Summary of Syndax Pharmaceuticals FY Conference Call Company Overview - **Company**: Syndax Pharmaceuticals (NasdaqGS:SNDX) - **Focus**: Oncology with two newly commercialized products: Revumenib and Niktimvo [4][6] Key Products and Performance Revumenib - **Indications**: Approved for KMT2A and NPM1 - **Quarterly Sales**: $32 million with a 25% growth since the last quarter [4] - **Market Penetration**: Aiming for 50% penetration in a 2,000 patient incidence market by year-end [5] - **Patient Treatment Dynamics**: - 70% of patients are treated in second or third line settings [10] - Increased transplant rates from 25% to about one-third in commercial settings [11] - Expected return of patients to maintenance treatment post-transplant, potentially increasing revenue [12][13] - **Combination Use**: 30%-40% of utilization is in combination therapies, indicating strong physician interest [18] Niktimvo - **Indication**: CSF1R antibody for third-line cGVHD - **Quarterly Sales**: $46 million, up from $36 million [6] - **Market Potential**: Estimated billion-dollar-plus opportunity in GVHD, with potential expansion into frontline settings [36][37] - **Profit Sharing**: 50/50 profit and loss split with Incyte, contributing 25%-30% to Syndax's P&L [40][41] Growth Potential and Market Position - **Stock Performance**: Despite strong product launches, stock performance has underperformed due to investor skepticism [9] - **Efficacy and Safety**: Revumenib is positioned as the most efficacious drug in its category, with a broad set of indications [24][25] - **Competitive Landscape**: Competitors do not have efficacy in KMT2A, providing a competitive edge for Revumenib [24] Clinical Development and Future Outlook - **Combination Studies**: Ongoing studies with venetoclax and other agents show promising results, with high complete response rates [30][31] - **IPF Study**: Anticipated data from the randomized phase two study in idiopathic pulmonary fibrosis (IPF) could lead to significant future opportunities [42][43] Regulatory and Safety Considerations - **QTc Warning**: Recent updates to the QTc warning have not altered physician perceptions significantly; management guidelines are well established [19][20] Conclusion - Syndax Pharmaceuticals is positioned for growth with strong product performance and a robust pipeline, despite current stock performance challenges. The company is focused on expanding its market presence and leveraging its competitive advantages in oncology treatments.

Core Insights - Syndax Pharmaceuticals reported total revenue of $45.9 million for Q3 2025, marking a 21% increase compared to Q2 2025 [1] - The company achieved FDA approval for Revuforj on October 24, 2025, for the treatment of relapsed or refractory NPM1m acute myeloid leukemia (AML) [1][5] - Syndax has $456.1 million in cash and investments, which is expected to fund the company to profitability [1][8] Financial Performance - Revuforj generated $32.0 million in net revenue for Q3 2025, a 12% increase from Q2 2025, with total prescriptions rising by 25% [4][5] - Niktimvo reported $45.8 million in net revenue, with Syndax recording $13.9 million in collaboration revenue from this product [9][11] - The net loss attributable to common stockholders for Q3 2025 was $60.7 million, or $0.70 per share, an improvement from a net loss of $84.1 million, or $0.98 per share, in the same period last year [13][29] Business Highlights - Strong demand for Revuforj and Niktimvo resulted in over $75 million in combined net sales for the quarter [2] - Revuforj was included in the NCCN Guidelines for R/R NPM1m AML as a category 2A recommended treatment option [5] - The company is advancing multiple clinical trials for Revuforj and Niktimvo, targeting various indications and patient populations [10][18] Research and Development - Research and development expenses decreased to $56.3 million in Q3 2025 from $71.0 million in the prior year, primarily due to the absence of a milestone payment related to Niktimvo's approval [11] - Selling, general, and administrative expenses increased to $44.9 million from $31.1 million, driven by higher commercial costs associated with the launches of Revuforj and Niktimvo [12] Future Outlook - The company expects total operating expenses for 2025 to be between $380 million and $385 million, excluding an estimated $45 million in non-cash stock compensation [14] - Syndax anticipates that its current cash reserves, combined with expected product revenue, will enable it to reach profitability [15]

