CRISPR in vivo gene editing therapy lowers LDL cholesterol, triglycerides in phase 1 trial

CRISPR Therapeutics announced positive phase 1 data from its ongoing clinical trial evaluating CTX310, an investigational, in vivo CRISPR/Cas9 gene-editing therapy targeting ANGPTL3, a key protein that regulates triglycerides (TG) and of low-density lipoprotein (LDL) levels.

In the trial, a single-course treatment with CTX310 produced dose-dependent, durable reductions in circulating ANGPTL3 with a mean reduction from baseline of -73%, a mean reduction in TG of -55% and a mean reduction of LDL of -49% at the highest dose. These data demonstrate the potential of CTX310 to deliver meaningful and sustained lipid lowering following a single-course IV infusion.

CRISPR’s CTX310 is a lipid nanoparticle (LNP) delivered CRISPR/Cas9 therapy designed to precisely edit the ANGPTL3 gene in hepatocytes following IV administration. ANGPTL3 encodes a key protein that regulates TG and LDL levels, both well-established risk factors for atherosclerotic cardiovascular disease. By reducing ANGPTL3 expression, CTX310 has the potential to durably lower TG and LDL cholesterol in patients with severe or refractory dyslipidemia.

In other news for CRISPR Therapeutics, the company revealed in its third quarter financial results that it is discontinuing work on its off-the-shelf CAR-T therapy targeting CD70, known as CTX131, which was previously in development for both solid tumors and hematologic malignancies. According to the company, despite “encouraging” phase 1 data, CRISPR will instead advance other programs with the “greatest potential for long-term value creation.”