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]

Core Viewpoint - Adverum Biotechnologies is advancing its gene therapy candidate Ixo-vec for the treatment of wet age-related macular degeneration (AMD), with significant clinical data updates and a focus on commercialization strategies. Corporate Highlights - Jason Mitchell has been appointed as Chief Commercial Officer, bringing over 20 years of experience in retinal disease, including the launch of SYFOVRE® [3] - The company has $153.2 million in cash and equivalents, expected to fund operations into late 2025 [4][9] - The planned initiation of the pivotal Phase 3 trial is set for the first half of 2025 [4] Upcoming Anticipated Milestones - In Q4 2024, Adverum will present LUNA 52-week data, OPTIC 4-year clinical data, and updates on the Phase 3 trial design [4] - The initiation of the Phase 3 trial is planned for the first half of 2025 [4] Financial Results - For Q3 2024, cash and cash equivalents increased to $153.2 million from $96.5 million at the end of 2023 [4][9] - Research and development expenses were $20.4 million, slightly down from $20.7 million in Q3 2023 [4][10] - General and administrative expenses decreased to $9.8 million from $13.8 million in the same period last year [4][10] - The 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 [4][10] About Wet AMD - Wet AMD is a leading cause of blindness in individuals over 65, with approximately 20 million affected globally [5] - The incidence of new cases is expected to rise significantly as populations age, with AMD projected to impact 288 million people by 2040 [5] About Ixo-vec - Ixo-vec is a gene therapy product candidate designed for a one-time intravitreal injection to treat wet AMD, aiming to reduce the need for frequent anti-VEGF injections [6] - The therapy has received Fast Track and RMAT designations from the FDA, as well as PRIME designation from the European Medicines Agency [6]

Core Insights - Adverum Biotechnologies has appointed Jason L. Mitchell as chief commercial officer, who has over 20 years of experience in the commercial sector, particularly in retinal diseases [1][2] - The company is advancing its gene therapy candidate, ixoberogene soroparvovec (Ixo-vec), which is currently in Phase 2 clinical trials and aims to establish a new standard of care for wet age-related macular degeneration (wet AMD) [1][5] - Adverum plans to announce 52-week data from the LUNA trial and pivotal program details in Q4 2024, with the initiation of the pivotal program expected in the first half of 2025 [1][2] Company Overview - Adverum Biotechnologies is a clinical-stage company focused on developing gene therapies for prevalent ocular diseases, aiming to restore vision and prevent blindness [4][5] - The company utilizes a proprietary intravitreal (IVT) platform to create durable, single-administration therapies that reduce the need for frequent ocular injections [5] Leadership Background - Jason L. Mitchell previously led the successful launch of SYFOVRE® for geographic atrophy and has held significant roles in sales, marketing, and operations at various pharmaceutical companies [2][3] - His expertise is expected to enhance Adverum's strategy for introducing Ixo-vec as a leading gene therapy for wet AMD [2]

Core Viewpoint - Adverum Biotechnologies (ADVM) has been upgraded to a Zacks Rank 1 (Strong Buy) due to an upward trend in earnings estimates, which is a significant factor influencing stock prices [1][2]. Earnings Outlook - The Zacks rating upgrade reflects a positive earnings outlook for Adverum Biotechnologies, which is expected to positively impact its stock price [2]. - For the fiscal year ending December 2024, Adverum is projected to earn -$4.64 per share, representing a 60% change from the previous year's reported number [5]. Earnings Estimate Revisions - Analysts have increased their earnings estimates for Adverum Biotechnologies, with the Zacks Consensus Estimate rising by 8.4% over the past three months [5]. - The correlation between earnings estimate revisions and near-term stock movements is strong, indicating that tracking these revisions can be beneficial for investment decisions [4]. Zacks Rank System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with Zacks Rank 1 stocks historically generating an average annual return of +25% since 1988 [4]. - Adverum's upgrade to Zacks Rank 1 places it in the top 5% of Zacks-covered stocks, suggesting a strong potential for market-beating returns in the near term [7].

