Sangamo: SB-318 results show dose-dependent rise in leukocyte IDUA activity

Sangamo Therapeutics presented interim data from the Phase 1/2 EMPOWERS Study evaluating the SB-318 zinc finger nuclease in vivo genome editing product candidate in patients with Mucopolysaccharidosis Type I. These data, along with interim results of the CHAMPIONS Study evaluating SB-913 for MPS II, were presented today at the WORLDSymposium 2019 being held in Orlando, Florida. Sangamo believes data from these two studies provide complementary evidence supportive of a favorable safety profile and of the activity of the ZFN in vivo genome editing technology used in both SB-318 and SB-913. “The results so far suggest a dose-dependent increase in leukocyte IDUA enzyme activity,” said Dr. Paul Harmatz, a professor at UCSF Benioff Children’s Hospital Oakland and a lead investigator on the study. “Leukocytes are an easily accessible target tissue for IDUA and therefore provide an estimate of tissue enzyme activity for patients with MPS I. Whether these observed increases will translate into clinical benefit from SB-318 is yet to be determined.” The primary objective of the EMPOWERS Study is to determine the safety and tolerability of SB-318, and secondary objectives include evaluation of change from baseline in IDUA activity and urine GAG levels. Biochemical measurements of urinary GAGs, as well as plasma and leukocyte IDUA activity, are assessed at screening and baseline visits, and every two to four weeks during the initial phase of the trial. Patients with mild MPS I receiving weekly ERT were enrolled in the study. The results suggest a dose-dependent increase in leukocyte IDUA activity, with activity levels rising above baseline and in the normal range. Plasma IDUA activity was unchanged from baseline in all three patients. Baseline urine GAG measurements for the three patients in the EMPOWERS Study were in a range considered to be at or slightly above normal. In the limited duration data set available at the time of the WORLDSymposium presentation, urine GAG measurements show no meaningful change.
https://thefly.com/landingPageNews.php?id=2861097