Neovascular AMD Gene Therapy Cleared for Trials


A phase 1 clinical trial of EXG102-031 is expected to initiate in the first quarter of 2023.

The FDA has cleared Exegenesis Bio’s investigational new drug application (IND) for its novel gene therapy EXG102-031 for the potential treatment of neovascular age-related macular degeneration (nAMD).

Exegenesis plans to initiate a phase 1 clinical trial to evaluate the safety, tolerability, and preliminary efficacy, as measured by visual acuity and central retinal thickness, of the gene therapy in the first quarter of 2023. The company stated that EXG102-031 is the first clinical stage gene therapy for treatment of nAMD that targets all known subtypes of vascular endothelial growth factor (VEGF) and angiopoietin-2 (ANG2). The therapy is administered via intraocular injection and consists of a recombinant adeno-associated virus vector that expresses a therapeutic fusion protein that is able to neutralize the subtypes of VEGF and ANG2.

"We are excited by the progress that our company has made and pleased to have reached this critical milestone; this is our second IND approval and the first in North America since the inception of Exegenesis Bio 3 years ago," Zhenhua Wu, chief executive officer, Exegenesis Bio, said in a statement. "This is a strong validation of the world-class R&D, CMC, quality and regulatory capabilities that we have built. We look forward to accelerating development of our innovative gene therapy pipeline in areas with high unmet medical needs and bringing these innovative treatments to patients worldwide."

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The first gene therapy that Exegenesis received IND approval for is EXG001-307, a novel AAV gene therapy designed to express the SMN gene. The company presented preclinical data on EXG001-307 that demonstrated the therapy’s efficacy in mouse models of spinal muscular atrophy at the 2022 American Society of Gene & Cell Therapy (ASGCT) meeting. The data were compared to that of the approved gene therapy onasemnogene abeparvovec (Zolgensma) and the novel therapy showed higher tissue-specific SMN expression and reduced off-target toxicity.

“EXG001-307... has demonstrated a better extended survival, greater motor improvement and significantly reduced toxicity in a mouse model of SMA,” Wu, who was first author of the poster, and colleagues, wrote.

EXG001-307 and EXG102-031 are Exegenesis’ lead candidates in the pipeline, however, the company has gene therapy programs in hemophilia A, phenylketonuria, and an undisclosed liver target in IND-enabling studies, and has programs in Parkinson disease, Bietti’s crystalline dystrophy, and 2 other undisclosed programs targeting central nervous system and ocular diseases in the discovery phase.

1. Exegenesis Bio announces FDA clearance of investigational new drug (IND) application for EXG102-031; A novel gene therapy for the treatment of neovascular age-related macular degeneration (nAMD). News release. Exegenesis. January 18, 2022.
2. Wu Z, Zhu P, Wang Q, et al. A novel AAV-based gene therapy for spinal muscular atrophy. Presented at: ASGCT 25th Annual Meeting, May 16–19, 2022, Washington, D.C. and virtual. Abstract #541.
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