Syndax Pharmaceuticals, Inc.

Good day, everyone, and welcome to the Syndax fourth quarter 2022 conference call. Today's call is being recorded. At this time, I would like to turn the call over to Sharon Clary, head of investment relations at Syndax Pharmaceuticals.

Thank you, Operator. Welcome, and thank you all for joining us today for a review of Syndax's fourth quarter and full year 2022 financial and operating results. I'm Sharon Clary, and with me this afternoon to provide an update on the company's progress and to discuss financial results are Michael Metzger, Chief Executive Officer, Dr. Briggs-Morrison, President and Head of R&D, and Keith Goldan, Chief Financial Officer. Also joining us on the call today for question and answer session are Dr. Vitora Dentler, Chief Scientific Officer, and Dr. Anjali Kangula, Chief Business Officer. This call is accompanied by a slide deck that has been posted on the investor page of the company's website. You can now turn to our forward-looking statement on slide two. Before we begin, I'd like to remind you that any statements made during this call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the risk factors section in the company's most recent annual report on Form 1010. as well as other reports filed with the SEC. Any forward-looking statements may represent our views as of today, February 28, 2023 only. A replay of this call will be available on the company's website, www.cindex.com, following its completion. With that, I'm pleased to turn the call over to Michael Metzger, Chief Executive Officer, CINDEX.

