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spk02: Good day, and thank you for standing by. Welcome to the Addi 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 the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. 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 Addi Bioscience. Ms. Gross, please go ahead.
spk18: Thank you.
spk19: Good morning and welcome to the Addi 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 AddiBioScience website at addibio.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 adibio.com. In addition, any forward-looking statements made on this call represent our views only as of today, August 7th, 2024, and should not be relied upon as representing our views as of any subsequent date. We specifically just claim any obligation to update or revise any forward-looking statements. On the call is Dr. Dave Lennon, our President and CEO, Scott Giacobbello, 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?
spk09: 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 Adi's story, where we are today, and where we're going in the weeks and months ahead. On slide five, you'll see at ADI, 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 FIARO for the treatment of advanced malignant pachoma, an ultra-rare soft tissue sarcoma with poor outcomes and high biological evidence of the mTOR pathway activation. FIARO has cemented its position as preferred treatment for malignant pachoma 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 FIARO has had and will continue to have for patients with this rare and aggressive cancer. Building on this commercial backbone, we're also exploring napserolimus for larger indications across multiple types of mTOR-driven tumors. 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 inactivating alterations. This trial is fully enrolled and expected to complete by the end of the year. In a moment, I'll talk more about PRECISION-1 and the opportunity it represents for patients and providers. We're also evaluating nabsterolimus 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's an estimated 10,000 cases of EEC diagnosed annually in the U.S. alone. 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 creates a potential opportunity for this combination to be used in the first and second line settings. The second trial is in neuroendocrine tumors of lung, gastrointestinal tract, and pancreas. Neuroendocrine tumors, or NETs, are rare and have a historically low response rate to treatment with oral rapalogs and other agents, which nonetheless are used clinically and recommended in treatment guidelines. In preclinical animal models, NAPSER alignments demonstrated improved target suppression relative to other mTORs, warranting further exploration of NAVSTAR alignments in this indication. These Phase II open-label studies are both enrolling well, and we look forward to presenting initial data from these trials later this year. ADI is led by an accomplished team with deep expertise and a track record of responsible capital management. With sustained commercial success of FIARO, cash runaway is anticipated to extend into Q4 2025, with a catalyst-heavy 2024 and 2025 ahead of us. We believe ADDIE 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 TSC1 or TSC2 inactivating alterations. As of May, the trial has fully enrolled 120 patients across a broad array of tumor types. TSC1 or TSC2-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-1 is a single trial, 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-1 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. 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, Napserolimus is the last available line of systemic therapy for these patients and truly tests the ability of Napserolimus 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. 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 rate. Now looking at 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. These data demonstrated sustained tumor reductions in a heavily pretreated population based upon investigator-assessed responses across both arms. For TFC1, we reported an investigator-assessed overall response rate of 26%, which was within the range of our expectations. These responses appear to be early, deep, and durable, which is especially noteworthy given this heavily pretreated population with a medium 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 11% overall response rate. This arm had a medium 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 erinolimus 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 of treatment. I also want to highlight that ongoing conversation with experts reinforced this view. 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-1 closely follows the most up-to-date guidance from regulators on how they would like to see tumor agnostic studies for targeted therapies run. 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 inactivating alteration. By design, PRECISION-1 will not have more than 25% contribution 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. 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 mutations. Now looking at the market opportunity on slide 9, TSC1 and TSC2 mutations define a large mutation-driven oncology population with broad distribution amongst tumor indications and specialty Our latest internal analysis indicates there's 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 decisions. There are some populations in particular for whom NGS testing is more common, so-called high NGS testing specialties. 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 cancers. According to our research with a product profile similar to our interim results to date, high NGS testing specialties indicate they would be likely to use napserolimus after second- and third-line preferred treatments, which aligns with what we observed in Precision 1. We anticipate that market adoption would 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 treatment options. Even if we limit the majority of NAV serolimus utilization to be in the third line with these high NGS testing segments, TSC1 and TSC2 mutated cancers would represent a significant $300 million to $600 million projected market opportunity in the U.S. alone. So if Precision 1 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 Napserolimus beyond the coma. With that, I'll now turn it over to Scott for updates on our Q2 financial progress. Scott? Thanks, Dave.
