Core Viewpoint - The company is discussing interim Phase I data from the AEROW trial focused on cystic fibrosis, indicating progress in their research and development efforts [2]. Group 1: Company Overview - The call features key personnel including the Co-Founder and CEO, the Lead Principal Investigator from National Jewish Health, and a Co-Head from the Cystic Fibrosis Center at SickKids Research Institute [4]. - The company encourages stakeholders to visit their Investor Relations website for further details, including a press release and access to the webcast recording [2]. Group 2: Research and Development - The AEROW trial is a significant focus for the company, highlighting their commitment to advancing treatment options for cystic fibrosis [2]. - The involvement of leading experts in the field, such as Dr. Jennifer Taylor-Cousar and Dr. Felix Ratjen, underscores the trial's credibility and potential impact [4].

Summary of 4D Molecular Therapeutics Conference Call Company Overview - **Company**: 4D Molecular Therapeutics (NasdaqGS:FDMT) - **Focus**: Development of gene therapy for cystic fibrosis (CF) using AAV vectors Industry Context - **Cystic Fibrosis**: A genetic disorder affecting over 100,000 people globally, with a significant unmet need for effective therapies - **Current Treatments**: Existing modulators have improved outcomes for some patients, but many remain without effective options Key Points and Arguments Gene Therapy Development - **Need for Effective Gene Delivery**: The company emphasizes the urgent need for effective AAV vectors for gene delivery in CF, as previous attempts have failed due to ineffective delivery and expression [2][3] - **AAV Vector Technology**: Utilizes a novel AAV vector (A101) designed to penetrate mucus, transduce all airway cell types, and resist pre-existing immunity [2] - **Administration Method**: The therapy (4D-710) is administered via the FDA-approved AeroEclipse II nebulizer, ensuring widespread delivery throughout the airways [2] Clinical Trial Design and Results - **Phase 1 Trial Focus**: The trial aimed to find the optimal dose for safety and CFTR expression levels, with a focus on dose-finding and safety assessments [4][5] - **Dose Ranging**: Initial doses started at 1 x 10^15 vector genomes, with adjustments made based on safety and expression data [5] - **Safety Profile**: The lower dose (2.5 x 10^14 vector genomes) showed excellent safety and tolerability, with no significant adverse events beyond day 14 [8][9] Clinical Activity and Efficacy - **Endpoints**: The trial included multiple endpoints such as FEV1, Lung Clearance Index (LCI), and quality of life measures [18][31] - **Improvements Observed**: Participants receiving the selected lower dose showed greater improvements in clinical endpoints compared to those on higher doses [26][30] - **Durability of Expression**: Data indicated that the AAV-based approach could deliver durable CFTR expression for one to three years, supporting the decision to proceed with the selected dose in phase 2 [32][34] Regulatory Considerations - **FDA Engagement**: The company has had productive discussions with the FDA regarding the use of LCI as a primary efficacy endpoint, especially in pediatric studies [42][46] - **Future Plans**: The company plans to leverage data from ongoing studies to inform future regulatory submissions and potential accelerated approval pathways [66] Financial and Strategic Outlook - **Funding**: The program is fully funded by the Cystic Fibrosis Foundation, alleviating financial pressure on the company [53] - **Partnership Potential**: The company is open to future partnerships but aims to retain rights until more data is available [72] Additional Important Insights - **Patient Variability**: The variability in patient responses highlights the need for a diverse participant pool in future trials [39][41] - **Redosing Strategy**: The company anticipates a redosing interval of 12 to 18 months based on durability data, with LCI serving as a leading indicator for treatment effect [80] This summary encapsulates the critical aspects of the conference call, focusing on the company's innovative approach to treating cystic fibrosis through gene therapy and the ongoing clinical development of its lead product, 4D-710.

