4D-710

Announced positive interim results from the Population Extension cohort of the Phase 2 PRISM clinical trial for 4D-150 in a broad wet age-related macular degeneration (wet AMD) population, which includes patients representative of the planned Phase 3 study population, affirming favorable safety profile and robust clinical activityStrengthened senior leadership team and announced formation of a world class Ophthalmology Advisory Board to drive late-stage development of 4D-150 in wet AMD and diabetic eye diseasesPRISM Phase 1/2 interim data, which includes longest available follow-up in patients with severe disease activity (Dose Exploration and Expansion) and broad disease activity (Population Extension), are expected to be presented at the 24th EURETINA Congress on September 19, 2024In conjunction with the EURETINA presentation, the Company will host a virtual 4D-150 Development Day to discuss the PRISM interim data and final Phase 3 design in wet AMD with details to be announced ahead of the eventU.S. Food and Drug Administration (FDA) removed clinical hold on the Phase 1/2 INGLAXA study for 4D-310 in Fabry disease cardiomyopathy; enrollment expected to resume in H2 2024$578 million in cash and equivalents as of June 30, 2024, expected to fund operations into H1 2027 EMERYVILLE, Calif., Aug. 08, 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 reported second quarter 2024 financial results, provided operational highlights and outlined expected upcoming milestones. “4DMT continues to drive strong progress and execution toward our goal of becoming a leading late-stage genetic medicines company. We are excited to bolster our senior leadership team with clinical and commercial experts and honored to welcome world-renowned retinal disease experts to our Ophthalmology Advisory Board, which will support our strategy to be a leader in large market ophthalmology indications,” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “At our inaugural 4D-150 Development Day in September 2024, we plan to report on the durability of 4D-150 by presenting the longest available follow-up data from the Phase 2 PRISM study in wet AMD patients who have been followed through up to 2.5 years and discuss the final wet AMD Phase 3 clinical trial design.” Recent Corporate Highlights Bolstered Senior Leadership Team: Dhaval Desai, PharmD, joined as Chief Development Officer; will oversee late-stage product development, Medical Affairs, Scientific Communications, Regulatory and Quality operations. Dr. Desai was most recently SVP & Chief Development Officer at Iveric Bio (an Astellas company) where he led development and approval of IZERVAY™Christopher Simms named Chief Commercial Officer, effective September 25, 2024; will oversee Pre-commercial and Commercial organizations and pre-launch preparations and development. Mr. Simms was most recently SVP & Chief Commercial Officer at Iveric Bio (an Astellas company) where he led commercial strategy and execution for the launch of IZERVAYCarlos Quezada-Ruiz, M.D., FASRS, joined as SVP, Therapeutic Area Head, Ophthalmology; will lead the Ophthalmology franchise and oversee early- and late-stage clinical development. Dr. Quezada-Ruiz was most recently Group Medical Director, Ophthalmology at Genentech where he led clinical development and approval of VABYSMO and SUSVIMO Formation of Ophthalmology Advisory Board comprised of world-renowned retina specialists and thought leaders to support development strategy and registration across large market ophthalmology indications including wet AMD, DME, diabetic retinopathy and geographic atrophy: Dr. Arshad Khanani (Chair), Dr. David Boyer, Dr. Frank Holz, Dr. Anat Loewenstein, Dr. Dante Pieramici Recent Highlights in Large Market Ophthalmology Portfolio 4D-150 for wet AMD & DME (Data cutoff: June 24, 2024): 4D-150 continues to be safe and well tolerated in 139 patients treated to date across wet AMD (PRISM clinical trial) and DME (SPECTRA clinical trial) No significant inflammation reported in 51 patients treated to date with planned Phase 3 dose (3E10 vg/eye) and topical corticosteroid regimenOverall rate of mild (Grade 1) inflammation ~2%; previously reported episode of mild to moderate inflammation in low dose patient (1E10 vg/eye) determined by Principal Investigator to be not related to 4D-150 Presented initial interim 24-week landmark data from the Population Extension cohort of the PRISM Phase 2 Clinical Trial at the American Society of Retina Specialists (ASRS) Annual Scientific Meeting in July: Two loading doses of aflibercept at Week -1 and Week 4 are consistent with loading regimens seen in earlier lines of treatment of wet AMD to maintain patient safety during ramp up of aflibercept transgene expression over 8-12 weeksRobust reduction in anti-VEGF injection treatment burden demonstrated in 30 patients treated with planned Phase 3 dose (3E10 vg/eye) with 89% reduction in annualized injection rate; 93% of patients received 0 or 1 injection and 77% were injection-freeImprovement in mean best corrected visual acuity (BCVA) from baseline at 3E10 vg/eye dose (+4.2 letters)3E10 vg/eye dose demonstrated