Full Press Release Details
R&D Day NOVEMBER 2020 Exhibit
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forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our current and prospective product candidates; the design,
commencement, enrollment and timing of ongoing or planned clinical trials and regulatory pathways; the timing of patient recruitment and enrollment activities, clinical trial results, and product approvals; the timing and results of our ongoing
preclinical studies; the anticipated benefits of our gene therapy platform including the potential impact on our commercialization activities, timing and likelihood of success; the anticipated benefits and safety profile of busulfan as a
conditioning agent; the expected benefits and results of our manufacturing technology, including the implementation of our plato platform in our clinical trials and gene therapy programs; the expected safety profile of our investigational gene
therapies; the potential impact of the COVID-19 outbreak on our clinical trial programs and business generally, as well as our plans and expectations with respect to the timing and resumption of any development activities that may be temporarily
paused as a result of the COVID-19 outbreak; and the market opportunity for and anticipated commercial activities relating to our investigational gene therapies;. Any such statements in this presentation that are not statements of historical fact
may be deemed to be forward-looking statements. Any forward-looking statements in this presentation are based on our current expectations, estimates and projections about our industry as well as management's current beliefs and expectations of
future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and
uncertainties include, but are not limited to, the risk that any one or more of our product candidates will not be successfully developed or commercialized; the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our
collaborators; the risk that we may not successfully recruit or enroll a sufficient number of patients for our clinical trials; the risk that we may not realize the intended benefits of our gene therapy platform, including the features of our
plato platform; the risk that our product candidates or procedures in connection with the administration thereof, including our use of busulfan as a conditioning agent, will not have the safety or efficacy profile that we anticipate; the risk
that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving our product candidates; the
risk that we will be unable to obtain and maintain regulatory approval for our product candidates; the risk that the size and growth potential of the market for our product candidates will not materialize as expected; risks associated with our
dependence on third-party suppliers and manufacturers; risks regarding the accuracy of our estimates of expenses and future revenue; risks relating to our capital requirements and needs for additional financing; risks relating to clinical trial and
business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our development timeline and/or increase our development costs or that data collection efforts may be
impaired or otherwise impacted by such crises; and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important
factors, any of which could cause AVROBIO's actual results to differ from those contained in the forward-looking statements, see the section entitled "Risk Factors" in AVROBIO's most recent Quarterly Report on Form 10-Q, as
well as discussions of potential risks, uncertainties and other important factors in AVROBIO's subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements
except to the extent required by law. Note regarding trademarks: plato is a registered trademark of AVROBIO. Other trademarks referenced in this presentation are the property of their respective owners. Note regarding future updates: The
statements contained in this presentation reflect our current views with respect to future events, which may change significantly as the global consequences of the COVID-19 pandemic rapidly develop. Accordingly, we do not undertake and specifically
Vision Bring personalized gene therapy
to the world. Purpose Freedom from a lifetime of genetic disease.
Cell and gene therapy is redefining
medicine 804 trials Sources: 1Alliance for Regenerative Medicine: 2016 Annual Data Report; 2Alliance for Regenerative Medicine: Sector Report 1H 2020; 3FDA.gov press release at: https://bit.ly/2GcPftr 20161 1,034 trials 20202 10-20 approvals/year
Ex vivo lentiviral gene therapy has
emerged as a leading modality across multiple genetic diseases Industry-wide data demonstrate proven record, broad utility TOLERABILITY DURABILITY EFFICACY WIDE REACH BROAD UTILITY Approved ALD Beta thalassemia Investigational Fanconi anemia Hurler
syndrome MLD Sanfilippo A Sanfilippo B SCID-ADA SCID-X Sickle cell disease Wiskott-Aldrich syndrome X-CGD >350 patients >1,000 patient years Pediatrics and adults All mutations No exclusions due to pre-existing antibodies >12 years
