ADVM Adverum Biotechnologies Inc

Adverum Biotechnologies, Inc. (Nasdaq: ADVM), a clinical-stage gene therapy company targeting unmet medical needs in ocular and rare diseases, today announced the completion of a review of its ADVM-022 program, outlined plans for the next stage of development in wet age-related macular degeneration (wet AMD) and provided anticipated key milestones for 2022.

Dr. Laurent Fischer, M.D., president and chief executive officer at Adverum Biotechnologies, stated: “We are pleased to conclude a thorough review of the totality of data generated in all 55 patients treated with ADVM-022, in wet AMD and diabetic macular edema, some of whom have been followed for over 2.5 years. The data analysis confirms our strategy to advance development of ADVM-022 in wet AMD. We intend to conduct a Phase 2 trial of ADVM-022 in wet AMD at 2 X 10^11 vg/eye dose and a new lower 6 X 10^10 vg/eye dose, with three new enhanced steroid prophylaxis regimens including topical, intravitreal and a combination of systemic and local steroids. Based on learnings from the OPTIC and INFINITY trials and extensive preclinical datasets, as well as the input and support of experts and members of our Scientific Advisory Board, we are confident in the plans we are sharing today to safely develop ADVM-022 in wet AMD, realizing the promise and full potential of our innovative gene therapy.”

Dr. Fischer continued, “I believe we have the right plan in place to establish the benefits and safety of ADVM-022 and progress our development pipeline. We have focused our capital on our development strategy prudently, with adequate financial resources in hand to complete the planned Phase 2 study, and I very much look forward to providing an update on our progress in 2022.”

Future Development of ADVM-022 for Wet AMD:

Phase 2 Trial Design. Subject to regulatory review, Adverum is finalizing the design for a Phase 2 trial of ADVM-022 in wet AMD investigating the 2 X 10^11 (2E11) vg/eye dose and a lower 6 X 10^10 vg/eye (6E10) vg/eye dose, with three new enhanced steroid prophylaxis regimens, which the company anticipates will include a topical, intravitreal (IVT) and a combination of systemic and local steroids. The trial is expected to enroll approximately 72 patients and evaluate similar endpoints to the Phase 1 OPTIC trial in wet AMD. This study design is based on extensive analysis conducted by the company’s clinical development team and incorporates feedback from Adverum’s scientific advisory board and key retina, uveitis and gene therapy experts.

• IND Amendment. Adverum intends to file an investigational new drug (IND) amendment in the first half of 2022 and engage with the FDA with the aim of securing agreement on the Phase 2 trial design. The company anticipates completing this process by mid-2022.
• Phase 2 Initiation. Adverum is beginning preparations for the Phase 2 trial of ADVM-022 in wet AMD, with the intention of dosing the first patient in Q32022. Early feedback from potential Phase 2 investigators suggests completion of trial enrollment by year end 2022.
• Fully Resourced. Adverum reiterates its expectation that its cash position is sufficient to fund the company’s operations, including its development plans for ADVM-022, into 2024.

"The long-term efficacy seen in the OPTIC trial after a single injection of ADVM-022 has been remarkable for my patients, who required frequent injections prior to entering the trial. The long-term safety data supports using the lower 2E11 vg/eye dose and a new lower 6E10 vg/eye dose with an enhanced steroid prophylaxis regimen. I look forward to evaluating ADVM-022’s potential to provide a safe and durable gene therapy from a single, in-office injection in patients with wet AMD in the upcoming Phase 2 trial," said Arshad M. Khanani M.D., M.A., managing partner and director of clinical research, Sierra Eye Associates, member of Adverum’s Scientific Advisory Board, and the highest enrolling investigator in the wet AMD Phase 1 OPTIC trial.

Review of ADVM-022 Program:

During the second half of 2021, Adverum undertook a comprehensive review of the company’s ADVM-022 program, including analysis of its preclinical and clinical data. The review solidified the following rationale underpinning the development strategy and Phase 2 study design outlined today for ADVM-022 in wet AMD:

