8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

February 8, 2024

Date of Report (Date of earliest event reported)

Adverum Biotechnologies, Inc.

(Exact Name of Registrant as Specified in Its Charter)

Delaware	001-36579	20-5258327
(State or Other Jurisdiction of Incorporation)	(Commission File Number)	(IRS Employer Identification Number)

100 Cardinal Way

Redwood City, CA 94063

(Address of principal executive offices, including zip code)

(650) 656-9323

(Registrant’s telephone number, including area code)

N/A

(Former name or former address, if changed since last report.)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title Of Each Class	Trading Symbol	Name Of Each Exchange On Which Registered
Common Stock	ADVM	Nasdaq Capital Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 7.01 Regulation FD.

On February 8, 2024, Adverum Biotechnologies, Inc. (the “Company”) updated its corporate presentation for use in meetings with investors, analysts and others. A copy of the corporate presentation is filed as Exhibit 99.1 hereto.

The information furnished under this Item 7.01, including Exhibit 99.1, shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section. The information under this Item 7.01, including Exhibit 99.1, shall not be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.

Item 8.01 Other Events.

On February 8, 2024, the Company announced preliminary efficacy and safety data from the LUNA Phase 2 trial of Ixoberogene soroparvovec (Ixo-vec) in patients with wet age-related macular degeneration (AMD).

LUNA Trial Background and Baseline Demographics

The LUNA trial is an ongoing double-masked, randomized, Phase 2 trial. 60 patients with wet AMD were enrolled equally across two dose cohorts, 2E11 and 6E10 vg/eye. The study is designed to assess optimized prophylactic regimens, with patients receiving one and/or two locally administered corticosteroid regimens, with or without oral prednisone.

The LUNA trial builds on the Company’s experience with the OPTIC study, where landmark 2-year data was recently published in The Lancet’s eclinicalmedicine.

The cut-off for these data is November 15, 2023, except for treatment burden reduction, which is as of January 2, 2024.

LUNA Preliminary Efficacy and Safety Data Summary

Both the 2E11 and 6E10 doses demonstrated maintenance of visual and anatomic outcomes. Notably, both doses resulted in reduction in annualized anti-vascular endothelial growth factor (VEGF) injections and the percentage of patients remaining free of annualized injections, with data trending similar to or better than the OPTIC study.

• Treatment Burden Reduction

• At 26 weeks, Ixo-vec demonstrated annualized reduction in anti-VEGF injection rates of 90% (n=19) at 6E10 and 94% (n=20) at 2E11.

• At 26 weeks, Ixo-vec demonstrated injection free rates of 68% (n=19) at 6E10 and 85% (n=20) at 2E11.

• Visual (BCVA) and Anatomic (CST) Outcomes:

• Visual acuity was maintained at both dose levels - mean BCVA change from baseline to last visit (95% CI):

• 2E11: -1.7 (-4.5, 1.2)

• 6E10: +0.5 (-2.2, 3.3)

• Anatomic endpoints were maintained at both dose levels - mean CST (µm) change from baseline to last visit (95% CI):

• 2E11: -16.4 (-31.5, -1.3)

• 6E10: -7.9 (-30.9, 15.0)

• In a sub-group analysis of patients with higher baseline CST, a greater reduction in CST was demonstrated

• Safety

• Preliminary data suggest corticosteroid prophylaxis optimization at both the 2E11 and 6E10 doses appears to result in improved inflammatory profiles in LUNA as compared to OPTIC study results.

• Ixo-vec was generally well-tolerated, and when present, intraocular inflammation was responsive to local corticosteroids.

• No Ixo-vec related serious adverse events were reported.

• No episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion or hypotony were reported.

• Preliminary data indicate that select prophylactic regimens are outperforming others that do not provide sustained prophylaxis.

• Early on in the study, the Company implemented a protocol amendment to augment the Ozurdex-containing regimens with a course of Durezol eye drops.

• Preliminary data indicate that the amended Ozurdex + Durezol regimen may be the favorable prophylactic regimen for future pivotal studies.

• In this potential “go-forward” regimen, the vast majority of patients had no inflammation, with over 90% of these patients having no or minimal inflammation. Oral corticosteroids showed no incremental benefit.

