Working on a first-in-class tumor-targeted oncolytic vaccine
President and CEO: Sammy Farah
Based: Ottawa, Ontario
Clinical focus: The foundation of Turnstone’s tech, the Maraba platform, uses rhabdovirus isolates to penetrate cancer cells and then destroy them, all the while whipping up a T-cell cancer vaccine attack on tumors.
The scoop: This Canadian biotech is hoping to buck what has been a difficult trend in the research world of oncolytic viruses and cancer vaccines to create a truly next-generation therapy in immuno-oncology.
What makes Turnstone Fierce: A few years back, oncolytic viruses were full of promise, but a series of trial setbacks and the relative commercial weakness of Amgen’s Imlygic (talimogene laherparepvec) have scaled back hope and hype. Attention has shifted toward gene editing in the form of CRISPR and CAR-T and away from cancer virus and cancer vaccine work.
Imlygic, approved by the FDA in 2015, uses a genetically modified live oncolytic herpes virus therapy that is injected directly into melanoma lesions, where it replicates inside cancer cells and causes the cells to rupture and die. Amgen gained access to the medicine in 2011, when it paid $425 million, plus $575 million in biobucks, to acquire Imlygic from its original inventor, Biovex. Now, it's estimated by analysts to peak at just $200 million in annual sales.
Turnstone is looking to do things differently as it harnesses oncolytic viruses to treat a range of solid tumors, both on its own and in combo with checkpoint inhibitors, and even added to the latest CAR-T medications.
CEO Sammy Farah acknowledges the negative press in this research area, and says Amgen’s med was always limited in how many patients it could treat. Turnstone's leading program works differently and, he believes, better. “We have a best-in-class program here,” he says.
“We’ve designed our platform mindful of the shortcomings that have occurred in other drugs and trials," Farah says. "What we have is an oncolytic virus that is differentiated from everything else in the field."
Turnstone's oncolytic virus was discovered through Maraba, which was found in Brazilian sand-flies. "This virus is highly oncolytic, and we can engineer it into a very nice safety window that leaves other cells alone, while attaching to cancer cells," Farah says.
“What really separates us is that we deliver this systemically, whereas most other oncolytic viruses, including Imlygic, are not delivered in this way. For these types of drugs to really make an impact in cancer, you need systemic delivery.”
Without that, he says, treatments won't work in as many people or treat disease when it is spreading, and he thinks this is a key reason why Turnstone’s program is truly next-gen. The features of the virus itself enable this systemic approach; most people have not been exposed to the virus previously, and it has the kinds of characteristics needed to use it across the body.
Farah admits that trying to get an oncolytic virus to find and kill cancer cells “isn’t enough,” as such therapies appear to work best when they can also engage the immune system.
“[W]hat worked for us in the end is to actually encode tumor antigens within the virus and have those antigens express what we need it to," he says. "So, not only do we have an oncolytic virus, but we’ve also produced within it a cancer vaccine to drive a very strong immune response against the target tumor antigens.”
Farah admits this is a bold statement, but says the responses Turnstone has seen are best-in-class in cancer vaccines. "A lot of that has to do with the specific virus we’re using and our overall platform.”
The company is starting with non-small cell lung cancer, breast cancer, and esophageal cancers, testing the candidate on its own and in combo with Merck’s Keytruda in non-small cell lung cancer. Two other programs in the pipeline are tabbed for work next year in HPV-positive cancers, and one more in prostate cancer. By the middle of next year, the company is set for four active clinical programs.
Farah says Turnstone's therapy can work on its own or in combination with checkpoint inhibitors to create a three-pronged attack. Potentially, given its method of action, the candidate could also be used alongside the next wave of CAR-T meds, a field that saw its first approval at the end of August.
As with oncolytic viruses, cancer vaccines have suffered a series of disappointments, and Fierce asked Farah whether he has a PR battle to win. “We are aware of that of course, but our science and the money talks for itself: We got off a $41 million plus series B round and we’re well funded, and I think that speaks volumes. We’re getting data in for proof of concept, and as I say, we’re seeing some genuinely exciting data, with the potential for more from combos with next-gen I-O.”
Investors: OrbiMed with participation from new investor F-Prime Capital Partners and existing investors FACIT and Versant Ventures.