- Data From New GTx-mAb Platform Demonstrated Proof of Principle for AAVHSCs to Deliver One-Time In Vivo Gene Therapy to Produce Antibodies in Humanized Murine Model -
- Additional Data for HMI-203 Gene Therapy in Hunter Syndrome and HMI-103 Gene Editing in PKU Support Planned Phase 1/2 Clinical Trial Initiations by End of 2021 -
- On Track to Report Initial Phase 2 Data From pheNIX PKU Clinical Trial by Year End -
- Conference Call / Webcast Today, May 13 at 8:15 a.m. ET -
BEDFORD, Mass., May 13, 2021 – Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today the presentation of data in multiple disease areas supporting the Company’s human hematopoietic stem cell-derived adeno-associated virus vector (AAVHSC) platform. Among Homology’s presentations are data from its new GTx-mAb platform targeting complement protein 5 (C5), which showed proof of principle in paroxysmal nocturnal hemoglobinuria (PNH). The Company also presented data from its gene therapy program for MPS II (Hunter syndrome) and gene editing program for phenylketonuria (PKU), both of which are on track to enter the clinic this year. Presentations also focused on the Company’s internal commercial GMP manufacturing process and platform. These data were featured at the American Society of Gene & Cell Therapy (ASGCT) 24th Annual Meeting.
“Our new GTx-mAb platform is designed to leverage our AAVHSCs to deliver one-time in vivo gene therapy to produce antibodies from the liver and secrete them throughout the body,” stated Albert Seymour, Ph.D., Chief Scientific Officer of Homology Medicines. “These data demonstrated once again that our vectors are highly efficient in targeting the liver. With this approach, we showed our vectors enabled the liver to produce antibodies that resulted in sustained expression levels in the serum of a humanized murine model that inhibited red blood cell destruction using an ex vivo assay. These PNH data are exciting, given the high unmet need, and underscore the potential to address other complement-related diseases, as well as diseases with larger patient populations. We are on track to name our first development candidate from the GTx-mAb platform in PNH this year.”
Dr. Seymour continued, “Our multiple presentations at ASGCT highlight the maturation of our pipeline, which is expected to yield two additional clinical programs this year, including our Phase 1/2 clinical trials in Hunter syndrome and our first in vivo gene editing candidate for PKU. We plan to share additional details about our GTx-mAb platform and our ASGCT data during our conference call and webcast this morning.”
Highlights from Homology’s 2021 ASGCT Presentations
Homology’s first-ever data from its GTx-mAb platform in the presentation “Transducing the Liver as an Antibody Factory using AAVHSCs” showed:
- Proprietary vector containing a full-length antibody against C5 was delivered via AAVHSCs and engineered to express in the liver
- Expression levels in the serum of two mouse models were consistent with C5 antibody therapeutics
- Sustained and robust immunoglobulin G (IgG) expression in vivo for the duration of the study in mice (up to 20 weeks)
- In vivo expression of C5mAb had potent functional activity, as shown in an ex vivo hemolytic assay
In the presentation “Long-Term Expression of HMI-203: Investigational Gene Therapy Candidate for Mucopolysaccharidosis Type II (MPS II), or Hunter Syndrome,” a single I.V. dose of HMI-203 in the murine model:
- Demonstrated long-term transduction and expression in the brain, kidney, heart, lung, liver and spleen
- Resulted in sustained secretion of iduronate-2-sulfatase (I2S) into the serum
- Reduced glycosaminoglycan heparan sulfate (GAG-HS) in all tissues tested
- Achieved phenotypic correction of joints and skeletal features
- Significantly reduced GAG-HS levels in cerebrospinal fluid (CSF) at all doses at 12 weeks post dose
In the presentation “Investigational Genetic Medicine Approaches for Phenylketonuria (PKU),” a single I.V. dose of AAVHSC15-based gene therapy or gene editing resulted in a sustained reduction of phenylalanine (Phe) in a murine model of PKU on a normal diet, supporting the potential to address the underlying cause of PKU in individuals with either a fully developed or growing liver. In the study, the AAVHSCs:
- Achieved a sustained reduction of Phe in PAHenu2 mice on a normal diet
- Integrated into the human target PAH locus with the human-specific gene editing vector
- Showed integration levels that were similar with the human- and mouse-specific gene editing vectors and at rates that have resulted in sustained reduction of serum Phe in a murine model
In “Functional Characterization of AAVHSCs Compared to AAV serotypes: Activation of Cellular Pathways In Vitro and In Vivo Transduction Properties,” the characterization of AAVHSCs compared to AAV capsids 1-8 in human induced pluripotent stem cells (iPSC) showed AAVHSCs:
