A compound from AstraZeneca in the same chemical class as Novartis’ Glivec (imatinib) and Roche’s Tarceva (erlotnib) is the first drug candidate to enter Cancer Research UK’s Clinical Development Partnerships (CDP) programme.

Under the CDP initiative, which was launched in 2006, the UK charity and its development and commercialisation arm, Cancer Research Technology (CRT), take “deprioritised” but potentially valuable anticancer agents through early clinical development at no cost to the originator. AstraZeneca’s tyrosine kinase inhibitor AZD0424 is expected to start Phase I clinical trials within the next 18 months.

Cancer Research UK’s Drug Development Office, which has moved more than 100 potential anticancers into clinical trials since 1982, will conduct the studies on AZD0424 under the terms of the partnership deal. AstraZeneca retains the option to assume further development and marketing of the drug, with the charity set to receive an undisclosed share of any future revenues.

Brent Vose, vice president for Astra Zeneca’s Oncology Therapeutic Area, noted that the company had a number of promising new targeted anticancers in development and was looking forward “to seeing the results of some key studies this year”.

In the meantime, he said, “we are actively pursing innovative new ways to progress the many new drug candidates being discovered by our dedicated cancer scientists. The CDP initiative presents an exciting opportunity to supplement our own development activities and ensure that we can develop as many of our candidates as possible”.

Lower than average

Clinical Development Partnerships (CDP) are targeted mainly at leading pharmaceutical and biotechnology companies with large pipelines that have to make difficult decisions about which compounds to advance into Phase I. “Oncology agents have a lower than average success rate for reaching the market compared with treatments for other diseases and may be deselected on this basis alone,” Cancer Research UK points out.

With companies under pressure to meet business objectives and patient demands, they need to make drug development more cost-efficient and maximise the value of their shelved assets, the charity says.

“Drugs with a lower probability of getting to market often have a higher expected return if they succeed and, in the case of niche indications, agents may be fast-tracked through clinical development, bringing them to market sooner,” it comments. “Working with CDP provides companies with an alternative route to take these agents through early clinical development and increase the number of successful new treatments being developed for cancer.”

The programme’s main interest is in novel molecularly targeted small molecules and select biological therapeutics, in particular monoclonal antibodies. CDP will also consider repurposed agents – i.e., compounds that have previously been in clinical trials in another therapeutic area – as well as improved derivatives, back-up drugs (which have a different mode of delivery, and/or may be developed for a different cancer indication, from a lead compound) and novel rationally designed drug combinations.

“We will also consider repeating Phase I clinical trials where we believe the trial design could be improved to add value to the programme and bring it back into clinical development,” Cancer Research UK says.

The charity carries out Phase I and II trials with partnered compounds through its established network of oncology centres across the UK. Non-clinical safety studies, formulation development and final product manufacture can also be delivered in Cancer Research UK’s own facilities or contracted out if required.

Risk-reward

Partnerships are formed on a shared risk-reward basis, under which the clinical data are optioned to the company at the end of the study. As more than 40% of clinical trials fail at Phase I, this removes a significant portion of the risk from the originator as well as the expense of initial trials, Cancer Research UK points out. And in contrast to other outlicensing strategies, the company keeps its rights to the existing intellectual property throughout the trial.

“In most cases, if the trial is successful we would anticipate that the company will wish to exercise its option and acquire rights to the clinical data,” the charity comments. “However, if having completed the trial the company is not interested in progressing further with the programme, then the rights to the existing intellectual property would be transferred to Cancer Research Technology and an alternate licensee sought.”

The revenue share split is based on the value each party adds to the project but will vary depending on the type of agent, the stage of development, availability of materials and funding provided by the respective partners.

“The revenue share may be broken down into standard licence terms in the event the company takes the product forward themselves rather than through a licensee,” Cancer Research UK notes. “This would include a series of success milestones and royalty payments.”