sustained and greater anatomic control without fluctuations 4D-175 for Geographic Atrophy: Received FDA clearance of Investigational New Drug (IND) application for 4D-175 Recent Highlights in Other Pipeline Programs 4D-710 for Cystic Fibrosis (CF) Lung Disease: Positive interim data from Phase 1/2 AEROW clinical trial of aerosolized 4D-710 for modulator-ineligible/-intolerant cystic fibrosis presented at 47th European Cystic Fibrosis Conference in June: Aerosolized 4D-710 was well tolerated at doses up to 1E15 vg (n=6)Clinically meaningful improvements in ppFEV1 at 12 months observed in 2 of 3 trial participants with mild to moderate baseline lung function impairment (ppFEV1 50-80%) and >6 months follow upDose-dependent and widespread 4D-710-mediated CFTR transgene RNA and protein expression observed in all lung biopsies from all trial participants evaluated to datePre-existing AAV immunity cross-reactive with A101 did not affect transgene expression, biological activity or safety1E15 vg dose cleared for evaluation in Phase 2 Dose Expansion cohort 4D-310 for Fabry Disease Cardiomyopathy: FDA removed clinical hold on the Phase 1/2 INGLAXA study for 4D-310 in Fabry disease cardiomyopathy Expected Upcoming Milestones in Large Market Ophthalmology Portfolio 4D-150 for Wet AMD: Interim longest available follow up data up to 2.5 years from its Phase 1/2 PRISM clinical trial evaluating intravitreal 4D-150 in wet AMD are expected to be presented at the 24th EURETINA Congress on September 19, 2024: Severe disease activity: Phase 1 Dose Exploration cohort, Phase 2 Dose Expansion cohortBroad disease activity (which includes patients representative of the planned Phase 3 study population): Phase 2 Population Extension cohort 52-week landmark analyses for both 1) severe disease activity (Dose Expansion) & 2) broad wet AMD disease activity (Population Extension) cohorts of PRISM expected in February 2025 (last patient, last visit January 2025)First Phase 3 clinical trial initiation expected in Q1 2025 4D-150 for DME: Interim data from SPECTRA Phase 2 Part 1 Dose Confirmation cohort (n=22) expected in Q4 2024 Virtual 4D-150 Development Day Planned in September 2024: Company will host a Corporate Webcast during which senior leadership and key opinion leaders will review clinical data from the PRISM clinical trial and final wet AMD Phase 3 clinical trial designParticipating key opinion leaders and details regarding the webcast will be provided in advance of the event 4D-175 for Geographic Atrophy: Phase 1 enrollment expected to begin in H2 2024 Expected Upcoming Milestones in Other Pipeline Programs 4D-710 for CF Lung Disease: Interim data update from AEROW clinical trial is expected in mid-2025Phase 3 initiation is expected in H2 2025 4D-725 for Alpha-1-Antitrypsin Deficiency Lung Disease: Program update expected in Q4 2024 4D-310 for Fabry Disease Cardiomyopathy: Resume enrollment in H2 2024 with program update expected in 2025 4D-110 for Choroideremia and 4D-125 for X-Linked Retinitis Pigmentosa: Program updates expected in Q4 2024 Q2 2024 Financial Results Cash and Cash Equivalents and Marketable Securities: Cash and cash equivalents and marketable securities were $578 million as of June 30, 2024, as compared to $299 million as of December 31, 2023. The net increase in cash was primarily a result of cash inflows from approximately $316 million of net proceeds from our public offering of common stock completed in February including partial exercise of underwriters’ option to purchase additional shares. We currently expect cash and cash equivalents to be sufficient to fund operations into the first half of 2027. R&D Expenses: Research and development expenses were $31.9 million for the second quarter of 2024, as compared to $23.6 million for the second quarter of 2023. This increase was driven by the progression of our existing clinical trials, primarily Phase 2 4D-150 trials in wet AMD and DME, along with increased payroll and stock-based compensation expense due to higher headcount. G&A Expenses: General and administrative expenses were $10.6 million for the second quarter of 2024, as compared to $8.8 million for the second quarter of 2023. Net Loss: Net loss was $35.0 million for the second quarter of 2024, as compared to net loss of $29.6 million for the second quarter of 2023. 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 six clinical-stage and one preclinical product candidate, 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 U.S. Food and Drug Administration (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, as well as the plans, announcements and related timing for the clinical development of, 4DMT’s product candidates, and statements regarding our financial performance, results of operations and anticipated cash runway. 