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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: AUGUST 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 r

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AUGUST 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; our plans and expectations with respect to the development of our clinical and preclinical product candidates, including timing, design and initiation
of our potential clinical and registration trials and anticipated interactions with regulatory agencies; the timing of anticipated clinical and regulatory updates; 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; 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 that regulatory agencies may disagree with our anticipated development approach for any one or more of our product candidates, including that we may not be able to utilize our planned registration
trial of AVR-RD-01 for full approval but instead be required to conduct additional testing, that we may be required to conduct our planned testing in a more time-consuming, expensive, challenging or otherwise different manner than we envision or
have conducted for our existing trials, particularly in light of the FDA's preference for clinical trials to be double-blinded and potentially include sham controls, the risk that we may not be able to utilize our envisioned surrogate endpoint
to support full approval of AVR-RD-01 but instead be required to measure a different endpoint such as a clinical outcome, and the risk that regulatory agencies may require additional testing and/or clinical trials for our product candidates prior to
initiating registration trials for such product candidates; 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, 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
Vision Bring personalized gene therapy
to the world. Purpose Freedom from a lifetime of genetic disease.
Leadership in ex vivo lentiviral gene
therapy 4 Patients dosed across 3 indications of patients out >6 months show durability; Longest out 3.5 years SOC: Standard of Care 18 100% Leading pipeline for 6 lysosomal disorders First-in-class gene therapies Multi-billion dollar market
potential >50,000 target patient population ~$4.8 billion annual net sales SOC Industry-leading platform: plato Foundation for worldwide commercialization and pipeline expansion Planning for multiple registration trials in 2022; Pivoting to
commercial readiness
Leading lysosomal disorder gene therapy
pipeline Multiple milestones across pipeline expected over the next 12 months 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 IND-Enabling Phase 1/2 Planned Upcoming Milestones
1Q22 - Clinical and regulatory update at WORLDSymposium Mid22 - Initiate registration trial 1H22 - Clinical trial update 1Q22 - Clinical trial and regulatory update 2H22 - Initiate company-sponsored clinical
trial 2H22 - Initiate Phase 1/2 clinical trial 2H22 - Initiate registration trial 2H22 - Initiate Phase 1/2 clinical trial Indication WHOLLY-OWNED/LICENSED Planned regulatory milestones subject to regulatory agency
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 Pipeline of
first-in-class indications targeting > 50,000 patients 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
Significant advantages over standard of
care 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 PATIENT 6 PATIENT 7 PATIENT 8 PATIENT 9 Gaucher Type 1 Phase 1/2 PATIENT 1 Cystinosis Phase 1/2 PATIENT 1 PATIENT 2
PATIENT 3 Durability demonstrated across clinical programs First patient out 3.5 years; 10 patients out 1 year or more * Data not yet available
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
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
*** Plan to increase to up to 14 patients with protocol amendment, including females Two AVR-RD-01 Fabry clinical trials 14 patients dosed across Phase 1 and 2 OBJECTIVES PATIENTS Safety and tolerability Efficacy n = 8-12 patients*** (9 dosed
to-date) 16 - 50 year-old males*** Treatment na ve ACTIVELY RECRUITING PHASE 2 Investigator-Sponsored Trial* AVROBIO FAB-GT Trial **
100% substrate reduction 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 87% substrate reduction 1 Year (48 weeks) Scored by 2 independent, blinded pathologists NEW DATA
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 Rx 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; Rx: Therapy
Gene Rx + Off ERT Gene Rx + 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
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
Cystinosis opportunity Standard of
care (SOC): Cysteamine pills & eye drops Not curative, relentless progression of disease continues; significantly shortened lifespan; kidney transplant often required Burdensome and expensive - high pill burden and hourly eye drops; 5-year
treatment cost with SOC ~$4.3 million* Caused by CTNS gene defect, resulting in cystine buildup in lysosomes Cystinosis Target Product Profile**: Prevents, halts or reverses disease; extends/normalizes lifespan Addresses all patient segments -
male & female; kidney transplant independent; all ages Lifelong durability - single infusion; off cysteamine pills and eye drops Impacts hard-to-reach organs - e.g., eye, endocrine organs, brain Well tolerated Unmet needs with SOC:
Vision Corneal cystine accumulation, photophobia, involuntary eyelid closure Endocrine disorders Softening & deformation of bones, hypothyroidism, diabetes, infertility Everyday burden of illness, reduced life expectancy High pill burden causes
GI discomfort; sulfur body odor and breath CNS complications Myopathy, hypotonia, tremors, swallowing, neurodevelopmental issues Kidney function Renal Fanconi syndrome, proteinuria, CKD, kidney failure Jaxon, living with cystinosis Affects ~
1:170,000 people * WAC pricing from Redbook using standard dosing assumptions ** Note: these are target attributes for a first-line therapy
Steady enrollment in AVR-RD-04 IST
trial in cystinosis AVR-RD-04 trial sponsored by University of California, San Diego; IST does not use plato platform Note: AVR-RD-04 aka CTNS-RD-04 IST: Investigator Sponsored Trial OBJECTIVES PATIENTS Safety and tolerability Hypothesis
Last updated: Aug 9, 2021