AGA

4D-310 demonstrated clinically meaningful cardiac endpoint improvements through 12-24 months in contractility (echocardiography), peak VO2 (cardiopulmonary exercise testing) and/or cardiac quality of life (KCCQ) in all five evaluable patients Cardiac biopsies were obtained from a patient at week 6 and 24 and showed robust and durable delivery, transgene expression and clearance of Gb3 substrate in cardiomyocytes No new treatment-related adverse events > Grade 1 since last interim update and through 12-33 months; previously reported cases of atypical hemolytic uremic syndrome (aHUS) (n=3) fully resolved FDA submission of data from non-human primate (NHP) study evaluating 4D-310 with rituximab/sirolimus (R/S) immunosuppressive regimen in Q2 2024 Efficient delivery, transgene expression and clinical activity now demonstrated in the clinic with three proprietary vectors generated from 4DMT’s Therapeutic Vector Evolution platform EMERYVILLE, Calif., Feb. 12, 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 updated interim safety and efficacy data on six adults with Fabry disease cardiomyopathy treated with a single intravenous (IV) infusion of 4D-310 (1E13 vg/kg) with follow-up of 12-33 months overall, including 12-24 month follow-up data on cardiac contractility, exercise capacity, quality of life and cardiac biopsy data. The data was presented in a late-breaking session at WORLDSymposium™ 2024 in San Diego, California on Friday, February 9, 2024. “We are pleased to see 4D-310 continue to consistently demonstrate clinical activity across multiple important cardiac endpoints including cardiac function, exercise capacity and quality of life,” said Robert Kim, M.D., Chief Medical Officer of 4DMT. “Current therapies do not adequately address Fabry-related cardiovascular manifestations, and cardiovascular disease is the most common cause of death in these patients. 4D-310 continues to be well tolerated, with the previously reported cases of aHUS having fully resolved and no new drug-related adverse events over Grade 1 reported.” “These promising clinical results continue to validate our Therapeutic Vector Evolution platform, as well as the potential of the C102 vector for targeted IV delivery to cardiomyocytes. Cardiac biopsies also showed robust and durable delivery and transgene expression from 4D-310, and remarkably, a reduction in Gb3 substrate in cardiomyocytes,” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “No approved therapy has been shown to definitively clear accumulated Gb3 from cardiomyocytes in patients with Fabry disease, which speaks to 4D-310’s highly differentiated profile. We remain on-track to submit results from the non-clinical study to evaluate 4D-310 in NHPs with the R/S immunosuppressive regimen to the FDA in Q2 2024 to address the clinical hold.” INGLAXA Phase 1/2 Clinical Trial Design & Enrollment Dose escalation and dose expansion trial assessing a single IV infusion of 4D-310 in a broad and diverse Fabry disease patient population Enrolled six patients, each treated with 1E13 vg/kg of 4D-310 and a prophylactic corticosteroid immunosuppressive regimen Protocol amended to change immunosuppressive regimen to rituximab and sirolimus (enrollment on this amendment pending) Cardiac biopsies allowed at week 6 and 26 in the INGLAXA-2 trial (to date, one patient had biopsies performed) INGLAXA Phase 1/2 Interim Data Summary (Data Cutoff: December 5, 2023) Safety and Tolerability Previously reported cases of aHUS (n=3) have fully resolved No clinically significant cardiac or liver toxicities No new 4D-310–related adverse events > Grade 1 since the last interim update in February 2023 Echocardiography Contractility Assessments (Global Longitudinal Strain, GLS) Improved GLS in all five evaluable patients by month 12 Two patients who reached 24 months of follow-up both showed clinically meaningful improvement with change from baseline exceeding the minimal detectable difference of -1.5% (-2.8 and -2.9%, respectively) Cardiopulmonary Exercise Testing (CPET) Peak VO2 Assessments 3 of 4 evaluable patients demonstrated clinically meaningful improvement by CPET peak VO2 with change from baseline exceeding the minimal clinically important difference (MCID) of +1.5 at month 12 (+1.8, +2.0 & +7.0) One patient who reached 24 months of follow up continued to show meaningful improvement with change from baseline exceeding the MCID of +1.5 (+7.8) Cardiac Quality of Life Assessments (Kansas City Cardiomyopathy Questionnaire) Two patients had low baseline scores <90 (scale 0-100); both patients had clinically meaningful improvements in QOL (exceeding the MCID of +5) One patient had 12 months follow-up: Clinical & Overall Summary Scores improved by +5.7 and +11.7, respectively One patient had 24 months follow-up: Clinical & Overall Summary Scores improved by +12.5 and +8.3, respectively Three patients had baseline values >90 (92.7, 100 & 100); all remained stable through 12-24 months (+1.1 to -1.6). Cardiac Biopsy Assessments of Transgene Expression and Substrate Clearance Cardiac biopsies at week 6 and 26 from one patient showed robust & durable 4D-310–mediated transgene expression