Ixoberogene Soroparvovec (Ixo-vec) IVT Gene Therapy for Neovascular AMD: First Time 26-Week Interim Analysis Results from the Phase 2 LUNA Study Charles C. Wykoff, MD, PhD Director of Research, Retina Consultants of Texas Professor of Clinical Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital Paul Hahn, MD, PhD, Eduardo Uchiyama, MD, Sean D. Adrean, MD, Mark R. Barakat, MD, Cameron Javid, MD, Dante J. Pieramici, MD, Bill Tan, PharmD, Adam Turpcu, PhD, Kalliopi Stasi, MD, PhD, Star Seyedkazemi ...

Adverum Biotechnologies, Inc. (NASDAQ:ADVM) 26-Week Interim Analysis of the LUNA Phase 2 Trial Update Call July 17, 2024 8:00 AM ET Company Participants Mike Zanoni - Head of IR Laurent Fischer - President & CEO Charles Wykoff - Director of Research, Retina Consultants of Texas Conference Call Participants Joon Lee - Truist Securities Joseph Thome - TD Cowen Francois Brisebois - Oppenheimer Graig Suvannavejh - Mizuho Securities Luca Issi - RBC Capital Daniil Gataulin - Chardan Operator Hello, ladies and gen ...

Summary of Adverum Biotechnologies, Inc. Conference Call on LUNA Phase 2 Trial Company and Industry Overview - **Company**: Adverum Biotechnologies, Inc. (NASDAQ:ADVM) - **Industry**: Gene therapy for ophthalmic conditions, specifically targeting wet age-related macular degeneration (AMD) Key Points and Arguments 1. **LUNA Phase 2 Trial Overview**: The call discussed the 26-week interim analysis of the LUNA Phase 2 trial for Ixo-vec, a gene therapy product candidate aimed at treating wet AMD, presented at the 2024 ASRS Annual Meeting in Stockholm, Sweden [6][3][4]. 2. **Goals of the LUNA Study**: The primary objectives include selecting the appropriate dose and regimen for pivotal Phase III trials, expected to start in the first half of 2025 [7][49]. 3. **Clinical Activity and Efficacy**: The interim analysis showed a greater than 90% reduction in treatment burden, with 76% of patients remaining injection-free at the 6E10 dose and 83% at the 2E11 dose after six months [9][24]. Visual acuity was maintained, and central subfield thickness (CST) remained stable [9][28]. 4. **Safety Profile**: Ixo-vec demonstrated an improved safety profile compared to previous studies, with no serious adverse events related to the drug. Over 90% of participants experienced no or minimal inflammation [10][36]. The most common adverse event was dose-dependent anterior cellular inflammation, manageable with local corticosteroids [35][34]. 5. **Patient Preference Survey**: A survey indicated that 88% of patients preferred Ixo-vec over prior treatments, with 100% of patients in the 6E10 difluprednate cohort expressing a desire for Ixo-vec therapy in their other eye if affected by wet AMD [12][48]. 6. **Market Potential**: The wet AMD market is large and growing, with a significant need for innovative treatments that reduce the treatment burden associated with current anti-VEGF therapies [13][14]. Ixo-vec's potential for lifelong therapeutic benefit positions it favorably against existing treatments [16]. 7. **Long-term Efficacy**: Data from the OPTIC trial indicated sustained therapeutic levels of Ixo-vec beyond four years, suggesting a long-term solution for wet AMD patients [17][18]. 8. **Regulatory Engagement**: The company is actively engaging with regulatory bodies like the FDA and EMA to facilitate the development and approval of Ixo-vec [49]. Additional Important Content 1. **Challenges in Current Treatments**: The treatment burden of wet AMD is significant, often leading to under-treatment and poor outcomes due to missed visits and limited access [14][15]. 2. **Comparative Analysis**: Ixo-vec showed superior reduction in annualized injections compared to other gene therapy agents, with a higher injection-free rate [45][46]. 3. **Prophylactic Regimens**: The study evaluated various prophylactic regimens to minimize inflammation, leading to protocol amendments that improved safety outcomes [37][38]. 4. **Future Directions**: The company plans to present further data from the LUNA trial in the fourth quarter of 2024 and initiate pivotal trials in 2025 [49]. This summary encapsulates the critical insights from the conference call regarding Adverum Biotechnologies' ongoing efforts in the gene therapy space for treating wet AMD, highlighting the promising results of the LUNA Phase 2 trial and the potential market impact of Ixo-vec.

