Homology Medicines : Corporate Presentation - July 2023

Initial Clinical Data from

Phase 1 pheEDIT Trial Evaluating HMI-103 in Adults with Phenylketonuria (PKU),

and Corporate Update

July 27, 2023

Forward-Looking Statements

This presentation contains forward-looking statements. We intend such forward-looking statements to be covered by the safe harbor provisions for forward- looking statements contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements contained in this presentation that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding: our expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of our product candidates, including HMI-103 for the treatment of PKU; the projected global market opportunity for HMI-103; the potential of our gene therapy and gene editing platforms, including our GTx-mAb platform; our plans and timing for the release of additional preclinical and clinical data; our plans to progress our pipeline of genetic medicine candidates; our anticipated clinical development timelines; our plans to evaluate strategic options and the expected financial and operational impacts of our restructuring initiatives. The words "believe," "may," "will," "estimate," "potential," "continue," "anticipate," "intend," "expect," "could," "would," "project," "plan," "target," and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements use these words or expressions. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of our development efforts; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process; interim, topline and preliminary data may change as more patient data become available, and are subject to audit and verification procedures that could result in material changes in the final data; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties, including for the manufacture of materials for our research programs, preclinical and clinical studies; failure to obtain U.S. or international marketing approval; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; securities class action litigation; the impact of the COVID-19 pandemic and general economic conditions on our business and operations, including our preclinical studies and clinical trials; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property; and significant costs incurred as a result of operating as a public company. These and other important factors discussed under the caption "Risk Factors" in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2023, and our other filings with the Securities and Exchange Commission could cause actual results to differ materially from those indicated by the forward-looking statements made in this presentation. Any such forward-looking statements represent management's estimates as of the date of this presentation. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.

This presentation also includes statistical and other industry and market data that we obtained from industry publications and research, surveys and studies conducted by third parties or us. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of such information. All of the market data used in this presentation involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. While we believe these industry publications and third-party research, surveys and studies are reliable, we have not independently verified such data. The industry in which we operate is subject to a high degree of uncertainty, change and risk due to a variety of factors, which could cause results to differ materially from those expressed in the estimates made by the independent parties and by us.

© Copyright 2023 Homology Medicines, Inc. All rights reserved.	2 |

Agenda

Overview of PKU and Market Potential

Unmet Medical Need

Albert Seymour, Ph.D.

President and CEO

HMI-103 and pheEDIT Trial Design

Initial Efficacy and Safety Data Observations

Corporate Update

Julie Jordan, M.D.

Chief Medical Officer

© Copyright 2023 Homology Medicines, Inc. All rights reserved.	3 |

Encouraging Initial Data from First Dose Level in pheEDIT Trial Warrants Dose Escalation

HMI-103 was generally well-tolerated by all three participants

Two participants achieved meaningful reductions in plasma Phe at first dose level

Participant 1	Rapid onset of action with plasma Phe below U.S. ACMG PKU treatment threshold of <360 μmol/L* at Week 4 post-dose
	Clinically meaningful reduction in plasma Phe concentration of 59% to 319 μmol/L maintained at Week 31 even after dietary
	protein supplementation initiated at Week 14
Participant 2	Meaningful plasma Phe reduction of 49% at Week 17 and majority of post-dose Phe levels are below baseline
Participant 3	Recently dosed, and Phe levels above baseline; additional data needed to make a meaningful conclusion

* Participants 2 and 3 have self-liberalized protein intake above baseline Phe-restricted diet

Dose escalation warranted to identify optimal dose

Homology to evaluate strategic options to maximize shareholder value

Based on anticipated clinical development timeline for HMI-103 and current financing environment, stopping further program development efforts while we evaluate strategic options

Related reduction in force of 87%

*American College of Medical Genetics and Genomics (ACMG) PKU treatment threshold: Vockley J., et al., Genet Med. 2014

Data cut-off date: July 26, 2023

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PKU is Caused by Genetic Variants in the PAH Gene Which Can Lead to Toxic Levels of Phe

PKU is an inborn error of metabolism caused by variants in PAH gene

Results in loss of function of phenylalanine hydroxylase (PAH) enzyme responsible for metabolism of phenylalanine (Phe)

If untreated, toxic levels of Phe accumulate and result in progressive and severe neurological impairment

© Copyright 2023 Homology Medicines, Inc. All rights reserved.

	PKU Pathway
	Protein
Phenylalanine (Phe)
PAH
Enzyme
	Tyrosine (Tyr)
Melanin	Neurotransmitters
	5 |