Financial Restatement and Internal Controls - Adverum Biotechnologies identified non-cash errors in accounting for tenant improvement allowances related to an operating lease, necessitating restatement of financial statements for the years ended December 31, 2022 and 2023[15]. - The restated financial statements include corrections for misstatements affecting non-cash assets, liabilities, and general and administrative expenses[19]. - The Audit Committee concluded that the misstatements indicate a material weakness in internal control over financial reporting as of December 31, 2024[20]. - The company has identified a material weakness in internal control over financial reporting, which could adversely affect investor confidence and the value of its common stock if not remedied[30]. - Adverum's financial statements for the restated periods should be relied upon, as previously issued statements are no longer valid[18]. Financial Performance and Going Concern - Adverum has incurred significant operating losses since inception and expects to continue incurring losses for the foreseeable future[29]. - The company faces substantial doubt regarding its ability to continue as a going concern without raising additional funding[29]. Drug Development Challenges - Drug development is characterized by long timelines and high costs, with potential delays or failures at any stage[29]. - The company relies on third parties for various aspects of research and development, which may impact the success of clinical trials[29]. Intellectual Property and Competitive Landscape - Adverum's success is contingent on its ability to protect its intellectual property and proprietary technologies[29]. - The company anticipates facing intense competition from larger pharmaceutical companies and other entities in the biopharmaceutical industry[112]. - The proprietary AAV.7m8 vector is expected to compete with existing anti-VEGF therapies, which are widely accepted as standard-of-care treatments for wet AMD[113]. Clinical Trials and Product Development - The lead product candidate, Ixo-vec, is designed for a single in-office intravitreal injection to treat wet age-related macular degeneration (wet AMD), with top-line results from the LUNA Phase 2 trial showing a reduction in annualized anti-VEGF injections by 88% and 92% for the 6E10 and 2E11 doses, respectively[36]. - The OPTIC trial demonstrated that nearly 50% of patients were injection-free four years after Ixo-vec treatment, with an 86% reduction in annualized anti-VEGF injections[35]. - Ixo-vec has received several regulatory designations, including Fast Track designation from the FDA and Priority Medicines (PRIME) designation from the EMA, aimed at expediting its development and review[38]. - The company aims to initiate the second Phase 3 trial, AQUARIUS, in the second half of 2025, following the initiation of the ARTEMIS trial in March 2025[37]. - The ARTEMIS Phase 3 trial aims to enroll 284 patients, focusing on non-inferiority in mean BCVA change between Ixo-vec (6E10) and aflibercept (2mg Q8W)[93]. Market Potential and Treatment Demand - Approximately 20 million individuals worldwide are living with wet AMD, and the incidence of age-related macular degeneration is expected to impact 288 million people globally by 2040, with wet AMD accounting for about 10% of those cases[33]. - The global sales of standard-of-care anti-VEGF therapies for wet AMD were approximately $14 billion in 2023, highlighting the demand for effective treatments[40]. - Wet AMD affects approximately 20 million individuals worldwide, with an expected increase in incidence as populations age, potentially impacting 288 million people by 2040[52]. Manufacturing and Production - The company is focused on developing scalable manufacturing processes for Ixo-vec to meet the needs of a large patient population affected by wet AMD[39]. - The AAV manufacturing process utilizes the Baculovirus Expression Vector System (BEVS), designed for high yield and cost-effectiveness, capable of producing AAV vectors at a scale of up to 2000 liters[115]. - The company has produced multiple batches of Ixo-vec at proposed commercial scale for use in Phase 3 clinical trials[111]. - The company maintains control over key aspects of the manufacturing process, including scalable processes and GMP quality controls, while contracting clinical manufacturing to third parties[107]. Regulatory Environment and Compliance - The FDA regulates gene therapy products under the FD&C Act and PHS Act, requiring an investigational new drug application (IND) before human clinical testing[138]. - Clinical trials are conducted in three phases, with Phase 3 trials being pivotal for FDA approval[144]. - The FDA aims to review Biologics License Applications (BLAs) within six months for priority reviews and ten months for standard reviews, starting from the acceptance of the application[154]. - The centralized procedure for Marketing Authorization (MA) in the EU allows a single application to be submitted to the EMA, with a maximum evaluation timeframe of 210 days[164]. - The FDA has established expedited development and review programs for new drugs addressing serious or life-threatening conditions[174]. Pricing and Market Access Challenges - Increased scrutiny on drug pricing practices by U.S. federal prosecutors could negatively impact revenue and future profitability if regulatory proposals limit price increases[204]. - The company may need to conduct expensive pharmacoeconomic studies to demonstrate the medical necessity and cost-effectiveness of its products for third-party payer coverage[208]. - Legislative changes related to the Affordable Care Act could affect the number of individuals with health coverage, impacting the company's ability to commercialize product candidates[210]. - The Budget Control Act of 2011 triggered automatic reductions of Medicare payments to providers by 2% per fiscal year, effective April 1, 2013, and will remain in effect through 2032 unless further congressional action is taken[212].

