4D Molecular Therapeutics, Inc. — FY 2022 Form 10-K
Reporting period: Fiscal year ended December 31, 2022; filed March 15, 2023. This is an annual report, not a quarterly filing. 4D Molecular Therapeutics is a clinical-stage genetic medicines company with no approved products and no product-sales revenue.
Business context and pipeline
The company uses its Therapeutic Vector Evolution platform to develop targeted AAV genetic medicines. At year-end, it reported five clinical-stage candidates: 4D-150 (wet AMD; DME development planned), 4D-710 (cystic fibrosis), 4D-310 (Fabry disease cardiomyopathy), 4D-125 (XLRP) and 4D-110 (choroideremia). 4D-175 for geographic atrophy and 4D-725 for alpha-1 antitrypsin deficiency lung disease were in preclinical development.
Financial performance and liquidity
| Metric | FY 2022 | FY 2021 | Change |
|---|---|---|---|
| Collaboration and license revenue | $3.1 million | $18.0 million | Down 83% |
| Research and development expense | $80.3 million | $61.4 million | Up 31% |
| General and administrative expense | $32.9 million | $28.0 million | Up 17% |
| Total operating expenses | $113.2 million | $89.4 million | Up 27% |
| Loss from operations | $(110.0) million | $(71.3) million | Loss widened |
| Net loss | $(107.5) million | $(71.3) million | Loss widened 51% |
| Net loss per share, basic and diluted | $(3.32) | $(2.57) | |
| Net cash used in operating activities | $86.7 million | $69.1 million | Use increased |
Revenue was principally from uniQure in 2022. The prior-year comparison included $17.2 million from Roche; its collaboration terminated in September 2021. Higher research and development costs reflected increased clinical-trial activity, personnel and facilities. The filing does not provide product gross margins; product sales have not begun.
At December 31, 2022, cash and cash equivalents were $52.4 million and marketable securities were $166.1 million, totaling $218.5 million. Total assets were $261.8 million, total liabilities $30.5 million, and stockholders’ equity $231.3 million. The filing reports no outstanding borrowings; lease liabilities were $16.1 million, with $20.9 million of undiscounted future minimum lease payments. Management said existing cash and securities were expected to fund planned operations for at least one year from issuance of the financial statements. No committed external funding source was in place.
Cash used in investing activities was $17.1 million, including $11.5 million of property and equipment purchases, partly offset by net marketable-security maturities. Financing provided $3.1 million, primarily from option exercises and employee stock purchases; there was no 2022 public offering. The company reported a $773,000 unrealized loss on marketable securities in other comprehensive loss, with no other-than-temporary impairment recognized.
Material changes, outlook and notable items
- 4D-310 safety and regulatory status: In January 2023, the company paused enrollment in both INGLAXA trials after three transient atypical hemolytic uremic syndrome (aHUS) events, including one Grade 4 dose-limiting toxicity. The FDA subsequently placed the program on clinical hold and directed long-term follow-up of treated patients. The IND remained open and active. The company proposed protocol changes, including an immunosuppressive regimen and excluding patients with pre-dose complement activation; FDA alignment on amendments was not established in the filing.
- Other clinical updates: Interim 4D-150 wet AMD data from five patients showed no dose-limiting toxicities or clinically significant inflammation at the reported cutoff; the company reported a 96.7% reduction in annualized anti-VEGF injection rate during follow-up. These were interim, small-cohort results. For 4D-710, three patients in the initial cohort showed transgene delivery and expression in sampled lung tissue, with no treatment-related adverse events reported at the cutoff. These early findings do not establish efficacy.
- Planned development: The company expected to begin enrollment in the 4D-150 DME SPECTRA study in Q3 2023 and anticipated additional 4D-710 data in 2023. It expected 4D-125 and 4D-110 clinical updates in 2024. These are forward-looking expectations, not assured milestones.
- Funding: A $100 million at-the-market (ATM) program had no shares sold by December 31, 2022. By March 3, 2023, approximately $9.6 million in net proceeds had been raised, with $90.1 million remaining available. Future financing could dilute shareholders or require less favorable arrangements.
- Collaboration and intellectual property: Roche’s termination ended further milestone and royalty rights under that agreement; 4D-110 rights reverted to the company. The company gave notice in February 2023 to terminate its UC/UPenn license agreement, effective May 23, 2023.
- Controls and audit: Management concluded disclosure controls and internal control over financial reporting were effective at year-end. PwC gave an unqualified opinion on the financial statements; no auditor attestation of internal controls was included under the emerging-growth-company exemption.
Management expects continuing operating losses and negative operating cash flows, with research, development, manufacturing and administrative costs likely to rise. The filing provides no numeric revenue or earnings guidance. Key risks include clinical and regulatory uncertainty, gene-therapy safety and manufacturing challenges, dependence on additional capital, competition, intellectual-property and licensing exposure, and potential trial or supply delays. No material legal proceedings were reported.
Most important facts for investors to verify
- Current FDA clinical-hold status and any agreed protocol changes or restart conditions for 4D-310, including follow-up of the six enrolled patients.
- Updated safety, durability and efficacy data for 4D-150 and 4D-710, beyond the preliminary cohorts and cutoffs described in the filing.
- Actual cash burn, financing proceeds and remaining ATM capacity, and whether the stated runway remains valid as development plans and costs evolve.
- Progress, enrollment and timelines for the DME study and other clinical programs versus the company’s stated expectations.
- Effects of the UC/UPenn license termination and any remaining royalty, milestone, or other obligations under licenses and collaborations.