Q1 2024 Syndax Pharmaceuticals Inc Earnings Call

Operator: Good day, everyone, and welcome to the Syndex first quarter 2024 earnings conference call. Today's call is being recorded. At this time, I'd like to turn the call over to Sharon Klahre, Head of Investor Relations at Syndex Pharmaceuticals.

Good day, everyone and welcome to this index first quarter 2024 earnings Conference call. Today's call is being recorded at this time I would like to turn the call over to Sharon <unk> head of Investor Relations at <unk> Pharmaceuticals.

Sharon Klahre: Thank you, Operator. Welcome, and thank you all for joining us today for a review of Syndax's First Quarter 2024 Financial and Operating Results. I'm Sharon Klahre, and with me this afternoon to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer, Dr. Neil Gallagher, President and Head of R&D, Steve Kloster, Chief Commercial Officer, and Keith Goldan, Chief Financial Officer. Also joining us on the call today for the question and answer session are Dr. Peter Ordentlich, Chief Scientific Officer, and Dr. Anjali Ganguli, Chief Business Officer.

Sharon: Thank you operator, welcome and thank you all for joining US today for a review of <unk> first quarter 2024 financial and operating results.

Sharon: I think Larry and with me. This afternoon to provide an update on the company's progress and discuss financial results are Michael Metzger, Chief Executive Officer, Dr. Neil Gallagher, President and head of R&D.

Speaker Change: <unk> cluster, Chief commercial officer, and Keith go their Chief Financial Officer also joining us on the call today for the question and answer session are Dr. Peter <unk>, Chief Scientific Officer, and Dr. Angela Ganguly Chief business Officer.

Sharon Klahre: This call is accompanied by a slide deck that has been posted on the investor page of the company's website. Now, you can turn to our forward-looking statements on slide two. Before we begin, I'd like to remind you that any statements made during the call that are not historical are considered to be forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. However, actual results may differ materially from those indicated by these statements as a result of various important factors, including those discussed in the risk factor section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC

Speaker Change: This was 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 statements on slide two before we begin I'd like to remind you that any statements made during the call that are not historical are considered to be forward looking statements within the meaning of the private Securities Litigation Reform Act of 19 nine.

Speaker Change: Actual results may differ materially from those indicated by statements as a result of various important factors, including those discussed in the risk factor section in the company's most recent quarterly report on Form 10-Q, as well as other reports filed with the SEC.

Sharon Klahre: Any forward-looking statements made represent our views as of today, May 8, 2024, only. A replay of this call will be available on the company's website, www.syndax.com, following its completion. With that, I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of Syndax.

Speaker Change: Any forward looking statement made represent our views as of today may eight 2020 for only a replay of this call will be available on the Companys website Ww that index Dot com. Following its completion with that I am pleased to turn the call over to Michael Metzger, Chief Executive Officer of syntax.

Michael A. Metzger: Thank you, Sharon, and good morning, everyone, and thank you for joining us on the call today. I'd like to begin by welcoming Steve Kloster to the call.

Michael A. Metzger: You Sharon and good morning, everyone and thank you for joining us on the call today.

Michael A. Metzger: I'd like to begin by welcoming Steve closer to the call.

Michael A. Metzger: Steve joined us in March as Chief Commercial Officer. He brings over 30 years of commercial experience to Syndax, which includes establishing winning teams and leading successful product launches. Steve is building on the excellent framework that was in place prior to his arrival, and we are already benefiting from his keen insights as we prepare for commercialization. In the quarter, we made significant progress on executing against our corporate strategy.

Michael A. Metzger: <unk> joined Us in March as Chief commercial officer.

Michael A. Metzger: He brings over 30 years of commercial experience. This index, which includes establishing winning winning teams and leading successful product launches.

Michael A. Metzger: <unk> is building on the excellent framework that was in place prior to his arrival and we are already benefiting from his keen insights as we prepare for commercialization.

Michael A. Metzger: In the quarter, we made significant progress on executing against our corporate strategy as you can see on slide three we achieved several significant milestones this quarter, including security priority review from the FDA for both the revenue minute NDA filing and the <unk> BLA filing we also completed enrolling.

Michael A. Metzger: As you can see on slide three, we achieved several significant milestones this quarter, including securing priority review from the FDA for both the Revumentib NDA filing and the Axotilumab BLA filing. We also completed enrollment in the NPM1 AML cohort of the Augment 101 Pivotal Trial, bringing us one step closer to expanding the market opportunity for RevuMenip. We look forward to reporting data from the initial trial in the fourth quarter of this year, which could serve as the basis for a supplemental NDA filing in the first half of 2025.

Michael A. Metzger: Matt.

Michael A. Metzger: In the <unk> AML cohort of augment 101 pivotal trial, bringing us one step closer to expanding the market opportunity for <unk>.

Michael A. Metzger: We look forward to reporting data from the initial trial in the fourth quarter of this year.

Michael A. Metzger: Which could serve as the basis for a supplemental NDA filing in the first half of 2025.

Michael A. Metzger: These accomplishments set us up for an eventful 2024 that we expect will include two full U.S. regulatory approvals, NPM1 pivotal data readout, additional combination data for Revimenib in KMT2a and NPM1, initiation of a pivotal trial for Revimenib in frontline KMT2a and NPM1 acute leukemia in combination with venetoclax, as well as the initiation of two combination As we approach our expected approvals, we are working to ensure that we are fully prepared to successfully launch the product at any time during the third quarter with an ability to reach all patients in need as rapidly as possible. Steve will provide additional details on our launch preparations later in the call.

Michael A. Metzger: These accomplishments set us up for an eventful 2024 that we expect will include two for U S regulatory approvals.

Michael A. Metzger: PM one pivotal data readout additional combination data for <unk> and <unk>.

Michael A. Metzger: And <unk> the initiation of a pivotal trial for <unk> in frontline <unk> and NPM, one acute leukemia in combination with genetic class as well as the initiation of two combination trials for <unk> in frontline chronic graft versus host disease as we approach our expected approvals we are working to ensure.

Michael A. Metzger: Sure that we are fully prepared to successfully launch at any time during the third quarter with an ability to reach all patients in need as rapidly as possible Steve will provide additional details on our launch preparations later in the call.

Michael A. Metzger: Syndax has a differentiated profile as a SMITCAP biotech with two first and best-in-class drugs on the cusp of their potential first approval. Notably, revumentib has a potential second significant indication and near-term expansion opportunity in relapsed or refractory MPM1 that meaningfully extends the target patient population in acute leukemia. This is unique in a launch year as it quickly broadens the market opportunity for Revumentum in the relapsed or refractory setting to up to 6,500 patients.

Michael A. Metzger: <unk> has a differentiated profile as a smid cap biotech with two first and best in class drugs on the cusp of their potential first approvals.

Michael A. Metzger: Notably <unk> has a potential second significant indication and near term expansion opportunity in relapsed or refractory NPM, one that meaningfully extends the target patient population in acute leukemia.

Michael A. Metzger: This is unique in the launch here as it quickly broadens the market opportunity for revenue in the relapsed or refractory setting to up to 6500 patients multiple opportunities beyond the initial relapsed or refractory indication exists for both assets and trials are ongoing that can drive significant long term value for these franchises.

Michael A. Metzger: Multiple opportunities beyond the initial relapse or refractory indication exist for both assets, and trials are ongoing that can drive significant long-term value for these franchises for years to come. We are well funded with $522 million in cash as of March 31st, which we expect will provide significant capital through 2026. Our current balance sheet not only supports our planned commercial launches and clinical trials but also allows us to expand beyond our core registration indications and pursue select business development opportunities. I'll now ask Neil to provide an overview of the pipeline. Neil?

Michael A. Metzger: For years to come.

We are well funded with $522 million in cash as of March 31 that we expect will provide significant capital through 2026.

Michael A. Metzger: Our current balance sheet not only supports our planned commercial launches and clinical trials, but also allows us to expand beyond our core registration indications and pursue select business development opportunities.

Michael A. Metzger: I'll now ask Neal to provide an overview of the pipeline Neal. Thank you Michael in the first quarter at the NDA filing for at the amount of a highly selective <unk> inhibitor was granted priority review by the FDA for the treatment of adult and pediatric relapsed or refractory <unk> rearranged or came to to keep the <unk> and <unk>.

Neil Gallagher: Thank you, Michael. In the first quarter, the NDA filing for reviomenib, or highly selective menin inhibitor, was granted priority review by the FDA for the treatment of adult and pediatric relapsed or refractory KM22A rearranged or KM22AR acute leukemia and issued a pedophilic target date of 26th September 2024. The filing is being reviewed under the Real-Time Oncology Review, which provides a more efficient review process and has historically led to earlier approval times.

Neal: Target date of 26th of September 2024.

Neal: Refining is being reviewed under the real time oncology review, which provides a more efficient review process and has historically led to earlier approval timelines.

Neil Gallagher: The submission is based on data from the Pivotal Augment 101 trial outlined on slide 4, where single-agent revumenib induced a high percentage of blast-free responses in heavily pre-treated KMT2AR acute leukemia patients, thereby enabling many of them to undergo potentially curative mitopoietic stem cell transplantation and to continue revumenib monotherapy following transplantation. We've also completed enrollment in the final pivotal cohort of the Augment 101 trial of 64 adult relapsed or refractory NPM1 AML patients in March, and we expect to report the pivotal results from this population in the fourth quarter of this year.

Neal: The submission is based on data from the pivotal augment 101 trial outline.

On slide four where single agent regimen had been due to high percentage of blast flip free responses in heavily pre treated <unk>, our acute leukemia patients, thereby thereby enabling many of them to undergo potentially curative hematopoietic stem cell transplant and to continue recommended monotherapy following transplant.

Neal: We've also completed enrollment in the final pivotal cohort of the augment 101 trial of 64 adults relapsed to refractory <unk> AML patients in March and expect to report the pivotal results from this population in the fourth quarter of this year.

Neil Gallagher: I'll take a moment to review the phase one data on slide five that underlines our confidence in the pivotal results for patients with relapsed or refractory MPM1 AML. Multiple presentations generated by us in both the relapsed or refractory and front-blind settings have highlighted the consistency of menin inhibition across NPM1 mutations and KMT2A rearrangements, and we see the enthusiasm building for Revium Enib in NPM1.

Neal: I'll take a moment to review the phase one data on slide five that underlines our confidence in the pivotal results for patients with relapsed or refractory <unk> AML.

Neal: Multiple presentations generated by us in both the relapsed or refractory and frontline settings have highlighted the consistency of menin inhibition across NPM, one mutations and came to tweak Kmt two eight re arrangements and we see the enthusiasm building for the resi for revenue that had been MTN one day.

Neil Gallagher: The Phase 1 NPM1 data that we've reported supports our conviction that Revumenib could be an important treatment for this AML population. In the Phase 1 part of Augment 101, 50% of NPM1 patients achieved an overall response, and 36% achieved complete remission or CR with partial pathological recovery. And importantly, all patients with CR-CRH were MRD negative.

Neal: The phase one <unk> one data that we've reported supports our conviction that <unk> could be an important treatment for this AML population.

Neal: And the phase one part of augment 101, 50% of NPM one patients achieved an overall response and 36% achieved complete remission or CR with partial metallurgical recovery unimportant, but importantly, all patients with CRC rates were <unk> negative.

Neil Gallagher: Consistent with the Cain-228R population, RevuMenop also enabled a high percentage of NPM1 responders to proceed to transplant, 43%, and responses have been durable. This is despite many of the patients having failed prior venetoclax therapy and prior stem cell transplants. It's worth noting that Revumenop has been well tolerated in patients with relapsed or refractory ampium 1 AML. In phase 1, there were no grade 4 or 5 QT prolongation events, no patient experienced greater than grade 2 differentiation syndrome, and no patients discontinued due to treatment-related adverse events.

Neal: Consistent with the <unk> population Regiment have also enabled a high percentage of NPM. One responders to proceed to transplant, 43% and responses have been durable. This is despite many of the patients who have failed prior <unk> therapy and prior stem cell transplants.

