4DMT Announces Positive Interim Clinical Data from 4D-710 AEROW Phase 1 Clinical Trial in Cystic Fibrosis Lung Disease
- Clinically meaningful lung function activity, measured by ppFEV1 and LCI2.5, with follow-up through 1 year at dose selected for Phase 2
- Durable CFTR transgene expression within target therapeutic range with follow-up through at least 1 year
- Data support 4D-710's potential to be a durable, redosable, variant-agnostic, disease-modifying treatment for people with cystic fibrosis lung disease with high unmet need
- Webcast today at 8:00 a.m. ET with distinguished cystic fibrosis KOLs
EMERYVILLE, Calif., Dec. 17, 2025 (GLOBE NEWSWIRE) -- 4D Molecular Therapeutics (NASDAQ:FDMT, 4DMT, or the Company)), a leading late-stage biotechnology company advancing durable and disease-targeted therapeutics with potential to transform treatment paradigms and provide unprecedented benefits to patients, today announced positive interim clinical data from the 4D-710 Phase 1 AEROW clinical trial for the treatment of cystic fibrosis (CF) lung disease.
"The emerging data from the AEROW trial are highly encouraging, demonstrating the selected Phase 2 dose of 4D-710 was well tolerated and achieved physiologically relevant levels of CFTR expression, with evidence of clinical benefit across multiple lung function and pulmonary symptom measures," said Jennifer L. Taylor-Cousar, M.D., MSCS, Professor, Departments of Medicine and Pediatrics, Co-Director of the Adult Cystic Fibrosis Program, and Director of the Cystic Fibrosis Therapeutics Development Center, National Jewish Health, as well as lead Principal Investigator in the AEROW clinical trial. "I look forward to continuing to enroll participants in the Phase 2 trial."
"Lung clearance index, or LCI2.5, was developed to measure lung disease progression earlier and with lower variability than ppFEV1, making it a complementary measure to ppFEV1 for assessing clinical activity in trials like AEROW," said Felix Ratjen, M.D., Ph.D., FRCP(C), FERS, Professor of Paediatrics at the University of Toronto, Program Head and Senior Scientist in the Translational Medicine research program at SickKids Research Institute, and Co-Head of the Cystic Fibrosis Center at SickKids. "While, historically, ppFEV1 has been used in most CF trials, it measures large- and mid-airway disease and is effort-dependent and variable. LCI2.5 can detect changes in the small airways, where CF lung disease initially progresses, even before FEV1 declines, providing a more complete view of lung health. I am encouraged by the data from the AEROW trial and look forward to the continued advancement of 4D-710 for the CF community."
"Based on the data shared today, we continue to believe in 4D-710's potential as a durable, redosable and variant-agnostic genetic medicine that could become a foundational therapy for many people living with CF," said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. "We are grateful for the support from our trial participants, investigators and the Cystic Fibrosis Foundation in advancing 4D-710 as a potentially transformative option for people with CF and look forward to sharing additional updates in the second half of 2026."
AEROW Phase 1 Interim Data (data cutoff as of December 1, 2025)
- Enrolled 16 participants with CF lung disease who were ineligible for or intolerant of CFTR modulator therapy across four dose cohorts (2E15, 1E15, 5E14 and 2.5E14 vg)
- As of the data cutoff of December 1, 2025, participants had 4 months to 3.5 years of follow-up
- No new pulmonary or other safety events occurred since previous update in higher-dose cohorts (1E15 and 2E15 vg) with up to 3.5 years of follow-up
- In lower-dose cohorts (4 to 24 months of follow-up), 4D-710-related adverse events were generally mild, transient and resolved by 2 months, with no 4D-710-related severe adverse events
- Airway biopsy and brushing results demonstrated consistent and dose-dependent CFTR transgene RNA levels at or above physiologically relevant levels in non-CF control samples. In 2.5E14 vg dose cohort, results met target expression profile
- In 2.5E14 vg dose cohort, consistent evidence of clinically meaningful activity detected in all endpoints, including ppFEV1, LCI2.5 and quality of life (CFQ-R-R) through 1 year
- Based on evaluation of safety, tissue expression and efficacy data, 2.5E14 vg was selected as the Phase 2 dose
Next Steps and Upcoming Expected Milestones
- Complete enrollment of AEROW Phase 2 Dose-Expansion cohort (target n=6) in H1 2026
- Program update in H2 2026
Corporate Webcast Details
| Title: | AEROW Phase 1 Interim Data for 4D-710 in Cystic Fibrosis |
| Date/Time: | Wednesday, December 17, 2025, at 8:00 a.m. ET |
| Registration: | Link |
An archived copy of the webcast will be available for up to one year by visiting the "Investors & Media" section of the 4DMT website: https://ir.4dmoleculartherapeutics.com/events.
