Adverum Biotechnologies — Technical Presentation (November 2024)
78 slides from Adverum Biotechnologies's technical presentation, Nov 18, 2024
Slide 1: Preserving Sight for Life: Webcast on LUNA and OPTIC Results
Exhibit 99.1 Preserving ® Sight for Life Webcast to Present 52-Week LUNA and 4- Year OPTIC Results and Pivotal Program th November 18 , 2024
Slide 2: Forward-Looking Statements
Forward-Looking Statements Statements contained in this document and any accompanying presentation regarding matters, events, statistics, or clinical or financial results that may occur in the future are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act
Slide 3: Today's Agenda
Today’s Agenda Welcome & Key Takeaways Patient Preference Survey 01 05 Laurent Fischer, MD Laurent Fischer, MD President & Chief Executive Officer President & Chief Executive Officer Ixo-vec & Wet AMD Commercial Opportunity 02 06 Laurent Fischer, MD Jason Mitchell President & Chief Executive Officer
Slide 4: Adverum Participants
Adverum Participants Laurent Fischer, MD Rabia Gurses Ozden, MD Star Seyedkazemi, PharmD President and Chief Medical Officer Chief Development Officer Chief Executive Officer Linda Rubinstein Mike Zanoni Jason Mitchell Peter Soparkar Chief Financial Officer Head of Investor Relations Chief Commercia
Slide 5: Key Opinion Leader Participants
Key Opinion Leader Participants Szilárd Kiss, MD Charles C. Wykoff, MD, PhD Mark Barakat, MD Distinguished Professor of Ophthalmology, Director of Research, Director of Clinical Research Director of Retina Service Retina Consultants of Texas Retina Macula Institute of Arizona Cornell University Adve
Slide 6: Key Takeaways
Key Takeaways
Slide 7: Ixo-vec's Derisked Phase 3 and Commercial Profile
Ixo-vec’s Derisked Phase 3 and Commercial Profile Clinical updates underscore Ixo-vec’s potential best-in-class product profile • Potential best-in-class product profile >50% injection free and >80% treatment burden reduction in hard-to-treat patients • 10X safety margin with >4 years follow-up • No
Slide 8: 5+ Years of Clinical Experience Establish 10x Safety Margin
5+ Years of Clinical Experience Establish 10x Safety Margin Ixo-vec 6E10 with extended prophylaxis de-risks Phase 3 & commercialization 6E11 N=15 2E11 N=15 4+ Years Clinical Data 8 DATA CUT: OPTIC 21AUG2024, LUNA 29AUG2024 Dose (vg/eye) 10x Safety Margin
Slide 9: 5+ Years of Clinical Experience Establish 10x Safety Margin
5+ Years of Clinical Experience Establish 10x Safety Margin Ixo-vec 6E10 with extended prophylaxis de-risks Phase 3 & commercialization 6E11 Phase 3 Dose N=15 ü Enhanced Safety Profile ü Extended Steroid Prophylaxis ü Potential Best-in-Class Efficacy Profile 2E11 2E11 N=15 N=30 6E10 N=30 4+ Years Cl
Slide 10: 6E10 Dose Selected to Maximize Phase 3 and Commercial Success
6E10 Dose Selected to Maximize Phase 3 and Commercial Success Demonstrates potential best-in-class product profile Benefit Safety Treatment Burden % Receiving ≤ 1 Injection Injection Free % With AC ≥1+ Ph3 Go-Forward Dose Reduction Steroids for IOI 6E10 88% 75% 54% 0% 4% (n = 28) N=1 2E11 92% 79% 69
Slide 11: Reliable Benefit & Predictable Safety Profile Enable True Paradigm Shift
Reliable Benefit & Predictable Safety Profile Enable True Paradigm Shift 4-year OPTIC & 52-week LUNA data underscore Ixo-vec’s profile Demonstrated Reliable Long-Term Benefit 78% of patients who were injection free through year 1 remained injection free through year 4 88% of patients who were inject
