Syndax Pharmaceuticals, Inc. — FY2023 Form 10-K
Reporting period: Fiscal year ended December 31, 2023. Filed February 27, 2024. Syndax is a clinical-stage biopharmaceutical company with no approved products or product sales.
Business context and pipeline
- Revumenib: Menin inhibitor being developed for relapsed or refractory KMT2A-rearranged acute leukemia and NPM1-mutant AML; also being studied in metastatic colorectal cancer and combination/frontline settings.
- Axatilimab: CSF-1R antibody being developed for chronic graft-versus-host disease (cGVHD) and idiopathic pulmonary fibrosis (IPF), in collaboration with Incyte.
- Entinostat development has been deprioritized. Syndax operates as one reportable segment and relies on third parties and Incyte for manufacturing.
Financial results and liquidity
| Metric | FY2023 | FY2022 |
|---|---|---|
| Revenue | $0 | $0 |
| Research and development expense | $163.0 million | $118.5 million |
| Selling, general and administrative expense | $66.9 million | $33.3 million |
| Operating loss | $230.0 million | $151.8 million |
| Net loss | $209.4 million | $149.3 million |
| Basic and diluted loss per share | $2.98 | $2.46 |
| Net cash used in operating activities | $160.6 million | $133.7 million |
- Revenue and profit margins are not meaningful for 2023 because the company had no revenue; the 2021 profit was driven by $139.7 million of license-fee revenue, not product sales.
- Interest income rose to $21.2 million from $5.9 million, largely reflecting higher interest rates and a larger average investment balance. Total other income was $20.6 million.
- Cash, cash equivalents and short- and long-term investments totaled $600.5 million at year-end, versus $481.3 million a year earlier. Cash and cash equivalents alone were $295.4 million. Management said available funds should cover planned operating and capital needs for at least 12 months.
- Operating cash outflow increased by $26.9 million year over year. Financing provided $264.1 million, principally from a December public offering ($215.9 million net) and ATM sales ($42.1 million net). Investing activities provided $117.6 million, primarily reflecting net maturities of marketable securities.
- The Hercules term loan was repaid and terminated in September 2022. At December 31, 2023, reported liabilities were $58.7 million, chiefly current accrued expenses and collaboration payables; remaining lease and equipment-lease liabilities were approximately $1.6 million.
- Common shares outstanding increased to 84.8 million from 68.1 million during 2023. An additional ATM program of up to $200 million was authorized; unused capacity and future use could dilute shareholders.
Material changes versus prior year
- Net loss widened by $60.0 million, while operating expenses rose 52% to $230.0 million. R&D increased 38%, including higher revumenib trial, regulatory and personnel costs; SG&A doubled as commercial-readiness work and headcount expanded.
- Revumenib-related R&D expense rose 36% to $64.1 million. Axatilimab-related expense declined 4% to $32.1 million; Incyte reimbursements of development costs were $12.3 million in 2023 versus $25.9 million in 2022.
- Cash and investments increased, supported by equity financing, while operating cash burn also increased. Syndax recorded a $10.0 million UCB milestone expense in Q4 2023, payable in Q1 2024.
Clinical progress, outlook and risks
- Revumenib: The pivotal Phase 2 AUGMENT-101 KMT2A-rearranged cohort met its primary endpoint at interim analysis: CR/CRh was 23% (13/57) in pooled acute leukemia and 24.5% (12/49) in KMT2A-rearranged AML. Median response duration was 6.4 months at the July 2023 data cutoff. Grade 3 differentiation syndrome and QTc prolongation were reported in 15% and 14% of patients, respectively; no Grade 5 events of either type were reported. The company submitted an NDA for adult and pediatric relapsed/refractory KMT2A-rearranged acute leukemia under FDA Real-Time Oncology Review and expected an FDA action date in Q1 2024. It expected to complete NPM1-mutant AML cohort enrollment in late Q1 or early Q2 2024 and report topline data in Q4 2024.
- Axatilimab: In AGAVE-201, all three dose cohorts met the primary endpoint. The 0.3 mg/kg cohort had a 74% overall response rate within six months; 60% of responders remained in response at one year. The FDA accepted the BLA for cGVHD after at least two prior systemic therapies, granted Priority Review, and set an August 28, 2024 PDUFA date. In January 2024, Syndax exercised its option to co-commercialize axatilimab in the U.S. with Incyte. Incyte planned cGVHD combination trials for mid-2024; a Phase 2 IPF trial was open for enrollment.
- Management anticipated higher 2024 commercial, personnel and operating expenses as it prepared for potential launches. The filing does not provide financial earnings or revenue guidance.
- Principal risks include clinical and regulatory uncertainty, possible delays or failure to obtain approval, evolving safety data, patient-enrollment challenges, dependence on Incyte and contract manufacturers, competition, reimbursement and pricing pressure, intellectual-property exposure, and the need for additional capital beyond the stated runway. Development milestones and collaborator payments are contingent and uncertain.
- No material legal proceedings or recorded contingent liabilities were reported. Management and Deloitte concluded internal control over financial reporting was effective; the financial-statement audit opinion was unqualified.
Important facts for investors to verify
- Current FDA review status and outcomes for the revumenib NDA and axatilimab BLA, including any action dates, requested information, label conditions or post-marketing requirements.
- Final and updated efficacy, durability and safety results for revumenib and axatilimab; interim clinical results may change as data mature and are verified.
- Enrollment and timing for the revumenib NPM1-mutant AML cohort, planned combination trials, and the axatilimab IPF study.
- Actual cash burn, investment liquidity and runway as launch preparation and clinical programs progress; management’s 12-month funding estimate depends on assumptions.
- Potential dilution from equity awards, warrants and any further ATM or public offerings, as well as the terms and economics of U.S. axatilimab co-commercialization with Incyte.