Ixo-vec Phase 2 Results from the 26-Week Interim Analysis Company Conference Call July 17th, 2024 Forward-Looking Statements Statements contained in this press release regarding events or results that may occur in the fu

Ixo-vec Phase 2 Results from the

26-Week Interim Analysis Company Conference Call July 17th, 2024

Forward-Looking Statements Statements contained in this press release regarding events or results that may

occur in the future are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include but are not limited to statements regarding the favorable safety profile and potential

best-in-class efficacy of Ixo-vec, anticipated timing of interim data and trial design update for the Phase 2 LUNA trial and

initiation of a Phase 3 trial, and the potential of Ixo-vec to shift the treatment paradigm for patients with wet AMD. Actual results could differ materially from those anticipated in such forward-looking

statements as a result of various risks and uncertainties, including risks inherent to, without limitation: Adverum s novel technology, which makes it difficult to predict the timing of commencement and completion of clinical trials; regulatory

uncertainties; enrollment uncertainties; the results of early clinical trials not always being predictive of future clinical trials and results; and the potential for future complications or side effects in connection with use of Ixo-vec. Additional risks and uncertainties facing Adverum are set forth under the caption Risk Factors and elsewhere in Adverum s Securities and Exchange Commission (SEC) filings and reports,

including Adverum s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024 filed with the SEC on May 9, 2024 and subsequent filings with the SEC. All forward-looking statements

contained in this press release speak only as of the date on which they were made. Adverum undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as

Overview & Key Takeaways Laurent Fischer, MD President and Chief Executive Officer

Key Learnings from OPTIC Informed the LUNA Phase 2 Study Robust and sustained therapeutic levels of

aflibercept beyond four years. The mean annualized anti-VEGF injection rate was reduced by 84% at 2E11 vg/eye at three years 53% of participants receiving 2E11 vg/eye were injection free at three years. Ixo-vec in wet AMD was well tolerated and ocular inflammation was minimal and responsive to corticosteroid eye drops. No correlation between NAbs titer and safety events, including inflammation, was observed.

Phase 2 study in wet AMD investigating Ixo-vec at 2E11 vg/eye dose and a lower 6E10 vg/eye dose, as well as new enhanced prophylactic corticosteroid regimens. 4

Ixo-vec Demonstrates Potential Best-In-Class Profile 6E10 Dose Selected for Phase 3 Key Takeaways Potential Best-in-Class Product Profile for Ixo-vec at 6E10 Dose Industry Leading Proportion of Patients Injection Free: 76% of patients injection free Treatment Burden Reduction: 90% reduction in annualized injections Visual and Anatomic

Endpoints: maintained through 26 weeks Improved Safety Profile Compared to OPTIC 2E11 Dose: 100% of 6E10 difluprednate-alone patients had no or minimal inflammation No 6E10 difluprednate-alone patients received corticosteroids

for treatment of inflammation beyond the scheduled prophylaxis Strong Patient Preference for Ixo-vec (with Prophylaxis) over Standard of Care 88% of LUNA participants prefer Ixo-vec over their prior anti-VEGF injections 93% would want to receive Ixo-vec in the fellow eye 6E10 Selected for Phase 3 with Local Prophylaxis 5

Envisioning the Future of Treatment for Wet AMD, Leading Cause of Blindness in Patients Over 65 1.5M patients

U.S.1,2 20M worldwide.1,2 Today Tomorrow ~200,000 new cases every year.1,2 Life Long IVT Injections Gene Therapy s Potential 3,4 Lifetime vision Real world loss of vision preservation One and done Lifetime injections burden outpatient IVT 13%

of Medicare Part B cost5 Direct and indirect $139B due to vision loss6 health-system Up to 42% develop bilateral disease within 2-3 years of initial diagnosis7 savings 1Bright Focus Foundation. Age-Related Macular Degeneration: Facts & Figures. 2Wong WL, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and

2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2:106 16. 3Holz FG et al. Br J Ophthalmol 2015; 99 (2): 220 226. 4Khanani A, et al. Ophthal. Retina 2020 Feb; 4(2):122-123.

