John Carroll’s series on biotechs to watch turns to the Golden Triangle in the UK, anchored by London, Oxford and Cambridge. Some of the world’s top scientists are clustered here, and they’ve helped advance a new oncolytic virus pipeline at PsiOxus which promises to surpass the pioneering therapy now on the market.
Back in 2013, Oxford-based PsiOxus put out a statement giving Amgen a thumbs-up on a new batch of positive data for their oncolytic virus cancer therapy T-Vec. For an infinitely smaller, rival biotech at a much earlier stage of development in the same field, that might have been viewed at the time as a bit cheeky—a kind of willful disregard for the realities of a David-and-Goliath matchup. But from where we’re sitting now in 2016, it looks far more like a casual nod to a pioneering validation point for PsiOxus, which plans to do much, much better with what it has in the clinic.
T-Vec has since been approved and hit the market as Imlygic, but analysts’ meager expectations have underscored what a number of observers had already concluded: The drug, which is injected directly into a tumor, is an interesting improvement, but it’s not nearly as good as it should be to warrant its regular use.
“What we’ve seen for oncolytic viruses is very interesting,” PsiOxus CEO John Beadle tells me. “But what you really need to do is to deliver it systemically.”
Minimal improvement for very advanced-stage cancer is what the FDA looks for in a first-of-its kind drug like this is. In Amgen’s case, the data were good enough for an OK on melanoma, but with none of the gains on overall survival needed to attract oncologists and their patients. An approval was warranted on data demonstrating that “16.3 percent of the study participants who received Imlygic experienced a decrease in size of their skin and lymph node lesions, lasting for a minimum of six months, compared to 2.1 percent of the study participants receiving the comparator therapy,” according to the FDA.
And it arrived after a series of new drug regimens came along and completely disrupted the generally unreliable way that melanoma had been treated.
“The market has completely changed,” says Beadle. “I think also delivery is a real sticking point with that product. Intratumoral delivery is not something oncologists do in a routine practice.” To have an effect, you have to get the needle into the tumor. And even then it’s likely to have an erratic effect.
“Like a lot of these things, a combination therapy is where it’s going to be effective,” says the PsiOxus CEO. And introducing a systemic drug like enadenotucirev is just going to be a lot more practical when used in combination with other systemic treatments.
Bristol-Myers Squibb thinks so as well. The big biotech signed a deal just a few weeks ago to partner on a combo of Opdivo with the biotech’s enadenotucirev, looking for a better objective response rate and durability of effect. And unlike a lot of these pair-ups in the clinic, Bristol-Myers Squibb has some real skin in the game, paying USD 10 million to the biotech to get the pact started and sharing development costs while leaving Phase I in PsiOxus’s hands.
Merck was the first to the table, agreeing to provide Keytruda, the other big PD-1 checkpoint, for a combo study with PsiOxus’ oncolytic virus. But that study is going to the sidelines as PsiOxus focuses on the Bristol-Myers pact, Beadle says.
“The honest truth is now that we’ve done the deal (with Bristol-Myers) we decided to close down the Keytruda work,” says the CEO.
He sees both therapies as “pretty interchangeable.” But Bristol, he says, is being far more collaborative about this than Merck was prepared for.
PsiOxus put together a great video to answer the basic question of how their oncolytic virus works in attacking cancer. Essentially, they infuse a virus to infect a cancer cell, triggering rapid replication of the virus that in turn destroys the cell. The path of destruction is focused on reducing and eliminating tumors. In this particular case, PsiOxus boasts about the extensive work it did to select a chimeric adenovirus that was naturally more likely to gather in tumors and infect cancer cells, while unable to infect most normal cells. The virus spreads from cancer cell to cancer cell. As the cancer cells explode, the released antigens help drive an immune response in a mop up operation.
That same appealing strategy is driving a slew of new development programs. Philip Astley-Sparke, who helmed BioVex before Amgen bought it up for T-Vec, co-founded Replimune, another next-gen oncolytic virus player. Mitchell Finer, the former CSO at bluebird bio, took the helm at the upstart Oncorus, which just raised a USD 57 million venture round and is using a herpes simplex virus for their work on glioblastoma. And Duke University’s Dr. Matthias Gromeier has genetically engineered his virus to keep it focused on cancer, and away from healthy tissues. Meanwhile Canada’s Oncolytics Biotech and the Pink Army Cooperative—a very unusual, open source collective commanded by Amgen vet Andrew Hessel—are also in play.
“As you’ve seen, there are new companies getting in. It is a hot area,” agrees Beadle. “I think there will be competition. As a class there’s lots of variation from virus to virus, using different pathways.”
The next-gen approach can be found in PsiOxus’s AbEnAd program, which encodes an antibody molecule or fragment in the oncolytic virus, which is designed to actually produce therapeutic antibodies in the tumor. And Beadle has been seeing the kind of efficacy and safety payoffs in animal models that are exciting him about its potential for human studies—though there’s a considerable way to go before reaching proof-of-concept data in humans.
The company is financed well enough to find out. The biotech picked up a USD 39 million round in the spring of 2015, and Beadle is considering another crossover round for next year, with an IPO possible in the second half.
Over the years, PsiOxus has seen its staff grow to 40. And Beadle expects that its plans will require even faster growth now, with the roster growing to about 70 by the end of next year.
That’s still nowhere near a giant like Amgen. But with years of experience, PsiOxus still likes the way it fares in a head-to-head comparison on the oncolytic virus approach to treating cancer.
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