PsiOxus Therapeutics is listed in FierceBiotech’s 2017 Fierce 15

Treating solid tumors through the systemic delivery of oncolytic viruses.

CEO: John Beadle, M.D.
Based: Abingdon, United Kingdom
Founded: 2006
Clinical focus: Solid tumors

The scoop: PsiOxus thinks it has figured out how to systemically deliver viruses that only replicate in tumor cells. That turned heads at Bristol-Myers Squibb, which struck two deals with PsiOxus last year, and provided a launchpad for a pipeline that uses viruses to directly kill cancer cells. PsiOxus’ next-generation approach gets tumors to express molecules that bring about their own destruction.

What makes PsiOxus Fierce: PsiOxus’ pipeline is built around enadenotucirev, singled out for its ability to kill tumor cells, leave healthy cells alone and stay potent in the presence of fresh human blood. Early clinical data suggest enadenotucirev is suitable for intravenous delivery, unlike the field’s pioneering product—Amgen’s Imlygic—and some other rivals’ pipeline prospects that must be administered directly into tumors.

PsiOxus’ first goal is to develop enadenotucirev as a direct, non-apoptotic destroyer of cancer cells. And it has now moved enadenotucirev through first-in-human tests and into a phase 1/2 ovarian cancer trial.

Along the way, PsiOxus generated data showing enadenotucirev encourages lymphocytes to infiltrate tumors, including colorectal cancers typically resistant to checkpoint inhibitors. This potential for enadenotucirev to turn cold tumors hot caught the attention of Bristol-Myers, which paid $10 million to run an Opdivo combination trial without acquiring commercial rights to PsiOxus’ virus.

If that had been the end of PsiOxus’ story, it is debatable whether it would qualify as Fierce. But that was PsiOxus 1.0. The next step is to use enadenotucirev as a gene delivery vector. That opens up an array of therapeutic approaches.

“It’s the flexibility of what can be done with the platform that I think is really interesting,” Beadle said. “We’ve essentially got a gene vector system for cancers. So gene therapy for cancers becomes something we can consider doing. [We can force] the tumor to produce a full-length antibody so that you get high concentrations within the tumor and very low systemic concentrations. And [we have] the potential to deliver combination immunotherapies.”

Beadle cites a single drug that hits co-inhibitory immune checkpoint targets PD-1 and CTLA-4 and co-stimulatory target GITR as an example of the combinations the platform can create. PsiOxus can load its viruses with up to three different genes comprising up to 3 kilobase pairs of genetic information.

The platform’s flexibility has given rise to a clutch of candidates now barreling toward the clinic, the most advanced of which is the Bristol-Myers-partnered NG-348. Bristol-Myers paid $50 million up front and committed to close to $1 billion in total to pick up the rights to a preclinical program that turns the CAR-T concept on its head.

“348 is the mirror image of the CAR-T approach. Whereas with a CAR-T approach you modify the T cell to interact with the tumor cell, with our approach you modify the tumor cell to interact with the T cell,” Beadle said.

Bristol-Myers is working to move NG-348 into the clinic around the end of the year. In parallel, PsiOxus is pushing its wholly-owned candidates toward the IND stage. Beadle thinks two will get there by the end of next year, with a third following early in 2019.

The advance of the candidates tees PsiOxus up to go back to the deal table. PsiOxus wants to take at least two of its follow-up pipeline programs forward on its own. But it is looking for a partner for one or more programs. Beadle expects to sign a deal within the next 12 months.

If the terms for NG-348 are indicative of what the follow-up programs are worth, that deal could provide PsiOxus with another useful slug of nondilutive funding. The $60 million Bristol-Myers paid last year allowed PsiOxus to kick its next financing further down the road than was anticipated when it put together its £25 million ($32 million) series C in 2015.

PsiOxus is now nearing the point at which it wants to raise more money, though. Beadle plans to do a crossover-type round in the next six months before executing long-gestating IPO plans in 2019.

That timeline sets PsiOxus up for a busy 2019. With the coming 12 months dotted more with trial starts than readouts, 2019 is when PsiOxus will start to gather clinical data on multiple pipeline programs.

Investors: Touchstone Innovations, Invesco Perpetual, Mercia Technologies, SR-one, Lundbeckfonden and Woodford Funds

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