Precision medicine company Function Oncology has officially launched with the goal of revolutionizing the future of targeted cancer treatment by developing a CRISPR-powered, personalized functional genomics platform. Rather than relying on traditional gene sequencing, the San Diego-based startup is committed to advancing the next generation of targeted cancer treatments by measuring gene function at the level of individual patients.
Co-founder twins Srinath Sampath, MD, PhD, and Srihari Sampath, MD, PhD, have raised $28 million in a Series A round of funding led by a16z and Section 32 and includes Casdin Capital and Alexandria Venture Investments.
“This is really a new clinical use of CRISPR to power precision medicine,” CEO Srinath Sampath told GEN Edge. “We think of it as an upgraded operating system for cancer precision medicine, going from genomics to functional genomics. We’re filled with conviction that the future of genomics overall is going to be functional, and that really needs CRISPR. We are the only ones in the space that we know of so far.”
Two birds, one stone
Srinath says that sitting on a tumor board and seeing cancer patients get presented can be depressing. “There’s nothing that we can do to give [patients] something that looks like precision or personalized medicine,” said Srinath. “We realized that this relates to a gap in our understanding of that patient’s cancer.”
According to Srinath, this comes down to two issues. From a clinical diagnostic standpoint, there’s basically one tool for understanding any one patient’s cancer: tumor DNA sequencing. And if a patient doesn’t have a known mutation or a variant of unknown significance, that’s pretty much the end of the story for getting something like precision medicine. From a drug development standpoint, the development of new targeted therapies for cancer is more or less confined to the question of dealing with known mutated genes in human cancer.
The Sampath twins came to the realization that these two seemingly disparate problems, the clinical precision medicine problem and the drug development problem, were just one problem. “It was the question of being able to identify and get to the ground-state truth about which genes are important for human cancer,” said Srinath. “So, we set out to solve that problem through technology, and that’s where Function Oncology as a company came from.”
Walking the walk
The idea of using functional genomics in cancer—or any medical condition, for that matter—isn’t exactly new. If you do a quick Google image search for “CRISPR-powered Personalized Genomics Oncology Platform,” you’ll find an array of schematics depicting a workflow for generating and analyzing genome-edited cells (or mice). As Srinath put it, “It looks great as a cartoon.”
So, how does this idea get turned into an implementable technology? “If I made a cartoon diagram of what we do and compared it to the cartoon diagram of preclinical CRISPR workflows, those cartoons are going to look similar,” Srinath told GEN Edge. “The difference is that every single preclinical step doesn’t work when you translate it over into primary patient samples, from the design to the delivery of the CRISPR reagents to the actual readouts that you can use. Everybody believed it would not be possible to do this in clinical samples.”
To make this possible in clinical samples, Function Oncology had to essentially reinvent every step of that process, from making CRISPR reagents and delivering them into cancer cells to collecting data for analysis. “All of that had to be developed, and it was pretty much a bit over two years worth of just technology to get that to work,” said Srinath.
That’s exactly why the Sampath twins brought Scientific Advisory Board Member William Hahn, MD, PhD, aboard. Hahn helped lead some of the largest public-scale CRISPR screening efforts at the Broad and Dana-Farber Cancer Institute and has been instrumental in the development of the platform at Function Oncology.
The whole process starts with sample collection, which then gets sent to Function Oncology. “We are developing this as a central lab test,” said Srinath. “Essentially, a sample is taken from a patient and sent to us. What they get in return is data and a report stating the target dependence for all FDA-approved target oncology agents. I think that’s the data everybody wants, but there hasn’t been enough technology so far to actually get it.”
Right now, Function Oncology’s turnaround time is very much analogous to the standard of care, which is panel-based NGS that generally takes around 14 days. While there are some regulatory pieces that Function Oncology still has to navigate to ensure clinical deployment, Srinath said that the platform is about to go out and collect data at scale, putting this technology into the hands of clinicians so that they can start using it to impact clinical care. “When we see something that pops up on our test or our assay, we by definition know something incredibly important about that patient. It’s wonderful to start off knowing that, at an observational level, this is critically and potentially important for the patient.”
Deploying this technology at scale both helps patients in the present and also collects data sets that will enable identifying high-value drug targets and the patients that would benefit from drugs that hit those targets in the future. Srinath said that this platform presents the opportunity to collect a type of information that’s never been accessible before. “In a vacuum, what everybody would want, whether they’re a clinician or a drug developer, is the ability to know what target dependency looks like in human cancer on a patient-by-patient basis,” Srinath told GEN Edge. “That’s what everybody wants to know, but there has not yet been a technology that allows you to actually answer that question. We think we’ve built that technology.”
Theoretically, using CRISPR to interrogate gene function can identify high-value targets that become grist for the mill for either in-house or partner drug development. “Some things are going to make a lot of sense when you work with partners and push them forward really efficiently,” said Srinath. “For instance, you can imagine a scenario where there’s an approved agent in a particular type of cancer, and then we realized that it could have really high utility in this other form of cancer for reasons that were not originally anticipated. That’s not hypothetical. We’ve already seen those things happen. And then there may be other opportunities where there’s a compelling opportunity for us to bring something forward on our own. We wouldn’t take any of those options off the table. It just depends on the specifics.”
While the biotech and pharma industries seem to generate a steady stream of anticancer molecules, patient stratification for precision medicine remains a major challenge. “Finding those patients that actually require that drug target has been a really inefficient process,” said Srinath Sampath. “We think that this technology allows us to solve that part of the problem and unlock the value of some of these wonderful drugs, which just haven’t found their right home yet because nobody understood how to find the right patients to get those drugs to. That’s something that we’re really compelled by because it’s a path forward to bringing clinical value for new drugs to patients relatively quickly.”
As Function Oncology gears up to deploy this technology, Srinath said that the team is figuring out how to bring their technology to as many small collaborators as possible. In addition to setting up a wide range of relationships and collaborations with academic medical centers, the team at Function Oncology has also considered working with healthcare systems. “In the right context, [working with healthcare systems] could make a lot of sense,” said Srinath Sampath, “because it’s an opportunity to deploy the technology and then collect data in a really organized way and follow-up to really understand—not just from a validity standpoint, but also from an economic and healthcare impact standpoint— what this technology can do for patients.”