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nAMD: Clinical Progress from the LUNA Phase 2 Trial Charles C. Wykoff, M.D., Ph.D. Director of Research, Retina Consultants of Texas Professor of Clinical Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital Disclosures: C= Consultant |
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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 the potential benefits of Ixo-vec as a treatment of wet AMD, including the potential best-in-class product profile, clinical activity, favorable safety profile and long-term
benefit including quality of life benefits; plans and milestones related to Adverum's product candidates, clinical studies and trials, and regulatory filings; the therapeutic potential of Adverum's product candidates; the potential of
Ixo-vec to transform the TM treatment paradigm for patients with wet AMD; the potential of ixo-vec to be a One-And-Done IVT injection; the potential of ixo-vec to address the unmet need of patients with wet AMD; the design of Adverum's
clinical trials and anticipated timing of completion; the potential of Ixo-vec to meaningfully and sustainably reduce treatment burden while providing robust and durable disease control; and other statements containing the words
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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
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representations made by, Adverum. The safety and efficacy of Ixo-vec for the treatment of wet AMD have not been established. Ixo-vec has not been approved for any use by any regulatory authority, including the US FDA.
Ixo-vec: A Potentially Transformative Therapy for Wet AMD Ixo-vec Gene
therapy designed to preserve vision with a single intravitreal injection Single intravitreal Gold standard vector Transgene encoding Biofactory approach for injection in routine office for IVT gene therapy aflibercept, a clinically durable
therapeutic setting validated anti-VEGF protein levels 3 AMD, age-related macular degeneration; IVT, intravitreal.
Observations from OPTIC and LUNA Informed Phase 3 Trials * ARTEMIS
enrollment completed Population: Previously treated wet AMD patients with a high anti-VEGF injection burden 2-year Outcomes 5-year Outcomes 4-year Outcomes Ixo-vec OPTIC Phase 1 Study (N=30) Extension Study Corticosteroid Prophylaxis 6E11 vg/eye Key
Safety and tolerability Oral prednisone, 13 days 2E11 vg/eye Topical difluprednate, 6 weeks Outcomes Change from baseline in BCVA and CST Supplemental anti-VEGF injections Population: Previously treated wet AMD patients with a high anti-VEGF
injection burden 2-year Outcomes 5-year Outcomes 1-year Outcomes Ixo-vec LUNA Phase 2 Study (N=60) Extension Study Corticosteroid Prophylaxis Difluprednate 22 weeks oral prednisone 10 wks Safety and tolerability Key 2E11 vg/eye Ozurdex IVT +
difluprednate after week 4 prednisone oral 10 weeks Outcomes Change from baseline in BCVA and CST Randomized 2:1 local versus local + oral 6E10 vg/eye Supplemental anti-VEGF injections *Target enrollment (N=284) achieved.
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 to a Confidential and Proprietary 4 longer interval at
the discretion of investigator in consultation with medical monitors (n=6 did not receive difluprednate as part of prophylaxis). BCVA, best corrected visual acuity; CST, central subfield thickness; IVT, intravitreal.
