LONDON Horizon Discovery plc is putting its money where its mouth is, in a deal to in-license a series of kinase inhibitors and shape them up for development as personalized medicines, using its genomics discovery research technologies.
In return for carrying out this preclinical research, Horizon will be in line for payments of more than £50 million (US$76.6 million) in development milestones plus royalties on sales of any products, from partner Servier SA.
Under terms of the agreement, Servier has the first option to license back the compounds. If it chooses not to, Cambridge, UK-based Horizon will be free to find another partner. In this case, Servier would receive payments as any program advanced.
The kinase inhibitors that are the subject of the deal were discovered in a collaboration between Neuilly-sur-Seine, France-based Servier and the UK company Vernalis plc.
In previous preclinical studies the compounds have shown potential to treat a range of cancers. However, currently the precise mechanism of action is unclear and there are no biomarkers to guide clinical development.
Darrin Disley, CEO of Horizon, told BioWorld Today it will take 18 months to two years to reach the point where there is a clear clinical development plan. The company will apply technologies including isogenic cell lines, Crispr Cas9 and other gene-editing techniques to create patient-specific cell lines, and ultra-high throughput combination screening to find biomarkers with which to identify the patients who are most likely to respond and that are indicative of drug efficacy.
"In the era of personalized medicine, companies are no longer going to do a number of clinical trials treating all patients; they need to have a defined development plan," Disley said. The problem is that it's necessary to understand the mechanism of action and have some means of finding likely responders.
Horizon points to two examples where its translational genomics technologies have informed stratification. The first involved using precisely engineered cell lines to identify the 4.8 percent of lung cancer patients with specific EGFR mutations who would respond to Iressa (gefitinib).
Another example is Erbitux (cetuximab), in the treatment of metastatic colon cancer, where 40 percent of patients who have a mutant K-Ras gene that makes them resistant to the drug are excluded from therapy. However, there are many different variants of mutant K-Ras and a study using Horizon's human cell lines has shown not all variants are equal and that some patients currently excluded could benefit from Erbitux treatment.
Normally Horizon does this type of genomics detective work on a fee-for-service basis, but in the case of the kinase inhibitors that are the subject of this deal, the company approached Servier, an existing customer, with the proposal to in license the compounds and to carry out the research at its own expense.
Horizon has inside knowledge of the compounds because Jon Moore, the company's chief scientific officer, previously was head of biology at Vernalis plc. In addition to cancer, Disley said, "there is a strong scientific rationale" for using the kinase inhibitors in other disease areas and Horizon has secured the rights to explore other indications.
While this is the first such deal Horizon has signed, Disley said pharma companies are sitting on a range of assets that have been parked or have failed in clinical development, because the knowledge needed for stratification was not at hand. He expects to reach similar agreements in the future.
"We are utilizing the drug discovery tool box we have developed to take on assets from pharma," Disley said. "We have the knowhow and the technology to take parked programs further and expect to move more stranded or halted assets forward."
He pointed to Axovant Inc.'s acquisition of Glaxosmithkline plc's Alzheimer's disease treatment RVT-101, for $5 million up front, following the drug's failure in late-stage development.
After dusting off the development program, Axovant raised $315 million in an IPO on the New York Stock Exchange in June. Then on Monday, the Hamilton, Bermuda-based company announced the start of a 24-week 1,150 patient trial in mild to moderate Alzheimer's.
Armed with a FDA special protocol assessment, a successful outcome to the trial could lead to a new drug application as soon as 2017.
"There is going to be more and more of this type of thing happening," Disley said. "This is particularly so in cancer genomics, where you need strategies to build out from covering 5 percent of patients, or where products have failed, but may work in stratified populations or in different indications."