Company Overview - Adverum Biotechnologies, Inc. is a clinical-stage company focused on gene therapy for prevalent ocular diseases aiming to establish a new standard of care [2] - The company is developing a one-time, intravitreal injection therapy, ixoberogene soroparvovec (Ixo-vec), for patients with neovascular or wet age-related macular degeneration [2] - Adverum's goal is to create durable therapies that eliminate the need for frequent ocular injections, thereby transforming the treatment landscape for debilitating ocular diseases [2] Upcoming Events - Adverum will present at the H.C. Wainwright 26th Annual Global Investment Conference on September 10th at 3:30 p.m. ET [1] - The company will also participate in Chardan's 8th Annual Genetic Medicines Conference on October 1st at 8:00 a.m. ET [1] - Additionally, Adverum will be featured in the UBS Virtual Ophthalmology Day on October 2nd at 10:30 a.m. ET [1] Access to Information - On-demand webcasts of the presentations will be available under the Events and Presentations section on Adverum's website [1] - Each webcast will be accessible for at least 30 days following the events [1]

Core Viewpoint - Adverum Biotechnologies (ADVM) shows potential for significant upside based on Wall Street analysts' short-term price targets, with a mean estimate of $30 indicating a potential increase of 332.3% from the current price of $6.94 [1] Price Targets and Analyst Consensus - The mean estimate consists of seven short-term price targets with a standard deviation of $11.02, indicating variability among analysts [1] - The lowest price target of $12 suggests a 72.9% increase, while the highest target of $40 implies a surge of 476.4% [1] - A low standard deviation indicates a high degree of agreement among analysts regarding the stock's price movement direction [4] Earnings Estimates and Market Sentiment - Analysts have shown increasing optimism about ADVM's earnings prospects, with a 15.6% increase in the Zacks Consensus Estimate for the current year, supported by six upward revisions and no negative revisions [5] - ADVM holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimate factors, suggesting strong potential for near-term upside [5] Caution on Price Targets - While consensus price targets can provide insights, they should not be the sole basis for investment decisions due to historical inaccuracies in predicting actual stock price movements [3][4] - Analysts may set overly optimistic price targets influenced by business relationships, which can lead to inflated expectations [3]

Financial Position - As of June 30, 2024, the company had an accumulated deficit of $963.0 million and expects to incur substantial expenses and continuing losses in the foreseeable future [71]. - The accumulated deficit as of June 30, 2024, was $963.0 million, with cash, cash equivalents, and short-term investments totaling $173.8 million [99]. - The company has not generated positive cash flow or net income from operations since inception and may need substantial additional funding in the future [74]. - The company expects existing cash and cash equivalents to fund operations into late 2025, but may need to raise additional funds sooner due to various risks [99]. Revenue Generation - The company has not generated any revenue from product sales to date, relying instead on research, collaboration, and license arrangements with strategic partners [77]. - License revenue for the six months ended June 30, 2023, was $3.6 million, primarily from a milestone payment, while no license revenue was recorded for the same period in 2024 [89]. Clinical Trials 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 [68]. - Ixo-vec has received multiple regulatory designations, including Fast Track designation from the FDA and Priority Medicines designation from the EMA [69]. - The company plans to initiate a Phase 3 clinical trial of Ixo-vec in wet AMD in the first half of 2025 [68]. - Ixo-vec is designed to provide long-term durable therapeutic levels of aflibercept with a single in-office injection, targeting wet AMD [63]. - The company anticipates needing to raise substantial additional capital for the development and commercialization of product candidates, influenced by various factors including clinical trial outcomes and regulatory approvals [101]. - The company may delay or terminate development programs if unable to raise additional funds when needed [101]. Financial Performance - The net loss for the three months ended June 30, 2024, was $18.5 million, a decrease