GSK's Virtual-Proof-of-Concept Unit in Tune with Lilly's Chorus

Many readers will have heard of Eli Lilly's Chorus initiative, designed to drive compounds through to proof-of-concept as cheaply and quickly as possible. A less well-publicized but similar discovery-on-a-budget initiative is GlaxoSmithKline's VPoC--virtual-proof-of-concept--unit.

Many readers will have heard of Eli Lilly & Co.'s Chorus initiative, designed to drive compounds through to proof-of-concept as cheaply and quickly as possible. ( See "Lilly Tries to Buy Time," this issue (Also see "Lilly Tries to Buy Time" - In Vivo, 1 Dec, 2009.) and " Lilly's Chorus Experiment," IN VIVO , May 2007 (Also see "Lilly's Chorus Experiment" - In Vivo, 1 May, 2007.).) Less well-publicized is GlaxoSmithKline PLC's development-on-a-budget initiative, known as the VPoC, or virtual proof-of-concept.

The six-person operation, conceived and run by SVP, Molecular Discovery Allen Oliff, MD, is actually a drug performance unit (DPU), set up 18 months ago at the same time as the two dozen or so other biotech-like-units that now comprise GSK's discovery and early development organization. (See "GSK R&D Tries to Mimic Real-World Biotech," IN VIVO , February 2009 (Also see "GSK Tries to Mimic Real-World Biotech" - In Vivo, 1 Feb, 2009.).)

Oliff reckons the VPoC can produce PoC compounds--three of them in three years, to be precise--"at substantially lower cost" than in standard R&D. That's at least in part thanks to "entirely outsourced" activities including chemistry, running assays, drug metabolism and pharmacokinetic experiments plus some clinical work, most of which occurs in China and India.

Not that absolutely everything's contracted out; "we create the assays and high-throughput screens" in-house, explains Oliff, who still spends 75% of his time at the coal-face in molecular discovery research. Once the compounds hit proof-of-concept, they flow back into GSK's Medicine Development Centers. As such, "we're essentially cutting out the middle."

For the most part, VPoC gets its molecules from GSK's own de-prioritized compounds. The unit has so far selected three. It is also working on five targets identified outside, looking to create molecules using standard chemistries. Like Chorus, VPoC—based at GSK's R&D site in Upper Providence, Pennsylvania—also saves money by being small, flexible, efficient—and very good at out-sourcing.

But Chorus and VPoC aren't working exactly on the same theory. Chorus doesn't plan to get drugs approved faster or cheaper. Its goal is to give Lilly Research Laboratories more and better choices about which drugs to push into full development. The basic principle: since any early-stage compound is far more likely to fail than succeed, it should only do those experiments that show whether the compound works in people. Chorus thus eschews traditional pre-PoC tasks, like heavy-duty CMC and formulation work that are predicated on the assumption that the product will work. If a compound does reach positive PoC, the development organization still must go back and do much of the work that Chorus didn't do.

VPoC, on the other hand, really does aim to lower the cost and speed up development. Oliff insists that at GSK, "we progress assets reasonably quickly, in a standard format, without cutting corners."

That's perhaps why GSK's other Centers of Excellence for Drug Discovery (therapeutically-aligned groups, typically comprising several smaller, pathway-focused DPUs of their own) are so interested in piggybacking on VPoC's budget-sparing work to help shave down their own costs. (Since last year, the CEDDs have been working on a three-year financing cycle, with future funding contingent on achieving pre-agreed objectives.) "We're constantly getting calls...to ask how budgets can be extended," explains Oliff. "We're like the advanced troops," he continues, sniffing out the best CROs in China, for example, where "a lot of work is now starting to flow in from other CEDDs and DPUs."

But the VPoC—even though made up of highly experienced VPs—also needs GSK. "I couldn't do this with five others in isolation," says Oliff. His team, which has no particular TA focus, is in regular contact with GSK experts across all functions within the other CEDDs. "I can pick up the phone for any information I need. I don't need to spend lots of money on consultants; this little organization can feed off the expertise that's here," elaborates Oliff. And yes, he adds, whatever group or individuals lent a hand "would get credit as well," in the case of success.

The bonus system across GSK R&D is focused strongly on downstream results rather than near-term achievements. Scientists are rewarded not at the point of delivering a particular milestone (such as proof-of-concept), but when an asset is actively taken into the next stage. "If we ask for proof-of-concept," illustrated GSK's Chairman, R&D, Moncef Slaoui at Elsevier's Pharmaceutical Strategic Alliances conference in September, "you don't get money when you get to PoC, but when the compound passes into Phase III, for example." And even then, a scientist may only get 10% of his or her bonus pot—described by Slaoui as 'significant'--upon entry into Phase III, with a further 90% materializing when the drug is approved.

The success or otherwise of the VPoC experiment will be determined by if, when and how quickly assets progress to the Medicines Development Centers (the DPU's three-year objective also specifies two "commit-to-Medicines Development" assets). Oliff hopes to deliver "at least one, hopefully more" PoC assets by next year.

Perhaps he's right to be optimistic. Chorus appears to have delivered. The company has put 28 NMEs into the system—it started with 11 five years ago. It's completed 14 PoC studies of which five were positive and four of those are now in Lilly's main development group (the fifth is being out-licensed). The company expects to see the first NME to have graduated through Chorus launched before 2014. Indeed, Lilly feels that Chorus deserves duplication and as such the company joint ventured with India-based Jubilant Life Sciences Ltd. to combine Chorus' rapid-PoC model with Jubilant's lower cost structure. [See Deal] And now it's setting up a Chorus clone in Indianapolis (the groups have to stay small to be effective—roughly 30 people can handle 15 molecules, says Rob Armstrong, PhD, VP, global external R&D any bigger and the group loses focus and speed). Meanwhile, independent, VC-backed biotech Flexion Therapeutics Inc.—created in 2007 by Chorus' founders Neil Bodick, MD, PhD, and Michael Clayman, MD, to provide the same "cheap 'n' fast" treatment to non-Lilly assets--appears to be gaining ground; it is shortly expected to announce a handful of deals with Big Pharma. (See "Flexion: The In-Licensing Advantage of Cheap Proof-of-Concept," START-UP , December 2007 (Also see "Flexion: The In-Licensing Advantage of Cheap Proof-of-Concept" - Scrip, 1 Dec, 2007.).)

If VPoC delivers, no doubt GSK will follow suit in reproducing the unit; "we'd be foolish not to do more," declares Oliff. So, likely, would most other Big Pharma.

--Melanie Senior