LONDON—WNT ligands are key regulators of cell reproduction,development and survival, mediating a range of functions such as regenerationand injury repair in adult tissues in a process that involves regulating anumber of biochemical signaling pathways. Now, Cancer Research Technology(CRT), the commercial arm of Cancer Research UK, along with the Institute ofCancer Research (ICR) in London and Merck Serono, a division of Darmstadt,Germany-based Merck KGaA, have signed a licensing deal to discover and developanticancer drugs that block the WNT signaling pathway.
The groups are all very familiar with each other already, asthis licensing deal actually extends a previous alliance to discover anddevelop anticancer drugs that block the WNT signaling pathway. This new dealalso grants Merck Serono the rights to develop molecules discovered through therecently completed four-year research collaboration between Merck Serono, CRT,ICR and Cardiff University.
As part of the new work, ICR, CRT and Merck Serono arebeginning a two-year collaboration to progress the existing compounds towardcandidates for clinical trials and design further molecules to target the WNTsignaling pathway. They will also collaborate to discover biomarkers for targetinhibition and patient selection. Merck Serono will have rights to theintellectual property from this two-year project just as they now have IPrights for the previous four years' work.
"Originally, we had set up a three-year collaboration withMerck Serono and they extended that by a year, and at the end they decided toexercise their license option," Dr. Phil L'Huillier, CRT's director of businessdevelopment, tells DDNews. "But on topof that, they decided to keep working with us and ICR. It's been a veryeffective collaboration, and a very effective team. It's also been a verystable team, and there are complementary skill sets that just made it toovaluable not to continue working together. I think what stands out in our workis well and how quickly this collaboration has moved and the recognition thatsticking together is the quickest path toward success."
The new drug discovery work will be carried out byscientists at ICR in London and at Merck Serono's headquarters in Darmstadtwith some financial support from Cancer Research UK.
Merck Serono will pay an upfront license fee to CRT and makefurther payments to CRT upon reaching development milestones. Merck Serono willalso pay royalties from potential future drugs. CRT will share revenue with ICRand Cardiff University.
The WNT pathway derives its name from the Drosophila (fruit-fly) "Wingless" gene and the mouse "INT-1"gene. Faults in the WNT pathway can leave it permanently switched on, and thisis linked to the development of colorectal, breast and other cancers, note CRT,ICR and Merck Serono, as well as an aberrantly activated WNT pathway possiblyplaying a role in establishing and maintaining cancer stem cells within tumors.
"Signaling through the WNT pathway is critical touncontrolled cell proliferation in a number of tumor types, particularlycolorectal cancer. In some cases the WNT pathway is permanently switched on bymutations in components of this signaling cascade, leading to uncontrolledgrowth," noted Prof. Julian Blagg, the project's lead scientist at ICR, in thenews release about the new licensing deal and collaboration. "In a fast-movingand successful collaboration, we have discovered small-molecule modulators ofcancer cell signaling and we are excited by the opportunity to further progressthis work in collaboration with Merck Serono. The announcement today helps tobring us a step closer to new treatments for cancer patients."
L'Huillier notes that while the work between theorganizations will no doubt involve outside parties, such as contract researchorganizations and others that can help move the work along, there are no plansto involve any other partners in the collaboration deal.
Details of the work to come are still being mapped out, soL'Huillier couldn't comment on the specific next steps in the process.
"In the end, though, we are just very pleased to see a veryearly-stage collaboration extend out and to see the fruits of that taken on byour commercial partner," L'Huillier says. "From our perspective, that is veryrewarding and a strong validation of the quality of our work together."