post-infusion Head-to-toe, including: Brain Muscle Bone ALD: Adrenoleukodystrophy; SCID-ADA: Severe Combined Immunodeficiency-Adenosine Deaminase Deficiency; SCID-X: X-Linked Severe Combined Immunodeficiency; MLD: Metachromatic Leukodystrophy;
X-CGD: X-Linked Chronic Granulomatous Disease
Leading lysosomal disorder gene
therapy pipeline Built on strong strategic fit IND: Investigational New Drug Fabry AVR-RD-01 Gaucher type 1 AVR-RD-02 Cystinosis AVR-RD-04 Hunter AVR-RD-05 Gaucher type 3 AVR-RD-06 Pompe AVR-RD-03 Proof-of-Concept IND-Enabling Phase 1/2
Disease Approx. 2019 Global Net
Sales Five-Year SOC Cost per U.S. Patient* Selected Companies w/ Marketed Therapies Fabry $1.4B $1.7M Cystinosis $0.2B $4.3M Gaucher $1.4B $2.3M Hunter $0.6B $2.4M Pompe $1.0B $3.2M A multi-billion dollar market opportunity Targeting larger
rare lysosomal disorders Sources: Rombach S et al., Orphanet J Rare Dis, 2013; van Dussen L et al., Orphanet J Rare Dis, 2014 * WAC pricing from Redbook using standard dosing assumptions 2019 Net Sales from company annual and other reports
Horizon's Procysbi oral therapy (delayed release cysteamine bitartrate); midpoint between avg. adult and pediatric Note: Shire acquired by Takeda in 2019 SOC: Standard of Care Total: $4.6B
PROGRAM PATIENT MONTHS POST-INFUSION
Fabry Phase 1 PATIENT 1 PATIENT 2 PATIENT 3 PATIENT 4 PATIENT 5 Fabry Phase 2 PATIENT 1 PATIENT 2 PATIENT 3 PATIENT 4 Gaucher Phase 1/2 PATIENT 1 Cystinosis Phase 1/2 PATIENT 1 PATIENT 2 PATIENT 3 Durability across programs Note: Based on data
cut-off date of Nov. 12, 2020
Blood GI System Leukopenia Lymphopenia
Neutropenia Febrile neutropenia Thrombocytopenia Anemia Abdominal pain Diarrhea Mucositis Nausea Vomiting Days Post Gene Therapy Emerging tolerability profile has been predictable and manageable Conditioning-related grade 3-4 AEs were transient in
first 2 plato patients Bu90 TCI Mean Toxicity Grade Bu90-TCI: Busulfan 90-Target Concentration Intervention; AE: Adverse Event; GI: Gastrointestinal Bu90- TCI Busulfan 90 Target Concentration Intervention (TCI) Observations to-date show
short-term side effects start ~1 week after infusion, peak over the next 3-5 days and subside Day 0
Unrivaled commercial-scale platform
in plato MOBILIZATION & APHERESIS Patient Consent & Screening Patient Monitoring CONDITIONING & GENE THERAPY ADMINISTRATION CELL SEPARATION & CULTURE TRANSDUCTION CLOSED, AUTOMATED SYSTEM HARVESTING & CRYOPRESERVATION DRUG
PRODUCT TESTING 1 2 3 4 5
Fabry Gaucher type 1 Cystinosis
Hunter Gaucher type 3 Pompe COMMERCIAL CALL POINTS REGULATORY PATHWAYS CLINICAL EXECUTION TECHNICAL & MANUFACTURING Halo effect' driven by strong pipeline synergies Replicable path to market
Patient enrollment activities
accelerating across trials By the end of 2021, we expect to have dosed a total of 30 patients. Q4 20 Recruiting Objective Clinical Trial Site Expansion Cumulative 2021 Patient Dosing Goal ENROLLED CONSENTED DOSED Active clinical sites: 7
CURRENTLY 23 PLANNED BY Q4 2021
Key takeaways for today Fabry
advancing toward potential accelerated approval pathway in one or more major markets Exciting early data in cystinosis and Gaucher Clear advantages of Bu90-TCI conditioning plato platform reimagines CMC / analytics Leading lysosomal disorder
gene therapy franchise Bu90-TCI: Busulfan 90-Target Concentration Intervention; CMC: Chemistry, Manufacturing, and Controls
Today's agenda Bu90-TCI:
Busulfan 90-Target Concentration Intervention; CMC: Chemistry, Manufacturing, and Controls Time Clinical updates New data and update on future regulatory plans 9:15 Precision conditioning designed to enable durability and head-to-toe reach The
Bu90-TCI advantage 10:00 Addressing industry manufacturing challenges with advanced CMC and analytic solutions AVROBIO's platform for global gene therapy commercialization 10:35 The second wave Working to prevent irreversible damage to body
Rob Hopkin, M.D. Genetic Medicine
Specialist, Fabry KOL at Cincinnati Children's Hospital Perspective from leading KOLs Harry Malech, M.D. Chief of Genetic Immunotherapy Section and Deputy Chief of Laboratory of Clinical Immunology and Microbiology, NIAID, NIH Anthony Davies,
Ph.D. Founder and CEO, Dark Horse Consulting Group Dr. Rob Hopkin is a consultant to AVROBIO and Dr. Anthony Davies is the CEO of Dark Horse, an AVROBIO vendor KOL: Key Opinion Leader; NIAID: National Institute of Allergy and Infectious Diseases;
NIH: National Institutes of Health; CEO: Chief Executive Officer
Gaucher Disease Type 1 Meet
"Fatigue is, for me, probably
really the one symptom that plagues me the most I wake up tired, I'm tired in the middle of the day, and I go to sleep tired Gaucher is always there." - Cyndi, living with Gaucher disease type 1 DIFFERENTIATED TARGET
