Third Quarter 2026 Earnings Call - SYNDAX PHARMACEUTICALS INC

Explicit Guidance:

• Reviforge (Mennin Inhibitor) Peak Revenue: Exceed $2 billion in peak annual net revenue in the U.S. alone, driven by anticipated frontline indications.
• Nictinvo (GVHD) Annual Run Rate: Expected to reach $260 million annually, with collaboration revenue from the partner annualizing at over $90 million and expected to grow as penetration in third/fourth-line chronic GVHD increases.
• Nictinvo Collaboration Margin: Expected to stabilize in the low to mid-30% range (down from a slight high of ~34% this quarter due to a one-time adjustment), an increase from the previously guided 25%–30% range.
• Total R&D + SG&A Expenses (FY2026): Maintained guidance of approximately $400 million, excluding $50 million in non-cash stock compensation.
• Cash Position: Ended Q3 2026 with $551 million in cash, equivalents, and investments, deemed sufficient to fund commercial/R&D priorities through the pipeline's proof-of-principle stages.

Business-Segment Outlook:

• Reviforge (Relapse/Refractory AML):
  • Transplant Dynamics: Short-term headwind as patients pause for transplant, transitioning to long-term tailwind as post-transplant patients resume therapy.
  • Resumption Rates: Expect 70%–80% of KMT2A patients to return to therapy for 1–2 years; current resumption rates are ~60% (up from 50% last quarter). NPM1 post-transplant resumption is ~50% (up from lower historical levels), with a growing trend to 60%.
  • Treatment Duration: Average duration for post-transplant patients is at least 9 months, expected to increase. Non-transplant patients average >7 months.
  • Market Share: Projected to account for >80% of all Mennin inhibitor sales this quarter, maintaining market leadership.
• Nictinvo (Chronic GVHD):
  • Line of Therapy Expansion: Positive results from ongoing combination trials with frontline chronic GVHD could establish a new treatment paradigm and unlock a multi-billion dollar opportunity.
  • Adoption: Currently holds ~33% of the third-line-plus market, with increasing uptake in the fourth line and steady growth in the third line.
• Pipeline Assets:
  • SNDX-4321 (EGFR-mutated NSCLC): On track to submit IND by end of 2026; first monotherapy assessment expected early 2028.
  • SNDX-62122 (Next-Gen Menin Inhibitor for Myelofibrosis): On track to enter clinic next year (2027); Phase 1-2 POC trial expected to initiate Q4 2027 with initial data in H2 2028.
  • Axatilimab (Chronic GVHD): Top-line results for Phase 2 (combo with ruxolitinib) expected Q1 2027; Phase 3 (combo with corticosteroids) expected early 2028.

Market and Competitive Outlook:

• Frontline AML Opportunity: Aiming to be the first to market with a Mennin inhibitor for newly diagnosed AML, a high unmet need area.
• Competitive Landscape: Management expects no significant differentiation from upcoming competitor data (e.g., J&J, Sumitomo), citing Reviforge's broadest clinical profile, two years of commercial data, and dominant share across age groups and indications (NPM1 and KMT2A) as key differentiators.
• Real-World Evidence (RWE): Leading in prescriber adoption with >620 accounts (up 8% QoQ); formulary coverage near 100% of covered lives.
• NUP98 Rearranged AML: Landmark data publication expected in Q4 2026 for this 2–5% of AML cases to support guideline inclusion, potentially expanding the treatable patient population.

Macro / Industry Outlook:

• Clinical Paradigm Shifts: Anticipated shift toward earlier treatment lines and combination therapies (e.g., with venetoclax) to improve overall response rates (ORR) and drive higher transplant eligibility.
• Transplant Trends: Growing trend of patients proceeding to stem cell transplant post-Reviforge (40% of NPM1, 50% of KMT2A), which is expected to drive durable franchise growth through extended therapy duration.
• Pricing/Formulary: Strong formulary coverage and broad prescriber base suggest resilience against pricing pressure; no specific FX or regulatory headwinds mentioned beyond standard biopharma risks.

Strategic Initiatives:

• Leadership Transition: Aaron Andre appointed as new CFO effective November 9, 2026, succeeding retiring CFO Keith Goldan.
• Frontline Trial Execution: Pivotal frontline trials (EVOlve 2, REVEAL) are well-established with global site activation; aiming to update data sets at ASH (December 2026) to support approval timelines.
• Post-Transplant Maintenance: Advancing Phase 1 trial data for Reviforge as post-transplant maintenance, aiming to capture patients for 1–2 years of therapy.
• Dosing Optimization: Published data (Agave 201) supports transitioning from 2-weekly to 4-weekly axatilimab dosing, potentially informing future labeling and reducing healthcare burden.
• MRD Erasure: Advancing "Intercept" trial data to support early intervention for MRD-positive disease, aiming to intervene before morphological relapse.

Risks and Headwinds to Outlook:

• Transplant Pause: Short-term revenue headwinds caused by patients pausing therapy during transplant cycles; full financial benefit delayed until post-transplant resumption "stacks."
• Competitor Data: Upcoming data from competitors (e.g., at ASH) could alter the competitive dynamic, though management remains confident in their lead.
• Clinical Trial Uncertainty: Dependence on positive readouts for Phase 3 frontline trials and Phase 2/3 axatilimab combination trials to unlock multi-billion dollar markets.
• Guidance Caveats: Actual results may differ due to factors in the Form 10Q; forward-looking statements represent views as of November 2, 2026.

Management Tone on the Future:

• High Confidence: Management expresses strong conviction ("unmatched body of clinical evidence," "world-class R&D capabilities") in achieving profitability and dominating the Mennin inhibitor space.
• Momentum: Describes the business as having "gained a lot of steam" in Q3 with "robust demand" and "decisive" moves toward profitability.
• Long-Term View: Framing the transplant pause as a "long-term tailwind" and emphasizing the transition from "foundation" to "finish line" of commercial success.

Miscellaneous:

• Awards: Reviforge received the "Best Product for Rare Orphan Diseases Award" and recognition by Time as one of the best innovations of 2026.
• Data Publication: NUP98 data and real-world evidence updates scheduled for Q4 2026; Axatilimab Phase 2 data expected Q1 2027.
• Patient Cohorts: ~50% of new Reviforge patients are NPM1 (up from 35% of revenue last quarter); expanding adoption in community practices alongside Tier 1/2 accounts.