U.K Drug-Repurposing Program Expands, Attracts Industry Support

Britain moves ahead with a drug-repurposing research program that brings together big pharma and academic researchers in novel collaborations.

A pilot program in the U.K. that takes selected compounds from pharmaceutical companies’ back catalogues and gathers ideas on their potential scientific use and possible commercial development is being expanded.

The repurposing scheme, begun in 2011 and piloted by AstraZeneca PLC and the U.K.’s Medical Research Council (MRC), is similar to the repurposing program set up the same year by the U.S. National Institutes of Health’s National Center for Advancing Translational Sciences (NCATS), and which moved into top gear in 2013 (Also see "NCATS May Consider Requesting “Active” Compounds For Repurposing Program" - Pink Sheet, 1 Jul, 2013.).

Seven companies have said they will supply more de-prioritized compounds to the U.K. program later this year. They include AstraZeneca, GlaxoSmithKline PLC, Janssen R&D LLC, Eli Lilly & Co., Pfizer Inc., Takeda Pharmaceutical Co. Ltd.and UCB Group.Other drug makers are expected to join the program in the near future. The offered compounds have undergone some previous development by companies, but usually have stalled, often due to a lack of efficacy in the disease targeted by the company.

Under the plan, the MRC then will draw up a list of potentially useful compounds from those submitted, and researchers will put forward their research ideas, with the most promising ideas being short-listed and a final proposal later drawn up in a joint effort by academic and company researchers. The MRC then would choose which projects to finance. The Medical Research Council is the main conduit for the funds and grants from the U.K. government in support of academic clinical research.

There are subtle differences between the programs pursued by the U.K.’s MRC and the U.S. NCATS. According to MRC Director of Translation and Industry Chris Watkins, the U.K. initiative is more about using the compounds as “exquisite probes” to identify and clarify mechanisms of human disease. “But if out of this research come repurposing opportunities, that’s a great outcome,” he said in an interview.

In contrast, “NCATS is supporting studies that reveal new therapeutic opportunities for drugs that have stalled in development, for whatever reason. It is funding preclinical ideas that have a clear progression into clinical studies in a year or so,” the MRC executive suggested.

The perceived success of the pilot program set up with AstraZeneca is one reason for expanding the U.K. scheme, Watkins said. Another is because the scheme brings pharmaceutical company researchers into close contact with academic researchers in a way that is valued by both sides. The use of “crowdsourcing” to gather innovative ideas from researchers is also novel, he noted.

In 2011, AstraZeneca provided 22 compounds to the pilot program that previously had been in clinical development but were de-prioritized for varying reasons (Also see "AstraZeneca Collaboration With Medical Research Council May Mean New Life For 22 Compounds" - Pink Sheet, 5 Dec, 2011.). The MRC then solicited proposals to use the compounds, and more than 100 were received by the MRC. Fifteen compounds were chosen for research funding (Also see "Abandoned AstraZeneca Compounds “Given” To U.K. R&D Academics" - Pink Sheet, 30 Oct, 2012.).

Cough Research Benefited

One of those research programs is bearing fruit already, the use of a compound lesogaberan in chronic cough research. AstraZeneca originally took it as far as Phase III trials in patients with reflux before halting development because of poor efficacy.

Lesogaberan has been used by a U.K. research team led by Jacky Smith, a professor at Manchester University, to research the role of the nervous system in chronic cough conditions. Chronic cough can ruin a patient’s quality of life, but understanding neuronal control has not been a priority for respiratory medicine experts, who mainly have focused on inflammation, Smith said in an interview.

The neurological control of the stomach sphincter might play a role in cough because it might allow non-acid reflux that induces the cough reflex, Smith explained. Lesogaberan already has been studied in healthy volunteers with experimental cough, and Phase IIa studies to test its effects on the cough reflex and stomach reflux in patients are being designed. Results should be available by the end of 2015. AstraZeneca researchers worked with the academic researchers on the grant application and will work with them on the protocol for the clinical studies.

Chronic cough, and the role of respiratory nerves in its evolution, slowly is becoming a more competitive area and one in which drugs developed for other conditions such as pain can be repurposed, Smith said.

VCs have supported a U.K. company Ario Pharma Ltd., for example, that has repurposed a TRPV1 ion channel antagonist for the treatment of cough, having been developed previously for the treatment of overactive bladder (Also see "U.K.’s Ario Pharma Raises $3M Series A For Cough Therapy" - Pink Sheet, 17 Dec, 2013.).

Researchers Driving Expansion

Academic researchers like Smith are driving the program’s expansion. “The best way of doing experimental medicine studies is to use human participants, and we need probes that are safe to use. A very good source of those is the pharmaceutical industry,” MRC director Watkins explained.

Corporate researchers also have benefited.

“The companies recognize that this is a good opportunity to help in discovery science that enables effective drug discovery,” Watkins added. They also get to work with academics that previously may have been completely off their radar. A range of collaborations are envisaged, ranging from full collaborative working to a hands-off approach.

The intellectual property rights have been made clear, Watkins said. The company owns the IP on the molecule, but the new IP that emerges from the program will be held usually by the academic institution. The company will have first rights to discuss an exclusive license to exploit and commercialize the emergent knowledge. All scientific outcomes of MRC-funded research are put in the public domain, and this scheme will be no different.

NCATS Evaluating Seven Compounds

NCATS initiated funding for nine U.S. repurposing projects involving seven compounds in mid-2013, with the projects expected to continue for up to three years (Also see "NCATS May Consider Requesting “Active” Compounds For Repurposing Program" - Pink Sheet, 1 Jul, 2013.). The Center is also helping promising drugs to cross the so-called “valley of death” between preclinical studies and clinical proof-of-concept. The first project to bridge the gap and find a development partner, AesRx LLC’s potential sickle cell anemia compound Aes-103, was acquired by Baxter International Inc. Baxter bought out AesRx and will take the compound into late development (Also see "NIH Drug Development Strategy Gets First Candidate Through Valley Of Death" - Pink Sheet, 14 Jul, 2014.).