Thank you, Sharon, and thank you to all of you joining on the webcast today. Now, turning to slide three, 2022 was a year of growth and strong execution for Syndex. We made great progress working towards our long-term goals, all of which put us firmly on the path to becoming a fully integrated commercial-stage biopharmaceutical company, delivering two best-in-class products to patients in areas of high unmet medical need. On Revumentive, we made significant progress in enrolling patients in the Augment 101 pivotal trials, announced breakthrough therapy designation for patients with relapsed refractory KMT2A rearranged acute leukemia, and presented robust updated phase one data that further supported Revimenid's best-in-class clinical profile in two oral sessions at the 2022 American Society of Hematology Annual Meeting. Further, we initiated additional phase one trials designed to test Revimenid in a variety of settings, including combinations with standard of care regimen. For axotilumab, we completed enrollment in the Pivotal Agave 201 trial, published the initial Phase 1-2 chronic graft-versus-host disease dataset in the Journal of Clinical Oncology, and made progress expanding the axotilumab development program in collaboration with our partner, Insight. We are fortunate to have Insight as a strong collaborator to help us successfully advance axotilumab development. Additionally, in December, we bolstered our balance sheet with a 172 $5 million follow-on offering. Our cash runway is now expected to extend into the second half of 2025, allowing us to appropriately invest to maximize the value of our pipeline, prepare for two potential U.S. commercial launches in 2024, and pursue potential business development opportunities. Our focus, determination, and unending commitment to patients has propelled us forward to this critical year. A year that we expect will be marked by pivotal readouts and registration filings for our two lead drug candidates, both of which are first and potentially best-in-class treatments. 2023 is an incredibly significant year for Syntax, and I'm confident that we have the expertise and resources to execute on our goals, along with the determination to realize a future in which people with cancer live longer and better than ever before. Turning to slide four, we provide a high-level summary of our current corporate priorities. Starting with Revimentum, our highly selected menin inhibitor. Our pivotal Phase II Augment 101 trial evaluating Revimentum in patients with relapsed refractory NPM1 mutant or KMT2A rearranged acute leukemia is progressing well. We are happy to report that we have completed enrollment of a sufficient number of patients with a KMT2A rearrangement to support a registration filing, and we are on track to report top-line data from the TRIAL IN THE THIRD QUARTER OF 2023. THIS DATA WOULD PROVIDE THE BASIS FOR AN NDA FILING BY YEAR END 2023. I WILL PROVIDE MORE DETAILS ON AUGMENT 101 LATER IN THE CALL. IN ADDITION TO THE AUGMENT 101 TRIAL, WE HAVE ONGOING TRIALS TESTING REVUMENTIV IN EARLIER LINES OF THERAPY AND IN COMBINATION WITH STANDARD OF CARE MEDICINES TO TREAT THESE FORMS OF ACUTE LEUKEMIA. WE ARE COMMITTED TO UNLOCKING THE FULL POTENTIAL OF THIS IMPORTANT THERAPY. With that goal in mind, we expect to have several additional data readouts in 2023 for Revumented. These include initial top-line data from Augment 102 chemocombination trial in relapsed refractory acute leukemia patients, safety data from the dose escalation phase of the BEAT-AML cooperative trial of Revumented in combination with venetoclax and astatidine in newly diagnosed AML patients, and initial top-line data from the first solid tumor proof-of-concept trial in metastatic colorectal cancer. Moving to axotilumab, our antibody against CSF1R. We remain on track to report top-line data in mid-2023 from the pivotal Phase II Agave201 trial, evaluating axotilumab in patients with chronic graft-versus-host disease, or CGBHD, and plan to submit a BLA filing by the end of 2023. To maximize the value of the axotilumab program, we anticipate initiating additional trials in 2023, including a combination of axotilumab and ruxolitinib in frontline CGBHD that we expect insight to be in later this year, as well as a phase two trial of axotilumab in idiopathic pulmonary fibrosis, or IPF, that we anticipate kicking off in the first half of 2023. We continue to evaluate potential opportunities to in-license earlier-stage targeted oncology compounds that we believe could become high-value differentiated assets. We believe that we have sufficient capital to bring in new early-stage assets, but our bar for doing so is quite high, as any compound would need to complement our current pipeline and fit in with our long-term corporate strategy. Let's now turn to slide five, and I'll provide further details on the recommended program. As you recall, the Phase II portion of Augment 101 is designed as three single-arm pivotal trials with distinct patient populations that enroll independently. These patient populations are KMT2A rearranged ALL, KMT2A rearranged AML, and MPM1 mutant AML. The primary endpoint of each pivotal trial is the percentage of patients achieving CR, CRH, with secondary endpoints including durability of CR-CRH response, transfusion independence, overall survival, and safety. In December, we received breakthrough therapy designation, or BTD, for remunerated for the treatment of all adult and pediatric patients with relapse or refractory KMT2A rearranged acute leukemia, whether presenting as acute myeloid or acute lymphoid phenotype. The receipt of BTD underscores the potential, if approved, for Revimenib to be the first drug to address the breadth of unmet medical needs in KMT2AR leukemia, accounting for up to 10% of all acute leukemias. Based on the broad breakthrough therapy designation and our ongoing conversations with regulators, we will pool the data generated from both the AML and ALL KMT2AR cohorts into a single NDA filing aimed at an indication to treat all relapsed refractory acute leukemia patients with a KMT2A rearrangement. Thanks to the enthusiastic support of our investigators, we have already enrolled a sufficient number of patients with KMT2A rearrangements in the phase two portion of the Augment 101 trial to enable this filing strategy. We expect to share top line data from this population in the third quarter and file an NDA for the treatment of relapsed refractory, KMT2AR, acute leukemia in adult and pediatric patients by the end of 2023. Separately, we continue to enroll relapsed refractory NPM1 mutant AML patients and expect to report completion of enrollment for these patients in the second half of 2023. These trials are enrolling well, and there was significant excitement for review by investigators at the ASH annual meeting in December, where we presented updated phase one data that Briggs will take you through on slide six. Briggs?

All right. Thank you so much, Michael. So as many of you know, at the ASH annual meeting in December of last year, Dr. Gus Issa from the MD Anderson Cancer Center presented updated results from the Phase I portion of the Augment 101 trial in two oral presentations. Of the 60 patients available for efficacy in the Phase I portion, 30% attained a CR-CRH. And notably, in patients treated at the recommended Phase II dose, CR-CRH was the same in both KMT2AR and and NPM1 subsets at 27%. The median duration of CRCRH response was impressive in this very advanced patient population at 9.1 months. There was a high MRD negativity rate of 78% among patients achieving a CRCRH, which is very meaningful in this patient population as it enables patients to proceed to potentially curative bone marrow transplant. We also reported compelling data on 12 patients who achieved a response on revumetid treatment and then went on to receive a stem cell transplant. And additionally, three transplant patients who were treated with revumetid maintenance therapy in the compassionate use setting following stem cell transplant or non-myoablative stem cell boost, two of whom remained in remission for over a year as of the data cutoff. As a reminder, in the pivotal trial, patients can be restarted on revumetid after bone marrow transplant, a design feature that provides data on the potential role of RevuMedib in the post-transplant maintenance setting. RevuMedib continues to be well-tolerated, and there have been no discontinuations due to treatment-related adverse events. As you look across the development landscape, we believe the data continue to support RevuMedib's compelling clinical profile and position it as not only first-in-class but a best-in-class treatment. I'll now turn it back over to Michael.

