Gaining Momentum in Gene TherapyOIS@AAO Annual MeetingOctober 10, 2019

Aaron Osborne, MBBS MRCOphthChief Medical Officer

Forward-looking Statements

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Pioneering Novel Gene Therapies for Ocular Diseases

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Well positioned to execute:§ Leadership team with extensive ophthalmology, drug development expertise§ ~$177.6M in cash* to fund operations into 2021

Industry-leading AAV platform and capabilities§ AAV.7m8 vector optimized for IVT delivery; next-generation vectors developed through proprietary directed

evolution platform§ Robust patent portfolio§ Scalable manufacturing process

*Cash, cash equivalents, and short-term investments as of June 30, 2019 (unaudited)

ADVM-022 in wet AMD§ OPTIC phase 1 trial conducted in patients who require frequent injections to manage their wet AMD§ Zero rescue injections required, durable efficacy signal observed, through week 24 in Cohort 1 (n=6)§ Cohort 1 (52-week) and Cohort 2 (24-week) data releases planned 1H20

ADVM-022: Intravitreal gene therapy for VEGF-driven retinal diseases§ Advanced AAV.7m8 candidate designed to deliver long-lasting efficacy in a single intravitreal injection§ Long-term efficacy from a single injection can address the greatest unmet clinical needs in:

§ Wet AMD – serious lifelong disease affecting 1.2M patients in the US§ Diabetic retinopathy – the leading cause of vision loss in working age people; 8M patients in US

1. Brown DM, et al. N Engl J Med. 2006;355:1432-1444. 2. Busbee DM, et al. Ophthalmology. 2013;120:1046-1056. 3. Heier JS, et al. Ophthalmology.2012;119:2537-2548. 4. Martin DF,et al. N Engl J Med. 2011;364:1897-1908. 5. Rosenfeld PJ, et al. N Engl J Med. 2006;355:1419-1431. 6. Cohen SY, et al. Retina. 2013;33:474-481. 7. Holz FG, et al. Br J Ophthalmol.2015;99:220-226. 8. Holz FG, et al. Br J Ophthalmol. 2013;97:1161-1167.

Real-world Anti-VEGF Patient Outcomes:Treatment Burden Results in Suboptimal Vision from Under-dosing

› Burden of frequent intravitreal (IVT) injections for patients and caregivers

› Real-world visual acuity outcomes fall short of clinical trial results due to under-dosing

› A solution is needed to reduce treatment burden and improve real-world patientoutcomes while providing clinical benefit to patients with wet AMD

Clinical trials1-5 vs Real-world Studies6-81-Year Outcomes With Ranibizumab 0.5 mg

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ANCHOR MARINA HARBOR VIEW 1 VIEW 2 CATT AURA LUMIERE WAVE

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Clinical Trials Real World

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IntravitrealInjection

Outpatient Visit

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Ocular Gene Therapy Approaches: Intravitreal Offers Benefits over Subretinal

› Intravitreal injection is the current standard-of-care for wet AMD

› Potential for wide distribution of vector, thus able to transduce a broader tissue area

SubretinalInjection

Requires Surgical Setting

1 Hossein S, et al. Overview of retinal differentiation potential of mesenchymal stem cells: A promising approach for retinal cell therapy. Annals of Anatomy - Anatomischer Anzeiger,Vol 210, 2017: 52

› Surgical procedure is complex and time-consuming

› Risks associated with vitrectomy surgery

› Not all retinal specialists are equipped or trained to do procedure

› Limited vector distribution, transduction is localized to cells under or near the bleb

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ADVM-022 is Specifically Designed for Long-term Intraocular VEGF Suppression With a Single Intravitreal Injection

ADVM-022AAV.7m8 capsid

ITR aflibercept ITRC11

Aflibercept expression cassette

Target retinal cell expresses aflibercept

AfliberceptRNA

ITR, inverted terminal repeatSource: Grishanin, R. et al. Mol. Ther. 2019;27:118–29

AAV.7m8 was developed using directed evolution to:

› Enable efficient intravitreal delivery› Increase transduction of retinal cells› Increase protein expression

AAV.7m8 Unique Properties

Preclinical Data Demonstrate the Potential for Long-term Efficacy with a Single Intravitreal Injection of ADVM-022

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5%*

ADVM-022 given 13 months prior to laser CNV is as effective as aflibercept at the time of laser2

Sustained aflibercept protein expression at pharmacologically relevant levels through 30 months1

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6%*IVT ADVM-022

40%

13 months post-injection

(2x1012 vg/eye)

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ADVM-022 OPTIC Phase 1 Trial for Wet AMD –Dosing Completed in Cohorts 1 and 2

†Patients receive rescue aflibercept (2mg IVT) if any of the following criteria are met: 1. Loss of ≥10 letters in BCVA from baseline due to intraretinal or subretinal fluid observed by SD-OCT; 2. Increase in central subfield thickness >75μm from baseline as assessed by SD-OCT; 3. Presence of vision-threatening hemorrhage due to macular degeneration

Day 1: ADVM-022

Baseline assessment Treatment evaluation Follow-up

Day -14 to -7: aflibercept

244 8 12 16 20 104Weeks:

24-week safety and efficacy assessment

52-week safety and efficacy assessment

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Treatment evaluation

Rescue at any time if disease activity meets retreatment criteria†

Prophylactic oralcorticosteroid taper

(13 days total)Primary endpoint (Safety) 24 weeks

Secondary endpoints (efficacy)

