JP Morgan is usually not a data conference. But there are always exceptions to data that can make or break a business, which arouses the interest of potential investors and partners.
Data, for example, such as Sekar bringing Kathiresan to the virtual conference, which shows that a one-time treatment with Verve Therapeutics’s editor-in-chief can keep PCSK9 levels low and thus lower LDL cholesterol, or the bad kind, to 6 months. In non-human primates.
The two takeaways are 61% LDL cholesterol reduction and 89% reduction in the average PCSK9 protein level in blood. This is the same reduction for PCSK9 as the treatment registered at 2 weeks, when the researchers documented a 59% decrease in LDL-C.
“What you are seeing is sustained lowering of cholesterol and consistent lowering of LDL cholesterol 6 months after administration of the gene-editing treatment,” Kathiresan said Endpoints News in a preview.
While preclinical, the results are an important step for the in vivo use of the next generation no-till tool, known as basic care. While the first generation CRISPR gene processing molecules could cut the DNA sequence and have it repaired on its own, the basic processing works by converting one letter in the genome into another.
In this case, the construct, VERVE-101, made a single change from A to G in the genetic sequence of the PCSK9 gene in the liver, with the aim of deactivating the gene forever.
As liver cells turn around about every 200 days, Kathiresan added, six-month durability data provide reasonable confidence that the changes are there to stay.
‘The fundamental problem with coronary heart disease is cumulative exposure to LDL over time, ok? And the fundamental treatment is to reduce the cumulative exposure as much as possible, ‘says the CEO, who has left an academic career and a directorship at the Mass General’s Center for Genomic Medicine to manage the biotechnology. ‘The way to think about this is kind of the area under the curve analysis, you know? You want to keep the LDL down as long as possible and down constantly. ‘
VERVE-101 talks about the pharmacological validation offered by monoclonal antibodies and siRNA therapies that target PCSK9, but the need for chronic treatment disappears. Each one foresees his own compliance issues that could lead to inadequate protection.
With toxicology studies underway, Verve expects his first patient to dose sometime in 2022. By targeting the initial clinical indication of heterozygous familial hypercholesterolemia, the company will develop a genetic treatment for a genetic disease before moving on to ‘coronary heart of garden diversity’. disease. ”
PCSK9 will only be a start. Kathiresan has identified seven other genes that, as he has discovered over years of studies in population genetics, contain protective mutations – one of which is ANGPTL3, for which Verve also provided two-week preclinical data. All eight targets fall into one of three pathways: LDL-C, triglyceride or lipoprotein (a).
“Each of these pathways is a supplement to a patient’s risk,” he said. A drug that targets each of these pathways must therefore be complementary in terms of benefit. ‘