Adverum Biotechnologies Presents Nonclinical Data in Support of Ixo-vec’s Phase 2 Clinical Development at ASGCT 2023 Annual Meeting

REDWOOD CITY, Calif., May 18, 2023 (GLOBE NEWSWIRE) — Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases, today announced new nonclinical data supporting the use of ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022) at the American Society of Gene & Cell Therapy (ASGCT) 2023 Annual Meeting in Los Angeles, California. Ixo-vec is currently being evaluated in the Phase 2 LUNA trial in wet age-related macular degeneration (wet AMD). The data being presented at ASGCT are featured in an oral presentation on the identification of dose-dependent immune landscape signatures in nonhuman primates (NHPs), an oral presentation of nonclinical data that supports the potential for staggered, bilateral dosing of Ixo-vec and a poster presentation evaluating Ixo-vec per cell vector genome (vg) biodistribution and mRNA expression in NHPs. “Our nonclinical data presented at ASGCT support the use of the human equivalent doses 2×10^11 vg/eye and 6×10^10 vg/eye doses being evaluated in the LUNA trial,” stated Brigit Riley, Ph.D., chief scientific officer at Adverum. “It is well understood that gene therapy products cause dose-dependent inflammation regardless of serotype and route of administration.   We were pleased to see that the Ixo-vec doses advanced in the LUNA trial can achieve therapeutic aflibercept levels in NHPs that improve the inflammation profile.   These data support our development efforts around lower dose administration of Ixo-vec and enhanced prophylactic corticosteroid regimens being evaluated in LUNA. We look forward to sharing interim 14-week aflibercept protein levels for a percentage of the cohort in the LUNA trial in the third quarter of this year.” Data Highlights Ixo-vec aflibercept protein levels were consistent across 2×10^11 vg/eye (2E11) and 6×10^10 vg/eye (6E10) doses, suggesting lower doses may offer similarly robust levels of efficacy with improved inflammation profiles.Immune landscape signatures demonstrated a dose-dependent activation of innate and adaptive immune response consistent with AAV-associated inflammation. No evidence that harnessing ocular cells as biofactories to produce aflibercept leads to aflibercept expression-related toxicity/inflammation.No evidence that ciliary body architecture was directly affected by Ixo-vec. In an encore to the company’s recent presentation at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, 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 and 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. 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 revealed: Intraocular fluid convection together with anterior and posterior fluid outflow influence ubiquitous distribution of vgs from IVT-delivered ocular gene therapy products.Ixo-vec drives aflibercept mRNA expression in anterior and posterior tissues with most prominent expression in the macula and peripheral retina.Localization of aflibercept mRNA expression in retina is influenced by the internal limiting membrane (ILM) barrier.We are now able to identify on a per cell basis what ocular cells produce Ixo-vec together with a more robust picture of vector flow within the eye that informs ongoing Ixo-vec product development. The ASGCT poster and oral presentations will be made available on the Publications page of the Adverum website. About Wet Age-Related Macular DegenerationWet AMD, also known as neovascular AMD or nAMD, is an advanced form of AMD affecting approximately 10% of patients living with AMD. Wet AMD is a leading cause of blindness in people over 65 years of age, with approximately 20 million individuals worldwide living with this condition. New cases of wet AMD are expected to grow significantly worldwide as populations age. AMD is expected to impact 288 million people worldwide by 2040, with wet AMD accounting for approximately 10% of those cases. Additionally, wet AMD is a bilateral disease and incidence of nAMD in the second eye is up to 42% in the first two to three years. About Ixo-vec in Wet AMDAdverum is developing ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), its clinical-stage gene therapy product candidate, for the treatment of wet AMD. Ixo-vec utilizes a proprietary vector capsid, AAV.7m8, carrying an aflibercept coding sequence under the control of a proprietary expression cassette. Unlike other ophthalmic gene therapies that require surgery to administer the gene therapy under the retina (sub-retinal approach), Ixo-vec is designed to be administered as a one-time IVT injection in the physician’s office, deliver long-term efficacy, reduce the burden of frequent anti-vascular