4DMT Announces Positive Interim Clinical Data from 4D-710 AEROW Phase 1 Clinical Trial in Cystic Fibrosis Lung Disease

Rhea-AI Summary

4D Molecular Therapeutics (Nasdaq: FDMT) announced positive interim Phase 1 AEROW data for 4D-710 in cystic fibrosis lung disease (data cutoff Dec 1, 2025).

Key points: 16 participants enrolled across four dose cohorts (2E15, 1E15, 5E14, 2.5E14 vg) with follow-up from 4 months to 3.5 years. The company selected 2.5E14 vg as the Phase 2 dose after dose-dependent, durable CFTR transgene expression at or above physiologically relevant levels and clinically meaningful improvements in ppFEV1, LCI2.5 and CFQ-R through 1 year. Safety: no new pulmonary or other safety events in higher-dose cohorts; lower-dose AEs were generally mild and transient. Next milestones: complete Phase 2 dose-expansion (target n=6) in H1 2026; program update in H2 2026.

Positive

• Durable CFTR transgene expression at or above target levels
• Clinically meaningful activity in ppFEV1 through 1 year
• Clinically meaningful activity in LCI2.5 through 1 year
• Selected Phase 2 dose: 2.5E14 vg based on safety and efficacy
• No new pulmonary safety events in higher-dose cohorts up to 3.5 years

Negative

• Small Phase 1 sample size: 16 participants
• Phase 2 dose-expansion target is limited: n=6 in H1 2026
• Lower-dose cohorts have shorter follow-up (4–24 months)

Key Figures

Participants enrolled 16 participants AEROW Phase 1 CF lung disease trial

Dose cohorts 2E15, 1E15, 5E14, 2.5E14 vg Four AEROW Phase 1 dose levels

Follow-up duration 4 months to 3.5 years Participant follow-up as of Dec 1, 2025

Phase 2 dose 2.5E14 vg Selected AEROW Phase 2 dose based on safety and efficacy

Safety follow-up Up to 3.5 years No new pulmonary or other safety events at higher doses

Adverse events Mild, transient; resolved by 2 months 4D-710-related AEs in lower-dose cohorts

Target expression Met at 2.5E14 vg Airway CFTR RNA levels hit target profile

Phase 2 enrollment target n=6 AEROW Phase 2 dose-expansion cohort planned completion in H1 2026

Market Reality Check

$7.32 Last Close

Volume Volume 958,030 is 21% above the 20-day average of 792,039 ahead of this update. normal

Technical Price $11.52 is trading above the 200-day MA of $6.23, reflecting a prior uptrend into this data.

Peers on Argus

FDMT gained 5.21% on positive CF data, while close biotech peers were mixed: DSGN +5.83%, OCGN +7.25%, MBX -1.56%, LRMR -3.61%, TECX +2.47%, suggesting a company-specific driver.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 12	Inducement grants	Neutral	+1.0%	RSU grants to new employees under 2025 inducement award plan.
Dec 08	Conference appearance	Neutral	+3.5%	Announcement of upcoming J.P. Morgan Healthcare Conference presentation.
Nov 20	Conference participation	Neutral	-4.3%	Evercore Healthcare Conference fireside chat and investor meetings.
Nov 17	CFO appointment	Neutral	+1.5%	Appointment of new CFO to lead finance and strategic initiatives.
Nov 14	Inducement grants	Neutral	+1.5%	RSU awards to new employees under inducement award plan.

Pattern Detected

Recent non-clinical headlines (conferences, governance, inducement grants) have generally led to modest single-digit price moves without a consistent directional bias.

Recent Company History

Over the last six weeks, FDMT news has focused on corporate events and investor outreach rather than data catalysts. Inducement grant announcements on Nov 14 and Dec 12, plus conference and JPM presentations, produced modest moves between about -4% and +4%. A CFO appointment on Nov 17 also saw a small positive reaction. Against this backdrop, today’s positive Phase 1 AEROW data for 4D-710 represents a more substantive clinical milestone than recent news flow.

Market Pulse Summary

The stock dropped -20.1% in the session following this news. A negative reaction despite positive AEROW data would contrast with FDMT’s typical double‑digit average move of 12.23% on past clinical updates, where data have often supported the longer-term story. With the stock already above its 200-day MA and close to its 52-week high, some investors may have focused on prior valuation gains or event-driven positioning, and volatility around data events has historically been significant for this name.

