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]

Financial Performance - The company reported a net loss of $48.0 million for the three months ended March 31, 2025, compared to a net loss of $32.4 million for the same period in 2024, representing a 48% increase in losses[142]. - The company has an accumulated deficit of $624.2 million as of March 31, 2025, and does not expect positive cash flows from operations in the foreseeable future[142]. - The company experienced a net loss of $48.0 million for the three months ended March 31, 2025, compared to a net loss of $32.4 million for the same period in 2024[180][181]. - Net cash used in operating activities was $47.8 million for the three months ended March 31, 2025, compared to $29.1 million for the same period in 2024[179][181]. Revenue and Funding - Collaboration and license revenue decreased by 50% from $28,000 to $14,000 for the three months ended March 31, 2025, compared to the same period in 2024[154]. - The company has not generated any revenue from product sales since inception and relies on equity financing and collaboration agreements for funding[143][158]. - The company completed a public offering in February 2024, raising net proceeds of $281.2 million from the sale of 6,586,015 shares at $29.50 per share[139]. - The company completed the 2024 Offering, raising net proceeds of $281.2 million after deducting underwriting discounts and commissions[165]. - The company entered into a License Agreement with AGT, receiving an upfront payment of $20.0 million for its 4D vector technology[164]. Expenses - Research and development expenses increased by $12.8 million, or 46%, from $27.9 million in Q1 2024 to $40.7 million in Q1 2025, driven by higher trial and personnel costs[156][157]. - General and administrative expenses rose by $2.6 million, or 26%, from $10.3 million in Q1 2024 to $12.9 million in Q1 2025, primarily due to increased personnel-related costs[157]. - Payroll and personnel expenses increased by $4.8 million, including a $0.9 million rise in employee stock-based compensation due to a higher headcount in research and development[162]. - Clinical trial costs rose by $4.5 million, primarily due to increased activity for product candidates, especially 4D-150[162]. - The company anticipates continued increases in research and development and general administrative expenses for the foreseeable future[170]. Product Development - The company is prioritizing the development of its lead product candidates, 4D-150 and 4D-710, while seeking strategic alternatives for other clinical-stage candidates[135]. - 4D-150 is currently in a Phase 3 clinical trial for the treatment of wet AMD, with the first patients enrolled in March 2025[136]. - The company anticipates significant increases in operating losses as it continues to advance its product candidates through clinical development and regulatory approval processes[141]. Cash Position - Cash, cash equivalents, and marketable securities totaled $458.4 million as of March 31, 2025[168]. - Future capital expenditures are expected to increase significantly for building commercial manufacturing capacity[170].

Financial Performance - 4D Molecular Therapeutics reported a net loss of $48.0 million for Q1 2025, compared to a net loss of $32.4 million in Q1 2024, reflecting an increase in operational expenses[12]. - General and administrative expenses rose to $12.9 million in Q1 2025 from $10.3 million in Q1 2024, driven by increased professional services[12]. - The accumulated deficit increased to $624.2 million as of March 31, 2025, compared to $576.2 million at the end of 2024[20]. Research and Development - Research and development expenses increased to $40.7 million in Q1 2025 from $27.9 million in Q1 2024, primarily due to the initiation of the Phase 3 clinical trial for 4D-150 in wet AMD[11]. - The first patients were enrolled in the Phase 3 clinical trial (4FRONT-1) for 4D-150 in wet AMD, with over 50 clinical trial sites currently open[5]. - Topline data from both Phase 3 trials (4FRONT-1 and 4FRONT-2) for 4D-150 is expected in H2 2027[5]. - In a Phase 2b cohort, 4D-150 demonstrated an 83% reduction in injection burden compared to projected on-label aflibercept 2 mg Q8W, with 70% of patients requiring 0-1 supplemental injection[9]. Cash and Funding - The company had $458 million in cash, cash equivalents, and marketable securities as of March 31, 2025, down from $505 million at the end of 2024, expected to fund operations into 2028[10]. - The company has paused significant additional capital allocation for other programs pending financing or partnerships, extending its cash runway into 2028[6]. Regulatory Designations - The company received RMAT designation from the FDA for 4D-150 in diabetic macular edema, adding to previous designations for wet AMD[5].

