Verve Therapeutics(US:VERV)2023-05-18 17:49Cardiovascular Disease Burden and Current Treatment Limitations - Atherosclerotic cardiovascular disease (ASCVD) is the number one cause of death worldwide, with one person dying every 34 seconds from cardiovascular disease in the U S [2] - Despite available treatments, only 27% of ASCVD patients in the U S are at their LDL-C goal [11] - In a global registry of Heterozygous FH (HeFH) patients, only 3% attain LDL-C < 70 in current chronic care model [13] Verve Therapeutics' Gene Editing Approach - Verve Therapeutics is developing 'once-and-done' gene editing medicines to treat cardiovascular disease [1] - Verve-101 targets PCSK9 for HeFH and ASCVD, while VERVE-201 targets ANGPTL3 for Homozygous FH and refractory hypercholesterolemia [15] - Individuals who naturally lack ANGPTL3 gene have lifelong low blood LDL-C & TG, are healthy, and resistant to ASCVD [9] - People with PCSK9 gene switched off have ~50 mg/dl lower LDL cholesterol in blood and ~50% lower risk for ASCVD [10] VERVE-101 Clinical Development and Results - VERVE-101 is currently being tested in a Phase 1b clinical trial [16] - In non-human primates, a precursor to VERVE-101 demonstrated an 88% reduction from baseline in LDL-C [27] - VERVE-101 testing in NHPs showed an 89% reduction in blood PCSK9 and a 68% reduction in blood LDL-C at one year after a single intravenous infusion [33] VERVE-201 Preclinical Results - In non-human primates, VERVE-201 achieved a mean liver ANGPTL3 editing of 63% at a higher dose [49] - VERVE-201 achieved a mean 96% reduction in blood ANGPTL3 protein at a higher dose in non-human primates [51]