biOasis Technologies Ord Shs V.BTI.H

RE:RE:RE:Big siRNA deal

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It seems that Alnylam is currently relying upon intrathecal injection. Promising non-human primate and rodent results. xB3 could allow for intravenous delivery of siRNAs and other RNAi therapies to get across the brain without the need to more invasive intrathecal delivery. However, the tissue distribution for intrathecal vs. intravenous delivery is likely different. This may or may not be an issue depending upon the therapeutic application. Here's a paragraph from an Alnylam press release from last year.

"In NHP studies, a single intrathecal (IT) injection of a siRNA conjugate targeting the ubiquitously expressed β-catenin mRNA transcript resulted in broadly distributed target gene silencing across the brain and spinal cord. Robust and durable silencing of β-catenin mRNA was observed after a single dose at day 31 post injection. Specifically, a single 72 mg dose (approximately 24 mg/kg) resulted in over 80 percent target silencing in the spinal cord and approximately 50 percent silencing across regions of the brain. Widespread distribution of the novel siRNA conjugate was observed across the CNS, including the frontal and temporal cortex, deep brain structures such as basal ganglia and dentate gyrus, cerebellum, brain stem and spinal cord, with evidence for cellular localization in neurons, astrocytes, and microglia. In additional rat studies, further optimization of novel conjugates was reported using siRNAs targeting superoxide dismutase 1 (SOD1), a genetically defined disease gene implicated in amyotrophic lateral sclerosis (ALS). Additional optimization of the conjugate design resulted in an over ten-fold improvement in potency, with a dose as low as 0.07 mg (approximately 0.25 mg/kg) resulting in approximately 50 percent SOD1 silencing across the CNS. In both rat and NHP studies, intrathecal administration of these novel siRNA conjugates was found to be generally well tolerated. Consistent with previous guidance, Alnylam expects to select its first CNS Development Candidate (DC) by the end of 2018 with an initial Investigational New Drug (IND) or equivalent application in late 2019 or early 2020."

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