Core Insights - 4D Molecular Therapeutics reported significant advancements in its clinical pipeline, particularly with 4D-150 for wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME), and initiated its first Phase 3 clinical trial [2][5][12] Financial Performance - As of March 31, 2025, the company had cash, cash equivalents, and marketable securities totaling $458 million, down from $505 million at the end of 2024, with expectations to fund operations into 2028 [9][20] - Research and development expenses for Q1 2025 were $40.7 million, an increase from $27.9 million in Q1 2024, primarily due to the initiation of the Phase 3 clinical trial for 4D-150 [10] - General and administrative expenses rose to $12.9 million in Q1 2025 from $10.3 million in Q1 2024 [11] - The net loss for Q1 2025 was $48.0 million, compared to a net loss of $32.4 million in Q1 2024 [11][18] Clinical Development Highlights - The first patients were enrolled in the 4D-150 Phase 3 clinical trial (4FRONT-1) for wet AMD, with over 50 clinical trial sites currently open [5][6] - The second Phase 3 clinical trial (4FRONT-2) is expected to initiate in Q3 2025, with topline data from both trials anticipated in H2 2027 [5][6] - 4D-150 received RMAT designation from the FDA for DME, adding to its previous designations for wet AMD [5][6] Product Pipeline Focus - The company has identified core programs: 4D-150 for wet AMD and DME, and 4D-710 for cystic fibrosis lung disease, while pausing investment in other programs pending additional financing or partnerships [6][12] - Development of 4D-110 for choroideremia and 4D-125 for X-linked retinitis pigmentosa has been terminated [6] Upcoming Milestones - Data and programmatic updates for 4D-150 in wet AMD and DME, as well as for 4D-710 in cystic fibrosis, are expected in H2 2025 [2][5]

Core Insights - 4D Molecular Therapeutics has received RMAT designation from the FDA for its product 4D-150, aimed at treating diabetic macular edema (DME) [1][2] - The RMAT designation highlights the potential of 4D-150 to meet significant unmet medical needs in DME, following a similar designation for wet age-related macular degeneration (wet AMD) [2] - 4D-150 is designed to provide multi-year sustained delivery of anti-VEGF therapies through a single intravitreal injection, reducing treatment burden for patients [3][5] Company Overview - 4D Molecular Therapeutics is a late-stage biotechnology company focused on developing durable and disease-targeted therapeutics [5] - The lead product candidate, 4D-150, targets blinding retinal vascular diseases, specifically wet AMD and DME, with ongoing Phase 3 clinical trials [5] - The company also has a second product candidate, 4D-710, aimed at cystic fibrosis treatment [5] Product Details - 4D-150 utilizes a customized intravitreal vector, R100, to deliver anti-VEGF therapies effectively [3] - The product aims to alleviate the treatment burden associated with frequent injections currently required for DME and wet AMD [3][4] - DME affects approximately one million individuals in the U.S., characterized by inflammation and swelling in the macula, leading to vision loss [4]

Company Overview - 4D Molecular Therapeutics (4DMT) 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 [2][3] - 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 [2][3] - 4D-150 offers multi-year sustained delivery of anti-VEGF through a single intravitreal injection, reducing the treatment burden associated with current bolus injections [2] Recent Developments - On April 8, 2025, the compensation committee of 4DMT's board of directors granted 16,500 Restricted Stock Units (RSUs) to three new non-executive employees [1] - The RSUs were issued under the Company's 2025 Employment Inducement Award Plan, which was approved in February 2025 [1] Product Pipeline - All product candidates from 4DMT are currently in clinical or preclinical development and have not yet received approval from the U.S. Food and Drug Administration or other regulatory authorities [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 via aerosol delivery [2]

EMERYVILLE, Calif., March 10, 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 that the first patients have been enrolled across multiple sites in the 4FRONT-1 Phase 3 clinical trial evaluating 4D-150 for the treatment of wet age-related macular degeneration (wet AM ...

