today, we will provide an overview of operational activity and some financial results for the fourth quarter and full year of 2020. We will open the line for questions at the end of the call following closing comments. 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 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 www.aadibio.com. In addition, any forward-looking statements made on this call represent our views only as of today, We specifically disclaim any obligations to update or revise any forward-looking statements. With that, I'll turn the call over to Dave for his opening statement. Dave?

Thank you good morning, and welcome to the anti Bioscience conference call to provide an operational update and review results of the fourth quarter and full year 2023.

On the call is Dr. David <unk>, our president and CEO, Scott Jacobellis, our CFO and Chief Medical Officer, Dr. Loretta Itchy.

We will provide an overview of operational activity and select financial results for the fourth quarter and full year of 2023.

We'll open the line for questions at the end of the call following closing comment.

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.

Putting 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 SEC Gov or on our website at www Dot antibody O dot com.

In addition, any forward looking statements made on this call represent our views only as of today March 13, 2024, and should not be relied upon as representing our views as of any subsequent date.

Specifically disclaim any obligation to update or revise any forward looking statements.

With that I'll turn the call over to Dave for his opening statement Dave.

David J. Lennon: Morning, everyone, and thank you for joining us today to review our financial and operational results for the fourth quarter and full year of 2020. At Aadi, we are focused on unlocking the full potential of mTOR inhibition by uniquely combining NAP technology with the potent mTOR inhibitor serolime. We believe Napsirolimus has the potential to deliver deeper inhibition and ultimately better outcomes for patients living with cancers that are dependent on the mTOR pathway. And 2023 was a year marked by progress and increasing momentum for the company as we delivered strong execution against both commercial and development goals. First, RO sales remain solid, achieving a cumulative $24.4 million for the full year of 2023, representing a 60% growth over prior years. BRO2 types have penetration in academic and community settings and are considered the preferred treatment for malignant pacoma.

Good morning, everyone and thank you for joining us today to review, our financial and operational results for the fourth quarter and full year of 2023.

At <unk>, we are focused on unlocking the full potential of <unk> inhibition by uniquely combining gnat technology and a potent <unk> inhibitor Sierra lineup.

We believe napster alignment has potential to deliver deeper inhibition and ultimately better outcomes for patients living with cancers that are dependent on the <unk> pathway.

In 2023 was a year marked by progress and increasing momentum for the company as we delivered strong execution against both commercial and development goals.

First <unk> sales remained solid achieving a cumulative $24 $4 million for the full year of 2023, representing a 60% growth over prior year.

<unk> high penetration in the academic and community settings and is considered the preferred treatment for malignant sarcoma.

David J. Lennon: Clinically, a key focus for our organization has been realizing the potential of navisor alignments for patients with solid tumors harboring either TSC-1 or TSC-2 and activating alterations. These types of genetic alterations are thought to activate the mTOR pathway, leading to uncontrolled cell growth, and our PRECISION-1 trial is an interventional study designed to elucidate the potential of Napsirolimus to treat all types As a reminder, the unmet need for TSC1 and TSC2 mutated cancers is sizable, whether considered together or independently, and represents about 2% of all solid tumor cancers. Our latest internal analysis indicates there are approximately 16,000 new patients with these mutations across a variety of tumor types each year in the US alone. With mutations roughly evenly split between genes, each mutation represents a potential multi-billion dollar addressable market for NAPS serolizers. TSC-1 or TSC-2 driven cancers are found across a wide range of tumor types clustering in lung, gastrointestinal, general urinary, breast, and gynecological locations, and are often very difficult to treat.

Clinically a key focus for our organization has been realizing the potential of napster alignments for patients with solid tumors harboring, either <unk> or <unk> and activating alterations beast.

These types of genetic alterations or thought to activate them toward pathway, leading to uncontrolled cell growth in our precision. One trial is interventional study designed to elucidate the potential of napster lineup to treat all types of solid tumors with either of these alterations.

As a reminder, the unmet need in <unk> mutated cancers, a sizeable whether considering together independently and represents about 2% of all solid tumor cancer patients. Our latest internal analysis indicates there are approximately 16000, new patients with these mutations across a variety of tumor types each year in the U S.