Neal: Worth, noting that <unk> has been well tolerated in patients with relapsed or refractory <unk> AML in the phase one there were no grade four or five Qt prolongation events, no patient experienced greater than grade two differentiation syndrome, and no patients discontinued due to treatment related adverse events.

Neil Gallagher: We believe that Revumena will form the backbone of treatment for patients with both KMT2AR and MPM1 acute leukemias. Our clinical strategy extends beyond the initial relapsed or refractory populations and into the frontline and post-transplant maintenance settings, including combinations with approved therapies. We have several combination trials ongoing with different standards of care across the continuum of patients, including in the fit and unfit settings that are listed on slide six. Investigators presented data from multiple Phase I combination trials, including BEAT-AML, SAVE-AML, and AUGMENT-101, during the American Society of Hematology conference in December, demonstrating review management's ability to safely and effectively combine with standard of care.

Neal: We believe that revenue amount of a form the backbone of treatment for patients with both came to today are under MQM, one acute leukemias.

Neal: Our clinical strategy extends beyond the initial relapsed or refractory population sent into the frontline and post transplant maintenance settings, including combinations with approved therapies. We have several combination trials ongoing with different standards of care across the continuum of patients, including in the fit and unfit settings that are listed on slide six.

Neal: Investigators presented data from multiple phase one combination trials, including beat AML save AML on augment 101 during the American Society of Hematology conference in December demonstrating <unk> ability to safely and effectively combined with the standards of care.

Neil Gallagher: We expect to provide updated data from these trials later this year. In the first quarter, we initiated another phase one combination trial with standard of care intensive chemotherapy, also known as 7 plus 3. Beyond acute leukemia, we're investigating the opportunity to expand to solar tumors. Our proof of concept signal-seeking phase one clinical trial in metastatic colorectal cancer is ongoing, and we expect to provide an update on the progress of the dose escalation phase of the trial later this quarter. Turning to Isotonab on slide seven.

Neal: We expect to provide updated data from these trials later this year.

Neal: In the first quarter, we initiated another phase one combination trial with standard of care intensive chemotherapy also known as <unk> seven plus three.

Neal: Beyond the acute leukemia, we are investigating the opportunity to expenses solid tumors, our proof of concept signal seeking phase one clinical trial in metastatic colorectal cancers ongoing and we expect to provide an update on the progress of the dose escalation phase of the trial later this quarter.

Neal: Turning to <unk> on slide seven.

Neil Gallagher: Also in the first quarter, the BLA-filing Fraxetilumab, or CSF1R, antibody was granted priority review by the FDA for the treatment of chronic graft-versus-host disease, or chronic GVHD, after failure of at least two prior lines of systemic therapy, with a PDUFA date of August 28, 2024. The submission is based on data from the Pivotal Agave 201 trial, where treatment with single-agent axotilamide led to an overall response rate of 74%, with 60% of responders still in response at one year. Importantly, axotilamab has a differentiated mechanism of action from currently approved therapies for chronic GVHD. It is the first investigational chronic GVHD agent to target inflammation and fibrosis through the inhibition of disease-associated macrophages.

Also in the first quarter, the BLA filing <unk> CSF, one antibody was granted priority review by the FDA for the treatment of chronic graft versus host disease or chronic gvhd. After failure of at least two prior lines of systemic therapy with a <unk> date of August 22020 for.

Neal: The submission is based on data from the pivotal Agave 201 trial are treatment with single agent <unk> led to an overall response rate or <unk> of 74% with 60% of responders response at one year.

Neal: Importantly, <unk> has a differentiated mechanism of action from currently approved therapies for chronic gvhd. It is the first investigational chronic gvhd agent target inflammation.

Neal: Excuse me information inflammation and fibrosis through the inhibition of disease associated macrophages, we're excited about the opportunity to expand <unk> into the frontline setting in combination with the standards of care and that other fibrotic diseases, where monocyte macrophage lineage place, a kilo, including idiopathic pulmonary fibrosis or IPF, where we're currently enrolling.

Steve Kloster: We're excited about the opportunity to expand lexotilamab into the frontline setting in combination with standards of care and other fibrotic diseases where the monocyte macrophage lineage plays a key role, including idiopathic pulmonary fibrosis (or IPF), where we are currently enrolling a phase two clinical trial. The team has been working hard to increase awareness of the compelling review benefits of Augment 101 and the Axotilumab Agave 201 data ahead of the respective potential approval.

Neal: <unk> II clinical trials.

Neal: The team has been working hard to increase awareness of the compelling ROI.

Neal: The amount of augment 101, and the access to them.

Neal: I have a 201 data ahead of their respective potential approvals and.

Steve Kloster: In April, investigators presented pediatric data from Augment 101 at a plenary session of the American Society of Pediatric Oncology that further supports the consistency of the data across subgroups. Also in April, investigators presented additional analyses from Agave 201 at the European Society for Blood and Marrow Transplantation Congress, highlighting axotilamide's impressive clinical activity in fibrosis-dominant organs, which, as I We have an ambitious publication plan underway, and we look forward to detailing more of the clinical benefits of Exetomab and Revumenib to the prescribing community. I'll now turn the call over to Steve to talk about preparation for the planned commercial launches and the market opportunity. Steve. Thank you, Neil.

Neal: In April investigators presented pediatric data from augment 101.

Neal: Plenary session of the American Society of pediatric hematology oncology that further supports the consistency of the data across subgroups.

Neal: Also in April investigators presented additional analyses from <unk> hundred one at the European Society for blood and marrow transplantation.

Neal: Congress, highlighting <unk> impressive clinical activity and fibrosis dominant Oregon switch as I mentioned earlier is a key point of differentiation. We have an ambitious publication plan underway and we look forward to detailing more if the clinical benefits of <unk> and recommended to the prescribing community I'll now turn the call over to Steve to talk about.

Neal: Reparation for our planned commercial launches on the market opportunities Steve.

Steve Kloster: Thank you, Neil. This is an exciting time to be at Syndax, and we're looking forward to launching two first-in-class and meaningfully differentiated agents this year. As Michael indicated earlier, we'll be ready to launch both Revumativ and Axotilumab in the third quarter, and we've made significant progress so far this year to prepare ourselves and the market to realize the full potential of these medicines for patients, for healthcare professionals, and the company. Our key focus areas are highlighted on slide 8.

Steve: Thank you Neil this is an exciting time to be its index and we're looking forward to launching two first in class and meaningfully differentiated agents. This year as Michael indicated earlier, we will be ready to launch both revenue amount of <unk> in the third quarter and we've made significant progress so far this year to prepare ourselves.

Steve: Market to realize the full potential of these medicines for patients for health care professionals in the company are.

Steve: Our key focus areas are highlighted on slide eight.

Steve Kloster: Our pre-commercialization strategy has focused on developing an efficient, effective, and purpose-built infrastructure to support the business and prioritize relationships with important external stakeholders in the healthcare provider as well as the payer space to accelerate uptake at launch. For RevuMed, our pre-launch activities have been centered around disease awareness, the mechanism of disease education, and market access, as well as ensuring patient support services are in place at the time of launch. The customer-facing leadership team has been in the field for some time and focuses on disease state awareness and building relationships with health care providers.

Steve: Our pre commercialization strategy is focused on developing an efficient effective and purpose build infrastructure to support the business and prioritize relationships with important external stakeholders.

Steve: In the health care provider as well as the payer space to accelerate uptake at launch for.

Steve: For revenue, our prelaunch activities have been centered around disease awareness mechanism of disease education and market access as well as ensuring patient support services are in place at the time of launch customer.

Steve: Customer facing leadership team has been in the field for some time and focus on disease state awareness and building relationships with health care providers.

Steve Kloster: The team is actively profiling accounts, understanding workflows, and identifying the patient journey at the largest and most influential academic centers in the country. This has allowed us to have important conversations with health care providers and other health care organization decision makers and gain valuable insights into the market, which has helped us define our outreach strategy. We launched our non-branded campaign last year, focused on improving the knowledge and understanding around the role of men and inhibition across key segments of acute leukemia, including KMT2A rearrangements, as well as follow-on indications like NPM1 mutant AML.

Steve: <unk> is actively profiling accounts understanding workflows and identifying the patient journey at the largest and most influential academic centers in the country.

Steve: This has allowed us to have important conversations with health care providers and other health care organization decision makers and gained valuable insights on the market, which has helped us define our outreach strategy. We launched our non branded campaign last year focused on improving the knowledge and understanding around the role of Menin inhibition across key segments of acute.

Steve: EMEA, including Kmt <unk> rearrangements as well as follow on indications like NPM, one mutant AML. This effort will expand as we approach a potential launch.

Steve Kloster: This effort will expand as we approach a potential launch. We've recruited a talented and highly experienced sales team with an average of 22 years of experience, primarily in hematology and oncology, with an average of six product launches per representative. This is obviously a very experienced group with existing relationships and proven past success.

Steve: We've recruited a talented and highly experienced sales team with an average of 22 years of experience primarily in hematology oncology.

Steve: An average of six product launches per representatives. This is obviously, a very experienced group with existing relationships and proven past success the customer facing field team will play a multidisciplinary role in supporting health care professionals and patients.

Steve Kloster: The customer-facing field team will play a multidisciplinary role in supporting healthcare professionals and patients. With regard to market access, our team has been educating commercial and Medicare payers on the burden of relapsed or refractory acute leukemia to prepare them to conduct timely and evidence-based reviews and ultimately access decisions upon potential FDA approval while formulary approval builds over time. We have little doubt that Revumentum will be covered for reimbursement while plans review the product for formulary inclusion.

Steve: With regard to market access our team has been educating commercial and Medicare payers on the burden of relapsed or refractory acute leukemia to prepare them to conduct timely and evidenced based reviews and ultimately access decisions upon potential FDA approval, while formulary approval builds overtime, we have little doubt that <unk> will be.

Steve: Covered for reimbursement, while plans to review the product for formulary inclusion.

Steve Kloster: We've been meeting with pharmacy benefit managers and payers since 2023, sharing relevant market and product information, and expect to reach plans covering more than 90% of all lives prior to Revumentum's anticipated approval. Payers are telling us that they recognize a significant unmet need in KMT2AR acute leukemia patients and the benefit that Revumetib could provide as supported by the Augment 101 data. This is important due to the acute nature of the disease and the high mortality and morbidity of relapsed or refractory KMT2AR acute leukemia, making the urgency to treat it quickly absolutely critical. I'm excited about our progress to date and look forward to sharing more about our ongoing efforts in the future. Turning now to slide nine.

Steve: We've been meeting with pharmacy benefit managers and payers since 2023 sharing relevant market and product information and expect to reach plans covering more than 90% of all lives prior to <unk> anticipated approval.

Steve: Payers are telling us that they recognize the significant unmet need and Kmt <unk> acute leukemia patients and the benefit that <unk> could provide as supported by the augment 101 data. This is important due to the acute nature of the disease and the high mortality and morbidity in relapsed or refractory <unk> acute leukemia.

Steve: Making the urgency to treat quickly absolutely critical.

Steve: Excited about our progress to date and look forward to sharing more about our ongoing efforts in the future.

Steve: Turning now to slide nine.

Steve Kloster: KMT-2AR and MPM1 acute leukemias represent up to 40% of all AML patients, and there are no FDA-approved targeted therapies for this population. We believe relapsed or refractory KMT-2AR acute leukemia alone represents a total addressable market of approximately $750 million in the U.S. The annual incidence of KMT-2AR acute leukemia is about 2,600 patients, and the majority are refractory to front-line standard care treatment.

Steve: Kmt <unk> and NPM, one acute leukemias represent up to 40% of all AML patients and there are no FDA approved targeted therapies for this population, we believe relapsed or refractory <unk> acute leukemia alone represents a total addressable market of approximately $750 million in the U.

Steve: The annual incidence of KFC <unk> acute leukemia is about 2600 patients and the majority of our refractory to frontline standard of care treatments. We estimate a median duration of therapy across the treated population of approximately nine months and we believe the clinical data supports pricing competitively to other targeted therapies in AML as such.