endothelial growth factor (VEGF) injections, optimize patient compliance and improve vision outcomes for patients with wet AMD. In recognition of the need for new treatment options for wet AMD, the U.S. Food and Drug Administration granted Fast Track designation for Ixo-vec for the treatment of wet AMD. Ixo-vec also received PRIME designation from the European Medicines Agency and the Innovation Passport from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency for the treatment of wet AMD. About LUNA Trial of Ixo-vec in Wet AMDThe LUNA trial is a double-masked, randomized, Phase 2 trial being conducted at approximately 40 sites in the U.S. and Europe. LUNA will evaluate Ixo-vec in subjects with wet AMD who are 50 years or older and have demonstrated a response to anti-VEGF treatment. Up to 72 subjects will be randomized equally between the previously evaluated 2E11 vg/eye dose and a new, lower 6E10 vg/eye dose. Four prophylactic corticosteroid regimens will be studied with the aim of establishing a prophylactic corticosteroid regimen with minimal need for inflammation management post prophylaxis. Prophylactic regimens being evaluated include 22 weeks of a tapered regimen of topical difluprednate (Durezol®), a single administration of IVT dexamethasone (Ozurdex®), and a combination of either topical Durezol® or IVT Ozurdex® with up to 10 weeks of a tapered regimen of oral prednisone. All four prophylactic corticosteroid regimens in LUNA cover the period of peak immunogenicity observed in non-clinical studies and in the Phase 1 OPTIC study. The LUNA trial primary endpoints are mean change in best corrected visual acuity (BCVA) from baseline to one year, as well as the incidence and severity of adverse events. Important secondary endpoints in LUNA include the mean change in central subfield thickness (CST) from baseline to one year and assessing the effectiveness of prophylactic corticosteroid regimens on minimizing inflammation. Additionally, LUNA will assess aflibercept protein levels starting at Week 14 and include an interim analysis at Week 26. Study participants will have the option to enroll in a long-term extension study. About Adverum BiotechnologiesAdverum Biotechnologies (NASDAQ: ADVM) is a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases with the aspiration of developing functional cures to restore vision and prevent blindness. Leveraging the capabilities of its proprietary intravitreal (IVT) platform, Adverum is developing durable, single-administration therapies, designed to be delivered in physicians’ offices, to eliminate the need for frequent ocular injections to treat these diseases. Adverum is evaluating its novel gene therapy candidate, ixoberogene soroparvovec (Ixo-vec, formerly referred to as ADVM-022), as a one-time, IVT injection for patients with neovascular or wet age-related macular degeneration. By overcoming the challenges associated with current treatment paradigms for debilitating ocular diseases, Adverum aspires to transform the standard of care, preserve vision, and create a profound societal impact around the globe. For more information, please visit www.adverum.com. Forward-looking Statements Statements contained in this press release regarding events or results that may occur in the future are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include but are not limited to statements regarding the potential benefits of Ixo-vec in the treatment of wet AMD, the design of and enrollment in the LUNA trial, including the prophylactic corticosteroid regimens, and anticipated interim data from the LUNA trial. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including risks inherent to, without limitation: Adverum’s novel technology, which makes it difficult to predict the timing of commencement and completion of clinical trials; regulatory uncertainties; enrollment uncertainties; the results of early clinical trials not always being predictive of future clinical trials and results; and the potential for future complications or side effects in connection with use of Ixo-vec. Additional risks and uncertainties facing Adverum are set forth under the caption “Risk Factors” and elsewhere in Adverum’s Securities and Exchange Commission (SEC) filings and reports, including Adverum’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2023 filed with the SEC on May 11, 2023. All forward-looking statements contained in this press release speak only as of the date on which they were made. Adverum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. Corporate, Investor and Media Inquiries Anand ReddiVice President, Head of Corporate Strategy, External Affairs and EngagementAdverum Biotechnologies, Inc.T: 650-649-1358E: [email protected]