Summary of Adverum Biotechnologies (ADVM) FY Conference - August 13, 2025 Company Overview - **Company**: Adverum Biotechnologies - **Ticker**: ADVM - **Focus**: Developing potential one-time gene therapies for debilitating ocular diseases, specifically targeting wet age-related macular degeneration (AMD) [1][5] Core Points and Arguments - **Product Development**: - Adverum is in Phase 3 of developing Ixavec, an intravitreal gene therapy delivering aflibercept, which is the gold standard for wet AMD treatment [3][6] - Ixavec aims to provide sustained aflibercept production in the retina, potentially for life [6] - **Clinical Trial Results**: - In the OPTIC and LUNA trials, Adverum achieved 50% injection freedom and an 80% reduction in treatment burden for hard-to-treat patients [7] - The ARTEMIS trial is currently enrolling rapidly, indicating strong interest from investigators and patients [7] - **Market Need**: - There are over 1.5 million wet AMD patients in the US and over 20 million globally, with a significant annual diagnosis rate [9] - Despite existing anti-VEGF therapies, many patients experience vision decline due to under-treatment and missed injections, highlighting a large unmet need for more durable treatments [9][10] - **Competitive Landscape**: - The gene therapy approach is seen as transformational, offering the potential for injection-free treatment, which is highly favored by retina specialists [11][12] - Adverum's Ixavec is positioned as best-in-class with the highest injection-free rates compared to competitors [28] - **Patient Preference**: - In the LUNA trial, 93% of patients preferred Ixavec over previous treatments, and 95% would choose it if diagnosed with wet AMD in both eyes [25] - **Phase 3 Trial Details**: - The ARTEMIS trial will randomize approximately 284 patients into two cohorts: one receiving Ixavec and the other receiving aflibercept [27] - The primary endpoint is non-inferiority in best-corrected visual acuity (BCVA) at 52-56 weeks [27] Additional Important Content - **Safety Profile**: - Ixavec has shown a favorable safety profile with no serious adverse events related to the treatment, and inflammation, when it occurred, was manageable with local steroids [23][24] - **Long-term Efficacy**: - Patients in the OPTIC trial maintained vision levels and showed significant reductions in central subfield thickness over four years, indicating a disease-modifying effect [14][22] - **Market Potential**: - Wet AMD represents a large market opportunity for gene therapy, with the potential for mass market pricing due to high prevalence and annual incidence [28] - **Future Plans**: - Adverum plans to initiate a second Phase 3 trial, Aquarius, in the second half of the year and release additional long-term follow-up data from the LUNA trial in Q4 [29]

PART I [Financial Statements](index=5&type=section&id=Item%201.%20Financial%20Statements) Adverum Biotechnologies reported a widened net loss and significant decline in cash and equity for H1 2025, raising substantial doubt about its going concern ability [Condensed Consolidated Balance Sheets](index=5&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) As of June 30, 2025, total assets decreased significantly, liabilities increased, and stockholders' equity shifted to a $20.2 million deficit Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $42,418 | $60,652 | | Short-term investments | $1,979 | $65,039 | | Total current assets | $48,391 | $131,300 | | Total assets | $96,179 | $179,841 | | **Liabilities & Equity** | | | | Total current liabilities | $31,356 | $22,898 | | Total liabilities | $116,398 | $109,127 | | Total stockholders' (deficit) equity | $(20,219) | $70,714 | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) Net loss widened significantly for both the three and six months ended June 30, 2025, primarily due to increased research and development expenses Statement of Operations Summary (in thousands, except per share data) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Research and development | $37,125 | $17,097 | $65,872 | $32,507 | | General and administrative | $12,730 | $15,807 | $32,204 | $29,596 | | **Operating loss** | **$(49,855)** | **$(32,904)** | **$(98,076)** | **$(62,103)** | | **Net loss** | **$(49,191)** | **$(30,498)** | **$(96,210)** | **$(57,645)** | | Net loss per share | $(2.34) | $(1.46) | $(4.59) | $(3.08) | [Condensed Consolidated Statements of Stockholders' (Deficit) Equity](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders'%20(Deficit)%20Equity) Stockholders' equity transitioned from a positive balance to a $20.2 million deficit by June 30, 2025, primarily due to the net loss incurred - Stockholders' equity decreased from **$70.7 million** at December 31, 2024, to a deficit of **$20.2 million** at