spk22: Looking at slide 11 and starting with FIARO, BioroNet 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. 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. 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 that 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 Precision 1 trial and the programs in endometrial cancer and NETs. 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 right-sizing 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.
spk09: 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 TSE1 and TSE2 inactivating 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 1 later this quarter, and if appropriate, sharing those data with the FDA thereafter. We expect to complete Precision 1 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 Precision 1, 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.
spk21: Operator?
spk02: As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. And our first question comes from Roger Song with Jefferies. Your line is now open.
spk11: Great. Thanks for the update and taking our questions. Maybe we first talk about the precision, Dave, if we may. You know, 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 TSC 1 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 what would be the key topics there and then what could be the potential outcome out of the FDA discussion of the second interim as a follow-up. Thank you.
spk09: Sure. Thanks, Roger. I'll make a couple comments and ask Loretta if she has anything she'd like to add. Our precision one outcome in Q3 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, you know, draw any anticipation in terms of the direction of what 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, 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, 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. Roberta, anything you would add to that?
spk15: No, Dave, I think you covered it nicely. Thank you.
spk11: Got it. Yeah, thank you. And then, you know, since the enrollment for the EEC and the NET phase studies going pretty well. And then just curious, what should we expect from the latest year initial data update? Would that be focusing on maybe some of the safety, turbidity, 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.
spk09: Yeah, I'll let Loretta start by commenting on where we are with those trials, and I can follow up if there's anything to add. So, Loretta, why don't you comment on this?
spk15: Sure. Thanks, Dave, 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 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 fulsome 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 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.
spk09: 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 serolimus, which will be, you know, something we'll bring forward as we look at that data, dependent on, you know, the patient that we enroll in these early trials.
spk15: 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.
spk09: Thanks, Roger. Can we move on to the next set of questions?
spk02: Thank you. Our next question comes from Joe Catanzaro with Piper Sandler, your line is open.
spk05: Hey, guys. Thanks for taking my questions here. Maybe following up a bit on sort of what happens post the second two-thirds interim analysis here and the range of outcomes, I'm wondering if there's any scenario in which the design and execution of the remainder of Precision 1 is altered or changed in 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.
spk09: 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 good position on the full trial enrollment in terms of the 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're 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.
spk05: Okay, got it. That's helpful. There may be one quick one on Faiyaro. I know you maybe previously have spoken to, you know, expect patients 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.
spk09: Yeah, I do want to highlight that, you know, we did have a low Q1, which, you know, we Disgust likely was being 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 that's being sustained as we go into the next quarter. And that, you know, we're seeing from a demand perspective, you know, 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. And so we remain very positive on the outlook for continued incremental growth in the business in Q3 and Q4 of this year.
spk05: Okay, great. That's helpful. Thanks for taking my question.
spk06: Thanks, Joe. Next question, operator.
spk02: Thank you. Our next question comes from Tara Bancroft with TD Cowan. Your line is open.
spk24: Hi, this is Greg Wiesner on behalf of Tara Bancroft. So the – oh, sorry – 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.
spk09: Sure, Greg. Thanks for the question. This is, as I pointed out, I think, and we tried to discuss deeper in the slides, this is truly a tumor-agnostic approach. 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, you know, 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, you know, we submit and gain approval around that. And we don't, 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 any, 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 sensitive.
spk24: Okay, wonderful. Thank you. 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?
spk09: Yeah, we would imagine this will be a company presentation at this point. Great.
spk02: Thanks, Greg. Thank you. Go ahead, Daniel. Our next question comes from Ahu Damir with Lautenberg Thalmann. Your line is open.
spk17: Thank you very much for taking my question and 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 that 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?
spk09: 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 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.
spk17: Nice. It makes sense. And my second question is on the endometrial cancer program. You did mention the biggest idea of the trial is to compare it to the other mTOR inhibitors, and the patient baseline demographics can impact the trial results. significantly. So what was 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 because sometimes it's very challenging when we are comparing apples to oranges and baseline demographics can impact a lot.
