Poseida Therapeutics to present data on P-KLKB1-101 in hereditary angioedema

Poseida Therapeutics (PSTX) announced the upcoming presentation of new preclinical data supporting the potential of P-KLKB1-101, a liver-directed genetic medicine that uses the company’s Cas-CLOVER Site-Specific Gene Editing System, for the treatment of patients with hereditary angioedema, or HAE. The data showed high-fidelity KLKB1 gene editing for the targeted correction of HAE, the ability for controlled dose response, favorable tolerability and liver editing within the predicted therapeutic range. HAE is a rare inherited disorder characterized by recurrent episodes of fluid accumulation outside of blood vessels, causing rapid swelling of tissues. P-KLKB1-101 is a fully non-viral investigational gene editing therapy designed to enable high fidelity editing at the pre-kallikrein gene, or KLKB1, for correction of HAE. It utilizes the Cas-CLOVER nuclease, which is engineered for high specificity, to achieve site-specific gene editing. P-KLKB1-101 enabled highly efficient KLKB1 editing and reduction of kallikrein in cultured primary human hepatocytes, with all off-target edits consistently at or below 0.1%, including at high dose levels. P-KLKB1-101 yielded controlled, dose-dependent reductions in kallikrein protein levels and activity in a new humanized mouse model. The reduction in plasma kallikrein levels was stable and persisted for at least 180 days. Interim non-human primate data demonstrate that P-KLKB1-101 had favorable tolerability and achieved liver editing approaching the desired therapeutic range.