Core Viewpoint - Pomerantz LLP is investigating potential securities fraud and unlawful business practices involving Adverum Biotechnologies, Inc. following the company's announcement of the need to restate its financial statements due to accounting errors [1][2]. Group 1: Company Financials - On March 31, 2025, Adverum disclosed that certain previously issued financial statements should no longer be relied upon due to non-cash errors related to tenant improvement allowances for an operating lease in North Carolina [2]. - Adverum will restate its financial statements for the years ended December 31, 2022 and 2023, as well as the unaudited quarterly financial information for the periods in 2023 and 2024 [2]. - Following this announcement, Adverum's stock price fell by $0.54 per share, or 12.36%, closing at $3.83 per share on April 1, 2025 [2]. Group 2: Legal Context - Pomerantz LLP is recognized as a leading firm in corporate, securities, and antitrust class litigation, with a history of fighting for victims of securities fraud and corporate misconduct [3]. - The firm has a track record of recovering multimillion-dollar damages for class members [3].

Core Insights - Adverum Biotechnologies is participating in the 2025 RBC Capital Markets Ophthalmology Virtual Conference on April 3, 2025, at 10:45 a.m. ET [1] - The company focuses on gene therapy as a new standard of care for prevalent ocular diseases, aiming to develop functional cures to restore vision and prevent blindness [3] Company Overview - Adverum Biotechnologies is a clinical-stage company that leverages its proprietary intravitreal (IVT) platform to create durable, single-administration therapies [3] - The company is evaluating its gene therapy candidate, ixoberogene soroparvovec (Ixo-vec), as a one-time IVT injection for patients with neovascular or wet age-related macular degeneration [3] - Adverum aims to transform the standard of care for debilitating ocular diseases, preserving vision and creating a significant societal impact globally [3]

Core Insights - Adverum Biotechnologies has initiated the ARTEMIS Phase 3 study to evaluate the efficacy and safety of Ixo-vec for treating wet age-related macular degeneration (AMD) [1][4] - The trial aims to demonstrate that a single injection of Ixo-vec is non-inferior to the standard treatment with aflibercept, potentially transforming the treatment landscape for wet AMD patients [5][10] Company Overview - Adverum Biotechnologies is a clinical-stage company focused on gene therapy to treat prevalent ocular diseases, aiming to establish a new standard of care [11][12] - The company is developing Ixo-vec, a one-time gene therapy designed to deliver long-term efficacy and reduce the burden of frequent anti-VEGF injections for wet AMD patients [10][11] Study Design - The ARTEMIS trial is a randomized, double-masked, sham-controlled study involving approximately 284 patients, including both treatment-naïve and previously treated individuals [7][8] - The primary endpoint is the mean change in best corrected visual acuity (BCVA) from baseline at one year, with a non-inferiority margin of -4.5 letters [2][8] Treatment Context - Wet AMD affects around 20 million individuals globally and is a leading cause of blindness in those over 65 years of age [9] - Current treatment requires frequent injections, with up to 42% of patients discontinuing treatment after two years, leading to poor long-term vision outcomes [4][9] Ixo-vec Characteristics - Ixo-vec utilizes a proprietary vector for a one-time intravitreal injection, aiming to provide stable therapeutic levels of anti-VEGF and improve patient compliance [10][11] - The therapy has received Fast Track and Regenerative Medicine Advanced Therapy designations from the FDA, indicating its potential as a transformative treatment option [10]

