This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.
spk10: Good day, and thank you for standing by. Welcome to Addy Bioscience fourth quarter 2023 earnings conference call. At this time, all participants are on 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 11 on your telephone. You will then hear an automatic message advising your hand is raised. Please note that this conference is being recorded. I will now turn the call over to Audrey Gross, Head of Corporate Communications for Addi Bioscience. Ms. Gross, please go ahead.
spk01: Thank you. Good morning and welcome to the Addi Bioscience conference call to provide an operational update and review results of the fourth quarter and full year 2023. On the call is Dr. Dave Lennon, our President and CEO, Scott Giacobbello, our CFO, and Chief Medical Officer, Dr. Loretta Itri. Today we will provide an overview of operational activity and financial results for the fourth quarter and full year of 2023. 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 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 www.addibio.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. 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 statements. Dave?
spk07: 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 Addi, we are focused on unlocking the full potential of mTOR inhibition by uniquely combining NAP technology and the potent mTOR inhibitor, sirolimus. We believe NAP sirolimus 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 the year marked by progress and increasing momentum for the company as we delivered strong execution against both commercial and development goals. First, VRO sales remained solid, achieving a cumulative $24.4 million for the full year of 2023, representing a 60% growth over prior years. VRO achieves high penetration in the academic and community settings and is considered the preferred treatment for malignant PECOMA. Clinically, a key focus for our organization has been realizing the potential of nabsterolimus for patients with solid tumors harboring either TSC1 or TSC2 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 nabsterolimus to treat all types of solid tumors with either of these alterations. As a reminder, the unmet need in TFC1 and TFC2 mutated cancers is sizable, whether considering together or independently, and represents about 2% of all solid tumor cancer patients. 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 U.S. alone. With mutations roughly evenly split between genes, each mutation represents a potential multibillion-dollar addressable market for NAP-serial alignment. TSC1 or TSC2-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. We believe PRECISION1 is a cutting-edge trial testing our innovative therapy, Napserolimus, in these cancer types. Although PRECISION1 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 outcome. In Q4, we provided top-line results from a planned interim evaluation of the first 40 patients enrolled in Precision 1. 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 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. Importantly, responses appeared to be early, deep, and durable. 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 pretreated 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 TSC2 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 TSC2 results are challenging to interpret. Precision 1 continues to enroll steadily, and we now expect the trial to be fully enrolled by May. We are still on track for our next planned 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 and will evaluate the primary input in the study, independently assessed overall response rate, as opposed to our December analysis, which reported investigative responses. 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 of the previously announced phase two single indication trials for two promising mTOR-driven cancer targets. Overactivation and dysregulation of the mTOR pathway is commonly found in various tumors, and unique delivery and excellent safety profile of napserolimus provides the opportunity to combat these difficult-to-treat cancers. The first trial is evaluating napserolimus in neuroendocrine tumors, or NETs. NETs are rare, with approximately 3,500 patients per year. NETs have historically had a low response rate to treatment with oral rapalogs and other agents, which nonetheless are used clinically and recommended in treatment guidelines today. In preclinical animal models, NAP serolimus demonstrated improved target suppression relative to other mTORs, warning further exploration of NAP serolimus in this indication. We're excited about this trial because it provides the opportunity to demonstrate what we believe is napserolimus' best-in-class efficacy in a known mTOR-sensitive tumor type. The second trial we started last year is evaluating the therapeutic potential of napserolimus in advanced and recurrent endometrioid-type endometrial cancer 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 the 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 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 ongoing trial with combination of varieties KRAS inhibitor and lung cancer and other solid tumors. With a solid commercial foundation provided by FIARA, robust and bold clinical development programs 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 oncology company. I will now turn the call over to Scott for updates on our financial progress.
spk09: 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 current plans. FIARO 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 FIARO 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. For the year, R&D expense 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 initiation of the programs in endometrial cancer and NETs. 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. This increase is due primarily to higher legal and company infrastructure costs and increased marketing expenses related to FIARO. 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. 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. Dave?
spk07: Thank you, Scott. I'm so proud of the progress we made in Q4 and what the team accomplished in 2023. The RO remains a valuable asset with sustained demand to help meet the needs of patients with the coma. We're making tremendous progress against our clinical development plans with two sizable markets in TFC1 and TFC2 inactivating alterations, as well as other mTOR-driven cancers. We're looking forward to sharing the two-thirds interim analysis from Precision 1 in the third quarter with full enrollment inspected in May and study completion by the end of 2024. We can now open the line for questions. Operator?