Phase 1 OPTIC Trial 2E11 vg/eye: Marked and sustained reduction in
treatment burden (4-year results) BCVA and CST Maintained Through 4 Years Sustained Reduction in Injection Burden OPTIC OPTIC EXT Cumulative Annualized Reduction 12 9.9 500 Mean (90% CI) CST 10 84% 81% 84% 86% 400 8 6 300 4 200 1.9 1.6 1.6 1.4 2 100
0 0 12 24 36 48 60 72 84 96108120132144156168180192204 4 00 0 0.5 1 2 3 4 Prior Year 1 Year 2 Years 3 Years 4 Years Year 90 Mean (90% CI) BCVA Well Tolerated Through 4 Years 80 70 No hypotony, vasculitis, retinitis, choroiditis, or vascular
60 * occlusions 50 Inflammation was dose dependent, did not impact vision and, 40 when present, was responsive to local corticosteroids 30 000 12 24 36 48 60 72 84 96108120132144156168180192204 4 0 0.5 1 2 3 4 100% of inflammation
resolved by year 1 Year 5 *Cataract surgery. BCVA, best corrected visual acuity; CST, central subfield thickness. DATA CUT-OFF: 21AUG2024 Mean (90% CI) BCVA, Mean (90% CI) CST, m ETDRS letters Mean annualized injections
Ixo-vec Demonstrated Durable Therapeutic Levels After One Injection
Overlapping expression patterns across all 3 doses & 6E10 vg/eye consistent with higher doses Early aflibercept levels are predictive of long-term protein expression 100,000 1 NHP studies suggest aflibercept levels are ~ 7x higher in the back of
the eye 10,000 1,000 100 10 LUNA 2E11 vg/eye (n=19) LUNA 6E10 vg/eye (n=13) OPTIC 6E11 vg/eye (n=7) OPTIC 2E11 vg/eye (n=10) 1 0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228 240 252 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 Years In
OPTIC, all subjects tested had quantifiable aqueous humor aflibercept levels (one subject had levels above and below the limit of quantification [BLOQ, 25 ng/mL] at multiple time points). In LUNA, 32 of 38 subjects (84%) had quantifiable aqueous
humor aflibercept levels; the subjects with aflibercept concentrations BLOQ included subjects at both doses who remained injection free or experienced treatment burden reduction. Measurements BLOQ of the assay or within 8 weeks of supplemental
aflibercept 6 injections are not shown. LUNA protocol revised to stop collection of aqueous humor samples. 1. Kiss S et al. Mol Ther Method Clin Dev 2020;18:345-353. DATA CUT-OFF: OPTIC 21AUG2024, LUNA 29AUG2024 Aflibercept in Aqueous Humor
Observations from OPTIC and LUNA Informed Phase 3 Trial Design
Population: Previously treated wet AMD patients with a high anti-VEGF injection burden 2-year Outcomes 5-year Outcomes 4-year Outcomes Ixo-vec OPTIC Phase 1 Study (N=30) Extension Study Corticosteroid Prophylaxis 6E11 vg/eye Key Safety and
tolerability Oral prednisone, 13 days 2E11 vg/eye Topical difluprednate, 6 weeks Outcomes Change from baseline in BCVA and CST Supplemental anti-VEGF injections Population: Previously treated wet AMD patients with a high anti-VEGF injection burden
2-year Outcomes 5-year Outcomes 1-year Outcomes Ixo-vec LUNA Phase 2 Study (N=60) Extension Study Corticosteroid Prophylaxis Difluprednate 22 weeks oral prednisone 10 wks Safety and tolerability Key 2E11 vg/eye Ozurdex IVT + difluprednate
after week 4 prednisone oral 10 weeks* Outcomes Change from baseline in BCVA and CST Randomized 2:1 local versus local + oral* 6E10 vg/eye Supplemental anti-VEGF injections *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 to a longer interval at the discretion of Confidential and Proprietary 7 investigator in consultation with medical monitors (n=6 did
not receive difluprednate as part of prophylaxis). BCVA, best corrected visual acuity; CST, central subfield thickness; IVT, intravitreal.
Demographics and Baseline Characteristics LUNA evaluated Ixo-vec in nAMD
patients with a high injection burden 6E10 vg/eye 2E11 vg/eye Total N=30 N=30 N=60 Characteristics Mean (SD) age, years 75.4 (8.2) 77.7 (7.4) 76.6 (7.8) Female, n (%) 16 (53) 18 (60) 34 (57) Race, n (%) White 27 (90) 28 (93) 55 (92) Asian 2 (7) 2
(7) 4 (7) Mean (SD) years since nAMD diagnosis in study eye 3.0 (2.9) 3.0 (3.1) 3.0 (2.9) Mean (SD) annualized anti-VEGF injections in prior year 10.2 (1.7) 10.0 (3.3) 10.1 (2.6) Mean (SD) BCVA, ETDRS letters 72.9 (8.8) 71.8 (6.4) 72.3 (7.7) Mean
(SD) CST, m 360.6 (112.0) 340.5 (119.3) 350.6 (115.2) Phakic lens status, n (%) 11 (37) 11 (37) 22 (37) A total of 49 [82%] participants completed the year 2 study visit (n=26 [87%] and n=23 [77%] in the 6E10 and 2E11 groups, respectively).