Great. Thanks, Frank. Turning to slide seven, given the compelling clinical and safety profile we have observed with Revimenib, our clinical development plan seeks to expand its use beyond relapse for refractory setting into earlier setting and in combination with approved therapies. Here we highlight our ongoing trials of Revimenib across the full treatment landscape, starting with the Phase 1 Beat AML umbrella trial. As part of our collaboration with the Leukemia and Lymphoma Society, Revimenem is being combined with venetoclax and asacitidine to treat newly diagnosed AML patients with an MTM1 mutation or KMT2A rearrangement who are unfit for induction chemotherapy. Revimenem is the first menin inhibitor to be included in the trial, which will assess safety as well as initial efficacy. Enrollment is ongoing, and we expect initial safety data from this trial to be available in 2023. Longer term, we expect that positive the AML trial results could lead to a Phase 2-3 trial, which could serve as the basis for a future regulatory filing. We are also currently enrolling patients in the Augment 102 trial, designed to assess revimative in combination with standard salvage chemotherapies for patients with relapsed or refractory MPM1 mutant or KMT2A rearranged acute leukemias. We also expect to have initial data available from this trial in 2023. And finally, the Intercept trial, This trial was recently initiated as part of the Intercept Master Clinical Trial led by the Australia Asian Leukemia and Lymphoma Group. This trial is a creative approach to treating patients early in their disease course, as it is focused on investigating novel therapies to target early relapse and clonal evolution as preemptive therapy in AML. It is designed to explore the activity of Revimenta, the first Menden inhibitor to be included, as monotherapy in patients with AML who have MRD-positive disease following initial treatment, a group of patients at very high risk of relapse. We're also in the process of planning a trial in combination with standard of care intensive chemotherapy used to treat FIT patients in the frontline setting. We plan to initiate that study in the second half of this year. As is detailed on slide eight, unlocking the full potential of Revimenib beyond the relapse refractory acute leukemia setting by moving it earlier in treatment and in combination with other approved agents has the potential to add meaningful value both for our shareholders and even more importantly for patients in need. With these expansion opportunities, we see the potential to address upwards of 12,000 NPM1 mutant and KMT2A acute leukemia patients across various settings. These two forms of acute leukemia together represent up to 40% of the overall AML population, which to our knowledge will be the largest subpopulation of AML to be addressed by new targeted therapies. There are currently no FDA-approved therapies targeting KMT2A or MPM1 acute leukemias. We anticipate that Revimenem could become the backbone of choice for patients with KMT2AR and MPM1 mutant acute leukemias, and we are also looking to explore Revimenem as a treatment in solid tumors based on the compelling preclinical science supporting the role the MENIN-MLL1 interaction in beta-catenin-driven tumors. A proof-of-concept signal-seeking phase 1 clinical trial in colorectal cancer is open for enrollment, and we expect to report top-line data by year-end 2023. Let me now turn to axotilamab, our potentially best-in-class monoclonal antibody therapy targeting the CSF1 receptor that has the potential to serve as an effective practice-changing intervention in this underserved population. Slide 9 provides an overview of the pivotal Agave 201 dose-ranging trial evaluating axotilamab in patients with CGVHD. The trial has completed enrollment of 240 patients whose disease has progressed after two prior therapies, were at least two years of age, and have met overall entry criteria. Patients were randomized to one of three treatment groups, each investigating a distinct dose of axotilamab given either every once or every two weeks or once every four weeks. The primary endpoint is overall response rate using the 2014 NIH consensus criteria for CGBHD, while secondary endpoints include duration of response and validated quality-of-life assessments using the modified Least Symptom Scale. We continue to expect to report top-line data from the Agave 201 trial in mid-2023. Per the terms of our collaboration agreement, Insight will be leading the regulatory filing and see GVHD, which we expect will occur in the later part of 2023. Slide 10 details the results from the Phase 1-2 trial, which showed axotilumab's ability to provide meaningful clinical responses in chronic GVHD patients that have been refractory to multiple prior therapies. This data was presented at the 2021 ASH annual meeting and subsequently published in the Journal of Clinical Oncology in December. These data were well-received among thought leaders who recognized acotilumab as having a clinical profile that would be a benefit in the treatment of these heavily pretreated patients. The overall response rate in the trial was 68%, and the median time on treatment was over six months. The overall response rate in the phase two portion was 82% and the median time to response was rapid at four weeks. Importantly, clinical responses were accompanied by a reduction in the CGBHD symptom burden and improvements in all CGBHD involved organ systems. Additionally, more than half of the responders reduced their use of steroids. Axotilumab demonstrated a favorable safety profile in this refractory population with the most common adverse events consistent with on-target effects of CSF1OR inhibition. Slide 11 highlights the broad clinical and commercial opportunity for axotilumab. CGVHD represents a high unmet medical need and an important commercial opportunity with approximately 14,000 patients suffering from CGVHD in the U.S. today. We and Insight believe the data generated to date with axotilumab suggests it has the potential to play an important role in the treatment of CGVHD both as monotherapy and given a safety profile in combination with complementary medicines. Thus, in collaboration with Insight, we are enthusiastic about expanding the exotelmab program into frontline C-GVHD in combination with ruxolitinib, and we expect a phase one combination trial in patients with newly diagnosed C-GVHD to begin later in 2023. The successful commercial launches of Insight's Jacopi and Sanofi's Resiroc are encouraging both posting meaningful early revenues that begin to speak to the commercial opportunity in CGVHD. Axotilamab has a differentiated mechanism of action from these products and could potentially offer a unique set of benefits to patients once approved. Beyond CGVHD, we are excited about the opportunity to expand Axotilamab into fibrotic diseases where the monocyte macrophage lineage plays a key role. We expect to initiate a robust phase two trial in IPF in the first half of 2023. If successful, we believe this trial, along with one additional phase three trial, could form the basis for FDA approval for the treatment of IPF. Through combinations in the frontline setting, as well as the opportunity to expand to ex-U.S. markets, we envision the CGVHD opportunity growing meaningfully. I'll now turn the call over to Keith to review our financial results.