in cardiomyocytes All samples positive for transgene RNA (ISH) & AGA protein (IHC) At week 26, mean Gb3 inclusion body volume per cardiomyocyte was reduced 15% from week 6 and 61% vs. historical sample collected approximately 7 years prior to enrollment and analyzed independently by investigator Detailed results can be found in the Scientific Posters and Publications section of our website here. Next Steps for Development of 4D-310 FDA submission of data from the NHP study evaluating the safety and biodistribution of IV 4D-310 with the R/S immunosuppressive regimen compared to the prior prednisone regimen expected in Q2 2024 About 4D-310 and Fabry Disease Cardiomyopathy 4D-310 utilizes the cardiac targeted and evolved C102 vector to efficiently deliver a functional copy of the GLA gene (encodes for AGA enzyme) to the heart after a single low dose IV administration. The product candidate is designed to generate high local levels of AGA directly within heart tissue, as well as other affected organs, with the goal of reversing the cardiomyopathy in Fabry patients. Cardiomyopathy is the leading cause of death in the Fabry disease population. Affecting more than 50,000 people in the United States and European Union, Fabry disease is a genetic disorder of the GLA gene that results in the body’s inability to produce AGA, causing accumulation of the substrate globotriaosylceramide (Gb3) in critical organs, including the heart, kidney, and blood vessels. Cardiomyopathy is the leading cause of death in the Fabry disease patient population. Such substrate accumulation can lead to life-threatening hypertrophic cardiomyopathy, heart failure, arrhythmias, various degrees of kidney dysfunction and cerebrovascular stroke. Significant unmet medical needs remain for these patients despite enzyme replacement therapy (ERT), the current standard of care. ERT requires biweekly intravenous dosing which markedly decreases patients’ quality of life. In addition, while benefit has been demonstrated in the kidney, ERT has not been shown to clearly benefit the heart. 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 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 our clinical and preclinical product candidates, and related timing for the clinical development of 4D-310. 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 Communications Investor.Relations@4DMT.com 267-644-5097

Initiated single non-human primate (NHP) safety study evaluating intravenous 4D-310 combined with rituximab/sirolimus (R/S) immunosuppressive regimenAmended INGLAXA protocol to minimize risk of atypical hemolytic uremic syndrome (aHUS) associated with intravenous (IV) AAV dosing, including addition of R/S immunosuppressive regimen4D-310 combines a novel, targeted next generation AAV vector (C102) and GLA transgene for a single low dose IV delivery to cardiomyocytesInterim clinical data from INGLAXA expected to be presented in Q1 2024 EMERYVILLE, Calif., Oct. 30, 2023 (GLOBE NEWSWIRE) -- 4D Molecular Therapeutics (Nasdaq: FDMT, 4DMT or the Company), a clinical-stage genetic medicines company with three novel, highly targeted next generation AAV vectors currently in the clinic, today announced alignment with the U.S. Food and Drug Administration (FDA) on a plan to lift the clinical hold on the Phase 1/2 INGLAXA clinical trial in the United States for 4D-310 for Fabry disease cardiomyopathy. “We are delighted to have reached an agreement with the FDA on our proposed plan to address the clinical hold and continue trial development,” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “We have shared with the FDA the totality of the most up to date clinical activity and safety data already generated from INGLAXA trials, as of August 2023, and look forward to progressing this critical work on behalf of all patients with Fabry disease.” In January 2023, the Company announced that it would pause enrollment in both the United States and Asia-Pacific trials after observing instances of atypical hemolytic uremic syndrome (aHUS). Consistent with the Company’s plans, the FDA subsequently notified the Company of a clinical hold in the U.S. The Asia-Pacific clinical trial program was not placed on clinical hold by any regulatory agency. The Company’s plan includes a single non-clinical study, currently underway, that will evaluate the safety and biodistribution in NHPs of IV 4D-310 with the R/S immunosuppressive regimen compared to the prior prednisone regimen. 