Adverum Biotechnologies, Inc. provided an update on its ongoing Phase 2 LUNA trial evaluating ixoberogene soroparvovec (Ixo-vec) for the treatment of wet age-related macular degeneration (wet AMD). The primary LUNA cohort is evaluating the efficacy and safety of Ixo-vec in approximately 60 subjects randomized equally between the 2x10^11 vg/eye (2E11) and 6x10^10 vg/eye (6E10) doses. Subjects are also randomized across four prophylactic regimens.

Approximately 40 patients will receive one of two local ocular corticosteroid regimens. The remaining 20 subjects will receive one of the local ocular corticosteroid regimens, plus oral prednisone to inform the decision of whether to include an oral prophylactic in future trials. Recent Highlights: Innovation Passport: In April 2023, the United Kingdom?s Medicines and Healthcare Products Regulatory Agency granted Ixo-vec an Innovation Passport under the Innovative Licensing and Access Pathway (ILAP).

This designation is intended to accelerate the regulatory and market access interactions in the United Kingdom. To date, Adverum is the only ocular gene therapy company in wet AMD to have been granted Fast Track Designation by the U.S. FDA, PRIME designation by the European Medicines Agency and most recently the Innovation Passport under ILAP. Ixo-vec Nonclinical Data: Adverum presented an oral presentation of nonclinical data supporting Ixo-vec?s clinical development at the ASGCT 2023 Annual Meeting.

Ixo-vec Bilateral Dosing: Adverum presented data outlining the rationale for staggered, bilateral administration of Ixo-vec in patients with bilateral disease. Up to 42% of wet AMD patients experience neovascularization in the second eye in the first two to three years following diagnosis in the primary eye, indicative of an unmet need for many wet AMD patients globally. Ixo-vec was administered to one eye, then two months later to the fellow eye of NHPs.

Following the second, staggered administration of Ixo-vec, the fellow eye demonstrated aflibercept protein levels within the targeted therapeutic range. Staggered, bilateral intravitreal (IVT) administration of Ixo-vec was well tolerated, with encouraging therapeutic activity, as well as no increase in intraocular inflammation levels. These data demonstrate for the first time that the ocular humoral response in NHP is compartmentalized to the eye dosed with AAV capsid.

Ixo-vec Dosing at 2E11 and 6E10 Human Equivalent Doses: In an oral presentation of nonclinical data, Adverum demonstrated consistent aflibercept protein levels across the 2E11 and 6E10 doses in NHPs, indicating that the 6E10 dose may offer similarly robust levels of efficacy as the 2E11 dose with the potential of an improved inflammation profile. Ixo-vec Biodistribution: In a poster presentation, Adverum presented data on an evaluation of intraocular per cell biodistribution of Ixo-vec vg and aflibercept mRNA via in-situ hybridization in NHP eyes at the human equivalent dose of 2E11 and 6E10. Additional Pipeline Programs: Adverum unveiled IVT gene therapy programs for the treatment of Geographic Atrophy (GA) and for optogenetics at the ASGCT 2023 Annual Meeting.

Complement Factor I Program for Dry AMD /Geographic Atrophy: In a poster presentation, Adverum introduced its GA program delivering complement Factor I (CFI), a fundamental component and rate-limiting enzyme of the complement cascade, as a payload utilizing two IVT capsids: 7m8 and LSV1. Both the 7m8 and LSV1 capsids packaged with AAV-CFIco yielded robust intraocular human CFI levels in NHPs, and both proprietary capsids were well tolerated in non-human primates (NHPs). CaMeRaOpsin Program for Optogenetics: In a poster presentation, Adverum presented data on an optogenetic program utilizing an engineered melanopsin mutant that could serve as a therapeutic transgene for optogenetic vision restoration in indications with photoreceptor loss such as advanced GA.

Ray Therapeutics License: In June 2023, Adverum announced that it granted a non-exclusive, royalty-bearing license of its AAV.7m8 IVT vector capsid to Ray Therapeutics. Anticipated Milestones: Late third quarter 2023?Anticipate aflibercept protein levels for percentage of cohort with a minimum of 14 weeks of follow-up as of data cutoff. Fourth quarter 2023?

Anticipate LUNA preliminary efficacy and safety data for percentage of cohort.