Developing new cancer immunotherapies

More than two decades ago, WEHI researchers discovered ‘protein X’ was a key controller of immune cell behaviour. This drove the establishment of research tools including murine models and antibodies that enabled a deep understanding of the biology of protein X. WEHI also developed intellectual property around the use of protein X in certain immunotherapy modalities.

In 2017, WEHI entered into a partnership with a multinational pharma, ‘Partner A’. The goal of this partnership is to identify, characterise and optimise novel small molecule compounds inhibition the function of protein X, and assess their utility as cancer immunotherapies.

Separate high-throughput screens for the small molecules were undertaken in parallel by WEHI and Partner A, said Dr Jeff Mitchell, head of the National Drug Discovery Centre (NDDC) at WEHI.

“Protein X is a very challenging target. By undertaking two screens using separate libraries and combining our results, our partnership added power to the drug discovery process. The hits across the two screens had common features, helping us to identify the most promising leads,” he said.

Professor Guillaume Lessene, head of the New Medicines and Advanced Technologies theme at WEHI, which includes the NDDC, said “The short timeframe from project initiation in 2017 to hit validation in early 2019 has shown the strength of this collaborative approach. Other innovative approaches to drug discovery were also developed to complement the results from high-throughput screening, relying on structural biology and medicinal chemistry approaches, and using novel scaffolds,” he said.

“This specific target, protein X, is considered ’hard-to-drug’ and WEHI and Partner A scientists have been thinking creatively together to overcome drug discovery challenges.”

The collaboration encompasses target validation, high throughput screening, hit validation, hit-to-lead and lead optimisation stages, and will conclude when a preclinical candidate is selected. Partner A will then be responsible for conducting clinical development and obtaining regulatory approval, as well as for global commercial activities. WEHI will remain a partner in the project, receiving milestone payments and royalties on global sales as well as offering research expertise as required.

WEHI’s Head of Biotechnology and Commercialisation, Dr Anne-Laure Puaux, said it was uncommon, but beneficial for partnerships with industry to commence at such an early stage of drug discovery as in this project.

“Industry partnerships are typically formed after the discovery of a preclinical or a clinical candidate. However, in this case WEHI’s expertise in the underlying biology of the target, its comprehensive research tool kit and its capability in early stage drug discovery enabled this early stage collaboration to be initiated with Partner A – and its benefits have been proven with the rapid progression of the project on this difficult-to-drug, high-value target,” she said.

“WEHI and Partner A have complementary expertise, which drove the success of this collaboration. We are very excited to see a fundamental research discovery made at WEHI progressed towards a potential new cancer immunotherapy.”