Core Viewpoint - 4D Molecular Therapeutics announced positive results from the SPECTRA clinical trial for 4D-150 in diabetic macular edema (DME), indicating a potential shift in treatment paradigms and alignment with the European Medicines Agency (EMA) for a registrational pathway [1][6]. Clinical Trial Results - The SPECTRA trial demonstrated that 4D-150 is well tolerated with no intraocular inflammation observed at any timepoint or dose level [4] - The Phase 3 dose of 4D-150 achieved a clinically meaningful 78% reduction in treatment burden compared to the standard-of-care aflibercept 2mg every eight weeks [4][10] - Efficacy results showed a sustained gain in best corrected visual acuity (BCVA) of +9.7 letters and a reduction in central subfield thickness (CST) of -174 µm [5] Regulatory Alignment - Both the FDA and EMA have aligned on a single Phase 3 clinical trial as acceptable for regulatory submission for 4D-150 in DME, streamlining the path for marketing authorization [6][9] Product Overview - 4D-150 is designed to provide multi-year sustained delivery of anti-VEGF from a single intravitreal injection, aiming to reduce the treatment burden associated with current therapies [7][9] - The investigational agent targets both wet age-related macular degeneration and DME, addressing significant unmet medical needs in these conditions [7][11] Market Context - DME is a prevalent complication of diabetic retinopathy, affecting approximately one million individuals in the U.S., characterized by inflammation and swelling in the macula leading to vision loss [8]

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]. Presentation Details - The company will present interim results from the SPECTRA Phase 2a clinical trial evaluating intravitreal 4D-150 in adults with diabetic macular edema on July 31, 2025 [2]. - The presentation will include a 52-week primary endpoint analysis and a 60-week analysis, with all patients having reached 60 weeks as of the data cutoff date of May 2, 2025 [2]. - Additionally, results from the PRISM Phase 2b clinical trial evaluating intravitreal 4D-150 in adults with neovascular age-related macular degeneration will be presented on August 1, 2025 [2]. Product Candidates - The lead product candidate, 4D-150, is designed to provide multi-year sustained delivery of anti-VEGF therapies through a single intravitreal injection, significantly reducing the treatment burden associated with current bolus injections [3]. - 4D-150 is currently in Phase 3 development for wet age-related macular degeneration and is also being studied for diabetic macular edema [3]. - The second product candidate, 4D-710, is the first known genetic medicine to successfully deliver and express the CFTR transgene in the lungs of cystic fibrosis patients after aerosol delivery [3].

4D-150 Clinical Activity and Tolerability - 4D-150 demonstrates robust and durable clinical activity across all studied populations, including recently diagnosed patients with wet AMD[7] - 4D-150 exhibits a tolerability profile comparable to approved anti-VEGF agents[8] 4D-150 Injection-Free Rates in Wet AMD - In the severe wet AMD population, 44% of patients were injection-free through 52 weeks, with 48% requiring >1 injection and 8% requiring 1 injection, resulting in an 83% treatment burden reduction[13] - In the broad wet AMD population (including recently diagnosed), 70% of patients were injection-free through 52 weeks, with 20% requiring >1 injection and 10% requiring 1 injection, resulting in an 89% treatment burden reduction[16] - In the recently diagnosed wet AMD population, 87% of patients were injection-free through 52 weeks, with 13% requiring 1 injection, resulting in a 98% treatment burden reduction[19] 4D-150 Intraocular Inflammation (IOI) Profile - 4D-150 development is enabled by a favorable IOI profile, with IOI rates of 2-3%[22] 4FRONT Phase 3 Program Design - The 4FRONT Phase 3 program in treatment-naïve wet AMD is designed to maximize the probabilities of clinical, regulatory, and commercial success[10, 24, 35] - The 4FRONT-1 Phase 3 study's primary endpoint is BCVA noninferiority of 4D-150 3E10 vg/eye to Aflibercept 2mg Q8 weeks[33]