- Did not significantly elicit p53-mediated cell death or impact cell division (AAVHSC9/15/16/17) compared to non-Clade F vectors
- Did not alter the cell cycle and cell division in iPSC or primary human fibroblasts (AAVHSC15) compared to non-Clade F vectors
- Had different intracellular transport and nuclear accumulation kinetics (AAVHSC15) compared to AAV2
- Were determined to be the most efficient liver transducers, alongside AAV8 and AAV9, among all capsids tested as determined by luciferase expression and vector genomes
- Resulted in higher vector genomes and luciferase expression at the F8 locus when tested in vivo in mice compared to mice transduced with AAV6
On the manufacturing front, “Next Generation AAV Drug Products: Enhanced Stability & Clinical Ease for High Titer Preparations” demonstrated the marked stability of AAVHSCs in the liquid state and the impact of novel formulations on capsid stability, which:
- Achieved concentrations in excess of 1E14 vg/mL and demonstrated stability for a minimum of one year at 2-8°C and more than six months at room temperature, reducing the need for -80°C-storage infrastructure and simplifying the clinical supply chain by enabling 2-8°C storage at the manufacturing site and clinical pharmacy
In “Wildtype AAV2 Rep Protein Produces Higher Titer AAVHSC Vectors with Improved Packaging Profiles Compared to Clade F Associated Chimeric Rep,” wildtype AAV2 Rep protein was shown to be superior when compared with Clade F associated chimeric Rep (AAV9) protein. Vector produced with WT AAV2 Rep resulted in:
- Increased productivity in both adherent and suspension platforms across multiple AAV genome constructs, with an up to 88% increase in vector genomes and 40% increase in calculated full capsids
- Increased productivity across multiple production scales
- Improved or consistent quality attributes in vector packaging profile, infectivity and purity
In “Gene Therapy Candidate for Metachromatic Leukodystrophy (MLD): Summary of Preclinical In Vivo Data Following an Intravenous Delivery of HMI-202,” a single I.V. dose of HMI-202 showed a direct motor benefit in MLD mice as evidenced by distribution patterns required to show a functional effect.
- In the MLD mouse model, data showed:
- Long-term transduction, expression and ARSA activity in the peripheral and brain tissues
- Reduced sulfatides to normal levels in the brain
- Phenotypic rescue in the rotarod assay
- In non-human primates (NHPs):
- AAVHSCs crossed the blood-brain barrier (BBB) and blood-nerve barrier (BNB) with expression in relevant cell types
For more information about the presentations, visit Homology’s website at www.homologymedicines.com/publications.
In addition to the presentations at ASGCT 2021, Homology management will host a conference call and webcast at 8:15 a.m. ET to discuss the new GTx-mAb platform and share data highlights from the Company’s pipeline. The webcast will be accessible on Homology’s website in the Investors section, and the webcast replay will be available on the website for 90 days following the presentation. To access using the conference call line, dial (866) 244-8091 (U.S./Canada toll-free) or (602) 563-8623, with Conference ID 5548861.
About Homology Medicines, Inc.
Homology Medicines, Inc. is a clinical-stage 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. The Company’s intellectual property covers its family 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 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 without limitation statements regarding our expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of our product candidates the potential of our gene therapy and gene editing platforms, including our new GTx-mAb platform; our plans to name a development candidate in a new therapeutic area and potential thereof; our plans and timing for the release of additional preclinical and clinical data and to name a developmental candidate and potential thereof; our beliefs regarding our manufacturing capabilities; our position as a leader in the development of genetic medicines; and our participation in upcoming presentations and conferences. 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 impact of the COVID-19 pandemic on our business and operations, including our preclinical studies and clinical trials, and on general economic conditions; 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 capabilities of our manufacturing facility; 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; 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; failure to attract, retain and motivate qualified personnel; the possibility of system failures or security breaches; risks relating to intellectual property and significant costs 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, 2021 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.