Hello.

With mutations roughly evenly split between genes each mutation represents a potential multibillion dollar addressable market for Napster Airlines.

Tier one or tier two driven cancers are found across a wide range of tumor types clustering in lung gastrointestinal general urinate breast and gynecological locations and are often very difficult to treat.

David J. Lennon: We believe PRECISION-1 is a cutting-edge trial testing our innovative therapy, napsirolimus, in these cancers. Although PRECISION-1 is designed as a single trial, each arm is independently evaluated, providing us with the ability to assess one arm separately from the other. Given this design, PRECISION-1 can effectively be viewed as two separate studies, each with its own elements.

We believe precision one is a cutting edge trial testing, our innovative therapy napster alignments in these cancer types.

Now precision one is designed as a single trial each arm independently evaluated providing us with the ability to SaaS one arm separately from the other given this design precision one can effectively be viewed as two separate studies each with its own outcome. In Q4, we provided top line results from a planned interim evaluation of the first 40 patients enrolled in precision one.

David J. Lennon: In Q4, we provided top-line results from a planned interim evaluation of the first 40 patients enrolled in Precision One. These data demonstrated sustained tumor reductions in a heavily pre-treated population based on investigator-assessed responses in the first 40 patients across Baltimore. As a reminder, for the TFC1 arm, 19 efficacy-valuable patients were included in the cutoff date for the interim analysis who had at least one post-baseline scan. We reported an overall response rate of 26%, which was within the range of our expectations.

These data demonstrated sustained tumor reductions in a heavily pretreated population based on investigator assessed responses in the first 40 patients across both arms.

As a reminder, for the TLC one arm 19 efficacy Evaluable patients were included in the cutoff date for the interim analysis, who had at least one post baseline scan. We reported an overall response rate of 26%, which was within the range of our expectations importantly responses appeared to be early deep and durable medium time to response was one.

David J. Lennon: Importantly, responses appeared to be early, deep, and durable. The medium time to response was 1.4 months, and all responses were ongoing at the time of data cutoff. This is especially noteworthy given that this was a heavily pre-treated population with a median of three prior lines of therapy. Lastly, these responses were seen across four different tumor types, supporting a tumor agnostic indication. In the TSC-2 arm, we reported a lower response rate, but given these patients were heavily pre-treated, including 50% who had had at least five prior lines of therapy, these early TSC-2 results are challenging to interpret. Precision One continues to enroll steadily, and we now expect the trial to be fully enrolled by May. We are still on track for our next plant interim readout, which is expected in Q3 of 2024.

Four months at all responses were ongoing at the time of data cutoff.

This is especially noteworthy given that this was a heavily pretreated population with a median of three prior lines of therapy Lastly.

Lastly, these responses were seeing across four different tumor types supporting a tumor agnostic indication.

In the TSA to arm, we reported a lower response rate, but given these patients were heavily pretreated, including 50% who had had at least five prior lines of therapy. These early <unk> results are challenging to interpret.

Precision one continues to enroll steadily and we now expect the trial to be fully enrolled by May we are still on track for our next plant interim readout, which is expected in Q3 of 2024. This readout will include a total of 80 patients who have been followed for a minimum of six months more evaluate the primary endpoint in this study independently assessed overall response rate.

David J. Lennon: This readout will include a total of 80 patients who've been followed for a minimum of six months, and we'll evaluate the primary input in the study, independently assessed, overall response, as opposed to our December analysis, which reported only on investigators. We expect the study to be completed by the end of 2024, with full data in early 2020. In addition to Precision One, enrollment is underway for both of the previously announced Phase II single indication trials for two promising mTOR-driven cancer trials. Overactivation and dysregulation of the mTOR pathway is commonly found in various tumors, and the unique delivery and excellent safety profile of NAB serolimus provide the opportunity to combat these difficult-to-treat cancers. The first trial is evaluating Napsterolimus in neuroendocrine tumors, or NETs. NETs are rare, with approximately 3,500 patients per year.

As opposed to our December analysis, which reported investigator.

We expect the study to be completed by the end of 2024 with full data in early 2025.

