Homology Medicines

Homology Medicines

Homology owns a proprietary platform based on AAV vectors derived from human CD34+ cells. The company is building both a gene therapy and gene editing pipeline based on this technology which they licensed from City of Hope. Its lead program is HMI-102 which is an AAVHSC15 vector being developed for classic phenylketonuria (PKU) patients. PKU is an inborn error of metabolism where there are mutations in the PAH gene resulting in the inability to metabolize Phe, which can result in severe neu-rological impairment. Initial proof of concept data from a Phase I/II study showed a dose response in Phe reduction. The first gene editing program HMI-103 leverages the same delivery vehicle (AAVHSC) as its gene therapy relative HMI-102, but excludes a promotor and flanks the transgene with two homology arms to drive integration of the transgene into a specified region by homologous recombination. This poses an inherent safety advantage in comparison to other gene editing technologies that have to create single- or double-strand breaks in the patient DNA by cutting with an endo-nuclease (Cas9 or Fok-I), which mainly trigger error-prone no-homologues end joining (NHEJ) for repair as well as have higher associated risks of off-target cutting and on-target effects (large genomic rearrangements or deletions). The drawback is lower editing efficiency due to lack of endonuclease cutting.