Slide 12: Ixo-vec & wet AMD
Ixo-vec & wet AMD
Slide 13: Large and Growing Global Market Opportunity
Large and Growing Global Market Opportunity Wet AMD physicians and patients embrace innovation Wet Age-Related Macular Degeneration Multi-Billion Dollar Market Opportunity A leading cause of vision loss among older adults Growth driven by aging population and product innovation Global Wet AMD Sales
Slide 14: Real-World Vision Declines Due to Chronic Undertreatment
Real-World Vision Declines Due to Chronic Undertreatment 10 5 0 IRIS (N>160,000) -5 HORIZON (N=600) Gilles, al (N=1,212) CATT (N=647) -10 SEVEN-UP (N=65) -15 0 1 2 3 4 5 6 7 Years Up to ~40% STOP anti-VEGF over 2 years and up to 57% stop over 5 years Sources: https://futureofvision.global/home/the-r
Slide 15: Real-World Vision Declines Due to Chronic Undertreatment
Real-World Vision Declines Due to Chronic Undertreatment Ixo-vec designed to deliver stable aflibercept to maintain long-term vision Ixo-vec 10 5 0 IRIS (N>160,000) -5 HORIZON (N=600) Gilles, al (N=1,212) CATT (N=647) -10 SEVEN-UP (N=65) -15 0 1 2 3 4 5 6 7 Years Up to ~40% STOP anti-VEGF over 2 yea
Slide 16: Undertreatment Often Results from Barriers to Treatment
Undertreatment Often Results from Barriers to Treatment Physician ASRS survey underscores need for more durable treatments Barriers to Treatment More Durable Treatment Options Are Needed Physician Survey: Unmet Needs In Treating Wet AMD and DME Needle Anxiety Comorbidities 74% Greater Durability 79%
Slide 17: Ixo-vec Positioned to Transform Treatment Paradigm
Ixo-vec Positioned to Transform Treatment Paradigm In contrast, 2nd generation wet AMD treatments are only incremental advancements Ixo-vec designed to deliver stable and continuous aflibercept 5+ years % Injection Potential 2024 Free US Revenue 4D-150 (Investigational) Paradigm Shift Ixo-vec >50% [
Slide 18: Ixo-vec Delivers Aflibercept via Single Intravitreal Injection
Ixo-vec Delivers Anti-VEGF Aflibercept via Single Intravitreal Injection 7m8 capsid enables delivery of stable aflibercept levels into the retina AAV.7m8 AAV.7m8 ILM Ganglion Inner Nuclear Photoreceptors RPE IVT injection monomer Cells Membrane Loop IV Retina Loop IV 7m8 insert Promoter Aflibercept
Slide 19: 4-Year OPTIC & 52-week LUNA Results
4-Year OPTIC & 52-week LUNA Results
Slide 20: OPTIC First-in-Human Trial Design
OPTIC First-in-Human Trial Design 6E11 & 2E11 with short prophylaxis in hard-to-treat population Primary Objective Secondary Objectives • Vision maintenance (BCVA) Long-term safety and efficacy of Ixo-vec IVT in • Anatomy (SD-OCT) treatment experienced patients • Need for supplemental therapy Day -1
Slide 21: Preclinical Data Suggest Best-in-Class Potential at 6E10 Dose
Preclinical Data Suggest Best-in-Class Potential of Ixo-vec at 6E10 Dose NHP studies demonstrate consistent aflibercept production with low inflammation Less-than-dose-proportional aflibercept levels across 3 logs Improved inflammation scores with lower doses (no prophylaxis) Aqueous Humor Afliberce
Slide 22: Learnings from OPTIC Informed LUNA Phase 2 Trial
Learnings from OPTIC Informed LUNA Phase 2 Trial LUNA goal: optimize Ixo-vec benefit / risk going into pivotal trials Objective I Objective II Determine the Determine the Optimal Phase 3 Prophylactic Dose for Phase 3 Regimen 22
Slide 23: LUNA Phase 2 Trial Design