Steve Kloster: We estimate a median duration of therapy across the treated population of approximately nine months, and we believe the clinical data supports pricing competitively to other targeted therapies in AML, such as the FLT3 or IDH inhibitors. Physicians we've spoken with indicate an eagerness to prescribe Revumetiv early during an eligible patient's treatment journey to bring more patients to transplant and then extend responses by continuing with Revumetiv monotherapy following transplant and graft. We expect that our first mover advantage and the early experience physicians will gain treating patients with Revumetib will be vitally important to the long-term success of our brand.

Steve: As the flip III or ADH inhibitors <unk>.

Steve: <unk>, we've spoken with indicate an eagerness to prescribe revenue amount of early during an eligible patients treatment journey to bring more patients to transplant and then extend responses by continuing with <unk> monotherapy following transplant in graphics.

Steve: We expect that our first mover advantage and the early experience physicians will gain treating patients with <unk> will be vitally important to the long term success of our brand our significant market share is likely to extend meaningfully beyond Kmt <unk>, especially as we will be the first to deliver meaningful pivotal data in other indications such as.

Steve Kloster: Our significant market share is likely to extend meaningfully beyond KMT2-AR, especially as we will be the first to deliver meaningful pivotal data in other indications, such as NPM1-AML. We estimate that the two distinct market segments in acute leukemias, KMT2-AR and NPM1, have a total accessible population of 5,000 to 6,500 patients in the relapsed or refractory setting and an addressable market opportunity that approaches $2 Turning now to slide 10.

Steve: <unk> AML, we estimate that the two distinct market segments in acute leukemias, Kmt <unk> avail of total accessible population of 5000.

Steve: The 6500 patients in the relapsed refractory setting in an addressable market opportunity that approaches $2 billion in the U S.

Speaker Change: Turning now to slide 10.

Steve Kloster: Approximately 14,000 U.S. patients suffer from chronic GVHD, 50% of whom require treatment beyond second line due to disease progression, inadequate response, or disease manifestations that aren't wholly addressed with current treatment. There are no cures for this advanced chronic GVHD patient population. Patients initially treated with corticosteroids are then cycled through a variety of additional therapies based on the physician's experience and manifestations of the disease being addressed. The successful commercial launches of Jackify and Resiroc, and importantly, the speed by which both these agents gained adoption, really speak to the unmet need in chronic GVHD.

Speaker Change: Approximately 14000 U S patients suffer from chronic gvhd, 50% of whom require treatment beyond second line due to disease progression inadequate response or disease manifestations that arent wholly addressed with current treatments. There are no cures for this advanced chronic gvhd patient population patients initially treated with corticosteroids.

Speaker Change: Words are then cycled through a variety of additional therapies based on the physician's experience and manifestations of the disease being addressed.

Speaker Change: The successful commercial launches of Jakafi and reservoir rock and importantly, the speed by which both these agents gained adoption really speak to the unmet need in chronic gvhd. We also know that despite these recent advances the disease is still inadequately treated and physicians are looking for an agent that can better address the underlying fibrosis that ultimately.

Steve Kloster: We also know that despite these recent advances, the disease is still inadequately treated, and physicians are looking for an agent that can better address the underlying fibrosis that ultimately leads to organ damage. Furthermore, they are excited to have a drug with such a fast onset of action and impressive durability of response.

Speaker Change: <unk> leads to organ damage.

Speaker Change: Further they are excited to have a drug with such a fast onset of action and impressive durability of response. These key points of differentiation should enable <unk> to carve out a sizeable commercial opportunity within the estimated $1 billion U S refractory chronic gvhd market.

Steve Kloster: These key points of differentiation should enable axotilamab to carve out a sizable commercial opportunity within the estimated $1 billion U.S. refractory chronic GVHD market. As you know, Insight is our partner for Axitilumab and really the leader in the GVHD space. As of last year, we exercised our option with Insight to co-commercialize Axitilumab in the United States and provide 30% of the commercial effort, as we believe there is a considerable benefit to promoting two products simultaneously to a highly overlapping and targeted physician-prescriber universe.

Speaker Change: As you know insight as our partner Fracs until Nab and really the leader in the Gvhd space as of last year, we exercised our option with insights co commercialize <unk> in the United States and provide 30% of the commercial efforts as we believe there is a considerable benefits of promoting two products simultaneously to a highly overlapping.

Speaker Change: Targeted physician prescriber universe, we're working closely with insight to develop our go to market strategy Fracs until Nab and plan to align more fully with inside before sharing additional details. However, we expect to follow a similar set of strategic imperatives as we've just outlined for revenue management.

Steve Kloster: We're working closely with Insight to develop our go-to-market strategy for Axis Hill MAP and plan to align more fully with Insight before sharing additional details. However, we expect to follow a similar set of strategic comparisons as we've just outlined for Repumentum. Now, I'll turn the call over to Keith to review our financial results.

Speaker Change: Now I'll turn the call over to Keith to review our financial results.

Speaker Change: Thank you Steve.

Keith Alan Goldan: Turning to slide 11, as Michael mentioned earlier, the $522 million in cash, equivalents, and short and long-term investments on our balance sheet that March 31st is expected to provide runway through 2026. Our financial strength allows us to appropriately invest to maximize the value of our pipeline and, importantly, to transition into a commercial stage organization this year. Turning to the income statement, operating expenses in the first quarter were $79.5 million, comprised of $56.5 million of research and development expense and $23.0 million of selling general and administrative expense. Keeping in mind that we've always embraced a disciplined approach to resource allocations, we'd like to provide financial guidance for the second quarter and full year of 2024.

Keith: Turning to slide 11, and as Michael mentioned earlier.

Keith: $522 million in cash equivalents.

Keith: Short and long term investments on our balance sheet at March 31.

Keith: As expected to provide runway through 2026.

Keith: Our financial strength allows us to appropriately invest to maximize the value of our pipeline and importantly to transition into a commercial stage organization. This year.

Keith: Turning to the income statement.

Keith: Operating expenses in the first quarter was $79 $5 million.

Keith: Prized of $56 $5 million of research and development expense, and 23.0 or $1 million of selling general and administrative expense.

Keith Alan Goldan: For the second quarter, the company expects research and development expenses to be 50 to 55 million dollars and total operating expenses to be $80 to $85 million. For the full year 2024, there is no change to the existing guidance, and the company continues to expect research and development expenses to be $240 to $260 million and total operating expenses to be $355 to $375 million. Note that the guidance range for operating expenses for the full year 2024 is inclusive of an estimated $43 million of non-cash stock compensation.

Keith: Keeping in mind that we've always embraced a disciplined approach to resource allocation I'd like to provide financial guidance for the second quarter and full year of 2024.

Keith: For the second quarter, the company expense expects research and development expenses.

Keith: To be 50% to $55 million.

Keith: In total operating expenses to be $80 million to $85 million.

Keith: For the full year 2024, there is no change to the existing guidance and the company continues to expect research and development expenses to be $240 million to $260 million in.

Keith: In total operating expenses to be $355 million to $375 million.

Keith: Note that guidance range for operating expenses for the full year 2024 is inclusive of an estimated $43 million.

Keith: Of noncash stock compensation expense.

Keith Alan Goldan: In preparing for launch, I wanted to take a minute to lay out how we plan to recognize revenue for Axotillamab. Slide 12 includes an illustrative example of accounting for sales vectors from MAP and is not intended to provide any margin or other guidance. Commercially, our partnership with Insight is a 50-50 split of the economics in the U.S. We will report 50% of revenues earned net of cost of sales and commercial expenses.

Keith: In preparing for launch I wanted to take a minute to lay out how we plan to recognize revenue fracs with telematics.

Keith: Slide 12 includes an illustrative example of accounting for sales from that and is not intended to provide any margin or other guidance.

Keith: Commercially our partnership with insight is a 50 50 split of the economics in the U S.

Keith: We will report 50% of revenues earned net of cost of sales and commercial expenses.

Keith Alan Goldan: During a period where there is a net commercial profit for Exit Telemat, as in the top example of this slide, our 50% share of the net profit will be recognized on our P&L as collaborative arrangement revenue. Similarly, during a period where there is a net commercial loss for acetalamide, as in the bottom example of this slide. Our 50% share of the net commercial loss would be included in operating expenses designated as a separate line item called share of collaboration loss.

Keith: During the period, where there is a net commercial profit Brexit telling that as the top example of the slide our 50% share of the net profit will be recognized on our P&L as collaborative arrangements revenue.

Keith: During a period, where there isn't that commercial loss for <unk> is in the bottom example on this slide.

Keith: <unk>, 50% share of the net commercial loss would be included in operating expenses designated as a separate line item called share of collaboration loss.

Keith Alan Goldan: We also have various future U.S. commercial and regulatory milestones owed to us from Insight that would be recorded as partnership or milestone revenue on our income statement. Development expenses are shared 55-45 in the U.S., and our 45% share is included in the income statement as part of R&D expenses. Outside of the U.S., Insight is responsible for 100% of the development and regulatory expenses, and we are entitled to receive a Milestones Plus royalty on ex-U.S. sales. With that, I now turn the call back over to Michael.

Keith: We also have various future U S commercial and regulatory milestones owed to us from insight that would be recorded as partnership or milestone revenue on our income statement.

Keith: Development expenses, our shared 50 545 in the U S and our 45% share is included in the income statement as part of R&D expense.

Keith: Outside of the U S insight is responsible for 100% of the development and regulatory expenses and were entitled to receive a milestone milestones plus royalties on ex U S sales.

Keith: With that let me now turn the call back over to Michael.

Michael A. Metzger: Thank you Keith.

Michael A. Metzger: As you heard during the call, 2024 is shaping up to be a historic year for Syndax as we prepare to launch two first-in-class products, and I'm confident that we have the expertise, resources, and determination to bring these products to market. As an organization, we are truly excited to evolve into a commercial organization, and we are laser focused on bringing these important treatment options to patients in need. On slide 13, we lay out our key upcoming milestones for the balance of the year, and I look forward to updating you all on our progress in the coming months.

Michael A. Metzger: As you've heard during the call 2024 is shaping up to be a historic year for <unk> as we prepare to launch two first in class products and I am confident that we have the expertise resources and determination to bring these products to market.

Michael A. Metzger: As an organization we are truly excited to evolve into a commercial organization and we are laser focused on bringing these important treatment options to patients in need.

Michael A. Metzger: On slide 13, we lay out our key upcoming milestones for the balance of the year and I look forward to updating you on our progress in the coming months.

Michael A. Metzger: As always, I would like to express my sincere appreciation to the Syndax team, our collaborators, and, most importantly, the patients, trial sites, and investigators involved with our clinical program. Through your work and dedication, we are getting ever so close to delivering on our mission of improving the lives of patients with cancer. I'd also like to thank our committed long-term investors who continue to share in our vision and support us in building Syndax. With that, I'd like to open the call to questions.

Michael A. Metzger: And as always I would like to express my sincere appreciation to this index team our collaborators and most importantly, the patients trial sites and investigators involved with our clinical programs.

Michael A. Metzger: Your work and dedication we are getting ever so close to delivering on our mission of improving the lives of patients with cancer I'd also like to thank our committed long term investors, who continue to share in our vision and support us in buildings index.

Speaker Change: With that I'd like to open the call for questions operator.

Operator: At this time, I'd like to remind everyone that if you'd like to ask a question, please press star and then the number 5 on your telephone keypad. If you'd like to withdraw your question, press star and the number 5 once again. We'll pause just a moment to compile the Q&A rollout. Our first question is from Peter Lawson at Barclays. Your line is open, please go ahead.

Speaker Change: At this time I would like to remind everyone. If you'd like to ask a question. Please press star and then the number five on your telephone keypad. If you would like to withdraw your question Press Star and the number five once again, we will pause just a moment to compile the Q&A roster.

Neil Gallagher: Peter, thanks for the question. Maybe I'll ask Neil to comment on the importance of the guidelines. Yeah, thanks, Peter. So, as you know, the first approval for Avyamana will come in the third quarter, and that will be for CAME-22A rearranged acute leukemias and

Speaker Change: Our first question is from Peter Lawson at Barclays.

Peter Richard Lawson: Your line is open. Please go ahead.

