Proqr Therapeutics N.V. annual report, Q4 FY2022

ProQR Therapeutics N.V. — FY2022 Form 20-F

Reporting period: Fiscal year ended December 31, 2022; filed March 29, 2023. Financial statements are audited under IFRS as issued by the IASB and presented in euros. This is an annual filing, not a standalone Q4 report.

Business context

ProQR is a clinical-stage biotechnology company developing RNA therapies. In 2022 it shifted its focus exclusively to its Axiomer RNA-editing platform, winding down its ophthalmology programs and seeking partners for those assets. Its lead internal programs, AX-0810 and AX-1412, remained preclinical. Lilly’s expanded collaboration covers up to ten targets, with an option to add five more.

Financial performance and position

Metric (€ millions, unless noted)20222021
Revenue4.0371.354
Other income0.7651.043
Research and development expense50.86742.220
General and administrative expense18.65117.368
Operating loss(64.716)(57.191)
Net loss(64.891)(61.680)
Basic and diluted loss per share(€0.91)(€0.96)
Net cash used in operating activities(68.508)(26.012)
Cash and cash equivalents at year-end94.775187.524
Total assets / total equity171.321 / 65.113209.579 / 113.229
Total borrowings, including accrued interest6.77144.090

Revenue came from collaboration and research services, not product sales or royalties. There is no marketed product, so commercial revenue and product margins are not applicable. Operating costs rose 16.7% to €69.518 million; R&D spending increased, while the company reported that winding down the ophthalmology trials and expanding Axiomer work affected spending. Net loss widened 5.2% year over year.

Cash declined by €92.749 million to €94.775 million after operating and investing outflows and net financing outflows. The company used €43.372 million to repay Pontifax and Kreos debt in September 2022 and received €14.122 million from issuing shares to Lilly. Management estimated year-end cash would fund operations into 2026, subject to assumptions and execution. Year-end current assets were €154.460 million and current liabilities €21.112 million; current assets included a €56.254 million Lilly upfront receivable. Equity was €65.113 million and liabilities €106.208 million.

Material changes and unusual items

  • In February 2022, sepofarsen’s Phase 2/3 pivotal trial failed to meet its primary endpoint. During 2022 ProQR ended clinical development of sepofarsen and ultevursen and wound down its wider ophthalmology portfolio.
  • R&D costs increased €8.647 million year over year; total operating costs increased €9.930 million. Costs included the ultevursen trial and wind-down activity, reorganization and employee-retention costs, and Axiomer and Lilly collaboration work.
  • Financial results included a €3.627 million foreign-exchange gain, primarily on U.S.-dollar cash, and a €2.713 million gain from fair-value changes in derivative liabilities. Debt extinguishment generated a €2.534 million loss, partly offset by a €1.144 million gain from Amylon lender waivers.
  • In December 2022, Lilly received 9,381,586 shares for gross proceeds of €14.122 million. The expanded agreement also provided a $60 million upfront payment, received in February 2023 and reported at year-end as a €56.254 million receivable. Lilly may pay a further $50 million to exercise an option to add five targets.
  • The company reduced its workforce by approximately 50% through restructuring announced in April and August 2022; the actions were completed in March 2023.

Outlook, risks and contingencies

  • ProQR planned to present nonclinical proof-of-concept data for AX-0810 and AX-1412 within 12 months, provide translational-data updates within 18 months, and target clinical trials in late 2024 or early 2025. These are forward-looking plans, not assured milestones.
  • The Lilly collaboration provides eligibility for up to approximately $3.75 billion in milestone payments and potential sales royalties; these are contingent and depend on Lilly’s development and commercialization decisions and success.
  • ProQR expects continued losses and no product revenue for the foreseeable future. Management’s cash runway estimate is subject to uncertain R&D costs, timelines, financing needs and collaboration receipts. Additional financing could dilute shareholders or require unfavorable partnering terms.
  • Key risks include the early, unproven nature of RNA editing; technical, clinical and regulatory failure or delay; reliance on third-party research organizations and manufacturers; dependence on collaborators; intellectual-property disputes; and competition. ProQR disclosed patent oppositions involving Axiomer patents in Europe and Japan.
  • Potential FFB obligations include up to $33.8 million tied to ultevursen’s first commercial sale; a $13.5 million payment may apply if the program is transferred, sold, licensed or subject to a change of control, and may be credited against the commercial-sale obligation.
  • The company believes it was a passive foreign investment company (PFIC) for U.S. tax purposes in 2022, but PFIC status is determined annually. It also reported no material litigation at year-end. The auditor issued unqualified opinions on the financial statements and internal control over financial reporting.

Important facts for investors to verify

  • Confirm the timing and evidence for AX-0810 and AX-1412 milestones, including whether the planned late-2024/early-2025 clinical start remains achievable.
  • Track cash burn against the stated runway into 2026, including the impact of the €56.254 million Lilly receivable received in February 2023 and future collaboration spending.
  • Review Lilly’s progress, any exercise of the five-target option, and the conditions and timing attached to contingent milestones and royalties.
  • Assess partner interest and any FFB, grant-repayment, licensing or other obligations related to the discontinued ophthalmology assets.
  • Check actual dilution and potential overhang from equity awards and warrants. The filing identified 80,817,079 fully paid shares outstanding at year-end and 12,122,562 shares authorized for future employee-plan grants.
  • For U.S. holders, verify annual PFIC status and consult tax advisers regarding elections and reporting obligations.