4DMT expects to submit the results to the FDA in Q2 2024. In addition, the INGLAXA clinical trial protocol has been amended to minimize the risk of aHUS following IV 4D-310 dosing, including requiring the R/S immunosuppressive regimen. In February 2023, the Company presented positive interim clinical activity data of 4D-310 from 3 patients with 12 months of follow-up, which demonstrated improvements in multiple FDA-recommended cardiac endpoints along with selective and widespread transgene expression within ~50% of cardiomyocytes in a cardiac biopsy. Additional interim cardiac biopsy and clinical efficacy data, with follow-up of at least 12 -18 months for all 6 patients dosed with 4D-310 from the INGLAXA clinical trials, is expected to be presented in Q1 2024. Clinical investigators have previously demonstrated that the R/S immunosuppressive regimen is well-tolerated and is able to prevent the development of aHUS following IV administration of AAV gene therapeutics. About 4D-310 and Fabry Disease Cardiomyopathy 4D-310 utilizes the cardiac targeted and evolved C102 vector to efficiently deliver a functional copy of the GLA gene (encodes for AGA enzyme) to the heart after a single low dose IV administration. The product candidate is designed to generate high local levels of AGA directly within heart tissue, as well as other affected organs, with the goal of reversing the cardiomyopathy in Fabry patients. Cardiomyopathy is the leading cause of death in the Fabry disease population. Affecting more than 50,000 people in the United States and European Union, Fabry disease is a genetic disorder of the GLA gene that results in the body’s inability to produce AGA, causing accumulation of the substrate globotriaosylceramide (Gb3) in critical organs, including the heart, kidney, and blood vessels. Cardiomyopathy is the leading cause of death in the Fabry disease patient population. Such substrate accumulation can lead to life-threatening hypertrophic cardiomyopathy, heart failure, arrhythmias, various degrees of kidney dysfunction and cerebrovascular stroke. Significant unmet medical needs remain for these patients despite enzyme replacement therapy (ERT), the current standard of care. ERT requires biweekly intravenous dosing which markedly decreases patients’ quality of life. In addition, while benefit has been demonstrated in the kidney, ERT has not been shown to clearly benefit the heart. About 4DMT 4DMT is a clinical-stage biotherapeutics company with three novel, highly targeted next generation AAV vectors currently in the clinic targeting multiple large market diseases in ophthalmology and pulmonology, plus other therapeutic areas. 4DMT seeks to unlock the full potential of genetic medicines using its proprietary invention platform, Therapeutic Vector Evolution, which 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 product candidates. All of our vectors are proprietary to 4DMT and were invented at 4DMT, including the vectors utilized in our clinical-stage and preclinical pipeline product candidates: R100, A101, and C102. The Company is initially focused on five clinical-stage product candidates in three therapeutic areas for both rare and large market diseases: ophthalmology, pulmonology, and cardiology. The 4DMT customized and evolved vectors were invented with the goal of being delivered at relatively low doses through clinically routine, well-tolerated, and minimally invasive routes of administration, transducing diseased cells in target tissues efficiently, having reduced immunogenicity and, where relevant, having resistance to pre-existing antibodies. 4DMT is currently advancing five product candidates in clinical development: 4D-150 for wet AMD and DME, 4D-710 for cystic fibrosis lung disease, 4D-310 for Fabry disease cardiomyopathy, 4D-125 for XLRP, and 4D-110 for choroideremia. The 4D preclinical product candidates in development are: 4D-175 for geographic atrophy and 4D-725 for AATLD. 4D-150, 4D-710, 4D-310, 4D-125, and 4D-110 are our product candidates in clinical development and have not yet been approved for marketing by the US FDA or any other regulatory authority. No representation is made as to the safety or effectiveness of 4D-150, 4D-710, 4D-310, 4D-125, or 4D-110 for the therapeutic uses for which they are being studied. 4D Molecular Therapeutics™, 4DMT™, Therapeutic Vector Evolution™, and the 4DMT logo are trademarks of 4DMT. 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 and expectations regarding 4D-310. 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 SmithEvoke CanaleKatherine.Smith@evokegroup.com Investors: Julian PeiHead of Investor Relations and Corporate CommunicationsInvestor.Relations@4DMT.com267-644-5097

EMERYVILLE, CA, USA I February 22, 2023 I 4D Molecular Therapeutics (Nasdaq: FDMT, ‘4DMT’), a clinical-stage biotherapeutics company harnessing the power of directed evolution for targeted genetic medicines, today announced updated interim safety and efficacy data from the two 4D-310 INGLAXA Phase 1/2 clinical trials for Fabry disease cardiomyopathy. All three patients with 12 months of follow-up demonstrated improvement on cardiac contractility, exercise capacity and quality of life endpoints. Treatment was generally well tolerated, with transient acute aHUS being the only significant adverse event. Following a detailed investigation into the etiology of aHUS, 4DMT is engaging with the FDA to resume enrollment based on updated exclusion criteria and the highly effective rituximab/sirolimus immunosuppressive regimen. Data will also be presented at the WORLD Symposium ™ 2023 in Orlando, Florida on February 25th, 2023. “As demonstrated by the positive cardiac outcomes and biopsy biomarker data, these clinical proof-of-concept results with 4D-310 mark another important milestone for 4DMT,” said David Kirn, M.D., Co-founder and Chief Executive