spk10: Thank you. Ladies and gentlemen, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, simply press star one one again. Please stand by while we compile the Q&A roster. And our first question coming from the lineup, Joe Cantanzaro with Piper Sandler. You want to open?
spk08: Yeah, thanks. Appreciate you taking the questions here. Maybe first one, I know the first 40 patients were characterized as being very heavily pre-treated, so 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 the interim data disclosure. Thanks, and I have one follow-up.
spk07: Great. Joe, thank you for the question. Always appreciate talking more about Precision 1. Yes, so the first 40 patients were heavily pretreated. 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. 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 napserolimus in our trial. And so we anticipated continuing to enroll later Lyme 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.
spk08: Okay, thanks. And then my follow-up, 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. 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, you know, the adagrassive acquisition by Bristol. Thanks.
spk07: Yep. So, great questions. I think I mentioned earlier that we do anticipate potentially sharing data on endometrial or neuroendocrine trial later this year. Those are open-label, single-arm phase two 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 the patient, you know, 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, you know, initially a great sign in terms of folks' interests in these therapeutic regimens in each of those indications. And then on the Mirati, you know, 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.
spk08: Okay, thanks. That's helpful and thanks for taking my question.
spk07: Thanks, Joe.
spk10: Thank you. And our next question coming from the line of Liang Cheng with Jefferies. Your line is open.
spk05: Sure, thank you. This is Liang for Roger. So thank you for taking our questions. I guess from us, we have two questions. One is around FIARO. So just 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 FDA about the tumor agnostic. So what's, you know, in your understanding, what's the most important thing for FDA to consider and label as a tumor agnostic? Thank you.
spk07: Great. Thank you, Liang, and thanks for stepping in for Roger. So maybe in terms of FIARA Outlook, maybe 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, do you want to just comment on the FIARA Outlook for the coming year? Sure, absolutely. Yeah, thanks for the question, Liang.
spk09: Yeah, I think for FIARA, as you've seen, I mean, we're not going to provide guidance for this year. I think what we, you know, you've seen over the last few quarters, you know, the sales stabilizing around the $6 million mark or slightly above. And I think so, you know, the expectation there is, you know, we continue to be, you know, excited about the, 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 I think that's what we would expect for 2024.
spk07: 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 highly recognized as the preferred therapy for PECOMA. It is just an ultra rare population. And ultimately we may be reaching saturation of that market and expect, you know, more incremental growth from here on out. And then your second question was on, you know, 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 tumor agnostic indication and what's most important there. So, Loretta, do you want to comment?
spk03: 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. 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. In our case, since we already have approval and 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.
spk07: Thanks, Loretta. And just to you know, add on to what Loretta was saying, what we saw 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 in December. Thanks, Liang, for the questions, and I think if there's no follow-ups, we can move to the next set of questions.
spk05: Thank you. Thank you. Appreciate it. Thank you.
spk10: Thank you. And I'm As a reminder, ladies and gentlemen, to ask a question, please press star 11 on your telephone. And our next question coming from the line of Ahu Demir with Leidenberg. Your line is open.
spk02: Good morning. Thank you so much for taking my questions. I have two questions. A follow-up to Joel's question regarding endometrial cancers. One, could you give us a sense of the sites open, how many sites 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 pretreated? If you can provide a little bit of color, that would be great.
spk07: 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 number of sites or a 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 give you an update there. So, Loretta.
spk03: Good morning, Ahu. Always great questions, as usual, coming from you. So, basically, this is an open-label phase 2 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. So patients are treated with the same dose of nabsorolimus as they were in Tacoma. That is a well-established and safe dose. And 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? Would you like more detail?
spk02: 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 to you, Loretta, if I may. So you mentioned mTOR-sensitive tumors. Besides TSC1-2, could you comment on what other mutational backgrounds are sensitive to mTOR inhibitors?
spk03: 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.
spk11: Very helpful. Thank you so much.
spk03: You're most welcome.
spk07: Thanks, Ahu. Operator, are there any other questions?
spk10: And as you know, for the questions in the queue at this time, I'll now turn the call back over to you, Dr. Deflin, for any closing remarks.
spk07: 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 on our ability to deliver deliver against our number one priority, which is the Precision 1 trial. 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 got to discuss a little bit in the Q&A and look forward to providing updates on both our NET and endometrial trials later 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, but that continues to deliver solid sales for us as we go forward. Overall, otherwise, I thank you all for your time and attention today, and we look forward to the next update with you all. Thank you, and have a great day.