Peter Richard Lawson: A question.

Peter Richard Lawson: Just first question is around how important NCC and guidelines will be for an additional indications of to get the initial approval of recommended.

Peter Richard Lawson: Peter Thanks for thanks for the question, maybe I'll ask Neil to comment on the on the importance of the guidelines.

Neil Gallagher: Yeah, thanks, Peter. As you know, the first approval for Revumenib is expected in the third quarter, and that will be for CAME-22A rearranged acute leukemias in adults and children. So the approval will be, should be sufficient to actually have that indication included in the guidelines. In addition to that, we've also guided to the fact that we will, in fact, I referenced, it was referenced during the prepared remarks that we anticipate reporting pivotal data from the NPM1 cohort by the end of the year. So, suffice it to say that we have a plan.

Neil Gallagher: Yeah, Thanks, Peter so.

Neil Gallagher: As you know the first approval that we're anticipating that the first approval for Humana.

Neil Gallagher: We'll come in the third quarter and that will be for <unk> rearranged acute leukemias in adults and children.

Neil Gallagher: So the approval will.

Neil Gallagher: B should be sufficient to XD.

Neil Gallagher: Indications included in the guidelines. In addition to that we've also guided to the fact that we will in fact, I referenced and referenced during the prepared remarks.

Neil Gallagher: We anticipate reporting pivotal data from the MTM, one cohort by the end of the year.

Neil Gallagher: I mean, prior to approval, you know, presentation at a medical congress, along with publication of the data, could position us to at least start conversations with the NCCN committee regarding inclusion in the guidelines. As you're aware, the committee meets twice a year. The disease-specific committees meet at least once a year, but they also meet ad hoc once important new data become available. So, we're considering all of that, and clearly, you know, we want to make sure that the best possible information is made available to the committee as well as to prescribers when we publish our data. Thank you.

Neil Gallagher: So suffice it to say that we have a plan I mean prior to approval.

Neil Gallagher: <unk> presentation.

Neil Gallagher: Medical Congress along with.

Neil Gallagher: Publication of the data could position us to at least start conversations with the <unk> Committee regarding inclusion and the and the guidelines as Youre aware the committee meets twice a year disease specific.

<unk> meets at least once a year, but they also meet at Hawk once important new data become available. So we're considering all of that.

Neil Gallagher: Unfairly.

Neil Gallagher: We want to make sure that the best possible information is made available to the committee as well as to prescribers.

Neil Gallagher: When we publish our data.

Speaker Change: Okay. Thank you and then.

Speaker Change: As we think about expansion of dominion payments into solid tumors.

Speaker Change: Just if you could detail the kind of the.

Speaker Change: Expectations around CFC data.

Speaker Change: Yes.

Speaker Change: And when we should expect to see that day Twos Medical conference.

Speaker Change: The number of patients.

Neil Gallagher: Thanks, Peter. Thanks for the follow-up. The question was related to solid tumors and our plans there. And as we've disclosed and mentioned in the prepared remarks, we are continuing to work in the area of colorectal cancer. This is metastatic colorectal cancer, third line plus.

Speaker Change: Thanks, Peter Thanks for the follow up so.

Speaker Change: Question was related to solid tumors and our plans there.

Speaker Change: As we've disclosed and mentioned in the prepared remarks, we are.

Speaker Change: Continuing to work in the area of colorectal cancer. This is metastatic colorectal cancer third line plus so these are.

Speaker Change: And we are.

Speaker Change: Ducting, a phase one trial.

Neil Gallagher: So these are, and we are conducting a phase one trial. We had said that we planned to disclose some information, and update everyone on our progress there in the second quarter, and that remains to be the case. Let me remind everyone, this is a dose escalation trial, so this is roughly 10 to 20 patients, heavily pre-treated. And what we're essentially looking for, looking to see, is activity of revumentib, again, in this patient population, looking for prolonged stable disease in the four to six month, so I'll call it, range with perhaps around 15% of the patients in that stable disease category. So that's sort of the signal that would be, we think, impactful. Of course, patients don't do very well in this setting, and certainly, standard of care doesn't yield prolonged stable disease of that nature.

Speaker Change: We had we had said that we had planned to disclose some information update everyone on our progress there in the second quarter and that remains to be the case.

Speaker Change: Let me remind everyone. This is a dose escalation trial. So this is.

Speaker Change: Roughly 10% to 20 patients heavily pre treated.

Speaker Change: And what we're essentially looking forward looking to see as activity at <unk>.

Speaker Change: Again in this in this patient population.

Speaker Change: Looking for prolonged stable disease.

Speaker Change: Six months.

Speaker Change: So call it range with perhaps around 15% of the patients in that stable disease category. So that's sort of the the signal that would be we think impactful of course patients don't do very well in this setting.

Speaker Change: And certainly standard of care doesn't yield prolonged.

Speaker Change: Prolonged stable disease of that of that nature, so well.

Speaker Change: We'll obviously update when when we're ready to do so in the in the second quarter.

Speaker Change: Perfect. Thanks, so much.

Speaker Change: Okay.

Speaker Change: Thank you Peter.

Neil Gallagher: So we'll obviously update when we're ready to do so in the second quarter. Perfect. Thanks so much. Thank you, Peter. Our next question is from Anupam Rama at J.P. Morgan. Your line is open, please go ahead. Hey guys, thanks so much for taking the question. Maybe a quick one for Steven. Just wondering,

Operator: Our next question is from Anupam Rama at J.P. Morgan. Your line is open, please go ahead.

Speaker Change: Our next question is from Andrew Pam Rama at Jpmorgan. Your line is open. Please go ahead.

Speaker Change: Hey, guys. Thanks, so much for taking the question.

Speaker Change: Maybe a quick one for Steven just wondering.

Speaker Change: Before you joined <unk> when Youre doing your assessments will be opportunities for <unk>, what really attracted you to these products and then.

Speaker Change: The second one is also actually for Steven.

Speaker Change: You mentioned very broadly.

Speaker Change: What some of the levers for success in slide eight our for both of these launches, but anything more specific to regimented in Kmt each way that you'd highlight thanks so much.

Steve Kloster: Yeah, thanks. Thanks for the question. I'll answer both. The first is, you know, why did I probably come here? And it's a combination of things. I've been pretty careful over the course of my career.

Steven: Yes. Thanks. Thanks for the question I'll answer both first is why did I probably come here and it's a.

Speaker Change: Really a combination of things I have been pretty careful over the course of my career and I think this is my fourth organization in 30 years. So the bar is pretty high and I look at all opportunities.

Speaker Change: Three three different factors the first is that needs to be great products.

Speaker Change: Products that address unmet need products that have a great amount of clinical data.

Speaker Change: And really provides a differentiated attributes and I think both rapid access path that I knew that coming in and as I have seen the data and as I've.

Steve Kloster: I think this is my fourth organization in 30 years, so the bar is pretty high. And I look at all opportunities in three, three different ways. The first is, there needs to be great products, products that address unmet needs, products that have a great amount of clinical data, and really provide the differentiated attributes. And I think both REV and AXA have that. I knew that coming in.

Speaker Change: Reviewed lots of market research and actually engage with Kols, that's only been amplified.

Speaker Change: Thing that I really think about is really who I work with wanting to be a companies with great people and great leaders and that's exactly what we have here Michael the entire ELT. The board overall top tier very supportive and even walking in the commercial leadership team.

Steve Kloster: And as I've seen the data, and as I've, you know, reviewed lots of market research and actually engaged with KOLs, that's only been amplified. I think the second thing that I really think about is really who I work with, right, wanting to be at companies with great people and great leaders. And that's exactly what we have here. Michael, the entire ELT, and the board are all top tier, very supportive. And even walking in, the commercial leadership team that was in place was strong as well.

Speaker Change: Was in place was strong as well and the third thing for me is really the willingness to invest and plan for success and we have that here too. So I would say my expectations have been exceeded.

Speaker Change: Coming in and I'm more excited now than it was even before I started I think I'm at week eight.

Speaker Change: Second question is really around levers for success.

Speaker Change: On revenue matter than theirs.

Speaker Change: A lot we're building as a commercial organization and all of that will be in place I think as Neil mentioned and Michael mentioned in his remarks will be ready in Q3, so infrastructure processes. All of those things will be will be done I think from a strategic point of view.

Steve Kloster: And the third thing for me is really the willingness to invest and plan for success. And we have that here too. So I'd say my expectations have been exceeded coming in. And I'm, you know, more excited now than I was even before I started. I think I'm in week eight.

Steve Kloster: The second question is really around levers for success in REV-U-META. There's, you know, there's a lot we're building as a commercial organization, and all of that will be in place. I think, as Neil mentioned and Michael mentioned, his remarks will be ready in Q3.

Steve Kloster: So infrastructure processes, all those things will be done. I think from a strategic point of view, the three things that I think about that we are very focused on, really, the first is the population of patients is limited. We know that, right, and that'll, that opportunity will grow over time. But finding them is critical. Patients are fragile; they need treatment immediately. So we've got our focus there.

Speaker Change: The three things that I think about that we are very focused on really the first is the population of patients is limited we note that rate and that will that opportunity will grow over time, but finding them has critical patients a fragile they need treatment immediately.

Speaker Change: We've got focus there I think the second thing is just the landscape of health care delivery.

Speaker Change: There are multiple stakeholders out there that deliver care to patients physicians nervous sorry nurses.

Steve Kloster: I think the second thing is just the landscape of healthcare delivery. There are multiple stakeholders out there that deliver care to patients. Physicians, nurses, advanced practice providers, pharmacy, reimbursement, pathology, you name it. We have a customer-facing footprint that will address and directly engage with that dynamic. And the third point is really access. Right, Neil mentioned the CCN guidelines, which will be important. Payers are looking for that information. They're looking for other published data, too.

Speaker Change: Advanced practice providers pharmacy reimbursement pathology you name. It we have a customer facing footprint that will address and directly engage with that dynamic and the third third third point is really access right. Neil mentioned NCC guidelines, which will be important payors are looking for that they are looking for other published data that patients need access to <unk>.

Speaker Change: Treatment. So we've been deployed against the payer space for some time and making calls directly with payers and that it's in an effort to really expedite formulary review and.

Speaker Change: And in addition, we've built a support program to meet the needs of patients, which we know their need.

Speaker Change: So thanks. Thanks for the question for that was a good answer.

Operator: Our next question is from Brad Canino at Stiefel. Your line is open, please go ahead.

Steve Kloster: But patients need access to treatment, so we've been deployed against the payer space for some time. Making calls directly with payers, and that is in an effort to really expedite formula review. And in addition, we've built a support program to meet the needs of patients, because we know their needs. So thanks for the question, Alfred. That was a good answer. Our next question is from Brad Canino at CityFull. Your line is open, please go ahead. Hi, good morning. Relating to the plan for the Pivotal Vennaise combo trial to be initiated by year end, this will shift the emphasis.

Speaker Change: Our next question is from Brad can they know at Stifel. Your line is open. Please go ahead.

Brad: Hi, good morning relating to the plan for the pivotal vent as a combo trial to be initiated by year end. This will move the emphasis of clinical endpoints from CR towards remission durability, and Oss and I wanted to ask how does the company plan to evaluate data from the uncontrolled trial updates later this year both of them.

Brad: The combos and also the NPM one pivotal monotherapy in order to gain confidence in the randomized time to event endpoints for the frontline pivotal. Thank you.

Neil Gallagher: Brad, thanks for the question. I'm going to turn it over to Neil to address that. Yeah, thank you for the question.

Brad: Alright, Thanks for the question I'm going to turn it over to Neil to address that yes. Thank you for the question.

Neil Gallagher: Yeah, thank you for the question. Specific, I mean, of all of the combination studies that we've reported on, the one specific to this scenario, in other words, initiating the phase three venasus, revumenta venasa study by the end of the year is the BEAT AML study. As you're aware, the group reported data around the ASH meeting last year and anticipates updating those data during the course of this year. Those data are exciting, not only to the company but also to the investigators, and actually not just the beat AML investigators but the broader community.

Brad: Specific.

