— Company maintains focus on advancing ADVM-022 at low doses in patients with wet AMD —

REDWOOD CITY, CA, USA I October 09, 2021 I Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage gene therapy company targeting unmet medical needs in ocular and rare diseases, today is presenting data from the INFINITY clinical trial of ADVM-022 in patients with diabetic macular edema (DME) during the American Society of Retina Specialists (ASRS) 39th Annual Scientific Meeting and will be presenting an encore presentation of long-term data from the OPTIC trial of ADVM-022 for wet AMD on Monday, October 11, 2021 at 8:50 am CT (9:50 am ET). Adverum is planning clinical development of ADVM-022 at low doses (2 x 10^11 vg/eye and lower) in patients with wet age-related macular degeneration (wet AMD).

“While we are not planning any further development of ADVM-022 in DME, we are committed to transparently sharing data from the INFINITY study at this scientific meeting to inform future gene therapy development. We are truly grateful to the patients and investigators who took part in this study, our scientific advisors, and data and safety monitoring committee, who continue to support us by sharing their expertise,” said Laurent Fischer, M.D., president and chief executive officer at Adverum Biotechnologies. “Taken together with new long-term data from the OPTIC study presented at Retina Society’s meeting last weekend and again this Monday at ASRS, it has become clear that anti-VEGFs have different profiles in different indications and that the safety profile of our novel gene therapy was markedly different in DME patients with severe vascular and renal co-morbidities at our 6 x 10^11 dose. These findings further reinforce our strategy to focus the development of ADVM-022 on wet AMD, where we continue to observe a promising safety profile and durability of treatment effect that have been maintained in patients at a median of 1.7 years post-treatment with the 2 x 10^11 dose in OPTIC. We look forward to completing the review of our extensive data from the ADVM-022 program and to seeking input from investigators and regulatory agencies as we plan a Phase 2 trial with low doses and enhanced prophylaxis.”

“These collective results from INFINITY underscore the importance of underlying pathology of disease in addition to patient characteristics, dose selection, and optimal steroid prophylaxis in determining the therapeutic window which balances efficacy and safety for novel gene therapies,” said Charles C. Wykoff, M.D., Ph.D., director of research, Retina Consultants of Texas; chairman of research and clinical trials, Retina Consultants of America and a member of Adverum’s Scientific Advisory Board. “Focusing the future development of ADVM-022 on patients with wet AMD who require multiple anti-VEGF injections per year and evaluating low doses with enhanced prophylaxis is a prudent approach that keeps patient safety at the forefront while striving to address the unmet need of reducing treatment burden of frequent anti-VEGF injections.”

INFINITY Trial in DME Patients
INFINITY was a masked study in diabetic patients with DME initiated in May 2020, with cohorts evaluating two dose levels of ADVM-022 compared to a cohort with a single dose level of aflibercept. In early May 2021, the study was immediately unmasked to address patient safety and enhanced clinical management following an unexpected serious adverse event in a patient with DME treated at the high dose, presenting with hypotony, a rapid, clinically relevant decrease in intraocular pressure (IOP) with inflammation refractory to steroids and requiring surgical intervention. To date, two other patients required surgery and a total of five of the twelve patients treated with the high dose have experienced clinically relevant IOP events requiring additional immunosuppressive agents. All of these patients had a history of severe vascular and/or renal disease, and all events occurred 16-36 weeks post treatment. All patients in INFINITY have now been followed for a minimum of 36 weeks and no similar events have been seen in patients with DME treated at the low dose or in patients with wet AMD treated at either the high or low dose.

A photo accompanying this announcement is available at: https://www.globenewswire.com/NewsRoom/AttachmentNg/86364e7b-e506-4140-9f9f-ea97d03c80ba

INFINITY Trial Data in DME Patients Presented at ASRS
In data being presented from the INFINITY trial (June 22, 2021, cutoff date, n=34) at ASRS, patients with DME were randomized to receive either a single, IVT injection of low 2 x 10^11 vg/eye dose of ADVM-022, high 6 x 10^11 vg/eye dose of ADVM-022, or aflibercept.

  • Key Learnings: ADVM-022 dose and disease state appear to have an impact in determining the therapeutic window which balances efficacy and safety:
    • Dose-dependent inflammation observed in DME patients with dose-limiting toxicity at 6 x 10^11 vg/eye may be in part related to the study population which included patients with severe vascular and renal disease
    • No clinically relevant reduction in IOP was observed in the 2 x 10^11 vg/eye group
    • Further ADVM-022 development will focus on wet AMD and low doses (2 x 10^11 vg/eye and lower)

The data presentation is posted on the Publications page of the Pipeline section of the company’s website.

OPTIC Data in Wet AMD Patients 1-2 Years Post Treatment with ADVM-022
Last weekend, new long-term data from the OPTIC trial of ADVM-022 for wet AMD were presented at the Retina Society’s 54th Annual Scientific Meeting on October 1, 2021. An encore presentation of OPTIC data is scheduled for 8:50 am CT (9:50 am ET) on Monday, October 11, 2021, at ASRS and Adverum plans to post the data presentation on the Publications page of the Pipeline section of the company’s website at or prior to the start of the presentation.

  • Key Learnings: Data from the OPTIC trial (July 16, 2021 cutoff date, n=30) demonstrated in heavily treatment experienced patients that a single-IVT injection of ADVM-022 provides sustained durability, a greater than 80% reduction in the need for anti-VEGF and a promising safety profile.
    • Robust aflibercept expression and sustained efficacy providing CST stabilization observed
    • Low ADVM-022-related ocular adverse events occurred at the 2 x 10^11 vg/eye dose
    • No clinically relevant low IOP events observed in either dose
    • These results warrant further studies of ADVM-022 in wet AMD, including evaluation of low doses (2 x 10^11 vg/eye and lower) and enhanced prophylaxis
    • Long-term data from OPTIC and future studies may validate the importance of ADVM-022 in minimizing long-term fluctuations in CST

Anticipated Milestones for ADVM-022:

  • Plan to complete data analysis by year end 2021 to inform a protocol and seek investigator and regulatory feedback on a Phase 2 clinical trial in wet AMD
  • Plan to present additional long-term data from the OPTIC and OPTIC Extension studies in wet AMD

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 an in-office, 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 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.

SOURCE: Adverum Biotechnologies