Intellia Therapeutics, Inc. is presenting preclinical results for its CRISPR/Cas9-Based Therapy for HAE.
“The data from our HAE development program reinforce the modularity of Intellia’s non-viral delivery genome editing platform and how it is enabling independent, single-dose therapies for multiple monogenic diseases. For HAE, we expect to nominate a development candidate in the first half of this year,” says Intellia President and CEO John Leonard, M.D.
Intellia’s HAE treatment hypothesis involves knocking out the kallikrein B1 (KLKB1) gene to reduce kallikrein activity, which is involved in the biological pathway for release of bradykinin. Intellia expects this reduction to correlate with a decrease in bradykinin activity, thus, preventing the activation of endothelial cells that causes vascular leakage and angioedema in HAE patients. The data shows that the knockout of KLKB1 produces in non-human primates (NHPs) a 90% reduction in kallikrein activity, a level that translates to a therapeutically meaningful impact on HAE attack rates. This kallikrein activity reduction was sustained for at least five months in an ongoing NHP study, in a highly reproducible manner observed across both rodent and NHP studies.
Intellia’s potential HAE therapy utilizes the company’s modular non-viral lipid nanoparticle (LNP) system to deliver CRISPR/Cas9. Intellia’s proprietary LNP-based delivery system includes two basic components: Cas9 messenger RNA (mRNA) and a guide RNA (gRNA). The gRNA is the only variable portion of the LNP delivery system and is the sole component that needs to be changed from the LNP-based delivery system that forms the foundation of NTLA-2001, Intellia’s development candidate for the treatment of ATTR for which the company intends to submit an IND application in mid-2020.
Intellia continues to evaluate several potential guide RNAs and expects to nominate a development candidate for HAE in the first half of 2020. Intellia’s KLKB1 HAE program is subject to an option by Regeneron to enter into a Co/Co agreement, in which Intellia would remain the lead party.