Thank you, Michael. Let me take a few minutes to discuss our financial results for the fourth quarter and full year 2022. Turning to slide 12. The results of our operations for the fourth quarter of 2022 and the comparison to the prior year's quarter are included in our press release, so I will not repeat them in these remarks. Additional financial details are available in our fourth quarter and full year report, which was filed earlier this afternoon on Form 10-K. I'd like to point out that our net loss for the fourth quarter was $39.2 million, or $0.62 per share, compared to a net gain of $96.2 million, or $1.81 per share, for the same period last year. This difference is primarily attributed to the recognition of the upfront payment from Insight related to the acetilumab collaboration, which we entered into in December of 2021. For the full year of 2022, our net loss was $149.3 million, or $2.46 per share, compared to a net gain of $24.9 million, or $0.48 per share, for the same period last year. Again, the difference is largely due to the upfront payment in December 2021 from Insight. We ended the fourth quarter with $481.3 million in cash, equivalents, and marketable securities including the net proceeds of $162 million from our follow-on offering completed in December of 2022, and 69.3 million shares in pre-funded warrants outstanding. Our current cash is expected to provide a runway into the second half of 2025 and covers our aggressive development and pre-commercialization plans for both the Regumenta and AXA TILMAP programs, as well as provides us flexibility should we decide to selectively engage in early stage business development. Looking ahead, I'd like to provide financial guidance for the first quarter and full year of 2023. For the first quarter of 2023, we expect research and development expenses to be $30 to $35 million and total operating expenses to be $40 to $45 million. For the full year of 2023, the company expects research and development expenses to be between $160 to $175 million, and total operating expenses to be $225 to $240 million, including approximately $30 million of non-cash stock compensation expense. With that, let me now turn the call back over to Michael.

Thank you, Keith. And as you've heard during the call, 2022 was an exceptional year of growth and execution, but it It represents only the beginning of what Syndex aims to accomplish in the near future. With two pivotal trial readouts and potential registration filings in 2023 for our two lead drug candidates, both of which are first and potentially best in class treatments, Syndex is at the beginning of a significant transition into a fully integrated biopharmaceutical company serving multiple patient populations of high unmet medical need. In addition, both programs offer the potential for broad franchise opportunities beyond their initial registration indications, adding to Syndax's long-term growth potential. We have ambitious goals and milestones that I've set out for 2023, and I'm confident that we have the right plan and team in place to execute on them. Further, we are in a strong financial position with a balance sheet that allows us to deliver on key near-term milestones. As always, I want to express our deep appreciation to the Syndax team collaborators, and most importantly, the patients, trial sites, and investigators involved with our clinical programs. It is all of you who help us to execute on a mission of realizing a future in which people with cancer live longer and better than ever before. And I'd also like to thank our committed long-term investors who continue to share in our vision and support us in building Syndax. And with that, I'll turn it back over to the operator and open the call for questions. Thank you.