Core Insights - 4D Molecular Therapeutics is accelerating the 4D-150 4FRONT Phase 3 program for wet age-related macular degeneration (wet AMD) and has streamlined operations to manage increased expenses, ensuring cash runway into 2028 [1][6] - The company anticipates topline data for the 4FRONT-1 trial in the first half of 2027, an acceleration from the previous guidance of the second half of 2027 [3][6] - A workforce reduction of approximately 25% is being implemented to achieve annual cash compensation savings of about $15 million, supporting the accelerated clinical trial timelines [6] Company Overview - 4D-150 is designed as a backbone therapy for retinal vascular diseases, providing multi-year sustained delivery of anti-VEGF through a single intravitreal injection [5][9] - The company has a strong cash position with $458 million in cash, cash equivalents, and marketable securities as of March 31, 2025, sufficient to support ongoing clinical trials and preparations [6] - The company is transitioning towards becoming a commercial entity, focusing on delivering transformative genetic medicines to patients [4][9] Clinical Development - Initial enrollment and site activation for the 4FRONT-1 trial have exceeded projections, indicating strong engagement from investigators and patients [6] - The 4FRONT-2 trial has been initiated ahead of schedule, with topline data expected in the second half of 2027 [5][6] - Wet AMD is a prevalent disease, with over 4 million individuals expected to be affected in major markets within the next five years [8]

4DMT's Pipeline and Financial Status - 4DMT is officially a Phase 3 company[6] - 4DMT had $505 million cash as of December 31, 2024, providing runway into 2028[57] - 4DMT's pipeline is focused on large market indications with high unmet need[56] 4D-150 for Wet AMD - 4D-150 is a Phase 3 therapeutic designed to disrupt the global market for retinal vascular diseases and improve patient outcomes[8, 10, 18, 27, 37, 43] - The global market for retinal vascular diseases is $17 billion+ and growing[9, 11, 19, 28, 39, 45] - Topline data from wet AMD pivotal trials in the 4FRONT global registration program are expected in H2 2027[9, 11, 19, 28, 40, 45] - 4D-150 demonstrated transformative treatment burden reduction, with a projected 83% to 94% reduction in mean annual injections post 4D-150 in Phase 1/2a and Phase 2b populations[26] - In a Wet AMD population, 2.8% of patients experienced treatment-related 1+ vitreous cells at a single timepoint[32] 4D-150 for DME - In DME patients, there was no intraocular inflammation at any timepoint at any dose level[33] Market Dynamics - The total branded anti-VEGF market continues to grow, driven by incremental durability improvements, with aflibercept remaining the market leader[12] - The anti-VEGF market is expected to reach $17.1 million[14]

Summary of 4D Molecular Therapeutics (FDMT) FY Conference Call Company Overview - **Company**: 4D Molecular Therapeutics (FDMT) - **Focus**: Gene therapy with a focus on ophthalmology and pulmonology, specifically targeting conditions like wet age-related macular degeneration (AMD), diabetic macular edema (DME), and cystic fibrosis. Key Points Industry and Market Opportunities - **Gene Therapy Potential**: The company believes it has developed best-in-class vectors for various delivery methods, which opens up large sustainable markets in gene therapy [1][2] - **Market Size**: The potential market opportunities are significant, with estimates of 4,150 million for wet AMD and DME, and 4,710 million for cystic fibrosis lung disease [1] Clinical Development and Trials - **Phase III Trials**: The focus for the next twelve months is on executing Phase III trials for FORWARD I and FORWARD II in wet AMD and initial dose data for cystic fibrosis [2] - **Physician Feedback**: Positive feedback from physicians regarding the durability of treatments and reduced injection burden, with expectations of an 80-90% reduction compared to existing therapies [6][7] - **Safety Profile**: The company reports a strong safety profile with no inflammation observed in DME trials, which is critical for large markets like wet AMD and DME [9][10] Commercial Strategy - **Pricing Flexibility**: The cost of goods for treatments is around $500, allowing for competitive pricing strategies that can benefit patients and shareholders [26] - **Durability Demand**: Surveys indicate that durability and extended treatment duration are the top desires for both patients and physicians, positioning gene therapy as a leading option [22] Regulatory and Financial Position - **Regulatory Engagement**: Ongoing discussions with the FDA regarding potential accelerated approval pathways for cystic fibrosis treatments, especially for patients with no available therapies [41][43] - **Financial Health**: The company ended Q1 with $458 million in cash, primarily allocated to fund Phase III trials for wet AMD, with a runway extending into 2028 [51] Future Directions - **Partnership Opportunities**: The company is open to partnerships outside the U.S. for its products, particularly in the lung franchise, while retaining U.S. rights for ophthalmology [48][49] - **Platform Development**: The gene therapy platform has shown broad utility, with six open INDs and a focus on developing a portfolio of products efficiently [45][54] Additional Insights - **Market Differentiation**: The company emphasizes that not all gene therapies are the same, highlighting its unique approach to local application and cost management, which differentiates it from other programs in the field [56] This summary encapsulates the key insights and strategic directions discussed during the conference call, providing a comprehensive overview of 4D Molecular Therapeutics' current status and future outlook in the gene therapy market.

