CRISPR Therapeutics Unveils ASGCT Talk and New In Vivo Gene Editing Programs

CRISPR Therapeutics, a biopharmaceutical company specializing in gene-based medicines, unveiled new preclinical data at the 27th Annual Meeting of the American Society of Cell and Gene Therapy (ASGCT). The focus of the presentation was on lipid nanoparticle (LNP) mediated delivery for in vivo ocular gene editing, targeting the myocilin (MYOC) gene as a potential treatment for glaucoma.

In addition to this, CRISPR Therapeutics announced the expansion of its in vivo pipeline with two new preclinical programs. These programs employ LNP-mediated delivery of CRISPR/Cas9 gene editing tools to the liver. The first program, CTX340, targets the angiotensinogen (AGT) gene for treating refractory hypertension. The second, CTX450, targets the 5’-aminolevulinate synthase 1 (ALAS1) gene for treating acute hepatic porphyria (AHP).

Samarth Kulkarni, CEO and Chairman of CRISPR Therapeutics, highlighted the company's advancements in developing the LNP platform for liver delivery of CRISPR/Cas9. He emphasized that the expansion of the in vivo pipeline underscores the platform's scalability and the team’s capability to translate these advancements into meaningful therapies for both common and rare diseases.

CRISPR Therapeutics’ proprietary LNP platform is designed for the liver delivery of CRISPR/Cas9. The company's initial in vivo programs, CTX310 and CTX320, are targeting cardiovascular disease and are currently in clinical trials. The addition of CTX340 and CTX450 demonstrates the platform's versatility and potential to address a broader range of diseases.

Refractory hypertension, affecting about 1.5 million patients in the U.S., is a significant unmet medical need. CTX340 aims to inhibit the production of hepatic angiotensinogen (AGT), a key player in the renin-angiotensin-aldosterone system (RAAS), to normalize blood pressure with a one-time treatment. Preclinical studies of CTX340 showed approximately 60% liver editing and 90% AGT protein reduction, leading to a sustained 30 mmHg blood pressure reduction in the spontaneously hypertensive rat (SHR) model over three months.

Acute hepatic porphyria (AHP) is a rare genetic disorder affecting heme biosynthesis. Patients experience acute attacks with severe neurovascular symptoms and chronic issues like pain. CTX450 aims to inhibit ALAS1 production in the liver, preventing the buildup of neurotoxic compounds. Preclinical studies of CTX450 showed around 70% liver editing and 97% ALAS1 protein reduction, normalizing disease biomarkers in an AHP mouse model.

CRISPR Therapeutics has initiated studies to support investigational new drug (IND) and clinical trial applications for both CTX340 and CTX450, with plans to start clinical trials in the second half of 2025.

At the ASGCT presentation, CRISPR Therapeutics also shared initial data on their ability to deliver and edit genes in the eye, marking a potential new avenue for gene therapy. This research focuses on treating glaucoma, the second leading cause of blindness worldwide, by addressing mutations in the MYOC gene. In preclinical models, the company demonstrated efficient delivery to trabecular meshwork (TM) cells in the eye, achieving over 90% MYOC gene editing in vitro and significant reduction of the protein causing glaucoma in a mouse model.

Overall, CRISPR Therapeutics continues to advance its gene-editing capabilities, aiming to develop transformative therapies for a range of serious diseases through innovative delivery platforms and expanded therapeutic targets.