Summary of 4D Molecular Therapeutics Conference Call Company Overview - **Company**: 4D Molecular Therapeutics (NasdaqGS:FDMT) - **Focus**: Development of gene therapies for cystic fibrosis (CF) using AAV vector technology Key Industry Insights - **Cystic Fibrosis**: A life-shortening genetic disease affecting over 100,000 people globally, with 40,000 in the U.S. The disease leads to chronic lung infections and progressive respiratory failure. - **Current Treatment Landscape**: While CFTR modulators have improved outcomes for some patients, many still face high unmet needs and burdensome daily treatments. Core Findings from the ARROW Trial 1. **Safety and Tolerability**: - 4D-710 was well tolerated with adverse events typical of nebulized therapies, resolving quickly [4][13][14]. - No serious adverse events related to 4D-710 beyond day 14, with one mild liver enzyme elevation noted [14]. 2. **Clinical Efficacy**: - Significant improvements in lung function and quality of life were observed in participants receiving the 2.5 x 10^14 vector genomes dose compared to the 5 x 10^14 vector genomes dose [34][38]. - The trial demonstrated durable CFTR expression in lung tissue, persisting for at least one year [41]. 3. **Study Design**: - The phase I trial focused on dose finding, safety, and CFTR expression levels through lung biopsies and bronchoscopy [10][11]. - The trial included multiple endpoints, such as FEV1, lung clearance index (LCI), and CFQ-R quality of life measures [24][39]. 4. **Durability of Treatment**: - Paired biopsy data indicated that CFTR expression remained within therapeutic range for one to three years post-treatment, validating the AAV platform's effectiveness [41]. 5. **Future Directions**: - Phase II enrollment is expected to complete in the first half of 2026, with ongoing collection of paired biopsy data to inform redosing strategies [43]. - The company anticipates that repeat dosing will be feasible due to the natural turnover of lung epithelial cells [42]. Regulatory and Market Considerations - **Regulatory Engagement**: Productive discussions with the FDA regarding the use of LCI as a primary efficacy endpoint, especially in pediatric studies [50][54]. - **Market Need**: There is a significant demand for effective therapies among patients who do not currently have access to modulators, highlighting the urgency for 4D-710 [63]. Financial Aspects - The program is fully funded by the Cystic Fibrosis Foundation through the second half of 2026, minimizing financial strain on the company [60]. Additional Insights - **Endpoint Sensitivity**: LCI is recognized as a more sensitive measure for detecting early disease changes compared to FEV1, which is effort-dependent and less sensitive to small airway disease [28][29]. - **Patient Variability**: The trial acknowledges variability in patient responses, emphasizing the need for a diverse participant pool in future studies [47][51]. Conclusion 4D Molecular Therapeutics is advancing its gene therapy program for cystic fibrosis with promising early data on safety, efficacy, and durability. The company is positioned to address significant unmet needs in the CF patient population while navigating regulatory pathways for potential accelerated approval. Further data collection and analysis will guide future development and redosing strategies.

4D-710 Phase 1 Interim Data Key Takeaways - 4D-710 was well-tolerated with 4 to 24 months follow-up[14] - 4D-710 demonstrated clinically meaningful activity in lung function (FEV1, LCI2.5) and quality-of-life (CFQ-R-R)[14] - 4D-710 has durable CFTR transgene expression through at least 1 year[14] - Phase 2 enrollment is underway at Cohort 4 dose level[14] Cystic Fibrosis (CF) Market & 4D-710 Design - The CFTR modulator market size is approximately $11 billion in 2024[17] - 4D-710 is designed as a durable, redosable, variant-agnostic, disease-modifying therapy for CF lung disease[30] - 4D-710 utilizes aerosol delivery of a novel A101 vector invented with directed evolution[25] - The A101 vector enhances transduction of airway cells and overcomes potential barriers[26] Clinical Trial Results & Next Steps - In the Phase 1 trial, the 2.5E14 vg dose (Cohort 4) met the target expression profile of approximately 10-25% airway cells for CFTR RNA[63] - Durable expression of CFTR was observed with levels consistent with non-CF samples over 1 year[142] - The Cystic Fibrosis Foundation (CFF) has provided approximately $31 million in financial support for 4D-710 development[146] - The company expects to complete Phase 2 enrollment in H1 2026 and provide a program update in H2 2026[152]

Core Insights - 4D Molecular Therapeutics announced positive interim clinical data from the 4D-710 Phase 1 AEROW clinical trial for cystic fibrosis lung disease, indicating potential for transformative treatment options for patients [1][2] Clinical Trial Data - The AEROW trial demonstrated that the selected Phase 2 dose of 4D-710 was well tolerated and achieved significant CFTR expression levels, showing clinical benefits across various lung function and symptom measures [2] - Clinically meaningful lung function activity was observed, measured by ppFEV1 and LCI2.5, with follow-up through one year at the selected Phase 2 dose [4] - The trial enrolled 16 participants with CF lung disease who were ineligible for or intolerant of CFTR modulator therapy, with follow-up durations ranging from 4 months to 3.5 years [5] Safety and Efficacy - No new pulmonary or safety events were reported in higher-dose cohorts, and adverse events in lower-dose cohorts were generally mild and transient [5] - Airway biopsy results showed consistent CFTR transgene RNA levels at or above physiologically relevant levels, with the 2.5E14 vg dose cohort meeting target expression profiles [5] Future Developments - The company plans to complete enrollment of the AEROW Phase 2 Dose-Expansion cohort in the first half of 2026 and provide program updates in the second half of 2026 [11] - 4D-710 is positioned as a durable, redosable, and variant-agnostic genetic medicine that could serve as a foundational therapy for cystic fibrosis [8] Company Overview - 4D Molecular Therapeutics is a late-stage biotechnology company focused on developing durable and disease-targeted therapeutics, with 4D-710 being a key product candidate aimed at addressing the underlying causes of cystic fibrosis [9]