spk09: Yeah, understood. I probably oversimplified the comparison or 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. So, Loretta?
spk15: Sure, Dave. Good morning, Ahu, and thank you for that question. As usual, it's a good one. The design of the EEC study was largely based on an earlier study that was performed by GOG, the gynecologic oncology group. This was 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 and 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 study. 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 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.
spk16: Yes, definitely. Thank you, Loretta. Okay.
spk09: Thanks a lot. As I mentioned, you know, I do it too simply. Loretta does it wonderfully. So thank you for the question. Do you have a follow-up?
spk17: Well, one last question I have, Dave, if I may. You have two distinct approaches to assess NAB3 elements. So curious, when you talk to the KOL community, so where do you see the most excitement? Is it for more of the TSE 1.2 approach or which diagnostic approach or do you see more of an excitement for the endometrial and NET where there's an indication-specific approach?
spk08: I'll let Loretta comment first and then... Okay.
spk15: So, first of all, 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. 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.
spk09: I think that's a great summary of it, Loretta, from firsthand experience. I would say we also went out with the TSC 1 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, you know, 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 have progressed through multiple lines of therapy. And we had excellent reactions to the profile of nabsterolimus, especially amongst folks who are familiar with the mTOR pathway and or doctors who have seen this product in the coma setting. So thank you all for the questions. So operator, next question.
spk02: Thank you. Our next question comes from Robert Burns with HC Wainwright. Your line is now open.
spk04: Good morning. This is Dan on Parag. Thanks for taking our question. We wanted to ask, given the data demonstrating preferential tumor uptake for NAV serolimus versus, excuse me, TEN serolimus 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.
spk09: Sure. Thanks, Dan, for the questions. Yeah, so I think as you point out, you know, 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 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 think it's premature for us to comment on 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.
spk03: Thanks. That makes sense.
spk04: 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. Finish. Do you also have an updated view on what maximum sales and the PCOMAs could look like in the United States and around what that would be? I'm curious on the Paclitaxel versus Everlinus trials. How did those overall survivals compare back in the day?
spk07: Yeah, I'll let Loretta take the first question. Go ahead.
spk15: Okay, so I'll take the last question first because there were so many questions I kind of forgot what the earlier ones were. But I can tell you that the overall survival for the patients 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.
spk09: Loretta, thanks. The first question was in regards to the net trial expectations and any particular tumor types that we might see better responses.
spk14: Okay, you want me to answer that? Yeah, go ahead.
spk23: Thanks. If you could add.
spk15: So I wasn't clear with the question whether you were talking about subtypes of nets because nets 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 nets is going to have a better response rate. We just don't have enough information at this point in time.
spk09: Yep. And, Dan, if I can add on the net trial, you know, historically, mTOR inhibitors have been utilized in the setting for neuroendocrine tumors. The reality is that those i mean those approvals were driven off of uh progression pre-survival benefit that was demonstrated nets can be quite indolent and long-lasting um and there but there is benefit that has been derived from ntor inhibitors in terms of extending uh time on treatment for those patients relative to other approaches the reality is though that those um try those uh prior mTOR inhibitor trials show very low overall response rate, so often in the single-digit setting. And we think an early indication of the potential of our mTOR inhibitor would be to show superior or not superior, 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 Pacoma sales, we don't guide, we haven't provided guidance to the ultimate potential in Pacoma. What I would say is that Pacoma is a very rare indication. We're talking two to 300 patients in the U.S. in total. That means we're finding, you know, 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 Pacoma patient. And so therefore, You know, 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 nebcerolimus 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 and, you know, consistently is that, you know, we do believe we've penetrated most of the marketplace at this point and any further growth will be incremental.
spk04: Thank you. That makes sense. And I apologize for the inundation of questions. No worries. We take notes as we go. So thank you, Dan.
spk13: I apologize for my short attention span.
spk09: Thank you. Operator, are there any other questions on the line?
spk02: 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.
spk09: 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.