In addition to precision one enrollment is underway for both the previously announced phase two single indication trials for two promising <unk> driven cancer targets.

Overactor nation and Dysregulation of the <unk> pathway is commonly found in various tumors and unique delivery and excellent safety profile of Napster lineup provides the opportunity combat these difficult to treat cancers.

The first trial is evaluating napster alignment and neuroendocrine tumors or.

<unk> is a rare with approximately 3500 patients per year net of historically had a lower spot rate.

To treatment with oral rap allowance and other agents, which nonetheless are used clinically and recommended treatment guidelines today.

In preclinical animal models <unk> demonstrated improved target suppression relative to other end tourists warning further exploration of <unk> in this indication.

We're excited about this trial because it provides the opportunity to demonstrate what we believe is <unk> best in class efficacy and then known <unk> sensitive tumor type.

David J. Lennon: NETs have historically had a low response rate to treatment with oral rapalogues and other agents, which nonetheless are used clinically and recommended in treatment guidelines today. In preclinical animal models, Napsirolimus demonstrated improved target suppression relative to other mTORs, warranting further exploration of Napsirolimus in this indication. We're excited about this trial because it provides the opportunity to demonstrate what we believe is NAPS serolinase's best in class efficacy in a known mTOR sensitive tumor. The second trial we started last year is evaluating the therapeutic potential of Napster alignments in advanced and recurrent endometrioid-type endometrial cancer in combination with an aromatase inhibitor. 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.

The second trial, we started last year is evaluating the therapeutic potential of napster alignments and advancing our current endometrial type endometrial cancer in combination with aromatase inhibitor Letrozole Andrew.

Andrew Metrial cancer is the most common cancer of the female reproductive tract and one of the few cancers with increasing mortality.

There is an estimated 10000 cases of <unk> diagnosed annually in the U S alone prior clinical studies of the <unk> inhibitors combined with electric so ill have yielded promising results and recent changes in our recommended standard of care for early stage disease creates a potential opportunity for our combination to be used in these first and second line settings.

Both of these open label studies are actively enrolling and we plan to present initial data later this year.

Rounding out our clinical development program. We also have an ongoing trial with combination of our ice K Ras inhibitor in lung cancer and other solid tumors.

With a solid commercial foundation provided by our robust in both clinical development program spanning genetically driven tumors and other <unk> sensitive tumors and a cash runway into Q4 2025, we are well positioned to realize our ambition of becoming a multi indication precision oncology company.

Scott M. Giacobello: Prior clinical studies of the 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 R-combination to be used in these first and second line settings. Both of these open-label studies are actively enrolling, and we plan to present initial data later this year. Rounding out our clinical development program, we also have an ongoing trial with a combination of Maradi's KRAF inhibitor and lung cancer and other solid tumors. With a solid commercial foundation provided by FIARA, a robust and bold clinical development program spanning genetically driven tumors and other mTOR sensitive tumors, and a cash runway into Q4 2025, we are well positioned to realize our ambition of becoming a multi-indication precision I will now turn the call over to Scott for updates on our financial progress. Scott.

I'll now turn the call over to Scott for updates on our financial progress Scott.

Thanks, Dave.

We had a solid fourth quarter and ended 2023 with $108 $8 million in cash cash equivalents and short term investments.

In early 2024, we implemented measures to streamline our operations and reduce costs, which included head count reductions and our customer facing operations and corporate functions.

Following these measures we anticipate that our balance sheet will fund operations into Q4 2025 based on current plans.

<unk> net product sales were $6 3 million for the fourth quarter, representing 6% growth over Q3, 2023, and 21% over the prior year quarter.

Full year <unk> sales were $24 4 million, an increase of 60% over prior year sales of $15 2 million.

Scott M. Giacobello: Thanks, Dave. We had a solid fourth quarter and ended 2023 with $108.8 million in cash, cash equivalents, and short-term investments. In early 2024, we implemented measures to streamline our operations and reduce costs, which included headcount reductions in our customer-facing operations and corporate functions. Following these measures, we anticipate that our balance sheet will fund operations into Q4 2025, based on our current budget. BioraNet product sales were $6.3 million for the fourth quarter, representing 6% growth over Q3 2023 and 21% over the prior year quarter. Full year FIRO sales were $24.4 million, an increase of 60% over prior year sales of $15.2 million. Research and development expenses for the quarter increased to $12.8 million compared to $9.4 million in the prior year quarter.