Officer of 4DMT. “This is our third proprietary vector that has been validated in clinical trials across three different therapeutic areas, which further validates our Therapeutic Vector Evolution platform. We are developing 4D-310 for the treatment of Fabry disease cardiomyopathy, which is the primary cause of death and not addressed by current therapies. In addition, our focus on patient safety led us to voluntarily pause enrollment on our two INGLAXA trials in January 2023 after observing an aHUS dose-limiting toxicity, and FDA subsequently put the program on clinical hold. Following an in-depth investigation in collaboration with world experts in immunology and AAV gene therapy to understand and mitigate aHUS, we are confident that the rituximab and sirolimus immunosuppressive regimen and updated exclusion criteria will mitigate safety risks and potentially further improve patient benefit.” INGLAXA Phase 1/2 Clinical Trials Design Cardiac Outcomes 4D-310 Cardiac clinical endpoints results summary (data cut-off date of December 5, 2022): Safety and Tolerability Next Steps for Development of 4D-310 About 4D-310 and Fabry Disease Cardiomyopathy 4D-310 utilizes the targeted and customized C102 vector to efficiently deliver a functional copy of the GLA gene and was designed for a unique mechanism of action, specifically to directly correct the AGA enzyme function within cardiomyocytes (heart muscle cells) after a single low dose IV administration. C102 was invented at 4DMT through our proprietary Therapeutic Vector Evolution platform; we created this platform utilizing principles of directed evolution, a Nobel Prize-winning technology. The product is designed to generate both high local production of AGA directly within critically affected organs, including heart, blood vessels and kidney, as well as the potential for systemic tissue cross-correction. This product design has the potential to treat and potentially reverse the cardiomyopathy in Fabry patients which is the leading cause of death, as well as other significant unmet medical needs in patients with Fabry disease. Affecting more than 50,000 people in the United States and European Union, Fabry disease is a genetic disorder of the GLA gene that results in the body’s inability to produce an enzyme called alpha-galactosidase or AGA, causing accumulation of the substrate globotriaosylceramide (Gb3) in critical organs, including the heart, kidney, and blood vessels. Such substrate accumulation can lead to life-threatening hypertrophic cardiomyopathy, heart failure, arrhythmias, various degrees of kidney dysfunction and cerebrovascular stroke. Fabry disease progression results in increased morbidity, mortality and cost of care. Significant unmet medical needs remain for these patients despite enzyme replacement therapy (ERT), the current standard of care. ERT requires biweekly intravenous dosing which markedly decreases patients’ quality of life. In addition, while benefit has been demonstrated in the kidney, ERT has not been shown to clearly benefit the heart. Cardiovascular disease remains the leading cause of death and disability in Fabry disease patients. About 4DMT 4DMT is a clinical-stage biotherapeutics company harnessing the power of directed evolution for targeted genetic medicines. 4DMT seeks to unlock the full potential of genetic medicines using its proprietary invention platform, Therapeutic Vector Evolution, which combines the power of the Nobel Prize-winning technology, directed evolution, with approximately one billion synthetic AAV capsid-derived sequences to invent targeted and evolved vectors for use in our product candidates. All of our vectors are proprietary to 4DMT and were invented at 4DMT, including the vectors utilized in our clinical-stage and preclinical pipeline product candidates: R100, A101, and C102. The Company is initially focused on five clinical-stage product candidates in three therapeutic areas for both rare and large market diseases: ophthalmology, pulmonology, and cardiology (Fabry disease cardiomyopathy). The 4DMT targeted and evolved vectors were invented with the goal of being delivered at relatively low doses through clinically routine, well-tolerated, and minimally invasive routes of administration, transducing diseased cells in target tissues efficiently, having reduced immunogenicity and, where relevant, having resistance to pre-existing antibodies. 4DMT is currently advancing five product candidates in clinical development: 4D-150 for wet AMD and DME, 4D-710 for cystic fibrosis lung disease, 4D-310 for Fabry disease cardiomyopathy, 4D-125 for XLRP, and 4D-110 for choroideremia. The 4D preclinical product candidates in development are: 4D-175 for geographic atrophy and 4D-725 for alpha-1 antitrypsin deficiency. 4D-150, 4D-710, 4D-310, 4D-125, and 4D-110 are our product candidates in clinical development and have not yet been approved for marketing by the US FDA or any other regulatory authority. No representation is made as to the safety or effectiveness of 4D-150, 4D-710, 4D-310, 4D-125, or 4D-110 for the therapeutic uses for which they are being studied. SOURCE: 4D Molecular Therapeutics