In A First, Merck And AstraZeneca Team Up For Oncology Study

The two Big Pharmas have allied for early development of Merck’s AKT inhibitor and AZ’s Mek inhibitor. But where do they go from there?

Eighteen months after a chance meeting by two scientists in an airport security line sparked an idea, Merck and AstraZeneca have announced that they're teaming up to run a Phase I combination program for two first-in-class oncology candidates.

Merck will sponsor a safety and tolerability program that adds its Phase I MK-2206 AKT inhibitor to AstraZeneca's Phase II AZD6244, a mitogen-activated protein kinase 1 (Mek) inhibitor acquired from Array Biopharma in 2003 also known as ARRY-886.

The companies are billing the deal as a first-of-its-kind collaboration -never before have two large companies have done this kind of deal with two molecules so far from the market according to executives at both drug makers.

Costs of the program will be split evenly, and a joint steering committee comprising Merck and AstraZeneca representatives will design and implement the trial.

"Of course through competitive intelligence they had some information about what each company was up to ... and they said to one another, there's a compelling rationale for getting these molecules together," said Merv Turner, Merck's chief strategy officer and senior VP worldwide licensing and external research, when asked about the genesis of the partnership. After the encounter in 2007, the two scientists got their respective business development groups on the case, according to Turner.

That the deal to conduct one Phase I combination study took more than 18 months to finalize since that rendezvous at the Dublin airport says as much about the complexities of oncology drug development as it does the difficulties of intra-Big Pharma dealmaking.

Greater Understanding Of Tumor Biology Calls For Earlier Combos

Merck's MK-2206 is, according to Merck and Astrazeneca, the most advanced AKT inhibitor in development. AKT acts just downstream of phosphatidylinositol-3 kinase (PI3k) in that important cancer cell survival pathway. (The PI3k space has seen several recent deals, including Exelixis' $140 million up-front pact with Sanofi-Aventis, signed last week (¹ (Also see "Ahead of ASCO, Exelixis Inks Lucrative Deal With Sanofi For Its PI3 Kinase Inhibitors" - Pink Sheet, 28 May, 2009.)). Phase I data on MK-2206 were presented at this weekend's ASCO meeting.

AZ's '6244 hits Mek, an actor in an important signaling pathway that runs parallel to the PI3k pathway. Like the Merck compound, '6244 is further along than its competitors, according to AZ and Merck. The candidate has completed several Phase II monotherapy studies and its Phase II program continues apace in multiple tumor types.

A greater understanding of cancer biology, said Turner, should drive more deals like this one, where "the potential to short circuit what could otherwise be a long and combinatorial approach to finding the right pairs" of oncology therapies "becomes quite compelling."

There are over 800 molecules in development for various cancers. "We're learning more and more about the nature of tumorogenicity and the pathways involved and therefore how to select targets and populations expressing those targets ... and as we go forward into the new mechanism-driven approaches to tumor biology the rationale for combining agents which target complementary pathways becomes more clear," explained Turner.

"Cancer research tells us that tumors rarely have one thing wrong with them, so targeting multiple pathways and partnering to develop combinations is likely to become more and more common," AstraZeneca Senior VP of Strategic Planning and Business Development John Goddard said in an interview. "No single company's pipeline can provide for every interesting novel-novel combination, so partnering becomes the answer."

A Difficult And Rarely Trodden Deal Path

It's no surprise that the deal is initially somewhat limited in scope. Merck is already developing its own Mek inhibitor and AZ hopes to move its AKT inhibitor ahead in the clinic as well. In addition, because there is the potential to disrupt the different signaling cascades at multiple points, both drugmakers are hard at work studying additional targets. Such compounds could be useful in a variety of cancers, where the companies have individual ongoing programs.

"When we set out on this, to try to think through all the possibilities, we soon realized that the number of branches that arise if you try to construct a decision tree of all the things that might happen in development, it just becomes overwhelming," said Turner. So the companies are starting slowly, taking a step-wise approach to collaboration that need not go beyond this Phase I program.

The companies decided, "let's start with the easy part, work out how we'll do these experiments together in patients in Phase I, and if that succeeds, we'll go on to the next part," he said.

If the eventual goal is some sort of fixed-dose combination the companies will eventually have to jump in with two feet, perhaps partnering on multiple compounds or even entire pathways to ensure that Merck and AstraZeneca's interests are fully aligned. But that need not happen at all. "The first goal could be to have each party arrive at the marketplace [independently], with a label statement that supports use of the other agent in combination," said Turner.

A deal-making model for the future?

Big Pharma rarely do deals with one another that comprise both companies contributing individual assets to an asset pool. In part that's because there are tricky issues around control of development pathways, asset valuation, and overlap with other, non-partnered projects. These and other cultural and practical difficulties present high hurdles for two large companies to come together in even basic ways, despite the potential advances that might result (² (Also see "Collaborating for Better R&D Productivity" - In Vivo, 1 Feb, 2009.)).

But if these alliances aren't discouraged institutionally, they're certainly not highly sought after either. This may explain why the companies' deal came about not through any structured intra-Pharma business development outreach program at Merck or Astrazeneca, but by chance encounter.

Merck and AstraZeneca's pact is a necessary first step toward a broader, more strategic alliance. A successful Phase I program could make further collaboration more palatable - questions of valuation "are better addressed with data in hand," said Turner.

Whether or not these kinds of agreements catch on, or could eventually impact drug development costs and speed to market, or advance the standard of care in difficult diseases, remains to be seen.

But in order for any of that to happen, companies need to move beyond chance encounters into more institutionally driven tie-ups. That may yet occur. "If this works as advertised," sums up Turner, "we can think of it as a template for future similar deals."

- Christopher Morrison ([email protected])