Research and development expenses for the quarter increased to $12 8 million compared to $9 4 million in the prior year quarter.

For the year R&D expenses amounted to $48 $9 million.

Compared to $32 $7 million last year.

This increase was prior and primarily related to the continued progress of the ongoing precision <unk> trial and initiation of the programs in endometrial cancer and nuts.

Selling general and administrative expenses for the fourth quarter were $10 3 million.

Compared to $11 1 million in the same period in 2022.

For the year SG&A expenses totaled $44 5 million compared to $40 2 million in the prior year.

This increase is due primarily to higher legal and company infrastructure costs and increased marketing expenses related to <unk>.

Net loss for the fourth quarter was $16 3 million compared to $13 9 million in the fourth quarter of 2022.

Scott M. Giacobello: For the year, R&D expenses amounted to $48.9 million compared to $32.7 million last year. This increase is primarily related to the continued progress of the ongoing PRECISION-1 trial and the initiation of the programs in Endometrial Cancer and NET. Selling general administrative expenses for the fourth quarter were $10.3 million, compared to $11.1 million in the same period in 2022. For the year, SG&A expenses totaled $44.5 million, compared to $40.2 million in the prior year.

Net loss for the year was $65 $8 million compared to $60 5 million in the prior year.

For more information on our financial performance for 2023, a detailed discussion of the results reported on this call will be provided in our 10-K to be filed later today.

I'll now hand, the call back to Dave for his closing comments.

Thank you Scott I'm, so proud of the progress we made in Q4 and what the team accomplished in 2023.

<unk> remains a valuable asset with sustained demand to help meet the needs of patients with Tacoma.

We're making tremendous progress against our clinical development plans with two sizable markets in PSC, one in tier II and activating alterations as well other inventory driven cancers.

Scott M. Giacobello: This increase is due primarily to higher legal and company infrastructure costs and increased marketing expenses related to FIRO. Net loss for the fourth quarter was $16.3 million compared to $13.9 million in the fourth quarter of 2022. Net loss for the year was $65.8 million compared to $60.5 million in the prior year.

We're looking forward to sharing the two thirds interim analysis from precision one in the third quarter with full enrollment expected in may.

Study completion by the end of 2024.

We can now open the line for questions operator.

Thank you, ladies and gentlemen ask the question.

We'll need to press star one on your telephone and wait for your name to be announced to withdraw your question simply questioner one again please.

David J. Lennon: For more information on our financial performance for 2023, a detailed discussion of the results reported on this call will be provided in our 10-K to be filed later today. I'll now hand the call back to Dave for his closing comments.

Please standby, while we compile the Q&A roster.

Yes.

And our first question coming from the line of.

Joe Catanzaro with Piper Sandler Your line is open.

Yes. Thanks.

I appreciate you taking the questions here, maybe first one I know the first 40 patients.

Characterize as being very heavily pretreated. So wondering if you have any.

David J. Lennon: Thank you, Scott. I'm so proud of the progress we made in Q4 and what the team accomplished in 2023. VR remains a valuable asset with sustained demand to help meet the needs of patients with comas.

Visibility you updates around what the remainder of the trials look like.

And maybe along these lines, whether you've seen any change in enrollment dynamics in any way since.

Since the interim data disclosure, thanks, and I have one follow up.

Great Joe. Thank you for the question I appreciate it.

Talking more about precision one yes.

Operator: 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. We're looking forward to sharing the two-thirds interim analysis from precision one in the third quarter with full enrollment expected in May and study completion by the end of 2020. Operator.

Yes. So the first 40 patients were heavily pre treated we saw three or more lines of prior therapy as those patients enrolled in that first 40 group.

We anticipate by the trial design that this is we're going to get a number of late line patients patients have to have.

Satisfied that criteria for the indication that they enroll in in terms of being having received all appropriate standard of care prior to their entry and treatment with <unk>.