LUNA Phase 2 Trial Design 6E10 & 2E11 with extended prophylaxis in hard-to-treat patients Multicenter, double-masked, randomized, parallel-group Phase 2 study Key inclusion criteria: demonstrated response to anti-VEGF therapy and under active treatment for CNV secondary to nAMD (received a minimum o
Slide 24: Demographics and Baseline Characteristics
Demographics and Baseline Characteristics OPTIC & LUNA evaluated hard-to-treat patients LUNA LUNA LUNA OPTIC Demographics and Baseline 6E10 2E11 Total Total Characteristics N = 30 N = 30 N = 60 N = 30 Mean age, years (SD) 75.4 (8.2) 77.7 (7.4) 76.6 (7.8) 79.0 (7.3) Female, n (%) 16 (53%) 18 (60%) 34
Slide 25: Ixo-vec Demonstrates Durable Therapeutic Levels After One Injection
Ixo-vec Demonstrates Durable Therapeutic Levels After One Injection Sustained aqueous aflibercept levels up to 5 years Early aflibercept levels are associated with sustained long-term protein expression 100,000 NHP studies suggest aflibercept levels may be 7x higher in the back of the eye 10,000 1,0
Slide 26: Ixo-vec Demonstrates Durable Therapeutic Levels After One Injection
Ixo-vec Demonstrates Durable Therapeutic Levels After One Injection Sustained aflibercept levels measured with 6E10 at year 1 Early aflibercept levels are associated with sustained long-term protein expression 100,000 NHP studies suggest aflibercept levels may be 7x higher in the back of the eye 10,
Slide 27: Ixo-vec Reduced Treatment Burden Through Years
Ixo-vec Reduced Treatment Burden Through 4 Years 2E11 shows >80% reduction in annualized anti-VEGF injections in every year Mean Post Ixo-vec Annual Rate Through Year 1 | 2 | 3 | 4 | | | Mean Prior Annual Rate 11 9.9 10 9 8 7 60% 53% 47% 53% 6 Injection Free Injection Free Injection Free Injection F
Slide 28: Consistent Injection-Free Rates through Years
Consistent Injection-Free Rates through 4 Years Proportion of injection-free patients consistent in each year of follow-up Injection Free 60% 53% 67% 73% By Year * OPTIC OPTIC EXT 2E11 (n = 15) -1 0 1 2 3 4 Years Early Termination Aflibercept Bevacizumab Ranibizumab Unknown Visit with no supplementa
Slide 29: 52-Week LUNA and OPTIC Injection Burden Reduction are Consistent
52-Week LUNA and OPTIC Injection Burden Reduction are Consistent >80% reduction in annualized anti-VEGF injections, >50% injection free Mean Prior Annualized Rate Mean Post Ixo-vec Annualized Rate: LUNA OPTIC 11 10.2 10.1 9.9 10 -88% -92% -84% 9 8 75% 79% 73% 7 ≤ 1 Injection ≤ 1 Injection ≤ 1 Inject
Slide 30: Potential Best-in-Class Injection-Free Rates
Potential Best-in-Class Injection-Free Rates 52-week LUNA data demonstrate >50% injection free in hard-to-treat patients LUNA 52 Weeks Overall 6E10 2E11 (N = 57) (n = 28) (n = 29) Injection Free 61% 54% 69% ≤1 Injection 77% 75% 79% ≤2 Injections 89% 89% 90% Week -52 Week -26 Study Week Week 26 Week
Slide 31: Ixo-vec Maintains BCVA & CST
Ixo-vec Maintains BCVA & CST Demonstrated robust and durable activity through 4 years of follow up OPTIC OPTIC EXT 90 Mean BCVA Mean BCVA (90% CI) by Dose Over Time (letters) change 80 from baseline to last visit (90% CI) 70 -2.9 (-12.3, 6.5) 60 * 2E11 50 40 30 0 0 12 0 24 .5 36 48 1 60 72 1.5 84 96
Slide 32: Ixo-vec Maintains BCVA & CST
Ixo-vec Maintains BCVA & CST Both doses demonstrate robust and durable activity, consistent with OPTIC Least Squares Means Change in Best Corrected Visual Acuity (BCVA) Over Time by Dose* 15 LS Means BCVA Change 6E10 (n=29) 2E11 (n=29) from Baseline at Week 52, 10 Letters (95% CI) 5 -2.1 (-4.8, 0.7)
Slide 33: OPTIC 2E11 Well Tolerated through Years
