Developing targeted protein degraders into innovative cancer medicines

A shared ambition to develop a new class of anti-cancer therapeutics has brought WEHI and Boehringer Ingelheim, a leading research-driven pharmaceutical company, together in an effort to ‘drug the undruggable’.

Founded in 1885, Boehringer Ingelheim is a global pharmaceutical company focused on developing innovative drugs in the areas of cardiometabolic diseases, immunology and respiratory research, central nervous system diseases, retinal health, and oncology and cancer immunology.

The collaboration between WEHI and Boehringer Ingelheim builds on pioneering discoveries made at WEHI over the past 25 years, to reveal the biology of a family of proteins known as the inhibitor of apoptosis proteins (IAPs) and their role in cell death.

Innovative approach

A team involving laboratories across WEHI, led by cell death researcher Professor John Silke, will extend this knowledge to develop new therapeutics using an exciting new approach called targeted protein degradation.

Targeted protein degradation uses in-built protein recycling machinery within the cell to destroy a particular disease-causing protein of interest. In contrast, traditional drug discovery uses small molecule inhibitors to bind to proteins and block their action and is limited in its application to proteins with specific characteristics. Using targeted protein degradation, IAPs could also be harnessed to target other disease-causing proteins within the cell for destruction. It has the potential to dramatically expand the field of proteins that can be targeted by a therapeutic.

Professor Silke said he saw immense potential in this innovative approach. “We believe that, together with Boehringer Ingelheim, we can apply this novel IAP-based approach to a number of ‘undruggable’ disease targets that have proven intractable to more traditional drug discovery approaches. This collaboration will complement the drug discovery capabilities of the National Drug Discovery Centre at WEHI and expand our ability to translate research into new treatments for cancer.”

Visualisation of protein degradation
Above: In the Targeted Protein Degradation approach, a small drug molecule (pink, centre) is developed that can destroy a disease-causing protein (orange, left) by bringing it into proximity with part of the cell’s protein recycling machinery (multicoloured, right), such as an IAP protein. Image generated by Dr Michael Roy using UCSF ChimeraX

Academic-industry alliance to ‘drug the undruggable’

The partnership between WEHI and Boehringer Ingelheim combines broad and deep expertise in biology and therapeutic targeting of IAP proteins, protein degradation and drug discovery and development. The collaboration focuses on the generation of IAP-based protein degraders (IPDs) that can be used for therapeutic concept work and in vivo studies.

Head of Drug Discovery Sciences at Boehringer Ingelheim’s Vienna Research Site, Dr Peter Ettmayer, said he was looking forward to a fruitful collaboration.

“We have found unique, world-class scientific knowledge on the IAP family of proteins at WEHI. This partnership gives us the opportunity to leverage WEHI’s expertise and turn it into drug candidates through a collaborative program,” he said.

The three-year collaborative project will be conducted under the direction of a joint steering committee, leveraging existing capabilities and expertise within WEHI and Boehringer Ingelheim. Post collaboration, Boehringer Ingelheim will be responsible for further development, regulatory approvals and commercial activities while WEHI will receive milestone payments and royalties on sale. Financial terms of the collaboration remain undisclosed.

WEHI Head of Biotechnology and Commercialisation Dr Anne-Laure Puaux said the two organisations structured a sophisticated and mutually beneficial deal that established key business principles and laid the foundations for a strong relationship.

“This exciting collaborative program is a testament to our ability to work together with global industry partners to deliver potential ‘first-in-class’ drug candidates. Academic-industry partnerships hold immense potential for translating research discoveries into new treatments for patients,” Dr Puaux said.

Alliance Manager at Boehringer Ingelheim, Dr Karl-Heinz Heider, said the organisations had worked collaboratively to secure the deal.

“The alliance between WEHI and Boehringer Ingelheim was built upon insightful scientific discussions and has laid the foundations for a strong partnership built on trust between the two organisations,” he said.

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