Upcoming Ixo-vec Milestones

• LUNA 26-week interim analysis expected mid-2024

• Continued FDA and EMA formal and informal regulatory interactions

• Initiation of Phase 3 trial expected H1’25

Forward-Looking Statements

Statements contained in this Item 8.01 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 potential benefits of Ixo-vec as a treatment for wet AMD and anticipated timing of preliminary and interim data from the Phase 2 LUNA trial and initiation of a Phase 3 trial. 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: the Company’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 the Company are set forth under the caption “Risk Factors” and elsewhere in Company’s Securities and Exchange Commission (SEC) filings and reports, including the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2023 filed with the SEC on November 9, 2023. All forward-looking statements contained in this Item 8.01 speak only as of the date on which they were made. The Company 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 required by law.

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits.

99.1	Corporate presentation, dated February 8, 2024.
104	Cover Page Interactive Data File (embedded within the Inline XBRL document).

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

	Adverum Biotechnologies, Inc.
Dated: February 8, 2024	By:	/s/ Laurent Fischer, M.D.
		Laurent Fischer, M.D. President and Chief Executive Officer

EX-99.1

Ixo-vec Phase 2 Initial LUNA Safety and Efficacy Data Q1’24 Exhibit 99.1

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 of 1995. Such statements include, but are not limited to, statements regarding plans and milestones related to Adverum Biotechnologies, Inc.’s (“Adverum”) product candidates, process development and manufacturing, clinical studies and trials, regulatory filings, the therapeutic and commercial potential of Adverum’s product candidates and the sufficiency of Adverum’s resources to fund lead programs, all of which are based on certain assumptions made by Adverum based on current conditions, expected future developments and other factors Adverum believes are appropriate under the circumstances. Adverum may not consummate any of these plans or these product, clinical development, process development, manufacturing, or regulatory goals in a timely manner, or at all, or otherwise carry out the intentions or meet the expectations or projections disclosed in its forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, the risk that Adverum’s resources will not be sufficient for Adverum to conduct or continue planned development programs and planned clinical trials, the risk that preliminary or interim data from Adverum’s clinical trials may change as more patient data become available, the risk of a delay in the enrollment of patients in Adverum’s clinical studies or in the manufacturing of products to be used in such clinical studies, risks and uncertainties inherent in the product development and the regulatory approval process, the risk that Adverum will not be able to successfully develop, manufacture, or commercialize any of its product candidates and the risk that Adverum will be delayed in receiving or fail to receive required regulatory approvals. 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 September 30, 2023 filed with the SEC on November 9, 2023. All forward-looking statements contained in this document 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 required by law.   This document contains, and any accompanying presentation may contain, estimates, projections and other information concerning Adverum’s industry, business and the markets for certain drugs, including data regarding the estimated size of those markets, their projected growth rates and the incidence of certain medical conditions. Information that is based on estimates, forecasts, projections or similar methodologies is inherently subject to uncertainties and actual amounts may differ materially from amounts reflected in this information. Unless otherwise expressly stated, Adverum obtained this industry, business, market and other data from reports, research surveys, studies and similar data prepared by third parties, industry, medical and general publications, government data and similar sources believed to be reliable, but the accuracy or completeness of such information is not guaranteed by, and should not be construed as representations made by, Adverum. This document also contains, and any accompanying presentation may contain, cross-trial comparisons. Cross-trial comparisons are not head-to-head clinical trials and are inherently limited and may suggest misleading similarities or differences in outcomes. Results of head-to-head comparisons may differ significantly from those set forth herein.