Core Insights - Adverum Biotechnologies announced promising results from the 26-week interim analysis of the LUNA Phase 2 trial for Ixo-vec, a gene therapy for wet age-related macular degeneration (AMD), indicating a favorable safety and efficacy profile [1][2][6] Efficacy - 76% of patients receiving the 6E10 dose of Ixo-vec were injection-free at 26 weeks, maintaining visual acuity and fluid control [1][7] - Both 6E10 and 2E11 doses showed maintenance of visual and anatomic outcomes, with 83% of patients in the 2E11 cohort also being injection-free [6][7] - The mean annualized anti-VEGF injections were reduced by 90% for the 6E10 group and 95% for the 2E11 group at week 26 [7] Safety - 100% of patients receiving the difluprednate-alone prophylactic regimen had no or minimal inflammation, with no additional corticosteroids needed beyond scheduled prophylaxis [1][9] - Ixo-vec was well tolerated, with no serious adverse events related to the treatment and only mild to moderate adverse events reported [7][9] Patient Preference - A Patient Preference Survey indicated that 88% of patients preferred Ixo-vec over previous anti-VEGF treatments, and 93% would choose to receive Ixo-vec in the other eye if applicable [1][9] Upcoming Milestones - Key upcoming events include the presentation of the 9-month analysis and updates on Phase 3 trial design anticipated in Q4 2024, with the initiation of the Phase 3 trial planned for H1 2025 [10]

Core Viewpoint - Adverum Biotechnologies (ADVM) shows significant upside potential based on Wall Street analysts' price targets, with a mean target of $33.86 indicating a 290.5% upside from the current price of $8.67 [1] Price Targets and Analyst Consensus - The average price target for ADVM ranges from a low of $20 to a high of $60, with a standard deviation of $14.05, suggesting variability in analysts' estimates [1] - A low standard deviation indicates strong agreement among analysts regarding the stock's price movement direction, which can serve as a starting point for further research [4] Earnings Estimates and Market Sentiment - Analysts have shown growing optimism about ADVM's earnings prospects, as evidenced by a 6.6% increase in the Zacks Consensus Estimate over the past month, with 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 estimates, indicating strong potential for upside [5] Caution on Price Targets - While price targets are a popular metric, relying solely on them for investment decisions may not be prudent due to historical inaccuracies in predicting stock price movements [2][3] - Analysts may set overly optimistic price targets influenced by business relationships, which can lead to inflated expectations [3]

Core Viewpoint - Adverum Biotechnologies is advancing gene therapy as a potential new standard of care for wet age-related macular degeneration (wet AMD) and will present interim data from its LUNA Phase 2 study at the ASRS Annual Scientific Meeting [1][2]. Company Overview - Adverum Biotechnologies (NASDAQ:ADVM) is a clinical-stage company focused on developing gene therapies for prevalent ocular diseases, aiming to create functional cures to restore vision and prevent blindness [4]. - The company is leveraging its proprietary intravitreal (IVT) platform to develop durable, single-administration therapies that can be delivered in physicians' offices, reducing the need for frequent ocular injections [4]. Upcoming Events - A webcast will be held on July 17, 2024, at 8:00 a.m. ET to review the interim 26-week data from the LUNA Phase 2 study of ixoberogene soroparvovec (Ixo-vec) [1]. - Dr. Charles C. Wykoff will present the findings during the Wet AMD Symposium at the ASRS Annual Scientific Meeting on the same day at 8:45 a.m. CEST [2]. Presentation Access - The live webcast will be available on the company's website, and a replay will be accessible for at least 30 days following the event [3].

