Gaining Momentum in Gene Therapy

Transcription

1 Gaining Momentum in Gene Therapy Corporate Presentation November 2018

2 Forward-looking Statements Statements contained in this document 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 Such statements include, but are not limited to, statements regarding plans and milestones related to Adverum s product candidates, clinical studies, and 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 on current conditions, expected future developments and other factors Adverum believes are appropriate in the circumstances. Adverum may not consummate any of these plans or these product, clinical development 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 forwardlooking 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 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 or commercialize any of its product candidates and the risk that Adverum will be delayed in receiving or fail to receive required regulatory approvals. Risks and uncertainties facing Adverum are described more fully in Adverum s periodic reports filed with the SEC, including its Form 10-Q filed with the SEC on November 8, 2018, particularly in the section titled Risk Factors. 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. This document contains 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 events or circumstances may differ materially from events and circumstances 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. 2

3 Adverum is a Clinical-stage Gene Therapy Company with Industry-leading Expertise ADVM-022 for wet age-related macular degeneration (AMD): First intravitreally delivered gene therapy utilizing AAV.7m8 vector for wet AMD OPTIC Phase 1 trial initiated to evaluate ADVM-022 for patients with wet AMD Interim trial update expected by 1Q20 Industry-leading AAV platform and capabilities: Next-generation vectors Scalable manufacturing process ~$218M in cash* to fund development of lead programs at least through 1H20 Leadership team with extensive industry expertise *Cash, cash equivalents, and short-term investments as of September 30, 2018 (unaudited). 3

4 Advancing Gene Therapies for Ophthalmology and Rare Diseases Gene Therapy Candidate Research Preclinical Phase 1 Phase 2 Lead Programs Worldwide Rights ADVM-022 OPTIC Trial for Wet Age-related Macular Degeneration (AMD) Rare Disease Hereditary Angioedema (HAE) Rare Disease Alpha-1 Antitrypsin (A1AT) Deficiency Partnered Programs Up to 5 Undisclosed Targets X-linked Retinoschisis and 3 Undisclosed Targets Inherited Retinal Disease Ophthalmic Disease 4

5 Wet AMD: Large Market with Significant Opportunity to Improve Treatment Paradigm Wet AMD Wet age-related macular degeneration Intermediate AMD - 20/20-20/30 Vision Vision loss from abnormal blood vessel proliferation and leakage due to vascular endothelial growth factor (VEGF) activity Market Overview Wet AMD at Diagnosis - 20/80 Vision 1.2M U.S. patients 1, 3M globally $9.2B global sales for approved anti-vegf therapies 2 1 Prevalence of Age-Related Macular Degeneration in the United States, Arch Ophthalmol. 2004;122(4): doi: /archopht Based on 2017 public financial statements 5

6 Intravitreal Injections Visual Acuity (ETDRS Letters) Significant Opportunity to Improve Wet AMD Treatment Monthly Injections are Challenging Inability to Maintain a Regular Treatment Schedule Leads to Vision Loss 2 Optimal Therapeutic Benefit Vision loss at wet AMD onset Monthly therapy provides vision stability Vision loss at lower dosing frequencies -2.0 Recommended Injections Actual Injections Clinical Trial Duration Years 1 Clinical utilization of anti-vegf agents and disease monitoring in neovascular age-related macular degeneration, Am J Ophthalmol. 2014;157(4): , Holekamp NM, et al. 2 Multiple studies (MARINA/ANCHOR & HORIZON/SEVEN-UP, SECURE, CATT) indicate that vision benefits are lost at less than recomended dosing frequencies 6

7 ADVM-022: Designed to Treat Wet AMD with a Single Intravitreal Injection Proprietary vector AAV.7m8 delivers an anti-vegf standard-of-care therapy (aflibercept) with intravitreal injection Efficacy demonstrated in non-human primates (NHPs) comparable to an anti-vegf standard of care therapy Robust protein levels seen in NHP vitreous up to 52 weeks post injection Single Intravitreal injection and method of delivery of current standard of care