of $13.0 million compared to a net loss of $31.5 million for the same period in 2023 [88]. - The net loss for the six months ended June 30, 2024, was $43.3 million, compared to a net loss of $60.6 million for the same period in 2023 [103][104]. - Research and development expenses decreased by $3.5 million to $17.1 million for the three months ended June 30, 2024, from $20.6 million for the same period in 2023, primarily due to a reduction in facilities expenses [90]. - Research and development expenses for the six months ended June 30, 2024, decreased by $9.2 million to $32.5 million from $41.7 million for the same period in 2023, due to various cost reductions [91]. - General and administrative expenses decreased by $8.7 million to $3.8 million for the three months ended June 30, 2024, from $12.5 million for the same period in 2023, largely driven by a cumulative catch-up adjustment of sublease income [93]. - Other income, net increased by $0.8 million to $2.4 million for the three months ended June 30, 2024, from $1.6 million for the same period in 2023, primarily due to higher average invested balances [95]. Cash Flow and Financing - Net cash used in operating activities for the six months ended June 30, 2024, was $43.1 million, a decrease from $45.7 million in the same period of 2023 [102][103][104]. - Net cash provided by financing activities for the six months ended June 30, 2024, was $119.8 million, significantly higher than $0.2 million in the same period of 2023 [102][106][107]. - The company reported a net cash increase of $52.3 million for the six months ended June 30, 2024, compared to an increase of $42.9 million in the same period of 2023 [102]. - Net cash used in investing activities for the six months ended June 30, 2024, was $24.4 million, a decrease from $88.6 million provided in the same period of 2023 [102][105]. Operational Aspects - The company currently has no operational clinical or commercial manufacturing facilities and relies on third-party vendors for manufacturing [73]. - The company has a significant focus on research and development, with expenses primarily related to personnel, consulting, and clinical study materials [78]. Risk Factors - The company faces risks related to the emergence of competing technologies and adverse market developments [101]. Internal Controls - The evaluation of disclosure controls and procedures concluded that they were effective as of June 30, 2024 [110][111]. - There were no changes in internal control over financial reporting that materially affected the company during the most recent fiscal quarter [113].

```markdown [Overview and Key Highlights](index=1&type=section&id=Overview%20and%20Key%20Highlights) Adverum announced Q2 2024 results, selecting Ixo-vec's 6E10 dose for Phase 3 trials and reporting **$173.8 million** in cash - The 6E10 dose of Ixo-vec has been selected for Phase 3 pivotal trials following promising interim results[1](index=1&type=chunk) - The LUNA 26-week interim analysis demonstrated a potential best-in-class product profile for Ixo-vec, with similar efficacy and a more favorable safety profile compared to the earlier OPTIC study[1](index=1&type=chunk)[2](index=2&type=chunk) - The company holds **$173.8 million** in cash, cash equivalents, and short-term investments, which is expected to fund operations into late 2025[1](index=1&type=chunk)[8](index=8&type=chunk) [Ixo-vec Program Highlights](index=1&type=section&id=Ixo-vec%20Program%20Highlights) Ixo-vec achieved key milestones, including positive LUNA Phase 2 data leading to 6E10 dose selection for Phase 3, and FDA RMAT designation LUNA 26-Week Interim Analysis Highlights (6E10 dose) | Metric | Result | | :--- | :--- | | Injection-Free Patients | **76%** | | Safety Profile | Improved inflammatory profile compared to OPTIC | | Patient Preference (difluprednate-alone regimen) | **100%** would prefer Ixo-vec over prior treatments | - The U.S. FDA granted Regenerative Medicine Advanced Therapy (RMAT) designation to Ixo-vec for treating wet AMD, recognizing its transformative potential and offering benefits like intensive FDA guidance and potential priority review[4](index=4&type=chunk) [Corporate Updates and Outlook](index=2&type=section&id=Corporate%20Updates%20and%20Outlook) Adverum strengthened leadership with new appointments and outlined a roadmap for upcoming milestones, including Phase 3 trial initiation in H1 2025 - In June 2024, Dr. Rabia Gurses Ozden was appointed Chief Medical Officer, and Dr. Szilárd Kiss joined the Board of