Core Insights - Adverum Biotechnologies, Inc. will participate in a fireside chat at the H.C. Wainwright 5th Annual Ophthalmology Virtual Conference on August 13, 2025 [1] - The chat will feature Laurent Fischer, MD, and Szilárd Kiss, MD, discussing the company's advancements in gene therapy for ocular diseases [1] Company Overview - Adverum Biotechnologies is a clinical-stage company focused on gene therapy aimed at preserving sight in prevalent ocular diseases [3] - The company is developing a novel gene therapy candidate, ixoberogene soroparvovec (Ixo-vec), intended as a one-time intravitreal injection for patients with neovascular or wet age-related macular degeneration [3] - Adverum aims to transform the standard of care for ocular diseases by providing durable, single-administration therapies that reduce the need for frequent ocular injections [3]

Summary of Adverum Biotechnologies Conference Call Company Overview - **Company**: Adverum Biotechnologies (Ticker: ADVM) - **Industry**: Ocular Gene Therapy - **Focus**: Developing gene therapy to preserve sight in prevalent ocular diseases, particularly wet age-related macular degeneration (wet AMD) [1][3] Key Points and Arguments Market Potential - **Epidemiology**: Approximately 20 million patients worldwide suffer from wet AMD, with a projected market size of $13.5 billion by 2035 [4] - **Incidence**: Over 200,000 new diagnoses in the U.S. annually, with a 42% chance of bilateral disease within 2-3 years for affected patients [5] - **Current Treatment Costs**: Current anti-VEGF treatments account for 12% of Medicare Part B budget, with additional costs related to vision loss and fractures exceeding $80 billion in the U.S. [7][8] Product Development - **Ixabec**: A gene therapy utilizing aflibercept, designed to provide sustained anti-VEGF expression in the retina, potentially allowing for a "one and done" treatment approach [8][14] - **Delivery Method**: Administered via intravitreal injection, aligning with current treatment practices, thus minimizing procedural risks and complications [26][30] Clinical Data - **Phase 1 and 2 Studies**: - Nearly 50% of patients remained injection-free for four years in the OPTIC study [34] - Injection-free rates increased over time, indicating a potential disease-modifying effect [35] - Over 80% reduction in annualized anti-VEGF treatments [36] - Favorable safety profile with 100% of patients inflammation-free at year one through four [36] Patient Preference - High patient satisfaction with Ixabec, with 93% preferring it over previous treatments and 96% willing to recommend it to family and friends [39][40] Economic Impact - **Integration into Practice**: Ixabec is expected to enhance revenue and profitability for healthcare providers by front-loading treatment costs and reducing patient drop-off rates [31][32] - **Cost-Effectiveness**: Potential to lower overall healthcare costs by reducing treatment frequency and associated complications [33] Future Milestones - Upcoming long-term data presentation from the LUNA study in Q4 of this year [51] - Initiation of the AQUARIUS phase three study in the second half of the year [51] - Strong cash runway projected into the second half of the year, with confidence in funding ongoing clinical programs [53][54] Additional Important Content - **Challenges with Current Treatments**: Current anti-VEGF therapies require frequent injections, leading to patient burden and potential vision loss due to treatment gaps [10][18] - **Innovative Approach**: Ixabec aims to eliminate the oscillation of fluid in the retina, providing stable and durable visual outcomes [22][21] - **Regulatory and Commercial Success**: The ARTEMIS study is designed to maximize the probability of success in clinical and regulatory pathways [42] This summary encapsulates the critical insights from the Adverum Biotechnologies conference call, highlighting the company's innovative approach to treating wet AMD and the significant market opportunity it represents.