At this time, if you would like to ask a question, please press the star and one on your touchtone phone. You may remove yourself from the queue by pressing star and two. Once again, to ask a question, please press the star and one. And we'll take our first question from Madhu Kumar with Goldman Sachs. Your line is open.

Hi, this is Omari from Madhu. First, our first question is, does the FDA now consider KM22A rearranged AML and ALN1 cohort for filing purposes? And then second, what are you looking to see from the two different combo studies of review?

Yeah, Mari, thank you for the question. Yes, I think the answer to the first question, which is, does the FDA, as far as I heard this, does the FDA consider the KM22A one cohort for the filing purposes for K and T2A, and the answer is yes. We'll be combining both AML and ALL cohorts, pooling the patients, and filing them together. That's the plan. And the second question, I'm sorry, you cut out on the second half of it, so I couldn't hear it. Could you repeat that, please?

Sure. So the second question, what are you looking to see from two different combo studies at revenue?

Once again, it cut out. I think you said, what are we looking to see from the two studies? Is that correct?

Right, from the two combination studies for revenue.

Gotcha. So the combination studies, we have multiple combination studies ongoing. There's Augment 102, which is a chemo combo, which we'll have data on, we expect later in the year. And we have frontline trials going with Veneza, with Beat AML. and we'll be designing other trials in addition to that in the frontline setting. I think we haven't necessarily set out guidance on what we're looking to achieve. I think these are early studies where we're going to be looking at, first, of course, safety and early efficacy and trying to establish a recommended phase two dose. And I think that would be the main objective of those trials, which we'll hopefully achieve by the end of this year.

All right. Sounds good. Thanks for taking my question. Thank you.

Our next question comes from Phil Nadeau with Cohen Counting Company. Your line is open.

Good afternoon. Congrats on the progress, and thanks for taking our questions. First, a follow-up on the KMT2A population. So for the readout from the 101 trial, it sounds like both AML and ALL patients will be will be commingled in, I guess now it's a combined cohort. Will the CRCRH be analyzed regardless of myeloid versus lymphocytic etiology, or will there be any stratification for the underlying disease?

Yeah, thanks for the question, Phil. And maybe I'll let Briggs answer that question.

Yeah, so Phil, you may recall that When we announced the breakthrough therapy designation, and back to Omari's first question, the agency did accept that KMT2A rearranged leukemia is one disease, whether it presents as AML or ALL adults or kids. And part of the support for that was that the data we presented was a combination of AML, and ALL adults and PEDs. So we did break it out, and we will break it out for the agency to further support that designation. But the analysis is we'll be looking at that integrated population altogether.

Got it. Okay. And in terms of the patient numbers necessary, I know you've said that you've already recruited them. Is the number of patients necessary? equivalent to what we thought you were going to roll in cohort 2A and 2B in the study, or because they're now being combined, is the required number of patients actually equivalent to just really one cohort worth of patients?

Yeah, Phil, thanks for the follow-up. I think we haven't really guided, and we're not planning to guide on the specific number of patients in the combined cohorts. I think what we're What we've said is that it's a sufficient number based on both VTD and agency feedback. We feel that we're aligned on a strategy to have a sufficient number of patients that will constitute a filing by the end of the year. We'll have that data, of course, in the third quarter. But we're, you know, at this point, we're not guiding specifically to how many patients are in the pooled analysis.

Got it. Okay. And then... Last question on revenue before one question on access. In the NPM1 pivotal same data, or sorry, enrollment completion in the second half of the year, that seems to suggest data first half of 24, maybe mid-24, based on your prior guidance for the KMT2A population. Is that a fair assessment, or is there some reason why there could be a longer interval between enrollment completion and data in the NPM1 patients?

Thanks, Phil. I think the same rules apply. I think we say we follow patients for six months. We're not being specific as to exactly when in the second half we'll have the NPM1 enrolled. So I'm going to be a little bit conservative and not project out when we'll have top line data yet in 2024. But I think that's it's the same rules that apply to the KMT2A populations at the MPF when we follow them out for six months.