Neil Gallagher: All of this combination studies that we reported on the one specific to the scenario in other words initiating the phase III in <unk> <unk>.

Speaker Change: <unk> study by the end of the year as the beat AML study.

Speaker Change:

Speaker Change: As Youre aware.

Speaker Change: The group reported data.

Speaker Change: Around the Ash meeting last year and anticipate updating those data during the course of this year.

Speaker Change: Those data are exciting.

Speaker Change: Not only to the company, but also to the investigators and actually not just the beat AML investigators with the broader the bro.

Speaker Change: Our community so people are high.

Neil Gallagher: So people are highly enthusiastic about initiating the Phase 3 study. Just to remind you, the response rates, including the CRCRH rates that have been observed in the beat AML study to date have exceeded the historical controls observed in the LEA, including in terms of CR. In particular, molecular MRD negative CR was much, much higher in the beat AML study compared to the LEA.

Speaker Change: Highly enthusiastic about initiating the phase III study.

Speaker Change: Just to remind you the the response rates, including the CRC rates rates that were observed in the BDA amounts study to date.

Speaker Change: <unk> the historical controls observed in <unk>, including in terms of CR.

Speaker Change: And particular molecular.

Speaker Change: <unk> negative CR.

Speaker Change: It was.

Speaker Change: Much much higher and the beat AML study compared to.

Speaker Change: So the merchant's data.

Neil Gallagher: So the emerging data, including the observation that Revumenib is highly combinable—it doesn't appear to be adding toxicity to the backbone therapy—as well as providing incremental efficacy in the target patient population. And that's bolstered also by the observations from, for instance, the SAVE study, which is a combination of Revumenib with phenetoclax and oral dacitabine in a relapsed refractory setting, as well as our own Augment 102 trial, a combination trial in a relapsed refractory population in combination with chemotherapy.

Speaker Change: Including the observation that <unk> is highly combinable, it's not adding it doesn't appear to be adding toxicity to the backbone therapy.

Speaker Change: Well as.

Speaker Change: Being providing incremental efficacy in the target patient population and that's bolstered also by the observations from for instance, safe. The safety study, which was a combination is a combination of revenue amount up with phonetic lax and oral decided it'd been in the relapsed refractory setting as well as our own augment one or two trial the combination trial with.

Speaker Change: In a relapsed refractory population in combination with chemotherapy. So the the body of evidence is that <unk> is combinable with backbone standards of care is not adding toxicity in the target population for the phase III trial.

Neil Gallagher: So the body of evidence is that Revumenib is combinable with backbone standards of care, and it's not adding toxicity in the target population for the Phase 3 trial. For the Phase 3 trial in the newly diagnosed unfit population, the beat AML data are providing evidence that Revumenib is also adding notable efficacy to the backbone therapy. So, obviously, we will be having conversations with health authorities as we design the trial, and we don't typically comment on those, but we look forward to presenting more details about the study prior to initiation later in the year.

Speaker Change: For the phase III three trial in newly diagnosed unfit population. The beat AML data are providing evidence that our breath momentum is also adding notable efficacy to the backbone therapy. So obviously, we will be having conversations with health authorities as we design the trial and we don't typically comment on those but wed.

Speaker Change: Look forward to presenting more details around the study prior to initiation later in the year.

Operator: Our next question is from Phil Nadeau at TB Cohen. Your line is open; please go ahead. Good morning.

Speaker Change: Our next question is from Phil Nadeau at TB Cowen. Your line is open. Please go ahead.

Operator: Morning. Congratulations on the progress. Thanks for taking our questions. A few thoughts. First, in terms of the phase 2 doses in the combo trials or validating the phase 2 doses in the combo trials, this morning's press release notes that some of the trials have been expanded to validate the phase 2 doses. I was curious whether you'd be willing to disclose whether the full monotherapy dose of Revimanib is being used in those combinations.

Philip M. Nadeau: Congrats on progress thanks for taking our questions.

Philip M. Nadeau: First in terms of the phase two doses in the combo trials.

Philip M. Nadeau: Validating the phase two doses in the combo trials with this morning's press release notes that.

Philip M. Nadeau: Some of the trials have been expanded to validate that the phase II doses I was curious whether you'd be willing to disclose whether the full monotherapy dose of <unk> is being used in those combinations at this point.

Neil Gallagher: Yeah, thanks for the question. So just to remind everyone, the three studies that I just referenced in the answer to the previous question are the studies under discussion. So I won't repeat what those are. In all three of those studies, in all three of those trials, there were two doses of Revumetib that were investigated, 113 milligrams and 163 milligrams. And 163 milligrams is the presumptive monotherapy dose in combination with Astroxiv 3 or 4 that will be included on the label.

Speaker Change: Yes go ahead.

Speaker Change: Yes, thanks, and thanks for the question.

Speaker Change: So.

Speaker Change: Just to remind everyone. The three studies that I, just referenced and the answer to the previous question.

Speaker Change: The studies at the <unk>.

Speaker Change: It is under discussion so I won't repeat what those are and all three of those studies are all three of those trials. There were two doses of <unk> that were investigated 113 milligrams and 163 milligrams 163 milligrams.

Speaker Change: Is the presumptive monotherapy dose in combination with the strong some three or four that will be included in the label. So revenue benefits when given at full dose and all three.

Speaker Change: Trials by the time, we talked about some of the events around the Ash last December and all three the dose limiting toxicity windows for both doses have been cleared.

Neil Gallagher: So Revumetib has been given at full dose in all three trials, and by the time we talked about them at the event around ASH last December, in all three, the dose-limiting toxicity windows for both doses had been cleared. And both doses are being expanded in all three trials at this point in time. So when we talk about RP2D, we're continuing to characterize the two doses. But in general, our anticipation is that RevuMed, or our observations to date, is combinable at full monotherapy dose with backbone standards of care.

Speaker Change: And both doses are being expanded in all three trials at this point in time, So we haven't.

Speaker Change: We talk about <unk>, we're continuing to characterize.

Speaker Change: The two doses.

Speaker Change: But in general our anticipation is that.

Speaker Change: That revenue amount of our observation to data as that revenue amount of as combinable that for full monotherapy dose with backbone standards of care.

Michael A. Metzger: That is very helpful. Thank you. And then, second question, based on the... Milestone tables that you just presented, it doesn't seem like you're anticipating an advisory committee review for either Revimanib or Axotilumab. Is that accurate? And can you remind us, did the FDA explicitly say in the acceptance letters that adcoms would not be necessary for both drugs?

Speaker Change: That's very helpful. Thank you and then second question based on the.

Speaker Change: Milestone tables that you just presented it doesn't seem like Youre anticipating an advisory committee to review for either <unk> or <unk>.

Speaker Change: Is that accurate and can you remind us did the FDA explicitly say except in sweaters.

Speaker Change: At comps would not be necessary for both drugs.

Michael A. Metzger: Yeah, Phil, thanks for the question. I think our expectation is that neither Exotilamab nor Revimanib will require an adcom. But we haven't explicitly stated, nor do we comment on regulatory correspondence from the agency relative to things like that. So, but that is our expectation that neither will need an adcom. Perfect. And then, last question.

Speaker Change: Yes, Phil Thanks for the question.

Speaker Change: I think our expectation is that neither exit till a map.

Speaker Change: Knorr <unk> will require an ad com.

Speaker Change: But we haven't explicitly stated.

Speaker Change: Or do we comment on regulatory correspondence from the agency relative to things like that so.

Speaker Change: But that is our expectation that neither will need a an outcome.

Michael A. Metzger: And then, last question from us. You referenced the nine-month expected median duration of use for KMT2A patients. Can you remind us what proportion of patients going to transplant is assumed in that nine-month period?

Speaker Change: Perfect and then last question from Us.

Speaker Change: For the nine months expected median duration of use for <unk> patients can you remind us what proportion of patients go into transplant is assumed in that nine month figure.

Michael A. Metzger: Phil, thanks for the question. It's roughly about a third of that half, right? Sorry, for the patients I co-transcribed with.

Speaker Change: Yes. Thanks for the question, it's roughly about a third of that path.

Speaker Change: Sorry.

Speaker Change: But the patients echo.

Michael A. Metzger: So a third of patients who get into a relapsed refractory line would go to transplant, is the assumption.

Speaker Change: Transplant, so a third of patients who get in the relapsed refractory.

Speaker Change: Line would go to a transplant is the assumption.

Anjali Ganguli: Yeah, sorry, Phil, it's Anjali. I think what we've been saying is there are basically three groups of patients that seem, based on the trial, seem to all be about an equal size population. There were a third of patients that did not respond. Of the two thirds of patients that responded, half went to transplant. So overall, of the entire population, a third went to transplant. Got it.

Speaker Change: Yes.

Speaker Change: I think what we've been saying.

Speaker Change: Basically three groups of patients.

Speaker Change: Based on the trials into all of the about an equal size population. They were a third of patients that did not respond.

Speaker Change: Of the two thirds of patients that responded half.

Speaker Change: Lynn to transplant, so overall in the entire population necessary go to transplant.

Operator: Got it. That is very helpful. Thanks for taking our call.

Speaker Change: Got it that's.

Speaker Change: Very helpful. Thanks for taking our questions.

Speaker Change: Thank you Phil.

Operator: Our next question is from Michael Schmidt at Guggenheim. Your line is open, please go ahead.

Speaker Change: Our next question is from Michael Schmidt at Guggenheim. Your line is open. Please go ahead.

Operator: Hey guys, good morning. Thanks for taking my questions. I just had the one on the exeterium of launch, now that we're obviously closing in on the PDUFA day later this year, and as we think about this sort of $1.5 to $2 billion opportunity in a relapse refractory setting, wondering how we should think about perhaps the early launch trajectory, you know, subsequent to approval. Are there any good proxies we should look at, for example? And then, you know, what are your expectations for potential off-label use in the NPM1 subset? Obviously, we will have data later this year. You know, could that help next year to accelerate the launch early on?

Michael Werner Schmidt: Hey, guys. Good morning, Thanks for taking my questions I just had one on the <unk> launch now that obviously.

Michael Werner Schmidt: Closing in on that particular day later this year and as we think about this sort of one $5 billion to $2 billion opportunity.

Michael Werner Schmidt: <unk> refractory setting just wondering how we should think about perhaps the early launch trajectory.

Speaker Change: Subsequent to approval are there any good proxies, we should look at for example, and then.

Operator: Thanks so much.

Speaker Change: <unk>.

Speaker Change: What are your expectations for potential off label use in the NPM one subset obviously.

Speaker Change: We'll have data later this year could that help next year to accelerate the launch early on thanks, So much.

Anjali Ganguli: Yeah, Michael, thank you for the questions. I'm going to ask Anjali to comment on the launch. Yeah, thanks.

Speaker Change: Yes, Michael Thank you for the questions I'm going to ask Angela to comment on the on the launch.

Anjali Ganguli: No, we're really excited about this opportunity. I think what REVI-MEDEV has in front of us is a very unique situation. As you know, we got through clinical development in record time, first patient dose to NDA filing in four years. And then, on top of that, we also talked about all the combination data we've generated with REVI-MEDEV that allows them to think about multiple ways to use this drug and fit it into their treatment plans as they think best.

Anjali Ganguli: Yeah, thanks. Thanks, Michael.

Angela: Yeah. Thanks, Thanks, Mike.

Speaker Change: No.

Angela: Really excited about this opportunity.

Speaker Change: <unk> has been pregnant.

Speaker Change: Fragrances.

Speaker Change: Their unique situation.

Speaker Change: As you know we got through.

Speaker Change: The clinical development.

Speaker Change: Time first patient deaths.

Speaker Change: Filing in four years, we've generated data that support indications across AML in adults and pediatrics.

Speaker Change: And as you said, we're anticipating an approval.

Speaker Change: The third quarter of this year.

Speaker Change: And we'll have data for another very important patient population treated by the exact same.

Speaker Change: Set of health care providers and disease physicians can choose the best options for their patients.

Speaker Change: So and then on top of that we also talked about all the.

Speaker Change: Combination data that we've generated with are implemented that allow them to think about multiple ANC using chegg and fit it into their treatment plans as they think best So I think we have a very.

