CAR-T, Pre-clinical, Startups

California upstart Xyphos wants to tackle CAR-T’s big problems

A San Francisco biotech that’s been developing antibiotics for the past decade has spun out a new oncology startup that borrows ideas from existing CAR-T and antibody therapies — and combines them.

That’s according to the startup’s founder and CEO Jim Knighton. The new spinout, called Xyphos, considers its tech “second generation CAR-T” as it addresses many of the field’s notorious challenges (in animal models, at least).

“We’ve taken all the work that Kite, Juno, and Novartis have done in CAR and come up with a new set of ideas that builds on what they started to address some if not all of (CAR-T’s) shortcomings,” Knighton said.

CAR-T’s challenges

Jim Knighton

Although these experimental immunotherapies show immense upside, CAR-T therapies are not perfect. For one, they can trigger toxicity and potentially fatal immune reactions in cancer patients.

“In a sense, the product is too effective and causes such a large reaction that patients experience toxicity,” said Ezra Cohen, an oncologist and cancer researcher at UC San Diego. “Some have even died.”

Knighton said the tech being developed at Xyphos might hurdle these challenges by using its newly engineered CAR in combination with a modified antibody therapy. In short, the company’s CAR has been engineered to be inert when it enters the patient’s body. The CAR will not bind to (or attack) anything. It’s only activated when the patient is dosed with Xyhpos’ specially engineered antibody, which the company calls a “Micabody.” Once the two are bound, the CAR is activated and does its killer work.

If, however, the cancer patient begins experiencing toxicity, the doctor could stop the antibody therapy. The antibody then cycles out of the patient, and the CARs revert to harmless, inactive T cells. Its sort of like switching T cells on and off when needed.

Knighton said the idea works in mice, and now he needs money to move the research further along.

Cohen, an internationally recognized expert on novel cancer therapies and the director of Moore’s Cancer Center in San Diego, said innovation in CAR-T is certainly due.

“The approved products in CAR-T are quite simple in design,” Cohen said. “A lot of us are thinking about second, third, and fourth generation CAR-T. How do we modify it? Make it stronger? Control it? The next wave of CARs will be tremendously better.”

The spinout’s origin

The tech behind Xyphos has been quietly studied in the labs of an antibiotics company called AvidBiotics since about 2012. Why is an antibiotics company dabbling in cancer drugs? Knight said there’s no shared technology between AvidBiotics and Xyphos. Instead, the research was the result of “corporate ADD.”

David Martin

“We had an idea. Rather than going out and starting a new company, we just hired a couple of people internally to work on the problem independently,” Knighton said.

Now the tech is developed enough to split from AvidBiotics. In fact, the company is splitting into two new parts: one oncology company (Xyphos) and a newly formed antibiotics company called Pylum Biosciences, which will carry on AvidBiotics’ research programs.

Knighton is serving as CEO of Xyphos, while AvidBiotics’ former chief executive David Martin will lead Pylum as CEO. As of now, there are no executives with oncology backgrounds working at Xyphos.

The money

Knighton said both new entities will need to raise $20 million to $30 million right away before beefing up the C-suite with experienced folks.

AvidBiotics has raised $38 million since its 2006 inception, primarily from corporate collaborations with DuPont (now DowDuPont) and Cubist (before Merck’s acquisition). That capital also includes NIH grants, and contributions from friends, family and the founders.

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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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