June 30, 2025[18](index=18&type=chunk) - The primary driver for the decrease in equity was the net loss of **$96.2 million** for the six months ended June 30, 2025[15](index=15&type=chunk)[18](index=18&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) Net cash used in operating activities nearly doubled for H1 2025, leading to an overall decrease in cash despite investing inflows, with no significant financing activities Cash Flow Summary (in thousands) | Cash Flow Activity | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(81,538) | $(43,089) | | Net cash provided by (used in) investing activities | $63,184 | $(24,354) | | Net cash provided by financing activities | $120 | $119,764 | | **Net (decrease) increase in cash** | **$(18,234)** | **$52,321** | [Notes to Condensed Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) Notes highlight substantial doubt about going concern, limited cash runway into Q4 2025, a significant subtenant lease default, and a recent $10.0 million private placement - There is substantial doubt regarding the Company's ability to continue as a going concern, as its cash, cash equivalents, and proceeds from an August 2025 financing are insufficient to fund operations for at least twelve months[28](index=28&type=chunk) - The company's cash runway, including proceeds from the August 2025 private placement, is expected to fund operations only into the **fourth quarter of 2025**[29](index=29&type=chunk) - A subtenant for the company's North Carolina premises defaulted on rent payments in March 2025, and Adverum remains obligated under the head lease with a total future rent obligation of **$118.3 million** and has initiated a lawsuit to recover damages[45](index=45&type=chunk)[47](index=47&type=chunk) - On August 11, 2025, the company entered into an agreement for a private placement to raise gross proceeds of **$10.0 million**[68](index=68&type=chunk)[69](index=69&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=17&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses Ixo-vec's clinical progress, increased R&D expenses, and reiterates substantial doubt about the company's going concern ability due to limited cash runway [Overview](index=17&type=section&id=Overview) Adverum is a clinical-stage company developing Ixo-vec gene therapy for wet AMD, with the ARTEMIS Phase 3 trial initiated and AQUARIUS planned, holding key regulatory designations - The lead product candidate is ixoberogene soroparvovec (Ixo-vec), a single, in-office intravitreal injection gene therapy for wet AMD[71](index=71&type=chunk) - The first Phase 3 trial, ARTEMIS, was initiated in February 2025, with enrollment expected to complete in Q1 2026 and top-line data in H1 2027[71](index=71&type=chunk)[77](index=77&type=chunk) - The second Phase 3 trial, AQUARIUS, is planned for Q4 2025, but is subject to the availability of additional funding[71](index=71&type=chunk)[77](index=77&type=chunk) - Ixo-vec has received several key regulatory designations: FDA Fast Track, FDA RMAT, EMA PRIME, and UK MHRA Innovation Passport[78](index=78&type=chunk) [Results of Operations](index=20&type=section&id=Results%20of%20Operations) Operating expenses significantly increased for H1 2025, driven by higher R&D for Ixo-vec's Phase 3 development and G&A expenses related to a defaulted sublease Comparison of Operating Expenses (in thousands) | Expense Category | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Research and development | $37,125 | $17,097 | $65,872 | $32,507 | | General and administrative | $12,730 | $15,807 | $32,204 | $29,596 | | **Total operating expenses** | **$49,855** | **$32,904** | **$98,076** | **$62,103** | - The increase in R&D expense was primarily driven by a **$27.3 million** increase in spending on Ixo-vec for the six-month period, mainly due to Phase 3 clinical development activities[96](index=96&type=chunk) [Liquidity, Capital Resources and Plan of Operations](index=22&type=section&id=Liquidity,%20Capital%20Resources%20and%20Plan%20of%20Operations) Liquidity is severely constrained, with cash expected to fund operations only into Q4 2025, leading to substantial doubt about going concern and necessitating significant additional capital - As of June 30, 2025, the company had **$44.4 million** in cash, cash equivalents, and short-term investments[101](index=101&type=chunk) - Management has determined there is substantial doubt about the company's ability to continue as a going concern for the next twelve months[101](index=101&type=chunk)[105](index=105&type=chunk) - Existing cash, combined with the **$10.0 million** gross proceeds from the August 2025 Private Placement, is expected to fund operations only into the **fourth quarter of 2025**[105](index=105&type=chunk) - The company will need to raise substantial