Core Viewpoint - 4D Molecular Therapeutics is a late-stage biotechnology company focused on developing durable and disease-targeted therapeutics that aim to transform treatment paradigms and provide significant benefits to patients [1][3]. Group 1: Company Overview - 4DMT's lead product candidate, 4D-150, is designed to treat blinding retinal vascular diseases through multi-year sustained delivery of anti-VEGF with a single intravitreal injection, reducing the treatment burden associated with current methods [3]. - The primary indication for 4D-150 is wet age-related macular degeneration, which is currently in Phase 3 development, while the second indication is diabetic macular edema [3]. - The second product candidate, 4D-710, is the first genetic medicine to successfully deliver and express the CFTR transgene in the lungs of cystic fibrosis patients via aerosol delivery [3]. Group 2: Upcoming Events - 4D Molecular Therapeutics will present at the 44th Annual J.P. Morgan Healthcare Conference on January 14, 2026, at 7:30 a.m. PT [2]. - A webcast of the presentation will be available for one year on the company's investor relations website [2].

Summary of 4D Molecular Therapeutics FY Conference Call Company Overview - **Company**: 4D Molecular Therapeutics (NasdaqGS:FDMT) - **Focus**: Development of gene therapies, particularly for retinal diseases and cystic fibrosis (CF) Key Points on 4D-150 Program - **Long-term Data**: Recent data on the 4D-150 program shows encouraging results with a treatment burden reduction of approximately 80% in severe patient populations, maintaining this reduction over two years [2][9][10] - **Phase 3 Enrollment**: The company is deep into Phase 3 trials for both 4FRONT-1 and 4FRONT-2 programs, with enrollment rates accelerating and expected completion in 2026 [2][4] - **Competitive Landscape**: The retinal therapy market is evolving, with a focus on reducing treatment burden. Current therapies require multiple injections per year, and 4D-150 aims to significantly reduce this frequency [4][5] - **Physician Feedback**: Positive feedback from physicians regarding the potential of 4D-150 to reduce treatment burden, which is a significant unmet need in the market [5][10] Safety and Efficacy - **Safety Profile**: The safety profile of 4D-150 is comparable to existing therapies like Eylea, with no significant long-term safety concerns reported [11][12] - **Efficacy Measurement**: The primary efficacy endpoint in Phase 3 trials will focus on treatment burden reduction, which is critical for commercial adoption [16][17] Market Strategy - **Pricing Strategy**: The company aims to price 4D-150 affordably to ensure broad access, with a cost of goods reported to be less than $1,000. The goal is to avoid pricing it as a niche product [24][26] - **Adoption Expectations**: The company anticipates a strong adoption rate among retina specialists, despite the typical slow adoption seen in gene therapies. Education on the benefits of 4D-150 will be crucial [21][23] Cystic Fibrosis (CF) Program Insights - **Upcoming Data**: The company plans to release updates on its CF program, focusing on safety and efficacy measures, particularly using lung clearance index as a primary endpoint [27][28] - **Target Population**: The initial focus will be on patients with the highest unmet needs who are not eligible for existing therapies, representing about 15% of the CF population [30] Conclusion - **Future Outlook**: 4D Molecular Therapeutics is positioned to make significant advancements in gene therapy for retinal diseases and cystic fibrosis, with promising data and a clear strategy for market entry and adoption. The emphasis on reducing treatment burden and ensuring safety will be pivotal in their upcoming trials and commercial strategy [2][10][30]

