BEDFORD, Mass., July 16, 2018 - Homology Medicines, Inc., a genetic medicines company, announced today a peer-reviewed publication demonstrating that Homology's technology induces efficient and precise in vivo gene editing. The publication, by senior author Saswati Chatterjee, Ph.D., Department of Surgery, member of the Beckman Research Institute at City of Hope in California, and scientific co-founder of Homology, also highlights the platform's use of homologous recombination, the cells' natural DNA correction pathway, for nuclease-free gene editing.
"This early academic research provided the foundation for our gene therapy and gene editing platform, and we have already translated that discovery into a scalable process to enable the potential development of genetic medicines," said Albert Seymour, Ph.D., Chief Scientific Officer of Homology Medicines. "We continue to expect to nominate a gene editing development candidate this year and begin a clinical trial of our PKU gene therapy program next year."
The publication in the Proceedings of the National Academy of Sciences (PNAS) titled, "Stem Cell-Derived Clade F AAVs Mediate High-Efficiency Homologous Recombination-Based Genome Editing," details the capabilities of the adeno-associated virus vectors originally derived from human hematopoietic stem cells (AAVHSCs):
AAVHSCs Mediated Nuclease-Free In Vivo Gene Editing
Efficient in vivo gene editing was observed following a single intravenous (IV) injection of an AAVHSC15 editing vector targeting a murine safe harbor locus. The editing vector contained a promoterless luciferase cDNA flanked by homology arms specific to the murine locus. After IV injection, whole-body imaging demonstrated luciferase expression persisting throughout the 63-day study and in a longer term 112-day study. In comparison, the editing vector without homology arms showed no luciferase expression, and a non-Clade F AAV8 editing vector showed limited expression. Organ-specific luciferase expression revealed highest levels in the liver, followed by muscle, as well as heart, lungs, kidneys and brain.
In Vivo Editing was Precise, On-Target and Confirmed at Molecular Level
In vivo gene editing was shown to be precise and on-target using linear amplification PCR, a method to confirm DNA insertion at the targeted location. The studies demonstrated accurate insertion of the luciferase construct into the safe harbor locus with no on-target insertion/deletion (indel) mutations or inverted terminal repeats (ITRs). Targeted insertion was further confirmed using Southern blot analysis.
In Vitro Nuclease-Free Editing was On-Target, Precise and Confirmed at Molecular Level
AAVHSC vectors induced green fluorescent protein (GFP) expression in multiple human cell types, including primary human CD34+ hematopoietic stem cells. AAVHSC editing vectors packaged with homology arms and a promoterless GFP construct demonstrated a higher percentage of cells expressing GFP compared to non-Clade F vectors. Molecular characterization of in vitro gene editing with AAVHSC vectors was shown to be on-target and precise, with no evidence of sequence alterations, indel mutations or ITR insertion using a targeted integration assay and confirmed by next-generation sequencing.
AAVHSC Gene Editing was Mediated by Homologous Recombination
AAVHSC editing vectors were tested in multiple human cell lines with mutations in key DNA repair-responsible genes and showed GFP expression in all except those deficient in BRCA2, an essential mediator of homologous recombination.
About Homology Medicines, Inc.
Homology Medicines, Inc. is a genetic medicines company dedicated to transforming the lives of patients suffering from rare genetic diseases with significant unmet medical needs by curing the underlying cause of the disease. Homology's proprietary platform is designed to utilize its human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to precisely and efficiently deliver genetic medicines in vivo either through a gene therapy or nuclease-free gene editing modality across a broad range of genetic disorders. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a particular focus on rare diseases, and intellectual property covering its suite of 15 AAVHSCs. Homology believes that its compelling preclinical data, scientific expertise, product development strategy, manufacturing capabilities and intellectual property position it as a leader in the development of genetic medicines. For more information, please visit http://www.homologymedicines.com.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including statements regarding the anticipated timing of nomination of a gene editing development candidate; our expectations surrounding initiation of clinical trials for our PKU gene therapy program; our goal of improving the lives of patients with rare genetic diseases; the potential of HMI-102 and our AAVHSC platform; the anticipated timing of the release of clinical data; beliefs about preclinical data; our ability to help patients with ophthalmic disorders; and our position as a leader in the development of genetic medicines. 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: the fact that 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 marketable products; the early stage of our development efforts; our failure or the failure of our collaborators to successfully develop and commercialize drug candidates; risks relating to the regulatory approval process; 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; the inability to obtain orphan drug exclusivity; failure to obtain international marketing approval; failure to obtain U.S. marketing approval; ongoing regulatory obligations; effects of significant competition; unfavorable pricing regulations, third-party reimbursement practices or healthcare reform initiatives; product liability lawsuits; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property; the price of our common stock may be volatile; significant costs as a result of operating as a public company; and any securities class action litigation. 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, 2018 and our other filings with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management's estimates as of the date of this press release. 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.
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Proceedings of the National Academy of Sciences