spk02: This concludes today's conference call. Thank you for participating. You may now disconnect. Thank you. you Thank you. Bye. Bye. Good day, and thank you for standing by. Welcome to the Addi 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 the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. 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 Addi Bioscience. Ms. Gross, please go ahead.
spk18: Thank you.
spk19: Good morning and welcome to the Addi 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 Addi Bioscience website at addibio.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 adibio.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 as of any subsequent date. We specifically just claim any obligation to update or revise any forward-looking statements. On the call is Dr. Dave Lennon, our President and CEO, Scott Giacobbello, 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 statements. Dave?
spk09: 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 ADI's story, where we are today, and where we're going in the weeks and months ahead. On slide five, you'll see at ADI, we are focused on unlocking the full potential of mTOR inhibition by uniquely combining NAB technology and the potent mTOR inhibitor, serolimus. With more complete mTOR target inhibition, greater tumor suppression, and a wider therapeutic index, We believe Napsir-Limus 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 FIARO for the treatment of advanced malignant pachoma, an ultra-rare soft tissue sarcoma with poor outcomes and high biological evidence of the mTOR pathway activation. FIARO has cemented its position as preferred treatment for malignant pachoma 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 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 napserolimus for larger indications across multiple types of mTOR-driven tumors. 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 inactivating alterations. This trial is fully enrolled and expected to complete by the end of the year. In a moment, I'll talk more about Precision-1 and the opportunity it represents for patients and providers. We're also evaluating nabsterolimus 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's an estimated 10,000 cases of EEC diagnosed annually in the U.S. alone. 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 creates a potential opportunity for this combination to be used in the first and second-line settings. The second trial is in neuroendocrine tumors of lung, gastrointestinal tract, and pancreas. Neuroendocrine tumors, or NETs, are rare and have a historically low response rate to treatment with oral rapalogs and other agents, which nonetheless are used clinically and recommended in treatment guidelines. In preclinical animal models, Napsur-Limus demonstrated improved target suppression relative to other mTORs, warranting further exploration of Napsur-Limus in this indication. These Phase II open-label studies are both enrolling well, and we look forward to presenting initial data from these trials later this year. Addy is led by an accomplished team with deep expertise and a track record of responsible capital management. 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 Addy 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 TSC1 or TSC2 inactivating alterations. As of May, the trial has fully enrolled 120 patients across a broad array of tumor types. TSC1 or TSC2-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 1 is a single trial, TSC1 and TSC2 arms are independently evaluated and can effectively be viewed as two separate studies, each with its own outcome. Importantly, by design, patients in Precision 1 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. 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, NAB-serial alignment is the last available line of systemic therapy for these patients. and truly test the ability of napserolimus 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. 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 rate. Now looking at 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 1. These data demonstrated sustained tumor reductions in a heavily pretreated population based upon investigator-assessed responses across both arms. For TSC1, we reported an investigator-assessed overall response rate of 26%, which was within the range of our expectations. These responses appear to be early, deep, and durable, which is especially noteworthy given this heavily pretreated population with a medium of three prior lines of therapy. These responses were seen across four different tumor types, potentially supporting a tumor agnostic indication. For the TSC2 arm, we reported 11% overall response rate. 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 II trial of erylimus 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 of treatment. I also want to highlight that ongoing conversation with experts reinforced this view. 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-1 closely follows the most up-to-date guidance from regulators on how they would like to see tumor agnostic studies for targeted therapies run. 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 inactivating alteration. By design, PRECISION-1 will not have more than 25% contribution 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. 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 mutations. Now looking at the market opportunity on slide 9, TSC1 and TSC2 mutations define a large mutation-driven oncology population with broad distribution amongst tumor indications and specialty Our latest internal analysis indicates there's 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 decisions. There are some populations in particular for whom NGS testing is more common, so-called high NGS testing specialties. 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 cancers. According to our research with a product profile similar to our interim results to date, high NGS testing specialties indicate they would be likely to use napserolimus after second- and third-line preferred treatments, which aligns with what we observed in Precision 1. We anticipate that market adoption would 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 treatment options. Even if we limit the majority of NAV serolimus utilization to be in the third line with these high NGS testing segments, TSC1 and TSC2 mutated cancers would represent a significant $300 million to $600 million projected market opportunity in the U.S. alone. 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 Napserolimus beyond the coma. With that, I'll now turn it over to Scott for updates on our Q2 financial progress. Scott? Thanks, Dave.