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 to be filed on or about the date hereof, 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. Statements of Operations (Unaudited)(in thousands, except share and per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2024 2023 2024 2023 Collaboration and license revenue $5 $239 $33 $538 Operating expenses: Research and development 31,860 23,584 59,727 46,002 General and administrative 10,601 8,791 20,898 16,777 Total operating expenses 42,461 32,375 80,625 62,779 Loss from operations (42,456) (32,136) (80,592) (62,241)Other income (expense), net: 7,503 2,520 13,238 3,943 Net loss $(34,953) $(29,616) $(67,354) $(58,298)Net loss per share, basic and diluted $(0.63) $(0.77) $(1.29) $(1.63)Weighted-average shares outstanding used in computing net loss per share, basic and diluted 55,282,754 38,335,219 52,277,369 35,661,995 Balance Sheet Data (Unaudited)(in thousands) June 30, December 31, 2024 2023 Cash and cash equivalents and marketable securities $577,661 $299,186 Working capital 533,230 277,637 Total assets 620,117 339,891 Total liabilities 31,777 32,062 Accumulated deficit (482,681) (415,327)Total stockholders’ equity 588,340 307,829 Contacts: Media: Katherine SmithInizio Evoke CommsKatherine.Smith@inizioevoke.com Investors: Julian PeiHead of Investor Relations and Corporate FinanceInvestor.Relations@4DMT.com

Clinically meaningful improvements in ppFEV1 at 12 months observed in 2 of 3 participants with mild to moderate baseline lung function impairment (ppFEV1 50-80%) and >6 months follow up Aerosolized 4D-710 was well tolerated at doses up to 1E15 vg (n=6) Dose-dependent and widespread 4D-710-mediated CFTR transgene RNA and protein expression observed in all lung biopsies from all participants evaluated to date Pre-existing AAV immunity cross-reactive with A101 did not affect transgene expression, biological activity or safety 1E15 vg dose cleared for evaluation in Phase 2 Dose Expansion stage; enrollment expected to begin in H2 2024 and next interim data update expected in mid-2025 Company to host live webcast today at 8:00 a.m. ET with Dr. Jennifer L. Taylor-Cousar, lead Principal Investigator in the AEROW clinical trial EMERYVILLE, Calif., June 06, 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 positive interim clinical data from the 4D-710 Phase 1/2 AEROW clinical trial for the treatment of cystic fibrosis (CF) lung disease. Interim data from the study will be presented by Jennifer L. Taylor-Cousar, M.D., MSCS, in an oral presentation titled, “CFTR transgene expression in airway epithelial cells following aerosolized administration of the AAV-based gene therapy 4D-710 to adults with cystic fibrosis lung disease,” at the 47th European Cystic Fibrosis Conference held in Glasgow, UK on Thursday, June 6 at 5:00 p.m. BST. “We are pleased with the widespread CFTR transgene and protein expression in airway cells from all participants at all doses in the AEROW clinical trial,” said Jennifer L. Taylor-Cousar, M.D., MSCS, Professor, Departments of Medicine and Pediatrics, and Co-Director, Adult Cystic Fibrosis Program, Director, Cystic Fibrosis Therapeutics Development Center, National Jewish Health and lead Principal Investigator in the AEROW clinical trial. “The consistent widespread 4D-710–mediated CFTR expression and initial clinical activity in Phase 1 are encouraging and suggest that 4D-710 has the potential to be the first treatment option for those living with cystic fibrosis who do not currently benefit from available disease-modifying therapies.” “The clinical data to date from the AEROW clinical trial continues to strongly support the advancement of 4D-710 to the next stage of development for CF lung disease,” said Alan H. Cohen, M.D., SVP, Therapeutic Area Head of Pulmonology of 4DMT. “Based on the emerging favorable safety and clinical activity profile, we look forward to beginning our Phase 2 Dose Expansion stage in participants with mild to moderate lung function impairment, to confirm the clinical activity of the 1E15 vg dose.” “The interim data we shared today from the AEROW clinical trial continues to showcase the breadth and depth of our platform, product engine and pipeline,” said David Kirn, M.D., Co-Founder and Chief Executive Officer of 4DMT. “4D-710 is well positioned as the lead program in our pulmonology portfolio as we move into mid to late-stage development. These clinical results also support continued use of our next-generation A101 pulmonary vector for large-market lung diseases such as alpha-1 antitrypsin deficiency lung disease, for which we are developing 4D-725, an aerosolized genetic medicine currently in IND-enabling preclinical studies.” AEROW Clinical Trial Phase 1 Dose Exploration Stage Background & Summary 10 participants with CF lung disease who are ineligible for or intolerant of CFTR modulator therapy have been enrolled in the Phase 1 Dose Exploration stage across four dose cohorts: 2E15 vg Cohort: n=4 1E15 vg Cohort: n=3 5E14 vg Cohort: n=2 2.5E14 vg Cohort: n=1 Participants enrolled in the Phase 1 Dose Exploration stage had a broad range of baseline ppFEV1 impairment ranging from 56% to 100% Participants received a single aerosolized dose of 4D-710 administered via an AeroEclipse II breath-actuated nebulizer All results below are based on best available data as of May 24, 2024 Interim Safety Data High Dose – 2E15 vg (n=4): Complete resolution of previously reported serious adverse event (SAE) (pneumonitis not