Summary of Conference Call Company Overview - **Company**: 4D Molecular Therapeutix (4D MT) - **Lead Product**: 4,150 for wet Age-related Macular Degeneration (AMD) and Diabetic Macular Edema (DME) Industry Context - **Market Size**: The market for retinal vascular diseases is estimated to reach **$20 billion** by the time the product is launched [3] - **Current Treatments**: The current treatment landscape includes EYLEA and Vabismo, with a focus on improving durability and reducing treatment burden [29][30] Key Product Updates - **Clinical Trials**: The Forefront I Phase III trial is currently underway with over **50 clinical trial sites** activated, targeting a total of **100 sites** [2] - **Product Designation**: 4,150 is the first known genetic medicine to receive RMAT designation, indicating its potential as a breakthrough therapy for wet AMD and DME [3][46] - **Efficacy**: In Phase 1/2 trials, 4,150 demonstrated an **83% reduction** in injection burden for hard-to-treat patients, with some recently diagnosed patients showing over **90% reduction** [12][13] Core Product Advantages - **Durability and Safety**: The product aims to provide greater durability with a favorable safety profile, comparable to EYLEA [4][15] - **Treatment Burden Reduction**: The anticipated reduction in treatment burden is projected to be between **80% to 90%**, significantly higher than existing therapies [8][30] - **Patient Convenience**: The product is designed for seamless integration into clinical practice, allowing for routine intravitreal injections [4] Market Dynamics - **Physician Feedback**: There is significant interest from physicians and patients regarding gene therapy, with a focus on durability and treatment burden reduction [30][31] - **Payer Environment**: The majority of wet AMD patients are Medicare patients, which is seen as a favorable payer environment for launching the product [43] Regulatory Insights - **FDA Alignment**: The FDA has agreed that a single Phase III trial can serve as the basis for BLA submission for DME, which is a significant regulatory milestone [51] - **RMAT Designation**: This designation is expected to facilitate more efficient interactions with regulatory bodies and potentially streamline the review process [46][47] Financial Considerations - **Cost of Goods**: The cost of goods for 4,150 is projected to be less than **$1,000**, providing flexibility in pricing strategies [44] - **Funding for DME Trial**: The company is exploring non-equity financing and partnerships for funding the DME trial, with current cash reserves sufficient to support wet AMD programs through data readout [53] Future Milestones - **Upcoming Data Releases**: Key data updates are expected in Q4 for Phase 1/2 trials, with continued updates on enrollment and site openings for Phase III trials [61] - **Cystic Fibrosis Program**: The company is also advancing its 4,710 product for cystic fibrosis, with updates expected in the second half of the year [25][59] Conclusion 4D Molecular Therapeutix is positioned to potentially revolutionize the treatment landscape for wet AMD and DME with its innovative gene therapy approach, focusing on significant reductions in treatment burden and improved patient outcomes. The company is actively engaging with regulatory bodies and exploring funding options to support its clinical programs.

4D-150 Product & Clinical Development - 4D-150 is designed to disrupt the global market for retinal vascular diseases and improve patient outcomes[9, 11, 19, 29, 39, 44] - 4D-150 has received Regenerative Medicine Advanced Therapy (RMAT) designation for both wet AMD and DME[8] - 4D-150 Phase 3 4FRONT global registration program topline data from wet AMD pivotal trials is expected in H2 2027[10, 12, 20, 30, 41, 46] - Phase 1/2a data showed a 83% reduction in mean annual injections post 4D-150 in recently diagnosed patients, and a 94% reduction in Phase 2b populations[28] - In wet AMD patients, treatment-related 1+ vitreous cells at a single timepoint were observed in 2 of 71 patients, representing 2.8%[32, 34] - In DME patients, there was no intraocular inflammation at any timepoint at any dose level[35] Market Opportunity & Financials - The global market for retinal vascular diseases is $17 billion+ and growing[10, 12, 20, 30, 41, 46] - The company had $458 million cash as of March 31, 2025, providing runway into 2028[58] 4FRONT Phase 3 Trial Design - The 4FRONT Phase 3 trials are global, multicenter, randomized, double-masked, aflibercept Q8W comparator-controlled studies[47, 50] - The trials aim for noninferiority to enable global registration in wet AMD[47, 50]

