AVROBIO : Pipeline Prioritization and Fabry Data Presentation

ReprioritizesPipeline Programs

J A N U A R Y 2 0 2 2

Disclaimer

This presentation has been prepared by AVROBIO, Inc. ("AVROBIO") for informational purposes only and not for any other purpose.

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 plans and expectations for reprioritizing our program pipeline, including the deprioritization of our Fabry disease clinical program; 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 expected benefits and results of our manufacturing technology, including the implementation of our plato® platform in our clinical trials and gene therapy programs; the potential

use of monoclonal antibody conditioning agents; the expected safety profile of our investigational gene therapies; and our financial position and cash runway expectations. 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; 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 or potential use of monoclonal antibody conditioning agents, 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 ongoing COVID-19 pandemic 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 trademark of AVROBIO. Other trademarks referenced in this presentation are the property of their respective owners.

Copyright© 2022 AVROBIO, Inc. All rights reserved.

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Today's press release

• Deprioritizing Fabry disease program and shifting focus to other clinical-stage programs in lysosomal disorder pipeline
• • New data from five most recently dosed patients in Phase 2 FAB-GT trial show variable engraftment
  • Decision driven by several factors, including significantly extended development timeline and increasingly challenging market and regulatory environment for Fabry disease
  • Based on our investigation, we believe due to large degree of heterogeneity in Fabry disease, in some cases there may be intrinsic resistance to engraftment related to the unique underlying pathophysiology of untreated Fabry disease, potentially caused by persistently stressed vascular endothelium
  • Also reviewed potential procedure-related factors and conditioning parameters, including possible impact, in the context of untreated Fabry disease, of previous clinical trial protocol amendment for five most recently dosed patients which prolonged the conditioning agent washout period by up to 48 hours
  • Drug product specifications for all patients met all release criteria
• No observed read-through to other clinical trials to date
• • Data from 13 patients previously reported have shown durable engraftment out 9 to 54 months
  • • 4 previously dosed patients in FAB-GT trial
    • 5 dosed in Phase 1 Fabry disease trial
    • 3 dosed in Phase 1/2 cystinosis trial
    • 1 dosed in Phase 1/2 Gaucher disease type 1 trial
• Cash runway to be extended into Q1 2024
• Multiple data and regulatory updates expected in 2022

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Two AVR-RD-01 Fabry clinical trials

14 patients dosed across Phase 1 and 2

PHASE 1

Investigator-Sponsored Trial*

FULLY ENROLLED

OBJECTIVES	PATIENTS	OBJECTIVES
•	Safety and	• n = 5 patients	•	Safety and
	tolerability	• 18 - 59 year-old males		tolerability
•	Preliminary	• On ERT >6 months prior to enrollment	•	Efficacy
	efficacy

PHASE 2

AVROBIO FAB-GT Trial **

PATIENTS

• n = 8-12 patients (9 dosed to-date)
• 16 - 50 year-old males
• Treatment naïve

• Sponsored by FACTs team (Fabry Disease Clinical Research and Therapeutics) in Canada
• FAB-GTf/k/a FAB-201

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Phase 2 FAB-GT

Reduction to near baseline in AGA enzyme activity in 3 of 5 most recently dosed patients 3-9 months post-gene therapy

Patients 1-4			Patients 5-9

AGA leukocyte normal reference range between 24-56 nmoles/hr/mg protein; AGA plasma normal reference range is 5.1-9.2 nmoles/hr/ml