-CTX310™ led to durable reductions of angiopoietin-like 3 protein (ANGPTL3) and triglyceride levels in non-human primates (NHPs) after a single dose-
-CTX320™ led to durable reductions of lipoprotein(a) (Lp(a)) levels in NHPs after a single dose-
-Both CTX310™ and CTX320™ were well-tolerated in NHPs at clinically relevant dose levels-
-Clinical trial initiated for CTX310™, targeting ANGPTL3-
-CTX320™ targeting Lp(a) is on track to enter the clinic in the first half of 2024-
ZUG, Switzerland and BOSTON, MA, USA I November 06, 2023 I CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today announced preclinical data from the Company’s investigational programs for the treatment of cardiovascular disease, at the American Heart Association (AHA) Scientific Sessions 2023. The data will be presented on Saturday, November 11, 2023, in two oral sessions, entitled “CTX310: An Investigational in vivo CRISPR-Based Therapy Efficiently and Durably Reduces ANGPTL3 Protein and Triglyceride Levels in Non-Human Primates After a Single Dose” and “CTX320: An Investigational in vivo CRISPR-Based Therapy Efficiently and Durably Reduces Lipoprotein(a) Levels in Non-Human Primates After a Single Dose.”
“We’re excited to share these preclinical data at AHA highlighting the progress made across our in vivo programs targeting ANGPTL3 and Lp(a). The findings demonstrate the potential of a one-time treatment to produce clinically meaningful, long-lasting reductions in risk factors for atherosclerotic cardiovascular disease,” said Phuong Khanh (P.K.) Morrow, M.D., FACP, Chief Medical Officer at CRISPR Therapeutics. “These data increase our confidence in our goal to shift the treatment paradigm for patients at risk of cardiovascular disease away from burdensome chronic care to a potentially one-time, durable therapy.”
CRISPR Therapeutics is advancing a pipeline of in vivo gene editing programs using lipid nanoparticle (LNP) delivery of Cas9 mRNA and a guide RNA (gRNA) to the liver. The first two in vivo programs, CTX310 and CTX320, each aim to reduce expression of a validated target for cardiovascular disease.
CTX310 is an investigational in vivo CRISPR/Cas9 gene editing therapy designed to knock out hepatic expression of angiopoietin-like 3 protein (ANGPTL3). In humans, naturally occurring loss-of-function variants in ANGPTL3 are associated with reduced levels of serum lipids and reduced risk of atherosclerotic cardiovascular disease. In the preclinical data to be presented at AHA, treatment of non-human primates (NHPs) with a single dose of CTX310 led to mean editing of ANGPTL3 in the liver of 70%, and corresponding mean reductions in plasma ANGPTL3 protein of more than 85% and triglycerides of 60%. Reductions in ANGPTL3 protein and triglycerides were durable past a year post-treatment. CTX310 was well-tolerated in NHPs with only transient elevation of liver enzymes that resolved without intervention. These data suggest that CTX310 has the potential to be used to treat dyslipidemias in humans.
CTX320 is an investigational in vivo CRISPR/Cas9 gene editing therapy to reduce hepatic expression of lipoprotein(a) (Lp(a)). Genetic and epidemiological studies in humans have identified elevated levels of Lp(a) as an independent risk factor of atherosclerosis and related diseases. In the preclinical data to be presented at AHA, treatment of NHPs with a single dose of CTX320 led to a mean reduction in plasma Lp(a) of 95%. This reduction was durable past a year post-treatment. CTX320 had a well-tolerated safety profile similar to that of CTX310. These data suggest CTX320 has the potential to be used to reduce plasma Lp(a) levels in humans.
About CRISPR Therapeutics
CRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and cardiometabolic diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic partnerships with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts and San Francisco, California, and business offices in London, United Kingdom. For more information, please visit www.crisprtx.com.
CRISPR THERAPEUTICS® standard character mark and design logo, CTX310™ and CTX320™ are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners.
SOURCE: CRISPR Therapeutics