Great. And then last question from us on Axotelnet. Would you be willing to provide any additional details on the IPF phase two now, or will we have to wait until the trial is underway?

Yeah, thanks for the question, Phil. We were excited to obviously get that trial started, and we'll probably share more details on the trial and the design as we Once we're underway, I think that's probably all we'll say for now.

Okay, great. Thank you. Thanks, Bill.

Our next question comes from Anupam Rama with J.P. Morgan. Your line is open.

Hi, this is Priyanka on for Anupam Rama. Just a quick question from us. Between the two KMT2A cohorts, could you provide any color or clarity on enrollment breakdown?

Yeah, thank you for the question. As I said previously, we're not going to give specific guidance on how many patients were contributed from the, you know, either of the two cohorts. What we're guiding to is that we have a sufficient number that we can complete the analysis, and we'll provide that top line data in the third quarter. So I think we'll have to be satisfied with that for now. I think that's the guidance we're sticking with.

Understood. Thank you.

Thanks for the question.

Our next question comes from . Your line is open.

Hi, Jim. This is . Thanks for taking my questions. Just on NPM1, do you have clarity on the number of NPM1 patients you need to enroll? to hit your timeline, have you spoken with the FDA on specifically NPM1?

Yeah, thanks for the question. We had previously disclosed 64 patients, NPM1 patients, as we had laid out the three cohorts. 64 patients is the number that we'll look to enroll. And we have, of course, spoken with the agency about not only NPM1, but KMT2A. We've had a fair amount of interaction with them over the several months since we started this program. Um, and we've aligned on our, not only our design, but all the statistics that, uh, go into each of the cohorts. So, uh, yeah, not, nothing really new there. It's, it's still, it's still the same. It's still the same number of patients that we had guided to use.

Okay. Are you able to provide any, any clarity on where you are in terms of fitting, uh, the 64 patient number?

Only that we've, yeah, thanks for the follow-up. Only that we've, um, We've guided to the second half of the year. Sometime in the second half of the year, we'll be able to officially announce that we've enrolled to 64, and you'll be able to figure out from there exactly whereabouts we are with presenting comp-line data.

Okay, got it. And maybe one more on axotilumab. For the frontline combo trial with ruxolitinib, which you're studying later this quarter, How should we be thinking about maybe the combinability of acetilinab with afaxalitinib, maybe in terms of potential for overlapping toxicities, maybe such as pneumonia or liver enzymes, for example? Is there any color you can share on combinability?

Thanks. Yeah, thanks. Thanks for the question, Asher. Maybe I'll have Briggs address the overlapping toxicities. And just to point out, I think the trial, this is insights. combination trial that they'll be kicking off. And I think the guidance is later this year. We didn't specify the first quarter in particular, but I think it's a trial we're all looking forward to and maybe breaks if you could address the overlapping toxicities.

Yeah, look, I think that was part of the keen interest of Insight and wanting to partner with us on Axtelomat because at least if you look at the monotherapy toxicities of each agent, they look like they would combine quite well. That, of course, is the purpose of the initial phase of the combinations is to characterize that. But going into that trial, we would be quite optimistic that we could get full doses of both agents.

Okay, got it. Thanks for taking my questions.

Thank you.

Our next question comes from Brad Canino with Stiefel. Your line is open.

Good afternoon. Thanks for taking the questions. This is Brad. It doesn't sound like I can get more out of you on Augment 101, so maybe I'll ask about the status of the Phase 1 ClinPharm work you're doing around the multiple doses of Revu for the CYP inhibitor strength. Should we expect a data disclosure from that this year?

Brad, thanks for the question. As you, I think, pointed out in your question, these are supportive trials, or this particular trial is supportive piece of our filing, central filing for Revimentib, and that work is ongoing. I don't think we've guided to when we would necessarily disclose data from that trial. I think we related to certain pieces of this. There may be, there will be data that comes out in the ultimate filing when we disclose data, but I don't think there's any particular timeline related to when we might disclose for that particular study. But thanks for the question.

Okay. And then maybe one on the safety data for the beat AML, because it's exciting to get some combo data this year. I guess to set expectations for that, can you discuss the Revu dose being used there? Is it all the 163 on a strong SIP? Or is there any dose escalation of Revu taking part in that combo? And then for the VenAza component, what is the schedule for Ven? does it require continuous dosing or can physicians use the shortened schedule that's often used in clinical practice now? Thank you.