5CMS/Office of Enterprise Data & Analytics (OEDA), January 2022. Nguyen X. Nguyen, T. Anders Olsen, Steven H. Sheingold, and Nancy Delew. Medicare Part B Drugs: Trends in Spending and Utilization, 2008- 2021. Washington, DC: Office of the

Assistant Secretary for Planning and Evaluation, U.S. Department of Health and Human Services. June, 2023. 6 6In 2021; based on Department of HHS and corporate anti-VEGF revenue reports. 7Gangnon RE et al. (2015) JAMA Ophthalmol; 133 (2):

125 132. Rasmussen A. et al., (2017) Eye 31, 978 980 (2017). Wong TY, et al. (2020) Retina. 40, 599-611 Zarranz-Ventura J et al. (2014). Ophthalmology; 121 (10): 1966 1975.

Ixo-vec May Preserve Vision Over Time With a Single Injection

Illustrative Long-Term Vision Outcome Ixo-vec Levels 15 Aflibercept Ixo-vec* 10 Continuous stable aflibercept levels (4.5 years demonstrated in OPTIC) baseline) 5 Acuity

0 SoCfrom Real-world change -5 evidence Levels Visual Aflibercept (letter -10 Missed Injection Missed Injection Missed Injection Up to 57% STOP anti-VEGF over 5 years** -15 Bolus injections AND undertreatment lead to fluctuations in anti-VEGF and to CST -20 0 1 2 3 4Years 5 6 7 8 9 10 SoC curve is based on CATT, HARBOR, and 7UP extension out

to 5 years, with years 5-10 modeled. Sources: Weng CY, Singh RP, Gillies MC, Regillo CD. Optimizing Visual Outcomes in Patients With Neovascular Age-Related Macular

Degeneration: the Potential Value of Sustained Anti-VEGF Therapy. Ophthalmic Surg Lasers Imaging Retina. 2023 Nov;54(11):654-659, *Potential Ixo-vec curve illustrated

based on OPTIC results Khanani et al. Lancet eClinical Medicine THE LANCET Discovery Science 7 2024. **Boulanger-Scemama E, et al. Ranibizumab for exudative age-related macular degeneration: A five year

study of adherence to follow-up in a real-life setting. J Fr Ophtalmol. 2015;38:620 7.

The Evolution of Wet AMD Treatment and Potential Future Advancements Past Present Future Reduction in treatment

burden Prevention of significant Gain of vision on + Extended durability + Preservation vision loss treatment initiation and/or vision gain 1st Generation 2nd Generation TKIs & PDS Gene Therapy Laser Photocoagulation Ixo-vec CLS-AX Axpaxli EYP-1901 4D-150 Verteporfin Photodynamic Therapy (PDT) ABBV-RGX-314 4-8 weeks 4-16 weeks ~6 months 3 years to lifetime 8 TKI = tyrosine kinase

inhibitors; PDS = Port Delivery System, or Susvim ; 1-3 lead-in aflibercept injections required as part of trial design.

OPTIC Data Suggest Potential Best-in-Class Reduction in

Injections, Vision Preservation > 3 Years, and Aflibercept Up to 4.5 Years OPTIC Key Takeaways , Durability demonstrated with aflibercept levels to 4.5 years in the longest wet AMD IVT gene therapy dataset , Highest 3-year % injection free , Greatest annualized injection rate reduction 53% of Patients , 2E11 dose well tolerated through 3 years of follow-up Free of

Injections Through 3 Years *Cataract surgery 9 Khanani et al. Lancet eClinincal Medicine THE LANCET Discovery Science. 2024; Regillo CD. AAO Annual Meeting 2023. San Francisco, CA

Efficacy & Safety Results Charles C. Wykoff, MD, PhD Director of Research, Retina Consultants of Texas

Professor of Clinical Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital

LUNA Phase 2 Trial in Previously Treated Patients with nAMD 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 of 2 injections within 4 months of entry), study eye BCVA in the range of 25

83 ETDRS letters Day -21 to -14: DAY -7: DAY 1: WEEK 26: WEEK 52: FIVE YEAR: Baseline Randomization Interim Analysis

Primary Endpoints EXT Completion IVT Aflibercept 2mg IVT Ixo-vec 2x1011 vg/eye (n=30) Long-term Screening Period extension ends 6x1010 vg/eye (n=30) at year five Corticosteroid prophylaxis (21 weeks post-dose)