Core Insights - Kura Oncology and Kyowa Kirin announced that results from the KOMET-007 trial of ziftomenib will be presented at the ASH 2025 Annual Meeting on December 8, 2025 [1][2] Group 1: Trial Details - KOMET-007 is a Phase 1a/b study assessing ziftomenib in combination with standard chemotherapies for adults with NPM1-mutated or KMT2A-rearranged acute myeloid leukemia (AML) [2] - The upcoming presentations will include data on newly diagnosed adults with NPM1-m AML and updated results for relapsed or refractory cases treated with ziftomenib combined with venetoclax and azacitidine [2][3] Group 2: Presentation Information - Two oral presentations will take place on December 8, 2025, focusing on the safety and clinical activity results from the KOMET-007 trial [5] - The presentations will provide more mature data, including additional response-evaluable patients and expanded safety summaries [3] Group 3: Company Overview - Kura Oncology is a clinical-stage biopharmaceutical company focused on precision medicines for cancer treatment, with a pipeline targeting hematologic malignancies and solid tumors [6] - Ziftomenib is a menin inhibitor aimed at specific genetic drivers of acute myeloid leukemias, with ongoing efforts to advance menin inhibition in various cancer types [6]

Core Insights - Syndax Pharmaceuticals has received FDA approval for Revuforj (revumenib) as the first and only therapy for both relapsed or refractory (R/R) acute myeloid leukemia (AML) with an NPM1 mutation and R/R acute leukemia with a KMT2A translocation, marking a significant advancement in treatment options for these aggressive blood cancers [2][3][4] Company Developments - Revuforj is now approved for use in adult and pediatric patients aged one year and older who have no satisfactory alternative treatment options, expanding its indication from a previous approval for R/R acute leukemia with a KMT2A translocation [2][11] - The approval is based on data from the Phase 2 portion of the AUGMENT-101 trial, which demonstrated a complete remission (CR) plus CR with partial hematological recovery (CRh) rate of 23% among patients with R/R NPM1 mutated AML [3][4] - The median time to CR or CRh response was reported at 2.8 months, with a median duration of 4.5 months [3] Industry Impact - The inclusion of Revuforj in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines as a category 2A recommended treatment option for R/R NPM1 mutated AML and R/R acute leukemia with a KMT2A rearrangement underscores its significance in the oncology landscape [5][6] - The approval of Revuforj is expected to set a new standard of care for patients with these difficult-to-treat blood cancers, as highlighted by experts in the field [4][5] - The company is committed to supporting patient access through its SyndAccess program, which provides personalized support and financial assistance for eligible patients [8]

Efficacy of Icovamenib - In Severe Insulin-Deficient Diabetes (SIDD) patients (Arm B), 12 weeks of icovamenib treatment resulted in a mean HbA1c reduction of 1.5% at Week 52 (p=0.01)[46, 55, 65] - Patients on GLP-1 based therapy who were not achieving target HbA1c levels experienced a clinically meaningful HbA1c reduction of 1.3% at Week 52 (p=0.05) after 12 weeks of icovamenib treatment[56, 66] - Higher icovamenib exposure, measured by PK Mean AUC, was associated with greater HbA1c reduction across all dosing arms[43, 44] - The company believes data suggest that a readily achievable exposure level could provide ≥1.5% HbA1c reductions in T2D patients[47, 56] Safety and Tolerability - Icovamenib was generally well-tolerated, with no adverse-event related discontinuations and no related serious adverse events reported[29, 66, 70] - The percentage of patients with at least one Treatment Emergent Adverse Event (TEAE) in the combined icovamenib arms was 27% (55 out of 201 patients), comparable to the placebo arm at 27% (18 out of 66 patients)[59] - No deaths were reported in any of the treatment arms[59] Trial Design and Patient Characteristics - The COVALENT-111 study was a Phase 2 randomized, double-blind, placebo-controlled study in participants with Type 2 Diabetes (T2D)[10] - The study included 216 planned participants, with a 3:1 randomization ratio of icovamenib to placebo[11] - The Per Protocol Population on 1 or More Antihyperglycemic Agents at Baseline included 163 patients, with 114 in the combined icovamenib arms and 49 in the placebo arm[15, 17, 18] Next Steps - The company plans to optimize icovamenib exposure and define dosing criteria with a Food Effect Study (COVALENT-121)[71] - The company plans to investigate icovamenib in severe insulin deficient diabetes patients in a Phase IIb Type 2 Diabetes Study (COVALENT-211)[71] - The company plans to investigate icovamenib in combination with a GLP-1 based therapy in a Phase II Type 2 Diabetes Study (COVALENT-212)[71]

