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Disclaimer This presentation has been prepared by AVROBIO, Inc. ("AVROBIO") for informational purposes only and not for any other purpose. Certain information contained in this presentation and statements made orally dur

Key Takeaway: MARCH 2021 Corporate Presentation Disclaimer This presentation has been prepared by AVROBIO, Inc. ("AVROBIO") for informational purposes only and not for any other purpose. Certain information contained in this presentation and statements made orally during this presentation re

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MARCH 2021 Corporate Presentation
Disclaimer This presentation has been
prepared by AVROBIO, Inc. ("AVROBIO") for informational purposes only and not for any other purpose. Certain information contained in this presentation and statements made orally during this presentation relate to or are based on
studies, publications, surveys and other data obtained from third-party sources and AVROBIO's own internal estimates and research. While AVROBIO believes these third-party sources to be reliable as of the date of this presentation, it has not
independently verified, and AVROBIO makes no representation as to the adequacy, fairness, accuracy or completeness of any information obtained from third-party sources. While AVROBIO believes its internal research is reliable, such research has not
been verified by any independent source. This presentation may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and
phrases such as "aims," "anticipates," "believes," "could," "designed to," "estimates," "expects," "forecasts," "goal,"
"intends," "may," "plans," "possible," "potential," "seeks," "will," and variations of these words and phrases or similar expressions that are intended to identify
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; the market opportunity for and anticipated commercial activities relating to our investigational gene therapies; and statements regarding our financial and cash position and expected cash reserves. 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 Annual Report on Form 10-K, 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
Vision Bring personalized gene therapy
to the world. Purpose Freedom from a lifetime of genetic disease.
Leading lysosomal disorder gene therapy
pipeline 14 patients dosed to date across three indications 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. 2020 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 $1.5B $2.3M Hunter $0.6B $2.4M Pompe $1.1B $3.2M Multi-billion dollar market opportunity Over 50,000 patients
across target indications 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 2020 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: $4.8B
Lifelong treatments vs. potential
single-dose therapy Treatment burden Enzyme or protein level DISEASE PROGRESSION CONTINUES COULD HALT, PREVENT OR REVERSE DISEASE Enzyme Replacement Therapy (ERT) Temporary bolus of enzyme, not curative Bi-Weekly ERT Plasma Pharmacokinetics of ERT
Life-long infusions Transient, intermittent elevation Bi-weekly IV infusions AVROBIO Gene Therapy Designed for 24/7 expression of protein, curative potential Functional Protein Expression in Transduced HSCs and Their Progeny 24/7 expression One-Time
Gene Therapy Long-term, continuous elevation Single IV infusion ERT: Enzyme Replacement Therapy; IV: Intravenous; HSC: Hematopoietic Stem Cells Ability to impact CNS No Yes
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 PATIENT 5 Gaucher Type 1 Phase 1/2 PATIENT 1 Cystinosis Phase 1/2 PATIENT 1 PATIENT 2 PATIENT 3 * Data not yet available for
patient #5 in Fabry Phase 2 Note: Based on data cut-off date of January 11, 2021 Durability demonstrated across clinical programs First patient out 3.5 years; 10 patients out 1 year or more
Bu90-TCI conditioning-related side
effects have been predictable and transient in first two plato patients Note: FAB-GT, f-k-a FAB-201, safety data cut-off December 7, 2020; Gaucher safety data cut-off January 4, 2021 * Source: Bartelink IH et al., Lancet Haematol, 2016