Industry Overview - The global wet age-related macular degeneration market is experiencing robust growth due to an aging population, increased awareness, and advancements in treatment options [2][4] - The market represents a significant challenge for healthcare systems globally, impacting quality of life and imposing economic burdens [2] Market Trends - Emerging trends include the development of long-acting therapies, integration of advanced diagnostic technologies like AI for early detection, and a focus on personalized medicine [3] - The demand for affordable, effective, and accessible treatments, especially in underserved regions, presents significant opportunities for market expansion [3] Treatment Approaches - Key therapeutic approaches include anti-VEGF therapies, photodynamic therapy, and laser surgeries, with anti-VEGF drugs holding the largest market share due to their efficacy [5] - Emerging treatments such as cell and gene therapy and stem cell therapy are gaining attention as potential future solutions [5] Demographic Drivers - The aging global population is the most significant driver for the market, with the UN projecting the number of people aged 80 and older to increase from 143 million in 2019 to 426 million by 2050 [6] Technological Advancements - Technologies like optical coherence tomography (OCT) and fundus photography enhance early detection of wet age-related macular degeneration, allowing for timely interventions [7] - The adoption of advanced diagnostic tools is driving market growth by enabling healthcare providers to identify patients who would benefit from treatments [7] Market Challenges - High treatment costs, side effects, limited access to care, and the challenge of offering curative treatments are significant factors restricting market potential [8] - Companies need to focus on reducing treatment costs, improving patient adherence, and advancing research for long-term therapies [8] Competitive Landscape - Major players in the market, such as Regeneron Pharmaceuticals Inc., Kubota Pharmaceutical Holdings Co. Ltd, and Adverum Biotechnologies Inc., are innovating to improve product effectiveness and comfort [9] - These companies are heavily investing in research and development to introduce new, technologically advanced solutions [9] Regional Insights - The market is diverse, with numerous players across different regions offering a wide range of products [10] - As consumer preferences shift towards discreet, comfortable, and affordable solutions, the market will continue to evolve, creating new opportunities for established and emerging companies [11]

Financial Status - Adverum held approximately $174 million in cash, cash equivalents, and short-term investments as of June 2024, which is expected to fund operations into late 2025[8] Ixo-vec Clinical Development (Wet AMD) - Ixo-vec demonstrates a potential best-in-class product profile for wet AMD treatment, aiming for a one-time IVT injection to turn the eye into an anti-VEGF biofactory[10] - In the LUNA trial, 76% of patients at the 6E10 dose remained injection-free at 26 weeks, and 88% preferred Ixo-vec to prior injections[10] - The LUNA Phase 2 study results show a 90% to 95% reduction in anti-VEGF treatment burden across both the 6E10 and 2E11 Ixo-vec doses, aligning with OPTIC study results[70] - In the LUNA trial, 76% to 83% of patients were injection-free across both Ixo-vec doses, consistent with the OPTIC trial[73] - Among patients with ≤ 6 prior injections, 90% were injection-free at Week 26 in the LUNA study[78] - 100% of patients previously receiving Faricimab (Vabysmo) remained injection-free across both Ixo-vec doses in the LUNA study[81] - Both Ixo-vec doses in the LUNA study maintained visual and anatomic outcomes through 26 weeks[84] - Local corticosteroid prophylaxis was effective in minimizing inflammation, with 91% of participants having no or minimal inflammation at any study visit through Week 26[105] Market Opportunity - The global wet AMD market is large and growing, with approximately 1.5 million patients in the U S and 20 million worldwide, and about 200,000 new cases annually[14] - The global sales for wet AMD are projected to be around $9 billion by 2025[17] - A 1% market share for a gene therapy like Ixo-vec could translate to approximately $260 million to $440 million in sales, assuming a 3-5 year benefit[18]

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 Points - Adverum Biotechnologies granted inducement awards to seven new employees, including non-qualified stock options for 32,620 shares and restricted stock units (RSUs) for 16,310 shares under its 2017 Inducement Plan [1][2] - The stock options have an exercise price of $3.33 per share, equal to the closing price on the grant date, and vest over four years [2] - The RSUs vest over three years, with one-third vesting on each anniversary of the applicable vesting commencement date [2] Company Overview - Adverum Biotechnologies is a clinical-stage company focused on gene therapy to preserve sight in prevalent ocular diseases, aiming to develop functional cures to restore vision and prevent blindness [3] - The company utilizes its proprietary intravitreal (IVT) platform to create durable, single-administration therapies, reducing the need for frequent ocular injections [3] - Adverum 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]

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].