AAV2.7m8 capsid Promoter Aflibercept (anti-VEGF) AAV2.7m8 capsid engineered via directed evolution for enhanced transduction carrying a coding sequence for the anti-VEGF protein aflibercept Following a one-time IVT Ixo-vec injection, transduced retinal cells become the source of continual aflibercept production OPTIC 2x1011 vg/eye Participant with No Supplemental anti-VEGF Injections Through 3 Years Long-term data from the FIH OPTIC study demonstrate sustained efficacy outcomes through 3 years IVT injection of Ixo-vec Ixo-vec IVT Gene Therapy is Designed to Provide Continuous Delivery of Aflibercept for Long-term nAMD Management and Preservation of Vision IVT: intravitreal; FIH: first-in-human Grishanin, R, et.al. Molecular Ther 2019; 27(1), 118-129; Khanani AM et al. Lancet eClinical Medicine. 2024; Regillo CD. AAO Annual Meeting 2023. San Francisco, CA Baseline BCVA (ETDRS): 75 Year 3 BCVA (ETDRS): 80

Demonstrated Clinical Activity Reduction in Treatment Burden in patients requiring > 9 annualized anti-VEGF injections: >90% reduction in anti-VEGF injections 85% and 68% of patients remain free of injections at 6 months at 2E11 and 6E10 doses Visual Acuity: maintained BCVA at both doses Anatomic Endpoints: demonstrated stable CST at both doses Improved Safety Profile and Promising Prophylaxis: Promising local prophylactic options identified: Ozurdex + difluprednate drops led to > 90% of patients having no or minimal inflammation (0 or 0.5+ AC cells) Inflammation (primarily AC cells) responsive to local corticosteroids per protocol; no Ixo-vec related SAEs Key Takeaways Potential Best-In-Class Activity, Improved Safety Profile and Promising Prophylaxis for Pivotal Program Preliminary analysis of an ongoing trial, results may change.

Envisioning the Future of Treatment for Wet AMD, Leading Cause of Blindness in Patients Over 65 Today Tomorrow Real world loss of vision3,4 One and done outpatient IVT Lifetime vision preservation Direct and indirect health-system 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. 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. 1.5M patients U.S.1,2 Up to 42% develop bilateral disease within 2-3 years of initial diagnosis7 ~200,000 new cases every year.1,2 13% of Medicare Part B cost5 $139B due to vision loss6 Lifetime injections burden 20M worldwide.1,2 Life Long IVT Injections Gene Therapy’s Potential

Ixo-vec May Preserve Vision Over Time With a Single Injection 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 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. Ixo-vec* Real-world evidence Years Visual Acuity (letter change from baseline) Illustrative Long-Term Vision Outcome SoC Continuous stable aflibercept levels (4.5 years demonstrated in OPTIC) Aflibercept Levels Ixo-vec Bolus injections AND undertreatment lead to fluctuations in anti-VEGF Aflibercept Levels Missed Injection Missed Injection Missed Injection Up to 57% STOP anti-VEGF over 5 years**

The Evolution of Wet AMD Treatment and Potential Future Advancements Reduction in treatment burden Gain of vision on treatment initiation Laser Photocoagulation Past Present Future Verteporfin Photodynamic Therapy (PDT) 2nd Generation 4-16 weeks TKIs Axpaxli EYP-1901 CLS-AX ~6 months Gene Therapy Ixo-vec 4D-150 ABBV-RGX-314 ≥ 3 years to lifetime Prevention of significant vision loss 1st Generation 4-8 weeks + Extended durability + Preservation and/or vision gain TKI = tyrosine kinase inhibitors; 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 *Cataract surgery Khanani et al. Lancet eClinincal Medicine – THE LANCET Discovery Science. 2024; Regillo CD. AAO Annual Meeting 2023. San Francisco, CA 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 2E11 dose well tolerated through 3 years of follow-up 53% of Patients Free of Injections Through 3 Years

Corticosteroid Prophylaxis Supplemental Injection Criteria Difluprednate 22 wks ± prednisone oral 10 wks Ozurdex IVT + difluprednate after week 4 ± prednisone oral 10 wks Randomized 2:1 local versus local + oral Increase in CST > 75 μm from BL confirmed by the CRC OR Loss of ≥ 10 letters in BCVA from BL due to new/worsening IRF or SRF OR New vision-threatening hemorrhage due to nAMD LUNA Phase 2 Trial in Previously Treated Patients with Wet AMD 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 Study timeline and length of arrows depicted are not to scale Protocol amended early in study to include difluprednate after week 4 to match the taper in difluprednate regimens. Long-term extension ends at year five Screening Period 2x1011 vg/eye (n=30) 6x1010 vg/eye (n=30) WEEK 52: Primary Endpoint Week 26: Interim Analysis Day 1: IVT Ixo-vec randomization Aflibercept IVT 2mg FIVE year: EXT Completion Corticosteroid prophylaxis (21 weeks post-dose)