additional funding to finance its operations and continue clinical development, with partnering discussions active and ongoing[106](index=106&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=25&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, Adverum Biotechnologies, Inc. is not required to provide the information for this item - The company is not required to provide information on market risk as it qualifies as a smaller reporting company[119](index=119&type=chunk) [Controls and Procedures](index=25&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded disclosure controls and procedures were ineffective as of June 30, 2025, due to a material weakness in lease accounting controls, with remediation ongoing - A material weakness in internal control over financial reporting was identified as of December 31, 2024, related to controls over lease accounting[121](index=121&type=chunk) - As a result of this material weakness, the Chief Executive Officer and Chief Financial Officer concluded that disclosure controls and procedures were not effective as of June 30, 2025[124](index=124&type=chunk) - A remediation plan is underway, involving increased rigor, engagement of outside experts, and enhanced monitoring of lease agreements and subtenant creditworthiness[122](index=122&type=chunk) PART II—OTHER INFORMATION [Legal Proceedings](index=26&type=section&id=Item%201.%20Legal%20Proceedings) The company initiated a lawsuit against its subtenant and guarantor for defaulting on a North Carolina sublease, leaving Adverum responsible for a $118.3 million head lease obligation - On April 10, 2025, the company initiated a lawsuit against its subtenant (AMP) and the guarantor (Jaguar) for defaulting on a sublease for its North Carolina (NC) Premises[127](index=127&type=chunk) - The default occurred after the subtenant failed to remit rent payments from March 2025 onwards, and Adverum assumed responsibility for the payments, with a total future rent obligation of **$118.3 million** for the property[127](index=127&type=chunk) [Risk Factors](index=26&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant risks including substantial doubt about its going concern ability, dependence on a single product candidate, high development costs, and a material weakness in internal controls [Risks Related to Financial Position and Need for Capital](index=26&type=section&id=Risks%20Related%20to%20Our%20Financial%20Position%20and%20Need%20for%20Capital) Substantial doubt exists about the company's going concern ability, with cash funding operations only into Q4 2025, necessitating significant additional capital that may cause dilution - There is substantial doubt regarding the company's ability to continue as a going concern, with cash expected to fund operations only into the **fourth quarter of 2025**[129](index=129&type=chunk)[130](index=130&type=chunk) - The company has incurred significant operating losses since inception and expects them to continue for the foreseeable future, having accumulated a deficit of **$1.2 billion** as of June 30, 2025[10](index=10&type=chunk)[138](index=138&type=chunk) - The company is exposed to risks from subtenant defaults, as evidenced by the default on its NC Premises lease, leaving Adverum with a future rent obligation of **$118.3 million**[140](index=140&type=chunk) [Risks Related to Discovery and Development](index=28&type=section&id=Risks%20Related%20to%20the%20Discovery%20and%20Development%20of%20Our%20Product%20Candidates) Business success depends on Ixo-vec, a single clinical candidate, facing long, expensive, and uncertain development with high failure risk, potential side effects, and unpredictable timelines for novel gene therapy - The business depends substantially on the success of its one clinical product candidate, Ixo-vec[141](index=141&type=chunk) - A dose-limiting toxicity was observed at the 6E11 dose in the prior INFINITY trial in DME subjects, leading to the discontinuation of that indication and highlighting safety risks[147](index=147&type=chunk) - The company's gene therapy platform is a novel technology, making it difficult to predict the time, cost, and probability of obtaining regulatory approval, especially for a broad patient population like wet AMD[157](index=157&type=chunk)[158](index=158&type=chunk) [Risks Related to Manufacturing](index=36&type=section&id=Risks%20Related%20to%20Manufacturing) Significant manufacturing risks for gene therapy include developing scalable processes, reliance on limited third-party contractors, potential production delays, and costly comparability studies for method changes - Developing a commercially viable, robust, and reliable manufacturing process for gene therapy is difficult, expensive, and time-consuming[179](index=179&type=chunk) - The company