Corticosteroid Prophylaxis Supplemental Injection Criteria Difluprednate 22 wks prednisone oral 10 wks Increase in CST > 75 m from BL confirmed by the CRC OR Ozurdex IVT + difluprednate after week 4

prednisone oral 10 wks* Loss of 10 letters in BCVA from BL due to new/worsening IRF or SRF OR Randomized 2:1 local versus local + oral New vision-threatening hemorrhage due to nAMD Study timeline and length of arrows depicted

are not to scale. Baseline is defined as the day screening aflibercept is admini stered. *Protocol amended early in study to include difluprednate starting at week 4 to match the taper in difluprednate regimens; if initiated after week 4 visit,

difluprednate may be adjusted at the discretion of investigator in consult with medical monitors (6 participants did not receive difluprednate as part of prophylaxis). BCVA, best 11 corrected visual acuity; CST, central subfield thickness; BL,

baseline; CRC, central reading center; IRF, intraretinal fluid; SRF, subretinal fluid

LUNA Study Disposition Participant Disposition Number of participants randomized and dosed with Ixo-vec 60 Number of participants who completed Week 26 58 Number of participants who discontinued after Ixo-vec dosing 2 Reason for discontinuation (not related to Ixo-vec) Death (Abdominal mesenteric mass, multiple organ failure, and septic shock not related to study drug) 1 Adverse event (Dementia not related to study drug) 1 Patients who received

at least one injection of anti-VEGF agent in year prior to Screen Aflibercept 44 (73%) Bevacizumab 15 (25%) Ranibizumab 15 (25%) Faricimab 10 (17%) Other 1 (2%) Prespecified interim analysis performed when all

participants completed the 26-week study visit 12 Data cut: 14Feb2024

LUNA Demographics and Baseline Characteristics LUNA LUNA LUNA OPTIC Demographics and Baseline Characteristics

6E10 2E11 Total Total 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 (57%) 15 (50%) Race, n (%) White 27 (90%) 28 (93%) 55 (92%) 30 (100%) Asian 2 (7%) 2 (7%) 4 (7%) 0

Mean years since nAMD diagnosis in the study eye (SD) 3.0 (2.9) 3.0 (3.1) 3.0 (2.9) 3.7 (2.8) Mean annualized anti-VEGF injections in year prior to 10.2 (1.7) 10.0 (3.3) 10.1 (2.6) 9.9 (1.9) Day 1 (SD) Mean BCVA, ETDRS letters (SD) 72.9 (8.8) 71.8

(6.4) 72.3 (7.7) 65.4 (7.2) 360.6 340.5 350.6 397.0 Mean CST, m (SD) (112.0) (119.3) (115.2) (137.3) Phakic lens status, n (%) 11 (37%) 11 (37%) 22 (37%) 10 (33.3%) 13 Data cut: 14Feb2024

90 Ixo 95% vec Anti Doses, -VEGF on Track Treatment with OPTIC Burden Reduction Across Both 11 10.2 10.1

9.9 10 Injections 9 8 VEGF 7 Anti 6 5 90% 95% 86% 4 3 Annualized 2 1.4 1.0 0.5 Mean 1 0 Axis LUNA LUNA 6E10 10 LUNA UNA 2E11 2E11 OPTIC O C 2E11 2E11 N=29 N=29 N=15 Mean Prior Annualized Injections Mean Post-Ixo-vec Annualized Injections 14

76 on- 83% Track of with Patients OPTIC Injection Free Across Both Ixo-vec Doses, Injection Free Injection Free Injection Free 76% 83% 73% LUNA 6E10 LUNA 2E11 OPTIC 2E11 15 Data cut: 14Feb2024

79% Injection Free & > 90% Reduction in Treatment Burden Across Both Doses Ixo-vec % Injection Free Overall 79% (N=60) 6E10 76% vg/eye Participants 2E11 83% All vg/eye 7 Participants with 1 Injection 5 Participants with >1 Injection -1 Year Study

Week Week 26 Aflibercept Bevacizumab Ranibizumab Faricimab Other No supplemental injection given Supplemental injection administered out of protocol 16 Doses pooled in swim lane plot to preserve investigator masking in an ongoing double masked

study. Data cut: 14Feb2024

Both Doses of Ixo-vec Maintained Visual & Anatomic Outcomes

Mean Best Corrected Visual Acuity (BCVA) Over Time by Dose 90 LS Means BCVA Change from 6E10 (n=30) 2E11 (n=30) OPTIC 2E11 (n=15) 85 Baseline at Week 26, letters (CI) 80 -1.1

