Preserving Sight for Life® Corporate Presentation October 2024 Forward-Looking Statements Statements contained in this document and any accompanying presentation regarding matters, events, statistics, or clinical or financial 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 plans and milestones related to Adverum's product candidates, clinical ...

Financial Performance - As of March 31, 2025, the company had an accumulated deficit of $1.1 billion and has not generated positive cash flow or net income since inception [76]. - The operating loss for the three months ended March 31, 2025, was $48.2 million, an increase of $19.0 million from the operating loss of $29.2 million in the same period of 2024 [89]. - Net loss for the three months ended March 31, 2025, was $47.0 million, compared to a net loss of $27.1 million for the same period in 2024, reflecting an increase of $19.9 million [89]. - The company expects to continue incurring net losses and operating cash outflows for at least the next several years as it develops its product candidates [97]. - General and administrative expenses increased by $5.7 million to $19.5 million for the three months ended March 31, 2025, from $13.8 million in the same period of 2024 [92]. - Other income, net decreased by $0.9 million to $1.2 million for the three months ended March 31, 2025, from $2.1 million for the same period in 2024 [93]. Cash Flow and Funding - Cash and cash equivalents decreased to $83.1 million as of March 31, 2025, down from $125.7 million as of December 31, 2024 [94]. - Net cash used in operating activities was $42.8 million for the three months ended March 31, 2025, compared to $23.2 million for the same period in 2024 [105]. - The company plans to raise substantial additional funding to finance operations through various means, including public or private equity or debt financings [98]. - For the three months ended March 31, 2024, the net cash used in operating activities was $23.2 million, primarily due to a net loss of $27.1 million from ongoing research and development activities [107]. - The net cash provided by financing activities for the three months ended March 31, 2024 was primarily $119.7 million from the issuance of common stock and Pre-Funded Warrants in Private Placements [109]. - Additionally, $0.1 million was generated from the exercise of stock options during the same period [109]. Research and Development - The company announced top-line 52-week results from the LUNA Phase 2 clinical trial, showing a reduction in annualized anti-VEGF injection rates of 88% for the 6E10 dose and 92% for the 2E11 dose [72]. - Nearly 50% of patients treated with Ixo-vec were injection-free through four years following treatment in the OPTIC trial [71]. - The company plans to initiate the AQUARIUS Phase 3 trial in the second half of 2025, following the initiation of the ARTEMIS trial in February 2025 [73]. - The LUNA trial enrolled 60 subjects, randomized between two doses, and assessed visual and anatomic outcomes at 52 weeks [72]. - The FDA granted Ixo-vec Fast Track designation in September 2018 and Regenerative Medicine Advanced Therapy designation in August 2024 [74]. - Research and development expenses include personnel-related costs, stock-based compensation, and external contract research expenses [81]. - Research and development expenses increased by $13.3 million to $28.7 million for the three months ended March 31, 2025, compared to $15.4 million for the same period in 2024 [90]. Operational Status - The company has not generated any revenue from product sales to date, relying on research and collaboration arrangements for revenue [80]. - The company currently has no operational clinical or commercial manufacturing facilities, relying on third-party contractors for clinical manufacturing [78].

Financial Performance - Cash, cash equivalents, and short-term investments were $125.7 million as of December 31, 2024, down from $153.2 million as of September 30, 2024, and up from $96.5 million as of December 31, 2023[4] - Net loss for the three months ended December 31, 2024, was $40.9 million, or $1.96 per share, compared to a net loss of $24.5 million, or $2.42 per share, for the same period in 2023[8] - Total stockholders' equity increased to $70.7 million as of December 31, 2024, compared to $67.2 million as of December 31, 2023[12] Expenses - Research and development expenses increased to $24.1 million for the three months ended December 31, 2024, compared to $15.3 million for the same period in 2023[8] - General and administrative expenses rose to $18.5 million for the three months ended December 31, 2024, compared to $11.7 million for the same period in 2023[8] Clinical Trials - The ARTEMIS trial, the first registrational intravitreal gene therapy trial for wet AMD, will evaluate Ixo-vec in approximately 284 patients[3] - The primary endpoint of the ARTEMIS trial is the mean change from baseline of best corrected visual acuity (BCVA) at one year with a non-inferiority margin of -4.5 letters[3] - The company plans to initiate the global AQUARIUS Phase 3 trial in the second half of 2025[5] - Results from the Phase 2 LUNA trial support the selection of the 6E10 dose, demonstrating potential best-in-class efficacy and favorable long-term safety[5] Regulatory Designations - Ixo-vec has received Fast Track and Regenerative Medicine Advanced Therapy (RMAT) designations from the FDA for the treatment of wet AMD[6]

