4DMT Announces Update on Regulatory Interactions and Development Path for 4D-710 for Treatment of Cystic Fibrosis
4D Molecular Therapeutics announces regulatory interactions and development path for 4D-710, an aerosolized genetic medicine for cystic fibrosis lung disease. Positive clinical data, technology transfer, and pivotal trial plans revealed.
The progression of 4D-710 into pivotal trials represents a significant milestone in the treatment landscape for cystic fibrosis (CF), particularly for patients with limited therapeutic options. The engagement with regulatory bodies like the FDA and EMA underscores the potential expedited pathway for a therapy addressing a high unmet medical need. The interim data from the Phase 1/2 AEROW clinical trial, which will be shared at the upcoming ECFS conference, is critical to understanding the safety profile and efficacy signals of 4D-710.
Furthermore, the exploration of lower doses could have substantial implications for the treatment's accessibility and affordability. A successful demonstration of efficacy at reduced doses could lead to a more cost-effective solution for health systems and patients. The development of an in-house GMP-ready manufacturing process at scale is a proactive step towards ensuring supply chain stability and cost management, which are pivotal factors in the commercial viability of new therapies.
The announcement from 4D Molecular Therapeutics about their development plans for 4D-710 has the potential to impact their financial outlook and market valuation. The transition to Phase 3 trials, anticipated in H2 2025, signals confidence in the treatment's prospects and may attract investor interest. The possibility of an accelerated approval pathway, if substantiated by compelling clinical and biomarker data, could lead to earlier monetization of the product and provide a competitive edge in the CF market.
Investors should also take note of the company's strategic decision to initiate technology transfer to a CDMO, which may be seen as a move to mitigate risk and leverage external expertise for large-scale manufacturing. This could have positive long-term financial implications by optimizing production costs and ensuring the company is well-positioned to meet commercial demand post-approval.
The anticipation of Phase 3 trial initiation for a novel CF treatment like 4D-710 is a significant event within the healthcare industry. The focus on patients who are ineligible for or cannot tolerate approved CF modulator therapies fills a niche in the CF market, potentially providing a new standard of care for a subset of the CF population. The company's proposed amendments to the AEROW trial, such as enrolling patients with lower baseline ppFEV1 and adding a second biopsy to assess long-term durability, reflect a thorough approach to clinical development that may enhance the robustness of the data.
These developments could also influence the strategic decisions of competitors and may lead to increased investment in genetic therapies for CF and other diseases with unmet medical needs. The ripple effects of such advancements could catalyze innovation and investment within the sector, with implications for patient outcomes and healthcare economics.
03/28/2024 - 08:00 AM
Conducted initial pivotal study interactions with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA); Company has clear registration path for 4D-710 for treatment of cystic fibrosis (CF) lung disease in people with CF (pwCF) who are ineligible for or cannot tolerate approved CF modulator therapies AEROW clinical trial Phase 2 Expansion Cohort dose selection and initiation expected in Q2 2024, with pivotal trial initiation anticipated in H2 2025 Initial GMP-ready suspension manufacturing process completed in-house at 500 liter scale; technology transfer initiation to commercial CDMO anticipated H1 2025 Phase 1/2 AEROW clinical trial interim clinical data expected at the European Cystic Fibrosis Conference June 5-8, 2024, including safety, lung biomarker and clinical activity data on all nine patients dosed across four dose level cohorts EMERYVILLE, Calif., March 28, 2024 (GLOBE NEWSWIRE) -- 4D Molecular Therapeutics (Nasdaq: FDMT, 4DMT or the Company), a leading clinical-stage genetic medicines company focused on unlocking the full potential of genetic medicines to treat large market diseases, today announced an update on its regulatory interactions and development path for 4D-710, an aerosolized genetic medicine for the treatment of CF lung disease.
Given high-level cystic fibrosis transmembrane conductance regulator (CFTR) transgene expression in all lung airway biopsies disclosed to date (significantly above normal lung CFTR levels), dose exploration continues with the evaluation of lower doses in the 4D-710 Phase 1/2 AEROW clinical trial in pwCF dosed at 5E14 vg (Cohort 3; n=1) and 2.5E14 vg (Cohort 4; n=1); nine pwCF total have been dosed to date (dose range 2.5E14 to 2E15 vg). Phase 2 Expansion Cohort dose selection is expected in Q2 2024 based on all clinical and lung biopsy data; the Company anticipates enrolling a total of six to nine pwCF in the Phase 2 Expansion Cohort. The Company submitted an AEROW trial amendment to the Cystic Fibrosis Therapeutics Development Network (TDN) as follows: 1) to enroll pwCF with lower baseline percent predicted forced expiratory volume in 1 second (ppFEV1 ) (50-90% ) to assess ppFEV1 response to 4D-710, and 2) to add a second lung biopsy procedure at a longer-term timepoint (12 months or later) to study long term durability of 4D-710 CFTR transgene expression and optimal timing for redosing. The Company plans to share the following at the 47th European Cystic Fibrosis Conference (ECFS) held on June 5-8, 2024 in Glasgow, United Kingdom: 1) interim AEROW clinical and lung biomarker data on all nine pwCF dosed to date, 2) update on AEROW trial amendment status, and 3) development plan update for pwCF who are on modulators.