Core Insights - Adverum Biotechnologies has appointed Dr. Rabia Gurses Ozden as Chief Medical Officer and Dr. Szilárd Kiss to its Board of Directors, enhancing its leadership team as it advances its gene therapy candidate Ixo-vec for wet age-related macular degeneration (AMD) [1][2][5] Company Developments - The company is progressing with the LUNA trial for Ixo-vec, which is positioned as a potential best-in-class treatment for wet AMD, aiming to transform the treatment paradigm by offering a long-term solution to preserve sight [2][5] - Dr. Ozden brings over 20 years of experience in ophthalmology drug development, particularly in AAV-based gene therapies, and has previously held leadership roles in other biotech firms [2][3] - Dr. Kiss, a renowned retina specialist, has over 20 years of experience in ocular gene therapy and has been involved in numerous clinical trials, contributing significant expertise to the Board [3][4] Product Focus - Ixo-vec is being developed as a one-time intravitreal injection aimed at treating neovascular or wet AMD, with the goal of reducing the burden of frequent eye injections currently required by standard care [5] - The company aims to leverage its proprietary intravitreal platform to create durable therapies that can be administered in a physician's office, potentially eliminating the need for frequent ocular injections [5]

Core Viewpoint - Adverum Biotechnologies (ADVM) is experiencing significant selling pressure, with a 19.7% decline over the past four weeks, but is now positioned for a potential trend reversal due to being in oversold territory and positive earnings expectations from Wall Street analysts [1]. Group 1: Technical Indicators - The Relative Strength Index (RSI) for ADVM is at 26.99, indicating that the stock is oversold and may be nearing a price reversal [2][4]. - RSI is a momentum oscillator that helps identify oversold conditions, typically when the reading falls below 30, suggesting potential entry opportunities for investors [2]. Group 2: Fundamental Indicators - There is a strong consensus among sell-side analysts that ADVM will report better earnings than previously predicted, leading to a 0% increase in the consensus EPS estimate over the last 30 days [4]. - An upward trend in earnings estimate revisions is generally associated with price appreciation in the near term, indicating a potential rebound for ADVM [4]. - ADVM holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimate revisions and EPS surprises, further supporting the stock's turnaround potential [4].

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 ___________________________________________________________________ FORM 10-Q ___________________________________________________________________ (Mark One) QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES ☒ EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2024 or TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES ☐ EXCHANGE ACT OF 1934 For the transition period from to Com ...