OPTIC 2E11 Well Tolerated through 4 Years 100% of patients who had inflammation resolved by year 1 OPTIC OPTIC EXT OPTIC 2E11 15 AC Cells ≥1+ VC Cells ≥1+ § 2E11 was generally well tolerated through 4 2E11 years of follow up 10 § Inflammation was dose dependent, did not 5 impact vision and, when pre
Slide 34: Safety Summary: LUNA 52-Week
Safety Summary: LUNA 52-Week Ixo-vec continues to be well tolerated, supporting potential best-in-class product profile Ixo-vec had a favorable safety profile and was well tolerated in total LUNA population • No Ixo-vec-related serious adverse events. All Ixo-vec-related adverse events (AEs) were ei
Slide 35: Extended Local Prophylaxis Effective in Minimizing Inflammation
Extended Local Prophylaxis Effective in Minimizing Inflammation Inflammation responded to local corticosteroids and resolved over time Initial IVT DEX IVT DEX + DFBA Initial IVT DEX IVT DEX + DFBA Prophylactic Steroid Prophylactic Steroid Injection Injection Usage** Usage** DFBA Prophylaxis Period (
Slide 36: Both LUNA Steroid Regimens Result in Enhanced Safety Profile
Both LUNA Steroid Regimens Result in Enhanced Safety Profile Topical eyedrops effective at minimizing inflammation & long-term steroid need Prophylactic Regimens: IVT DEX + DFBA Initial IVT DEX DFBA Only Injection Proportion of Participants Receiving Steroids within Scheduled Prophylaxis or for Infl
Slide 37: Extended Prophylaxis in LUNA Improves Upon OPTIC Experience
Extended Prophylaxis in LUNA Improves Upon OPTIC Experience Phase 3 regimen enhances overall safety profile & reduces long-term steroid need LUNA DFBA Prophylaxis Period OPTIC Proportion of Participants Receiving Steroids within Scheduled Prophylaxis or for Treatment of Inflammation 100% 75% 50% 25%
Slide 38: CST Maintained in Patients with High Disease Burden
CST Maintained in Patients with High Disease Burden Fluid reduction in patients with baseline CST >300 μm; maintenance in ≤300 μm 150 LUNA Baseline CST ≤300μm (n=27) LUNA Baseline CST >300μm (n=33) Mean CST Change from 100 Baseline at Week 52, μm (95% CI) 50 2.9 (-14.3, 20.2) BL ≤300 μm 0 -34.4 (-64
Slide 39: Consistent Anatomic Benefit in Broad Population
Consistent Anatomic Benefit in Broad Population Anatomic stability with reduction and maintenance of CST in injection-free patients 150 LUNA Baseline CST ≤300μm (n=27) LUNA Baseline CST >300μm (n=33) Mean CST Change from LUNA Baseline CST ≤300μm, Injection-Free (n=16) LUNA Baseline CST >300μm Inject
Slide 40: Ixo-vec Maintained Visual & Anatomic Outcomes
Ixo-vec Maintained Visual & Anatomic Outcomes BCVA maintenance demonstrated in overall population and injection-free patients Least Squares Means Change in Best Corrected Visual Acuity (BCVA) Over Time by Dose* 15 LS Means BCVA Change 6E10 (n=29) 2E11 (n=29) from Baseline at Week 52, 10 Letters (95%
Slide 41: 75% Injection Free in 6E10 Patients with Less Treatment Burden
75% Injection Free in 6E10 Patients with Less Treatment Burden Treatment-experienced patients with ≤6 injections in year prior MEAN INJECTION RATE: 4.7 Ixo-vec LUNA 52 Weeks Overall 6E10 2E11 (N = 13) (n = 4) (n = 9) Injection Free 69% 75% 67% ≤1 Injection 92% 100% 89% ≤2 Injections 92% 100% 89% Onl
Slide 42: Clinical Updates Underscore Ixo-vec's Potential Best-in-Class Profile
Clinical Updates Underscore Ixo-vec’s Potential Best-in-Class Profile • Potential best-in-class product profile Maintenance of visual and anatomic endpoints with over 80% reduction in injection burden and greater than 50% injection freedom • 10X safety margin with >4 years follow-up • No OPTIC 2E11
