-Data presented in a late-breaking presentation at the American Heart Association (AHA) Scientific Sessions 2025-
-Phase 1 clinical data for CTX310® demonstrate robust, dose-dependent reductions in circulating ANGPTL3 with a mean reduction from baseline of -73% (maximum -89%), a mean reduction in triglycerides (TG) of -55% (maximum -84%), and a mean reduction of low-density lipoprotein (LDL) of -49% (maximum -87%) at the highest dose-
-Among participants with elevated baseline TG (>150 mg/dL), a mean reduction of 60% in TG were observed at therapeutic doses-
-CTX310 was well tolerated with no treatment-related serious adverse events and no ≥Grade 3 changes in liver transaminases-
-Findings simultaneously published in The New England Journal of Medicine entitled “First-in-Human Phase 1 Trial of CRISPR-Cas9 Gene Editing Targeting ANGPTL3”-
ZUG, Switzerland and BOSTON, Nov. 08, 2025 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today announced positive Phase 1 data from its ongoing clinical trial evaluating CTX310®, an investigational, in vivo CRISPR/Cas9 gene-editing therapy targeting ANGPTL3. A single-course treatment with CTX310 produced dose-dependent, durable reductions in circulating ANGPTL3 with a mean reduction from baseline of -73% (maximum -89%), a mean reduction in triglycerides (TG) of -55% (maximum -84%) and a mean reduction of low-density lipoprotein (LDL) of -49% (maximum -87%) at the highest dose. These data demonstrate the potential of CTX310 to deliver meaningful and sustained lipid lowering following a single-course intravenous (IV) infusion.
These data were presented today during a late-breaking session at the American Heart Association (AHA) Scientific Sessions and published simultaneously in The New England Journal of Medicine (NEJM) in a peer-reviewed article entitled “Phase 1 Trial of CRISPR-Cas9 Gene Editing Targeting ANGPTL3.”
"The publication and presentation of these Phase 1 results mark an important milestone for CRISPR Therapeutics and for the field of in vivo gene editing,” said Naimish Patel, M.D., Chief Medical Officer of CRISPR Therapeutics. “For the first time, we’ve shown that a single-course in vivo CRISPR treatment can safely and durably lower ANGPTL3, leading to clinically meaningful reductions in triglycerides and LDL. These data provide strong support for continued advancement of CTX310 and our broader cardiovascular gene-editing portfolio.”
“Seeing a single-course treatment safely lower both LDL cholesterol and triglycerides is truly unprecedented,” said Stephen J. Nicholls, lead study investigator and director of the Victorian Heart Institute at Monash University. “If these findings are confirmed in larger studies, a one-time therapy could redefine how we manage lifelong lipid disorders and help prevent cardiovascular disease.”
“Adherence to cholesterol-lowering therapy remains a major challenge in treating patients with heart disease,” said Steven E. Nissen, M.D., senior author of the study and Chief Academic Officer at the Cleveland Clinic Heart, Vascular and Thoracic Institute. “Many patients discontinue therapy within the first year. The prospect of a one-time treatment with durable effects would be a major advance in cardiovascular prevention.”
CTX310
CTX310 is an investigational, lipid nanoparticle (LNP) delivered CRISPR/Cas9 therapy designed to precisely edit the ANGPTL3 gene in hepatocytes following a single-course IV administration. ANGPTL3 encodes a key protein that regulates TG and LDL levels, both well-established risk factors for atherosclerotic cardiovascular disease (ASCVD). Individuals with naturally occurring loss-of-function mutations in ANGPLT3 have lower TG, lower LDL and a reduced lifetime risk of cardiovascular disease compared to those without such mutations. By reducing ANGPTL3 expression, CTX310 has the potential to durably lower TG and LDL cholesterol in patients with severe or refractory dyslipidemia. More than 40 million people in the United States have elevated TG, elevated LDL, or both, underscoring the significant unmet medical need. CTX310 is initially being developed for patients at highest cardiovascular risk who have limited effective treatment options despite current lipid-lowering therapies.
Phase 1 Clinical Trial Design
The Phase 1, open label, dose-escalation trial evaluated single-course IV doses of CTX310 ranging from 0.1 to 0.8 mg/kg (lean body weight) targeting ANGPTL3 in four patient groups: homozygous familial hypercholesterolemia (HoFH), severe hypertriglyceridemia (sHTG), heterozygous familial hypercholesterolemia (HeFH), or mixed dyslipidemias (elevated TG and LDL). Eligible participants had uncontrolled TG levels >150 mg/dL and/or LDL cholesterol >100 mg/dL (or >70 mg/dL for those with established ASCVD) despite background standard of care per local guidelines.
The majority of participants were receiving statins and/or ezetimibe, while 40% were taking PCSK9 inhibitors. The trial was designed to evaluate safety and tolerability as primary endpoints, with changes in circulating ANGPTL3 protein, TG, and LDL as secondary endpoints.
About In Vivo Programs
CRISPR Therapeutics has established a proprietary lipid nanoparticle (LNP) delivery platform to enable gene editing in the liver using both CRISPR/Cas9 and its novel, proprietary SyNTase™ editing technologies. The Company’s in vivo portfolio includes its lead investigational programs, CTX310 (directed towards angiopoietin-related protein 3 (ANGPTL3)) and CTX320™ (directed towards LPA, the gene encoding apolipoprotein(a) (apo(a)), a major component of lipoprotein(a) [Lp(a)]). Both are validated therapeutic targets for cardiovascular disease. CTX310 and CTX320 are in ongoing clinical trials in patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, mixed dyslipidemias, or severe hypertriglyceridemia, and in patients with elevated lipoprotein(a), respectively. In addition, the Company’s research and preclinical development candidates include: CTX460™, targeting SERPINA1 for the treatment of alpha-1 antitrypsin deficiency (AATD); CTX340™, targeting AGT for the treatment of refractory hypertension; and CTX450™, targeting ALAS1 for the treatment of acute hepatic porphyria (AHP).
About CRISPR Therapeutics
Founded over a decade ago, CRISPR Therapeutics is a leading gene editing company focused on developing transformative medicines for serious diseases. The Company has evolved from a pioneering research-stage organization into an industry leader, marking a historic milestone with the approval of CASGEVY® (exagamglogene autotemcel [exa-cel]), the world’s first CRISPR-based therapy, approved for eligible patients with sickle cell disease and transfusion-dependent beta thalassemia. CRISPR Therapeutics is advancing a broad and diversified pipeline across hemoglobinopathies, oncology, regenerative medicine, cardiovascular and autoimmune, and rare diseases. The Company continues to expand its leadership in gene editing through the development of SyNTase™ editing, a novel and proprietary gene-editing platform designed to enable precise, efficient, and scalable gene correction. To accelerate and expand its impact, CRISPR Therapeutics has established strategic collaborations with leading biopharmaceutical partners, including Vertex Pharmaceuticals. 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.
CRISPR THERAPEUTICS® standard character mark and design logo, SyNTase™, CTX310®, CTX320™, CTX340™, CTX450™ and CTX460™ are trademarks and registered trademarks of CRISPR Therapeutics AG. CASGEVY® and the CASGEVY logo are registered trademarks of Vertex Pharmaceuticals Incorporated. All other trademarks and registered trademarks are the property of their respective owners.