Bu90-TCI: Busulfan 90-Target Concentration Intervention; AUC: Area Under the Curve; TCI: Target Concentration Intervention Adverse Event Probability 50 70 90 110 130 Busulfan Cumulative AUC (mg x hr/L) 0.0 0.2 0.4 0.6 0.8 Graft Failure Increased
Toxicity Analysis of 465 non-malignant patients identified optimum exposure for busulfan conditioning*: Bu90-TCI target Conditioning-related grade 3-4 AEs in first two plato patients Days Post Gene Therapy Bu90 TCI Mean Toxicity Grade Day 0
BLOOD GI SYSTEM OTHERS
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
"First Wave" Programs
Fabry, Gaucher Type 1, cystinosis
Fabry disease opportunity Standard
of care (SOC): ERT Not curative, relentless progression of disease continues Burdensome and expensive - bi-weekly ERT infusions required; 5-year treatment cost of ERT = ~$1.7 million* Caused by mutation in gene encoding for alpha-galactosidase
A enzyme Kidney function Proteinuria, polyuria, kidney failure Cardiac function Left ventricular hypertrophy, fibrosis, heart failure Neuropathic pain Pain and burning sensations in hands and feet, pain crises Everyday burden of illness, and life
expectancy Not curative, relentless progression of disease, shortened lifespan CNS complications TIA/stroke, depression, executive function deficit, white matter lesions Unmet needs with SOC: Fabry Disease Target Product Profile**: Prevents, halts
or reverses disease; extends/normalizes lifespan Addresses all patient segments - all genetic mutations, male and female, all ages Lifelong durability - single infusion; off ERT Impacts hard-to-reach organs - e.g., brain, heart,
kidney Well tolerated * WAC pricing from Redbook using standard dosing assumptions ** Note: these are target attributes for a first-line therapy Affects ~ 1:40,000 males and 1:118,000 females in U.S. Tom, living with Fabry disease
OBJECTIVES PATIENTS Safety and
tolerability Preliminary efficacy n = 5 patients 18 - 59 year-old males On ERT >6 months prior to enrollment FULLY ENROLLED PHASE 1 * Sponsored by FACTs team (Fabry Disease Clinical Research and Therapeutics) in Canada ** FAB-GT fka FAB-201
Two AVR-RD-01 Fabry clinical trials 10 patients dosed across Phase 1 and 2 OBJECTIVES PATIENTS Safety and tolerability Efficacy n = 8-12 patients (5 dosed to-date) 16 - 50 year-old males Treatment na ve ACTIVELY RECRUITING PHASE 2
Investigator-Sponsored Trial* AVROBIO FAB-GT Trial **
1 Year (48 weeks) Scored by 2
independent, blinded pathologists Patient 4 Clinically meaningful and statistically significant reduction in substrate in first two evaluable kidney biopsies FABRY PHASE 2 Baseline: The last available, non-missing observation prior to AVR-RD-01
infusion Note: With respect to Fabry disease, Gb3 inclusions per PTC is interchangeable with GL-3 inclusions per KIC PTC: Peritubular Capillary; Gb3: Globotriaosylceramide; GL-3: Globotriaosylceramide; KIC: Kidney Interstitial Capillary 1 Year (48
weeks) Scored by 2 independent, blinded pathologists NEW DATA 87% substrate reduction 100% substrate reduction
FDA guidance cites kidney biopsy as
surrogate endpoint for accelerated approval Fabry Disease: Developing Drugs for Treatment Guidance for Industry (fda.gov) "The purpose of this guidance is to provide recommendations to sponsors regarding clinical trial design features that can
support approval of drugs and biological products intended for the treatment of Fabry disease" "Sponsors can use histological reduction of GL-3 inclusion burden in biopsied kidney interstitial capillaries (KIC) as a surrogate endpoint
reasonably likely to predict clinical benefit to support accelerated approval" "When assessing (counting) KIC GL-3 inclusions in histology specimens, the sponsor should use validated and standardized assay methodologies, and scoring of
KIC GL-3 inclusions should be conducted by experienced pathologists in a blinded and systematic fashion" Complete guidance available at fda.gov
Precedent for use of kidney biopsy
