Fighting cancer often comes down to finding the right combination of drugs. But it’s difficult, impractical, and even unsafe to test ever-growing permutations of those cocktails.
Presage Biosciences has been working for seven years on a new way to efficiently test anti-cancer combinations. Today the Seattle biotech reported in Science Translational Medicine that its unusual technology, which injects tiny amounts of cancer drugs directly into living tumors, predicted how those tumors would respond to the same drugs delivered in a traditional manner.
As Xconomy wrote in 2013, Presage signed up Celgene (NASDAQ: CELG) as an investor and a user of its technology to find better drug combinations. That was well before the results reported today, which were based on animal tests. More recently, Presage began the first trial of its technology in humans.
The Presage system, dubbed CIVO, does much of its work in tumors that are still in the patient’s body. A delivery device, which looks like a toothbrush travel case with tiny needles protruding from one end, injects micro-doses of up to eight different cancer drugs into a tumor at once.
After a day, the tumor sample is surgically removed, and Presage software analyzes the tumor cells around each micro-injection site. For now, the system only works with tumors that are accessible from the surface, such as skin cancer, breast cancer, and certain lymphomas. It will take some engineering to go after tumors deeper in the body. In the future, the company aims to do the analysis through sophisticated imaging without removing the tumor from the body.
Tumors are not a single mass of identical cells gone haywire. Individual cells within a tumor can have important differences, which is why some cancers resist treatment entirely, or spring back to life after years of remission.
This is why, in addition to the needle device, Presage has developed software to explore which cells die and which survive, and to analyze other changes that suggest a particular drug is having its intended effect—say, shrinking the blood vessels that feed the tumor.
These are important questions to answer for drug developers, which would love to know as early as possible if a drug is working, and which combinations of two, three or more drugs might help patients the most. In 2013, Celgene paid $13 million upfront for an undisclosed stake in Presage and the nonexclusive right to use CIVO in its own cancer R&D.
Since then, Presage has dosed four lymphoma patients and counting at the Fred Hutchinson Cancer Research Center in Seattle, where the CIVO technology originated. This first human trial will assess CIVO’s safety and refine what president Nathan Caffo calls the “choreography” of the system: making sure the right drug gets into the right section of the tumor, and more. Safety is key; if the FDA is convinced that CIVO microinjections stay within the tumor and have no side effects on the patient, Preage would then aim to use the system with drugs that haven’t yet entered clinical trials.
CIVO wouldn’t be this far along, says Caffo, without the experience gained from testing the system on dogs whose owners brought them to local veterinarians for cancer treatment. (A doctor at BluePearl Veterinary Partners in Seattle is one of the publication’s co-authors.)
Presage has also advanced its analysis tools the past couple years, says chief scientific officer Rick Klinghoffer. With the progress in single cell analysis (I wrote about one new version in development here), Presage wants to use its technology to find the cells that should be destroyed by an injected drug, but aren’t, and understand them better. “We’re working now on dissecting out the rare cells in some of the drug response zones,” says Klinghoffer. “There first seems to be a complete response around the injection site, but if you look closely you’ll find rare cells that survive the initial assault.”
Those tenacious tumor cells are called “minimal residuals,” and they are the “bane of current cancer treatments,” says Klinghoffer. “Those are the ones we want to proactively eliminate to achieve durable remissions.”
The early success of immunotherapies such as ipilimumab (Yervoy), nivolumab, (Opdivo), and pembrolizumab (Keytruda)—known as checkpoint inhibitors—has set off a fresh round of research to find drugs to pair with them. At this week’s American Association for Cancer Research conference, one presenter gave a talk about the future of combination treatments and posted a slide that showed one box labeled “pembrolizumab” linked to another box labeled “your drug here,” says Klinghoffer.
The slide was meant to be tongue in cheek, but Presage hopes its technology makes the message more of a reality. Companies with checkpoint inhibitor programs could have a dozen or two combinations they want to test, “and not even the biggest pocketbooks can do all that in Phase 2,” says Caffo, referring to clinical trials that typically recruit tens or dozens of patients and can cost tens of millions of dollars to run.
Some of the company’s promotional materials look to the day when oncologists use CIVO to help shape a cancer patient’s drug regimen. But Caffo downplayed that scenario, saying right now CIVO is being developed to help make pharmaceutical R&D decisions—including at Presage, which hopes to build its own drug pipeline—not to help doctors make personalized medicine decisions.