LUNA Study Disposition (as of 15 Nov 2023) Participant Disposition Number of subjects randomized and dosed with Ixo-vec 60 Number of participants who completed Week 14 54 Number of participants who completed Week 26 26 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) Adverse event (Dementia – not related to study drug) 1 1 Patients who received at least one injection of anti-VEGF agent in year prior to Screen Aflibercept Bevacizumab Ranibizumab Faricimab Other 43 (72%) 15 (25%) 15 (25%) 10 (17%) 1 (2%) Safety outcomes, AH aflibercept levels, BCVA, and CST current through 15Nov2023. Supplemental anti-VEGF data current through 02Jan2024. A prespecified interim analysis will be conducted when all participants complete their 26-week study visit

LUNA Demographics and Baseline Characteristics Demographics and Baseline Characteristics Ixo-vec 6E10 vg/eye N = 30 Ixo-vec 2E11 vg/eye N = 30 LUNA Total N = 60 OPTIC 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 Asian 27 (90%) 2 (7%) 28 (93%) 2 (7%) 55 (92%) 4 (7%) 30 (100%) 0 Mean years since nAMD diagnosis in the study eye (SD) 2.9 (2.8) 2.8 (3.1) 2.8 (2.9) 3.7 (2.8) Mean annualized anti-VEGF injections in year prior to Day 1 (SD) 10.0 (1.6) 9.7 (2.5) 9.9 (2.1) 9.9 (1.9) Mean BCVA, ETDRS letters (SD) 72.9 (8.8) 71.8 (6.4) 72.3 (7.7) 65.4 (7.2) Mean CST, mm (SD) 360.6 (112.0) 340.5 (119.3) 350.6 (115.2) 397.0 (137.3) Phakic lens status, n (%) 11 (37%) 11 (37%) 22 (37%) 10 (33.3%) Data cut: 15Nov2023

Compelling Injection Reduction at 6E10 and 2E11, on Track with OPTIC 91% 90% 85% 86% 95% 94% Mean Prior Annualized Injections Mean Post-Ixo-vec Annualized Injections Data cut: 02Jan2024 OPTIC 2E11 LUNA 2E11 LUNA 6E10

Compelling Injection Free Rates at 6E10 and 2E11, on Track with OPTIC 91% 90% 85% 86% 95% 94% Mean Prior Annualized Injections Mean Post-Ixo-vec Annualized Injections OPTIC 2E11 LUNA 2E11 LUNA 6E10 Injection Free 86% 68% Injection Free 87% 85% Injection Free 80% 73% Data cut: 02Jan2024

93% Anti-VEGF Treatment Burden Reduction Across Both Doses in Patients Needing Mean > 9 Annualized Injections Before Ixo-vec Data cut: 02Jan2024. 71% reduction of annualized injections across both doses in subset of patients who received supplemental Injections. Ixo-vec 9 Participants with 1 Injection 6 Participants with >1 Injection 93% Reduction in Annualized Anti-VEGF 75%  Injection Free -1 Year 26 14 18 22 10 8 6 4 30 34 38 42 48 52 Study Week

30 30 29 30 30 29 28 23 20 13 30 30 28 30 30 29 28 23 20 12 30 30 30 30 29 29 26 21 15 12 Visual and Anatomic Outcomes in LUNA Confirm Activity Observed in OPTIC Mean CST change from baseline to last visit, μm (CI) Mean Best Corrected Visual Acuity (BCVA) Over Time by Dose Mean Central Subfield Thickness (CST) Over Time by Dose N Mean BCVA change from baseline to last visit, letters (CI) +0.5 (-2.2, 3.3) 6E10 vg/eye -1.7 (-4.5, 1.2) 2E11 vg/eye N -7.9 (-30.9, 15.0) 6E10 vg/eye -16.4 (-31.5, -1.3) 2E11 vg/eye 30 30 30 30 29 29 26 21 15 12 N N +0.2 (-4.6, 5.0) 2E11 vg/eye OPTIC (n=15) Data cut: 15Nov20323. LUNA 95% CI; OPTIC 90% CI. LUNA and OPTIC differ in study visit cadence -92.9 (-153.32, -32.55) 2E11 vg/eye OPTIC (N=15)