8 Route of Administration is an Important Consideration When Developing Gene Therapies for Ocular Injection Intravitreal Injection Subretinal Injection STEP 1 STEP 2 Outpatient Visit STEP 1 STEP 2 Requires Surgical Setting Intravitreal injection has potential for wide distribution of vector, thus increasing access to surface area for retinal transduction Intravitreal injection can be performed as an outpatient procedure in the doctor s office, and is the same route of administration currently used for standard of care anti- VEGFs Subretinal injection is limited by amount of vector that can be delivered and the transduction is localized to cells under or near the bleb Other potential drawbacks of subretinal injection include: Risks associated with the procedure (e.g. cataracts, retinal detachment) Performance of subretinal surgery varies by retinal surgeon, which may lead to variable clinical outcomes Limited number of qualified surgery centers 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 8

9 Industry-standard Model Used to Test New Wet AMD Therapies Retinal Image after Laser Treatment Choroidal neovascularization (CNV) is induced experimentally by laser Nine lesions per eye are graded for severity (grades I-IV) Efficacy is assessed by reduction of the number of most severe, clinically relevant (grade IV) lesions Source: European Society of Gene and Cell Therapy (ESGCT) Conference, October

10 % Grade IV CNV Lesions 13-Month Efficacy in NHPs Comparable to Aflibercept Post Single Intravitreal Injection of ADVM-022 ADVM-022 Long-term Efficacy (AAV.7m8-aflibercept) 50% 40% 40% 13 months post-administration * p < vs. vehicle 30% 20% 10% 5% * 6% * 0% Vehicle (n=8 eyes) Aflibercept (n=8 eyes) ADVM-022 (n=8 eyes) Note: Data at 13 months is consistent with previously reported data at 28 days Source: Poster Presentation from the American Society of Gene and Cell Therapy (ASGCT) 21st Annual Meeting, May 2018 NHP = Non-human primates 10

11 Robust and Sustained Aflibercept Levels Detected in Vitreous up to 52 Weeks after Single Injection ADVM-022 ADVM-022 NHP Study 1 (2x10 12 vg/eye, n=2-4 eyes 1 ) ADVM-022 NHP Study 2 (2x10 12 vg/eye, n=14 eyes) n=2 eyes 1 ADVM-022 Study 1: 2 NHPs (4 eyes) at weeks 4, 8, and 12; 1 NHP (2 eyes) at weeks 26 and 52 Source: Targeting Ocular Disorders and the Retina Society, September 2017 NHP = Non-human primates 11

12 ADVM-022 OPTIC Phase 1 Study Design - Trial Initiated 4Q18 Baseline assessment Treatment evaluation Follow-up Day Weeks 104 Screening Anti-VEGF rescue therapy administered if retreatment criteria met Aflibercept injection ADVM-022 SD-OCT Injection Assessment Primary endpoint (Safety) 24 weeks Secondary endpoints (Efficacy) Inclusion Criteria Age 50 under active treatment for wamd and responsive to anti-vegf with 2-6 injections in last 8 months Demonstrate aflibercept response (assessed by SD-OCT during screening) BCVA ETDRS Snellen equivalent between 20/80 and 20/320 for sentinel patient; between 20/40 and 20/320 remaining patients Anti-AAV.7m8 neutralizing antibodies <1:5 titer Cohort 1: 6x10 11 vg n=6 DMC Safety Review (4 weeks) Cohort 2: 2x10 12 vg n=6 DMC Safety Review (4 weeks) Cohort 3: 6x10 12 vg n=6 DMC Safety Review (4 weeks) Patients will be administered a tapering prophylactic corticosteroid regimen Primary Endpoint Safety at 24 weeks: Type, severity, and incidence of ocular and systemic adverse events Secondary Endpoint Change in BCVA at 24 weeks Change in central retinal thickness at 24 weeks as measured by SD-OCT Percentage of subjects requiring anti- VEGF injections through 104 weeks Mean number of anti-vegf injections through 104 weeks OCT = Optical Coherence Tomography BCVA = Best Corrected Visual Acuity ETDRS = Early Treatment Diabetic Retinopathy Study 12