Core Insights - Adverum Biotechnologies has initiated the ARTEMIS Phase 3 study to evaluate the efficacy and safety of Ixo-vec for treating wet age-related macular degeneration (AMD) [1][4] - The trial aims to demonstrate that a single injection of Ixo-vec is non-inferior to the standard treatment with aflibercept [2][5] Study Design - ARTEMIS is a US-based, randomized, double-masked, sham-controlled trial involving approximately 284 patients, including both treatment-naïve and previously treated individuals [2][7] - The primary endpoint is the mean change in best corrected visual acuity (BCVA) from baseline at one year, with a non-inferiority margin of -4.5 letters [2][8] - All participants will receive three loading doses of aflibercept before administration of Ixo-vec [2][8] Significance of Ixo-vec - Ixo-vec is positioned as a potential best-in-class gene therapy that could provide long-term efficacy and reduce the treatment burden associated with frequent anti-VEGF injections [5][10] - The therapy is designed for a one-time intravitreal injection, which is expected to optimize patient compliance and improve vision outcomes [10][11] Unmet Medical Need - There is a significant unmet need for longer-acting therapies for wet AMD, with data indicating that up to 42% of patients discontinue treatment after two years, leading to poor long-term vision outcomes [4][9] - The current standard of care requires lifelong repeated injections, highlighting the potential impact of Ixo-vec in reducing treatment frequency [9][10] Regulatory Designations - Ixo-vec has received Fast Track and Regenerative Medicine Advanced Therapy (RMAT) designations from the FDA, as well as PRIME designation from the EMA [10][11]

Core Insights - Adverum Biotechnologies is a clinical-stage company focused on gene therapy for ocular diseases, aiming to establish a new standard of care [3] - The company will present at the Cowen 45th Annual Healthcare Life Sciences Conference on March 4, 2025 [1] - Adverum is developing a one-time intravitreal injection therapy, ixoberogene soroparvovec (Ixo-vec), for neovascular or wet age-related macular degeneration [3] Company Overview - Adverum Biotechnologies aims to develop functional cures to restore vision and prevent blindness through gene therapy [3] - The company utilizes a proprietary intravitreal (IVT) platform to create durable, single-administration therapies, reducing the need for frequent ocular injections [3] - Adverum's mission includes transforming the standard of care for debilitating ocular diseases and making a significant societal impact globally [3]

Company Overview - Adverum Biotechnologies, Inc. is a clinical-stage company focused on pioneering gene therapy as a new standard of care for prevalent ocular diseases [3] - The company aims to develop functional cures to restore vision and prevent blindness, utilizing its proprietary intravitreal (IVT) platform [3] - Adverum is working on a novel gene therapy candidate, ixoberogene soroparvovec (Ixo-vec), intended as a one-time IVT injection for patients with neovascular or wet age-related macular degeneration [3] Upcoming Events - Adverum will present at the Oppenheimer 35th Annual Healthcare Life Sciences Conference on February 11, 2025, at 4:40 p.m. ET [1] - The presentation will be accessible via a webcast, which will be available for replay on the company's website for at least 30 days following the event [2]

Core Viewpoint - Adverum Biotechnologies reported a quarterly loss of $1.30 per share, which was worse than the Zacks Consensus Estimate of a loss of $1.20, but an improvement from a loss of $3.30 per share a year ago [1][2] Financial Performance - The company posted revenues of $1 million for the quarter ended September 2024, exceeding the Zacks Consensus Estimate by 100%, compared to zero revenues a year ago [2] - Over the last four quarters, Adverum has surpassed consensus EPS estimates two times [2] - The current consensus EPS estimate for the upcoming quarter is -$1.20 on revenues of $0.53 million, and for the current fiscal year, it is -$4.64 on revenues of $1.03 million [7] Stock Performance - Adverum shares have declined approximately 1.6% since the beginning of the year, while the S&P 500 has gained 20.1% [3] - The stock currently holds a Zacks Rank of 3 (Hold), indicating it is expected to perform in line with the market in the near future [6] Industry Outlook - The Medical - Biomedical and Genetics industry, to which Adverum belongs, is currently ranked in the top 36% of over 250 Zacks industries, suggesting a favorable outlook [8] - Empirical research indicates a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can be tracked by investors [5]