spk22: Looking at slide 11 and starting with FIARO, BioroNet 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. FIARO has a 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. Turning to slide 12, the end of the second quarter of 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 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 Precision 1 trial and the programs in endometrial cancer and NETs. 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 right-sizing 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.
spk09: 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 TSE1 and TSE2 inactivating 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 1 later this quarter, and if appropriate, sharing those data with the FDA thereafter. We expect to complete Precision 1 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 Precision 1, 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.
spk21: Operator?
spk02: As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. And our first question comes from Roger Song with Jefferies. Your line is now open.
spk11: Great. Thanks for the update and taking our questions. Maybe we first talk about the precision, 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 TSC 1 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 what would be the key topics there and then what could be the potential outcome out of the FDA discussion of the second interim as a follow-up. Thank you.
spk09: Sure. Thanks, Roger. I'll make a couple comments and ask Loretta if she has anything she'd like to add. Our precision one outcome in Q3 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, you know, draw any anticipation in terms of the direction of what 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, 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, 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. Roberta, anything you would add to that?
spk15: No, Dave, I think you covered it nicely. Thank you.
spk11: Got it. Yeah, thank you. And then, you know, since the enrollment for the EEC and the NET, phase studies going pretty well. And then just curious, what should we expect from the latest year initial data update? Will that be focusing on maybe some of the safety, turbidity, 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.
spk09: Yeah, I'll let Loretta start by commenting on where we are with those trials, and I can follow up if there's anything to add. So, Loretta, why don't you comment on this?
spk15: Sure. Thanks, Dave, 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 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 fulsome 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 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.
spk09: 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 navserolimus, which will be, you know, something we'll bring forward as we look at that data, dependent on, you know, the patient's that we enroll in these early trials.
spk15: 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.
spk09: Thanks, Roger. Can we move on to the next set of questions?
spk02: Thank you. Our next question comes from Joe Catanzaro with Piper Sandler, your line is open.
spk05: Hey, guys. Thanks for taking my questions here. Maybe following up a bit on sort of what happens post the second two-thirds interim analysis here and the range of outcomes, I'm wondering if there's any scenario in which the design and execution of the remainder of Precision 1 is altered or changed in 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 and sort of the various scenarios that may play out.
spk09: 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 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're 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.
spk05: Okay, got it. That's helpful. There may be one quick one on Soyaro. I know you maybe previously have spoken to, you know, expect patients 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.
spk09: Yeah, I want to, I mean, I do want to highlight that, you know, we did have a low Q1, which, you know, we Disgust likely was being 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 that's being sustained as we go into the next quarter. And that, you know, we're seeing from a demand perspective, you know, 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. And so we remain very positive on the outlook for continued incremental growth in the business in Q3 and Q4 of this year.
spk05: Okay, great. That's helpful. Thanks for taking my question.
spk06: Thanks, Joe. Next question, operator.
spk02: Thank you. Our next question comes from Tara Bancroft with TD Cowan. Your line is open.
spk24: Hi, this is Greg Wiesner on behalf of Tara Bancroft. So the – oh, sorry – 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.
spk09: Sure, Greg. Thanks for the question. This is, as I pointed out, I think, and we tried to discuss deeper in the slides, this is truly a tumor-agnostic approach. 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, you know, 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, you know, we submit and gain approval around that. And we don't, 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 any, 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 sensitive.
spk24: Okay, wonderful. Thank you. 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?
spk09: Yeah, we would imagine this will be a company presentation at this point. Great.
spk02: Thanks, Greg. Go ahead, Daniel. Our next question comes from Ahu Damir with Lautenberg Thalmann. Your line is open.
spk17: Thank you very much for taking my question and 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 that 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?
