|Professor Stephen Jane, Head of Central|
Clinical School, Monash University
The drugs – which are inhibitors of protein arginine methyltransferase 5 (PRMT5) – have potential clinical applications in both cancer and non-cancer blood disorders.
The importance of PRMT5 was first discovered by Professor Stephen Jane, Head of the Monash Central Clinical School, who initiated the search for inhibitory drugs.
These drugs were further developed by CTx, a Melbourne based Cooperative Research Centre (CRC) focused on the discovery and development of novel therapies for cancer, in collaboration with Professor Susan Charman, Director of the Centre for Drug Candidate Optimisation within the Monash Institute of Pharmaceutical Sciences, with support from the Wellcome Trust. Cancer Research Technology (CRT), the development and commercialisation arm of Cancer Research UK, has licensed rights to MSD on behalf of CTx in a package worth up to AU$730 million.
The PRMT5 protein is involved in many cellular processes including the epigenetic control of genes such as p53 – a gene that protects the cell against cancer-causing mutations and is faulty in nine out of 10 cancers. High levels of PRMT5 protein are found in mantle cell lymphoma (MCL), chronic lymphocytic leukaemia (CLL), melanoma, lung and breast cancers and are linked to poor survival.
In addition to applications for cancer, PRMT5 inhibitors switch on important genes in the development of blood, which could provide disease-modifying treatment options for patients with blood disorders like sickle cell disease and beta thalassemia.
Dr Ian Street, CTx chief scientific officer, said: “We are delighted to be working with CRT and MSD to progress the PRMT5 program to the clinic. This is why CTx was established, to leverage cutting edge research developed by Australian scientists and ensure that this knowledge is translated for the benefit of patients.”
Under the terms of the license, MSD will be responsible for research and development, including clinical development, and for worldwide commercialisation of products. As part of the research and development activities, MSD has entered into a research collaboration with CTx focusing on blood disorders, which MSD will fund.
CRT will receive an upfront payment of $21.3 million and is eligible to receive potential payments of up to $0.7 billion for achievement of development, regulatory and commercialisation milestones. In addition, the agreement provides for royalties on sales. All payments will be shared between CRT, CTx and the Wellcome Trust with the majority being returned to CTx and its Australian research partners. It is believed to be one of the largest licensing deals ever made for a drug target in Australia.
According to Professor Jane, the early process from initial discovery to commercialisation was “extremely difficult, and cobbled together with support from a variety of sources. Only with the advent of the partnership with CTx did the commercialisation pathway become clearer, emphasising the need for similar pathways for new discoveries in the future".
Dr Warwick Tong, CTx chief executive, said: “This is a great result for Australian science and the CRC Program as a whole and further demonstrates what can be achieved when science and commercialisation capabilities unite”.