Financial Performance - The company reported net losses of $160.9 million and $100.8 million for the years ended December 31, 2024 and 2023, respectively, with an accumulated deficit of $576.2 million as of December 31, 2024[161]. - The company anticipates that its future net losses will depend on the level of future expenditures and its ability to generate revenue[162]. - The company expects to continue incurring significant expenses and operating losses for the foreseeable future as it progresses its product candidates through preclinical and clinical development[163]. - The company will require substantial additional capital to finance its operations and may be forced to delay or reduce research and drug development programs if unable to raise such capital[165]. Cash and Assets - As of December 31, 2024, the company had $505.5 million in cash and cash equivalents and marketable securities[166]. Product Development and Clinical Trials - The company has no products approved for commercial sale and has not generated any product revenue to date[160]. - The company has initiated ongoing clinical trials and has additional product candidates in preclinical development[165]. - The company has not completed any clinical trials or obtained marketing approval for any product candidates[160]. - Clinical testing is expensive and time-consuming, with potential delays in clinical trials due to various factors, including regulatory authorization and patient recruitment[197]. - The company plans to initiate Phase 3 studies in 2025 comparing a single dose of 4D-150 to on-label aflibercept, with potential delays posing serious risks to business[197]. - The company faces challenges in patient enrollment for clinical trials due to factors such as disease severity, diagnostic difficulties, and patient access to medical professionals[199]. - Delays in manufacturing and testing processes could hinder the availability of product candidates for clinical trials[200]. - The limited number of patients with rare genetic diseases may complicate the enrollment and completion of clinical trials, impacting statistical significance[205]. - Clinical trials must demonstrate substantial evidence of safety and efficacy, which is essential for regulatory approval and commercialization[218]. - Most product candidates that begin clinical trials are never approved by regulatory authorities for commercialization[220]. - The company has limited experience in designing clinical trials, which may hinder marketing approval[221]. Regulatory Challenges - The regulatory approval processes for the company's product candidates are lengthy, expensive, and inherently unpredictable, which could delay commercialization[158]. - The regulatory approval process for novel product candidates can be more expensive and take longer than for extensively studied therapeutic modalities[177]. - The FDA and EMA have established specific committees to review genetic medicine products, which may lengthen the regulatory review process and increase development costs[178][182]. - The company may face significant regulatory oversight, requiring compliance with evolving guidelines that could delay or prevent approval and commercialization[184][183]. - Regulatory approval is uncertain, and the company has never submitted an application for any product candidate, which poses a significant risk to business[210]. - Changes in regulatory requirements or adverse findings could lead to clinical holds or trial terminations, affecting product development timelines[203]. - The company must ensure compliance with cGMP requirements, which involves significant time, money, and effort in production and quality control[245]. - Regulatory agencies may impose restrictions or withdraw approvals if compliance issues arise, which could significantly harm the company's business[266]. - The company may face challenges in maintaining regulatory compliance amid changing policies and new government regulations[268]. Market and Competition - The company faces substantial competition from major pharmaceutical and biotechnology companies, which may hinder its market position[228]. - Competitors may have significantly greater financial resources and expertise, impacting the company's ability to compete effectively[231]. - The company lacks a sales and marketing infrastructure, which may affect the commercialization of approved products[232]. - The company currently lacks a sales organization, which may hinder its ability to effectively market and sell products if approved[298]. - Establishing a sales organization is expected to be expensive and time-consuming, with significant risks involved in hiring and retaining qualified personnel[298]. Intellectual Property - The company has three granted patents and three pending patent applications, with potential government rights affecting their commercialization[318][319]. - The patent application process is uncertain, with risks including non-issuance of patents and challenges from competitors[321]. - The company may not be able to adequately protect its intellectual property, which could harm its competitive position[319][328]. - The lifespan of patents is limited, generally expiring 20 years after the first filing date, which may expose the company to competition[329]. - The company may face difficulties in enforcing patent rights, which could lead to significant expenses and management distraction[324][325]. - The company relies on exclusive license agreements with U.C. Berkeley and the University of Pennsylvania for critical intellectual property related to its product candidates, which may not provide adequate rights for all relevant fields or territories[343]. - The company may not be able to protect its intellectual property rights globally due to high costs and varying levels of protection in different jurisdictions[334]. - The company may face claims challenging the inventorship or ownership of its patents, which could result in costly litigation and loss of valuable intellectual property rights[337]. Collaborations and Third-Party Risks - The company relies on third parties for clinical trials and research, which may affect control over these activities and introduce risks if those parties do not perform satisfactorily[309][310]. - Collaborations with third parties for research and commercialization may limit the company's control and expose it to risks related to intellectual property and resource allocation[313][314]. - The company may incur additional losses and delays in product development if third-party manufacturers or distributors fail to perform as expected[312]. - The negotiation process for collaborations is complex and time-consuming, potentially requiring additional capital if collaborations are not established[316]. - Collaborators may not maintain or defend intellectual property rights effectively, leading to potential litigation and resource diversion[354]. Regulatory Designations and Incentives - The company has received Fast Track designation for 4D-310 for the treatment of Fabry disease, which may allow for more frequent interactions with the FDA during product development[269]. - The company has obtained orphan drug designation for 4D-710 for cystic fibrosis and for 4D-310 for Fabry disease, which may provide market exclusivity and financial incentives[270]. - The FDA may grant orphan drug exclusivity for a product if it is the first to receive approval for a specific disease, providing seven years of protection from competition[272]. - The company has received Regenerative Medicine Advanced Therapy (RMAT) and PRIority MEdicine (PRIME) designations for 4D-150 for the treatment of wet AMD, which may facilitate expedited regulatory review[274]. - The company has obtained a rare pediatric disease designation for 4D-710, which may qualify for a priority review voucher upon FDA approval[280]. Economic and Legislative Factors - Legislative changes, such as the Inflation Reduction Act of 2022, may impose price negotiations and rebates, affecting revenue potential[287]. - The ACA and subsequent legislation have led to reductions in Medicare payments, impacting the financial landscape for pharmaceutical companies[286]. - Increased scrutiny over drug pricing and reimbursement policies may pressure product pricing and demand[289]. - Future healthcare reforms may limit government payments for healthcare products, leading to reduced demand and pricing pressures[288].