Slide 43: Ixo-vec Pivotal Program
Ixo-vec Pivotal Program
Slide 44: Ixo-vec Pivotal Program for Wet AMD in Broad Patient Population
Ixo-vec Pivotal Program for Wet AMD in Broad Patient Population Designed to maximize probabilities of clinical, regulatory, and commercial success 5+ Years of Clinical Experience Ixo-vec Global Pivotal Program Broad Wet AMD 10X Safety Population Margin § Two double-masked randomized Phase 3 trials I
Slide 45: ARTEMIS Phase 3 Wet AMD Study Design
ARTEMIS Phase 3 Wet AMD Study Design Noninferiority trial designed to enable regulatory approval and drive commercial success Randomized, Double Masked, On-Label Aflibercept-Controlled Phase 3 Trial in Broad Population Objective To demonstrate that a single intravitreal injection of Ixo-vec 6E10 ach
Slide 46: ARTEMIS Phase 3 Wet AMD Study Design
ARTEMIS Phase 3 Wet AMD Study Design Broad target patient population enriched for anti-VEGF response Key Inclusion Criteria Treatment-naïve and previously BCVA: Anti-VEGF responsive: treated wet AMD 35 – 78 letters After two aflibercept loading doses -8 -4 D1 1 4 8 12 16 20 24 28 32 36 40 44 48 52 5
Slide 47: ARTEMIS Phase 3 Wet AMD Study Design
ARTEMIS Phase 3 Wet AMD Study Design Patients randomized after 3 aflibercept loading doses and assessed every 4 weeks for disease activity Key Inclusion Criteria Treatment-naïve and previously BCVA: Anti-VEGF responsive: treated wet AMD 35 – 78 letters After two aflibercept loading doses Diflupredna
Slide 48: Patient Preference Survey
Patient Preference Survey (e LUNA
Slide 49: Pre-specified Patient Preference Survey
Pre-specified Patient Preference Survey Designed to understand patient needs & commercial potential “…Patient preference refers to a patient’s perspective, expectations, and goals for health, as well as the processes involved in evaluating the potential benefits, harms, and costs of each treatment o
Slide 50: >90% of Patients Preferred Ixo-vec over Today's Standard of Care
>90% of Patients Preferred Ixo-vec over Today’s Standard of Care 52-week results from LUNA pre-specified patient preference survey Would you prefer Ixo-vec therapy Would you want to receive Ixo-vec Would you recommend Ixo-vec to over the prior treatment(s) you therapy in your other eye if you had yo
Slide 51: Topical Steroid Eyedrops were Easy or Very Easy to Manage
Topical Steroid Eyedrops were Easy or Very Easy to Manage 52-week results from LUNA pre-specified patient preference survey Was the steroid treatment you received easy to manage? 5% 5% 13% 35% 60% 88% 95% Difluprednate Ozurdex + Oral Prednisone + Only Difluprednate Difluprednate +/- Ozurdex (n=20) (
Slide 52: 100% of Ixo-vec 6E10 + Steroid Drops Preferred it over Standard of Care
100% of Ixo-vec 6E0 + Steroid Drops Preferred it over Standard of Care 52-week results from LUNA pre-specified patient preference survey Would you prefer Ixo-vec therapy Would you want to receive Ixo-vec Would you recommend Ixo-vec to over the prior treatment(s) you therapy in your other eye if you
Slide 53: Commercial Opportunity
Commercial Opportunity
Slide 54: Large and Growing Global Market Opportunity
Large and Growing Global Market Opportunity Wet AMD physicians and patients embrace innovation Wet Age-Related Macular Degeneration Multi-Billion Dollar Market Opportunity A leading cause of vision loss among older adults Growth driven by aging population and product innovation Global Wet AMD Sales
