JP Morgan is not typically a data conference. But there are always exceptions to data that can make or break a company, piquing the interest of potential investors and partners.
Data, for example, like what Sekar Kathiresan is bringing to the virtual conference, showing that a single treatment with the basic editor of Verve Therapeutics can keep PCSK9 levels low – thus lowering LDL cholesterol, also known as the bad type – for up to 6 months. In non-human primates.
The two values to take are 61% reduction in LDL cholesterol and 89% cut in the average level of PCSK9 protein in the blood. This is the same level of reduction for PCSK9 as the treatment recorded in 2 weeks, when the researchers documented a 59% drop in LDL-C.
“What you are seeing is a lasting reduction in cholesterol and a consistent reduction in LDL cholesterol 6 months after administering the gene editing treatment,” said Kathiresan Endpoints News in a view.
Although pre-clinical, the results mark a significant step towards the in vivo use of the next generation gene editing tool known as base editing. While the first generation of CRISPR gene editing molecules would cut the DNA sequence and let it repair on its own, basic editing works by converting one letter of the genome into another.
In this case, the VERVE-101 construct made a single change from A to G in the genetic sequence of the PCSK9 gene in the liver, with the aim of inactivating the gene forever.
Because liver cells change approximately every 200 days, Kathiresan added, the 6-month durability data offers reasonable confidence that the changes are there to stay.
“The fundamental problem with coronary heart disease is cumulative exposure to LDL over time, right? And the fundamental treatment is to decrease this cumulative exposure as much as possible, ”said the CEO, who left behind an academic career and a board at Mass General’s Center for Genomic Medicine to direct biotechnology. “The way to think about it is kind of an analysis of the area under the curve, you know? You want to keep LDL low and consistent for as long as possible. “
VERVE-101 rides on the pharmacological validation offered by monoclonal antibodies and siRNA therapies that target PCSK9, but eliminates the need for chronic treatment. Each of which he sees presenting his own compliance issues that can lead to insufficient protection.
With toxicology studies underway, Verve hopes to dose its first patient in 2022. Aiming at the initial clinical indication of heterozygous familial hypercholesterolemia, the company will be developing “a genetic treatment for a genetic disease” before turning to the “coronary heart. common”. disease.”
PCSK9 will be just a start. Kathiresan identified seven other genes that, as he discovered over years of studies in population genetics, harbor protective mutations – one of them being ANGPTL3, for which Verve also presented 2-week preclinical data. All eight targets fall into one of three pathways: LDL-C, triglycerides or lipoprotein (a).
“Each of these pathways is a complementary means in terms of risk to the patient,” he said. “Therefore, a drug targeted at each of these pathways must be additive in terms of benefit.”