Aprea Therapeutics, Inc. — 2021 Form 10-K
Reporting period: Fiscal year ended December 31, 2021. This annual filing reports full-year results, not a standalone fourth quarter. Aprea is a clinical-stage biopharmaceutical company developing cancer therapies intended to reactivate mutant p53; it has no approved products or product revenue.
Financial position and results
| Metric | 2021 | 2020 |
|---|---|---|
| Revenue | None | None |
| Research and development expense | $23.9 million | $37.9 million |
| General and administrative expense | $13.6 million | $14.9 million |
| Total operating expenses | $37.4 million | $52.8 million |
| Net loss | $37.1 million | $53.5 million |
| Net cash used in operating activities | $37.7 million | $41.8 million |
| Cash and cash equivalents at year-end | $53.1 million | $89.0 million |
| Total assets / total liabilities at year-end | $56.8 million / $7.3 million | $92.8 million / $15.4 million |
There is no meaningful sales margin to assess because the company had no product revenue. The filing reports no borrowings; recorded liabilities were primarily accounts payable, accruals, and lease obligations. Year-end current assets were $56.6 million versus current liabilities of $7.3 million. Management estimated existing cash would fund operating expenses and capital expenditures into 2023, subject to assumptions and without assurance.
Material changes and operating developments
- Net loss narrowed by $16.4 million year over year, mainly as research and development spending declined following completion of enrollment in key trials and the absence of 2020 NDA-preparation and commercial-scale-up costs. R&D expense fell $14.0 million; G&A fell $1.4 million.
- The pivotal Phase 3 frontline MDS trial of eprenetapopt plus azacitidine did not achieve statistical significance on its primary complete-remission endpoint: CR was 33.3% versus 22.4% for azacitidine alone (P=0.13). The FDA cited safety and risk-benefit concerns and continued a partial clinical hold on three myeloid-program trials in early 2022; new enrollment was prohibited, although benefiting patients could continue treatment.
- A separate Phase 2 post-transplant study reported updated one-year relapse-free survival of 60% and overall survival of 79% among 33 patients. A registrational-trial design was under discussion, with enrollment then planned for 2023.
- In a Phase 1/2 AML study, the triplet of eprenetapopt, venetoclax, and azacitidine showed a 39% CR rate and 56% CR/CRi rate among 39 evaluable patients in the reported update. These are early clinical findings, not evidence of regulatory approval or established benefit.
- The FDA lifted the clinical hold on the lymphoid program in December 2021. A new Richter’s transformed NHL trial was in planning. Solid-tumor combination testing was completed; reported responses came from small patient cohorts. APR-548’s first Phase 1 dosing cohort was completed, with no current plans to enroll more patients.
Outlook, risks, and unusual items
Management planned dose-optimization studies in relapsed/refractory MDS/AML and Richter’s transformed CLL, with preliminary data potentially available in late 2022 or 2023 depending on the study. The company reported FDA clearance in early 2022 to proceed with a new relapsed/refractory MDS/AML trial. These are plans and estimates, not assured milestones.
Key risks include the failed Phase 3 primary endpoint, continuing myeloid clinical holds, serious adverse events and deaths reported in trials, dependence on eprenetapopt, ongoing losses and need for additional capital, small eligible patient populations, and reliance on third parties. A single contract manufacturer produces eprenetapopt’s active ingredient, with no redundant supply arrangement in place at year-end. Eprenetapopt has no composition-of-matter patent protection because its chemical structure is in the public domain; its patent estate relies on other claims. COVID-19, regulatory decisions, competition, reimbursement, and intellectual-property challenges may also affect development and financing.
The company sold 366,773 shares under its ATM program in 2021 for approximately $1.5 million net. Stock-based compensation was $7.8 million. The auditor issued an unqualified opinion on the financial statements; the auditor did not provide an internal-control attestation, consistent with the company’s emerging-growth-company status. Management reported effective disclosure controls and internal control over financial reporting.
Important facts for investors to verify
- Current cash, quarterly cash burn, financing plans, and whether the stated runway into 2023 remains achievable.
- FDA status and requirements for the three myeloid trials under partial hold, and progress and design of the replacement studies.
- Full and final clinical data, safety findings, and statistical analyses for the Phase 3 MDS, post-transplant, AML, and solid-tumor programs.
- Whether planned trial timelines and the proposed 2023 post-transplant study enrollment remain feasible.
- Manufacturing continuity, potential qualification of alternative API suppliers, and the strength and remaining term of relevant intellectual-property protection.