Just one year after bagging a $76 million series B, KSQ Therapeutics is at it again. This time, the biotech has reeled in $80 million in financing, which will advance its lead program, an adoptive T-cell therapy for PD-1 resistant tumors, into human trials and support the development of three more cancer programs through IND. 

Over the past year, the Cambridge, Massachusetts-based company has started and advanced 12 drug discovery programs, including in immuno-oncology, adoptive cell therapies and targeted therapies. Its programs are based on its CRISPRomics platform, which enables the use of CRISPR-Cas9 gene editing on the whole-genome scale, said CEO David Meeker, the former Genzyme CEO who signed on with KSQ last year. 

The biotech has used the technology to interrogate 20,000 human genes across 600 cancer models, something Meeker thinks KSQ does well, but also something "conventional" that other companies are pursuing. 

"What’s unique to KSQ is that we’ve been able to use this platform to screen T cells in vivo, knocking out one at a time all 20,000 genes in a T cell and asking the question of which gene being knocked out increases the capability of the T cell to get into a tumor," Meeker said. 

"Then we count—we can see which gene being knocked out resulted in the greatest number of T cells entering a tumor." 

The team suspected that PD-1 would score strongly—which it did—but so did a few other targets. When asked why KSQ chose PD-1 resistance as its first focus, Meeker replied simply, "Because the need is massive." 

KSQ’s lead candidate, a modified adoptive cell therapy, has shown promise in animal models of PD-1 resistance, and will enter the clinic in the next 18 months. 

PD-1 blockade has seen success in certain cancers, but it doesn't work for everyone. There has been a rush in recent years to develop combination treatments—companies left and right are trying to come up with a drug that makes PD-1 inhibitors, such as Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo, work for more people and more cancers. 

"That’s where we first started. We thought PD-1 might be best, so we looked for things that you can maybe combine with PD-1, like the rest of the world," Meeker said. But that’s not the route KSQ ultimately followed. The company has identified some targets and is working on agents that work as well or better as a monotherapy. 

And the company is intent on not being a one-trick pony. 

"Our goal […] is that we’re not holding back on any program and advancing everything as fast as science will allow in parallel. We’ve been able to do this as a smaller company because we are highly leveraged—we have twice the number of employee equivalents working through CRO networks." 

While KSQ hopes to grow to 100 employees in the next year, it will continue in this fashion, doing the bulk of its work using "external resources supervised by internal resources." 

And it’s not stopping at cancer—KSQ plans to apply CRISPRomics to other areas, including rare disease and immunology. Just as the platform identified which genes increase a T cell’s ability to kill a tumor, it also picked out those genes that inhibit or decrease a T cell’s ability to kill a tumor. These targets could come in handy should the company’s next focus be autoimmune disease.  

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