Syndax Pharmaceuticals, Inc. — 2022 Form 10-K
Reporting period: Fiscal year ended December 31, 2022. This is an annual report, not a standalone fourth-quarter filing; quarterly results are not clearly provided in the filing text. Syndax is a clinical-stage biopharmaceutical company with no approved products and no product sales.
Business context and pipeline
- Revumenib: Menin inhibitor in clinical development for relapsed or refractory KMT2A-rearranged acute leukemia and NPM1-mutant AML. The pivotal Phase 2 portion of AUGMENT-101 was enrolling three patient cohorts.
- Axatilimab: CSF-1 receptor antibody being developed for chronic graft-versus-host disease (cGVHD), with Incyte, and for potential use in idiopathic pulmonary fibrosis (IPF). Enrollment in pivotal cGVHD trial AGAVE-201 was complete.
- Entinostat: Development deprioritized; Syndax retains licensing arrangements, including an Asian-territory license to Eddingpharm.
Financial performance and liquidity
| Metric | 2022 | 2021 | Change/context |
|---|---|---|---|
| Revenue | $0 | $139.7 million | 2021 included nonrecurring license revenue from Incyte and KKC; no product revenue in either year. |
| Research and development expense | $118.5 million | $88.2 million | Up 34%, primarily from increased clinical activity and employee costs. |
| General and administrative expense | $33.3 million | $25.2 million | Up 32%, primarily from higher employee-related costs and professional fees. |
| Operating loss (income) | $(151.8) million | $26.2 million | Shifted to a loss as license revenue recognized in 2021 did not recur. |
| Net loss (income) | $(149.3) million | $24.9 million | 2022 loss per share was $2.46; 2021 earnings per share were $0.48 basic and $0.46 diluted. |
| Net cash from (used in) operating activities | $(133.7) million | $29.1 million | 2021 operating cash flow benefited from license-related receipts and income. |
| Cash, cash equivalents and short- and long-term investments | $481.3 million | — | Management expected available resources to fund planned expenses and capital needs for at least 12 months from the financial-statement issuance date. |
- At December 31, 2022, total assets were $497.2 million, total liabilities were $29.8 million, and stockholders’ equity was $467.4 million. Current assets were $489.8 million and current liabilities were $29.1 million.
- Operating expenses exceeded revenue in 2022; profit margins are not meaningful because the company had no revenue.
- Net cash used in investing activities was $186.2 million, mainly reflecting purchases of available-for-sale securities net of maturities. Net cash provided by financing activities was $172.3 million, principally from equity issuances.
- The company repaid its term loan in full in September 2022, paying approximately $21.5 million including fees. No term loan remained outstanding at year-end.
- In December 2022, Syndax issued 7.84 million common shares for gross proceeds of approximately $172.5 million. It also raised approximately $19.4 million net through its at-the-market program during 2022.
Material changes, outlook and risks
- Revumenib trial data: In the Phase 1 efficacy-evaluable population of 60 patients, the filing reports an overall response rate of 53% (32/60), a CR/CRh rate of 30% (18/60), and median CR/CRh response duration of 9.1 months. These were interim results as of the March 2022 cutoff and are subject to change. The filing notes QT prolongation as the only dose-limiting toxicity; no treatment-related discontinuations were reported.
- Regulatory and clinical outlook stated in the filing: Following Breakthrough Therapy Designation for revumenib in relapsed or refractory KMT2A-rearranged acute leukemia, Syndax expected to report cohort data in the third quarter of 2023 and submit an NDA by year-end 2023. It also expected to complete enrollment in the NPM1-mutant AML cohort in the second half of 2023.
- Syndax and Incyte expected axatilimab AGAVE-201 topline results in mid-2023 and, if successful, a BLA submission by year-end 2023. A Phase 2b IPF trial was planned for the first half of 2023; a combination trial with ruxolitinib in cGVHD was also planned.
- These are forward-looking expectations, not guarantees. The company cautions that clinical outcomes, regulatory review, enrollment, manufacturing and commercialization are uncertain. Clinical-stage status, lack of product revenue, ongoing cash burn and the need for future capital are central risks.
- Other material risks include reliance on Incyte for axatilimab development and commercialization, third-party manufacturing and supply, competitive therapies, intellectual-property protection, reimbursement and pricing pressure, and potential clinical-trial delays or adverse effects. Inflation and market volatility could increase costs or constrain financing, although management reported no material inflation impact to date.
- Incyte collaboration terms include up to $220 million in development and regulatory milestones, up to $230 million in commercial milestones, and tiered royalties; these contingent payments are not assured. Syndax bears 45% of shared global and U.S.-specific development costs, while Incyte bears 55% and all costs for trials specific to ex-U.S. countries.
- The filing reports no material legal proceedings. Management and Deloitte concluded that disclosure controls and internal control over financial reporting were effective as of year-end; Deloitte issued unqualified audit opinions on the financial statements and internal controls.
Most important facts for investors to verify
- Confirm subsequent revumenib trial results, FDA filing status and review outcomes; the reported response data are interim and were based on a March 2022 cutoff.
- Verify axatilimab pivotal-trial results, regulatory progress and the status of the planned IPF and combination studies.
- Track cash burn against the $481.3 million year-end cash-and-investment balance and management’s stated runway; assess whether additional financing may be needed.
- Review equity issuance and potential dilution, including outstanding pre-funded warrants, stock options and future ATM sales.
- Assess the terms and execution of the Incyte collaboration, including cost sharing, milestone conditions, royalties and commercialization responsibilities.
- Check the full audited financial statements and notes for investment composition, accrued clinical and milestone costs, licensing obligations and any developments after the filing date.