Summary of Syndax Pharmaceuticals Conference Call on Revuforge Approval Company Overview - **Company**: Syndax Pharmaceuticals (NasdaqGS: SNDX) - **Product**: Revuforge, a first-in-class menin inhibitor - **Date of Call**: October 24, 2025 Key Industry and Company Insights FDA Approval and Indications - Revuforge received FDA approval for its second indication, targeting adults and pediatric patients with relapsed or refractory NPM1 mutated acute myeloid leukemia (AML) [6][10] - This approval follows the initial FDA approval in November 2024 for relapsed or refractory acute leukemia patients with KMT2A translocation [6][10] - Revuforge is now the first and only menin inhibitor approved for multiple acute leukemia subtypes in both adults and pediatrics [6][10] Clinical Efficacy and Data - The approval is based on pivotal data showing a 47% overall response rate (ORR) and an 11% transplant rate in patients treated with Revuforge [8][19] - The median overall survival for responders was nearly two years, with a median duration of response of 4.5 months [19][20] - Revuforge demonstrated compelling efficacy across multiple genetic subtypes of acute leukemia, establishing a strong clinical profile [8][20] Market Opportunity - The total addressable population for Revuforge has expanded from approximately 2,000 KMT2A incident patients to 6,500 patients, representing a market opportunity exceeding $2 billion in the relapsed refractory setting [25][26] - Approximately 40-45% of AML patients have either an NPM1 mutation or a KMT2A translocation, indicating a significant market potential [26] Commercial Strategy and Execution - Syndax has established a strong commercial foundation with a trusted presence in leading cancer centers across the U.S. [10][28] - The company has achieved nearly $50 million in net revenue in the first two full quarters post-launch, despite some KMT2A patients pausing treatment for transplants [27][28] - Revuforge is on formulary for 97% of covered lives, facilitating rapid access for patients [29][30] Safety Profile and Monitoring - The updated label includes a boxed warning for QTc prolongation and torsades de pointes, based on a non-fatal case identified during clinical trials [16][51] - Management of QTc prolongation remains straightforward, with physicians already familiar with monitoring protocols [41][51] Future Outlook - Syndax plans to expand Revuforge into additional indications and frontline settings, with ongoing clinical trials [11][35] - The company is positioned for continued growth, with a strong pipeline and a focus on innovative therapies for difficult-to-treat diseases [24][35] Additional Important Points - The NCCN Guideline Committee has added Revuforge as a recommended treatment option for relapsed refractory NPM1 mutated AML, validating the strength of the clinical data [10][11] - The company has a comprehensive clinical development plan aimed at unlocking a market opportunity exceeding $5 billion in the U.S. [11] - Syndax's commercial team has extensive experience in hematology and oncology, enhancing their ability to engage with healthcare providers effectively [32][34] This summary encapsulates the critical insights from the conference call regarding Syndax Pharmaceuticals, its product Revuforge, and the broader implications for the acute leukemia treatment landscape.