Core Insights - Biomea Fusion, Inc. announced positive 52-week results from its Phase II COVALENT-111 study for icovamenib in type 2 diabetes patients, indicating durable efficacy and safety [1][2][5] Study Design and Results - COVALENT-111 is a double-blind, randomized, placebo-controlled trial involving adult patients with type 2 diabetes diagnosed within the last 7 years, with specific HbA1c and BMI criteria [3][4] - The study evaluated three dosing regimens of icovamenib, with a total of 267 patients receiving at least one dose, focusing on a modified intent-to-treat population of 163 patients [4] - Positive results were observed across multiple subgroups, with severe insulin-deficient patients showing a durable HbA1c reduction of 1.2% (p=0.01) sustained through Week 52 [5][8] - Patients on GLP-1-based therapy who did not achieve glycemic targets also showed a 1.3% reduction in HbA1c (p=0.05) after 8 or 12 weeks of treatment [6][8] Safety Profile - Icovamenib maintained a favorable safety profile throughout the 52-week observation period, with no treatment-related serious adverse events reported [7][8] Future Plans - The company plans to initiate Phase II trials in severe insulin-deficient diabetes patients and those not achieving glycemic targets with GLP-1 therapy in the fourth quarter of 2025 [8][15] Mechanism of Action - Icovamenib is a selective covalent inhibitor of menin, which is believed to enable the proliferation and preservation of healthy insulin-producing beta cells, addressing the underlying dysfunction in diabetes [12][13] Market Context - Diabetes is a significant health issue, with over 38 million people in the U.S. affected, highlighting the need for effective treatments [14]

Core Insights - Ziftomenib is being evaluated in combination with approved FLT3 inhibitors for frontline treatment of acute myeloid leukemia (AML) [1][2] - FLT3 mutations are prevalent in approximately 30% of newly diagnosed adult AML patients and up to 50% in those with NPM1-mutated AML, highlighting the significance of FLT3 as a target [1] - The KOMET-007 clinical trial has commenced, focusing on ziftomenib's efficacy alongside cytarabine, daunorubicin, and quizartinib for newly diagnosed AML patients [1][2] Company Overview: Kura Oncology - Kura Oncology is a clinical-stage biopharmaceutical company focused on precision medicines for cancer treatment, with a pipeline targeting hematologic malignancies and solid tumors [4] - Ziftomenib, a menin inhibitor, is under development to address specific genetic drivers of acute myeloid leukemias [4] Company Overview: Kyowa Kirin - Kyowa Kirin is a Japan-based Global Specialty Pharmaceutical Company with over 70 years of experience in drug discovery and biotechnology innovation [5] - The company is committed to developing novel medicines and treatments for high unmet medical needs, including hematological diseases and rare diseases [5]

Core Insights - Ziftomenib is being evaluated in combination with approved FLT3 inhibitors for frontline treatment of acute myeloid leukemia (AML), addressing a significant unmet need in patients with FLT3/NPM1 co-mutations [1][2] - FLT3 mutations are prevalent in approximately 30% of newly diagnosed adult AML patients and up to 50% in those with NPM1-mutated AML, highlighting the importance of targeting this genetic alteration [1] - The KOMET-007 clinical trial has commenced, focusing on the safety and efficacy of ziftomenib combined with standard chemotherapy and quizartinib for newly diagnosed AML patients [1][2] Company Overview - Kura Oncology is a clinical-stage biopharmaceutical company dedicated to developing precision medicines for cancer treatment, with a focus on small molecule drug candidates targeting cancer signaling pathways [4] - Kyowa Kirin is a global specialty pharmaceutical company with over 70 years of experience in drug discovery and biotechnology innovation, aiming to develop novel therapies for high unmet medical needs [5] Clinical Development - Ziftomenib has received Breakthrough Therapy Designation from the FDA for treating adult patients with relapsed or refractory NPM1-mutated AML, indicating its potential significance in the treatment landscape [1] - The KOMET-007 trial will assess the combination of ziftomenib with intensive chemotherapy and quizartinib, with primary endpoints including complete remission and composite complete remission [2]