22 22 22 21 21 18 13 8 6 26 25 26 26 25 24 20 18 12 Stable Visual and Anatomic Control Maintained in Supplemental Injection Free Patients Mean CST change from baseline to last visit, μm (95% CI) Mean Change in BCVA Over Time in Supplemental Injection Free Participants, by Dose Mean Change in CST Over Time in Supplemental Injection Free Participants, by Dose Mean BCVA change from baseline to last visit, letters (95% CI) +2.7 (0.0, 5.4) 6x1010 vg/eye -1.2 (-4.1, 1.7) 2x1011 vg/eye -2.8 (-19.7, 14.2) 6x1010 vg/eye -14.8 (-32.1, 2.4) 2x1011 vg/eye 22 22 22 21 21 18 13 8 6 26 24 26 26 25 24 20 18 11 Data cut: 15Nov2023 N N N N

No minimum aqueous humor aflibercept threshold for clinical benefit observed Aqueous Aflibercept Levels at Both Doses in LUNA Demonstrate Ixo-vec Therapeutic Benefit Data cut: 15Nov2023. 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.  Early aflibercept levels are associated with sustained long-term protein expression OPTIC: all patients received therapeutic benefit OPTIC 2x1011 vg/eye (n=7) LUNA 2x1011 vg/eye (n=14) LUNA 6x1010 vg/eye (n=12) Data cut: 15Nov2023 * **

Ozurdex + Difluprednate Eyedrops Identified as Potential “Go-Forward” Regimen Ixo-vec was well-tolerated, with inflammation that was responsive to protocol-defined local corticosteroids No Ixo-vec related SAEs; Ixo-vec related AEs were all mild to moderate No episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion or hypotony Most common Ixo-vec related AEs were dose-related anterior inflammation (primarily AC cells) and anterior pigmentary changes; consistent with OPTIC 2E11 Local prophylaxis regimens are promising Ozurdex + Difluprednate regimen resulted in > 90% of patients having no or minimal inflammation (0 or 0.5+ AC cells) Optimized prophylaxis resulted in an improved inflammatory profile versus OPTIC 2E11, manageable with local steroids Ozurdex alone (± oral) did not provide adequate prophylaxis Oral corticosteroids showed no incremental benefit Data cut: 15Nov2023. OPTIC: Khanani et al. Lancet eClinincal Medicine – THE LANCET Discovery Science. 2024 LUNA Preliminary Safety Summary

Ozurdex + Difluprednate Eyedrops Identified as Potential “Go-Forward” Regimen Data cut: 15Nov2023. 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 subject had more than 2+. * Mixed pigmented and non-pigmented cells; pc, pigmented cell. 1. Includes post-data cut review of outcomes in 4 individual patients. The second patient in the LUNA Vitreous Cells Heatmap had 0.5+ vitreous cells in both eyes starting from Week 4 with both eyes resolving at Week 18 Preliminary LUNA data confirm that ocular inflammation is primarily located in anterior chamber, mild to moderate, and responsive to local corticosteroids1 LUNA ANTERIOR CHAMBER CELLS LUNA VITREOUS CELLS GRADING SCALE

Ozurdex + Difluprednate Eyedrops Identified as Potential “Go-Forward” Regimen Preliminary LUNA data confirm that ocular inflammation is primarily located in anterior chamber, mild to moderate, and responsive to local corticosteroids1 LUNA ANTERIOR CHAMBER CELLS LUNA VITREOUS CELLS GRADING SCALE Data cut: 15Nov2023. 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 subject had more than 2+. * Mixed pigmented and non-pigmented cells; pc, pigmented cell. 1. Includes post-data cut review of outcomes in 4 individual patients. The second patient in the difluprednate cohort had 0.5+ vitreous cells in both eyes starting from Week 4 with both eyes resolving at Week 18