[Executive Summary & Q1 2024 Highlights](index=1&type=section&id=Executive%20Summary%20%26%20Q1%202024%20Highlights) The company reports Q1 2024 results, highlighting a strong cash position and upcoming LUNA trial data presentation - Adverum Biotechnologies announced Q1 2024 financial results and pipeline highlights, with the Phase 2 LUNA interim analysis to be presented at ASRS on July 17, 2024[1](index=1&type=chunk) - CEO Laurent Fischer highlighted Ixo-vec's potentially **best-in-class** product profile and the upcoming LUNA trial data presentation as a basis for FDA end-of-Phase 2 meeting, aiming to confirm optimal dose(s) for pivotal studies and shift the wet AMD treatment paradigm[1](index=1&type=chunk) Key Financial and Operational Highlights | Metric | Value | | :----- | :---- | | Cash, cash equivalents and short-term investments | $193.3 million | | Funding Horizon | Into late 2025 | [Ixo-vec Program Updates](index=1&type=section&id=Ixo-Vec%20Program%20Highlights) The company provides updates on its Ixo-vec program, including trial data, presentation plans, and future milestones [LUNA Phase 2 Interim Analysis Presentation](index=1&type=section&id=LUNA%20Phase%202%20Interim%20Analysis%20to%20be%20presented%20at%20ASRS) The 26-week interim analysis from the LUNA Phase 2 study will be presented at the ASRS meeting in July 2024 - The 26-week landmark interim analysis from the LUNA Phase 2 study of Ixo-vec for wet AMD will be presented at the American Society of Retina Specialists (ASRS) Annual Scientific Meeting from July 17-20, 2024[2](index=2&type=chunk) [Preliminary LUNA Trial Data (Efficacy & Safety)](index=1&type=section&id=Preliminary%20Ixo-vec%20LUNA%20Trial%20Data%20at%20Macula%20Society%202024) Preliminary LUNA trial data shows positive efficacy and safety, with significant reductions in anti-VEGF injections - Positive preliminary efficacy and safety data from the LUNA Phase 2 trial of Ixo-vec in wet AMD patients were announced in February 2024[3](index=3&type=chunk) - Ixo-vec was **generally well tolerated**, with intraocular inflammation responsive to local corticosteroids and no Ixo-vec related serious adverse events, episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion or hypotony reported[4](index=4&type=chunk) LUNA Trial Efficacy Data (through 26 weeks) | Dose | Mean Reduction in Annualized Anti-VEGF Injections | Patients Free of Supplemental Injections | | :--- | :------------------------------------------------ | :--------------------------------------- | | 2E11 | 94% | 85% | | 6E10 | 90% | 68% | [Anticipated Milestones](index=2&type=section&id=Anticipated%20Milestones) Key upcoming milestones include regulatory interactions, data presentations, and the initiation of a Phase 3 trial - Key anticipated milestones include continued regulatory interactions and data presentations leading to a Phase 3 trial initiation in H1 2025[5](index=5&type=chunk) Anticipated Milestones Timeline | Milestone | Timing | | :-------- | :----- | | Continued FDA and EMA regulatory interactions | 2024 | | Presentation of landmark LUNA 26-week interim analysis at ASRS | July 2024 | | Ixo-vec Phase 3 program and regulatory update | 4Q 2024 | | Presentation of landmark LUNA 52-week analysis | 1Q 2025 | | Initiation of Phase 3 trial | H1 2025 | [Financial Results for Q1 2024](index=2&type=section&id=Financial%20Results%20for%20the%20Three%20Months%20Ended%20March%2031%2C%202024) The company reports a strengthened cash position, reduced operating expenses, and a lower net loss for Q1 2024 [Key Financial Highlights](index=2&type=section&id=Key%20Financial%20Highlights) The company improved its cash position, extended its operational runway, and reduced both expenses and net loss per share - The company expects its cash, cash equivalents and short-term investments to fund operations into **late 2025**[7](index=7&type=chunk) Cash and Investment Position | Metric | March 31, 2024 | December 31, 2023 | Change | | :----- | :------------- | :---------------- | :----- | | Cash, cash equivalents and short-term investments | $193.3 million | $96.5 million | +$96.8 million | Q1 2024 vs Q1 2023 Expense and Loss Comparison | Metric | Q1 2024 ($M) | Q1 2023 ($M) | Change ($M) | Change (%) | | :----- | :----------- | :----------- | :---------- | :--------- | | Research and development expenses | 15.4 | 21.1 | (5.7) | -27.0% | | General and administrative expenses | 11.4 | 12.8 | (1.4) | -10.9% | | Net Loss | 24.8 | 29.1 | (4.3) | -14.8% | | Net Loss per share (basic and diluted) | (1.50) | (2.90) | 1.40 | -48.3% | [Condensed Consolidated Balance Sheet Data](index=5&type=section&id=Cash%20and%20cash%20equivalents%2C%20and%20marketable%20securities) The balance sheet reflects a significant increase in cash, total assets, and stockholders' equity as of March 31, 2024 Condensed Consolidated Balance Sheet Data (in thousands) | Metric | March 31, 2024 (Unaudited) | December 31, 2023 | | :----------------------------------------------- | :------------------------- | :---------------- | | Cash and cash equivalents, and marketable securities | $193,328 | $96,526 | | Total assets | $267,828 | $173,010 | | Total current liabilities | $21,549 | $24,914 | | Total liabilities | $85,540 | $89,541 | | Total stockholders' equity | $182,288 | $83,469 | [Condensed Consolidated Statements of Operations](index=6&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) The Q1 2024 statement of operations shows lower operating expenses and a reduced net loss compared to the prior year Condensed Consolidated Statements of Operations (in thousands, except per share data) | Metric | Three months ended March 31, 2024 (Unaudited) | Three months ended March 31, 2023 | | :----------------------------------------------- | :------------------------------------ | :-------------------------------- | | License revenue | $— | $3,600 | | Research and development expenses | $15,410 | $21,059 | | General and administrative expenses | $11,429 | $12,780 | | Total operating expenses | $26,839 | $33,839 | | Operating loss | $(26,839) | $(30,239) | | Other income, net | $2,052 | $1,200 | | Net loss | $(24,787) | $(29,056) | | Net loss per share — basic and diluted | $(1.50) | $(2.90) | | Weighted-average common shares outstanding | 16,479 | 10,030 | [Disease and Product Information](index=3&type=section&id=Disease%20and%20Product%20Information) This section details Wet AMD, the current standard of care, and the Ixo-vec gene therapy candidate [About Wet Age-Related Macular Degeneration (Wet AMD)](index=3&type=section&id=About%20Wet%20Age-Related%20Macular%20Degeneration) Wet AMD is a leading cause of blindness, with current treatments requiring frequent injections - Wet AMD is a VEGF-driven advanced form of AMD, affecting approximately **10% of AMD patients** and is a leading cause of blindness in people over 65, with an estimated **20 million individuals worldwide** living with this condition[8](index=8&type=chunk) - The current standard of care involves frequent, life-long anti-VEGF injections, while IVT gene therapy aims to provide stable therapeutic levels of anti-VEGF to control macular fluid, potentially preserving vision and reducing injections for the patient's life[8](index=8&type=chunk) [About Ixo-vec in Wet AMD](index=3&type=section&id=About%20Ixo-vec%20in%20Wet%20AMD) Ixo-vec is a one-time IVT gene therapy candidate designed to reduce treatment burden for Wet AMD patients - Ixo-vec (ixoberogene soroparvovec) is a clinical-stage gene therapy product candidate for wet AMD, designed as a **one-time intravitreal (IVT) injection** using a proprietary AAV.7m8 vector carrying an aflibercept coding sequence[9](index=9&type=chunk) - Ixo-vec aims to deliver long-term efficacy, reduce the burden of frequent anti-VEGF injections, optimize patient compliance, and improve vision outcomes for wet AMD patients[9](index=9&type=chunk) - Ixo-vec has received **Fast Track designation** from the U.S. FDA, **PRIME designation** from the European Medicines Agency, and the **Innovation Passport** from the UK's MHRA for wet AMD treatment[9](index=9&type=chunk) [Company Information](index=2&type=section&id=Company%20Information) This section provides an overview of Adverum Biotechnologies and details on a recent inducement grant [About Adverum Biotechnologies](index=3&type=section&id=About%20Adverum%20Biotechnologies) Adverum is a clinical-stage company developing gene therapies for prevalent ocular diseases - Adverum Biotechnologies is a clinical-stage company pioneering gene therapy for highly prevalent ocular diseases, aiming to develop **functional cures** to restore vision and prevent blindness[10](index=10&type=chunk) - The company leverages its proprietary intravitreal (IVT) platform to develop durable, single-administration therapies, eliminating the need for frequent ocular injections[10](index=10&type=chunk) [Inducement Grant](index=2&type=section&id=Inducement%20Grant) A stock option grant was issued to a new non-executive employee as an inducement to employment - On May 6, 2024, Adverum granted a new non-executive employee a stock option to purchase **21,000 shares** of common stock at an exercise price of $10.66 per share, vesting over four years, as an inducement to employment[6](index=6&type=chunk) [Legal & Contact Information](index=4&type=section&id=Legal%20%26%20Contact%20Information) This section includes forward-looking statements, risk disclosures, and company contact details [Forward-looking Statements](index=4&type=section&id=Forward-looking%20Statements) The report contains forward-looking statements subject to risks and uncertainties detailed in SEC filings - Statements in the press release regarding future events or results are 'forward-looking statements' under the Private Securities Litigation Reform Act of 1995, covering topics like cash runway, Ixo-vec's potential, and trial timelines[11](index=11&type=chunk) - Actual results could differ materially due to various risks and uncertainties, including market conditions and those detailed in Adverum's SEC filings, such as the Annual Report on Form 10-K and subsequent 10-Q reports[11](index=11&type=chunk) [Corporate, Investor and Media Inquiries](index=4&type=section&id=Corporate%2C%20Investor%20and%20Media%20Inquiries) Contact information is provided for corporate, investor, and media inquiries - Contact information for corporate, investor, and media inquiries is provided via email: ir@adverum.com[12](index=12&type=chunk)