relies on a limited number of vendors, including single-source vendors, for manufacturing and testing, who are subject to significant regulation and may not meet requirements or have sufficient capacity[187](index=187&type=chunk) - Manufacturing is susceptible to product loss from contamination, equipment failure, or operator error, and any deviations could lead to supply disruptions, recalls, or termination of development programs[200](index=200&type=chunk)[202](index=202&type=chunk) [Risks Related to Reliance on Third Parties](index=41&type=section&id=Risks%20Related%20to%20Our%20Reliance%20on%20Third%20Parties) Heavy reliance on third parties for R&D and manufacturing reduces control, and their poor performance or delays could significantly impact clinical trials and regulatory submissions - The company relies on third parties for vector production, manufacturing, testing, clinical trials, and other R&D activities, reducing its control over these functions[203](index=203&type=chunk)[204](index=204&type=chunk) - If third-party CROs or investigators fail to meet deadlines, adhere to protocols, or meet regulatory requirements, clinical development could be delayed or unsuccessful[206](index=206&type=chunk)[208](index=208&type=chunk) [Risks Relating to Intellectual Property](index=42&type=section&id=Risks%20Relating%20to%20Our%20Intellectual%20Property) Success depends on uncertain patent and trade secret protection in a litigious landscape, reliance on potentially terminable third-party licenses, and U.S. government rights over some intellectual property - Commercial success depends on obtaining and maintaining patent and trade secret protection, which is uncertain and may not provide a competitive advantage[210](index=210&type=chunk) - The company relies on licenses from third parties for key technology, and the loss of these licenses could materially harm the business[227](index=227&type=chunk) - Some in-licensed intellectual property was developed with U.S. government funding and is subject to federal regulations, including "march-in" rights[246](index=246&type=chunk) [Risks Related to Commercialization](index=50&type=section&id=Risks%20Related%20to%20Commercialization%20of%20Our%20Product%20Candidates) Commercial success of Ixo-vec is not guaranteed due to approval uncertainties, market acceptance challenges, intense competition, uncertain reimbursement, and the company's lack of sales and marketing capabilities - The company faces intense competition from established therapies like Eylea and Vabysmo, as well as other gene therapies in development from companies like 4D Molecular Therapeutics and REGENXBIO[263](index=263&type=chunk)[267](index=267&type=chunk) - Market acceptance and sales will depend significantly on obtaining adequate coverage and reimbursement from third-party payers, which is a costly and uncertain process[272](index=272&type=chunk) - The company has no internal sales, marketing, or distribution capabilities and would need to build them or partner with a third party, which involves significant cost and risk[295](index=295&type=chunk) [Risks Related to Business Operations](index=59&type=section&id=Risks%20Related%20to%20Our%20Business%20Operations) Operational risks include negative public perception of gene therapy, dependence on key personnel, intense competition for talent, significant cybersecurity risks, and complex data privacy and healthcare law compliance - Negative public opinion and increased regulatory scrutiny of gene therapy could damage perception of the company's products and delay approvals[296](index=296&type=chunk) - The company is dependent on retaining key executives and scientific staff and faces intense competition for qualified personnel[300](index=300&type=chunk) - The company and its partners are subject to significant risks from cyber-attacks and must comply with stringent, evolving data privacy and security laws globally, with non-compliance carrying heavy penalties[304](index=304&type=chunk)[331](index=331&type=chunk) [Risks Related to Common Stock](index=68&type=section&id=Risks%20Related%20to%20Our%20Common%20Stock) Common stock faces high volatility, potential negative impact from a material weakness in internal controls, anti-takeover provisions, and exclusive forum provisions limiting stockholder litigation options - The trading price of the company's common stock has been and is expected to continue to be highly volatile[353](index=353&type=chunk) - The identified material weakness in internal control over financial reporting could erode investor confidence and negatively impact the stock price[356](index=356&type=chunk)[360](index=360&type=chunk) - Anti-takeover provisions in the company's charter documents and under Delaware law may delay or prevent an