Core Insights - Adverum Biotechnologies reported strong progress in its gene therapy pipeline, particularly with Ixo-vec for wet AMD, and initiated its first pivotal trial, ARTEMIS [2][4][5] - The company highlighted the potential of Ixo-vec to provide long-term vision preservation with a single injection, reducing the need for frequent anti-VEGF treatments [2][7][10] Financial Performance - For the three months ended March 31, 2025, Adverum reported a net loss of $47.0 million, or $2.25 per share, compared to a net loss of $27.1 million, or $1.65 per share for the same period in 2024 [9][15] - Research and development expenses increased to $28.7 million from $15.4 million year-over-year, driven by higher clinical trial costs and material production [9][15] - General and administrative expenses rose to $19.5 million from $13.8 million, attributed to higher facility and professional service costs [9][15] Pipeline Highlights - The ARTEMIS trial is the first registrational intravitreal gene therapy trial for wet AMD, enrolling approximately 284 patients [5][6] - New data presented at ARVO 2025 demonstrated the first human cell-level mapping of Ixo-vec transduction and aflibercept mRNA expression, supporting its potential for lifelong vision preservation [3][4] - The company plans to initiate the global AQUARIUS Phase 3 trial in the second half of 2025 and present two-year follow-up data from the LUNA study in Q4 2025 [9][10] Product Overview - Ixo-vec (ixoberogene soroparvovec) is designed for a one-time intravitreal injection, aiming to provide long-term efficacy and improve patient compliance compared to current treatment paradigms [7][10] - The product utilizes a proprietary AAV.7m8 vector, which has shown a five-fold increase in transduction efficiency compared to natural AAV2 [9]

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][3]. Group 1: Investigation Details - Pomerantz LLP is representing investors of Adverum and is looking into claims of securities fraud or other unlawful practices by the company and its officers or directors [1]. - The investigation was prompted by Adverum's disclosure that certain previously issued financial statements should no longer be relied upon due to non-cash errors related to tenant improvement allowances [3]. Group 2: Financial Impact - On March 31, 2025, Adverum announced it would restate its financial statements for the years ended December 31, 2022 and 2023, as well as unaudited quarterly financial information for 2023 and 2024 [3]. - Following the announcement, Adverum's stock price dropped by $0.54 per share, representing a decline of 12.36%, closing at $3.83 per share on April 1, 2025 [3]. Group 3: Company Background - Pomerantz LLP is recognized as a leading firm in corporate, securities, and antitrust class litigation, with a history of recovering significant damages for victims of securities fraud and corporate misconduct [4].

Core Viewpoint - Pomerantz LLP is investigating potential securities fraud or 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][3]. Group 1: Investigation Details - Pomerantz LLP is representing investors of Adverum and is looking into claims of securities fraud or other unlawful practices by the company and its officers/directors [1]. - Investors are encouraged to contact Pomerantz LLP for more information regarding the class action [2]. Group 2: Financial Disclosure - 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 [3]. - The company announced it will restate its financial statements for the years ended December 31, 2022, and 2023, as well as for the quarterly periods in 2023 and 2024 [3]. - Following this announcement, Adverum's stock price dropped by $0.54, or 12.36%, closing at $3.83 per share on April 1, 2025 [3].