BCVA, best corrected visual acuity: CST, central subfield thickness; 8 ETDRS, Early Treatment Diabetic Retinopathy Study; nAMD, neovascular age-related macular degeneration; SD, standard deviation; VEGF, vascular endothelial growth factor. DATA
Sustained Anatomic Control and Visual Acuity Through 2 Years Robust and
durable clinical activity observed in both dose groups Least Squares Mean Change in Central Subfield Thickness (CST) 150 LS Mean (95% CI) 6E10 (n=30) 2E11 (n=30) 100 Change at 2 Years 50 9.8 (-10.7, 30.2) 6E10 vg/eye 0 -14.8 (-36.2, 6.6) -50 2E11
vg/eye -100 -150 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 Week Least Squares Mean Change in Best Corrected Visual Acuity (BCVA) 15 LS Mean (95% CI) 6E10 (n=30) 2E11 (n=30) 10 Change at 2 Years 5 0.5 (-2.7, 3.7)
6E10 vg/eye 0 -2.3 (-5.7, 1.1) -5 2E11 vg/eye -10 -15 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 Week 9 Transient fluctuations in BCVA observed in year 2 may have been influenced by cataract progression/surgery .
Least squares means are based on Mixed Model Repeated Measures (MMRM) including dose group, baseline value, visit and visit dose group. DATA CUT-OFF: 29AUG2025 LS Mean (95% CI) change LS Mean (95% CI) change in BCVA, ETDRS Letters CST,
Robust and Consistent Reduction in Injection Burden 46%-61% of
participants received 1 injection cumulatively through 2 years High Need Population: Total Injections (2 Years) Least Squares Mean Change in Central Subfield Thickness (CST) 150 LS Mean (95% CI) 100 Change at 2 Years 50 9.8 (-10.7, 30.2) 0
6E10 vg/eye -50 -14.8 (-36.2, 6.6) -100 2E11 vg/eye 46% 61% -150 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 of participants received of participants received Least Squares Mean Change in Best Corrected Visual
Acuity (BCVA) 1 injection through 1 injection through 15 2 years 2 years LS Mean (95% CI) 10 Change at 2 Years 5 0.5 (-2.7, 3.7) 0 6E10 vg/eye -5 -10 -2.3 (-5.7, 1.1) 6E10 vg/eye 2E11 vg/eye 2E11 vg/eye -15 0 4 8 12 16 20 24 28 32 36
40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 Week 10 n=26 (6E10 vg/eye) and n=23 (2E11 vg/eye). DATA CUT-OFF: 29AUG2025 LS Mean (95% CI) LS Mean (95% CI) change in BCVA, change CST, m
Robust and Consistent Reduction in Injection Burden * 75% 100% of
participants with lower treatment burden received 1 injection cumulatively through 2 years Low Burden Population: Total Injections (2 Years) Least Squares Mean Change in Central Subfield Thickness (CST) 150 LS Mean (95% CI) 100 Change at 2
Years 50 9.8 (-10.7, 30.2) 0 6E10 vg/eye -50 -14.8 (-36.2, 6.6) -100 2E11 vg/eye 75% 100% -150 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 of participants received of participants received Least Squares Mean
Change in Best Corrected Visual Acuity (BCVA) 1 injection through 1 injection through 15 2 years 2 years LS Mean (95% CI) 10 Change at 2 Years 5 0.5 (-2.7, 3.7) 0 6E10 vg/eye -5 -10 -2.3 (-5.7, 1.1) 2E11 vg/eye 6E10 vg/eye 2E11 vg/eye
-15 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 Week 11 * 6 anti-VEGF injections in the 12 months prior to enrollment and diagnosed at least 12 months prior to enrollment (n=4 per dose group). DATA CUT-OFF:
29AUG2025 LS Mean (95% CI) LS Mean (95% CI) change in BCVA, change CST, m
Robust and Consistent Reduction in Injection Burden Through Year 2 ~90%
reduction in mean annualized anti-VEGF injections in a high need population Mean Prior Annualized Injection Rate Mean Post Ixo-vec Annualized Injection Rate 11 10.2 10.0 10 9 8 7 -89%-89% -92%-90% 6 5 4 3 2 1.2 1.1 0.9 0.8 1