(-3.5, 1.2) 75 6E10 vg/eye (CI) 70 65 -2.2 (-4.5, 0.2) BCVA 60 2E11 vg/eye 55 -1.8 (-5.8, 2.2) 50 45 2E11 vg/eye 40 // OPTIC BL 2 4 6 8 10 12 14 16 18 20 22 24 26 28 Week Mean Central Subfield Thickness (CST) Over Time by Dose 550 6E10 (n=30) 2E11 (n=30) OPTIC 2E11 (n=15) LS Means CST Change from

500 Baseline at Week 26, m (CI) 450 -12.6 (-30.2, 5.0) (CI) 400 6E10 vg/eye m 350 300 -12.0

(-30.0, 6.0) CST 250 2E11 vg/eye 200 150 -71.1 (-130.79, -11.47) 100 // 2E11 vg/eye BL 2

4 6 8 10 12 14 16 18 20 22 24 26 28 OPTIC Week 17 LUNA 95% CI; OPTIC 90% CI. LUNA and OPTIC differ in study visit cadence. LUNA: Least Squares Means change in BCVA and CST shown (based on Mixed Model Repeated Measures [MMRM] including dose group,

baseline value, visit and visit*dose group). OPTIC: Mean change in BCVA and CST shown Data cut: 14Feb2024

Both Doses of Ixo-vec Maintained Visual and Anatomic Outcomes in

Supplemental Injection-Free Participants Mean Change in BCVA Over Time in Supplemental Injection Free Participants, by Dose 15 6E10 (n=23) 2E11 (n=25) Mean BCVA Change 10 from Baseline at Week 26, BCVA Letters (95% CI) CI) 5 +0.3 (-2.6, 3.2) Change(95% 0 6E10 vg/eye Mean -5 -2.1 (-5.8, 1.6)

-10 2E11 vg/eye -15 // BL 2 4 6 8 10 14 18 22 26 Week Mean Change in CST Over Time in Supplemental Injection Free Participants, by Dose 200 6E10 (n=23) 2E11 (n=25) Mean

CST Change m 150 from Baseline at Week 26, m (95% CI) 100 CST 50 -11.4 (-29.2, 6.4) CI) 6E10 vg/eye Change(95% 0 -50 -15.9 (-38.4, 6.6) Mean -100 2E11 vg/eye -150 -200 //

BL 2 4 6 8 10 12 14 16 18 20 22 24 26 18 Week Data cut: 14Feb2024

Ixo-vec Maintains Anatomic Control with Greater CST Reduction Among

Participants with Baseline CST >300 m 150 LUNA Baseline CST 300 m (n=27) LUNA Baseline CST >300 m (n=33) m Mean CST Change from 100 Baseline at Week 26, m (95% CI) Baseline, 50 7.4 (-8.6, 23.5) BL

300 m fromCI) 0 -30.2 (-55.2, -5.1) (95% BL >300 m Change -50 CST Mean -100 -150 // BL 2 4 6 8 10 14 18 22 26 Week Baseline Characteristic for Subgroup CST 300 m CST >300 m Mean CST, m (SD) 269.9 (18.7) 416.6 (119.1) 19

Aqueous Aflibercept Levels of Ixo-vec Demonstrate Therapeutic Levels

Beyond 3 Years Early aflibercept levels are associated with sustained long-term protein expression No minimum aqueous humor aflibercept threshold for clinical benefit observed Data cuts: LUNA as of 15Nov2023, OPTIC as of 23Aug2023. LUNA Week 14

aflibercept levels plotted for 26 of 30 individual participants. 4 samples across both the 2E11 and 6E10 doses had aqueous aflibercept levels (ELISA assay BLOQ: <25 ng/ml). Of these, 2 were free of injections and 2 had either 1 or 2 supplemental

injections through at least week 26. LUNA revised to stop collection of AH samples. *Participant received supplemental aflibercept injections at weeks 36, 52, 64, 68, 76, 80, 88, 92, 100, 130, 143, 156. 58% reduction in annualized anti-VEGF

injections 3 years post-Ixo-vec compared to 12 months prior to Ixo-vec. **Participant received supplemental aflibercept injections at weeks 24, 64, 72, 80, and 156. 81% reduction in annualized anti-VEGF

injections 3 years post-Ixo-vec compared to 12 months prior to Ixo-vec. At three timepoints (not indicated on plot), aflibercept levels were BLOQ. 20

