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spk02: Good day and thank you for standing by. Welcome to the Addi Bioscience Third 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 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 today's conference is being recorded. I would now like to hand the conference over to your speaker today, Marcy Graham, Senior Vice President of Investor Relations and Corporate Communications, Addi Bioscience. Ms. Graham, please go ahead.
spk05: Thank you. Good morning and welcome to the Addi Bioscience conference call to provide an operational update and review results for the third quarter 2023. Joining me on the call today, Dr. David Lennon, our president and CEO, Scott Giacobbello, our CFO, and our chief medical officer, Dr. Loretta E. Tree. Today we will provide an overview of operational activity and financial results for the third quarter of 2023 and an update on our Precision 1 trial and clinical development plans going forward. 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 filings with the Securities and Exchange Commission, which can be found at www.sbc.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, November 8, 2023, and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements. With that, I will turn the call over to our CFO, Scott Giacobbello, for his opening statement. Scott?
spk09: Thank you, Marcie, and good morning, everyone. Thank you for joining us today to review our financial and operational results for the third quarter of 2023. Before we discuss our progress in the third quarter and activities currently underway, I would like to take this opportunity to introduce Dave Lennon, who joined us as president and CEO at the start of the fourth quarter. Dave comes to us with more than 20 years of pharmaceutical leadership and deep expertise in mTOR-driven diseases, with a history in oncology and rare disease and a strong background in U.S. and global commercialization, all experiences that make him the perfect choice to guide Addy through our next phase of growth and development. I'm excited about the future and look forward to working with Dave, continuing in my role as CFO. Now I'd like to turn the call over to Dave for his initial comments. Dave?
spk11: Thank you, Scott. I appreciate the warm welcome and introduction. I would also like to thank you for taking the role of interim CEO prior to my joining, and thank the entire management team for all their hard work in getting us to where we are today. The unique combination of technology, timing, and team is what drew me to ADDIE. There's a great opportunity here to build on the success of the mTOR inhibitor class in cancer. Our groundbreaking therapy, nabsterolimus, allows us to generate deeper inhibition of the mTOR pathway at the site of tumor and hopefully more potent anti-cancer activity, resulting in better patient responses. We've proven this in our first indication of PECOMA, a rare soft tissue sarcoma, and at our unique moment as a company where we expect to have multiple data readouts over the next 12 to 18 months from our highly anticipated tumor agnostic study, precision one. I am also fortunate to be joining Addy with an excellent team who continue to execute on an ambitious commercial and clinical programs focused on building a leading precision oncology company. And I'm very happy to share their strong performance over the third quarter. Importantly, precision one continues to enroll rapidly, and we now expect to present early interim data by mid-December. We will share more of our trial progress and upcoming catalysts in a moment. VRO sales remain solid at $6 million in the third quarter, a 40% growth over the prior year, and $18 million in cumulative sales in the first nine months of 2023. We are also executing on our previously announced development strategy with the initiation of two phase two studies of navsterolimus, one in combination with standard of care in endometrial cancer, and the other as a single agent in neuroendocrine tumors. These are in addition to our ongoing trial in combination with Mirati's KRAS inhibitor in lung cancer and other solid tumors. A key focus of our organization has been realizing the potential of NAPSEER alignments for patients with solid tumors harboring either TSC1 or TSC2 inactivating 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 tumors with either of these alterations. The unmet need in TSC1 and TSC2 mutated cancers is sizable, whether considered together or independently. We presented data at this fall's ENA symposium or triple meeting based on next generation sequencing of mutations of nearly 440,000 cancer patients from the foundation medicine database. This large real world evidence provides the best look at data to date on TSC1 or TSC2 mutation frequencies across all common tumor types. This corroborates our previous estimate that patients with TSC1 or TSC2 represent about 2% of all cancer patients. Our latest internal analysis indicates there are approximately 16,000 patients with these mutations across a variety of tumor types. With mutations roughly evenly split between genes, each mutation represents potential multi-billion dollar total addressable market for NAB serolimus. TSC1 or 2 driven cancers are found across a wide range of tumor types, clustering in lung, gastrointestinal, general urinary, breast, and gynecological locations, and are often difficult to treat. We believe PRECISION-1 is a cutting-edge trial testing our innovative therapy, napsuralimus, in these cancer types. With that background, I'd like to turn it over to Loretta, who will speak further to the details of this unique tumor-agnostic trial and our plans going forward. Loretta?