13 Advancing ADVM-022 for Wet AMD RECENT UPDATES Dosed first patient in OPTIC Phase 1 Trial 4Q18 Presented long-term preclinical protein expression data at ESGCT Received Fast Track Designation from FDA 4Q18 3Q18 NEXT STEPS OPTIC trial enrollment update Interim trial update expected 1H19 By 1Q20 NHP = Non-human primates ESGCT = European Society of Gene and Cell Therapy 13

14 Dual Manufacturing Strategy: Leveraging In-house Expertise & External Capacity Process development capabilities to deliver scalable process to GMP contract manufacturing organizations (CMOs) Baculovirus/Sf9 production system applicable to multiple AAV serotypes State-of-the-art bioindustry technology for purification Process is readily transferred to CMO Assay development capabilities and GMP quality control to optimize product release for human use Potential to expand manufacturing capabilities Plan to scale up manufacturing process to 2000 liter scale Ability to leverage in-house cgmp manufacturing capacity in addition to CMO usage 14

15 Proprietary Platform in Novel Vector Development Next-generation Vectors Directed evolution and rational design of AAV capsids: Enhanced transduction efficiency for specific tissues or altered transduction properties (e.g., crossing retinal inner limiting membrane or the blood brain barrier) Opportunity for novel tropism in cell types that were previously incompatible with existing raav vectors Immune response evasion Adverum s Unique Advantages Proprietary cell library technology to overcome the challenge of cross-packaging, improving the odds of finding a desired variant upon screening Ability to generate large amounts of AAV capsid libraries allows for screening in NHPs instead of rodents, to increase the probability that selected variants work in humans Minimizing the rate of false positives during capsid rescue results in highly efficient screening 15

16 Leadership in Ophthalmic Gene Therapy Drives Collaborations Next-generation AAVs CRISPR-based Genome Editing Expertise Next-generation AAVs Proprietary Molecules & Ophthalmology Expertise Up to 5 ophthalmic indications CRISPR technology delivery $1M upfront to evaluate next-generation AAV vectors Up to a mid-teen, million-dollar amount in development and commercialization milestones for each product Tiered royalties from mid-single digits to low-teens on net sales of each product Up to 8 ocular therapeutic targets (4 already identified) AVA-311 for juvenile X-Linked Retinoschisis (XLRS) as first collaboration program Adverum has option to share up to 35% on profits and development costs for two targets $8M initial payment, up to $640M in payments upon achievement of milestones, low to mid-single digit royalties on WW net sales Initial 3-year collaboration term extended by additional 3 years to May

17 Upcoming Corporate Milestones ADVM-022 for Wet AMD OPTIC trial enrollment update Interim OPTIC trial update 1H19 By 1Q20 Rare Disease Programs Update on preclinical plan 1H19 In-house Manufacturing Capabilities Move into new facility with 2000L scale and GMP capabilities 2H19 ~$218M in cash* to fund further development of lead programs *Cash, cash equivalents, and short-term investments as of September 30, 2018 (unaudited). 17

18 Team with Significant Industry Experience Name Background Experience Leone Patterson Chief Executive Officer, Director and Chief Financial Officer 20+ years experience in management and financial operations Mehdi Gasmi, Ph.D. President and Chief Scientific Officer Jennifer Cheng, Ph.D., J.D. VP and General Counsel Katherine Bock VP, Investor Relations and Corporate Communications 20+ years experience developing gene therapy vectors 15+ years experience in biotechnology companies, including legal and intellectual property counsel and research 15+ years experience in the life sciences industry, including research, finance, corporate development and investor relations 18

19 Nasdaq: ADVM