Speaker Change: Unique.

Speaker Change: <unk> coals that were going to be.

Speaker Change: We're going to be generating in real time, I don't I don't think there's a perfect analogue that addresses all of these aspects.

Speaker Change: What's coming in the next 12 months.

Speaker Change: But we have seen very significant excitement around ramping that is around this new class of agents and how they can utilize it.

Speaker Change: To bring care to patients that have had nothing.

Speaker Change: And I think Youll recall, the last ash meetings.

Speaker Change: Very focused on.

Speaker Change: The data that we've been generating.

Speaker Change: I think that that shows how much education is already out there and Steve talked about Theres a lot more that we're doing to make sure everybody is aware.

Speaker Change: All of that.

Speaker Change: Support.

Anjali Ganguli: So I think we have a very unique launch curve that we're going to be generating in real time. And I think you'll recall the last two ASH meetings have been very focused on the data that we've been generating, and I think that shows how much education is already out there, patient support is in place to allow utilization, and we're really excited to have a really strong launch of RevuMetabolic.

Speaker Change: Patient.

Speaker Change: Patient support is in place.

Speaker Change: To allow utilization.

Speaker Change: We're really excited to have a really strong launch in France.

Speaker Change: Maybe just a follow up.

Anjali Ganguli: Can you just remind us what percentage of the AML market is under Medicare and how you think about pricing in the Medicare population, any sort of expectations for free drug programs as we sort of think about the early stages?

Speaker Change: Can you just remind us what percentage of the ammo market is.

Speaker Change: Under Medicare and how do you think about pricing in the Medicare population any so expectations for free drug programs asked me sort of think about that early launch again later this year.

Steve Kloster: Yeah, let me let me ask you. Thanks, Michael. I'm going to ask Steve to comment on those questions. Yeah, I mean, it's a good question.

Speaker Change: Yeah, Let me, let me ask Scott, Thanks, Michael I'm going to ask Steve to comment on on those question, Yes, I mean, it's a good question in the payer space is different for <unk> versus NPM, one it'll be more of a <unk>.

Steve Kloster: And the pair space is different for KMT2AR versus NPM1. It'll be more of a commercial patient, you know, for the KMT2A launch, just based on the age of the patient. You know, we'll expect coverage, honestly, at launch. Formula acceptance will happen over time, right? Typically, it takes six to nine months for that to happen.

Speaker Change: Commercial patient for the cancer to a launch just based on the age of the patient.

Steve: We will expect coverage honestly at launch formulary acceptance will happen over time typically takes six to nine months.

Steve Kloster: But in the meantime, you know, health care providers, and their staff are very fluent in how to get through the medical exception process. That's where the NCCN guidelines are helpful and other published data. Medicare payers will be less important for KMT2AR, but for NPM1, due to the patient population, which is a little bit older, it's going to change. So our approach has been really over the last nine months, even a year, to approach all plans.

Steve: For that to happen, but in the Meanwhile, health care providers. Their staff are very fluent on how to get through the medical exception process, that's where the NCC guidelines are helpful. In all of their other published data Medicare.

Steve: Medicare payers will be less important for cancer <unk> due to the patient population, which is a little bit older. It is going to change. So our approach has been really over the last nine months, even a year is really to approach all plans, we've been delivering pipe information exchanges. That's the preapproval information exchange. So we've had some very good interactions with <unk>.

Steve Kloster: We've been delivering PI information exchanges. That's the preapproval information exchange. So we've had some very good interactions with payers. They recognize the unmet need and the criticality of patient care. And I think, as Anjali said, it's a unique launch where you've got a launch followed by, we'll just say, another launch within a year. So we're preparing for both at the same time. You know, it takes time to build coverage. So we've got the whole payer space.

Speaker Change: They recognize the unmet need with the criticality of patient care.

Speaker Change: I think it's honestly said its unique launch where you've got launch followed by the St. Other launch within a year. So we're preparing for both at the same time. It takes time to build coverage. So we've got the whole payer space and I think in my prepared remarks, we will we will talk to payers that cover 90% of covered lives in this country, which is as good as it gets in.

Steve Kloster: And I think in my prepared remarks, well, we will talk to payers that cover 90 percent of covered lives in this country, which is as good as it gets in advance of approval. So we're prepared for success.

Speaker Change: Vance approval, so we're prepared for success.

Operator: Okay, great. And then maybe just a housekeeping question as we think about the F2MF filing and potential approval. Are there any milestones due from inside for that that we should incorporate into our models this year?

Speaker Change: Great and then maybe just a housekeeping question assay.

Speaker Change: Think about the time that filing and potential approval at any milestones do.

Speaker Change: From inside for that that we should incorporate in our models this year.

Keith Alan Goldan: Yeah, thank you, Michael. Keith, do you have one? Oh, yeah, Michael, we do.

Speaker Change: Yes, Thank you Michael Keith Dan Yes.

Keith Alan Goldan: We do, as disclosed in this queue and as we've disclosed in past queues and caves, We do have not only development regulatory milestones but commercial milestones for us from Insight. Total milestones for development and regulatory under the agreement were $220 million. Total commercial milestones were $230 million. So a total of $450 million did we do. You could expect those to come at major, certainly major regulatory events such as approval. I think that's a reasonable expectation, but we haven't been more specific as to the amounts. Thanks for coming.

Speaker Change: Michael we do.

Speaker Change: As disclosed in this Q and as we've disclosed in past accusing case.

Speaker Change: We do have not only development and regulatory milestones, but commercial milestones do us.

Speaker Change: From insight.

Speaker Change: Total milestones for development of regulatory.

Speaker Change: Under the agreement with $220 million total commercial milestones were $230 million. So a total of $450 million. Due US you can expect those to come at major.

Speaker Change: Major certainly major regulatory events, such as approval I think thats, a reasonable expectation, but we haven't been more specific as to the amounts.

Operator: Thanks so much, guys.

Speaker Change: Thanks, so much guys.

Speaker Change: Thank you Mike.

Operator: Our next question is from Yigal Nochomovitz at Citigroup. Your line is open, please go ahead.

Speaker Change: Our next question is from Yigal not to move it at Citigroup. Your line is open. Please go ahead.

Operator: Yeah, hi, thanks very much for taking the question. Just curious, on the NPM-1 Regulatory Pathway, do you think you may follow the RTOR pathway? Even if we break through or give it to the SNDA, those options are not really necessary.

Yigal: Yes, hi, thanks, very much for taking my question just curious.

Yigal: Tim.

Yigal: You may followed Heartsore pathway.

Yigal: Great.

Yigal: Forgiven.

Yigal: Yes.

Yigal: Are those options and that really necessary.

Michael A. Metzger: Yigal, thank you for your question. You broke up a little bit, but I think I have it.

Speaker Change: Thank you for your for your question you broke up a little bit, but I think I captured it.

Michael A. Metzger: So, as you know, we've had breakthrough therapy designation for KMT2A. For MPM1, we have the opportunity to potentially get breakthrough therapy designation. It's probably most important for your first indication, and I think the engagement around KMT2A and the molecule and the submission package has been very strong.

Speaker Change: As you know we have we've had breakthrough therapy designation for <unk>.

Speaker Change: For NPM, one we have the opportunity to potentially get breakthrough therapy, probably most important for your first indication and I think the engagement around Kmt in the molecule and the submission package has been very strong we have priority review as well I think for NPM. One we will look to leverage some of the same.

Michael A. Metzger: We have priority review as well. I think for MPM1, we'll look to leverage some of the same access points with the agency, but we're, I'd say, pretty well advantaged by what's come our way already. But we'll see.

Speaker Change: Access points with the agency, but we are.

Speaker Change: I'd say pretty well advantaged by what what we've what's.

Speaker Change: Whats come our way already.

Michael A. Metzger: We don't generally comment on regulatory strategy, but the opportunity to submit for BTD at a point in the future is open to us. So I think it's obviously a program that we'll have data on later this year. We'll have a submission, we hope, in the not-too-distant future beyond that, and then look to get the drug approved in 2025. So that'll be through an SNDA process. So it's all, I'd say, call it an expedited pathway through some of the designations we have in hand already or some of the things that we may avail ourselves of in the future.

Speaker Change: But we will say, we don't generally comment on regulatory strategy, but the opportunity to submit for BTG and at point in the future as size open to us so.

Speaker Change: Thank you.

Speaker Change: I think it's a obviously a program that will.

Speaker Change: We will have data on later this year, we will have a submission we hope in the not too distant future beyond that.

Speaker Change: And then.

Speaker Change: Look to get the drug approved in 2025, so that'll be through an SDA process. So it is all I'd say.

Speaker Change: Call it an expedited pathway through some of the designations we have in hand already or some of the things that we may avail ourselves of the future.

Operator: Okay, thanks. And then when you think more broadly about the Revumentib in terms of the spectrum of care and AML both in the frontline and in the relapsed refractory, and given the fact that there's a good chance that you're going to be initiating a pivotal trial in the frontline in combo with Venetoclax, when you start to think about the commercial build there, are you making assumptions around the potential free treatment with Revumentib for patients that received Revumentib in the frontline in a combination setting?

Speaker Change: Okay. Thanks, and then when you think more broadly about the recommended in terms of the spectrum of care in AML, both in the frontline and in relapsed refractory and given the fact that.

Speaker Change: There's a good chance that youre going to be initiating a pivotal trial in the frontline in combo with <unk>. When you start to think about the commercial build there are you, making assumptions around the potential re treatment regimen for patients that received revenue.

Speaker Change: Frontline in the combination setting whether it's net of tax.

Operator: Whether it be with Venetoclax or perhaps even with the 7 plus 3, including those patients in the build for Revumentib in a relapsed refractory setting, or once they're being treated in the frontline, then that wouldn't be part of your assumption set. Thank you.

Speaker Change: Even with <unk> III <unk>.

Speaker Change: <unk> those patients and the builds for revenue in the relapsed refractory setting are once they are on <unk>.

Speaker Change: Treated in the frontline then that wouldn't that wouldn't be part of your assumption set. Thank you.

Michael A. Metzger: Yeah, thanks, Yigal. I think our assumption is that once you're treated with a menin inhibitor, at least from our vantage point, the way we see it today, I think once you're treated with one in the frontline setting, it's less likely that you're going to be treated in the relapsed refractory setting again with another menin inhibitor. And Neil, I want to make a comment. Yeah, I

Speaker Change: Yeah. Thanks, Joe I think the I think our assumption is that once you are treated with amended inhibitor at least from a from our vantage point the way we see it today I think once you are treated with it.

Speaker Change: In the frontline setting, it's less likely that youre going to be treated in the relapsed refractory setting again with another <unk> inhibitor in the comments.

Neil Gallagher: Yeah, I agree. I agree with Michael's comments there that I think that, you know, it's a little, it is a little bit nuanced because I think, longer term, there, I can foresee situations where patients could, for instance, if they've been treated and relapsed a long time later, or MPM1 positive or cancer 2A positive, might get, might, might be re-exposed But I think in general, I, in general, I agree with Michael's points. We shouldn't be sort of expecting a lot of patients to fall into that category.

Joe: Yes, I agree I agree with Michael's comments, there that I think that.

Speaker Change: It's a little it is a little bit nuanced, because I think longer term I can foresee situations where patients could for instance have either been treated in relapsed a longtime later on where <unk> had positive or Kingston is very positive.

Speaker Change: Mike might be re exposed, but I think in general.

Speaker Change: In general I agree with Michael's points, we shouldn't be sort of.

Speaker Change: Expecting a lot of patients to follow up to that got it.

Operator: One on AXA, do you have any timelines for the IPF trial in terms of enrollment and data?

Speaker Change: And just one one on Axa do you have any timelines for the IPF trial in terms of enrollment and data.

Michael A. Metzger: Thanks, Yigal. No, not at this point. I think we are enrolling. As you know, we started recently bringing sites and enrolling patients, and it's going nicely, and so we'll have more to say in terms of milestones, both for enrollment as well as data, as we get further into the year, maybe into next year.

Axa: Thanks, you got no no not at this point I think we are enrolling as you know we started recently.

