Adverum Presents 2-Year OPTIC Data Demonstrating Sustained Durability and Promising Safety Profile from Single Intravitreal Injection of ADVM-022 in Wet AMD Patients Who Previously Required Frequent Anti-VEGF Injections

-- Results featured in a presentation today at the Retina Society’s 54^th Annual Scientific Meeting --

-- Robust aflibercept protein expression sustained through 2 years --

-- Over 80% reduction in annualized anti-VEGF injection frequency at 2 x 10^11 vg/eye --

-- More than half of patients free of injection at median follow-up of 1.7 years at 2 x 10^11 vg/eye --

REDWOOD CITY, Calif., Oct. 01, 2021 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage gene therapy company targeting unmet medical needs in ocular and rare diseases, today announced new long-term data from the OPTIC clinical trial of ADVM-022 single, in-office intravitreal (IVT) injection gene therapy in patients requiring frequent anti-VEGF injections for their neovascular or wet age-related macular degeneration (wet AMD). Safety and efficacy data from patients followed through 2 years post injection are being presented at the Retina Society’s 54^th Annual Scientific Meeting in Chicago, Illinois. The presentation is available on the Publications page in the Pipeline section of Adverum’s website.

“We have now followed all wet AMD patients in the OPTIC trial for a minimum of a year, and in some cases beyond two years, after treatment with a single in-office intravitreal injection of ADVM-022. We are very pleased to report that both the promising safety profile and durability of treatment effect continue to be maintained in this patient population,” said Laurent Fischer, M.D., president and chief executive officer at Adverum Biotechnologies. “We are excited to see that ADVM-022 has the potential to extend the treatment benefit from weeks to years.”

Dr. Fischer stated, “We continue to analyze all data from patients receiving ADVM-022 in OPTIC and our INFINITY study in diabetic macular edema. We will present data from the latter on October 9 at the American Society of Retina Specialists Annual Scientific Meeting, followed by an encore presentation of OPTIC data on October 11. We look forward to completing our analysis of the data from our ADVM-022 program to meet with investigators and regulators as we outline our path forward in wet AMD. We are planning a Phase 2 trial to evaluate doses of ADVM-022 at 2 x 10^11 and lower with enhanced prophylaxis, with the goal of further improving the safety profile of ADVM-022 as we aim to deliver this novel therapy to patients.”

Key Efficacy Data (July 16, 2021 cutoff date) - 2 x 10^11 vg/eye dose (n=15), planned to be evaluated in a future Phase 2 trial:

• >80% reduction in annualized anti-VEGF injection frequency¹ in patients who previously required frequent injections
  
  
• >50% of patients (8/15²) after median follow-up of 1.7 years remained entirely free of any supplemental anti-VEGF injection
  
  
• Robust aflibercept expression levels continue to be sustained through 2 years after a single injection of ADVM-022
  
  
• Vision (mean BCVA³ versus baseline) maintained over time
  
  
• Retinal anatomy (mean CST⁴ versus baseline) maintained to improved
  

Key Safety Data (July 16, 2021 cutoff date) - 2 x 10^11 vg/eye (n=15) and 6 x 10^11 vg/eye (n=15) doses:

• All ADVM-022-related ocular adverse events (AE) were mild (81%) to moderate (19%) across all wet AMD patients in OPTIC, and patients have reached a follow-up period of between 1 and 2 years post treatment
  
  • No dose-limiting toxicities
  • No clinically relevant decreases in intraocular pressure
  • No vasculitis, retinitis, choroiditis, vascular occlusions, or endophthalmitis

• At the 2 x 10^11 vg/eye dose, ocular inflammation was minimal and responsive to steroid eye drops
  

1 Annualized rate (Before) = (number of IVTs in 12 months prior to ADVM-022) / (days from the first IVT in the past 12 months to ADVM-022 / 365.25)
Annualized rate (After) = (number of aflibercept IVTs since ADVM-022) / (days from ADVM-022 to the last study follow-up / 365.25)
2 All patients from Cohort 2 (n=6) and Cohort 3 (n=9) treated with the 2 x 10^11 vg/eye dose
3 Best corrected visual acuity (BCVA)
4 Central subfield thickness (CST)

“As the highest enroller in OPTIC, I have observed the potential of ADVM-022, a novel intravitreal gene therapy, to significantly reduce the treatment burden for my patients with neovascular age-related macular degeneration. In the latest data from the OPTIC trial, we have seen a manageable safety profile, robust aflibercept expression and sustained anatomical improvements 21 months after a single 2 x 10^11 dose of ADVM-022,” said Arshad M. Khanani, M.D., M.A., Managing partner and Director of Clinical Research, Sierra Eye Associates; Clinical Associate Professor, University of Nevada, Reno School of Medicine and a member of Adverum’s Scientific Advisory Board. "I look forward to continuing to provide input into the future development plans for ADVM-022 in patients with neovascular AMD.”