Slide 55: Ixo-vec is Poised to Transform How wAMD is Treated
Ixo-vec is Poised to Transform How wAMD is Treated Potential product profile designed to fit needs of key stakeholders Seamless Patient Powerful and Emerging Predictable Practice Preference Durable Safety Profile Product Profile Efficacy Profile Integration & Impact • Sustained vision • No new onset
Slide 56: Market Leadership in Wet AMD May Require Best-in-Class Profile
Market Leadership in Wet AMD May Require Best-in-Class Profile that First Demonstrates Success in Hard-to-Treat Patients Annual Injection Burden (IRIS Registry, Weighted Average) Adoption over time >9 Injections 7-9 Injections 4-6 Injections 1-3 Injections Early Adopters Subsequent Expansion Hard-to
Slide 57: Wet AMD May be the First Large-Market Indication for Gene Therapy
Wet AMD May be the First Large-Market Indication for Gene Therapy Market Epidemiology Economics Environment HIGH MASS MARKET URGENCY FOR ADOPTION PREVALENCE PRICING Lack of maintained vision in the Large addressable Lower cost per patient real-world suggest early adoption market at launch than orpha
Slide 58: CMC Positioned to Support Pivotal Program and Commercial Scale Up
CMC Positioned to Support Pivotal Program and Commercial Scale Up Ixo-vec currently manufactured at commercial scale Commercial-scale manufacturing in place at global CDMO Supported by robust regulatory CMC input All Ixo-vec Phase 3 material has been manufactured Cost-efficient Sf9 suspension proces
Slide 59: KOL Panel
KOL Panel (e LUNA
Slide 60: KOL Panel with Leading Retinal Specialists
KOL Panel with Leading Retinal Specialists Discussing LUNA and OPTIC Results, and Pivotal Trial Design M O DE RA T O R Charles C. Wykoff, MD, PhD Director of Research, Retina Consultants of Texas Star Seyedkazemi, PharmD Chief Development Officer Szilárd Kiss, MD Mark Barakat, MD Distinguished Profe
Slide 61: Conclusion & Takeaways
Conclusion & Takeaways
Slide 62: Largest Treatment Burden Reduction in Hard-to-Treat Patients
Largest Treatment Burden Reduction in Hard-to-Treat Patients from 6 Months to > 4 Years % Annualized Reduction in Injection Burden 95% 92% 90% 89% 88% 86% 86% 85% 84% 84% 81% 81% 80% OPTIC (2E11) 76% 71% LUNA (6E10) 68% LUNA (2E11) RGX-314 SCS (2.5E11) RGX-314 SCS (5E11) RGX-314 SCS (1E12) 4D-150 (1
Slide 63: Highest Injection-Free Rates in Hard-to-Treat Patients
Highest Injection-Free Rates in Hard-to-Treat Patients from 6 Months to > 4 Years % Injection-Free 83% 76% 73% OPTIC (2E11) 69% LUNA (6E10) 63% 60% LUNA (2E11) 54% 53% 53% 50% 50% 47% 37% 37% RGX-314 SCS (2.5E11) RGX-314 SCS (5E11) 29% 25% RGX-314 SCS (1E12) 4D-150 (1E10) 4D-150 (3E10) Month 6 Year:
Slide 64: 5+ Years of Clinical Experience Establish 10x Safety Margin
5+ Years of Clinical Experience Establish 10x Safety Margin Ixo-vec 6E10 with extended prophylaxis de-risks Phase 3 & commercialization 6E11 Phase 3 Dose N=15 ü Enhanced Safety Profile ü Extended Steroid Prophylaxis ü Potential Best-in-Class Efficacy Profile 2E11 2E11 N=15 N=30 6E10 N=30 4+ Years Cl
Slide 65: Reliable Benefit & Predictable Safety Enable True Paradigm Shift
Reliable Benefit & Predictable Safety Enable True Paradigm Shift 4-year OPTIC & 52-week LUNA data underscore Ixo-vec’s profile Demonstrated Reliable Long-Term Benefit 78% of patients who were injection free through year 1 remained injection free through year 4 88% of patients who were injection free
Slide 66: Ixo-vec's Derisked Phase 3 and Commercial Profile
