The deal will allow Cephalon to see not only how their drugs interact with target kinases, but also with other kinases that could be causing side effects. The resulting data could provide evidence of the move toward ever more targeted and personalised medicine.
Under the terms of the agreement Ambit's KinomeScan-driven discovery capabilities will be combined with Cephalon's chemistry, discovery and development capabilities, significantly compressing typical timelines for discovery and development of small molecule pharmaceutical products.
Kinases play key roles in cancer, inflammation, diabetes and other diseases. With more than 30 kinase inhibitors in clinical trials or approved for human use including Gleevec, Tarceva and Sutent, this important class of proteins is a rich area for drug development.
However, kinases share similarities that make them difficult to target specifically, and off-target inhibition can result in side effects or toxicity.
Financial obligations will see Cephalon pay an up-front fee of $18m (€14m) to Ambit for access to Ambit's proprietary KinomeScan technology.
In addition, the companies will collaborate on advancing two programs targeting undisclosed kinases, with Ambit having primary responsibility for delivering clinical candidates that Cephalon will further develop in exchange for additional milestone payments to Ambit of up to $232.5m and royalties on commercial sales.
Ambit will also have the opportunity to utilise Cephalon library compounds to discover and develop products that are effective inhibitors of certain undisclosed kinases.
"While they are our fourth major collaborator, Cephalon is the first pharmaceutical company to take complete advantage of Ambit's proprietary discovery platform," said Scott Salka, Chief Executive Officer of Ambit.
"The cornerstone of the collaboration is Ambit's unequalled ability to screen chemical libraries across a panel of 300 kinases, which will be used to rapidly annotate Cephalon's focused library of potential kinase inhibitors," he added.
Ambit's KinomeScan technology is a new way to evaluate libraries of compounds by testing them simultaneously against a large number of human kinases.
This provides information regarding how strongly the compounds bind to both intended and unintended kinases, revealing the best candidates for preclinical optimisation as well as off-target interactions that could either cause unwanted side effects or reveal new indications.
Additionally, the speed of KinomeScan, which can routinely provide a three-day feedback loop between chemistry, pharmacology and screening, allows the technology to be utilised throughout the optimisation process until a drug's desired kinase inhibition profile is obtained.
While Kinases remain a popular drug target for pharma and biotechnology companies, the problem with kinases is that it is difficult to hit the ones you want without also hitting ones you don't want - and that can cause side effects.
As recently as last week, the enrolment of the drug Exelixis was suspended in a Phase 2 trial with a kinase inhibitor due to cardiovascular adverse events…probably because that drug targets multiple kinases, which increases the risk of side effects).
"Our structurally diverse, proprietary chemical library of kinase inhibitors is among our most valuable assets. We see this collaboration as an opportunity to extract the maximum value from this asset in the shortest period of time," said Jeffry Vaught, Executive Vice President, research & development at Cephalon.
"Coupled to our collaborative discovery programs with Ambit, we expect to rapidly and efficiently identify drug candidates that effectively inhibit the targeted kinases while minimising side effects due to off-target kinase modulation," he added.