In addition, the Company recently had discussions with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), regarding the registrational path for 4D-710 for treatment of CF lung disease in pwCF who are ineligible for or cannot tolerate approved CF modulator therapies. With regards to a full product approval in this patient population, the Company anticipates a Phase 3 randomized, controlled pivotal study enrolling approximately 60-80 pwCF with low baseline ppFEV1 (planned to be approximately 40-80% ). Phase 3 clinical endpoints include changes after 4D-710 treatment in ppFEV1 , quality-of-life (Cystic Fibrosis Questionnaire Revised Respiratory Domain, CFQ-R-RD) and frequency of pulmonary exacerbations. 4DMT is preparing for initiation of a Phase 3 clinical trial in H2 2025.
Given the high unmet need in this CF population, an accelerated approval path may be feasible. The Company intends to have discussions with the FDA and EMA on an accelerated approval pathway, in parallel with Phase 3 planning, following additional AEROW clinical and lung biomarker data in pwCF with low baseline ppFEV1 . 4D-710 is the first genetic medicine product candidate to demonstrate widespread and high-level CFTR expression (both RNA and protein) in the airways of pwCF; the Company will continue to evaluate the correlation between clinical endpoints and biomarker endpoints in participants with low baseline ppFEV1 in anticipation of further interactions on an accelerated approval pathway.
In addition, the Company has completed in-house process development of a suspension GMP-ready manufacturing process for 4D-710 at 500 liter scale for the pivotal study and potential commercialization. This process, in combination with investigating lower doses, enables potentially lower cost of goods. The Company anticipates initiation of technology transfer to a commercial contract development and manufacturing organization (CDMO) in H1 2025.
“We are encouraged by our productive interactions with the FDA and EMA on pivotal development plans for 4D-710, which we believe has the potential to be a transformative therapy for people with the highest unmet medical need for CF lung disease,” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “We are committed to advancing 4D-710 into pivotal trial development efficiently, while maintaining our current focus on initiation and completion of two Phase 3 wet AMD studies with 4D-150. Our goal is to initiate Phase 3 development in H2 2025 with 4D-710 suspension GMP process clinical trial material. We look forward to sharing interim clinical data from the AEROW Phase 1/2 clinical trial at the ECFS conference in June 2024.”
About Cystic Fibrosis Lung Disease and 4D-710
Cystic fibrosis (CF) is an inherited, progressive disease caused by mutations in the CFTR gene. It affects the lungs, pancreas, and other organs. According to the Cystic Fibrosis Foundation, close to 40,000 people in the United States and an estimated 105,000 people people have been diagnosed with CF across 94 countries, 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. The complications of the disease result in progressive loss of lung function, increasing need for IV antibiotics and hospitalizations, ultimately leading to end-stage respiratory failure.-15% of people whose disease is not amenable to existing CFTR modulator medicines (based on variant-eligibility and/or drug intolerance) targeting the CFTR protein. In people with CFTR mutations whose disease is amenable to modulator medicines, and in some people with CF the improvement in lung function is incomplete and is variable. We therefore expect to potentially develop 4D-710 in this broader population, as a single agent and/or in combination with CFTR modulator small molecule medicines. 4D-710 has received the Rare Pediatric Disease Designation and Orphan Drug Designation from the FDA.
About 4DMT
4DMT is a leading clinical-stage genetic medicines company focused on unlocking the full potential of genetic medicines to treat large market diseases in ophthalmology and pulmonology. 4DMT’s proprietary invention platform, Therapeutic Vector Evolution, combines the power of the Nobel Prize-winning technology, directed evolution, with approximately one billion synthetic AAV capsid-derived sequences to invent customized and evolved vectors for use in our wholly owned and partnered product candidates. Our product design, development, and manufacturing engine helps us efficiently create and advance our diverse product pipeline with the goal of revolutionizing medicine with potential curative therapies for millions of patients. Currently, 4DMT is advancing five clinical-stage and two preclinical product candidates, each tailored to address rare and large market diseases in ophthalmology, pulmonology, and cardiology. In addition, 4DMT is also advancing programs in CNS through a gene editing partnership. 4D Molecular Therapeutics™, 4DMT™, Therapeutic Vector Evolution™, and the 4DMT logo are trademarks of 4DMT.
All of our product candidates are in clinical or preclinical development and have not yet been approved for marketing by the FDA or any other regulatory authority. No representation is made as to the safety or effectiveness of our 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 therapeutic potential, and clinical benefits of 4DMT’s product candidates, as well as the plans, announcements and related timing for the clinical development of 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 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 as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent 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 explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.
Contacts:
Media:
Katherine SmithKatherine.Smith@inizioevoke.com
Investors:
Julian PeiInvestor.Relations@4DMT.com
What is the focus of 4D Molecular Therapeutics' update?
The update focuses on regulatory interactions and development path for 4D-710, a genetic medicine for cystic fibrosis lung disease.
When is the Phase 2 Expansion Cohort dose selection expected?
The Phase 2 Expansion Cohort dose selection is expected in Q2 2024.
What data is expected at the European Cystic Fibrosis Conference in June 2024?
Interim clinical data on all nine patients dosed in the AEROW trial, including safety, lung biomarker, and clinical activity data.
What is the anticipated timeline for Phase 3 clinical trial initiation?
The Phase 3 clinical trial initiation is anticipated in H2 2025.
What is the significance of 4D-710 in the CF population?
4D-710 is the first genetic medicine product candidate to demonstrate widespread and high-level CFTR expression in the airways of people with CF.
