A team of Walter and Eliza Hall Institute researchers have been recognised for their role in the development of a new anti-cancer medicine, receiving the 2018 Clunies Ross Knowledge Commercialisation Award from the Australian Academy of Technology and Engineering (ATSE).
(L-R) Professor Andrew Roberts, Associate Professor Guillaume Lessene, Associate Professor Peter Czabotar and Professor David Huang have received the 2018 Clunies Ross Knowledge Commercialisation Award.
Venetoclax (marketed as VENCLEXTA® and VENCLYXTO®) is a medicine that is now approved for clinical use in Australia, North America and Europe for the treatment of people with certain advanced forms of chronic lymphocytic leukaemia (CLL). CLL the most common type of leukaemia diagnosed in Australia.
At a glance
The ATSE’s Clunies Ross Awards recognise Australians who have shared their vision and knowledge to apply technology for the benefit of Australia.
The 2018 Clunies Ross Knowledge Commercialisation Award recognises the contributions of a team of Walter and Eliza Hall Institute scientists to the development of anti-cancer agent venetoclax.
Venetoclax was co-developed by Walter and Eliza Hall Institute scientists in collaboration with the companies Genentech, a member of the Roche Group, and AbbVie, and has its basis in fundamental research discoveries made at the Institute.
Translating research discoveries to a treatment
The development of venetoclax has its foundation in a research discovery at the Institute in the 1980s, that a protein called BCL-2 can make cancer cells immortal by preventing a form of programmed cell death called apoptosis.
Professor David Huang, whose research has investigated cell death since the 1990s, said the team had a long-term goal of developing a new anti-cancer treatment that killed cancer cells by inhibiting BCL-2. “Venetoclax was the first drug of this kind to be approved for regular use in the clinic,” he said.
“It has been thrilling to work with our team and our industry partners to see the translation of our laboratory research to clinical benefit. We are honoured to receive the Clunies Ross Award from ATSE.”
Clinical trials of venetoclax demonstrated its benefit as a treatment for people with certain forms of CLL who had no other treatment options, said Professor Andrew Roberts, who is the Head of Clinical Translation at the Walter and Eliza Hall Institute, a clinical haematologist at the Royal Melbourne Hospital and the Peter Mac, and also holds the Metcalf Chair of Leukaemia Research at the University of Melbourne and Victorian Comprehensive Cancer Centre.
“It was exciting and rewarding to be part of the journey that saw a fundamental research discovery developed to benefit patients,” Professor Roberts said.
“The initial clinical trials of venetoclax took place at sites including the Royal Melbourne Hospital and the Peter Mac, which meant that Australian patients were the first in the world to benefit from Australian innovation.”
The power of collaboration
The three-dimensional structure of BCL-2 family proteins were key to the development of venetoclax.
The research fields of structural biology and medicinal chemistry were crucial for the development of venetoclax. Associate Professor Peter Czabotar led research that revealed three-dimensional structures of target proteins. These provided ‘blue-prints’ for developing venetoclax through the team’s collaboration with AbbVie and Genentech.
“Our research benefited from the depth of structural biology expertise in the Institute, and from our access to the Australian Synchrotron,” Associate Professor Czabotar said. “By visualising detailed structures of BCL-2 family proteins, we could see how medicines could be developed that were highly specific for BCL-2.”
The early work to develop drug-like molecules that specifically blocked BCL-2 family proteins was led by Associate Professor Guillaume Lessene. “These proteins presented technical challenges that needed to be overcome in our quest for inhibitory molecules,” Associate Professor Lessene said. “The depth of expertise in medicinal chemistry at the Institute was critical for the project to reach the point at which we could secure industry collaborations to progress the research further.”
Walter and Eliza Hall Institute director Professor Doug Hilton AO said the story of venetoclax was an important example of Australian science having a global impact.
“Venetoclax is a great demonstration of the power of collaboration,” he said. “David, Andrew, Peter and Guillaume led the team that brought together skills in cancer research, structural biology, medicinal chemistry and clinical translation that, when combined with the strengths of our commercial partners AbbVie and Genentech, enabled us to see a laboratory discovery translated into a new medicine.
“I hope the recognition the Clunies Ross Knowledge Commercialisation Award provides to this team will inspire other Australian researchers to pursue similar journeys.”
The Walter and Eliza Hall Institute acknowledges the contributions of its funding partners to its cell death research, including the Australian Cancer Research Foundation, the Australian Government, Cancer Council Victoria, the Leukaemia Foundation of Australia, the Leukaemia and Lymphoma Society, and the Victorian Government.