Operator: Thank you. Ladies and gentlemen, to ask a question, you will need to press star 1 1 on your telephone and wait for your name to be announced.

Operator: To withdraw your question, simply press star 1 1 again. Please stand by while we compile the Q&A roster. And our first question, coming from the line of... Joe Catanzaro, Wood Piper, Sam Lurie, Yolanda Selpin... Yeah, thanks. I appreciate you taking the questions here. Maybe the first one.

Napster alignment in our trial and so we anticipate it continuing to enroll later line patients within the trial I wouldn't comment on the overall nature of what we're going to end up with we're still enrolling patients in the trial and we'll obviously report out the next or the total 80 patients at the two thirds interim.

Later this year.

David J. Lennon: I know the first 40 patients were characterized as being very heavily pre-treated, so I'm wondering if you have any visibility or updates around what the remainder of the trials look like. And maybe, along these lines, whether you've seen any change in enrollment dynamics in any way since... Great, Joe, thank you for the question. I always appreciate talking more about Precision One.

Okay. Thanks, and then.

Maybe unrelated to precision one wondering if there are any.

Early expectations around when you could report initial data from the endometrial or net studies I. Appreciate those are still in early days and then any updates on the AD aggressive combo trial I'm wondering maybe if theres been any changes there with.

At aggressive acquisition by.

David J. Lennon: Yes, so the first 40 patients were heavily pre-treated. We saw three or more lines of prior therapy as those patients enrolled in that first 40 group. We anticipate, right, by the trial design that this is, we're going to get a number of late-line patients. However, patients have to have satisfied the criteria for the indication that they enroll in, in terms of having received all appropriate standard of care prior to their entry and treatment with Napsirolimus in our trial. And so we anticipate continuing to enroll later-line patients within the trial. But I wouldn't comment on the overall nature of what we're going to end up with.

But by Bristol. Thanks.

Yes.

So great questions I think I mentioned earlier that we do anticipate potentially sharing data on endometriosis.

Trio or neuroendocrine trial later this year those are open label single arm Phase II studies, and we have the opportunity to enroll those will share the data when we think it's appropriate and we have something meaningful to say about how that data is those patients are enrolling in that data is maturing I'm.

I'm happy to say the pace. Both studies are actively enrolling patients and theres a good engagement with the community on generated patients for each of those trials, which we just think is.

Initially a great sign in terms of folks interests.

These.

David J. Lennon: We're still enrolling patients in the trial, and we'll obviously report out the next or the total 80 patients at the two-thirds interim later this year. Okay, thanks, and related. I'm wondering if there are any early expectations around when you could report initial data from the endometrial or NET studies; I appreciate those are still in the early days. And then any updates on the adagrassive combo trial, wondering maybe if there's been any changes there with... at Aggressive Acquisition by Bristol. Yep.

Therapeutic regimens and each of those indications.

And then on the.

Marathi BMS collaboration.

That continues and is ongoing we are enrolling patients into that trial and we don't have any further updates at this point.

Okay. Thanks, that's helpful and thanks for taking my questions.

Thanks, John.

Thank you.

Our next question coming from the line of Liang Chen with Jefferies. Your line is open.

David J. Lennon: So, great questions. I think I mentioned earlier that we do anticipate potentially sharing data on endometrial or neuroendocrine trials later this year. Those are open-label, single-arm phase 2 studies, and we have the opportunity to enroll those. We'll share the data when we think it's appropriate and we have something meaningful to say about how that data is – those patients are enrolling, and that data is maturing. I'm happy to say both studies are actively enrolling patients, and there's good engagement with the community on generating patients for each of those trials, which we just think is, initially, a great sign in terms of folks' interest in these therapeutic regimens in each of those indications. And then on Maradi, you know, BMS collaboration that continues and is ongoing. We are enrolling patients into that trial, and we don't have any further updates. Okay, thanks, that's helpful. Thank you. And our next question coming from the lineup, Liang Cheng with Jefferies, your line is open. Sure, thank you. This is Leon, for Roger.

Sure. Thank you.

Downpour Roger.

