J.P. Morgan 2022: Reaching New Heights, Looking to New Horizons

Reaching New Heights, Looking to New Horizons

Bobby Gaspar, M.D., Ph.D., chief executive officer

40th Annual J.P. Morgan Healthcare Conference

January 13, 2022

From Clinician to CEO: The Evolution of HSC Gene Therapy

Photo courtesy of Great Ormond Street Hospital

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We aspire to end the devastation caused by genetic and other severe diseases through the curative potential of HSC gene therapy.

2022: Reaching New Heights, Looking to New Horizons

Reaching New	Looking to New	The Journey
Heights	Horizons	Ahead

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Forward-looking Statements

Certain information set forth in this presentation and in statements made orally during this presentation contain "forward-looking statements". Except for statements of historical fact, information contained herein constitute forward-looking statements and may include, but are not limited to, the Company's expectations regarding: (i) the safety and efficacy of Libmeldy and its product candidates; (ii) the Company's ability to establish the infrastructure necessary to enable the treatment of eligible MLD patients and the adequacy of the Company's supply chain and ability to commercialize Libmeldy; (iii) the expected development of the Company's business and product candidates; (iv) the timing of regulatory submissions for approval of its product candidates; (v) the

timing of interactions with regulators and regulatory submissions related to ongoing and new clinical trials for its product candidates; (vi) the timing of announcement of preclinical data for its product candidates and the likelihood that such data will be positive and support further development and regulatory approval of these product candidates; (vii) the timing and likelihood of approval of such product candidates by the applicable regulatory authorities; (viii) the adequacy of the Company's manufacturing capacity and plans for future investment and commercialization;

1. execution of the Company's vision and growth strategy, including with respect to global growth; (x) the size and value of potential markets for Libmeldy and the Company's product candidates; and (xi) expected financial performance and financial condition. The words "may," "should," "expects," "intends," "plans," "anticipates," "believes," "estimates," "predicts," "potential," "continue," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements are provided to allow investors the opportunity to understand management's beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment.

These statements are neither promises nor guarantees of future performance. Such forward-looking statements necessarily involve known and unknown risks and uncertainties, many of which are beyond the Company's control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, these risks and uncertainties include, without limitation, the risk that Libmeldy will not be successfully commercialized, including the risk that the Company may not secure adequate pricing or reimbursement to support continued development of Libmeldy or its product candidates, if approved; the risk that any one or more of Orchard's product candidates, including OTL-200, will not be approved, successfully developed or commercialized; the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials of Orchard's product candidates will not be repeated or continue in ongoing or future studies or trials involving its product candidates; the risk that the market opportunity for Libmeldy or its product candidates may be lower than estimated; and, the severity of the impact of the COVID-19 pandemic on Orchard's business, including on preclinical and clinical development, its supply chain and commercial programs. You are cautioned not to place undue reliance on forward-looking statements. For additional disclosure regarding these and other risks faced by the Company, see the disclosure contained in the Company's public filings with the U.S. Securities and Exchange Commission (the "SEC"), including in the Company's quarterly report on Form 10-Q filed with the SEC on November 4, 2021, as well as subsequent filings and reports filed with the SEC. These forward-looking statements speak only as of the date of this presentation. The Company undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

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