About Cystic Fibrosis Lung Disease
Cystic fibrosis (CF) is an inherited progressive disease caused by variants in the CFTR gene. According to the CF Foundation, nearly 40,000 people in the United States and more than 105,000 people worldwide are living with CF, with approximately 1,000 new cases of CF diagnosed in the United States each year. Lung disease is the leading cause of morbidity and mortality in people with CF. CF causes impaired lung function, inflammation, and bronchiectasis and is commonly associated with persistent lung infections and repeated exacerbations due to the inability to clear thickened mucus from the lungs. People with CF require lifelong treatment with multiple daily medications, resulting in a high treatment burden. The complications of the disease result in progressive loss of lung function, increasing need for IV antibiotics and hospitalizations, and ultimately leading to end-stage respiratory failure.
About 4D-710
4D-710 is designed to be a durable, redosable, and variant-agnostic genetic medicine that addresses the underlying cause of CF to improve airway function throughout the lungs, resulting in enhanced quality of life. We believe 4D-710 has the potential to become a foundational therapy for many people with CF, regardless of their specific CFTR variant. Combining our targeted and evolved next-generation aerosolized AAV vector, A101, with a codon-optimized CFTR∆R transgene, 4D-710 is the first known genetic medicine to demonstrate successful delivery and expression of the CFTR transgene throughout the airways of people with CF after aerosol delivery. The ongoing AEROW Phase 1/2 clinical trial is assessing 4D-710's impact on overall lung health, including changes to small airway function, airway structure, and quality of life. 4D-710 has received the Rare Pediatric Disease Designation and Orphan Drug Designation from the U.S. Food and Drug Administration (FDA).
About 4DMT
4DMT is a leading late-stage biotechnology company advancing durable and disease-targeted therapeutics with potential to transform treatment paradigms and provide unprecedented benefits to patients. The Company's lead product candidate 4D-150 is designed to be a backbone therapy forming the foundation of treatment of blinding retinal vascular diseases by providing multi-year sustained delivery of anti-VEGF (aflibercept and anti-VEGF-C) with a single, safe, intravitreal injection, which substantially reduces the treatment burden associated with current bolus injections. The Company's lead indication for 4D-150 is wet age-related macular degeneration, which is currently in Phase 3 development, and the second indication is diabetic macular edema. The Company's second product candidate is 4D-710, which is the first known genetic medicine to demonstrate successful delivery and expression of the CFTR transgene in the lungs of people with cystic fibrosis after aerosol delivery. 4D Molecular Therapeutics™, 4DMT™, Therapeutic Vector Evolution™, and the 4DMT logo are trademarks of 4DMT.
All of the Company's product candidates are in clinical or preclinical development and have not yet been approved for marketing by the U.S. Food and Drug Administration or any other regulatory authority. No representation is made as to the safety or effectiveness of the Company's product candidates for the therapeutic uses for which they are being studied.
Learn more at www.4DMT.com and follow us on LinkedIn.
Forward-Looking Statements:
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding the plans, announcements and related timing for the clinical development of, as well as the clinical benefits and therapeutic potential of our product candidates, including 4D-710. The words "may," "might," "will," "could," "would," "should," "expect," "plan," "anticipate," "intend," "believe," "expect," "estimate," "seek," "predict," "future," "project," "potential," "continue," "target," and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties, and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including: (i) risks that clinical trial results may not support regulatory approval or demonstrate sustained therapeutic benefit; (ii) risks that our product candidates may not demonstrate sufficient safety or efficacy; (iii) risks related to regulatory approval processes and evolving standards for gene therapies; (iv) risks that 4D Molecular Therapeutics may not receive additional CF Foundation funding or may require additional capital; (v) risks related to manufacturing complexity and supply chain for gene therapies; and (vi) risks of competition and rapidly evolving treatment landscape; as well as other risks and uncertainties that are described in greater detail in the section entitled "Risk Factors" in 4D Molecular Therapeutics' most recent Quarterly Report on Form 10-Q filed on November 10, 2025, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statement represents 4D Molecular Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. 4D Molecular Therapeutics undertakes no obligation to update any forward-looking statements to reflect events or circumstances after the date of this press release, except as may be required by law. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.
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