Financial Data and Key Metrics Changes - In Q2 2025, Syndax reported net revenue of $28.6 million for Revuforge, a 43% increase quarter over quarter, with combined net product sales for Revuforge and Nyktymbo reaching nearly $100 million in the first half of the year [6][7][19] - Nyktymbo generated $36.2 million in net revenue in its first full quarter, significantly up from $13.6 million in the first two months of launch [15][40] - The company maintains a strong financial position with $518 million in cash and equivalents as of June 30, 2025, and expects to reach profitability with current resources [43][44] Business Line Data and Key Metrics Changes - Revuforge has treated over 500 patients, with approximately 90% of usage in KMT2A patients, and is increasingly being used in earlier lines of therapy [10][20] - Nyktymbo is already profitable for Syndax, contributing $9.4 million in collaboration revenue in Q2 2025 [16][41] - The average treatment duration for Revuforge is expected to build to 4-6 months in the first year and potentially 6-12 months in the second year as treatment patterns mature [23][68] Market Data and Key Metrics Changes - Revuforge has penetrated 25% of the annual 2,000 patient incidents of relapsed-refractory KMT2A acute leukemia, with expectations to reach 50% by year-end [20][83] - Nyktymbo is positioned in a $2 billion market for chronic GVHD treatments, with a total addressable market of $2 billion based on current indications [28][49] - The company anticipates expanding Revuforge's market opportunity to over $2 billion with the approval of its supplemental new drug application for relapsed-refractory mutant NPM1 AML [13][14] Company Strategy and Development Direction - Syndax aims to extend its leadership in the menin inhibition space, with ongoing trials for Revuforge in both frontline and relapsed settings [35][37] - The company is focused on developing Nyktymbo for additional patient populations, including idiopathic pulmonary fibrosis (IPF) [38] - Syndax's strategy includes maintaining stable operating expenses while investing in the successful launches of Revuforge and Nyktymbo [41][54] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's trajectory towards profitability, driven by strong physician enthusiasm and robust adoption of both products [45][46] - The anticipated approval of the supplemental new drug application for Revuforge is expected to significantly enhance its market position [13][96] - Management highlighted the importance of treatment duration and patient outcomes as key drivers for future growth [90] Other Important Information - The company has strengthened its leadership team with the addition of Nick Botwood as Head of R&D and Chief Medical Officer [17] - Syndax has retained worldwide rights to Revuforge, with patent protection extending through at least the late 2030s [48] Q&A Session Summary Question: Path to profitability and assumptions for top line growth - Management indicated that profitability is expected with existing resources, and both product launches are outperforming expectations [52][53] Question: Patients proceeding to transplant and maintenance therapy - Management noted that patients typically proceed to transplant after 2-3 cycles of treatment, with expectations for a high percentage of patients to return to maintenance therapy [57][62] Question: Treatment duration observations in real-world practice - Management confirmed that the average treatment duration is expected to be 4-6 months in the first year, potentially extending to 6-12 months as more patients are treated earlier [64][68] Question: KMT-2A patient penetration and revenue growth - Management clarified that there is still significant growth potential in the KMT-2A population, with expectations to reach 50% penetration by year-end [78][88] Question: FDA approval confidence and remaining open items - Management expressed confidence in the FDA approval process, indicating that discussions with the agency have been positive [95][99]

Financial Data and Key Metrics Changes - The company achieved $20 million in sales for the first quarter, surpassing expectations [8][9] - The sales for Niktinvo marked $13.6 million, indicating strong demand and a good start for the product [61] Business Line Data and Key Metrics Changes - RAV4's launch has seen a broad and growing user base, with approximately 44% of tier one and tier two institutions having written prescriptions by March, expected to exceed 50% [10][12] - Formulary coverage has improved significantly, rising from just above 70% in March to over 90% [12] Market Data and Key Metrics Changes - The company is positioned well in the U.S. market with robust supply chains and minimal impact from external factors such as tariffs [6][7] - The KMT2A population is the primary focus, with expectations to achieve over 50% market penetration in the first year [14] Company Strategy and Development Direction - The company aims to expand beyond relapsed-refractory markets and build long-lasting franchises with its first and best-in-class medicines [5] - There is a strong focus on moving into frontline combinations and addressing both fit and unfit patient populations through randomized control studies [51][52] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's positioning amidst evolving policies on drug pricing and tariffs, stating that the supply chains are robust [6][7] - The company anticipates significant growth opportunities in the coming year, particularly with the expected approval of the sNDA for the NPM1 patient population [70][71] Other Important Information - The company is actively enrolling patients in the EVOLVE study, which is a large multi-site international study with dual