Financial Data and Key Metrics Changes - The FDA has accepted the new drug application for Ziftamenib based on positive results from the COMET-one trial, with a PDUFA target action date of November 30, 2025 [5][39]. - The company reported having over $700 million on the balance sheet as of the end of the first quarter, with potential to earn an additional $375 million in near-term milestones [46]. Business Line Data and Key Metrics Changes - The COMET-one trial demonstrated a 35% overall response rate and a 25% complete remission with and without hematologic recovery (CRCRH) rate in patients treated with Ziftamenib [14][22]. - Among the 92 patients in the phase two portion of the study, the CRCRH rate was 23%, significantly superior to the historical 12% rate with conventional chemotherapy [14][22]. Market Data and Key Metrics Changes - The company is targeting the relapsed refractory acute myeloid leukemia (AML) patient population, where there is a high unmet medical need, with 20% being primary refractory and 50% relapsing within one year [39]. - Physicians have expressed positive feedback regarding Ziftamenib's overall survival among responders, which is longer than expected in this patient population [36]. Company Strategy and Development Direction - The company is pursuing an aggressive development and commercialization strategy for Ziftamenib, aiming to treat up to 50% of AML patients who may benefit from menin inhibitor therapy [5][25]. - A comprehensive development strategy is in place to address patients in both frontline and relapsed refractory settings, utilizing both company-sponsored and investigator-initiated studies [25][28]. Management's Comments on Operating Environment and Future Outlook - Management emphasized the importance of Ziftamenib's favorable safety profile, which positions it as a potentially best-in-class menin inhibitor for AML [44]. - The company is focused on supporting the FDA review process and preparing for a potential launch in the fourth quarter of 2025 [44][46]. Other Important Information - The COMET-one study showed that Ziftamenib was well tolerated, with low rates of myelosuppression and no clinically significant QTc prolongation [19][22]. - The differentiation syndrome was observed in 23% of patients, but with effective management strategies, the majority of patients continued therapy [21][80]. Q&A Session Summary Question: Can you talk about predicting patient responses to Ziftamenib? - Management indicated that currently, there is no clear way to predict which patients will respond to Ziftamenib, although some patients with IDH1 co-mutations appeared to respond better [50][53]. Question: What are the plans for commercial launch preparation? - The company is building out its capabilities to ensure product availability upon approval, learning from the market experience of other menin inhibitors [56][60]. Question: How are physicians managing differentiation syndrome? - Experienced investigators have implemented early recognition and mitigation strategies for differentiation syndrome, leading to better management and patient retention in studies [78][80]. Question: What differentiates Ziftamenib from other products in the market? - Convenience and safety are highlighted as key differentiators, with Ziftamenib being a once-daily oral medication that does not require extensive monitoring [86][90]. Question: What is the expected average duration of therapy for Ziftamenib? - The expected duration of therapy is approximately six months, based on the time needed for patients to achieve a response and the duration of that response [94][97]. Question: Why might FLT3 ITD patients have a lower response rate? - The lower response rate in FLT3 ITD patients may be due to their heavily pretreated status and the development of resistance to multiple therapies [100][101].

Financial Data and Key Metrics Changes - Collaboration revenue from the Kyowa Kirin partnership for Q1 2025 was $14.1 million compared to no revenue in Q1 2024 [20] - Research and development expenses for Q1 2025 were $56 million compared to $36.3 million for Q1 2024 [20] - General and administrative expenses for Q1 2025 were $22.8 million compared to $18.2 million for the same period in 2024 [20] - Net loss for Q1 2025 was $57.4 million compared to a net loss of $49.5 million for Q1 2024 [20] - As of March 31, 2025, the company had cash, cash equivalents, and short-term investments of $658.2 million compared to $727.4 million as of December 31, 2024 [21] Business Line Data and Key Metrics Changes - The Ziftamenib development program achieved its primary CRCRH endpoint in the Phase II trial for relapsed/refractory NPM1 mutant AML, with data to be presented at the 2025 ASCO Annual Meeting [11][12] - The company announced the first patients with advanced gastrointestinal stromal tumors (GIST) were dosed with the combination of Ziftamenib and imatinib [8] Market Data and Key Metrics Changes - The company is focusing on the NPM1 mutant AML market, which represents approximately 30% of new AML cases annually, indicating a significant unmet need [10] - The company is also targeting advanced GIST patients, where current treatment options are limited [15] Company Strategy and Development Direction - The company aims to commercialize Ziftamenib in acute myeloid leukemia (AML) and is preparing for multiple clinical data updates throughout the year [6][7] - The strategic partnership with Kyowa Kirin is expected to provide greater development, commercial, and operational resources, enhancing financial stability [19] - The company plans to initiate the COMMENT-seventeen Phase III trials in the second half of 2025, focusing on both intensive and non-intensive treatment regimens for AML [14][23] Management's Comments on Operating Environment and Future Outlook - Management remains optimistic about the potential for Ziftamenib to impact patients with relapsed/refractory NPM1 mutant AML, citing a collaborative relationship with the FDA [10] - The company is monitoring the macro landscape and believes the impact from tariffs will be negligible [19] Other Important Information - The company has a strong cash position, with sufficient capital to fund the Ziftamenib AML program to commercialization and advance its pipeline [21] - The company is preparing for upcoming milestones, including presentations at major oncology meetings and the initiation of new trials [23] Q&A Session Summary Question: Expectations for combo data coming later this year - Management emphasized safety as the top priority for the combination data and confirmed they are on track to start the study in the second half of 2025 [26][29] Question: Impact of regulatory changes on approval process - Management stated there have been no disruptions from regulatory changes and they expect to receive notification from the FDA regarding the application review in the second quarter [33][36] Question: Market share strategy for NPM1 market - Management believes they are not necessarily second to market and are prepared to compete aggressively for patients [66][70] Question: Patient segments responsive to GIST combination - The combination approach is expected to be mutationally agnostic, potentially benefiting both imatinib-refractory and naive patients [74][75] Question: Enrollment timeline for pivotal trials - Management indicated that there should not be a drag on enrollment for frontline trials, as no menin inhibitor is currently approved for that patient population [114][116]