Yeah, Brad, very good question. Maybe I'll let Briggs address both of those.

Yeah. So it, you know, the starting is the, the standard Veneza labeled regimen. Obviously there are protocol specified dose interruptions if needed, but we, the, the request was to start with the, the labeled regimen. Um, and then there is a dose escalation opponent to the, the revimenib, um, uh, but everybody is on a strong inhibitor.

Great. Thank you. Thank you, Brad.

Our next question comes from Peter Lawson with Barclays. Your line is open.

Great. Thanks for taking the questions. Um, I guess just around NPM1, just any update around how enrollment's proceeding there. And then I've got a question on axitimumab.

Thanks, Peter. Thanks for the question. NPM enrollment is going well. KMT2A is going well as well. So I think they're both, there's great enthusiasm. Certainly since ASH, I would say that investigators have you know, really engaged with us and have really related to the data that they saw at the meeting. And so NPM-1 enrollment is going well. So there's, you know, and I think that relates to our ability to complete enrollment in the second half of this year. And then you had a follow-up.

Yeah, just around Axanthillimab, just with Sanofi's Resiroc, just with that launch, kind of how do you look at that and Gauge your own potential launches. How should we think about peak revenues and whether you think this is ultimately a single agent or a combination agent regimen?

Thanks for the questions, Peter. So, yeah, look, I think you heard in my remarks, Resrock has done well. It's first year sales, upwards of $250 million in sales. Impressive. This is a Our drug has a different mechanism of action, and we think impressive results thus far in its clinical trials. And I think the opportunity here in chronic graft-versus-host disease is to access patients in the relapsed refractory setting. I think these patients tend to, over their course of their treatment journey, they tend to get multiple therapies. They cycle through the different therapies. And so our opportunity, we think, is is what Resiroc and or Jacopi experience in the third line, the ability to pick up meaningful share. Ultimately this, and that's his monotherapy, but ultimately the opportunity here extends itself well beyond just monotherapy into potential combinations. Resiroc is, you know, has its own opportunity for combinations potentially, but the mechanism of action of our drug is not overlapping with Jacopi. And so that's the, as Briggs pointed out, that's the reason why I think we're so excited about being able to combine it in a frontline setting and potentially reduce the use of steroids, which could really expand the use of this drug beyond what Resiroc has even shown in relapsed refractory in first year. If you think about that a little harder, first-year sales in 2 to 250, that's showing to be a potentially very large opportunity. And again, that's just in relapsed refractory, third-line plus disease. And so the opportunity to go in combination and get the patients earlier in their treatment journey, I think really pertains well for our drug. And I think, you know, is there something else to your question, Peter?

That was great. Thank you so much.

Yeah, thank you.

And our next question comes from Kalpit Patel with B. Reilly Securities. Your line is open.

Yeah, hey, good afternoon. Thanks for taking the questions. You mentioned that the enrollment for the NPM1 cohort is going well. So I'm just curious about the timing differences versus the KMT2AR cohort. Is that just a function of when these trials started enrolling? Just trying to understand the gap there.

Yeah, thanks, Scott. Good question. Look, as I said, we are pleased with the enrollment and the physician enthusiasm for both NPM1 and KMT2A. I do think that, you know, BTD has sort of advantaged our filing strategy for KMT2A and the ability to combine cohorts may have something to do with our ability to kind of move slightly more quickly with KMT2A. So I think that's part of it. The other part of it is that KMT2A, you know, there's probably a little less competition for patients with our competitors. And, you know, NPM1 may be drawing more patients into various studies. So I do think that there are some competing factors here, some contributing factors here. But ultimately, I think we're doing quite well with NPM1, and we feel that you know, getting to market as quickly as we can with KMT2A will advantage us greatly as we bring data behind for NPM1 and hopefully get that approved as well.

Okay. And then maybe one question on the combo studies. Has the dosing commenced for the beta AML study? I think you stated that we were just expecting safety this year, so I was just wondering if dosing started yet.

Yes. Thank you for the question, Calvin. So, yeah, the combination studies have initiated. So, there is the, again, the Augment 102 chemo combination that has been enrolling patients, as well as the beta-AML trial that is also enrolling patients, so they both start.

Okay. All right. Fantastic. Thanks for taking the questions. Thank you.

