THIRD QUARTER 2026 EARNINGS CALL - SYNDAX PHARMACEUTICALS INC

Explicit Guidance:

• Total Revenue Growth: Revenue from both Revuforge and Nictinvo expected to continue growing through the near term, advancing the company toward profitability.
• Nictinvo Collaboration Margin: Expected to normalize to the low to mid-30% range (down from current ~34% impacted by a one-time adjustment; prior guidance was 25–30%).
• R&D and SG&A Expenses: Total guidance for 2026 remains ~$400 million, excluding $50 million in non-cash stock compensation.
• Liquidity: Company remains fully funded with $551 million in cash, equivalents, and investments to execute commercial and R&D priorities.

Business-Segment Outlook:

• Revuforge (Acute Leukemia):
  • Peak Revenue: Potential to exceed $2 billion in peak annual net revenue in the U.S. with anticipated frontline indications.
  • Patient Flow: Expect post-transplant therapy resumption rates to reach 70–80% for KMT2A patients (currently ~60%) and 50–60% for NPM1 patients (currently ~50%), significantly extending average treatment duration.
  • Treatment Duration: Patients in the post-transplant setting currently average ≥9 months of therapy; non-transplant patients average >7 months.
  • Market Share: Intend to maintain >80% of the class revenue for Revuforge.
  • Data Catalysts: Publishing NUP98 rearranged AML data in Q4 2026; presenting extensive new data at ASH in December 2026.
• Nictinvo (Chronic GVHD):
  • Annual Run Rate: Currently annualizing at >$260 million; expected to grow as penetration increases in 3rd and 4th line settings.
  • Growth Trajectory: Targeting similar launch trajectory to Resiroc ($500M annual sales in 4 years) as 3rd line uptake accelerates.
• Pipeline (SNDX 4321 & 62122):
  • IND Timelines: Expect to submit IND for SNDX 4321 (NSCLC) by end of 2026; IND for SNDX 62122 (Myelofibrosis) in 2027.
  • Clinical Initiation: Both molecules expected to enter the clinic in 2027.

Market and Competitive Outlook:

• Revuforge Positioning: Anticipated to be first to frontline with a Menin inhibitor; dominant share of new patients in NPM1 and KMT2A across all age groups.
• Competitive Landscape: Expect competitor data (J&J, Sumitomo) at ASH; management views competition as "unlikely to be differentiated" given Revuforge's broad profile, real-world evidence, and physician trust.
• Nictinvo Expansion: Ongoing trials in newly diagnosed (frontline) chronic GVHD could redefine the treatment paradigm and unlock a multi-billion dollar opportunity if combination data with ruxolitinib or corticosteroids succeeds.

Macro / Industry Outlook:

• Transplant Trends: Management identifies a structural shift where increased transplant rates (40% for NPM1, 50% for KMT2A) create a short-term revenue headwind (treatment pause) but a long-term tailwind (extended duration post-transplant).
• Prescribing Behavior: Continued shift toward earlier line usage and combination therapies, driven by higher overall response rates enabling transplant eligibility.

Strategic Initiatives:

• Frontline AML Trials: Execution of pivotal Phase 3 trials (EVOLVE-2, REVEAL) and combination studies (BEAT-AML, SAVE) to establish Revuforge as the standard of care in newly diagnosed AML.
• Pipeline Advancement:
  • Revumenib Maintenance: Initiating Phase 1-2 proof-of-principle trial for Revumenib in Myelofibrosis in Q4 2027; initial data expected H2 2028.
  • Axatilimab: Reporting Phase 2 top-line results for frontline chronic GVHD combination with ruxolitinib in Q1 2027; Phase 3 results with corticosteroids expected in early 2028.
  • Reduced Dosing: Implementation of reduced frequency dosing (0.6 mg/kg q4w) for axatilimab based on Agave 201 data to improve patient convenience.
• Leadership Change: Transition of CFO role from Keith Goldan to Aaron Andre effective November 9, 2026.

Risks and Headwinds to Outlook:

• Transplant Disruption: Short-term revenue impact due to patients pausing therapy for stem cell transplants (estimated 2–5 months pause).
• Competitive Data: Potential registration-enabling data from competitors at ASH could influence market perception.
• Timing Risks: Data readouts for Axatilimab trials are subject to delays if durability data is insufficient (as seen with the shift to Q1 2027).
• Regulatory Uncertainty: Final approval timelines for frontline Revuforge dependent on successful Phase 3 enrollment and data maturity; management declined to update specific completion dates.

Management Tone on the Future:

• Confidence Level: Highly confident ("extremely confident," "very well positioned") regarding Revuforge's dominance in relapse/refractory and its first-mover advantage in frontline AML.
• Strategic Shift: Moving from a "relapse/refractory" focus to a "frontline" strategy, viewing the transition as a major value driver.
• Commercial Health: Describes momentum as "robust" with growing prescriber adoption (90% of Tier 1/2 accounts) and expanding real-world evidence.
• Financial Discipline: Emphasizes a "bold R&D vision" supported by a "solid financial position" and a clear path to profitability.

Miscellaneous:

• NUP98 Rearrangement: Estimated to represent 2–5% of AML cases with high unmet need; Revuforge is the only Menin inhibitor with reported clinical activity in this subtype, targeting guideline inclusion.
• Patient Cohort Growth: 20% quarter-over-quarter increase in new patients, driven by growth in both KMT2A and NPM1 populations.
• Commercial Foundation: Over 620 accounts active, with formulary coverage in place for nearly 100% of all covered lives.