Safety Summary of the LUNA 26-week Interim Analysis Ixo-vec was well tolerated at both doses No Ixo-vec-related serious adverse events. All Ixo-vec-related AEs were either mild or moderate No episcleritis, vasculitis, retinitis, choroiditis, vascular

occlusion, or hypotony Most common Ixo-vec-related AEs1 were dose-dependent anterior inflammation responsive to local corticosteroids and anterior pigmentary changes with no impact on vision Both local prophylaxis regimens are

promising Improved inflammatory profile observed with enhanced prophylaxis in LUNA as compared to OPTIC2 Oral prednisone did not demonstrate incremental benefit IVT dexamethasone without difluprednate did not provide adequate

prophylaxis Local corticosteroid prophylaxis3 was effective in minimizing inflammation with 91% of participants having no or minimal inflammation (0 or trace/0.5+ AC cells) at any study visit through Week 26 1Anterior chamber cell, anterior

chamber pigmentation, iris transillumination defect, iritis 21 2Khanani AM. Retina Society Annual Meeting Presentation 2021, Chicago, IL 3Topical difluprednate with or without IVT dexamethasone (N=34) Data cut: 14Feb2024

Benefit of Enhanced Local Corticosteroid Prophylaxis Highlighted in LUNA Interim Analysis Observed Benefit of

Difluprednate Added to No Observed Benefit of Oral Prednisone IVT Dexamethasone Highest Inflammatory AC Cell Grade Highest Inflammatory AC Cell Grade through Week 26 through Week 26 Grade 0 Grade 0.5+ Grade 1+ Grade 2+ Grade 3+ Grade 0 Grade 0.5+

Grade 1+ Grade 2+ 100 4% 100 90 17% 4% 6% 5% 17% 90 3% 5% 80 9% 17% 80 25% 70 70 60 Protocol amended to add Participants 60 difluprednate eye drops Participants of 50 33% 91% after week 4 of 50 40 91% 90% 66% 74% 40 82% 30 30 65% Percentage 20 20

33% Percentage 10 10 0 0 IVT dexamethasone IVT dexamethasone + Local corticosteroids only Oral prednisone + local oral prednisone (N=6) difluprednate oral (N=34) corticosteroids (N=20) prednisone (N=23) AC, anterior chamber. 100%

pigmented cells excluded from analysis. Protocol amended early in study to include difluprednate after week 4 to match the taper in difluprednate regimens; if initiated after week 4 visit 22 difluprednate may be adjusted at the discretion of

investigator in consult with medical monitors (6 participants did not receive difluprednate topical as part of prophylaxis). 4+ AC cells due to Staph. epidermidis+ endophthalmitis post-AC tap (unrelated to Ixo-vec) in one participant excluded. Cell grades as assessed by slit lamp; grade categories are based on the Standardization of Uveitis Nomenclature (SUN) criteria for white blood cells. Data cut: 14Feb2024

Local Corticosteroid Prophylaxis Regimens were Effective in Minimizing Inflammation Interim LUNA data indicate

that ocular inflammation is primarily located in anterior chamber and responsive to local corticosteroids ANTERIOR CHAMBER CELLS VITREOUS CELLS + (N=14) Not all participants had completed prespecified DEXAMETHASONE prophylaxis by Week 26 IVT

DIFLUPREDNATE All participants had completed (N=20) prespecified prophylaxis DIFLUPREDNATE by Week 26 Doses pooled in heatmaps to preserve investigator masking in an ongoing double masked study. *Mixed pigmented and

non-pigmented cells are graded with the same color scheme and 23 scale as non-pigmented cells. p, pigmented cell. AC, anterior chamber. V, vitreous. Cell grades as

assessed by slit lamp; grade categories are based on the Standardization of Uveitis Nomenclature (SUN) and National Eye Institute Scores for white blood cells. No participant in the displayed arms had more than 2+. Data cut: 14Feb2024

6E10 Difluprednate-Alone Patients Had No Grade 1+ AC/V Cells, Did Not Require Corticosteroids for Inflammation

Beyond Prophylaxis Local Corticosteroid Prophylaxis Arms (N=34) Difluprednate Alone Prophylaxis Arms (N=20) Proportion of Participants Who Completed Prespecified Prophylactic Regimen by Week 26 Ixo-vec Ixo-vec 100% (%) 6E10 2E11 80% Participants at Week 26, n N = 10 N = 10 AC Cell Grade 0.5+ 1 0 60% All participants in 1+ 0 0 Participants 100% difluprednate alone regimen of have completed prophylaxis, 2+ 0 1 40%