acquisition[355](index=355&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=71&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) There were no unregistered sales of equity securities during the reporting period that were not previously disclosed in a Form 8-K - No unregistered sales of equity securities were made during the period that had not been previously reported[367](index=367&type=chunk) [Defaults Upon Senior Securities](index=71&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) None - The company reported no defaults upon senior securities[368](index=368&type=chunk) [Mine Safety Disclosures](index=71&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) Not applicable - This item is not applicable to the company[369](index=369&type=chunk) [Other Information](index=71&type=section&id=Item%205.%20Other%20Information) On August 11, 2025, the company entered a private placement agreement for $10.0 million gross proceeds from common stock and pre-funded warrants, intended for R&D and general corporate purposes - On August 11, 2025, the company entered into a securities purchase agreement for a private placement with Frazier Life Sciences[371](index=371&type=chunk) August 2025 Private Placement Details | Security | Quantity | | :--- | :--- | | Common Stock Shares | 1.0 million | | Pre-Funded Warrants (to purchase common stock) | 3.5 million | | **Total Gross Proceeds** | **$10.0 million** | [Exhibits](index=73&type=section&id=Item%206.%20Exhibits) This section provides an index of the exhibits filed with the Quarterly Report on Form 10-Q, including corporate governance documents, compensatory plans, forms of agreements related to the recent private placement, and officer certifications - The report includes an index of all exhibits filed, such as the Restated Certificate of Incorporation, Bylaws, equity incentive plans, and forms of the Securities Purchase Agreement and Registration Rights Agreement[379](index=379&type=chunk)

[Management Remarks](index=1&type=section&id=Management%20Remarks) The CEO highlights excellent progress and ahead-of-schedule enrollment in the ARTEMIS Phase 3 trial for Ixo-vec, driven by strong interest from retina specialists - Enrollment in the ARTEMIS Phase 3 trial is progressing well ahead of schedule, with patient and specialist interest surpassing projections[3](index=3&type=chunk) - A recent survey of nearly 1,000 retina specialists indicated that almost **50%** view gene therapy as the most exciting advancement in the wet AMD field, far surpassing other treatment modalities like TKIs[4](index=4&type=chunk) - The company is engaged in active and ongoing partnering discussions, supported by the clinical progress of Ixo-vec[3](index=3&type=chunk) - Two-year follow-up data from the LUNA Phase 2 study is expected to be presented later in the year, aiming to reinforce the long-term safety and efficacy profile of Ixo-vec[5](index=5&type=chunk) [Pipeline and Corporate Highlights](index=1&type=section&id=Pipeline%20and%20Corporate%20Highlights) Adverum provided key updates on its Ixo-vec program, including accelerated ARTEMIS enrollment, LUNA and AQUARIUS study plans, and a **$10 million** private placement [Ixo-vec Program Update](index=1&type=section&id=Ixo-vec%20Program%20Update) ARTEMIS Phase 3 trial enrollment is ahead of schedule, with completion expected in Q1 2026 and topline data in H1 2027, alongside planned AQUARIUS initiation and LUNA data presentation - ARTEMIS Phase 3 trial enrollment is ahead of schedule, with completion expected in **Q1 2026** and topline data anticipated in **H1 2027**[7](index=7&type=chunk)[8](index=8&type=chunk) - The AQUARIUS Phase 3 study is expected to be initiated in **Q4 2025**, contingent on securing necessary funding[11](index=11&type=chunk) - Two-year long-term follow-up data from the LUNA Phase 2 study is planned for presentation in **Q4 2025**[7](index=7&type=chunk)[11](index=11&type=chunk) [Private Placement with Frazier Life Sciences](index=2&type=section&id=Private%20Placement%20with%20Frazier%20Life%20Sciences) Adverum secured approximately **$10 million** through a PIPE financing from Frazier Life Sciences, involving common stock and pre-funded warrants, expected to close by August 12, 2025 PIPE Financing Details | Metric | Value | | :--- | :--- | | **Investor** | Frazier Life Sciences | | **Amount** | ~$10 million | | **Type** | Private Investment in Public Equity (PIPE) | | **Price per Share** | $2.24 | | **Price per Pre-funded Warrant** | $2.2399 | | **Expected Closing Date** | August 12, 2025 | [Upcoming Anticipated Milestones](index=2&type=section&id=Upcoming%20Anticipated%20Milestones) The company outlined key upcoming milestones including LUNA data presentation, AQUARIUS trial initiation, ARTEMIS enrollment completion, and ARTEMIS topline data