data for FDA approval of drug candidate for Fabry disease Sources: Galafold (Migalastat), Multi-Discipline FDA Review; Germain 2019, Genet Med 21, 1987-1997 (2019) 12.1% -54.1% -42.6% -64.1% -36.3% -45.6% -27.3%
Plasma AGA Activity (nmol/hr/mL)
Leukocyte AGA Activity (nmol/hr/mg protein) Leukocyte AGA Enzyme Activity Plasma AGA Enzyme Activity Plasma AGA Activity Reference Range: 5.1-9.2 nmol/hr/mL; AGA: -galactosidase A Leukocyte AGA Activity Reference Range: 24-56
nmol/hr/mg protein; AGA: -galactosidase A Durability demonstrated over multiple measures up to 2.5 years Patient 4 dosed using plato FABRY PHASE 2 Patient 1 Patient 2 Patient 3 Patient 4 VCN: Vector Copy Number; PBL: Peripheral Blood
Leukocytes; dg: Diploid Genome Drug Product VCN/dg Patient 1: 0.7 Patient 2: 0.5 Patient 3: 1.4 Patient 4: 1.6 Vector Copy Number
Day 0 70% average plasma lyso-Gb3
reduction FABRY PHASE 2 Patient 1 Patient 2 Patient 3 Patient 4 Reduction from Baseline to Last Observation Patient 1 86% Patient 2 N/A Patient 3 55% Patient 4 69% Lyso-Gb3 Plasma Reference Value: 2.4 nM; Lyso-Gb3: Globotriaosylsphingosine Note:
Patient 2 has normal substrate, consistent with late-onset cardiac variant phenotype
ERT No ERT Gene Tx 25.3 26.1 58.5
29.1 15.8 Day 0 25% average plasma lyso-Gb3 reduction below baseline ERT All patients who have discontinued ERT remain off ERT* FABRY PHASE 1 * As of January 11, 2021 Lyso-Gb3: Globotriaosylsphingosine; ERT: Enzyme Replacement Therapy; Tx: Therapy
Gene Tx + Off ERT Gene Tx + ERT Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 25% reduction from baseline ERT OFF ERT 19.0 14.7 33.4 8.2 39.2 43% reduction from baseline ERT OFF ERT 48% reduction from baseline ERT ON ERT 44% reduction from
baseline ERT ON ERT 35% increase from baseline ERT OFF ERT
Day 0 Kidney function (eGFR) stable
up to 3.5 years* Normal Kidney Function Severe CKD Moderate CKD Mild CKD FABRY PHASE 1 & 2 * Eight of nine patients stable; other patient entered trial with more advanced kidney disease and a baseline eGFR level <50 mL/min/1.73m2; as
expected, this patient has not stabilized, and the patient remains on ERT Note: eGFR was calculated using the CKD-EPI formula eGFR: Estimated Glomerular Filtration Rate; CKD: Chronic Kidney Disease; CKD-EPI: Chronic Kidney Disease Epidemiology
Collaboration Fabry Phase 2 Fabry Phase 1
Cardiac function and mass stable
across multiple measures up to 1 year FABRY PHASE 2 Source: *Alfakih K et al, J Magn Reson Imaging, 2003 ; **Maceira AM et al, J of Cardiovascular Magnetic Resonance, 2006 *Reference Range Mean Values Male 20-39 yrs; EF: 64.3 4.2%; EDV: 178.6
30.1 mL; CO: 4-8 L/min; LV Mass Index: 67.8 10.7 g/m2 **Reference Range Mean Values Male 40-49 yrs; EF: 58-75 %; EDV: 117-200 mL; CO: 4-8 L/min; LV Mass Index: 58-91 g/m2
No unexpected safety events
identified Conditioning-related side effects have been manageable and transient (n=1 Bu) (n=3 Mel) No AEs or SAEs related to AVR-RD-01 drug product AEs across trials generally consistent with myeloablative conditioning, underlying disease or
pre-existing conditions Phase 1 AEs (n=94) Grade 3 or 4 (n=14) Phase 1 SAEs (n=2) resolved without clinical sequelae Post-AVR-RD-01 treatment: febrile neutropenia; thrombophlebitis Phase 2 AEs (n=111) Grade 3 or 4 (n=22) Phase 2 SAEs (n=6) resolved
without clinical sequelae Post-AVR-RD-01 treatment: dehydration; nausea; vomiting; febrile neutropenia Phase 2 conditioning-related grade 3/4 AEs Phase 1 & 2 AEs and SAEs Note: Phase 2 safety data cut-off December 7, 2020; Phase 1 safety data
cut-off November 26, 2020 AE: Adverse Event; Bu: Busulfan; Mel: Melphalan Day 0 Day 0 Gastrointestinal System Blood FABRY PHASE 1 & 2
Accelerating enrollment by adding
international referrals Global patient recruitment Expands pool of potential patients Helps navigate COVID-19 issues First global center of excellence established in Australia Long-term follow-up expected to take place in Brazil ONE Fabry patient
from Brazil has been dosed and THREE have been enrolled in Australia
Planned global regulatory strategy
Last updated: Mar 23, 2021