spk09: 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 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.
spk17: Nice. It makes sense. And my second question is on the endometrial cancer program. You did mention the biggest idea of the trial is to compare it to the other mTOR inhibitors, and the patient baseline demographics can impact the trial results. significantly. So what was 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 because sometimes it's very challenging when we are comparing apples to oranges and baseline demographics can impact a lot.
spk09: Yeah, understood. I probably oversimplified the comparison or 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. So, Loretta?
spk15: Sure, Dave. Good morning, Ahu, and thank you for that question. As usual, it's a good one. The design of the EEC study was largely based on an earlier study that was performed by GOG, the gynecologic oncology group. This was 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 and 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 study. 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 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.
spk16: Yes, definitely. Thank you, Loretta. Okay.
spk09: Thanks a lot. As I mentioned, you know, I do it too simply. Loretta does it wonderfully. So thank you for the question. Do you have a follow-up?
spk17: Well, one last question I have, Dave, if I may. You have two distinct approaches to assess NAV share limits. So curious, when you talk to the KOL community, so where do you see the most excitement? Is it for more of the TSE 1-2 approach? or do you see more of an excitement for the endometrial and NET where there's an indication-specific approach?
spk08: I'll let Loretta comment first, and then I have my own.
spk15: So, first of all, 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. 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.
spk09: I think that's a great summary of it, Loretta, from firsthand experience. I would say we also went out with the TSC 1 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, you know, physicians are quite interested in finding solutions for late-line patients, particularly through targeted mutations where there's an identifiable mutation and where often not just overall response rate but even stable disease is a meaningful outcome. for those patients who have progressed through multiple lines of therapy. And we had excellent reactions to the profile of nabsterolimus, especially amongst folks who are familiar with the mTOR pathway and or doctors who have seen this product in the coma setting. So thank you all for the questions. So operator, next question.
spk02: Thank you. Our next question comes from Robert Burns with HC Wainwright. Your line is now open.
spk04: Good morning. This is Danon Parab. Thanks for taking our question. We wanted to ask, given the data demonstrating preferential tumor uptake for NAV serolimus versus, excuse me, TEM serolimus 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.
spk09: 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 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 think it's premature for us to comment on 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.
spk03: Thanks. That makes sense.
spk04: 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. Do you also have an updated view on what maximum sales and the PCOMAs could look like in the United States and around what that would be? I'm curious on the Paclitaxel versus Everlinus trials. How did those overall survivals compare back in the day?
spk07: Yeah, I'll let Loretta take the first question. Go ahead.
spk15: Okay, so I'll take the last question first because there were so many questions I kind of forgot what the earlier ones were. But I can tell you that the overall survival for the patients 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.
spk09: Loretta, thanks. The first question was in regards to the net trial expectations and any particular tumor types that we might see better responses.
spk14: Okay. You want me to answer that? Yeah.
spk23: Go ahead. Thanks. If you could add.
spk15: So, I wasn't clear with the question whether you were talking about subtypes of nets because nets 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 nets is going to have a better response rate. We just don't have enough information at this point in time.
spk09: Yep. And, Dan, if I can add on the net trial, you know, historically, mTOR inhibitors have been utilized in the setting for neuroendocrine tumors. The Reality is that those approvals were driven off of progression-free survival benefit that was demonstrated. NETs can be quite indolent and long-lasting. But there is benefit that has been derived from NTOR 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 an early indication of the potential of our mTOR inhibitor would be to show superior or not superior, 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 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 two to 300 patients in the US 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 patient. And so therefore, You know, 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 nebcerolimus 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 and, you know, consistently is that, you know, we do believe we've penetrated most of the marketplace at this point and any further growth will be incremental.
spk04: Thank you. That makes sense. And I apologize for the inundation of questions. No worries. We take notes as we go. So thank you, Dan.
spk13: I apologize for my short attention span.
spk09: Thank you. Operator, are there any other questions on the line?
spk02: 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.
spk09: 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.
spk02: This concludes today's conference call. Thank you for participating.
spk09: You may now disconnect.
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