So thank you for taking my question I guess from US we have two questions one round of firewall.

<unk> in the coming year.

Can you provide us any.

Detailed guidance.

Or perhaps you're applying.

Second question is about.

I know you guys has been dropping with FDA about.

Hello tumor agnostic so what.

In your understanding of what the most important thing for FDA to consider label asset agnostic.

No.

Great. Thank you Liang and thanks for stepping in for Roger.

So maybe in terms of Sierra outlook, maybe I'll turn it over to Scott to talk a little bit about that and then we'll talk about your your second question was more but Scott do you want to just comment on.

Our outlook for the coming year.

Sure absolutely yeah. Thanks for the question, Yes, I think for <unk> I mean, as you're seeing I mean, we're not going to provide guidance.

For this year I think what you've seen over the last few quarters.

Sales stabilizing.

Around the $6 million.

Mark or slightly above and I think so.

The expectation there is.

We continue to be.

Excited about that.

Operator: So thank you for taking our questions. I guess from us, we have two questions. One is about FIARO.

<unk> has a potential to grow there, but I think that over the last few quarters, you've seen the sales stabilizing in that.

Six $6 $5 million range, and I think thats, what we would expect for 2024.

Operator: So guess for FIARO in the coming year, you know, can you provide us any Details, Guidelines, or Commercial Plans. Second question is about, you know, I know you guys have been interacting with the DEA about the tumor agnostic. So, you know, in your understanding, what's the most important thing for FDA to consider on a label? Thank you. Great, thank you, Liang. And thanks for stepping in for Roger.

Thanks, Scott It is it.

It is a very team has done a great job penetrating the market here we are.

<unk> and preferred for pet coma in the first line setting and widely recognized as the preferred therapy for Karma. It is just an ultra rare population and ultimately we may be reaching saturation of that market.

And expect more incremental growth from here on now.

Scott M. Giacobello: So maybe, in terms of FIERA Outlook, I'll turn it over to Scott to talk a little bit about that, and then we'll talk about your second question a little more. But Scott, you want to just comment on the FIARA Outlook for the coming year. Sure, absolutely. Yeah, thanks for the question, Liang. Yeah, I think for FIARO, I mean, as you've seen, we're not going to provide guidance for this year. I think what we've seen over the last few quarters, you know, the sales stabilizing around the $6 million mark or slightly above, and I think so, the expectation there is, you know, we continue to be excited about FIARO and the potential to grow there. But I think that over the last few quarters, you've seen the sales stabilizing in that, you know, six to six and a half million dollar range.

And then your second question was on.

What are the most important considerations when we think about the Fda's view on the tumor agnostic indication I'm going to turn it over to Loretta.

To give her thoughts on.

How we think or how we interpret the fda's guidance around the tumor agnostic indication, what's most important there. So do you want to comment.

I'm sure I'll be happy to.

I think.

From what we have seen recently.

Perhaps the most important.

Most important thing that the agency wants to see and tumor agnostic studies is a a variety of different tumor types.

What they do not want in a tumor agnostic study is to see concentrations.

Information in certain sub types of patients. They are looking for a representation of the mutation across a variety of different tumor types that that is why you do a tumor agnostic study. So I think that that is perhaps the <unk>.

David J. Lennon: And I think that's what we would expect for 2020. Thanks, Scott. It is, you know, Liang, it is a very, team's done a great job penetrating the market here. You know, we're available and preferred for PECOMA in the first line setting and widely recognized as the preferred therapy for PECOMA. It is just an ultra-rare population.

Our most important element in terms of their determination.

Regarding whether or not it's rod.

Classifieds for tumor agnostic approval and then of course I think they are looking for.

Loretta M. Itri: And ultimately, we may be reaching saturation in that market and expect, you know, more incremental growth. And then your second question was about what are the most important considerations when we think about the FDA's view on the tumor agnostic indication. I'm going to turn it over to Loretta to give her thoughts on how we think or how we interpret the FDA's guidance around the tumor agnostic indication and what's most important. Loretta, do you want to comment? I'm sure I'd be happy to. From what we have seen recently, perhaps the most important thing that the agency wants to see in tumor agnostic studies is a variety of different tumor types. What they do not want in a tumor agnostic study is to see concentrations of information in certain subtypes of patients.

