Poseida Therapeutics to Present Preclinical Data on Non-Viral Gene Editing for Hereditary Angioedema Treatment

Poseida Therapeutics, Inc. has announced the upcoming presentation of new preclinical data at the American College of Allergy, Asthma & Immunology (ACAAI) 2024 Scientific Meeting. This presentation will focus on the potential of P-KLKB1-101, a liver-directed genetic medicine, in treating hereditary angioedema (HAE). The company utilizes its proprietary Cas-CLOVER™ Site-Specific Gene Editing System to achieve high-fidelity gene editing for this purpose.

Blair Madison, Ph.D., Chief Scientific Officer of Gene Therapy at Poseida Therapeutics, expressed optimism about the preclinical data, highlighting the treatment's early indications of tolerability, safety, and efficacy. The data revealed a significant reduction of kallikrein in a preclinical mouse model at a low dose, which marks an improvement in the lipid nanoparticle delivery efficiency. This efficiency, along with the high-fidelity editing capabilities of Cas-CLOVER, could extend therapeutic gene editing to other liver-related targets.

HAE is a rare genetic disorder characterized by episodes of fluid accumulation outside of blood vessels, leading to rapid tissue swelling. This swelling results from the unregulated activation of the kallikrein-bradykinin cascade due to a deficiency in the C1 esterase inhibitor, a protein that regulates vascular permeability and the contact system. Patients with HAE currently require a durable and effective treatment to manage recurrent attacks.

P-KLKB1-101 is a non-viral investigational gene editing therapy designed to correct HAE by targeting the pre-kallikrein gene (KLKB1). It utilizes the Cas-CLOVER nuclease, an engineered enzyme for high specificity, to achieve site-specific gene editing.

The preclinical data to be presented includes several key findings. P-KLKB1-101 demonstrated efficient KLKB1 gene editing and kallikrein reduction in cultured primary human hepatocytes, with off-target edits consistently at or below 0.1%, even at high doses. In a new humanized mouse model, P-KLKB1-101 produced controlled, dose-dependent reductions in kallikrein protein levels and activity. Remarkably, the reduction in plasma kallikrein levels persisted for at least 180 days. A single dose achieved the targeted therapeutic level of KLKB1 editing, resulting in a 58% reduction in kallikrein at a minimally effective dose of 0.125 mg/kg.

Interim data from non-human primates (NHP) indicated favorable tolerability and liver editing nearing the desired therapeutic range. Continued optimization of P-KLKB1-101 has led to a 29% increase in potency compared to a historical benchmark. Additionally, Poseida's novel ionizable lipid and lipid nanoparticle (LNP) system has enabled effective in vivo delivery of P-KLKB1-101 with a controlled dose response.

The data will be presented on October 26, 2024, by Dr. Madison at the ACAAI Scientific Meeting in Boston, during the Distinguished Industry & Late-breaking Oral Abstracts session.

P-KLKB1-101 represents a significant development in non-viral gene editing therapies for hereditary angioedema, leveraging Poseida’s Cas-CLOVER™ Site-Specific Gene Editing System. This system, known for its high fidelity, employs dual RNA-guided DNA targeting, providing spatial restrictions that enhance specificity and minimize off-target edits.

Poseida Therapeutics continues to advance its pipeline of innovative genetic medicines and therapies. The company is committed to addressing high unmet medical needs through its proprietary genetic editing platforms, which include non-viral transposon-based DNA delivery systems, the Cas-CLOVER™ Site-Specific Gene Editing System, and other advanced technologies. Poseida has also formed strategic collaborations with Roche and Astellas to further develop cell therapies for cancer patients.