Core Viewpoint - Pomerantz LLP is investigating potential securities fraud or 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][3]. Group 1: Investigation Details - Pomerantz LLP is representing investors of Adverum and is looking into claims of securities fraud or other unlawful practices by the company and its officers or directors [1]. - Investors are encouraged to contact Pomerantz LLP for more information regarding the class action [2]. Group 2: Financial Disclosure - 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 [3]. - The company announced it will restate its financial statements for the years ended December 31, 2022, and 2023, as well as for the quarterly periods in 2023 and 2024 [3]. - Following this announcement, Adverum's stock price dropped by $0.54 per share, a decline of 12.36%, closing at $3.83 per share on April 1, 2025 [3].

Core Viewpoint - The Schall Law Firm is investigating Adverum Biotechnologies, Inc. for potential violations of securities laws related to misleading financial statements and disclosures [1][2]. Group 1: Investigation Details - The investigation centers on whether Adverum made false or misleading statements and failed to disclose critical information to investors [2]. - Adverum announced in an SEC filing on March 31, 2025, that certain previously issued financial statements should no longer be relied upon due to non-cash errors in accounting for tenant improvement allowances related to an operating lease in North Carolina [2]. - The company plans to restate its financial statements for the years ended December 31, 2022, and 2023, as well as unaudited quarterly financial information for 2023 and 2024 [2]. - Following this announcement, Adverum's shares dropped by over 12% on April 1, 2025 [2]. Group 2: Shareholder Rights - The Schall Law Firm encourages shareholders who suffered losses to participate in the investigation and offers free consultations regarding their rights [3]. - The firm specializes in securities class action lawsuits and shareholder rights litigation, representing investors globally [3].

Core Viewpoint - Adverum Biotechnologies is advancing its gene therapy candidate Ixo-vec for the treatment of wet age-related macular degeneration (AMD), with promising clinical trial results and a strong pipeline of upcoming studies aimed at redefining treatment standards for patients [2][3][6]. Financial Results - As of December 31, 2024, Adverum reported cash, cash equivalents, and short-term investments of $125.7 million, a decrease from $153.2 million as of September 30, 2024, but an increase from $96.5 million as of December 31, 2023 [8]. - Research and development expenses for Q4 2024 were $24.1 million, up from $15.3 million in Q4 2023, attributed to higher material production and preparation for Phase 3 trials [8]. - General and administrative expenses rose to $18.5 million in Q4 2024 from $11.7 million in Q4 2023, driven by increased consultant fees and a non-cash tenant improvement allowance [8]. - The net loss for Q4 2024 was $40.9 million, or $1.96 per share, compared to a net loss of $24.5 million, or $2.42 per share, for the same period in 2023 [8][11]. Pipeline Highlights - The ARTEMIS trial, the first registrational intravitreal gene therapy trial for wet AMD, has been initiated, evaluating Ixo-vec against aflibercept in approximately 284 patients [3]. - The primary endpoint of ARTEMIS is the mean change from baseline in best corrected visual acuity (BCVA) at one year, with a non-inferiority margin of -4.5 letters [3]. - Long-term data from the LUNA trial support the selected 6E10 dose for the pivotal program, showing potential best-in-class efficacy and favorable long-term safety [3][4]. Upcoming Milestones - The global AQUARIUS Phase 3 trial is expected to be initiated in the second half of 2025, with the presentation of two-year long-term follow-up data from the LUNA trial planned for Q4 2025 [8][9]. Product Overview - Ixo-vec, a gene therapy product candidate, is designed for a one-time intravitreal injection to treat wet AMD, aiming to provide long-term efficacy and reduce the burden of frequent anti-VEGF injections [6][7]. - The therapy has received Fast Track and Regenerative Medicine Advanced Therapy designations from the FDA, as well as PRIME designation from the EMA [6]. Company Overview - Adverum Biotechnologies is focused on establishing gene therapy as a new standard of care for prevalent ocular diseases, with aspirations to develop functional cures to restore vision and prevent blindness [7].

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].