January 29, 2019

First-in-class drug for blood cancers discovered by Ontario researchers receives record-setting industry investment

Years of hard work by OICR’s Drug Discovery group and Ontario partners moves potential new treatment for leukemia towards clinical trials

On January 29, 2019, Celgene Corporation made an investment of up to US$1 billion that will facilitate further research and development of the potential drug and support clinical trials in Ontario. The potential drug was designed to exploit a weakness in leukemia centred on the protein WDR5 that was discovered by Ontario researchers. If all options under the investment are exercised, the deal will be the largest transaction to date for a preclinical asset discovered in Canada.

“The progress of this pre-clinical drug towards the clinic is an example of how OICR, working with its partners, is accelerating cancer research in Ontario and increasing investment so that new innovations can help patients as soon as possible,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “This announcement shows how OICR and FACIT’s unique model for research and commercialization can generate long-term impact for the province of Ontario.” FACIT is OICR’s strategic commercialization partner.

The WDR5 project’s development demonstrates the unique expertise of OICR DD, the advantages to the OICR-FACIT model, and how OICR effectively harnesses the strengths of Ontario’s diverse cancer research ecosystem by collaborating with groups such as the Structural Genomics Consortium (SGC), the group that initially identified the potential of targeting WDR5 as a treatment for cancer.

This investment shows how Ontario’s innovative researchers and their collaborative spirit are driving the development of leading-edge cancer therapies to help patients worldwide and boosting Ontario’s economy by creating jobs in its life sciences sector. The path they took to this achievement is a unique, made-in-Ontario story.

Finding the ‘chemical hook’ for the gene MLL-1

MLL-1 is a gene well-known to play a role in driving the growth of many types of cancer. In particular, malfunction of MLL-1 has been identified as an important factor in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). There are still large unmet patient needs in these cancers that warrant additional research.

Over the last several years, OICR DD has been working with researchers from SGC at the University of Toronto to develop a chemical inhibitor that disables MLL-1 in a novel and ingenious way by specifically targeting WDR5, a scaffolding protein within the MLL-1 protein complex.

Given that WDR5 is a linchpin in this complex, the OICR-SGC team discovered that disrupting the MLL-1/WDR5 interaction with a drug-like compound provided a novel and efficient way to turn off MLL-1 and halt its ability to drive cancer.

“The method we have developed has the advantage of targeting a scaffolding protein that we hope will be more difficult for the cancer to mutate, reducing resistance and relapse. This will hopefully provide longer lasting remissions,” says Dr. Rima Al-awar, one of the leaders of the project and Director and Senior Principal Investigator, OICR DD. Additionally, by specifically targeting WDR5 the group has been able to optimize selectivity as opposed to targeting the MLL-1 complex itself, which has several close family members.

The WDR5 project began at SGC, a close collaborator of OICR DD that is also located in the MaRS Centre in Toronto. The team at SGC, led by Dr. Cheryl Arrowsmith, Chief Scientist, identified WDR5 as a potential target for disabling the activity of MLL-1. The group brought their findings to OICR DD, to further investigate WDR5 together and assess the potential for targeting the protein complex with drug-like molecules.

Dr. Aled Edwards, SGC’s Director, says that while the initial discovery of WDR5’s potential was exciting, it was difficult to see a clear path to move the project forward until they had what he calls a ‘chemical hook’, which in this case was a compound that could bind and block WDR5. “The group at OICR had done a lot of hard work in aggregating compound libraries that we then used together to try and find an inroad to making the chemistry work,” explains Edwards. “When we found a compound that fit WDR5, it was the inflection point, and things suddenly went from impossible to possible.”

Collaboratively building the path to commercialization

Moving innovative treatments into the clinic requires more than just great science. It also depends on having a strong commercialization strategy that can attract the necessary partners and investors to help research projects along the long road of development.

Early in the development of the WDR5 project, OICR DD partnered with FACIT to create a commercialization strategy and secure resources to bring their new innovation to the clinic. FACIT provided the necessary business, industry and management expertise as well as seed capital and start-up resources to support and accelerate the project. The early integration of FACIT and OICR’s expertise allowed them to develop the WDR5 inhibitor with a viable commercialization approach – a challenging feat for any laboratory. OICR DD leadership was essential in bringing extensive industry experience and perspectives to move this discovery towards the clinic.

“This partnership allows us to better position our projects to advance them into development, which is essential to the process of getting discoveries from bench to bedside,” says Al-awar. Together, OICR, FACIT and their differentiated approach to commercialization ensured the WDR5 project had the best chance to make an impact.

“Translating cancer breakthroughs requires many skill sets, from basic research to clinical and industrial expertise,” says Dr. David O’Neill, President, FACIT. “The OICR-FACIT model pulls these strengths together to maximize the benefits of Ontario’s innovations in the province. OICR’s collaboration with SGC provided a great foundation for the WDR5 project, which resulted in interest from several potential strategic partners to accelerate this program to patients.”

Generating value from open collaborations

WDR5 was a unique asset from a commercialization perspective because it began in 2014 as an open drug discovery project. As with many open science projects, data were shared with the scientific community, including the structure of an initial WDR5 chemical probe. Conducting research in an open manner allowed the team to tap into a vast international network of experts, especially those that were able to test and demonstrate the efficacy of the WDR5 probe in cells. “Open science projects have to deal with less red tape, and fewer costs and legal issues that can sometimes slow down other projects,” explains Edwards.

Often, open science initiatives and traditional drug discovery initiatives, which have proprietary intellectual property, have different business models and use incompatible approaches to commercialization. The WDR5 project showed these approaches can be compatible, and the unique collaboration produced a chemical probe that was shared with the global academic community, which led to a better understanding of leukemia biology and therapeutic strategies.

OICR scientists were able to refine the chemical probe into an improved drug-like compound, which can now be tested in clinical trials. In drug discovery, having a strong way to protect the market for a molecule is a necessary step to attract clinical trial support from industry partners and ensure economic return on innovative research. Hence, coming up with a candidate drug and advancing leukemia biology is a great success of the many scientists associated with the OICR-SGC collaboration.

Al-awar recognizes that although open drug development has its advantages, it can sometimes bring challenges. “In order to attract the necessary investment and partners to move our work toward a drug that can be used in the clinic, we took the open data and carved out something new and unique. By tapping into FACIT, we were able to visualize the commercial potential of the asset, and subsequently create and protect intellectual property (IP). FACIT has been an invaluable partner.”

A differentiated strategic partnership

Other challenges that come with commercializing oncology research include sustaining long development times, finding the right fit with investors and partners, securing seed funding at an early stage, and competing with established players in the biotech field. The unique strategic partnership between OICR and FACIT has been established to address these challenges and commercialize Ontario’s best oncology innovations.

“The WDR5 project and the value of this IP reflects the close-knit relationship of discovery and commercialization. In recognizing they had the expertise to accelerate and develop a potential first-in-class, druggable version of the probe, OICR Drug Discovery flagged this opportunity to FACIT,” says O’Neill.

Once the potential of WDR5 was realized, FACIT quickly provided tools and services to move the project along, including the establishment of a start-up company called Propellon Therapeutics and providing Propellon with interim management and invested seed capital.

“FACIT’s resources and funding ensured Propellon moved to the next stage of development and growth in Ontario,” says O’Neill. “The seed investment allowed the start-up to maintain momentum and begin to identify strategic partners in the pharmaceutical industry and additional investors most committed to development in the province.”