When XO1 was bought out by J&J a couple of years ago, the seed investors at Index, now Medicxi, made it Exhibit A for their business model on creating a portfolio of asset-based biotechs.
What started off with a bit of scientific sleuthing by a pair of researchers at Cambridge University — Trevor Baglin and Jim Huntington — led to an antibody program for a drug dubbed ichorcumab that promised to potentially act as an anticoagulant, without the inherent risk of severe bleeding that inevitably haunts the class.
Patrick Verheyen, who was running the J&J Innovation office in London at the time, called this deal a prime example of the way the pharma giant was able to reel in top scientific programs around the world.
But between the chance discovery based on an odd medical case dating back to 2008 and J&J’s acquisition, XO1, without building a staff or doing all the normal things associated with biotech startups, had to push through a critical preclinical study that could prove it had something of real value.
“What we really needed to do in XO1,” XO1 former chief and sole full time staffer Richard Mason tells me, “was to show this antibody we created was an anticoagulant that didn’t increase bleeding risk.”
That’s never been done in any similar development program before, by anyone.
To do that, Mason relied on a group in Cambridge, UK called RxCelerate. Co-founded by David Grainger, a Medicxi partner who also acted as chief scientific officer for XO1, the lab staff didn’t just run a preclinical study under contract. They built the study from the ground up, questioning every step along the way in a field beset by questions of legitimacy and integrity.
Says Mason: “They are the architects of the experiment.”
XO1’s experience underscores one of the hard truths about drug discovery projects. The literature is often misleading, the models in use may be suspect, sometimes some of the hardware described doesn’t even exist, says Mason. And all of that was on display in their groundwork on anticoagulation.
A scientist by training, Grainger and his colleagues at Medicxi have carved out a reputation for combining scientific rigor in early-stage research with a rep for carving the hard costs of doing a startup down to the bare essentials — including the creative use of outsourcing to keep their startups virtual.
Now RxCelerate has opened up a Boston/Cambridge office to introduce their work under US EVP Laura Hamilton, the former BD chief at MassBio.
“We are not a CRO,” Grainger tells me levelly. So I asked for a look at one case to explain what they do. And that led me to Mason, who didn’t just do a deal with J&J — a few months later he took Verheyen’s job running J&J Innovation in London. (Verheyen was promoted to run BD for all of J&J. Huntington, meanwhile, caught the serial entrepreneur bug and has since launched a series of biotech upstarts out of his Cambridge lab.)
The way RxCelerate works, Mason says, “it starts with the basic science and takes nothing for granted.”
Jill Reckless — the CEO at RxCelerate, who left with a group of researchers at Cambridge to launch the lab at RxCelerate with Grainger — started by reviewing the literature on thrombosis and bleeding models.
“We found that many of those papers had some problems with them,” says Mason. Then there was the rat tail clip model used to measure bleeding in rodents.
“We found substantial problems with the way that was done in the literature,” adds Mason. “Problems with reproducibility.”
Rather than replicate bad science, RxCelerate created new model experiments where necessary, and doubled down with larger animal models to demonstrate potential in humans.
“What we are trying to offer is the ability to outsource the thinking behind drug develoment,” says Grainger. CROs are great for defined tasks, he adds, but when it comes to doing the architecture: “CROs don’t do that very well.”
It’s the kind of work that appeals to anyone in a cash constrained environment, says Reckless, whether that’s a biotech startup or a major biopharma, working on a budget to see where it has assets of real value to pursue. It’s all about staying focused while remaining skeptical about what’s come before.
“By not doing the things that don’t need to be done,” says Grainger, “that’s where the bulk of the cost savings come.”
How’s J&J’s team doing with XO1’s drug, now dubbed “9375”?
So far so good, says Mason, who visited with the group in charge at J&J as they look for a next-generation antithrombin to follow Xarelto. They’re through Phase I and examining next steps for Phase II.
Says Mason: “Stay tuned.”
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