CRISPR-Cas9 makes headlines as a gene editing tool for potential therapies, but pharma and biotech are also using it to as a tool to discover new drugs. A high-powered startup, KSQ Therapeutics, is the latest firm to join their ranks.
Flagship Pioneering and Polaris Partners have been incubating the Cambridge, MA, company since 2015. KSQ has closed a $76 million financing and hired former top Sanofi Genzyme executive David Meeker—who left the company in April—as its CEO. Like another Boston-area startup unveiled a few weeks ago that Flagship, Kaleido Bioscience, KSQ makes its public debut as a sizeable company. It already has 40 employees, plans to double in size within a year, and touts preclinical programs in cancer immunology, according to Meeker.
The big gamble at KSQ is that CRISPR-Cas9—which as a therapeutic is inching closer and closer to human clinical testing in the U.S.—can help improve the notoriously low odds of success in drug development. KSQ has built an industry-scale, CRISPR-harnessing drug discovery system, which it calls “CRISPRomics.” It claims the suite of technologies—screening tools, large libraries of CRISPR RNA guides—might help the company do a better and faster job than others of identifying drugs and drug targets with a good shot of succeeding.
Those claims are unproven. Meeker (pictured) won’t say how far away the company is from human clinical trials, but says that the hope is “our timelines can be shorter” than the norm. KSQ is starting out developing cancer immunotherapy drugs.
An oft-cited statistic in biopharma is that around 90 percent of the compounds that begin clinical testing ultimately fail, and the reason is the complexity of human biology. In the scalding hot field of cancer immunotherapy, more than 1,000 clinical trials are testing a variety of approaches in combination. Cancer experts told Xconomy earlier this year that they were worried the studies weren’t being designed with enough care, and that more basic research should be done instead.
“What’s happening in our industry today is we have a large number of treatments in clinical trials based on an incomplete understanding,” Meeker says. “We have an inefficient process.”
KSQ hopes to improve that efficiency with CRISPR. The landmark technology, which may win a Nobel Prize someday, is a two-part biological system that can get into cells and irreversibly alter any DNA sequence with a precise cut. It is being studied heavily as a therapeutic tool by academic groups and U.S. companies like Editas Medicine (NASDAQ: EDIT), Intellia Therapeutics (NASDAQ: NTLA), and CRISPR Therapeutics (NASDAQ: CRSP), but in other ways as well, like genetically altering crops or—controversially—-human embryos.
KSQ’s scientific founders—Whitehead Institute member David Sabatini, Dana-Farber Cancer Institute Center for Cancer Genome Discovery director William Hahn, UCSF pharmacology professor Jonathan Weissman, and Tim Wang, a PhD student at MIT—have been among the increasing number of academics harnessing CRISPR in a different way: to look for potential drug targets, and to better understand the function of various genes in disease. At the American Association for Cancer Research’s annual meeting last year, for instance, Sabatini spoke on a panel about efforts to use CRISPR to help find the genes cancer truly needs to survive.
CRISPR is useful for drug discovery because it can be efficiently deployed to switch off, or “knock out” any gene to figure out what particular genes do. If a gene seems critical to a disease process, it could be a promising drug target But CRISPR is so widely used that academic labs and companies may soon be able to do, what KSQ is doing now, if they aren’t already. Another recently launched biotech in Cambridge, for instance, Repare Therapeutics, is incorporating CRISPR screening tools into a search for cancer drugs.
What makes KSQ, and its use of CRISPR different, says Meeker, is the speed and scale at which it can perform these experiments. Chief scientific officer Frank Stegmeier, a former Novartis oncology executive, says the company can examine the function of all the roughly 20,000 genes in the human genome “in parallel,” rather than doing so by the one, the hundred, or even the thousand. So far, KSQ has done these types of interrogations for 600 different cancer “models,” or systems—like cell lines—used to study human cancer.
“You have to take this to a scale of hundreds of cancer models really to derive meaningful conclusions,” Meeker says.
By working at such a large scale, “you basically ask the question of every possible gene that might be driving [a tumor’s] growth,” Meeker says. That, in turn, might make it easier to figure out which genes are important, which ones aren’t, and develop targeted therapies against the proteins the important genes produce. Meeker adds that running these experiments on a variety of cancer models generates more information that could better predict whether a drug candidate might be effective, safe, or lead to unintended side effects.
To start off, KSQ is testing its approach in oncology, where it hopes to discover either new drug targets, or existing ones that may have been overlooked. Other disease areas it may look to partners to push forward. Right or wrong, KSQ should know pretty early on in the process whether it is on to something.
“We can run very focused phase 1 clinical trials with the goal of really getting significant response rates early on in clinical development,” Stegmeier says.
Flagship led the financing and was joined by Polaris, Arch Venture Partners, and Alexandria Equities.