Ixo-vec’s Derisked Phase 3 and Commercial Profile Clinical updates underscore Ixo-vec’s potential best-in-class product profile • Potential best-in-class product profile >50% injection free and >80% treatment burden reduction in hard-to-treat patients • 10X safety margin with >4 years follow-up • No
Slide 67: ADVERUM
ADVERUM
Slide 68: Question & Answer Session
Question & Answer Session Laurent Fischer, MD Rabia Gurses Ozden, MD Star Seyedkazemi, PharmD President and Chief Medical Officer Chief Development Officer Chief Executive Officer Linda Rubinstein Mike Zanoni Jason Mitchell Peter Soparkar Chief Financial Officer Head of Investor Relations Chief Comm
Slide 69: www.adverum.com
www.adverum.com For additional questions reach out to: IR@adverum.com ® Preserving Sight for Life
Slide 70: Appendix: IVT Gene Therapy for the Treatment of wet AMD
Appendix IVT Gene Therapy for the Treatment of wet AMD
Slide 71: LUNA & OPTIC Study Disposition
LUNA & OPTIC Study Disposition 90 patients enrolled across LUNA & OPTIC trials LUNA OPTIC PARTICIPANT DISPOSITION Total Total Number of participants enrolled and dosed with Ixo-vec 60 30 Number of participants who completed 52-week visit 57 30 Number of participants enrolled in open-label extension
Slide 72: Response to Anti-VEGF in Treatment Naïve vs Treatment Experienced Wet AMD
Response to Anti-VEGF in Treatment Naïve vs Treatment Experienced Wet AMD: Similar BCVA Trajectories After Initial 2 Loading Doses Treatment Naive Treatment Experienced 10 15 8 10 5 6 0 -5 4 -10 2 -15 0 4 8 12 16 20 24 28 32 36 40 0 0 4 8 12 16 20 24 28 32 36 40 44 48 Weeks Weeks 6 15 5 4 10 3 2 5 1
Slide 73: CST Maintained in Patients with High Disease Burden
CST Maintained in Patients with High Disease Burden Fluid reduction in patients with baseline CST >300 μm; maintenance in ≤300 μm Mean CST Change from Baseline at Week 52, μm (95% CI) 150 LUNA Baseline CST ≤300μm (n=27) LUNA Baseline CST >300μm (n=33) 2.9 (-14.3, 20.2) BL ≤300 μm 100 6E10 9.2 (-24.6
Slide 74: Stable Intraocular Pressure at Both Doses
Stable Intraocular Pressure at Both Doses Mean IOP Over Time by Dose 6E10 30 6E10 Study Eye 6E10 Fellow Eye 25 20 15 10 5 0 // 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 BL Week 2E11 2E11 Study Eye 2E11 Fellow Eye 30 25 20 15 10 5 0 // BL 0 2 4 6 8 10 12 14 16 18 20
Slide 75: LUNA Overall Population: Frequency of Inflammation
LUNA Overall Population: Frequency of Inflammation No patients at 6E10 had inflammation at week 52 or at any subsequent visit Frequency of Inflammation Over Time by Dose 6E10 2E11 LUNA LUNA 30 30 25 25 20 20 15 15 10 10 5 5 0 0 0 2 4 6 8 1012141618202224262830323436384042444648505254565860626466 0 2
Slide 76: Case Study: Ixo-vec 2E11 Reduces Fluctuations in Fluid and CST
Case Study: Ixo-vec 2E11 Reduces Fluctuations in Fluid and Central Subfield Thickness (CST) 90-Year-Old Female with 9 IVTs in the 12 Months Prior to Ixo-vec -56 weeks Aflibercept Q5W prior to Ixo-vec -2 wks (baseline) 90 BCVA: 53 letters CST: 358 µm 80 70 Day 0 60 Ixo-vec administration 50 40 0 1 2
Slide 77: Case Study: Ixo-vec 2E11 Reduces Fluctuations in Fluid and CST
Case Study: Ixo-vec 2E11 Reduces Fluctuations in Fluid and Central Subfield Thickness (CST) 90-Year-Old Female with 9 IVTs in the 12 Months Prior to Ixo-vec -56 weeks Aflibercept Q5W prior to Ixo-vec 100% anti-VEGF injection free following Ixo-vec Ixo-vec -2 wks (baseline) 90 BCVA: 53 letters CST: 3
Slide 78: ADVERUM
ADVERUM
Adverum Biotechnologies — Technical Presentation (November 2024) on 6ix