primary endpoints [55] - The company expects to present updated data at the EHA Congress, which will include Kaplan Meier's around overall survival [59] Q&A Session Summary Question: What are the dynamics of the RAV4 launch? - The launch has exceeded expectations with a broad user base and improved formulary coverage, leading to strong sales momentum [9][12] Question: How is the company managing safety concerns with Revuforge? - Physicians are well-equipped to manage side effects, and early experiences have been positive with no significant hindrances to patient treatment [24][29] Question: What is the timeline for the NPM1 supplementary NDA review? - The supplementary NDA was submitted in April, with a six-month priority review expected to conclude around October [32] Question: How does the company plan to position Revuforge against competitors? - The company believes it has a compelling profile and is the only approved menin inhibitor, with strong efficacy data supporting its use [41][42] Question: What milestones should investors look for in the next twelve months? - Key milestones include data presentations at EHA, expected approval of the sNDA, and continued growth in KMT2A and NPM1 franchises [70][71]

Financial Data and Key Metrics Changes - For Q4 2024, Syndax Pharmaceuticals reported $7.7 million in net revenue from Revuforj, marking the company's first quarter with product revenue [10][46] - Operating expenses for Q4 were $104 million, which included $65.5 million in research and development expenses and $37.7 million in selling, general, and administrative expenses [46] - The company maintained a strong financial position with $692.4 million in cash, equivalents, and investments at year-end [47] Business Line Data and Key Metrics Changes - Revuforj, the first-in-class menin inhibitor, launched in November 2024, has shown strong early demand with $7.7 million in net revenue from the first five weeks of sales [10][11] - Niktimvo, launched in January 2025 for chronic graft versus host disease, is expected to capture a significant portion of the $1.5 billion to $2 billion market for third-line or later chronic GVHD treatment in the US [32] Market Data and Key Metrics Changes - Approximately 33% of Tier 1 and Tier 2 accounts have ordered Revuforj, indicating strong early penetration in key treatment centers [21][22] - The company is seeing rapid inclusion of Revuforj in payer coverage, with 56% of commercially covered lives and 53% of all managed care lives having formal coverage policies in place [25] Company Strategy and Development Direction - The company aims to expand Revuforj's indication to include mutant NPM1 AML by filing a supplemental new drug application in the upcoming quarter [12] - Syndax is focused on building a robust pipeline in oncology, with plans to extend its products into earlier line indications and develop additional targeted therapies [99][100] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's position for long-term growth, highlighting the strong market opportunities with Revuforj and Niktimvo [54] - The management team emphasized the importance of building a habit among physicians for prescribing Revuforj, which is expected to become the standard of care for KMT2A translocations [24][60] Other Important Information - The company received $350 million upfront from Royalty Pharma in exchange for a capped royalty on US net sales of Niktimvo, indicating the product's multi-billion-dollar potential [15] - The company expects R&D expenses for Q1 2025 to be between $65 million and $70 million, with total R&D plus SG&A expenses projected to be between $105 million and $110 million [48] Q&A Session Summary Question: Inventory levels and repeat prescribers for Revuforj - Management indicated that inventory levels are expected to remain stable at about two to three weeks, with revenue growth potentially increasing absolute inventory levels [62] - Approximately one-third of Tier 1 and Tier 2 accounts have ordered Revuforj, with most accounts having prescribed it more than once, indicating positive early adoption [65] Question: Activation of Tier 1/2 accounts and comparison to historic AML launches - Management expects continued activation of Tier 1 and Tier 2 accounts over the next 10 months, with a focus on the top 200 treatment centers [73] - The unique setup of Revuforj, including diagnostic testing for KMT2A patients, is expected to drive its adoption compared to other targeted therapies [78] Question: Off-label use and Expanded Access Program (EAP) - Anecdotal evidence suggests some off-label use of Revuforj, particularly in combination treatments, but specific numbers are not yet available [86] - The EAP remains lightly used, with no additional patients expected to transition from it at this time [87] Question: Future company vision and pipeline expansion - The company aims to build a larger pipeline in oncology and expects to have multiple commercial products by 2030, focusing on targeted therapies [100][101] Question: Safety feedback and physician experience with Revuforj - Feedback on Revuforj's safety profile has been positive, with comprehensive support provided to physicians through clinical nurse educators [110] Question: Gross to net adjustments and patient assistance programs - The gross to net adjustments for Revuforj are expected to remain tight due to the limited distribution channel, with a patient assistance program available for uninsured or underinsured patients [118][120] Question: Transplant dynamics and patient treatment pathways - Physicians are interested in getting patients to transplant, particularly for KMT2A, with expectations that many patients will return to maintenance therapy post-transplant [122]