Benefit of Difluprednate Added to Ozurdex No Observed Benefit of Oral Prednisone Preliminary Safety Analysis Prophylaxis for Ixo-vec IVT Gene Therapy Key Learnings Data cut: 15Nov2023 N=1 N=1 N=2 N=1 Protocol amended to add difluprednate eye drops after week 4 N=1 AC: anterior chamber cell. 100% pigmented cells excluded from analysis. One participant in Ozurdex alone arm had a single visit with 3+ AC cells that responded to local corticosteroids. Protocol amended early in study to include difluprednate after week 4 to match the taper in difluprednate regimens. 4+ AC cells due to Staph. epidermidis+ endophthalmitis post-AC tap (unrelated to Ixo-vec) in one participant excluded. *Includes one subject who received Ozurdex + difluprednate with 2+ AC cells at a single timepoint during an unscheduled visit. Cell grades as assessed by slit lamp, Grade categories are based on the Standardization of Uveitis Nomenclature (SUN) criteria for white blood cells

Benefit of Difluprednate Added to Ozurdex No Benefit of Oral Prednisone Preliminary Safety Analysis Prophylaxis for Ixo-vec IVT Gene Therapy Key Learnings Data cut: 15Nov2023 N=1 N=1 N=2 N=1 Protocol amended to add difluprednate eye drops after week 4 N=1 AC: anterior chamber cell. 100% pigmented cells excluded from analysis. One participant in Ozurdex alone arm had a single visit with 3+ AC cells that responded to local corticosteroids. Protocol amended early in study to include difluprednate after week 4 to match the taper in difluprednate regimens. 4+ AC cells due to Staph. epidermidis+ endophthalmitis post-AC tap (unrelated to Ixo-vec) in one participant excluded. *Includes one subject who received Ozurdex + difluprednate with 2+ AC cells at a single timepoint during an unscheduled visit. Cell grades as assessed by slit lamp, Grade categories are based on the Standardization of Uveitis Nomenclature (SUN) criteria for white blood cells

Ozurdex + Difluprednate Eyedrops Identified as Potential “Go-Forward” Regimen Optimized prophylaxis in LUNA resulted in an improved inflammatory profile versus OPTIC 2E11 Ozurdex + difluprednate resulted in > 90% of patients having no or minimal inflammation (0 or 0.5+ AC cells) Improved safety results in LUNA combined with efficacy on-track with OPTIC highlight potentially favorable benefit/risk profile of IVT Ixo-vec gene therapy for wet AMD Data cut: 15Nov2023. 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 subject had more than 2+. * Mixed pigmented and non-pigmented cells; pc, pigmented cell. Key Preliminary Learnings OPTIC 2E11 ANTERIOR CHAMBER CELLS LUNA ANTERIOR CHAMBER CELLS GRADING SCALE

Mean Intraocular Pressure is Stable at Both Ixo-vec Doses Mean IOP Over Time by Dose N 30 30 30 30 28 29 26 21 15 12 Data cut: 15Nov2023 30 30 29 30 30 29 28 23 20 13 2x1011 vg/eye 6x1010 vg/eye N

30 30 29 30 30 29 28 23 20 13 30 30 28 30 30 29 28 23 20 12 30 30 30 30 29 29 26 21 15 12 Visual and Anatomic Outcomes in LUNA Confirm Activity Observed in OPTIC Mean CST (μm) change from baseline to last visit (CI) Mean Best Corrected Visual Acuity (BCVA) Over Time by Dose Mean Central Subfield Thickness (CST) Over Time by Dose N Mean BCVA (letters) change from baseline to last visit (CI) +0.5 (-2.2, 3.3) 6E10 vg/eye -1.7 (-4.5, 1.2) 2E11 vg/eye N -7.9 (-30.9, 15.0) 6E10 vg/eye -16.4 (-31.5, -1.3) 2E11 vg/eye 30 30 30 30 29 29 26 21 15 12 N N +0.2 (-4.6, 5.0) 2E11 vg/eye OPTIC (n=15) Data cut: 15Nov20323. LUNA 95% CI; OPTIC 90% CI. LUNA and OPTIC differ in study visit cadence -92.9 (-153.32, -32.55) 2E11 vg/eye OPTIC (N=15)