Summary of 4D Molecular Therapeutics (FDMT) Conference Call Company Overview - **Company**: 4D Molecular Therapeutics (FDMT) - **Lead Product**: 4150, currently in phase three development for wet age-related macular degeneration (AMD) and diabetic macular edema (DME) [2][3] Industry Context - **Market Size**: The anti-VEGF market is valued at $17 billion and is expected to grow significantly due to an aging population [4] - **Competitive Landscape**: The market is competitive with existing therapies like aflibercept and new entrants like Babizmo, which has shown rapid uptake due to improved durability [4][5] Core Product Insights - **Durability**: 4150 aims to provide multi-year durability compared to existing therapies that offer only a few months of effectiveness [5][6] - **Injection Burden**: Current therapies require 8-10 injections per year, while 4150 could reduce this burden by 83-94% in various patient populations [7][8] - **Safety Profile**: The product has shown a favorable safety profile with no serious adverse events reported, and a low rate of mild transient effects [8][11] Clinical Development - **Phase Three Trials**: Top-line data for wet AMD pivotal trials is expected in the second half of 2027, designed to demonstrate non-inferiority in best corrected visual acuity (BCVA) and significant reduction in injection burden [12][20] - **Regulatory Designation**: 4150 has received RMAT designation for both wet AMD and DME, indicating a favorable regulatory outlook [3][16] Manufacturing and Commercialization - **Manufacturing Strategy**: Currently in-house manufacturing with plans to outsource as commercialization approaches, minimizing exposure to potential tariffs [19] - **Cost of Goods**: Estimated at $500, providing pricing flexibility and potential for favorable payer negotiations [11] Market Expectations and Physician Insights - **Initial Uptake**: Anticipated initial use in patients with high treatment burdens (8-10 injections/year), with gradual adoption in less severe cases as physician familiarity increases [29][30] - **Physician Feedback**: Physicians prioritize significant reductions in injection frequency over complete injection freedom, viewing an 80-90% reduction as a substantial benefit [22][24] Competitive Positioning - **Differentiation**: 4150 aims to set a new standard in durability, potentially offering years of effectiveness compared to competitors that may only extend treatment intervals by a few months [27][28] Additional Programs - **Other Developments**: Active program for 4710 targeting cystic fibrosis lung disease, with promising clinical activity expected to be updated later this year [13] Conclusion - 4D Molecular Therapeutics is positioned to disrupt the retinal vascular disease market with its innovative gene therapy, 4150, which promises significant improvements in treatment durability and patient outcomes while maintaining a strong safety profile. The company is on track for pivotal trial data and is strategically planning for commercialization amidst a competitive landscape.

Company Performance - 4D Molecular Therapeutics reported a quarterly loss of $0.86 per share, which was worse than the Zacks Consensus Estimate of a loss of $0.84, and compared to a loss of $0.66 per share a year ago, indicating a decline in performance [1] - The company posted revenues of $0.01 million for the quarter ended March 2025, missing the Zacks Consensus Estimate by 98.70%, and down from $0.03 million in the same quarter last year [2] - Over the last four quarters, the company has only surpassed consensus EPS estimates once and has not beaten consensus revenue estimates [2] Stock Performance - 4D Molecular Therapeutics shares have declined approximately 44.1% since the beginning of the year, contrasting with the S&P 500's decline of -4.3% [3] - The current consensus EPS estimate for the upcoming quarter is -$0.85 on revenues of $1.08 million, and for the current fiscal year, it is -$3.40 on revenues of $8.47 million [7] Industry Outlook - The Medical - Drugs industry, to which 4D Molecular Therapeutics belongs, is currently ranked in the top 26% of over 250 Zacks industries, suggesting a relatively strong industry performance [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, which could impact the stock's future performance [5]