spk10: Ladies and gentlemen, that does conclude our conference for today. Thank you for your participation. You may now disconnect. Thank you. you Bye. Thank you. Good day, and thank you for standing by. Welcome to Addy Bioscience fourth quarter 2023 earnings conference call. At this time, all participants are on 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 automatic message advising your hand is raised. Please note that this conference is being recorded. I will now turn the call over to Audrey Gross, Head of Corporate Communications for Addi Bioscience. Ms. Gross, please go ahead.
spk01: Thank you. Good morning and welcome to the Addi Bioscience conference call to provide an operational update and review results of the fourth quarter and full year 2023. On the call is Dr. Dave Lennon, our President and CEO, Scott Giacobbello, our CFO, and Chief Medical Officer, Dr. Loretta Itri. Today, we will provide an overview of operational activity and financial results for the fourth quarter and full year of 2023. 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 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 www.addibio.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. 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?
spk07: 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 Adi, we are focused on unlocking the full potential of mTOR inhibition by uniquely combining NAP technology and the potent mTOR inhibitor serolimus. We believe Napsuralimus 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 the year marked by progress and increasing momentum for the company as we delivered strong execution against both commercial and development goals. First, the RO sales remained solid, achieving a cumulative $24.4 million for the full year of 2023, representing a 60% growth over prior years. The ROA achieves high penetration in the academic and community settings and is considered the preferred treatment for malignant pachoma. Clinically, a key focus for our organization has been realizing the potential of napserolimus for patients with solid tumors harboring either TSC1 or TSC2 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 napserolimus to treat all types of solid tumors with either of these alterations. As a reminder, the unmet need in TFC1 and TFC2 mutated cancers is sizable, whether considering together or independently, and represents about 2% of all solid tumor cancer patients. 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 U.S. alone. With mutations roughly evenly split between genes, each mutation represents a potential multibillion-dollar addressable market for Napserolimus. TSC1 or TSC2-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. We believe Precision 1 is a cutting-edge trial testing our innovative therapy Napserolimus in these cancer types. 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 outcome. In Q4, we provided top-line results from a planned interim evaluation of the first 40 patients enrolled in Precision 1. 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 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. Importantly, responses appeared to be early, deep, and durable. 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 pretreated 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 TSC2 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 TSC2 results are challenging to interpret. Precision 1 continues to enroll steadily, and we now expect the trial to be fully enrolled by May. We are still on track for our next planned interim readout, which is expected in Q3 of 2024. 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 rate, as opposed to our December analysis, which reported investigated responses. 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 of the previously announced phase two single indication trials for two promising mTOR-driven cancer targets. Overactivation and dysregulation of the mTOR pathway is commonly found in various tumors, and unique delivery and excellent safety profile of napserolimus provides the opportunity to combat these difficult-to-treat cancers. The first trial is evaluating napserolimus in neuroendocrine tumors, or NETs. Nets are rare, with approximately 3,500 cations per year. Nets have historically had a low response rate to treatment with oral rapalogs and other agents, which nonetheless are used clinically and recommended in treatment guidelines today. In preclinical animal models, napsuralimus demonstrated improved target suppression relative to other mTORs, warning further exploration of napsuralimus in this indication. We're excited about this trial because it provides the opportunity to demonstrate what we believe is napserolimus' best-in-class efficacy in a known mTOR-sensitive tumor type. The second trial we started last year is evaluating the therapeutic potential of napserolimus in advanced and recurrent endometrioid-type endometrial cancer 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 the mTOR inhibitors combined with letroxol have yielded promising results, and recent changes in the 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 ongoing trial with combination of varieties KRAS inhibitor and lung cancer and other solid tumors. With a solid commercial foundation provided by FIARA, robust and bold clinical development programs 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 oncology company. I will now turn the call over to Scott for updates on our financial progress.
spk09: 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 current plans. FIARO 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 FIARO 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. For the year, R&D expense 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 initiation of the programs in endometrial cancer and NETs. 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. This increase is due primarily to higher legal and company infrastructure costs and increased marketing expenses related to FIARO. 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. 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.
spk07: Dave? Thank you, Scott. I'm so proud of the progress we made in Q4 and what the team accomplished in 2023. The RO remains a valuable asset with sustained demand to help meet the needs of patients with the coma. We're making tremendous progress against our clinical development plans with two sizable markets in TFC1 and TFC2 inactivating alterations, as well as other mTOR-driven cancers. We're looking forward to sharing the two-thirds interim analysis from Precision 1 in the third quarter with full enrollment inspected in May and study completion by the end of 2024. We can now open the line for questions. Operator?
spk10: Thank you. Ladies and gentlemen, to ask a question, you will need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, simply press star 11 again. Please stand by while we compile the Q&A roster. And our first question coming from the lineup, Joe Cantanzaro with Piper Sandler. Your line is open.