spk06: Thank you, Dave, and good morning, everyone. As Dave noted, PRECISION-1 is a unique study and one without cohorts segregated by specific tumor types, making it truly tumor agnostic. This is an ambitious and adaptive trial intended to elucidate the impact of nab serolimus on cancers expressing inactivating mutations of TSC-1 and TSC-2, regardless of tumor type. We are very pleased with the continuing advancement of the trial. The number of open sites has increased, as has access to patients, with more than 150 sites available to us using our just-in-time mechanism that allows us to open prequalified sites within as little as a two-week period. Working with our NGS partners and benefiting from the broad outreach afforded by our clinical sites, both academic and community-based, we are able to effectively identify and track patients with TFC1 or TFC2 inactivating alterations who have an interest in participating in our study. Accrual between the two arms has been remarkably even, as predicted by the real-world data recently published at the ENA Annual Meeting. We continue to have a very broad representation of solid tumors. with more than 25 discrete tumor types enrolled in the trial to date. It is important to remember that although PrecisionOne 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, PrecisionOne can effectively be viewed as two separate studies, each with its own outcomes. Additionally, these are not just two studies. They are two standalone tumor agnostic studies. Consistent with the adaptive statistical analysis plan, there are two preplanned interim analyses in the near future, one at one-third enrollment, which we plan to report in mid-December of this year, and another at two-thirds enrollment, which we expect to report in the third quarter of 2024. The interim analysis that will be performed when two-thirds of patients are accrued and have been followed for six months will evaluate the primary endpoint of the study, DMC-evaluated ORR, and will provide us with the opportunity to modify the study or to file early if the data warrant. The upcoming per-protocol interim analysis planned for later this year will include early data on tumor type distribution, safety, and investigator assessment of response using resist criteria on approximately 20 evaluable patients from each arm. We expect these results to reflect a broad representation of tumor types, varied treatment histories, and lines of therapy. We have built great momentum in our Precision I program and look forward to delivering on key milestones both later this year and throughout 2024. We expect to have completed enrollment by the spring of next year, well ahead of our planned delivery of the two-thirds interim readout in the third quarter, and to complete the study by the end of 2024. We remain very excited about the potential of this important study and the promise of nab serolimus and look forward to communicating the preliminary results from the PRECISION-1 trial in a few weeks. I'll now turn the call over to Scott for updates on our financial progress. Scott?
spk09: Thanks, Loretta. On the financial front, we remain well capitalized, ending the third quarter with $119.3 million in cash, cash equivalents, and short-term investments, which is expected to fund operations into 2025 based on current plans. Fiara sales were $6 million in the quarter, representing 40% growth over the same period in 2022. Research and development expenses for the quarter increased to $11.9 million as compared to $8.8 million in the prior year quarter. This increase is primarily related to the continued progress of the ongoing Precision 1 trial and the build out of the R&D organization. Selling general and administrative expenses for the third quarter were $11.2 million compared to $9.9 million for the same period in 2022. This increase is due primarily to the build-out of company infrastructure and increased marketing expenses related to FIOR. Net loss for the third quarter was $16.3 million compared to $14.4 million in the prior year quarter. For more information on our financial performance for the third quarter, a detailed discussion of the results reported on this call will be provided in our Form 10-Q. I'll now turn the call over to Dave for his closing comments. Dave?
spk10: Thanks, Scott. As I said earlier, we are truly excited about what lies ahead.
