Adverum Biotechnologies — Corporate Update (July 2024)
39 slides from Adverum Biotechnologies's corporate update, Jul 17, 2024
Slide 1: Ixo-vec Phase 2 Results from the 26-Week Interim Analysis
Ixo-vec Phase 2 Results from the 26-Week Interim Analysis Company Conference Call – July 17th, 2024
Slide 2: Forward-Looking Statements
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 regard
Slide 3: Overview & Key Takeaways
Overview & Key Takeaways Laurent Fischer, MD President and Chief Executive Officer
Slide 4: Key Learnings from OPTIC Informed the LUNA Phase 2 Study
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 thre
Slide 5: Ixo-vec Demonstrates Potential Best-In-Class Profile; 6E10 Dose Selected for Phase 3
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 a
Slide 6: Envisioning the Future of Treatment for Wet AMD
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 an
Slide 7: Ixo-vec May Preserve Vision Over Time With a Single Injection
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 (l
Slide 8: The Evolution of Wet AMD Treatment and Potential Future Advancements
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 Th
Slide 9: 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 OPTIC Key Takeaways ï,§ Durability demonstrated with aflibercept levels to 4.5 years in the longest wet AMD IVT gene therapy datasetï,§ Highest 3-year % injection freeï,
Slide 10: Efficacy & Safety Results
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
Slide 11: LUNA Phase 2 Trial in Previously Treated Patients with nAMD
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
Slide 12: LUNA Study Disposition
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
Slide 13: LUNA Demographics and Baseline Characteristics
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%
Slide 14: Anti-VEGF Treatment Burden Reduction Across Both Doses
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 Inject
Slide 15: Patients Injection Free Across Both Ixo-vec Doses
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
Slide 16: 79% Injection Free & >90% Reduction in Treatment Burden Across Both Doses
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 Fari
Slide 17: Both Doses of Ixo-vec Maintained Visual & Anatomic Outcomes
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 2E
Slide 18: Outcomes Maintained in Supplemental Injection-Free Participants
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
Slide 19: Anatomic Control with Greater CST Reduction Among Baseline CST >300 µm
Ixo-vec Maintains Anatomic Control with Greater CST Reduction Among Participants with Baseline CST >300 µm 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
Slide 20: Aqueous Aflibercept Levels Demonstrate Therapeutic Levels Beyond 3 Years
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.
Slide 21: Safety Summary of the LUNA 26-week Interim Analysis
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-ve
Slide 22: Benefit of Enhanced Local Corticosteroid Prophylaxis Highlighted in LUNA
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
Slide 23: Local Corticosteroid Prophylaxis Regimens Effective in Minimizing Inflammation
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 p
Slide 24: 6E10 Difluprednate-Alone Patients Had No Grade 1+ AC/V Cells
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 Wee
Slide 25: Enhanced Prophylaxis in LUNA Improves upon OPTIC 2E11
Enhanced Prophylaxis in LUNA Improves upon OPTIC 2E11 LUNA ANTERIOR CHAMBER CELLS LUNA vs OPTIC Comparison + (N=14) DEXAMETHASONE In LUNA, an extended prophylaxis beyond OPTIC’s IVT DIFLUPREDNATE 6-week topical regimen resulted in an improved inflammatory profile SCALE Local corticosteroid prophylax
Slide 26: Additional Analyses
Additional Analyses Laurent Fischer, MD Chief Executive Officer
Slide 27: 79% Injection Free & >90% Reduction in Treatment Burden Across Both Doses
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 Fari
Slide 28: 100% of Patients Previously Receiving Faricimab Remain Injection Free
100% of Patients Previously Receiving Faricimab (Vabysm ) Remain Injection Free Ixo-vec (N=10) Only 100% Injection Participants Free Faricimab -1 Year Study Week Week 26 Aflibercept Bevacizumab Ranibizumab Faricimab Other No supplemental injection given Supplemental injection administered out of pro
Slide 29: Ixo-vec: Greatest Reduction in Treatment Burden
Ixo-vec: Greatest Reduction in Treatment Burden at 6 Months to > 3 Years % Annualized Reduction in Injection Burden 90% 95% 86% 84% 84% 80% 80% 76% 68% Month 6 Year: 1 2 3 RGX-314 SCS (1E OPTIC (2E11) 4D-150 (1E10) Among IVT and Suprachoroidal gene therapy for wet AMD. ABBV-RGX-314 SCS in AAVIATE (N
Slide 30: Ixo-vec: Greatest % Injection Free
Ixo-vec: Greatest % Injection Free at 6 Months to > 3 Years % Injection Free 83% 76% 73% 60% 50% 50% 53% 53% 37% 29% Month 6 Year: 1 2 3 RGX-314 SCS (1E OPTIC (2E11) 4D-150 (1E10) Among IVT and Suprachoroidal gene therapy for wet AMD. ABBV-RGX-314 SCS in AAVIATE (NB: 21 of 56 subjects RGX-314 SCS (2
Slide 31: Pre-Specified Patient Preference Survey
Pre-Specified Patient Preference Survey Laurent Fischer, MD Chief Executive Officer
Slide 32: Patient Preference Survey: Questions Pre-specified in the LUNA Protocol
Patient Preference Survey: Questions at Week 26 Pre-specified in the LUNA Protocol Would you prefer Ixo-vec therapy over Would you want to receive Ixo-vec the prior treatment(s) you received to therapy in your other eye if you had wet treat your wet AMD? AMD in both eyes? 32 Based on a pre-specified
Slide 33: Vast Majority of LUNA Participants Prefer Ixo-vec Over Standard of Care
Patient Preference Survey: Vast Majority of LUNA Participants Prefer Ixo-vec Over Standard of Care anti-VEGF Would you prefer Ixo-vec therapy over Would you want to receive Ixo-vec the prior treatment(s) you received to therapy in your other eye if you had wet treat your wet AMD? AMD in both eyes? 1
Slide 34: 100% of LUNA 6E10 + Difluprednate Participants Prefer Ixo-vec
Patient Preference Survey: 100% of LUNA 6E10 + Difluprednate Participants Prefer Ixo-vec over Standard of Care anti-VEGF Would you prefer Ixo-vec therapy over Would you want to receive Ixo-vec the prior treatment(s) you received to therapy in your other eye if you had wet treat your wet AMD? AMD in
Slide 35: Ixo-vec Demonstrates Potential Best-In-Class Profile; Expected Milestones
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
Slide 36: 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 this pioneering research would not be pos
Slide 37: Appendix
Appendix
Slide 38: Mean Intraocular Pressure Stable at Both Ixo-vec Doses
Mean Intraocular Pressure Stable at Both Ixo-vec Doses Mean IOP Over Time by Dose 6x1010 vg/eye 2x1011 vg/eye 30 6E10 Study Eye 6E10 Fellow Eye 2E11 Study Eye 2E11 Fellow Eye 30 28 28 26 26 24 24 22 22 Hg 20 Hg 20 mm 18 18 16 mm 16 IOP 14 14 IOP 12 12 (SD) 10 10 (SD) 8 8 Mean 6 Mean 6 4 4 2 2 0 0 0
Slide 39: 90% Injection Free in Patients with ≤6 Prior Injections
90% were Injection Free Across Both Ixo-vec Doses in Patients with 6 Prior Injections in the Year Prior Ixo-vec % Injection Free (N=29) Overall 90% Injections 6x1010 100% Prior vg/eye 6 w/ 2x1011 82% vg/eye Participants 1 Participant with 1 Injection 2 Participants with >1 Injection -1 Year Study We
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