Sure.

A reasonable response rate and of course, a good safety profile in our case since we already have approval in a single indication I think they would be looking to see that the safety profile.

The agnostic.

Population.

Closely resembles what we see.

<unk> seen in Tacoma.

Thanks Loretta.

And just to add onto what Loretta was saying what we saw so far we have enrolled a very diverse tumor population within our trial and think you saw that even in the early results.

Where we had a kind of broad distribution of tumor types that we shared.

Loretta M. Itri: They are looking for a representation of the mutation across a variety of different tumor types. That is why you do a tumor agnostic study. So I think that that is perhaps the single most important element in terms of their determination regarding whether or not a drug classifies for tumor agnostic approval. And then, of course, I think they are looking for a reasonable response rate and, of course, a good safety profile.

Back in December.

Thanks for the questions and I think if there's no follow ups, we can move to the next.

Got it. Thank you thank you Christian.

Thank you.

Thank you.

As a reminder, ladies and gentlemen to ask a question. Please press star one on your telephone and our next question coming from the line of <unk>.

With Ladenburg Your line is now open.

Sure.

Good morning. Thank you so much for taking my questions I have two questions.

Loretta M. Itri: In our case, since we already have approval in a single indication, I think they would be looking to see that the safety profile in the agnostic population closely resembles what we have already seen in Tacoma. Thanks, Loretta. And just to, you know, add to what Loretta was saying, what we've seen so far, we have enrolled a very diverse tumor population within our trial. And I think you saw that even in the early results, where we had a kind of broad distribution of tumor types that we shared back. Thanks Liang for the questions, and I think if there are no follow-ups, we can... Thank you. Thank you. I appreciate it.

Follow up to John's question regarding endometrial cancers.

One could you give us a sense of the.

Hi, <unk>, how many sites are open and inclusion and exclusion criteria for the patients.

And what are you expecting to see this year.

Many patients already heavily pre treated if you can provide a little bit color that would be great.

Sure I think so.

Happy to answer those questions I'm going to turn it over to the right effort.

Some of the details but at the same time, we probably wouldnt discuss number of sites or a number of patients at this point just given where we are in the trial and it is active and were kind of continuing to build.

Operator: Thank you. And as a reminder, ladies and gentlemen, to ask a question, please press star one on your telephone. And our next question, coming from the line of Ahu Demir with Lettenberg, is open. Good morning. Thank you so much for taking my questions. I have two questions.

That story.

But maybe just in the design of the trial and what we might expect to see later this year, let Loretta give.

I'll give you an update there.

Got it.

Good morning, Andrew always great questions as usual coming from you.

Ahu Demir: A follow-up to Joe's question regarding endometrial cancers. One, could you give us a sense of the types open, how many types are open, and inclusion and exclusion criteria for the patients? And what are we expecting to see this year? How many patients? Are they heavily pre-treated? If you can provide a little bit of color, that would be great.

So basically this is an open label phase two study looking to evaluate the combination of Napster Allen Ms with Letrozole.

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Advanced Unresectable stage three or four.

David J. Lennon: Sure. I think, so Ahu, we're happy to answer those questions. I'm going to turn it over to Loretta for some of the details. But at the same time, we probably wouldn't discuss the number of sites or the number of patients at this point, just given where we are in the trial, and it is active, and we're kind of continuing to build that story. But maybe just in the design of the trial and what we might expect to see later this year, I'll let Loretta.

Or recurrence.

Dmitry like endometrial carcinoma.

Patients will have received either no or one prior line of chemotherapy. So this is a this is a population of patients who are relatively early in their treatment course.

Just somewhat differentiated of course from what we're doing in precision.

So patients are treated with the same dose.

Loretta M. Itri: I'll give you an update there, Loretta. Good morning, Ahu. Always great questions, as usual, coming from you. So basically, this is an open-label phase two study looking to evaluate the combination of nabsorolimus with letrozole in patients who have advanced and that would be advanced or unresectable stage three or four or recurrent endometrioid endometrial carcinoma. Patients will have received either no or one prior line of chemotherapy. So this is a population of patients who are relatively early in their treatment course, which is somewhat differentiated, of course, from what we're doing in precision. Patients are treated with the same dose of nabsirolimus as they were in Tacoma; that is a well-established and safe dose.