spk11: We've defined two sizable markets in cancers with TSC1 or TSC2 inactivating alterations and look forward to sharing the upcoming Precision 1 interim analysis plan for mid-December. Beyond that, we are excited about the new catalyst coming up in 2024, including our two-thirds interim analysis in the third quarter. We expect to reach full enrollment in the trial in the spring of next year, fully completing the study by the end of 2024. We can now open the line for questions. Operator?
spk02: Thank you. Ladies and gentlemen, if you have a question or a comment at this time, please press star 1 1 on your telephone. If your question has been answered, you wish to move yourself from the queue, please press star 1 1 again. We'll pause for a moment while we compile our Q&A roster.
spk03: Our first question comes from Boris Peeker with Cowan. Your line is open.
spk07: Great. Thanks for taking my question. Two questions for me. First, on that second interim analysis, which you estimate in 3Q of next year, what efficacy do you need to stop early? And second, In the Pekoma market for VR, do you have any sense of kind of what the duration of therapy is turning out to be? Thank you, John.
spk11: Boris, thanks very much for the questions. In terms of the second interim, I wouldn't comment at this point about what efficacy needs to be. Obviously, we have two arms running within this study, and the context of response rate and duration and that combination needs to be considered when we think about potential for stopping a study early. But of course, we do have that option at that point in time. On the pet coma side, in terms of duration, I think what we can see is that duration is consistent with what we've been seeing in the clinical trial, and that's what I would comment at this point.
spk07: Great. Thanks for taking my questions.
spk03: Thanks, Boris. One moment for our next question. Our next question comes from Joe Catanzaro with Piper Sandler.
spk02: Your line is open.
spk08: Hey, everybody. I appreciate you taking my questions. Maybe a couple from me on precision one. So for the initial interim expected by year end, with the minimum follow-up of four and a half months, can you just let us know what minimum amount of post-baseline scan that ensures? And then for the second interim analysis, I think this is the first we're hearing of this. Was this always the plan, and if not, what drove the decision to take another look? And then sort of along these lines, Loretta, if I heard you right, the second interim analysis will allow you to modify the study. Just wanted to understand that a little bit better, given it sounds like the study will be fully enrolled by that time, what modifications maybe you could potentially employ then? Thanks.
spk11: Sure. Loretta, do you want to comment on those first three areas?
spk10: Hi, Joe.
spk06: Thanks for your questions. So let me reply. I'm sorry. I kind of have the order of your questions a little bit confused. Do you think you could repeat the first one, please?
spk08: Yeah, yeah, sure. I'll be quick here. So the minimum amount of post-baseline scans that's ensured with four and a half months of follow-up and then the second interim analysis, was this always in those plans or is this something new and what drove the decision and then what modifications you could potentially take post the second interim analysis given that the trial would have been fully enrolled by that point?
spk06: okay great so um the four and a half month guarantees at least at least two uh post baseline scans so everyone will have at least uh the ability to have that kind of follow-up um the um the uh interim analysis uh the second interim analysis at two-thirds that you were asking question about has always been in the statistical analysis plan It is an adaptive design. This is very common when approximately two-thirds of patients are on study to have a look and to assess whether or not the sample size is sufficient to file early or whether or not you might want to consider resizing. So those are both options that we would have. when that interim occurs. But this analysis was always planned. And we will have six months of follow-up. This analysis will look at the independent review of radiologic scans and will be performed by an independent data monitoring committee. So, even though we will have completed enrollment in the study, presumably by that time, we will still be requiring additional follow-up on the entire cohort. Hope that addresses your questions.
spk08: Yes, it does. Super helpful. Thanks for taking my question. Thanks.
spk06: Oh, you're so welcome.
spk03: One moment for our next question. Our next question comes from Roger Song with Jefferies. Your line is open.
spk01: Great. Thanks for the update and taking our questions. A couple from us. In terms of the internal analysis, now we have two. Maybe can you let us know, I understand you're not going to providing the guidance right now, but at which internal analysis, if at all, you will contextualize the efficacy against the FDA statistical hurdle or, you know, the standard of care you have been providing to the FDA as the benchmark so we can know in each intra-analysis the efficacy or the OR will be reaching the goal you want to achieve.