Financial Performance - As of September 30, 2024, the company had an accumulated deficit of $990.2 million and has not generated positive cash flow or net income since inception[52]. - The company reported a net loss of $70.4 million for the nine months ended September 30, 2024, primarily due to ongoing research and development activities[73]. - Net loss before income taxes improved by $5.7 million to $(27.1) million for the three months ended September 30, 2024, compared to $(32.9) million for the same period in 2023[61]. - License revenue for the three months ended September 30, 2024, was $1.0 million, a decrease of $2.6 million compared to $3.6 million for the same period in 2023[62]. - The company has not generated any revenue from product sales to date, relying instead on research, collaboration, and license arrangements[54]. Cash Flow and Financing - As of September 30, 2024, the company had $153.2 million in cash, cash equivalents, and short-term investments, sufficient to fund operations into late 2025[53]. - During the nine months ended September 30, 2024, net cash used in operating activities was $64.2 million, compared to $69.6 million for the same period in 2023[73]. - Net cash provided by financing activities for the nine months ended September 30, 2024, was $119.8 million, mainly from the issuance of common stock and pre-funded warrants[75]. - The company expects that its existing cash and cash equivalents will be sufficient to fund operations into late 2025, but may need to raise additional funds sooner due to various risks and uncertainties[70]. - The company has a sales agreement with Cowen & Company to sell up to $100.0 million of common stock in an "at-the-market" offering, but no sales have been made as of November 4, 2024[70]. Research and Development - The LUNA Phase 2 trial of Ixo-vec was fully enrolled with 60 subjects, and interim analysis indicated maintenance of visual and anatomic outcomes[49]. - The company plans to initiate a Phase 3 clinical trial of Ixo-vec in wet AMD in the first half of 2025[49]. - Ixo-vec has received multiple regulatory designations, including Fast Track designation from the FDA and PRIME designation from the EMA[50]. - Research and development expenses include personnel-related costs, stock-based compensation, and external contract research expenses, with significant spending expected as the company advances into Phase 3 trials[55]. - Research and development expenses decreased by $0.3 million to $20.4 million for the three months ended September 30, 2024, from $20.7 million for the same period in 2023[65]. - Research and development expenses for the nine months ended September 30, 2024, were $52.9 million, a decrease of $9.5 million from $62.4 million for the same period in 2023[65]. General and Administrative Expenses - General and administrative expenses decreased by $4.0 million to $9.8 million for the three months ended September 30, 2024, from $13.8 million for the same period in 2023[66]. - General and administrative expenses for the nine months ended September 30, 2024, were $25.0 million, a decrease of $14.0 million from $39.0 million for the same period in 2023[66]. Other Income and Expenses - Other income, net increased by $0.4 million to $2.1 million for the three months ended September 30, 2024, from $1.7 million for the same period in 2023[67]. - Other income, net increased by $2.1 million to $6.5 million for the nine months ended September 30, 2024, from $4.4 million for the same period in 2023[67]. - Total operating expenses decreased by $4.3 million to $30.2 million for the three months ended September 30, 2024, from $34.5 million for the same period in 2023[61]. - Sublease income was $1.5 million for the three months ended September 30, 2024, compared to $1.3 million for the same period in 2023[61]. - The company reported $14.2 million in non-cash charges during the nine months ended September 30, 2024, primarily related to stock-based compensation[73]. Market and Manufacturing - The company utilizes third-party contract research organizations for clinical development and does not have its own operational clinical or commercial manufacturing facilities[52]. - The company aims to improve manufacturing processes for large-scale production to address the needs of prevalent diseases like wet AMD[51]. - The company incurred $37.4 million in net purchases from marketable securities during the nine months ended September 30, 2024, compared to $107.4 million in net maturities in the same period of 2023[74].

Financial Performance - Cash, cash equivalents, and short-term investments were $153.2 million as of September 30, 2024, up from $96.5 million as of December 31, 2023, expected to fund operations into late 2025[3] - Net loss for Q3 2024 was $27.1 million, or $1.30 per share, compared to a net loss of $32.9 million, or $3.26 per share, in Q3 2023[6] - Total assets as of September 30, 2024, were $234.4 million, compared to $173.0 million as of December 31, 2023[12] - Total stockholders' equity increased to $144.1 million as of September 30, 2024, from $83.5 million as of December 31, 2023[12] Expenses - Research and development expenses for Q3 2024 were $20.4 million, slightly down from $20.7 million in Q3 2023, attributed to lower facility-related expenses[4] - General and administrative expenses decreased to $9.8 million in Q3 2024 from $13.8 million in Q3 2023, due to lower facility-related and compensation expenses[5] Clinical Development - The company plans to present LUNA 52-week data and OPTIC 4-year data updates in Q4 2024, alongside a Phase 3 trial design update[3] - The planned initiation of the Phase 3 trial for Ixo-vec is set for the first half of 2025[3] - Ixo-vec is designed as a one-time intravitreal injection for the treatment of wet AMD, aiming to reduce the need for frequent injections[8] Leadership Changes - Jason Mitchell was appointed as Chief Commercial Officer in October 2024, bringing over 20 years of experience in commercial strategy for retinal diseases[2]