Naps around this is Jay.

They were in Tacoma that is a well established and safe dose.

And.

Sure.

I think.

Pretty much that this is a Simon two stage study so we.

Plan to enroll the first cohort.

We anticipate since this is an open label study.

April to report out.

Early results.

By the end of this year.

Does that address your question on who would you like more detail.

This is great. Thank you so much low right. So this is very helpful and thank you for your comp for Linzess.

Loretta M. Itri: I think pretty much that this is a Simon two-stage study, so we plan to enroll the first cohort and we anticipate, since this is an open-label study, being able to report out early results by the end of this year. Does that address your question, Ahu, or would you like more detail? This is great. Thank you so much, Loretta. This is very helpful, and thank you for your compliments as well. I have one more conceptual question for you, Loretta, if I may. So, you mentioned mTOR-sensitive tumors. Besides TSC1 and 2, could you comment on what other mutational backgrounds are sensitive to mTOR inhibitors? Well, I think that's quite a difficult question because I think there are many mutations along the mTOR pathway that may provide targets. However, I don't think that any of those specifically has been identified as a specific mutational target for mTOR inhibition. There are suggestions, but I don't think any of those are proven.

I have one more conceptual question to you Laura if I might.

So you mentioned amcor sensitive tumors.

PSC wanted to could you comment on what other mutational backgrounds versus jetson employing <unk>.

Well I think that's that's quite.

Difficult question because.

I think there are there are many mutations along into our pathway that may provide.

And that May provide targets. However, I don't think that any of those specifically has been identified.

As a.

As a specific mutation on target for.

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Or are there are suggestions that I don't think any of those are proven.

Very helpful. Thank you so much.

Youre most welcome.

Thanks Alan.

Operator are there any other questions.

And I see no further questions in the queue. At this time I will now turn the call back over to you Dr. Lin for any closing remarks.

Thank you operator.

Thank you everyone for joining the call today I think as you see we are delivering on the operational goals. We have set for both 2023 and looking ahead into 2024, we're very confident on our ability to deliver against our number one priority, which is the precision one trial.

Loretta M. Itri: Very helpful. Thank you so much. You're most welcome. Thanks. Operator, are there any other questions?

Operator: And as we have no further questions in the queue at this time, I'll now turn the call back over to you, Dr. Dave Flynn, for any closing remarks. Thank you, Operator. And thank you, everyone, for joining the call today. I think, as you see, we are delivering on the operational goals we have set for both 2023 and looking ahead into 2024. We're very confident in our ability to deliver against our number one priority, which is the Precision I trial, and we look forward to providing an update on that two-thirds interim phase later this year and finishing that trial within 2024. We're also excited about the new programs we mentioned today and got to discuss a little bit in the Q&A, and look forward to providing updates on both our NET, in vitro trials early this year. At the same time, we remain really confident in the continued progress we're making in the Pacoma market with VRO. This is an ultra-orphan indication, and we're highly penetrated within that market, and that continues to deliver solid sales for us as we go forward.

And we look forward to providing an update on that two thirds interim later this year and finishing that trial within 2024. We're also excited about the new programs, we mentioned today and that got to discuss a little bit in the Q&A.

Forward to providing updates on both our net and endometrial trials later this year.

At the same time, we remain really confident in the <unk>.

Continued progress, we're making in and become a market with Piero. This is an ultra orphan indication and we're highly penetrated within that market and that but that continues to deliver solid sales for us as we go forward.

Overall, otherwise thank you all for your time and attention today and we look forward to the next update with you all thank you.

Have a great day.

Ladies and gentlemen that does conclude our conference for today. Thank you for your participation you may now disconnect.

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David J. Lennon: Overall, otherwise, I thank you all for your time and attention today, and we look forward to the next update. Thank you. Have a great day. Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect. www.circlelineartschool.com

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Dan.

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