Company Overview - 4D Molecular Therapeutics is focused on developing an adaptable genetic medicines portfolio, particularly in ophthalmology and pulmonology [1] Lead Asset - The lead asset, 4D-150, targets wet AMD and DME, with the potential to significantly reduce treatment burden for patients [2] - The market for this therapy is estimated at approximately $17 billion annually, indicating a substantial commercial opportunity [2] - 4D-150 is expected to transform the field due to its safety, clear efficacy, and seamless integration into busy retina practices, providing a competitive advantage for commercialization [2] Cost Structure - The cost of goods for 4D-150 is notably low compared to most gene therapies, allowing for greater pricing flexibility [3] Additional Product - 4D-710 is an aerosol-delivered genetic medicine for cystic fibrosis, designed to deliver a CFTR transgene throughout the airways with consistent transduction and gene expression [3] - Updates on the Phase I program for 4D-710 are anticipated in December [3]

Core Insights - 4D Molecular Therapeutics is a late-stage biotechnology company focused on developing durable and disease-targeted therapeutics that aim to transform treatment paradigms and provide significant benefits to patients [3] Company Overview - The lead product candidate, 4D-150, is designed for the treatment of blinding retinal vascular diseases, specifically targeting wet age-related macular degeneration and diabetic macular edema, currently in Phase 3 development [3] - 4D-150 offers multi-year sustained delivery of anti-VEGF through a single intravitreal injection, significantly reducing the treatment burden compared to current bolus injections [3] - The second product candidate, 4D-710, is the first genetic medicine to successfully deliver and express the CFTR transgene in the lungs of cystic fibrosis patients via aerosol delivery [3] Upcoming Events - Management will participate in a fireside chat at the 8th Annual Evercore Healthcare Conference on December 3, 2025, at 2:35 p.m. ET [2] - One-on-one meetings with management will also be available during the conference [1]

Summary of 4D Molecular Therapeutics Conference Call Company Overview - **Company**: 4D Molecular Therapeutics (NasdaqGS:FDMT) - **Focus**: Developing adaptable genetic medicines, particularly in ophthalmology and pulmonology - **Lead Asset**: 4D-150, targeting wet Age-related Macular Degeneration (AMD) and Diabetic Macular Edema (DME) with a market potential of approximately $17 billion annually [2][5][6] Core Insights and Arguments 4D-150 - **Product Description**: 4D-150 is designed to reduce treatment burden for patients with wet AMD and DME by providing continuous expression of aflibercept directly in the retina [5][6] - **Market Opportunity**: The product aims to address high unmet needs in a market that is currently burdened by frequent injections (average of 36 injections over five years) [11][12] - **Efficacy**: Clinical data shows a significant reduction in treatment burden, with patients receiving an average of 4.3 injections over two years compared to a projected 20 injections without the treatment, representing nearly 80% reduction [18][19] - **Safety Profile**: 4D-150 has demonstrated a favorable safety profile with low rates of intraocular inflammation, comparable to or better than current standard treatments [21][22] Clinical Trials - **Phase 3 Trials**: Two ongoing trials, Forefront One and Forefront Two, are designed to evaluate the efficacy and safety of 4D-150 in treatment-naive populations, with top-line data expected in 2027 [20][22] - **DME Data**: In a phase one study for DME, 4D-150 showed a treatment burden reduction of 78%, with an average of 1.6 injections compared to a projected seven injections with aflibercept [24][25] Commercial Strategy - **Cost of Goods**: The low cost of goods for 4D-150 allows for flexible pricing strategies, enhancing commercial viability [5][26] - **Licensing Agreement**: An exclusive licensing agreement with Otsuka for the Asia Pacific region has provided $85 million upfront, with additional potential milestones and royalties [27] 4D-710 - **Product Overview**: 4D-710 is an aerosol-delivered genetic medicine for cystic fibrosis, targeting patients with rare mutations or those intolerant to existing modulators [28][29] - **Clinical Development**: Promising early data shows high-level expression of the CFTR transgene, with updates expected in December [29][30] Additional Important Points - **Patient Perspective**: The treatment burden reduction is crucial for patient adherence and quality of life, as frequent injections can lead to anxiety and logistical challenges [12][25] - **Market Positioning**: 4D-150 is positioned as a transformative therapy compared to existing anti-VEGF treatments and tyrosine kinase inhibitors, offering potentially lifelong benefits with fewer injections [33][34] - **Future Milestones**: The company has a robust pipeline with upcoming data releases and enrollment updates for ongoing trials, indicating a strong catalyst calendar [30][31] This summary encapsulates the key points discussed during the conference call, highlighting the innovative approach of 4D Molecular Therapeutics in addressing significant medical needs in ophthalmology and pulmonology.