Speaker Change: Up sites and enrolling patients and it's growing nicely.

Speaker Change: And.

Speaker Change: So we'll have more to say in terms of.

Speaker Change: In terms of milestones both for <unk>.

Speaker Change: Enrolment as well as data as we get further into the year maybe into next year.

Operator: Okay, thank you, Michael. Thank you all. Our next question is from Kalpit Patel at B Raleigh Security. Your line is open, please go ahead.

Speaker Change: Okay. Thank you Michael.

Michael: Thank you all.

Caltech: Our next question is from Caltech at B Riley Security. Your line is open. Please go ahead.

Caltech: Okay.

Caltech: Can you can you comment on what proportion of patients that you estimate.

Caltech: Be eligible to receive revenue management as a maintenance treatment after induction and consolidation.

Speaker Change: I'm trying to understand.

Speaker Change: The median duration of treatment in <unk>.

Speaker Change: That specific frontline setting would be higher than the nine months.

Speaker Change: Specced in the relapsed refractory setting.

Speaker Change: Okay.

Steve Kloster: Thanks for the question. I think if I interpreted your question correctly, I think in terms of patients who would be eligible for maintenance therapy in the relapsed refractory setting, I think if you're getting, if you had a successful transplant, there's no reason that all patients wouldn't necessarily be eligible. They need to be stable and engraft well. And I think that's usually the first step. And physicians remind us of that, that there is an engraftment period.

Speaker Change: But thanks for the question I think if.

Speaker Change: If I interpreted your question correctly I think in terms of patients who would be eligible for maintenance going in the relapse refractory setting.

Speaker Change: If youre getting if you add a successful transplant. There is no reason that all patients would necessarily be eligible they need to have.

Speaker Change: Be stable and graft well and I think that's usually the first step in patient and physicians remind us of that that there is an <unk> period, but for all intensive purposes, all patients should be eligible for <unk>.

Speaker Change: For maintenance, so I think thats.

Steve Kloster: But for all intents and purposes, all patients should be eligible for maintenance. That's our assumption, and that's, I think, been discussed with physicians on an ongoing basis. I think when you get to the frontline setting, the assumptions for long-term maintenance and how that would play out in the FIT population could very well differ if you were able to get to patients earlier and treat them successfully through transplant and put them back on therapy.

Speaker Change: That's our assumption and that's I think been discussed with physicians on an ongoing basis I think when you get to the frontline setting.

Speaker Change: The assumptions for.

Speaker Change: Long term maintenance and how that would play out in the fit population.

Speaker Change: Could very well differ if youre able to get to patients earlier and treat them successfully transplant and put them back on therapy I think the expectation is.

Steve Kloster: I think the expectation is that you treat patients earlier, they stay on, they do better, and they stay on longer. And so that should change how the assumptions work on the time on maintenance in the frontline compared to relapsed refractory. We don't have a good estimate of that yet. Obviously, we're generating that data. But over time, we'll understand that a little bit better.

Speaker Change: Treat patients earlier, they stay on they do better and they stay on longer and so that should change how the assumptions work on on time on maintenance and the frontline compared to relapsed refractory. We don't have a good estimate of that yet obviously, we're generating that data.

Speaker Change: But over time, we all understand that a little bit better.

Operator: Our next question is from Jason Zemansky at Bank of America. Your line is open, please go ahead.

Speaker Change: Our next question is from Jason Jason Domanski at Bank of America. Your line is open. Please go ahead.

Operator: Perfect. Thank you. Good morning and congratulations on the progress. Appreciate you taking the time to answer our questions.

Jason Eron Zemansky: Perfect. Thank you good morning, and congratulations on the progress I appreciate you taking our questions.

Operator: Regarding the commercialization plans for Revumentib and your initial outreach, I have to imagine there's already quite a bit of excitement across at least the more academic-focused community. But what sort of division between rapid adopters and non-rapid adopters do you expect? How quickly do you expect maybe the more community-based prescribers to come on board as far as awareness and education goes? And maybe bolus isn't quite the right descriptor given patient dynamics this late in treatment, but do you expect an initially large bump in patient numbers or more of a straight line uptake?

Jason Eron Zemansky: Regarding the commercialization plans for <unk> and <unk>.

Jason Eron Zemansky: Our initial outreach I have to imagine there's already quite a bit of excitement across at least the more academic.

Jason Eron Zemansky: Focused community, but what sort of division between rapid adopters and non do you expect how quickly.

Jason Eron Zemansky: Do you expect maybe the more community based prescribers to come onboard onboard as far as awareness and education goes and maybe bolus isn't quite the right descriptor given patient dynamics the slate in treatment, but do you expect an initial large bump in patient numbers or more of a straight line uptake.

Steve Kloster: Jason, thank you for the question. I'm going to turn it over to Steve to address your questions.

Jason Eron Zemansky: Jason. Thank you for the question I'm going to turn it over to Steve to address your questions, Yes, Hey, Jason. Thanks for the question I mean, Theres a theres a lot of excitement I think Predating me coming to the company the company has done.

Steve Kloster: Hey Jason, thanks for the question. I mean, there's a lot of excitement. I think, you know, prior to me coming to the company, the company's done quite a bit of research, market research, advisory boards, met with KOLs, the field medical team has been out there. So there's a lot of, we'll say, demand that's there because of a lack of treatment options. I've recently been out in New York yesterday at Cornell and Sloan and meeting with KOL.

Steve: Quite a bit of research market research advisory boards met with Kols field medical team has been out there. So there's a lot of what to say demand that's there because of lack of treatment options.

Steve: We've recently actually was out in New York yesterday at Cornell.

Steve: Sloan and <unk>.

Steve Kloster: So they're ready for the drug, literally, you know, cannot wait till it hits the market. So I think certainly the academic centers, you know, Jason, they'll have quick uptake, they are ready for this product. Awareness is already fairly high, for whether it's RevuMan or Borreman inhibitor.

Steve: Meeting with Kols, so they're ready for that literally cannot wait until it hits the market. So I think certainly the academic centers, Jason there'll be quick uptake. They are ready for this product awareness is already fairly high.

Steve: It's <unk> inhibitor.

Steve: I think.

Steve: <unk> stream in the community, it's going to take a little bit of time part of it is just they may not see a lot of patients. Initially so it's up to us to be there. So from a commercialization standpoint will have adequately sized team that's going to cover 95 plus percent of the opportunity. We will have a non personal promotional program that will reach folks in places that we may not be.

Steve Kloster: I think, you know, downstream in the community, it's going to take a little bit of time. Part of it is that they may not see a lot of patients initially. So it's up to us to be there. So from a commercialization standpoint, we'll have an adequately sized team that covers 95 percent plus of the opportunity. We'll have a non-personal promotional program that will reach folks in places that we may not be at as frequently.

Steve: As frequently.

Steve: So I think youll see a quick uptake across the board and a lot of it's just patients in the office ready to be treated so think leads to your second question and theres not going to be much of a bolus right. We have an EAP that's in place.

Steve Kloster: So I think you'll see a quick uptake across the board. And a lot of it is just patients in the office ready to be treated, which I think leads to your second question. And there's not going to be much of a bolus, right? We have an EAP that's in place, you know, it's I can't give the number, but it's a certain number of patients. But no one's withholding treatment for eligible patients, to your point.

Steve: I'm going to give the number but it's a certain number of patients no one's withholding treatment for eligible patients to your point. The criticality is just too high so there'll be a little a little.

Steve Kloster: The criticality is just too high. So there'll be a little extra use initially from the AP. That'll burn out over the beginning months of the launch. And then after that, we'll expect a typical uptick just based on our assumptions and available patients.

Steve: We'll say extra use initially from EAP that'll burn out over the beginning months of the launch and then after that we will expect the typical uptick just based on our assumptions and available patients.

Neil Gallagher: I got it. It makes sense. And then maybe just a quick follow-up on your Phase I trial for metastatic colorectal cancer. In terms of the go-no-go decision, I know you mentioned disease stabilization as important, but I was curious, is there a specific signal, I don't know, maybe a biomarker that you're looking for in terms of Menin's potential or hypothetical role in driving solid tumors that would make you feel confident about investing significantly in this potential expansion opportunity?

Speaker Change: Got it makes sense and then maybe just a quick follow up on your phase one in metastatic colorectal cancer in terms of Nip go No go decision I know you mentioned disease stabilization is important but was curious is there a specific signal I don't know maybe a biomarker that you're looking for in terms of men's potential or hyper.

Speaker Change: <unk> role in driving solid tumors that would just make you feel confident about investing significantly in this potential expansion opportunity.

Neil Gallagher: Jason, thanks for the follow-up on CRC. I'm going to turn it over to Neil to address. Yeah, thanks.

Speaker Change: Jason Thanks for the follow up on CRC I'm going to turn it over to Neil to address yes. Thanks.

Neil Gallagher: So, in the part of the study that has been conducted to date, I just should reiterate Michael's point. I mean, this is primarily a safety study. We are looking at, in addition to clinical responses. I mean, primarily, it's a safety study, but we're also looking at clinical responses. We're also looking at biomarker data, and our anticipation is that, you know, as we get to a point in the future where we can make a decision on future development in this space, the totality of the efforts will be taken into consideration.

Neil Gallagher: So in the part of the study.

Neil Gallagher: That has been conducted to date just to reiterate Michael's point I mean, this was primarily the safety safety part of the study.

Neil Gallagher: We are looking at in addition to clinical responses I mean, primarily its a safety. We're also looking at clinical responses rollouts and looking at biomarker data.

Neil Gallagher: And our anticipation is that.

Neil Gallagher: As we get to a point in the future, where we could make a decision on future development in this space.

Neil Gallagher: Policy that will be taken into that taken into consideration, we haven't specifically said what.

Neil Gallagher: We haven't specifically said what, you know, what correlative data we're looking at, but, you know, at some point in the future, we will provide more details around that. I wouldn't necessarily expect too much data in our update in the second quarter on, for instance, correlative data, but rest assured that we are pursuing correlative studies. And as I said, we'll take the totality of the evidence into consideration. Got it.

Neil Gallagher: Rod Correlative data, we're looking at but at some point in the future. We will provide more details around that I wouldn't expect necessarily too much data and in our updates.

Neil Gallagher: In the second quarter.

Neil Gallagher: For instance, correlative data, but rest assured that we are pursuing correlative studies and.

Neil Gallagher: As I said, we will take that.

Neil Gallagher: As evidence since it into consideration.

Operator: Got it. Well, thank you for the color. Thank you, Jason. As a reminder, if you would like to ask a question, please press star 5 on your telephone keypad to raise your hand.

Speaker Change: Got it well thank you for the color.

Speaker Change: Thank you Jason.

Operator: As a reminder, if you would like to ask a question, please press star 5 on your telephone keypad to raise your hand. Our next question is from Justin Zelin at BTIG. Your line is open, please go ahead.

Speaker Change: As a reminder, if you'd like to ask a question. Please press star five on your telephone keypad you raise your hand. Our next question is from Justin Zelenak <unk>. Your line is open. Please go ahead.

Steve Kloster: Sure, maybe I'll let Steve take that question. Yeah, I appreciate the question, Justin. In terms of sales force size, we're not prepared to provide the exact color and size of the team, but it'll be a team that I think can really address customer needs. Our goal, whether it's providers, or anybody within the healthcare delivery system, is that it's a great customer experience. So we're prepared to link up to all different aspects of healthcare organizations to make sure we're meeting the needs of patients and supporting providers in their treatment of patients. So I think I used the term plus 95% coverage. So we'll take the opportunity. There's no doubt about that.

Justin Reid Zelin: Thanks for taking my question and welcome to Steve. So ahead of two launches. This year I wanted to ask how large of a sales force youre looking at build share and could you talk to the overlap of providers, who treat both leukemia and chronic graft versus host disease for promotion of both products.

Speaker Change: Sure maybe I'll, let Steve take that question. Thanks, guys.

Steve: I appreciate the question just in terms of sales force size, we're not.

Steve: To provide the exact color and size of the team, but it will it will be a team that I think can really address customer needs. Our goal, whether it's providers anybody within the health care delivery system that it's a great customer experience. So we're prepared to link up to all different aspects of health care organizations to make sure we're meeting the needs and supporting providers in there.