otherwise specified); ppFEV1 in this participant improved by 6% from baseline to month 12 (last timepoint assessed) Lung biopsy results: No evidence of inflammation or toxicity from histological analysis of tissue samples Widespread expression of CFTR protein compared to normal (non-CF) lung samples and no increase vs. 1E15 vg dose Evidence of consistent CFTR protein expression in all major airway epithelial cell types, as well as in interstitial tissue cells; interstitial CFTR expression was not detected in normal lung control samples Based on all available data for 2E15 and 1E15 vg dose level participants, 1E15 vg was selected as the highest dose for Dose Expansion; 2E15 vg dose will not be further evaluated Lower Doses – 2.5E14 to 1E15 vg (n=6): 4D-710 was well tolerated, with no 4D-710–related adverse events after administration, no dose-limiting toxicities, and no SAEs Interim CFTR Biomarker Data Biomarker analyses demonstrated robust, consistent and widespread CFTRDR transgene mRNA and CFTR protein expression throughout all lung biopsy samples from all participants at all four dose levels Dose-dependent CFTR∆R transgene RNA expression, with the mean % of airway epithelial cells testing positive ranging from 14% to 53% Robust, widespread and above-normal CFTR protein expression at all doses Protein levels in lung tissue from 4D-710–treated participants 2–4 fold higher than in normal (non-CF) samples, and ~8-12 fold higher than in CF lung samples Protein expression observed in multiple airway epithelial cell types, including basal cells Pre-existing AAV immunity that cross-reacted with A101 did not affect transgene expression, biological activity or safety; transgene expression levels, clinical activity and safety were similar regardless of pre-existing immunity Interim Clinical Activity Data All participants in 2E15 vg and 1E15 vg Cohorts had at least 12 months of follow up (maximum duration of ppFEV1 assessments per original protocol) and had generally stable or improved in ppFEV1 at 12 months Two of three participants with baseline mild to moderate lung function impairment (ppFEV1 40-80%) showed clinically meaningful improvement in ppFEV1 at 12 months: 2E15 vg Cohort: +6% 1E15 vg Cohort: +5% Quality of Life (CFQ-R-R) scores in 1E15 vg Cohort showed durable and clinically meaningful mean improvement throughout 12 months Next Steps and Upcoming Expected Milestones for 4D-710 Advancing to AEROW Phase 2 Dose Expansion stage (n= up to 9), enrollment to begin in H2 2024 1E15 vg dose level cleared for enrollment Inclusion of 5E14 vg dose pending enrollment and follow-up of third participant in Phase 1 Amendment to AEROW protocol submitted to the Cystic Fibrosis Foundation-supported Therapeutics Development Network to open a new cohort to evaluate 4D-710 in participants on CFTR modulators with persistent moderate to severe CF lung disease; enrollment expected to begin in H2 2024 Interim data update from AEROW clinical trial is expected in mid-2025 Following supportive Phase 2 data, Phase 3 initiation is expected in H2 2025 Corporate Webcast Details: Title: 4D-710 Phase 1/2 AEROW Interim Clinical Data & Program Update Date/Time: Thursday, June 6, 2024 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: . The presentation from the 47th European Cystic Fibrosis Conference will also be available on the 4DMT website: . About Cystic Fibrosis Lung Disease Cystic fibrosis (CF) is an inherited progressive disease caused by variants in the CFTR gene. It affects the lungs, pancreas and other organs. According to the Cystic Fibrosis 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. 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 combines our targeted and evolved next generation AAV vector, A101, with a codon-optimized CFTR∆R transgene. 4D-710 has the potential to treat a broad range of people with CF, independent of the specific CFTR mutation, and is designed for aerosol delivery to achieve targeted CFTR expression within lung airway epithelial cells. 4D-710 is being developed for approximately 35% of people with CF initially. The AEROW Phase 1/2 clinical trial focuses initially on the ~15% of people with CF whose disease is not amenable to existing CFTR modulator medicines (based on variant-eligibility and/or drug intolerance). In people with CFTR variants that are amenable to modulator medicines, the improvement in lung function is variable and often incomplete. We therefore expect to develop 4D-710 for use in this broader “on modulator” population. 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 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 help 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®, 4D®, 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 U.S. Food and Drug Administration (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 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 and regulatory interactions regarding 4D-710 and 4D-725. 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 Smith Inizio Evoke Comms Katherine.Smith@inizioevoke.com Investors: Julian Pei Head of Investor Relations and Corporate Finance Investor.Relations@4DMT.com