announcement through H1 2027 - **4Q 2025:** Present Phase 2 LUNA two-year long-term follow-up data[11](index=11&type=chunk) - **4Q 2025:** Initiate AQUARIUS Phase 3 trial, pending funding availability[11](index=11&type=chunk) - **1Q 2026:** Complete enrollment in the ARTEMIS Phase 3 trial[11](index=11&type=chunk) - **1H 2027:** Announce topline data from the ARTEMIS Phase 3 trial[11](index=11&type=chunk) [Financial Results](index=2&type=section&id=Financial%20Results) Adverum reported a **net loss of $49.2 million** in Q2 2025, widening from **$30.5 million** due to increased R&D expenses, with cash decreasing to **$44.4 million** expected to fund operations into Q4 2025 [Statement of Operations Analysis](index=2&type=section&id=Statement%20of%20Operations%20Analysis) Q2 2025 R&D expenses more than doubled to **$37.1 million** due to the ARTEMIS trial, leading to a **net loss of $49.2 million** or **$2.34 per share** Q2 2025 vs. Q2 2024 Statement of Operations (in thousands) | Metric | Q2 2025 | Q2 2024 | | :--- | :--- | :--- | | Research and development | $37,125 | $17,097 | | General and administrative | $12,730 | $15,807 | | **Total operating expenses** | **$49,855** | **$32,904** | | **Net loss** | **$(49,191)** | **$(30,498)** | | **Net loss per share** | **$(2.34)** | **$(1.46)** | - The increase in R&D expenses was primarily due to higher clinical trial expenses and personnel-related costs associated with the ARTEMIS Phase 3 trial[11](index=11&type=chunk) - The decrease in G&A expenses was driven by lower facilities expenses and reduced stock-based compensation[15](index=15&type=chunk) [Balance Sheet and Cash Position](index=2&type=section&id=Balance%20Sheet%20and%20Cash%20Position) As of June 30, 2025, Adverum held **$44.4 million** in cash, a significant reduction from **$125.7 million** at year-end 2024, expected to fund operations into Q4 2025 Selected Balance Sheet Data (in thousands) | Metric | June 30, 2025 | Dec 31, 2024 | | :--- | :--- | :--- | | Cash, cash equivalents, and marketable securities | $44,397 | $125,691 | | Total Assets | $96,179 | $179,841 | | Total Stockholders' (Deficit) Equity | $(20,219) | $70,714 | - The company's current cash, cash equivalents, and short-term investments are expected to fund operations into the fourth quarter of 2025[11](index=11&type=chunk) [Company and Product Overview](index=3&type=section&id=Company%20and%20Product%20Overview) Adverum Biotechnologies is a clinical-stage company developing single-administration gene therapies for ocular diseases, with lead candidate Ixo-vec for wet AMD receiving key regulatory designations [About Ixo-vec in Wet AMD](index=3&type=section&id=About%20Ixo-vec%20in%20Wet%20AMD) Ixo-vec is Adverum's one-time, in-office intravitreal gene therapy for wet AMD, utilizing a proprietary AAV.7m8 vector for long-term efficacy, and holds multiple significant regulatory designations - Ixo-vec is designed as a one-time, in-office intravitreal injection, differentiating it from gene therapies requiring sub-retinal surgery[12](index=12&type=chunk) - The therapy utilizes a proprietary vector (AAV.7m8) to carry an aflibercept coding sequence, aiming for long-term efficacy[12](index=12&type=chunk) - Ixo-vec has received multiple significant regulatory designations, including FDA Fast Track, RMAT, EMA PRIME, and a UK Innovation Passport[12](index=12&type=chunk) [About Adverum Biotechnologies](index=3&type=section&id=About%20Adverum%20Biotechnologies) Adverum Biotechnologies is a clinical-stage company focused on establishing gene therapy as a new standard of care for prevalent eye diseases through durable, single-administration treatments - Adverum is a clinical-stage company focused on developing gene therapies for highly prevalent ocular diseases[13](index=13&type=chunk) - The company's strategic goal is to create durable, single-administration treatments to eliminate the need for frequent ocular injections[13](index=13&type=chunk) [Forward-Looking Statements](index=3&type=section&id=Forward-looking%20Statements) This section provides a legal disclaimer, cautioning that forward-looking statements regarding Ixo-vec's potential, clinical timelines, and financial sufficiency are subject to significant risks and uncertainties - Statements regarding Ixo-vec's potential, clinical milestones, cash runway, and partnering discussions are considered forward-looking[14](index=14&type=chunk) - Key risks include uncertainties inherent to novel technology, clinical trial completion, regulatory approvals, potential side effects, and the company's ability to continue as a going concern[16](index=16&type=chunk)

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.

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].

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].