spk08: Yeah, thanks. Appreciate you taking the questions here. Maybe first one, I know the first 40 patients were characterized as being very heavily pre-treated, so 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 the interim data disclosure. Thanks, and I have one follow-up.
spk07: Great. Joe, thank you for the question. Always appreciate talking more about Precision 1. Yes, so the first 40 patients were heavily pretreated. 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. Patients have to have satisfied the 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 napserolimus in our trial. And so we anticipated continuing to enroll later Lyme 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.
spk08: Okay, thanks. And then my follow-up, 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. 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, you know, the adagrassive acquisition by Bristol. Thanks.
spk07: Yep. So great questions. I think I mentioned earlier that we do anticipate potentially sharing data on endometrial or neuroendocrine trial later this year. Those are open label single arm phase two 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 the patient, you know, 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, you know, initially a great sign in terms of folks' interests in these therapeutic regimens in each of those indications. And then on the Mirati, you know, 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.
spk08: Okay, thanks. That's helpful and thanks for taking my question.
spk04: Thanks, Joe.
spk10: Thank you. And our next question coming from the lineup, Liang Cheng with Jefferies. Your line is open.
spk05: Sure, thank you. This is Liang for Roger. So thank you for taking our questions. I guess from us, we have two questions. One is around FIARO. So just for FIARO in the coming year, you know, can you provide us any details, guidance, or commercial plans? Second question is about, you know, I know you guys have been interacting with FDA about the tumor agnostic. So what's, you know, in your understanding, what's the most important thing for FDA to consider and label as a tumor agnostic? Thank you.
spk07: Great. Thank you, Liang, and thanks for stepping in for Roger. So maybe in terms of FIARA Outlook, maybe 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, do you want to just comment on the FIARA Outlook for the coming year? Sure, absolutely.
spk09: Yeah, thanks for the question, Liang. Yeah, I think for FIARA, as you've seen, I mean, we're not going to provide guidance this year i think what we you know you've seen over the last few quarters um you know the sales stabilizing uh around the the six million dollar mark or slightly above and i think so um you know the expectation there is you know we continue to be you know um excited about the about fiora and the potential to 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 I think that's what we would expect for 2024.
spk07: 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. And ultimately we may be reaching saturation of that market and expect, you know, more incremental growth from here on out. And then your second question was on, you know, 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 tumor agnostic indication and what's most important there. So, Loretta, do you want to comment?
spk03: 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. 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. In our case, since we already have approval and 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.
spk07: Thanks, Loretta. And just to you know, add on to what Loretta was saying, what we saw 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 in December. Thanks, Liang, for the questions, and I think if there's no follow-ups, we can move to the next set of questions.
spk05: Thank you. Thank you. Appreciate it. Thank you.
spk10: Thank you. As a reminder, ladies and gentlemen, to ask a question, please press star 1-1 on your telephone. And our next question coming from the line of Ahu Demir with Leidenberg. Your line is open.
spk02: Good morning. Thank you so much for taking my questions. I have two questions. A follow-up to Joel's question regarding endometrial cancers. One, could you give us a sense of the sites open, how many sites 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 pretreated? If you can provide a little bit of color, that would be great.
spk07: 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 number of sites or a 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 give you an update there. So, Loretta.
spk03: Good morning, Ahu. Always great questions, as usual, coming from you. So, basically, this is an open-label Phase II study looking to evaluate the combination of nab serolimus 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. So patients are treated with the same dose of nabsoralimus as they were in Tacoma. That is a well-established and safe dose. And 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? Would you like more detail?
spk02: 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 to you, Loretta, if I may. So you mentioned mTOR-sensitive tumors. Besides TSC1-2, could you comment on what other mutational backgrounds are sensitive to mTOR inhibitors?
spk03: 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.
spk11: Very helpful. Thank you so much.
spk03: You're most welcome.
spk07: Thanks, Ahu. Operator, are there any other questions?
spk10: And as you know, for the questions in the queue at this time, I'll now turn the call back over to you, Dr. Deflin, for any closing remarks.
spk07: 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 on our ability to deliver deliver against our number one priority, which is the Precision 1 trial. 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 got to discuss a little bit in the Q&A and look forward to providing updates on both our NET and endometrial trials later 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. Overall, otherwise, I thank you all for your time and attention today, and we look forward to the next update with you all. Thank you, and have a great day.
spk10: Ladies and gentlemen, that's our conference for today. Thank you for your participation. You may now disconnect.
Disclaimer