Directors[5](index=5&type=chunk)[6](index=6&type=chunk) Upcoming Anticipated Milestones | Timeline | Milestone | | :--- | :--- | | 2H 2024 | Continued FDA and EMA regulatory interactions | | 4Q 2024 | LUNA 9-month analysis clinical data | | 4Q 2024 | Phase 3 pivotal trial design update | | 1Q 2025 | LUNA 52-week analysis clinical data | | H1 2025 | Planned initiation of Phase 3 trial | [Financial Results](index=3&type=section&id=Financial%20Results) Adverum reported a Q2 2024 net loss of **$18.5 million**, reduced from Q2 2023 due to decreased expenses, with cash increasing to **$173.8 million** [Key Financial Metrics (Q2 2024)](index=3&type=section&id=Key%20Financial%20Metrics%20(Q2%202024)) In Q2 2024, Adverum's cash and investments grew to **$173.8 million**, with R&D and G&A expenses decreasing, improving net loss per share - Cash, cash equivalents, and short-term investments stood at **$173.8 million** as of June 30, 2024, compared to **$96.5 million** at the end of 2023[8](index=8&type=chunk) Operating Expenses (Three months ended June 30) | Expense Category | 2024 ($ millions) | 2023 ($ millions) | | :--- | :--- | :--- | | Research & Development | $17.1 | $20.6 | | General & Administrative | $3.8 | $12.5 | Net Loss Summary (Three months ended June 30) | Metric | 2024 ($ millions) | 2023 ($ millions) | | :--- | :--- | :--- | | Net Loss | $18.5 | $31.5 | | Net Loss per Share | $0.89 | $3.13 | [Financial Statements](index=5&type=section&id=Financial%20Statements) The report includes selected data from the Consolidated Balance Sheet and Statements of Operations, providing a snapshot of financial position Selected Consolidated Balance Sheet Data | Metric | June 30, 2024 (Unaudited, $ thousands) | Dec 31, 2023 ($ thousands) | | :--- | :--- | :--- | | Cash, cash equivalents, and marketable securities | $173,827 | $96,526 | | Total assets | $253,803 | $173,010 | | Total stockholders' equity | $168,029 | $83,469 | Condensed Consolidated Statements of Operations (Three months ended June 30) | Metric | 2024 (Unaudited, $ thousands) | 2023 ($ thousands) | | :--- | :--- | :--- | | Total operating expenses | $20,882 | $33,065 | | Operating loss | $(20,882) | $(33,065) | | Net loss | $(18,476) | $(31,510) | [Company and Product Information](index=3&type=section&id=Company%20and%20Product%20Information) This section provides background on wet AMD, the target indication for Ixo-vec, detailing the disease, technology, and regulatory designations [About Wet Age-Related Macular Degeneration (AMD)](index=3&type=section&id=About%20Wet%20Age-Related%20Macular%20Degeneration%20(AMD)) Wet AMD is a leading cause of blindness globally, affecting **20 million** people, with current treatments posing a burden gene therapy aims to alleviate - Wet AMD is a leading cause of blindness in people over 65, with about **20 million** individuals affected worldwide[10](index=10&type=chunk) The standard treatment requires frequent, lifelong injections into the eye [About Ixo-vec in Wet AMD](index=3&type=section&id=About%20Ixo-vec%20in%20Wet%20AMD) Ixo-vec is Adverum's clinical-stage gene therapy for wet AMD, a one-time IVT injection for long-term efficacy, with multiple expedited regulatory designations - Ixo-vec is a one-time intravitreal (IVT) injection gene therapy designed to deliver long-term efficacy by carrying an aflibercept coding sequence via a proprietary AAV.7m8 vector capsid[11](index=11&type=chunk) - The therapy has received multiple designations to expedite its development, including Fast Track and RMAT from the FDA, PRIME from the EMA, and the Innovation Passport from the UK's MHRA[11](index=11&type=chunk)[12](index=12&type=chunk) ```

Group 1 - Adverum Biotechnologies is a clinical-stage company focused on gene therapy for prevalent ocular diseases, aiming to establish it as a new standard of care [2] - The company is developing a gene therapy candidate, ixoberogene soroparvovec (Ixo-vec), for a one-time intravitreal injection to treat neovascular or wet age-related macular degeneration [2] - Adverum's proprietary intravitreal platform is designed to provide durable therapies that eliminate the need for frequent ocular injections, thereby transforming the treatment paradigm for ocular diseases [2] Group 2 - Laurent Fischer, M.D., the CEO of Adverum, will participate in a fireside chat at the H.C. Wainwright 4th Annual Ophthalmology Virtual Conference on August 15, 2024 [1] - The webcast of the fireside chat will be accessible on Adverum's website, with a replay available for at least 30 days post-presentation [1]