Anticipated Milestones for ADVM-022:

• Plan to present INFINITY data in diabetic macular edema (DME) at the American Society of Retina Specialists’ (ASRS) 39th Annual Scientific Meeting on Saturday, October 9, 2021 at 10:28 am CT (11:28 am ET). As previously disclosed, the company is no longer planning to develop ADVM-022 in DME.
• Plan to present an encore of OPTIC data at ASRS on Monday, October 11, 2021 at 8:50 am CT (9:50 am ET)
• Plan to complete data analysis by YE21 to develop a protocol and seek investigator and regulatory feedback on a Phase 2 clinical trial in wet AMD to evaluate low doses (2 x 10^11 vg/eye and lower) of ADVM-022 and enhanced prophylaxis
• Plan to present additional long-term data from the OPTIC and OPTIC Extension studies in wet AMD

About the OPTIC Trial of ADVM-022 in Wet AMD
This multi-center, open-label, dose-ranging trial is designed to assess the safety and tolerability of a single intravitreal (IVT) administration of ADVM-022 in patients with wet AMD. Patients in OPTIC are difficult-to-treat and had previously received frequent anti-vascular endothelial growth factor (VEGF) treatment. Patients received the 6 x 10^11 vg/eye dose of ADVM-022 in Cohort 1 (n=6) and Cohort 4 (n=9) and patients received the 2 x 10^11 vg/eye dose in Cohort 2 (n=6) and Cohort 3 (n=9). Patients in Cohorts 3 and 4 received six weeks of prophylactic steroid eye drops rather than 13 days of prophylactic oral steroids which were used in Cohorts 1 and 2. The primary endpoint of the trial is the safety and tolerability of ADVM-022 after a single IVT administration. Secondary endpoints include changes in best-corrected visual acuity (BCVA), measurement of central retinal thickness (CRT), as well as the need for supplemental anti-VEGF injections. Each patient enrolled will be followed for a total of two years.

For more information, please visit https://clinicaltrials.gov/ct2/show/NCT03748784 or the OPTIC trial or https://clinicaltrials.gov/ct2/show/NCT04645212 for the OPTIC Extension trial.

About ADVM-022 Gene Therapy
ADVM-022 utilizes Adverum’s propriety vector capsid, AAV.7m8, carrying a codon optimized aflibercept coding sequence under the control of a proprietary expression cassette. ADVM-022 is administered as a one-time intravitreal injection (IVT), designed to deliver long-term efficacy and reduce the burden of frequent anti-VEGF injections, and improve real-world vision outcomes for patients with wet age-related macular degeneration (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 ADVM-022 for the treatment of wet AMD.

About Wet AMD
Age-related macular degeneration (AMD) is a progressive disease affecting the macula, the region of the retina at the back of the eye responsible for central vision. In patients with wet AMD, an aggressive form of AMD, abnormal blood vessels grow underneath and into the retina. These abnormal blood vessels leak fluid and blood into and beneath the retina, causing vision loss.

Wet AMD is a leading cause of vision loss in patients over 60 years of age, with a prevalence of approximately 1.2 million individuals in the U.S. and 3 million worldwide¹. The incidence of new cases of wet AMD in the U.S. is approximately 150,000 to 200,000 annually, and this number is expected to grow significantly as the country’s population ages^2,3.

The current standard-of-care therapies for wet AMD are anti-VEGF proteins. These therapies can be burdensome, as patients generally require chronic intravitreal (IVT) injection of anti-VEGF protein every 4-12 weeks. Compliance with this regimen can be difficult for patients and their caregivers, leading to compliance deficiencies and loss of vision from underdosing. It is estimated that these standard-of-care branded anti-VEGF therapies used for the treatment of wet AMD, DR, retinal vein occlusion, and other ocular diseases generated in excess of $11 billion in sales worldwide in 2020⁴.

¹ Arch Ophthalmol. 2004;122(4):564-572. doi:10.1001/archopht.122.4.564.
² Brown GC, Brown MM, Sharma S, et al. The Burden of Age-Related Macular Degeneration: A Value-Based Medicine Analysis. Transactions of the American Ophthalmological Society. 2005.
³ California Retina Consultants. Advances in Wet AMD. Available at: https://www.californiaretina.com/advances-in-wet-amd/
⁴ Year-end 2020 financial statements from Regeneron, Roche, and Novartis.

About Adverum Biotechnologies
Adverum Biotechnologies (Nasdaq: ADVM) is a clinical-stage gene therapy company targeting unmet medical needs in serious ocular and rare diseases. Adverum is advancing the clinical development of its novel gene therapy candidate, ADVM-022, as a one-time, intravitreal injection for the treatment of patients with wet age-related macular degeneration. For more information, please visit www.adverum.com.

Forward-looking Statements
Statements contained in this press release regarding the 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 for ADVM-022 in treating wet AMD and statements under the heading “Anticipated Milestones for ADVM-022.” Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include risks inherent to, without limitation: Adverum’s novel technology, which makes it difficult to predict the time and cost of product candidate development and obtaining regulatory approval; the results of early clinical trials not always being predictive of future results; and the potential for future complications or side effects in connection with use of ADVM-022, such as the previously-reported Suspected Unexpected Serious Adverse Reaction (SUSAR) of hypotony (clinically-relevant decrease in ocular pressure) in Adverum’s INFINITY clinical trial evaluating ADVM-022 gene therapy for the treatment of DME. Risks and uncertainties facing Adverum are described more fully in Adverum’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2021 and any subsequent filings with the SEC under the heading “Risk Factors.” 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.

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