Adverum Biotechnologies Completes IND Amendment and Prepares to Initiate the Phase 2 LUNA Trial of ADVM-022 in Wet AMD

- Cash runway extended into 2025 due to corporate restructuring to prioritize the clinical development of ADVM-022 and provide additional resources beyond anticipated one-year topline results of the Phase 2 LUNA trial

- LUNA trial will enroll up to 72 patients and examine two dose levels of ADVM-022 along with four new enhanced prophylactic steroid regimens

- Anticipate dosing the first patient with ADVM-022 in the third quarter of 2022

REDWOOD CITY, Calif., July 06, 2022 (GLOBE NEWSWIRE) -- Adverum Biotechnologies, Inc. ADVM, a clinical-stage company that aims to establish gene therapy as a new standard of care for highly prevalent ocular diseases, today announced that it has completed its Investigational New Drug (IND) amendment with the U.S. Food and Drug Administration (FDA) and is preparing to initiate the Phase 2 LUNA trial of ADVM-022, a single intravitreal (IVT) injection for wet age-related macular degeneration (wet AMD). The World Health Organization's Review Council and the U.S. Adopted Names Council has adopted the name ixoberogene soroparvovec (Ixo-vec) for ADVM-022 as the international nonproprietary name.

"On the heels of receiving the European Medicines Agency PRIME designation in the European Union, highlighting the unmet medical need in the current treatments for wet AMD, we are delighted to advance Ixo-vec into Phase 2 development. We amended our IND and are on track to dose the first patient in the Phase 2 LUNA trial for the treatment of wet AMD in the coming months. We have also optimized our manufacturing strategy and have a scalable approach designed to provide an ample supply of Ixo-vec to support our clinical development program through biologics license application filing," commented Laurent Fischer, M.D., president and chief executive officer at Adverum Biotechnologies. "Additionally, we have taken measures to restructure our operations, including reductions in both headcount and expenses to prioritize Ixo-vec's clinical development, and focus our pipeline strategy on highly prevalent ocular diseases. These restructuring measures are intended to enable us to fully support our ADVM-022 development plan and extend our expected cash runway by approximately one year into 2025, providing us with additional resources beyond one-year topline LUNA results based on our current development timeline. As of March 31, 2022 Adverum had $271.1 million in cash, cash equivalents and short-term investments."

"We are excited to initiate our Phase 2 LUNA trial this quarter. We designed the LUNA trial after a thorough review of data generated in all 55 study participants treated to date with a single injection of ADVM-022, some of whom have now demonstrated continuous and stable aflibercept expression for over three years. We have deepened our understanding of adeno-associated virus (AAV) mediated ocular gene therapy, including the inflammatory response to AAV, and this is informing our strategy to mitigate immunogenicity," stated Richard Beckman, M.D., chief medical officer at Adverum Biotechnologies. "The LUNA trial is designed to build on the strong efficacy profile demonstrated in the OPTIC trial in wet AMD and to establish the most effective pairing of an Ixo-vec dose and prophylactic steroid regimen to optimize the risk benefit in patients with this debilitating disease. We look forward to sharing greater detail on the LUNA trial after we dose the first subject."

The LUNA trial is a multicenter, double-masked, randomized, parallel-group Phase 2 trial evaluating two doses of Ixo-vec, including 2x10^11 vg/eye (2E11) and a new, lower-dose 6x10^10 vg/eye (6E10), in up to 72 patients with wet AMD. The LUNA trial will assess four new enhanced prophylactic steroid regimens, including local steroids and combinations of local and systemic steroids to test the relative contribution of local versus systemic AAV exposure on ocular inflammation. Specific regimens include topical difluprednate (Durezol), IVT Ozurdex, or a combination of either topical Durezol or IVT Ozurdex with oral prednisone.

The trial will randomize the participants equally between the 2E11 and 6E10 Ixo-vec doses across four prophylactic steroid regimens and will be conducted at approximately 40 sites in the U.S. and Europe. The primary endpoints will be similar to the OPTIC trial and focus on mean change in best corrected visual activity from baseline to one year and incidence and severity of adverse events. The study will also evaluate the effectiveness and tolerability of the prophylactic steroid regimens. Other data points will include protein expression of aflibercept at 10 weeks and an interim analysis at 26 weeks.

"Results from the OPTIC trial demonstrate that ADVM-022 at the 2E11 dose has the potential to provide an effective and durable treatment with manageable safety for patients with neovascular AMD, with sustained aflibercept levels through three years. This has resulted in a dramatic reduction in the number of required anti-VEGF injections, thus addressing an important area of unmet medical need. I look forward to participating as a LUNA investigator and studying the new, lower 6E10 dose. The LUNA study is also designed to help us determine a safe and effective prophylactic steroid regimen for patients," commented Arshad M. Khanani, M.D., M.A., FASRS, managing partner and director of clinical research, Sierra Eye Associates, clinical associate professor, University of Nevada, Reno School of Medicine, and highest enrolling investigator in the OPTIC trial.

About LUNA Trial of Ixo-vec in Wet AMD

Ixoberogene soroparvovec (Ixo-vec) is Adverum's clinical-stage gene therapy product candidate being developed for the treatment of wet AMD. Ixo-vec utilizes a propriety 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 has the advantage of being administered as a one-time IVT injection in the office and is designed to deliver long-term efficacy and reduce the burden of frequent anti-vascular endothelial growth factor (VEGF) injections, optimize patient compliance, and improve vision outcomes for patients with wet AMD.

The LUNA trial is a multicenter, double-masked, randomized, parallel-group Phase 2 trial evaluating two doses of Ixo-vec, including the 2x10^11 vg/eye dose and a new, lower 6x10^10 vg/eye dose, in wet AMD. The trial will randomize up to 72 participants equally across two doses and four prophylactic steroid regimens in 40 sites in the US and Europe.

About Wet Age-Related Macular Degeneration 

Wet 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 patients over 65 years of age, with a prevalence of approximately 20 million individuals worldwide living with this condition. The incidence of new cases of wet AMD is 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. 

About Adverum Biotechnologies

Adverum Biotechnologies ADVM is a clinical-stage company that aims to establish gene therapy as a new standard of care for a number of highly prevalent ocular diseases with the aspiration of developing functional cures for these diseases to restore vision and prevent blindness. Leveraging the research 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, ADVM-022, ixoberogene soroparvovec (Ixo-vec), 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 these 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 Adverum's plans to initiate a Phase 2 study in wet AMD to investigate the 2x10^11 vg/eye dose and a lower 6x10^10 vg/eye dose of ADVM-022, as well as new enhanced prophylactic steroid regimens, including local steroids and a combination of local and systemic steroids, planned for the third quarter of 2022, as well as the benefits Adverum expects from this trial, and extension of Adverum's expected cash runway into 2025. 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; 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 ADVM-022. 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, 2022 filed with the SEC on May 12, 2022. 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 Inquiries

Anand Reddi
Vice President, Head of Corporate Strategy and External Affairs & Engagement
Adverum Biotechnologies, Inc.
T: 650-649-1358
E: areddi@adverum.com