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4D-175 consists of a low-dose intravitreal R100 AAV vector and a codon-optimized transgene encoding high-functioning human complement factor H (sCFH)
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Complement factor H (CFH) with reduced function is a well-established genetic risk factor for geographic atrophy (GA), with approximately 75% of patients with age-related macular degeneration (AMD) carrying a high-risk CFH variant.
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More than 150 patients have been treated using the R100 vector, including those with wet AMD and diabetic macular edema, further proving the versatility of our Therapeutic Vector Evolution platform.
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Enrollment for Phase 1 of the GAZE clinical trial is expected to begin in H2 2024
EMERYVILLE, Calif., June 24, 2024 (GLOBE NEWSWIRE) — 4D Molecular Therapeutics (Nasdaq: FDMT, 4DMT or the Company), a leading clinical-stage genetic medicine company focused on unlocking the full potential of genetic medicine to treat large markets . diseases, today announced the US Food and Drug Administration (FDA) approval of an Investigational New Drug Application (IND) for 4D-175, an intravitreal vector-based gene therapy for R100, for the treatment of patients with GA.
GAZE’s Phase 1 clinical trial will evaluate 4D-175 in patients with GA secondary to AMD. The study design is an open-label, randomized, double-blind, placebo-controlled phase III study, in which patients will receive a single intravitreal injection of 4D-175 at one of three dose levels. Clinical trial objectives include safety and tolerability, definition of the Phase 2 trial dose level), gene expression and biological activity. IND approval enables the establishment of GAZE clinical study sites, and 4DMT expects to begin enrollment in H2 2024.
“GA is the leading cause of irreversible vision loss in more than 5 million people worldwide and while current bolus inhibitor treatments slow the progression of GA lesions, they require monthly or bimonthly intravitreal injections and show no visual benefit, ” he said. David Kirn, MD, Co-Founder and Chief Executive Officer of 4DMT. “4D-175 has the potential for permanent clinical benefit with a single intravitreal injection, greatly reducing the current treatment burden for patients, which can lead to better long-term vision outcomes. In Phase 1, we aim to investigate the safety levels and variable expression to select Phase 2 concentrations. We expect to begin enrollment in the Phase 1 clinical trial of GAZE in the second half of 2024.”
sCFH is a designed and improved version of CFH which can fit into adeno-associated virus (AAV) vectors with stable expression and proven full functionality in human cells. in vitroand also in many animal models and species alive. This formulation was co-invented by Wenchao Song, Ph.D., Professor of Pharmacology at the Perelman School of Medicine at the University of Pennsylvania. Dr. Song has extensive experience researching inflammatory, autoimmune and neurodegenerative diseases. Returning CFH works through targeted delivery of treatment sCFH transgene can restore normal complement regulation and reduce the retinal injury that manifests as progressive GA. Preliminary proof of concept for this approach using 1) humans sCFH is delivered systemically using an AAV vector in a mouse model of atypical hemolytic uremia (aHUS) and 2) a mouse version of sCFH delivered using an AAV vector in mouse models of C3 glomerulopathy and aHUS each showed recovery from complement dysfunction, reduced organ damage and improved survival.
Preliminary data from 4D-175 in vitro and alive character studies were presented at the 2024 ARVO Scientific Meeting in May; the presentation can be found on the 4DMT website here.
About Geographic Atrophy
Geographic atrophy (GA) is a highly prevalent disease with a significant unmet medical need. It is estimated that there are approximately 2.5 million people with GA in the US and major European markets, and an estimated 5 million people worldwide. GA is an advanced and severe form of age-related macular degeneration (AMD) that causes irreversible vision loss. GA is characterized by atrophic lesions in the outer retina that affect central vision and cause irreversible vision loss. Loss of central vision causes difficulty driving, reading, and completing basic daily tasks. As a result, GA has a significant impact on quality of life. Associated inflammation is recognized as a major contributor to the development and progression of GA. The only FDA-approved treatment for GA is additional inhibitors administered by intravitreal injection (IVT) once every 4-9 weeks.
About 4D-175 for Geographic Atrophy
4D-175 combines a customized and modified intravitreal vector, R100, with a codon-optimized transgene encoding high-functioning human complement factor H (sCFH) gene drug candidate designed to produce sustained expression of the mutation in the retina without significant inflammation following a single low-dose intravitreal injection. The sCFH loading is designed to restore the normal control of the supplement, which has the ability to slow down the disease.
About 4DMT
4DMT is a leading clinical stage genetic medicine company focused on unlocking the full potential of genetic medicine to treat major market diseases in ophthalmology and pulmonology. 4DMT’s proprietary platform, Therapeutic Vector Evolution, combines the power of Nobel Prize-winning technology, directed evolution, and approximately one billion synthetic AAV capsid-derived sequences to develop customized and modified vectors for use in our product candidates. wholly owned by partners. Our product design, formulation, and manufacturing engine help us to effectively build and develop our product distribution pipeline with the goal of revolutionizing medicines and treatments that can cure millions of patients. Currently, 4DMT is advancing through six clinical stages and one preclinical product candidate, each designed to address rare and large market diseases in ophthalmology, pulmonology and cardiology. In addition, 4DMT also promotes programming in the central nervous system through synergistic gene editing. 4D Molecular Therapeutics™, 4DMT™, Therapeutic Vector Evolution™, and the 4DMT logo are trademarks of 4DMT.
All of our product candidates are in clinical or pre-clinical development and have not yet been approved for sale by the US Food and Drug Administration (FDA) or any other regulatory authority. No representation is made regarding the safety or efficacy of our product candidates for the medical use 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 Personal Insurance Claims Reform Act of 1995, as amended, including, without limitation, implied and implied statements regarding the possibility of treatment, and the benefits of health of 4DMT product candidates, as well as plans, announcements and related timelines for 4D-175 clinical development. The words “may,” “might,” “will,” “could,” “would,” “must,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “anticipate,” ” estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “goal” and similar words or phrases are intended to identify forward-looking statements, although not all forward-looking statements check 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 could cause actual events or results to differ materially from those expressed or implied by any forward-looking statements. expectations. contained in this press release, including the risks and uncertainties that are described in more 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 on the Securities and Exchange Commission. . In addition, any forward-looking statements represent 4D Molecular Therapeutics’ views as of today only and should not be relied upon as representing its views as of any subsequent date. 4D Molecular Therapeutics expressly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made as to the accuracy of such forward-looking statements.
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