Can CRISPR-Cas9, the landmark genome editing tool, help speed up drug discovery? That was the pitch behind KSQ Therapeutics when it started up in 2015. Three years later, the Cambridge, MA, startup says the CRISPR tool has allowed it to make the kind of progress it wouldn’t have otherwise, with 13 experimental cancer drugs in the works, including one on its way to human testing.
KSQ is announcing an $80 million Series C round to fund the work, starting with a cell immunotherapy the company is developing for solid tumors—the types of cancers that these cell therapies so far haven’t been able to touch.
The KSQ therapy is different than the two CAR-T treatments that have won FDA approval over the past year. CAR-T therapies are T cells, attack dogs of the immune system, that have been extracted from patients, genetically modified, and re-infused to find and kill cancer cells with a specific target. KSQ is going with an emerging, rival approach that involves harvesting, from a patient’s tumor sample, a mix of white blood cells known as a tumor-infiltrating lymphocytes (TILs). These are immune cells that have left the bloodstream and dug into a tumor, and thus may have more natural tumor-killing punch and broader reach than CAR-T cells. After the TILs are extracted, they’re modified to boost their cancer-fighting powers and put back into the patient. (Here’s more on TIL treatments from STAT.)
KSQ CEO David Meeker (pictured), who previously ran the rare disease drug specialist Genzyme, won’t say what cancer protein the TIL treatment targets. But the therapy should be ready for human testing within 18 months, and will be developed for solid tumors that are resistant to current immunotherapy treatments known as checkpoint inhibitors, he says.
The cell therapy program is unproven, of course. But it is an example of the type of work KSQ aims to do. The startup is trying to show that by using CRISPR tools to screen for and discover drug targets, it can more quickly find drugs and drug targets that have a better chance of success than those found via traditional methods.
CRISPR-Cas9 is best known as a gene editing system being developed as human medicines. Several publicly traded biotechs are trying to do this, though their path forward is likely long and winding, as it is with any new science.
But CRISPR is also being used widely as a tool in labs for other purposes too, like drug discovery. In that context, CRISPR can be efficiently deployed to switch off, or “knock out” a large number of genes, one at a time, across the genome, to figure out what particular genes do. If a gene seems critical to a disease process, it could be a promising drug target.
KSQ says it’s unique because it’s doing this CRISPR screening at a higher speed and larger scale than others. For example, it says it has been using CRISPR to examine the function of all the roughly 20,000 genes in the human genome in parallel, rather than doing so by the ones, the hundreds, or even the thousands. KSQ has done these types of interrogations in hundreds of different cancer “models,” —cell lines and lab animals used to study human cancer. That, in turn, has helped KSQ see “the big picture” and “systematically identify the highest value targets” while ruling out thousands of others, Meeker says.
“In essence, this is a more unbiased, genome-wide approach,” he says. “I would say it stands out to have a small biotech company generate 13 in vivo validated drug discovery programs from a standing start in less than three years.”
That process has led it to three different types of cancer drugs: cell therapies, targeted therapies, and antibodies targeting the immune system that KSQ hopes will surpass checkpoint inhibitors.
New investors Baillie Gifford, Cowen Healthcare Investments, Invus, and Lilly Asia Ventures participated in the funding round along with founding backers Flagship Pioneering and Polaris Partners and existing investors Arch Venture Partners and Alexandria Real Estate Equities.