Key Terms

ppfev1 medical

"Clinically meaningful lung function activity, measured by ppFEV1 and LCI2.5, with follow-up..."

ppFEV1 is the percent of the expected volume of air a person can forcefully exhale in one second, compared with a healthy reference for their age, sex, height and ethnicity. It acts like a fuel-gauge for lung function: lower percentages indicate weaker lungs and higher disease severity. Investors care because ppFEV1 is a primary measure used in respiratory drug and device trials, regulatory decisions, and market size estimates for treatments.

lci2.5 medical

"Clinically meaningful lung function activity, measured by ppFEV1 and LCI2.5, with follow-up..."

LCI2.5 denotes the lower bound of a 95% confidence interval — the value at the 2.5th percentile of an estimated range. Think of it as the “worst‑case” edge of a statistic: if you repeated the same study many times, only 2.5% of the lower bounds would fall below this number. Investors use it to gauge downside uncertainty around reported results, safety margins, or projected returns.

cftr medical

"Durable CFTR transgene expression within target therapeutic range with follow-up..."

CFTR is a gene that makes a protein acting like a tiny gate in cell membranes to control the flow of salt and water; when the gate works properly it helps keep mucus thin and organs functioning. Investors care because mutations in CFTR drive serious diseases and create demand for diagnostics, drugs and long-term treatment revenue; progress or setbacks in therapies, approvals or patents directly affect company value.

cftr modulator therapy medical

"participants with CF lung disease who were ineligible for or intolerant of CFTR modulator therapy..."

CFTR modulator therapy is a class of medicines that target and improve the function of a defective protein (CFTR) responsible for fluid balance in lungs and other organs, addressing the root cause of cystic fibrosis rather than just treating symptoms. Investors watch these therapies because regulatory approvals, dosing expansions, patent life or trial results can rapidly change a drug developer’s revenue prospects and the size of the treatable patient population — similar to upgrading a broken engine part that can restore overall vehicle performance.

vg medical

"across four dose cohorts (2E15, 1E15, 5E14 and 2.5E14 vg)"

vg stands for viral genomes (or vector genomes) and measures the number of viral particles in a gene‑therapy or viral‑vector dose. Think of it like counting delivery trucks carrying a genetic payload: more vg means more delivery vehicles, which affects how strongly the therapy acts, its safety profile, manufacturing scale and cost, and how regulators and investors judge dosing, consistency and trial results.

phase 1 medical

"4D-710 Phase 1 AEROW clinical trial for the treatment of cystic fibrosis..."

Phase 1 is the first stage of testing a new drug or medical treatment in people, focused primarily on safety, how the body handles the product, and finding a tolerated dose. Think of it as a short, tightly controlled experiment with a small group to check for dangerous side effects before wider testing; for investors it is an early milestone that reduces some uncertainty but still carries high risk and potential for both big value changes and setbacks.

phase 2 medical

"dose selected for Phase 2 ... continue to enroll participants in the Phase 2 trial."

Phase 2 is the mid-stage clinical trial where a new drug or treatment is tested in a larger group of patients to see if it works and to keep checking safety after initial human testing. Think of it as a field test that proves whether a product actually delivers its promised benefit. Investors watch Phase 2 closely because its results strongly influence a medicine’s chances of reaching the market, the size of its potential sales, and the company’s valuation.

AI-generated analysis. Not financial advice.

• Clinically meaningful lung function activity, measured by ppFEV₁ and LCI_2.5, 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 LCI_2.5, 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. LCI_2.5 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, LCI_2.5 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.

Contacts:

Media:
Jenn Gordon
dna Communications
Media@4DMT.com

Investors:
Julian Pei
Head of Investor Relations and Strategic Finance
Investor.Relations@4DMT.com

FAQ

What interim results did 4DMT (FDMT) report for 4D-710 on December 17, 2025?

4DMT reported positive interim AEROW Phase 1 data (data cutoff Dec 1, 2025) showing durable CFTR expression, clinically meaningful ppFEV1 and LCI2.5 improvements, and selection of 2.5E14 vg for Phase 2.

Why was 2.5E14 vg chosen as the Phase 2 dose for 4D-710 (FDMT)?

2.5E14 vg was selected based on safety, tissue CFTR RNA expression meeting target levels, and consistent clinical activity across endpoints through 1 year.

What safety findings did the 4D-710 AEROW Phase 1 update disclose for FDMT?

No new pulmonary or other safety events occurred in higher-dose cohorts through up to 3.5 years; lower-dose related adverse events were generally mild, transient, and resolved by 2 months.

How many participants were enrolled in the 4D-710 AEROW Phase 1 trial (FDMT)?

The interim dataset included 16 participants across four dose cohorts with follow-up ranging from 4 months to 3.5 years.

When will 4DMT (FDMT) complete Phase 2 dose-expansion enrollment and provide the next update?

4DMT expects to complete the Phase 2 dose-expansion (target n=6) in H1 2026 and provide a program update in H2 2026.