Anatomic Control Maintained with Greater CST Reduction Among Participants with Baseline CST >300 mm Mean CST change from baseline to last visit, μm (95% CI) 3.4 (-11.1, 17.9) BL ≤300 μm 27 27 27 26 27 24 23 18 14 N -24.9 (-45.8, -4.0) BL >300 μm N Data cut: 15Nov2023 Baseline Baseline Characteristic for Subgroup CST ≤300 mm CST >300 mm Mean CST, mm (SD) 270 (19) 417 (119) CST measurement missing for one participant at week 4 and week 26 33 31 33 33 31 30 21 17 10

N Anatomic Control Maintained with Greater CST Reduction in LUNA and OPTIC Participants with Baseline CST >300 mm LUNA Mean CST change from baseline to last visit, μm (95% CI) N Data cut: 15Nov2023 Baseline Characteristic for Subgroup CST >300 mm LUNA Mean CST, mm (SD) 417 (119) OPTIC Mean CST, mm (SD) 429 (175) OPTIC Mean CST change from baseline to week 28, μm (95% CI) -80.5 (-164.6, 3.5) BL >300 μm -24.9 (-45.8, -4.0) BL >300 μm 33 31 33 33 31 30 21 17 10 13 13 12 13 13 12 12 11 13 Baseline CST measurement missing for one participant at week 4 and week 26

93% Anti-VEGF Treatment Burden Reduction Across Both Doses in Patients Needing Mean > 9 Annualized Injections Before Ixo-vec Data cut: 02Jan2024. 71% reduction of annualized injections across both doses in subset of patients who received supplemental Injections. Ixo-vec 9 Participants with 1 Injection 6 Participants with >1 Injection 93% Reduction in Annualized Anti-VEGF 75%  Injection Free -1 Year 26 14 18 22 10 8 6 4 30 34 38 42 48 52 Study Week

Data cut: 02Jan2024. Participants had >9 mean annualized injections in the year prior to Ixo-vec. Ixo-vec 100% Injection Free 10 of 10 Patients Previously Receiving Bispecific Antibody Faricimab Remain Free of Injection After a Single IVT Ixo-vec Out to 34 Weeks -1 Year 26 14 18 22 10 8 6 4 30 34 38 42 48 52 Study Week

Early LUNA Data Support Favorable Benefit-Risk Profile for Ixo-vec  OPTIC demonstrated Ixo-vec 2E11 was well tolerated with significant activity, durability up to 4.5 years LUNA preliminary data demonstrate potentially: Continued potential best-in-class reduction in treatment burden, comparable to OPTIC 2E11 Confirmed activity based on visual acuity (BCVA) and anatomic endpoints (CST) Ozurdex + difluprednate is emerging as prophylaxis of choice with an improved safety profile versus OPTIC  LUNA Preliminary Data Indicate “Go Forward” Prophylactic Regimen for P3 at 2 Doses LUNA 26-week interim analysis expected mid-2024 Continued FDA and EMA formal and informal interactions Initiation of Phase 3 expected H1’25 Expected Next Steps Toward Phase 3

Thank You! Our special thanks to: LUNA investigators, study coordinator and the study teams LUNA participants and their families OPTIC participants and their families Our scientific advisors and key opinion leaders Adverum team members without whom pioneering research would not be possible.

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Document and Entity Information	Feb. 08, 2024
Cover [Abstract]
Security Exchange Name	NASDAQ
Amendment Flag	false
Entity Central Index Key	0001501756
Document Type	8-K
Document Period End Date	Feb. 08, 2024
Entity Registrant Name	Adverum Biotechnologies, Inc.
Entity Incorporation State Country Code	DE
Entity File Number	001-36579
Entity Tax Identification Number	20-5258327
Entity Address, Address Line One	100 Cardinal Way
Entity Address, City or Town	Redwood City
Entity Address, State or Province	CA
Entity Address, Postal Zip Code	94063
City Area Code	(650)
Local Phone Number	656-9323
Written Communications	false
Soliciting Material	false
Pre Commencement Tender Offer	false
Pre Commencement Issuer Tender Offer	false
Security 12b Title	Common Stock
Trading Symbol	ADVM
Entity Emerging Growth Company	false