Steve: Their treatment of patients. So I think I use the term plus 95% coverage so.

Steve: That will cover the opportunity. There is there is no doubt about that in terms of overlap between.

Steve Kloster: In terms of overlap between GVHD and REV, there's high overlap. I mean, we're likely, along with Insight, calling on the same treatment centers, right? Whether it's treatment for AML or treatment for transplantation.

Steve: Gvhd and.

Steve: And Rev. Theres high overlap I mean, we're likely along with insight calling on the same treatment centers right, whether it's treatment of AML or treatment of transplant.

Steve Kloster: And we'll leverage that call point. You know, there's probably a third overlap right now between our REV audience and the AXE audience. We'll obviously provide 30% of the effort. So we'll leverage our footprint, and we will cover the market opportunity in both opportunities.

Steve: And we will leverage that call point, Theres, probably a third overlap right now.

Steve: <unk> Rev audience with the ox audience, we will obviously provide 30% of all of the effort. So we will leverage our footprint and we will cover the market opportunity in really both both opportunities.

Speaker Change: Thanks for taking my questions.

Speaker Change: Thank you Justin.

Operator: Our next question is from Chris Shibutani at Goldman Sachs. Your line is open, please go ahead.

Speaker Change: Our next question is from Chris <unk> at Goldman Sachs. Your line is open. Please go ahead.

Operator: Thank you. Good morning.

Chris: Thank you good morning, a lot of questions on the focus.

Chris: Have already been asked so perhaps if I can ask a bigger picture longer term question.

Chris: Ties a little bit to your guidance in terms of operating expense spend on R&D.

Chris: Near term question is it looks as if to reach your full year guidance will have a considerable step up in the second half is that primarily attributed to the combination studies just to give us a sense there Keith and then secondly, honestly I think <unk> done a tremendous amount of work in building this portfolio and the company is now very focused on trying to launch two products.

Chris: But as you know investors are impatient to try and figure out what could come next what is your thought on capital allocation priorities further business development. What are you seeing out there what's your appetite. Thank you.

Operator: A lot of questions on the focus have already been asked. So perhaps if I can ask a bigger picture, longer-term question. It ties a little bit to your guidance in terms of operating expense spend on R&D. The near term question is it looks as if to reach your full year guidance, we'll have a considerable step up in the second half. Is that primarily due to the combination studies, just to give us a sense there, Keith?

Speaker Change: Great. Thank you Chris good questions.

Chris: Keith you want to take the first one on the longer term issue.

Keith Alan Goldan: And then secondly, Anjali, I think you've done a tremendous amount of work in building this portfolio, and the company is now very focused on trying to launch two products. But, as you know, investors are impatient to try and figure out what could come next. What is your thought on capital allocation priorities, further business development? What are you seeing out there? What's your appetite? Thank you.

Chris: So.

Chris: Chris.

Michael A. Metzger: Great. Thank you, Chris.

Speaker Change: I wouldn't.

Michael A. Metzger: Good questions. Maybe, Keith, you want to take the first one on the longer term? Yeah, sure. So.

Keith: I wouldn't necessarily agree that it is a big step up to us to use your words, we did.

Keith Alan Goldan: So, um, Chris. I wouldn't necessarily agree that it's a big step up, to use your words. You know, we did total operating expenses in 1Q approach to $80 million. The guidance range for the second quarter is $80 to $85. So, you know, if we were just to stay on that trajectory, we'd be, you know, $320 million-ish. So there is some increase that I think we would anticipate in the back half of the year.

Speaker Change: Total operating expenses in <unk> approached $80 million.

Speaker Change: The <unk>.

Speaker Change: <unk> range for the second quarters 80, 85. So if we were just to stay on that trajectory would be.

Speaker Change: $320 million ish. So there is some increase that I think we would anticipate.

Speaker Change: The back half of the year and I think yes.

Keith Alan Goldan: And I think, yes, you know, certainly as IPF ramps, as the first line 7 plus 3 combination trial with With REV continues to accrue, and as we get ready to launch the pivotal Phase 3 Beneza conference ride with REV, that's certainly going to add to some of our R&D expenses in the back half of the year, but also don't forget we're building out a commercial organization so on the SG&A side we would expect some some growth there for the sales force all the customers facing individuals that Steve commented on earlier as well as you know the the G&A support for those for that field force

Speaker Change: Certainly as.

Speaker Change: Pf ramps as the first line seven plus three combination trial with <unk>.

Speaker Change: With Rev continues to accrue and as we get ready to launch the pivotal.

Speaker Change: Phase III trial.

Speaker Change: With Rev. That's certainly going to add to some of our some of our R&D expenses in the back half of the year.

Speaker Change: <unk>.

Speaker Change: But also don't forget we are building out our commercial organization. So on the SG&A side, we would expect some growth there for the sales force all the customer facing.

Speaker Change: Individuals that Steve commented on earlier as well as the G&A support for those for that field force.

Keith Alan Goldan: And in terms of your second question, Chris, on business development, I'll start and turn it over to Anjali. So look, I think our strategy has been, and we've been, you know, pursuing the same business model for, you know, quite some time, which is to in-license and develop new molecules with differentiated profiles. I think we've been fortunate to have great success with our in-licensing strategy and have these two molecules that are nearing approval.

Speaker Change: And then in terms of your second question Chris.

Speaker Change: <unk> developed maybe I'll start and turn it over to Angela So look I think our strategy has been and we've been pursuing the same business model for quite some time, which is to in license and develop.

Angela: New molecules with differentiated profiles I think we've.

Angela: <unk> been fortunate to have great success with our in licensing strategy and having these two molecules that are nearing approval.

Keith Alan Goldan: And so the bar is always quite high with regard to new opportunities. I think it's incumbent upon us to be thoughtful about how we allocate capital. And so we do think that additional molecules, bringing them into the pipeline, backfilling the earlier part of the pipeline, are quite important, and we are interested in doing that. And so I don't know if Anjali wants to make a comment on our activities, but we remain quite disciplined about what we're doing. Yeah.

Angela: And so the bar is always quite high with regard to new opportunities I think it's incumbent upon us to be thoughtful about how we allocate capital and so we do think that that additional molecules, bringing them into the pipeline back filling the earlier part of the pipeline is quite important and we are interested in doing that and so.

Speaker Change: I don't know financials I want to make a comment.

Angela: On our activities, but we remain quite disciplined about what we're doing.

Michael A. Metzger: Yeah, no, I think you said it well, Michael. We're very actively engaged in the market, looking across a variety of sources for new opportunities and spending a lot of time on diligence, and hopefully, we'll have some exciting news to share. But, you know, there's definitely a lot to look at.

Speaker Change: No I think you said it well.

Speaker Change: We're very actively engaged in the market looking at cross that variety of choices for for new opportunities in.

Speaker Change: Steady at a time and diligence and hopefully we'll have some exciting news to share of it.

Speaker Change:

Speaker Change: Definitely a lot to look at.

Speaker Change: Yep.

Anjali Ganguli: Exciting times. Thank you, Chris.

Speaker Change: Citing times, thank you Chris.

Operator: Our next question is from George Farmer at Scotiabank. Your line is open, please go ahead.

Operator: Our next question is from George Farmer at Scotiabank. Your line is open, please go ahead. Hi, good morning. Thanks for taking my question. A competitor of yours is speaking.

Speaker Change: Our next question is from George Farmer at Scotia Bank. Your line is open. Please go ahead.

George Farmer: Hi, good morning, Thanks for taking my question.

George Farmer: <unk> talked about combining their menin inhibitor with other targeted therapies like flip three inhibitors and the like is there hasn't been too much conversation.

George Farmer: On the call about that this morning is that something that youre thinking about as well.

George Farmer: Detail.

Michael A. Metzger: George, thanks for the question. So, in terms of combinations, maybe I'll let Neil comment on what else is going on with targeted therapies. Obviously, we have the trials ongoing. The pillars of our strategy being VenAZA in the unfit population and Ven and CoV, if you will, is another interesting option for patients in relapsed refractory and perhaps in earlier patients as well. So, just think about it in terms of Ven

George Farmer: George Thanks for the question.

George Farmer: So in terms of combinations I'll, maybe I'll, let Neil comment on what else is going on with targeted therapies, obviously, we have.

George Farmer: The trial is ongoing the pillars of our strategy being.

Neil Gallagher: But then in the unfit population and then in <unk>. If you will is another interesting option for patients relapsed refractory and perhaps in earlier patients as well.

Neil Gallagher: So just think about it in terms of then combos and then on the fit side of the equation in combination with that with chemotherapy and we've already demonstrated that the drug's ability to be combined with chemotherapy in relapsed refractory setting.

Neil Gallagher: And then on the fit side of the equation, in combination with chemotherapy, we've already demonstrated the drug's ability to be combined with chemotherapy in a relapsed refractory study. We'll have data updates on that. We'll also have additional data, as we talked about, on the Ven combos this year, which so far looks extremely good. But I think there are options open to us. And Neil, I don't know if you want to comment on some of those.

Neil Gallagher: We'll have data updates on that will also have additional data as we talked about on the <unk> combos this year, which so far looks extremely good.

Speaker Change: But I think there is options open to us in the I don't know if you want to comment on some of those yeah sure.

Neil Gallagher: Yeah, sure. So we have investigator-initiated trials either planned or ongoing. Which will, in which Revumantib in combination with Giltaritumib or Midastorm will be investigated, either are or will be investigated. To Michael's point, conducting, for instance, a pivotal program in a frontline FIT population in patients with both MPM1 and FIT3 mutations is technically very challenging. It's not really core to our strategy. Of course, we haven't revealed overall what our strategy is, but it's not core to our strategy.

Speaker Change: So we have investigator initiated trials either planned or ongoing.

Speaker Change: And which revenue amount of in combination with <unk>.

Speaker Change: Or minus storm will be investing either are or will be investigated.

George Farmer: To Michael's point.

George Farmer: Conducting.

George Farmer: For instance, a pivotal program in the frontline fit population in patients with both NPM. One flit three mutations is technically very challenging it's not really core.

George Farmer: Core to our strategy.

George Farmer: Of course, we haven't revealed overall, what our strategy is but it's not core to our strategy of what we've said is that.

Neil Gallagher: What we've said is that, obviously, in addition to the unfit Phase 3 that we plan to initiate by year-end, that we're dose-ranging in combination with 7 plus 3, which will position us then to initiate a Phase 3 during 2025, but we can anticipate that that will not be in dual mutation patients because that's a very large and complicated study. So we prefer to generate evidence in that population as opposed to potentially pursuing a registration strategy.

George Farmer: In addition to the unfit phase phase III that will initiate we plan to initiate by year end.

George Farmer: That were dose ranging in combination with seven plus three.

George Farmer: Which will position us to initiate a phase III. During 2025, you can anticipate that that will not be in deal mutation patients because that's a very large and complicated studies. So we've we preferred to.

George Farmer: Generate evidence in that population as opposed to.

George Farmer: Potentially pursuing.

George Farmer: Registration strategy.

Speaker Change: Okay, that's very helpful. Thanks.

Speaker Change: Thank you George.

Operator: This concludes our question and answer session. I'll now turn the floor over to Mr. Michael Metzger for any additional comments or closing remarks.

George Farmer: This concludes our question and answer session I will now turn the floor over to Mr. Michael Metzger for any additional comments or closing remarks.

Michael A. Metzger: Thank you, operator. And thank you all for your questions. Appreciate you tuning in today. We look forward to seeing you all at our planned investor events, including the Bank of America conference in May and the Goldman Sachs conference in June. And with that, we wish you a great day.

Michael A. Metzger: Thank you operator, and thank you all for your questions. Appreciate you tuning in today, we look forward to seeing you all at our planned investor events, including the Bank of America Conference in May and the Goldman Sachs Conference in June and with that we wish you a great day.

Operator: The meeting has now concluded. Thank you for joining us. You may now disconnect.

Speaker Change: The meeting has now concluded. Thank you for joining you may now disconnect.

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