PRODUCT PROFILE for Gaucher Disease Type 1 Note: These are target attributes for a first-line therapy AAV: Adeno-Associated Viral vector; Bu90-TCI: Busulfan 90-Target Concentration Intervention; CNS: Central Nervous System; ERT: Enzyme Replacement
Therapy; GBA: Glucocerebrosidase; SRT: Substrate Reduction Therapy First-Line Therapy and Functional Cure Addresses all patient segments All Gaucher disease type 1 genetic mutations All age groups Male and female No AAV or ERT neutralizing antibody
limitations Well-tolerated No ERT/SRT-related side effects Mild-to-moderate, transient side effect profile consistent with Bu90-TCI No splenectomy medication and complications No liver toxicity or adverse immunogenicity Impacts hard-to-reach organs
Diseased macrophages (Gaucher cells) replaced by functional macrophages Brain: global distribution of genetically modified microglia Bone and bone marrow: global distribution of genetically modified macrophages and osteoclasts Lifelong durability
Single infusion for life Off ERT/chaperone No waning of efficacy Save millions of dollars in healthcare costs per patient Prevents, halts or reverses disease; normalizes lifespan Bone-related manifestations, prevention of physical deformity, bone
crises, bone pain, avascular necrosis Low hemoglobin and platelets Hepatosplenomegaly, risk of cirrhosis and splenectomy Risk of multiple myeloma Fatigue CNS: risk of GBA-Parkinson's disease
Even on ERT, patients endure
debilitating symptoms Incomplete therapeutic response is common: 60% failed to achieve at least one of six therapeutic goals after 4+ yrs of ERT1 Many continue to exhibit bone pain, organomegaly and cytopenia after 10 yrs of ERT2 25% have physical
limitations after 2 yrs of ERT, primarily due to bone disease3 Persistence after 10 years ERT Non-splenectomized Patients Splenectomized Patients Bone Pain 43% 63% Splenomegaly* 38% N/A Thrombocytopenia* 23% 1% Hepatomegaly* 14% 19% Anemia
12% 9% Bone Crisis 7% 17% * Higher persistence rates observed when more severe manifestations were present at baseline Persistence refers to the presence of anemia, bone pain, bone crisis, or at least moderate thrombocytopenia, splenomegaly,
or hepatomegaly, present after 10 years of ERT among those with baseline involvement of these parameters (from a registry of 757 GD1 patients; Weinreb et al., 2013) Following 10 years of treatment, ~26% of patients were receiving between 45-150 U/kg
EOW, and 96% of these individuals were receiving doses between 45-90 U/kg EOW. Data rounded to complete integer. GD1: Gaucher Disease Type 1; ERT: Enzyme Replacement Therapy; EOW: Every Other Week 1Weinreb N et al., Amer J Hematol, 2008; 2Weinreb N
et al., J Inherit Metab Dis, 2013; 3Giraldo P et al., Qual Life Res, 2005 Prospective registry of 757 GD1 patients on ERT after 10 years
Delivering genetically modified
cells head-to-toe Long-term engraftment in bone marrow Manufacturing', transportation and delivery in blood Target organs T NK B RBC Platelets Granulocytes DC Monocytes PROGENY Microglia Osteoclasts Macrophages CD34+ HSCs
DIFFERENTIATION Spleen, Liver, Lungs HSC: Hematopoietic Stem Cell; NK: Natural Killer; DC: Dendritic Cell; RBC: Red Blood Cell
Guard1: Phase 1/2 study in Gaucher
disease type 1 1 patient dosed to date OBJECTIVES PATIENTS Safety Efficacy Engraftment Enrollment goal: 8-16 patients 18-45-year-old males and females Have a confirmed diagnosis of GD1 based on: Deficient glucocerebrosidase enzyme activity Clinical
features consistent with GD1 An adaptive, open-label, multinational phase 1/2 study of the safety and efficacy of ex vivo, lentiviral vector-mediated gene therapy AVR-RD-02 for patients with Gaucher disease type 1. ACTIVELY RECRUITING: RECRUITING
PLANNED 1H '21: PHASE 1/2 AVR-RD-02 Gaucher disease type 1 patients who are: ERT-stable for >24 months or Treatment-na ve or Have not received ERT or SRT in the last 12 months GD1: Gaucher Disease Type 1; ERT: Enzyme Replacement
Therapy; SRT: Substrate Reduction Therapy; 1H: First Half
Toxic metabolite lyso-Gb1 reduced
below ERT levels at 3 months GUARD1: PATIENT 1 Lyso-Gb1 Plasma Normal Range: 0.5 - 1.2 ng/mL ERT: Enzyme Replacement Therapy; Lyso-Gb1: Glucosylsphingosine Plasma Lyso-Gb1 (ng/mL) Baseline (On ERT) 3 months (Off ERT) 22% reduction Lyso-Gb1, a
sensitive and specific marker of metabolite accumulation in Gaucher disease is decreased relative to baseline on ERT
GUARD1: PATIENT 1 Chitotriosidase
Plasma Activity Normal Range: 0.0-44.2 moL/L/h ERT: Enzyme Replacement Therapy Plasma chitotriosidase reduced below ERT levels at 3 months Plasma Chitotriosidase Activity ( moL/L/h) Chitotriosidase, a marker of activated macrophages
(Gaucher cells), is also decreased Baseline (On ERT) 3 months (Off ERT) 17% reduction 151
Platelet counts in normal range at
3 months, despite being off ERT GUARD1: PATIENT 1 Platelet Count Reference Value Adult: 130-400x109/L; grey line: local (safety) lab values; pink dots: central (efficacy) lab values ERT: Enzyme Replacement Therapy Platelet Count Day 0 Off ERT Normal