Poseida Therapeutics to Present New Preclinical Data Supporting Non-Viral Gene Editing with P-KLKB1-101 for the Treatment of Hereditary Angioedema
Data to be highlighted in a Distinguished Industry Oral Abstract presentation at the
"The newest preclinical data for P-KLKB1-101 support our goal to develop a gene editing treatment option for HAE with encouraging early tolerability, safety and efficacy results," said
HAE is a rare inherited disorder characterized by recurrent episodes of fluid accumulation outside of blood vessels, causing rapid swelling of tissues. The swelling is caused by unchecked activation of the kallikrein-bradykinin cascade due to deficiency of the C1 esterase inhibitor, a protein that is involved in regulating vascular permeability and the contact system. Patients with HAE are in need of a durable, effective, and convenient treatment option that eliminates recurrent attacks.
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.
Key Highlights from P-KLKB1-101 Data to be Presented at ACAAI
- 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 (latest time point assessed). In this model, the targeted therapeutic level of KLKB1 editing was achieved with a single dose, and a 58% reduction of kallikrein levels at the minimally effective dose of 0.125 mg/kg.
- Interim non-human primate (NHP) data demonstrate that P-KLKB1-101 had favorable tolerability and achieved liver editing approaching the desired therapeutic range. Ongoing lead optimization of P-KLKB1-101 yielded a 29% increase in potency (as measured by on-target KLKB1 editing) relative to a historical dose-matched benchmark.
- Poseida's novel ionizable lipid and lipid nanoparticle (LNP) enables potent in vivo delivery of P-KLKB1-101 and a controlled dose response.
Presentation Details
The data will be presented on
Title: Highly Specific Non-Viral Gene Editing with P-KLKB1-101 for Hereditary Angioedema
Abstract #: 8063
Session: Distinguished Industry & Late-breaking Oral Abstracts – Session 1
Session Date/Time: Saturday, October 26,
About P-KLKB1-101
P-KLKB1-101 is an investigational liver-directed non-viral gene editing approach designed using the Cas-CLOVER™ Site-Specific Gene Editing System, Poseida's proprietary high-fidelity nuclease. P-KLKB1-101 is designed for site-specific gene editing of the KLKB1 gene for the treatment of hereditary angioedema (HAE). This rare inherited disorder results in the swelling of the skin, intestinal tract, and airways, which can be both debilitating and life-threatening. Preclinical data demonstrates therapeutically relevant reduction of pre-kallikrein levels in both mouse and non-human primate models.
About Cas-CLOVER
The Cas-CLOVER™ Site-Specific Gene Editing System employs dual RNA-guided DNA targeting for high fidelity editing. The dual guide RNA targeting provides spatial restrictions on each of two Cas-CLOVER molecules after interacting with specific DNA sequences. This interaction then allows Clo051 cutting at the target site. The result is a highly specific edit by the Cas-CLOVER nuclease, and a low incidence of unwanted off-target edits, with 25-fold greater fidelity than CRISPR/Cas9.
About
Forward-Looking Statements
Statements contained in this press release regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the potential capabilities and benefits of the Company's technology platforms and product candidates, including P-KLKB1-101; the quote from
View original content to download multimedia:https://www.prnewswire.com/news-releases/poseida-therapeutics-to-present-new-preclinical-data-supporting-non-viral-gene-editing-with-p-klkb1-101-for-the-treatment-of-hereditary-angioedema-302285382.html
SOURCE