spk11: Thanks for the question, Roger. I'll take this one. It's important to note that this interim that we're presenting in December is based on one-third of patients enrolled and a minimum of four and a half months of follow-up. It's also investigator-assessed ORR, so this is not the primary endpoint of the study, which is independently assessed overall response rates. And the second interim is actually based on the primary endpoint, and it will be at that point we would be testing against the statistics of the plan.
spk01: Got it. So in the second interim analysis, you will do the primary endpoint analysis. Will be that the point you will let us know what's the hurdle for that, or you will just let us know, okay, we are not stopping the trial and will continue for the full data.
spk11: Yeah, we view the hurdle to be something that is probably is a review issue, and we probably wouldn't talk about that at that point in time, but rather give a sense of what the efficacy measures we're seeing are and whether, you know, where we are with the trial in terms of continuation.
spk01: Got it. Thank you. Maybe just a quick follow-up. Yeah, quick follow-up on this is you say you will complete the trial by the end of 2024, and when should we expect the full data from the trial? Thank you.
spk11: Yeah, it's still, you know, it's roughly at the end of 2024 or early 2025. We haven't, we anticipate it's probably more likely early 2025 at this point, but we'll give a further update once we complete enrollment.
spk01: Excellent. Thank you. That's it from us.
spk03: One moment for our next question. Our next question comes from .
spk02: Your line is open.
spk04: Good morning, team. Thank you so much for taking my questions. Two questions from us. First one is regarding the triple meeting presentation. It looks like T53 is the most frequently observed comorbidity. Curious how that might impact these comorbidities, how they might impact the viral activity. And during the interim analysis, will you disclose the other mutations in the patients or is it going to be more high level?
spk11: Yeah, so I'll take a first crack, and Loretta, back me up on this. You know, TP53 is the most common mutation, co-mutation that you see in that analysis for patients across 440,000 cancers that we looked at. And our internal calculations, when we look at those distributions, indicate there's potentially 16,000 new cancer patients each year with either TSC1 or TSC2 mutations. About 50% of those, if I recall the data correctly, had commutations in p53. And although that, while high overall, is very consistent with what you see across all tumor types and all types of cancers, p53 is the most common commutation in general for different types of tumors. And so it's not different from what you might expect overall. And given that we've seen responses to patients with TSC1 and TSC2 altered cancers in the past in the retrospective analysis that became the basis for Precision 1 and Precision 2, we wouldn't expect it to necessarily negatively or impact the trial in any way, and we believe it would work within that context. And Loretta, I don't know if you would add anything to that.
spk06: No, I think that's entirely correct. I would have answered it the same way.
spk11: Yeah. And then in the interim, we won't be presenting commutation status at this point in time. The numbers, while significant in terms of an initial indicative nature of how the trial is going, we don't believe would be sufficient to really do a detailed analysis of commutation status that would be robust enough to make any determinations on at this point. So we won't be sharing that data.
spk04: That's helpful. My second question is on the endometrial program. Now the trial is enrolling, how many sites are open, and when do you expect to see initial data from stage one portion of the study?
spk11: So we are, we've just started that study. I wouldn't comment on the number of sites we have, but we're, you know, we, the community is very excited about engaging in this study, and we hope to have an update on the study sometime in 2024. Great.
spk04: Thank you for taking my questions.
spk02: Thanks, Alan. And I'm not showing any further questions at this time. I'd like to turn the call back over to Dave for any closing remarks.
spk11: Super. Thank you very much, Kevin. And thank you, everyone, for joining us on today's call. As we mentioned, we're really excited about the progress we're making on the PRECISION I trial with the interim analysis plan for mid-December. and a number of exciting catalysts for 2024 that could propel our company to growth. We appreciate your time and look forward to the opportunities in the future to provide additional updates on our process or progress, I should say. Thank you for joining the call and have a great day, everyone.
spk02: Ladies and gentlemen, that's include today's presentation. You may now disconnect and have a wonderful day.
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