• Phase 1 Clinical Outcomes of ADVM-022 in Wet AMD:
  • In October 2021, Adverum presented two-year follow-up data from its Phase 1 OPTIC study in wet AMD patients at the Retina Society’s 54th Annual Scientific Meeting. The data presented demonstrated a greater than 80% reduction in annualized anti-VEGF injections following the 2E11 vg/eye ADVM-022 IVT injection that is expected to be validated in the Phase 2 study.
  • ADVM-022 in wet AMD has been well tolerated and ocular inflammation was minimal and responsive to steroid eye drops. At latest visit, all 2E11 vg/eye patients were inflammation-free and none required any steroid eye drops to treat inflammation.
• Underlying Pathology and Patient Characteristics:
  • The INFINITY data in diabetic macular edema (DME) indicate that poorly controlled diabetes with presence of microvascular and macrovascular diabetic complications are important criteria in the identification of an appropriate patient population for ADVM-022, and these criteria have been considered in the proposed design of the Phase 2 trial in wet AMD.
• Patient Safety Update:
  • No clinically relevant reduction in intraocular pressure (IOP) was observed in the 2E11 vg/eye dose group in wet AMD or DME in either OPTIC or INFINITY trials, respectively. Additionally, in the OPTIC trial, clinically relevant IOP decreases were not observed at the 6 X 10^11 (6E11) vg/eye doses in wet AMD patients. No OPTIC patients with diabetes at both 6E11 and 2E11 in wet AMD, had clinically meaningful reduction in IOP.
  • Adverum worked with its advisors and investigators to develop a treatment plan to halt progression to hypotony in DME patients who previously received the 6E11 vg/eye dose (a dose-limiting toxicity) in the INFINITY trial. While Adverum is no longer pursuing an indication in DME or continuing development of the 6E11 vg/eye dose in wet AMD, all patients who experienced hypotony in the 6E11 vg/eye dose in INFINITY have stabilized and the majority recovered a significant amount of vision following the treatment plan.
• ADVM-022 Dosing:
  • The company will evaluate a new lower dose of 6E10 vg/eye alongside the 2E11 vg/eye dose used in the OPTIC study. Adverum plans to submit data, including relevant non-human primate protein expression supporting the 6E10 vg/eye dose in humans, at an upcoming 2022 medical conference.
  • Adverum also undertook an analysis of the impact of baseline neutralizing antibodies (NAbs) to AAV.7m8, the company’s novel capsid, on ADVM-022’s treatment benefit to potentially inform the planned Phase 2 trial design. Importantly, in OPTIC patients, the >80% reduction in annualized anti-VEGF injections observed at the 2E11 vg/eye dose further increased when patients with high NAbs were excluded. These data are expected to be submitted to a medical conference in 2022.
• Enhanced Steroid Prophylaxis:
  • Adverum, in consultation with experts in retina, uveitis and gene therapy, is pursuing three steroid prophylaxis regimens as part of the Phase 2 study with the goal of establishing a predictable and effective prophylaxis to administer with ADVM-022 IVT gene therapy. Subject to regulatory review, the steroid prophylaxis treatments under consideration includes a local topical steroid regimen that is longer in duration than in the OPTIC trial, a local-IVT steroid to facilitate patient adherence, and an oral systemic steroid in combination with a local steroid option.

Leadership Update:

Today, Adverum indicated its plans to hire a chief development officer and a chief medical officer. Additionally, the board of directors is actively pursuing the addition of two new directors with gene therapy and operational expertise with the departures of Mehdi Gasmi, Ph.D. and Thomas F. Woiwode, Ph.D. from the Board, reported separately today.

“On behalf of Adverum and its board, I would like to thank Mehdi and Tom for their invaluable contributions, distinguished service and counsel over the years. Mehdi was instrumental in advancing development of ADVM-022, serving as Adverum’s past president and chief scientific officer before joining the Board in 2019. Tom has been a tremendous board member and major investor, helping guide and finance the company from preclinical to clinical stage. We wish them both well in all their future endeavors,” said Patrick Machado, J.D., board chair of Adverum. “Adverum is in the process of considering additions to its board of directors, with a focus on adding further expertise in gene therapy and has engaged a search firm to identify a diverse slate of candidates.”

Expected Near-Term Milestones

• 1H2022 – Anticipated leadership appointments to executive team and Board of Directors
• 2Q2022 – Present protein expression data supporting an ADVM-022 6E10 vg/eye dose at a medical conference
• 2Q2022 – Present data on baseline NAbs and ADVM-022 efficacy at a medical conference
• Mid-2022 – Complete IND amendment process to enable initiation of Phase 2 trial of ADVM-022 in wet AMD
• 3Q2022 – Plan to dose first patient in Phase 2 trial of ADVM-022 in 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 evaluating 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 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 Adverum’s plans to advance a Phase 2 trial of ADVM-022 in wet AMD at 2 X 10^11 vg/eye dose and a lower 6 X 10^10 vg/eye dose; statements under the caption “Future Development of ADVM-022 for Wet AMD,” including Adverum’s expected current cash runway; Adverum’s plans to hire a chief development officer and a chief medical officer, and to add two new directors to the Board; and statements under the caption “Expected Near-Term Milestones.” 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 time and cost of product candidate development and regulatory uncertainties; the results of early clinical trials not always being predictive of future results; the potential for future complications or side effects in connection with use of ADVM-022; and other risks and uncertainties facing Adverum described more fully in Adverum’s Form 10-Q filed with the SEC on November 4, 2021, 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.

Inquiries

Anand ReddiVice President, Head of Corporate Strategy and External Affairs & EngagementAdverum Biotechnologies, Inc.T: 650-649-1358OrLaurence WattsGilmartin GroupT: 619-916-7620E: laurence@gilmartinir.com

Source: Adverum Biotechnologies, Inc.