Core Insights - Ziftomenib monotherapy demonstrated significant clinical benefit in treating relapsed/refractory NPM1-mutated acute myeloid leukemia (AML) with a complete remission rate of 22% [4][5] - The drug showed consistent activity across various patient subgroups, regardless of previous treatments or genetic mutations [4][5] - Ziftomenib has a favorable safety profile, with manageable adverse events and no significant drug-drug interactions [6][8] Company Overview - Kura Oncology is focused on developing precision medicines for cancer treatment, with ziftomenib being a key investigational drug targeting menin inhibition [10] - Kyowa Kirin is a global specialty pharmaceutical company committed to drug discovery and biotechnology innovation, collaborating with Kura Oncology on ziftomenib [11] Clinical Trial Results - The KOMET-001 trial included 92 adult patients, achieving an overall response rate of 33% and a median duration of response of 4.6 months [3][4] - Median overall survival for all patients was reported at 6.6 months, with responders showing a median survival of 18.4 months [5] - The trial's findings support the New Drug Application for ziftomenib, with a target FDA action date set for November 30, 2025 [7]

Summary of Syndax Pharmaceuticals (SNDX) Conference Call - September 02, 2025 Company Overview - **Company**: Syndax Pharmaceuticals - **Products**: Revuforj (for KMT2A-rearranged acute leukemia) and Ictimo (for chronic graft-versus-host disease, cGVHD) - **Recent Achievements**: Two rapid approvals in succession, with a focus on addressing high unmet medical needs in oncology Key Points on Revuforj - **Launch Performance**: Revuforj has seen a **43% growth in net sales** with over **$50 million** generated since launch, treating over **500 patients** [3][5] - **Market Dynamics**: - Targeting **KMT2A-rearranged patients**, with a total addressable market (TAM) of **2,000 new patients annually** [5][6] - Currently treating **25%** of the available market, with expectations to increase to **50%** by year-end [5][6] - **Treatment Duration**: Average treatment duration expected to increase from **4-6 months** to **9 months** as more patients are treated earlier in their disease progression [9][10] - **Patient Demographics**: Shift from treating late-line patients to earlier-line patients, with **70%** of current patients being in the second or third line of treatment [7][12] - **Transplant Dynamics**: Approximately **33%** of patients are expected to go for transplant, higher than the **25%** seen in clinical trials [7][8] Upcoming Regulatory Milestones - **sNDA Submission**: An sNDA for Revuforj is under review with a PDUFA date of **October 25, 2025** [21][22] - **Market Expansion**: The NPM1-mutated patient market is larger than KMT2A, with an estimated **4,500 patients** [23][24] Key Points on Ictimo - **Launch Success**: Ictimo has generated nearly **$50 million** in sales in its first full quarter, with **700 patients** treated [42][43] - **Patient Retention**: **80-90%** of patients are remaining on the drug, indicating strong tolerability [42] - **Market Coverage**: Over **80%** of transplant centers have utilized Ictimo, with a majority using it multiple times [43][44] - **Partnership with Incyte**: Co-promotion with Incyte has been efficient, leveraging their existing infrastructure [44] Future Development Plans - **Subcutaneous Formulation**: Development of a subcutaneous formulation for Ictimo is underway, which could enhance patient convenience [48] - **Clinical Trials**: Ongoing studies in combination with dexamethasone and Jakafi for earlier lines of therapy in cGVHD [49][50] Financial Outlook - **Profitability Goals**: Syndax aims to reach profitability without needing additional financing, with operating expenses expected to remain flat through **2025** [61][62] - **Collaboration Revenue**: Ictimo is already profitable on a contribution profit basis, with **$9 million** in collaboration revenue reported [61] Competitive Landscape - **Market Position**: Syndax is positioned as the only approved menin inhibitor, with a focus on maintaining a competitive edge through efficacy and multiple indications [30][40] Conclusion - **Strategic Focus**: Syndax is concentrating on successfully commercializing Revuforj and Ictimo, advancing clinical development, and achieving profitability before considering new product investments [68][69]