All the obvious cancer targets have been found according to Horizon Discovery, which last week agreed to help AstraZeneca find some new ones using isogenic pairs of oncology relevant cells.
Under the deal, UK-based Horizon will use its proprietary siRNA screening platform and a principle known as ‘‘synthetic lethality’ to identify novel targets for AstraZenca’s cancer drug development programme according to the CROs oncology head, Jon Moore.
Moore told Outsourcing-pharma.com that: “The idea of the new deal is target identification and validation. AstraZeneca will be responsible for drug discovery, but Horizon is rewarded for enabling the firm’s success in this regard with the downstream milestones.”
He also set out Horizon’s approach, explaining that: “Synthetic lethality means exploiting the rewiring of signal transduction in cancer to exploit novel dependencies on non-mutated targets” citing the PARP inhibitors currently being developed to treat BRC1 and BRC2 breast cancers as an example.
“The most famous example [of synthetic lethality in use] is the development of PARP inhibitors, which block non-homologous end joining (NHEJ)-mediated DNA repair, for the treatment of breast cancers with mutations in the BRCA1 or BRCA2 genes.
“BRC1 and BRCA2 are tumour suppressors mutated in familiar cancers that lead to defects in homologous recombination (HR). If NHEJ is blocked in these particular breast cancer cells, they don’t have HR to repair DNA damage and therefore are killed; normal cells can tolerate the absence of NHEJ as they have HR to fall back on.”
The contract is the second Horizon has signed with AstraZeneca in 12-months. In April the Anglo-Swedish drugmaker licensed rights to HD-001, a kinase target programme Horizon developed and this relationship was key to the latest deal according to Moore.
“HD-001 was our first collaboration with AZ. Horizon started working on this undisclosed target back in early 2012, collaborating with Sentinel to discover low nM inhibitors of this novel kinase. This program was licensed to AZ in Q1 2013. AZ put a sizeable team of the scientists on the project and are also supporting two biologists at Horizon.”
“It is too early to tell how successful the first collaboration will be in terms of discovering a drug. However, we have formed a coherent well-integrated project team and Horizon and AZ are enjoying working together.
“Note that the HD001 collaboration is mainly with the AZ group in Cheshire, UK. The new collaboration is mainly involves AZ scientists at Gatehouse Park near Boston.”
AstraZeneca is one of a number of drug companies to be working with Horizon. The firm has signed target identification and validation deals with Eisai subsidiary, H3, and according to Moore, “is actively seeking more.”
News of the agreement – financial terms of which were not disclosed – is the latest in a number of agreements established by AstraZeneca. Last week the firm bought a programme from Probiodrug and licensed a T-cell immobilisation platform from Immunocore .