And our next question comes from Bert Haslund with BTIG. Your line is open.

Thanks. Thanks for taking the question. Just one or two for me. Could you just remind, with the consideration of revumet and post-transplant, is there a regulatory or an indication strategy there, or are you thinking about that as a compendium listing or publication strategy? Could you just frame how you're thinking about that from a regulatory perspective?

Sure. Frase, do you want to take that question from Bert, please?

Yeah. So Bert, in the ongoing pivotal trials, we allow patients to go back on to Revimentib after their, if they have a response, go to transplant, they can go back on Revimentib. That work in the pivotal trial, we don't anticipate a label indication for that. Best case scenario is we might be able to describe in the label how the trial was conducted. So I think that information will be mostly gotten out into the community through publications. It does set us up for potentially a formal maintenance trial down the road, but the way we're handling it in the pivotal trial, there won't be a claim regarding maintenance.

Okay. That's helpful. Thank you. And then just shifting gears from a corporate perspective, back to Axotilimab, I believe you have a co-promote option there, and you've hired a head of commercial relatively recently. How are you thinking about that decision, and is there a particular timing in which that needs to be executed on your part? Great.

Thanks for the question. Good question. You're correct. Our agreement with Insight does include a co-promotion option. on axotilumab. That election is made in proximity to filing. So it is something that we'll have to, you know, kind of let people understand a little bit better in the coming months as we get closer and closer to that time point. Obviously, we'll have a filing, as we said, before the end of the year. So we're thinking actively about it. I would just say that we have two programs that as we've described today, as you know, that are really on top of one another in terms of timing, both for filing and then approval. And so the commercial opportunities, while not the same, may have some synergy in terms of the doctors that are being called on and how we promote these products. So the thought potentially is that there could be some very nice synergy between what we do with Revumeneb and Axotilimab, and so that we're thinking actively about whether the co-promotion option makes sense for us.

Okay, thanks. And I know it may be early, but any thoughts on Salesforce sizing infrastructure, things like that?

Sure. It's a longer conversation. I would say that this is a focused commercial effort, meaning that these are not very large patient populations. More importantly, they're covered by a reasonably focused number of physicians. And so the field force to cover it is somewhere in the order of 40 to 50 physicians, 40 to 50 reps. We'll refine those estimates and start to give some more color to what the organization looks like that we're building, but we are actively engaged in bringing in leadership to the company in order to be ready in time for launch for both of these products.

Terrific. Look forward to more. Thanks. Thank you, Bert.

Our next question comes from Joel Beattie with Baird. Your line is open.

Okay. Thanks for taking the question. First one is on the pooled TMT 2A cohort. Do you anticipate that the efficacy will be presented just for the pooled cohort on the label, or could there also be a breakdown of AML and ALL on the label?

Yeah, Joel, great question. I think that was sort of alluded to or part of another question that was asked earlier. The strategy for pooling is that the, you know, we'll be presenting a, you know, total number of patients and they'll be analyzed. I think the, of course, the agency will look at all the subsets and we'll have a breakdown of that. And I think that that'll be part of our package, but essentially the, the analysis, the primary analysis that will be done is on the pooled patient

Okay, thanks. And then a question on R&D. It looks like we'll ramp up over the course of 2023. Any priorities that you anticipate will be a part of that increase?

Yeah, Joel, this is Keith. I'll take that one. So a lot of the increase in 2023 will go towards the initiatives that Michael laid out in his comments. You know, we have a pretty expansive development program for RevuMeta to realize the full potential. The current pivotal programs are focused in relapse refractory, obviously, but going forward, you know, you heard Michael expand upon all of the work needed to, again, recognize that full potential looking, you know, frontline combos, maintenance therapy, et cetera. Additionally, in anticipation of a filing by year end, And to be ready for a launch in 2024, there'll be an increase in CMC slash takeoff expenses to get our registration batches manufactured. Remember, we do have not only solid tablet formulation that we'll be bringing to market, but also a liquid formulation as well. So that's the majority of the increase.

Great. Thank you.

Thank you, Joel.

It appears we have no further questions at this time. I'll turn the program back to Michael Metzger for any additional or closing remarks.

Great. Thank you, operator. And thank you all. We look forward to seeing many of you at the Cowan and Barclays Healthcare Conferences in the next few weeks in March. And with that, I wish you all good night. Thank you.