Cohort 2: 2x1011 vg

n=6

Cohort 1: 6x1011 vg

n=6

üDMC safe to proceed

Additional Cohorts, If

Needed

Assess tolerability and efficacy

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OPTIC Cohort 1 Baseline Patient Characteristics

Characteristic ValueMean age, years 79Mean time since nAMD diagnosis, years 3.3Mean number anti-VEGF injections since initial diagnosis (range) 35.3 (7–109)Mean number anti-VEGF injections in 8 months prior to screening 6.2Average annualized injection frequency 9.3Mean BCVA study eye, mean ETDRS letters Approximate Snellen equivalent

65.8 20/50

Mean CST study eye, mean µm 369

Cohort of subjects requiring frequent injections to maintain vision

BCVA, best corrected visual acuity: CST, central subfield thickness; ETDRS, Early Diabetic Retinopathy Study; nAMD, neovascular age-related macular degeneration; VEGF, vascular endothelial growth factor

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Cohort 1: Safety Results through Week 24

*CTCAE v5.0 AE severity grading system, general guidelines

Systemic Adverse Events Ocular Adverse Events(potentially related to ADVM-022)

› No serious adverse events (AEs)

› No adverse events met criteria for

dose-limiting toxicity

› No drug-related non-ocular adverse events

› Inflammation observed in all patients

› 14 mild* AEs

› 5 moderate* AEs

› Anterior chamber cells x2

› Intermediate uveitis x2

› Vitreous cells

› No severe* AEs

Cohort 1: Mean BCVA Stable and Mean CST Reduced through 24 Weeks (Six Subjects)

BCVA, best corrected visual acuity; BL, baseline; CST, central retinal subfield thickness; D, day; W, weekDay 1 visit is 7–15 days after baseline visit90% CIs on mean change in BCVA and CST were calculated using the T-distribution.

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–2 letters90% CI (-9.1, 5.1)

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Sentinel Subject: Prior AMD Treatment Experience

Optical coherence tomography (OCT) scans and treatment intervals from most recent 5 anti-VEGF injections visits prior to OPTIC

7 weeks

5 weeks

6 weeks

6 weeks

76 year old malePrevious IVT, n 18

IVT in last 8 months, n 5

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Sentinel Subject: OCT Images in OPTIC

Aflibercept IVT

Week 4

Week 8

Day 1: ADVM-022

Week 12

Week 16

Week 20

Week 24

No rescue injection received over 24 weeks

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Anti-VEGF centurion: Prior nAMD Treatment Experience

Optical coherence tomography (OCT) scans and treatment intervals from most recent 5 anti-VEGF injections visits prior to OPTIC

62 year old malePrevious IVT, n 109

IVT in last 8 months, n 6

5 weeks

5 weeks

6 weeks

6 weeks

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Anti-VEGF centurion: OCT Images in OPTIC

No rescue injection received over 24 weeks

Aflibercept IVT

Week 4

Week 8

Day 1: ADVM-022

Week 12

Week 16

Week 20

Week 24

OPTIC Cohort 1: 24-Week Conclusions

§ Zero rescue injections required for any patient§ ADVM-022 was safe and well tolerated§ Mean BCVA stable§ Mean CST reduced§ 5/6 subjects showed complete anatomic response

BCVA, best-corrected visual acuity; nAMD, neovascular age-related macular degeneration; OCT, optical coherence tomography

ADVM-022 offers transformative potential to greatly reduce treatment burden and improve retinal anatomy with a single intravitreal injection in nAMD

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ADVM-022 is the Only Intravitreal Injection that has Potential to be a One-time Treatment for wet AMD

Anti-VEGF Intravitreal Injections

Advantages:• Office administration per current

SoC• Proven efficacy and safety profile• Potential for some patients to be

extended to longer treatment intervals

Limitations:• Short duration within eye• ~50% of patients require 4–8 weekly

injections to control disease• Real world outcomes fail to match

clinical trials due to undertreatment• Treatment burden unmanageable

for patients and healthcare systems

ADVM-022 Intravitreal Injection

Advantages:• Office administration per current

SoC• Potential long lasting VEGF

suppression with a single injection• Potential for anatomic

improvements in refractory patients• Could dramatically reduce treatment

burden and improve real-world vision outcomes

Limitations:• May be unsuitable for some patients

(eg history of uveitis)• May need neutralizing antibody

screening• Steroid prophylaxis may be required

Surgical

Advantages:• Potential long lasting VEGF

suppression with a single surgical procedure

Limitations:• Invasive surgical procedure in

operating room setting• Implant device requires refills

alongside rescue injections• Subretinal surgery requires

vitrectomy and steroid prophylaxis• Risks of surgical complications:

• Early: vitreous hemorrhage, retinal detachment; Later: cataract, endophthalmitis

Current and future Wet AMD Treatments

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MilestonesADVM-022 for Wet AMD – OPTIC Phase 1 Clinical Trial

ü Dosed first patient in second cohort (n=6, 2x1011 vg/eye) 2Q19ü Completed patient dosing in second cohort (n=6, 2x1011 vg/eye) 3Q19ü Positive 24-week data from first cohort (n=6, 6x1011 vg/eye)

Podium presentation at Retina SocietyLate-breakers podium presentation at AAO

9/201910/2019

Provide update on development plans for OPTIC 4Q1952-week data from first cohort expected to be presented 1H2024-week data from second cohort expected to be presented 1H20

ADVM-022 for Diabetic Retinopathy (DR)

Plan to submit IND in diabetic retinopathy 1H20

In-house Process Development Capabilities

Be able to occupy new facility with expanded in-house process development capabilities to 1000L YE19

Nasdaq: ADVM