Adverum Biotechnologies — Technical Presentation (February 2024)
32 slides from Adverum Biotechnologies's technical presentation, Feb 8, 2024
Slide 1: Ixo-vec Phase 2 Initial LUNA Safety and Efficacy Data Q1'24
Ixo-vec Phase 2 Initial LUNA Safety and Efficacy Data Q1’24 Exhibit 99.1
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: Ixo-vec IVT Gene Therapy Designed to Provide Continuous Delivery of Aflibercept
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 aflibercep
Slide 4: Key Takeaways: Demonstrated Clinical Activity
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 En
Slide 5: Envisioning the Future of Treatment for Wet AMD
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: F
Slide 6: Ixo-vec May Preserve Vision Over Time With a Single Injection
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: t
Slide 7: The Evolution of Wet AMD Treatment and Potential Future Advancements
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 Ix
Slide 8: OPTIC Data Suggest Potential Best-in-Class Reduction in Injections
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 Takeaw
Slide 9: LUNA Phase 2 Trial in Previously Treated Patients with Wet AMD
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 fro
Slide 10: LUNA Study Disposition
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 discont
Slide 11: LUNA Demographics and Baseline Characteristics
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 (%)
Slide 12: Compelling Injection Reduction at 6E10 and 2E11
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
Slide 13: Compelling Injection Free Rates at 6E10 and 2E11
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
Slide 14: 93% Anti-VEGF Treatment Burden Reduction Across Both Doses
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 Injecti
Slide 15: Visual and Anatomic Outcomes in LUNA Confirm Activity Observed in OPTIC
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 Thic
Slide 16: Stable Visual and Anatomic Control in Supplemental Injection Free Patients
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 Ove
Slide 17: Aqueous Aflibercept Levels at Both Doses in LUNA
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
Slide 18: Ozurdex + Difluprednate Eyedrops Identified as Potential Go-Forward Regimen
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, cho
Slide 19: Ozurdex + Difluprednate Eyedrops Identified as Potential Go-Forward Regimen
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
Slide 20: Ozurdex + Difluprednate Eyedrops Identified as Potential Go-Forward Regimen
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
Slide 21: Benefit of Difluprednate Added to Ozurdex; No Observed Benefit of Oral Prednisone
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% pig
Slide 22: Benefit of Difluprednate Added to Ozurdex; No Benefit of Oral Prednisone
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 ce
Slide 23: Ozurdex + Difluprednate Eyedrops Identified as Potential Go-Forward Regimen
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 resu
Slide 24: Mean Intraocular Pressure is Stable at Both Ixo-vec Doses
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
Slide 25: Visual and Anatomic Outcomes in LUNA Confirm Activity Observed in OPTIC
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 Thi
Slide 26: Anatomic Control Maintained with Greater CST Reduction Among Baseline CST >300
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
Slide 27: Anatomic Control in LUNA and OPTIC Participants with Baseline CST >300
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 (
Slide 28: 93% Anti-VEGF Treatment Burden Reduction Across Both Doses
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 Injecti
Slide 29: Patients Previously Receiving Faricimab Remain Free of Injection
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
Slide 30: Early LUNA Data Support Favorable Benefit-Risk Profile for Ixo-vec
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 OP
Slide 31: Thank You!
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.
Slide 32: ADVERUM
ADVERUM
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