0 1 2 Baseline 1 Year 2 Years Baseline 1 Year 2 Years (n=30) (n=28) (n=26) (n=30) (n=29) (n=23) 6E10 vg/eye 2E11 vg/eye Annualized rate (prior) = (number of injections in 12 months prior to Ixo-vec) / (days from the first injection in the past 12
months to Ixo-vec / 365.25). 12 Annualized rate (post) = (number of aflibercept injections since Ixo-vec) / (days from Ixo-vec to last follow-up within the analysis period / 365.25). DATA CUT-OFF: 29AUG2025 Mean annualized anti-VEGF injections,
Robust Reduction in Injection Burden in a High Need Population
65%-74% of participants received 1 annualized injection through 2 years Mean Prior Annualized Injection Rate Mean Post Ixo-vec Annualized Injection Rate 11 10.2 10.0 10 9 8 7 65% 74% 6 of participants received 1 of participants
received 1 annualized annualized 5 injection injection 4 3 2 1.2 1.1 0.9 0.8 1 0 1 2 Baseline 1 Year 2 Years Baseline 1 Year 2 Years (n=30) (n=28) (n=26) (n=30) (n=29) (n=23) 6E10 vg/eye 2E11 vg/eye Annualized rate (prior) = (number of
injections in 12 months prior to Ixo-vec) / (days from the first injection in the past 12 months to Ixo-vec / 365.25). 13 Annualized rate (post) = (number of aflibercept injections since Ixo-vec) / (days from Ixo-vec to last follow-up within the
analysis period / 365.25). DATA CUT-OFF: 29AUG2025 Mean annualized anti-VEGF injections, n
Intraocular Pressure Remained Stable in Year 2 in Both Ixo-vec Dose
Groups Mean Intraocular Pressure (IOP) 30 Study eye (n=30) Fellow eye (n=30) 25 20 6E10 15 vg/eye 10 5 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 Weeks 30 Study eye (n=30) Fellow eye (n=30) 25 20 2E11 15 vg/eye
10 5 0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100 104 Weeks 14 Based on observed data; for participants in 6E10: n=30 and n=26 at Year 1 and Year 2, respectively. For participants in 2E11: n=30 and n=23 at Year 1 and
Year 2, respectively. IOP, intraocular pressure; SD, standard deviation. DATA CUT-OFF: 29AUG2025 Mean (SD) IOP, mm Hg Mean (SD) IOP, mm Hg
LUNA 2-year Safety Results Ixo-vec Phase 3 dose well tolerated, no new
inflammation observed in year 2 * 6E10 vg/eye Participants Receiving Local Prophylaxis LUNA Year 1 LUNA Year 2 M15 M18 M21 M24 0 0 t 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 None ANTERIOR 0 0 0 0 0 0 0 0 0 0 0 t 0 0 0 0 0 0 0 0 0 6E10 t Trace 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 CHAMBER 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 vg/eye 1+ CELLS 0 0 0 0 0 0 0 0 0 0 t 1+ 0 0 1+ 0 0 0 0 0 0 2+ 0 0 0 0 0 0 0 0 0 0 0 (n=17) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 3+ 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 4+ 0 0 0 0 0 0 0 0 0 0 0 0 0 t 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 1+ t 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 et 0 0 0 0 0 0 0 0 0 0 0 t t 0 0 0 0 0 0 et 0 0 0 0 0 0 0 0 0 0 0 0 0 et 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 VITREOUS 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 6E10 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 CELLS 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 vg/eye 0 0 0 0 1+ 1+ t 0 t t 1+ 1+ t t t t t t t t t 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 (n=17) 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 et 0 0 0 0
0 0 0 0 0 0 t t t 0 0 0 0 0 0 et 0 0 0 0 0 0 0 0 0 0 0 0 0 et 15 No inflammation: no 1+ anterior chamber or vitreous cells. Pigmented cells observed at one or more visits in n=6 participants. *Difluprednate Ozurdex. et, early
termination; t, trace cells. DATA CUT-OFF: 29AUG2025 SCRN RAND W2 W4 W6 W8 W10 W14 W18 W22 W26 W30 W34 W38 W42 W48 W52
100% of Participants Receiving Phase 3 Dose + Steroid Eyedrops Alone *