Genetics was supposed to revolutionize cancer care. The ability to sequence a tumor sample to identify cancer-driving mutations gave physicians a precision medicine approach to selecting the most appropriate therapy for each patient. Next-generation sequencing has been life saving for some. But as things turned out, it doesn’t work for most, says Srinath Sampath, co-founder and CEO of Function Oncology.

The cancer field came to realize that genetic mutations that drive cancer are found in just a minority of patients, said Sampath, a physician and scientist whose experience includes research at Novartis. That means sequencing a tumor won’t benefit most cancer patients.

“Most patients do not have mutations that can get them a specific therapy,” Sampath said. “It’s frustrating, in 2023, that precision medicine doesn’t exist for most cancer patients. We don’t have the right data to get patients on the right therapy.”

Function Oncology aims to generate the right cancer target data. CRISPR is a crucial part of its approach. The San Diego-based startup emerged from stealth mode on Wednesday, revealing $28 million in financing along with plans to place its technology in the hands of clinicians soon.

Research with CRISPR has focused mainly on editing a gene to fix a disease-causing mutation, an approach being tested in rare inherited diseases. But the CRISPR system can also be used to inhibit genetic function, and it’s this capability that is key to Function Oncology’s approach. As an example, Sampath points to mutations to the BRAF gene that lead to cancers. Applying CRISPR to a sample of a patient’s tumor, the company’s technology inhibits BRAF function and then assesses whether that had any affect on the cancer. If it doesn’t, then blocking BRAF will not help, suggesting that the patient should not be prescribed a BRAF inhibitor, Sampath said.

The approach is repeated with other cancer targets. Instead of making predictions about cancer targets, the Function Oncology technology takes measurements, Sampath said. Do it enough times, and a personalized picture starts to form showing which genes a cancer depends on. Sampath describes it as a “functional fingerprint” that identifies the appropriate drug targets for the patient’s cancer.

“CRISPR as a technology is all about understanding gene function,” he said. “We can train the incredible power of that technology on the cancer precision problem.”

Sampath co-founded Function Oncology in 2019, shortly after leaving Novartis. The motivation was the wealth of targets that can be hit to treat cancer and the realization that most of them are not mutated. Sampath and his co-founders set out to build a technology platform that shines light on targets that are not mutated.

Function Oncology spent two years developing its platform and closed its Series A financing in late 2021. But the company remained stealthy, choosing to wait before unveiling its work. More details are coming soon. On April 16, during the annual meeting of the American Association for Cancer Research (AACR), Function Oncology will present data that offer clinical validation of the company’s technology in acute myeloid leukemia (AML).

AML was a practical cancer to showcase the Function Oncology technology, Sampath said. There’s a rich history of biobanking in leukemia, enabling the company to work with samples that already exist. He added that many targeted therapies are already available for AML, which are helpful in proving that the technology can match a patient sample to a drug. But Sampath added that AML is just a starting point and the company envisions applications in many types of cancer, both liquid and solid tumors.

Function Oncology plans to bring its technology to the market as a laboratory developed test, a pathway that does not require FDA review. As for real-world use, Sampath envisions the process happening much the same way tumor sequencing is done now. After taking a biopsy of a patient’s tumor, the sample is sent out for processing. Analysis takes about two weeks—comparable to current next-generation sequencing times. Function Oncology sends back patient-specific cancer data that guides treatment decisions. Sampath said the company aims to put the technology into physicians’ hands starting later this year.

Other companies are vying to take cancer drug selection beyond tumor sequencing. Durham, North Carolina-based Xilis is developing technology that encapsulates a patient’s cancer cells in tiny droplets representing the cancer environment. Those droplets, called MicroOrganoSpheres, serve as test beds for many drugs and drug combinations, yielding results that can inform treatment decisions. Seattle-based SEngine Precision Medicine has commercialized technology that tests more than 200 drugs against a patient tumor sample to identify treatment options that DNA sequencing cannot. Both Xilis and SEngine say their respective technologies can also be used to develop new cancer drugs.

The Function Oncology technology could also have applications in drug development, Sampath said. The startup can build a database of every approved cancer drug and all cancer targets. Interrogating these data will help guide researchers to other genetic targets for new drugs, he said. For these applications of the technology, Function Oncology is open to exploring partnerships with biotech and pharmaceutical companies. But Sampath added that his company also plans to use the technology to discover and develop its own drugs.

Function Oncology’s Series A financing was led by Andreessen Horowitz and Section 32. Also participating in the round were Casdin Capital and Alexandria Venture Investments.

Photo by Function Oncology