July 24, 2019

OICR funding for Ontario drug discovery projects will accelerate development of new cancer therapies

The Ontario Institute for Cancer Research (OICR) has selected two new Late Accelerator projects to receive support through its Cancer Therapeutics Innovation Pipeline (CTIP) initiative. The projects, detailed below, will each receive up to $250,000 per year, for up to two years, to advance the development of drug candidate molecules. The projects were selected by an international expert review panel from 18 applications.

By joining the CTIP portfolio, these projects will receive more than just financial support – they will also benefit from the guidance of the Therapeutics Pipeline Advisory Committee, a group of industry and academic experts that provides advice on the scientific and strategic direction of CTIP projects.

“CTIP projects have great potential to improve treatment for patients, promote scientific collaboration and drive investment to Ontario’s biomedical research sector,” says Dr. Christine Williams, OICR’s Deputy Director and Head of Therapeutic Innovation. “These new projects are great examples of the innovative cancer therapeutics research happening in our province. We are excited to add them to CTIP’s portfolio of promising drug candidates and look forward to their progress.”

Funded projects

Identification of kinase inhibitors to block the tumour-promoting activity of YAP/TAZ for cancer therapeutics

Liliana Attisano, Principal Investigator, University of Toronto

Rima Al-awar, Principal Investigator, OICR

Frank Sicheri, Co-investigator, Lunenfeld-Tanenbaum Research Institute

Jeff Wrana, Co-investigator, Lunenfeld-Tanenbaum Research Institute

David Uehling, Co-investigator, OICR

Richard Marcellus, Co-investigator, OICR

Methvin Isaac, Co-investigator, OICR

The highly conserved Hippo pathway is a key regulator of cell and tissue growth. Virtually all solid tumours display pathway disruptions, which drive cancer initiation and progression. Mutations in pathway components are rare, making it unclear how to target the pathway for cancer treatment. This research group has shown that certain kinases are key regulators of the pathway that promotes tumorigenicity and observed that diverse human cancers display elevated levels of these kinases. Kinases are highly amenable to the development of targeted inhibitors; therefore, this project will identify potent and specific inhibitors with the long-term goal of establishing novel cancer therapeutics.

Development of kinase inhibitors for ovarian cancer: A novel first in-class immune-oncology therapeutic agent targeting tumor intrinsic stress states

Rob Rottapel, Principal Investigator, Princess Margaret Cancer
Centre

Tracy McGaha, Principal Investigator, Princess Margaret Cancer
Centre

Rima Al-awar, Principal Investigator, OICR

Methvin Isaac, Co-investigator, OICR

David Uehling, Co-investigator, OICR

Richard Marcellus, Co-investigator, OICR

Ahmed Aman, Co-investigator, OICR

The development of new cancer immune therapeutics has triggered a revolution with the recent advent of diverse strategies that engage the patient’s immune system. This research group has identified a novel kinase target that has the unique property of being both an emergent essential gene in high-grade serous ovarian cancer and a repressor of the innate and adaptive immune system. Additionally, they have demonstrated that target inhibition sensitizes cancer cells to cisplatin – a standard of care chemotherapy drug. This project will work to develop a “first-in-class” dual-action, anti-tumour and immune-oncology kinase inhibitors for ovarian cancer and potentially other cancer types.

May 21, 2019

Activating the immune system to fight cancer

Dr. Brigitte Thériault, a Senior Research Scientist at OICR, discusses the work of the Drug Discovery team to develop new drugs that awaken the body’s immune system to recognize and attack cancer cells.

March 8, 2019

Moving in vivo: A case of navigating through translational research roadblocks

OICR’s Drug Discovery team and Princess Margaret Cancer Centre researchers collaborate to turn a research discovery into a potential cancer breakthrough

For more than three decades, researchers have tried to develop drugs that target the MYC oncoprotein – a protein that can contribute to half of all cancers – but traditional approaches to blocking MYC have not been successful. The structure of the MYC protein makes it ‘undruggable’; it cannot be blocked by a small molecule or a drug, so new strategies to inhibit the activity of this protein are needed.

Dr. Linda Penn, Senior Scientist at the Princess Margaret Cancer Centre, recently discovered a new way of preventing MYC from promoting cancer growth by stopping the interaction between the MYC protein and a ‘druggable’ partner protein, G9a.

Dr. Linda Penn

“We investigated MYC and discovered G9a as a key partner protein. We blocked G9a using both genetic and pharmacological strategies. We saw that inhibiting G9a using an inducible knockdown strategy had the potential to melt tumour cells away,” says Penn. “But for some reason, no matter what we tried, we didn’t see the tumour-fighting effect of the G9a compound inhibitor in animal models. Something didn’t line up.”

A discovery like Penn’s, however, can only be brought to patients if it can first be demonstrated in living experimental models, also known as in vivo. The results of Penn’s in vivo experiments were inconclusive, preventing her from publishing her promising findings in a top-tier journal and advancing this line of research.

Navigating the preclinical minefield

The compound – or molecule – that Penn’s team was using to block G9a in vitro wasn’t doing the same in vivo and they didn’t understand why. Lacking the medicinal chemistry expertise needed to solve this problem, Penn turned to OICR’s Drug Discovery group.

Dr. Ahmed Aman

“All of Dr. Penn’s experiments and all of the published literature implies that the compound should have worked, but unfortunately that wasn’t her observation,” says Dr. Ahmed Aman, Principal Research Scientist in the Drug Discovery group at OICR. “We had to break this problem down and solve it methodically while considering the various factors that could have contributed to these results.”

The Drug Discovery team evaluated the compound and found that it didn’t have the drug-like properties necessary to demonstrate activity in vivo. More specifically, they discovered that the compound would break down in the body before having a chance to inhibit G9a. Although the compound that they tested would not be useable as a drug, Penn’s study was now conclusive. Finding the missing piece of the puzzle allowed her team to publish their discovery in Cancer Cell and proceed with identifying and investigating new compounds to target G9a more effectively.

Collaboration to translation

Penn says that she worked with the Drug Discovery group because of their stellar reputation in the industry, strong track record and unique expertise.

“Without the Drug Discovery team, I really don’t know where I would have gone,” says Penn. “I simply didn’t have established relationships with medicinal and analytical chemists nor private industry to help me solve these chemistry problems.”

Together, Penn and the Drug Discovery group are continuing to investigate G9a and how to block it from interacting with the MYC protein. They are using another reported G9a inhibitor, which has been prepared in-house by the Drug Discovery team that Aman says should be able to work much more effectively in vivo.

“Our collaboration with the Penn group is a great example of how we hope to leverage our drug discovery capabilities to support investigators across Ontario and advance their research efforts,” says Dr. Rima Al-awar, Director and Senior Principal Investigator of OICR’s Drug Discovery group.

Learn more about OICR’s Drug Discovery services and capabilities through the Collaborative Research Resources directory.

February 21, 2019

OICR supports cancer drug discovery in Ontario with new funding for four promising early-stage projects

Toronto (February 21, 2019 | Updated July 15, 2019) – The Ontario Institute for Cancer Research (OICR) today announced that three Early Accelerator projects from across Ontario will each receive $100,000 for one year as part of OICR’s Cancer Therapeutics Innovation Pipeline (CTIP) initiative. The funding will be used to validate cancer targets and support experiments to screen molecules against these targets, finding those that can bind to them successfully and have potential to be developed into medicines.

Continue reading – OICR supports cancer drug discovery in Ontario with new funding for four promising early-stage projects

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.

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

September 13, 2018

FACIT invests in three top Ontario entrepreneur-teams from near record pool of applicants

Prospects Oncology Fund seeds developing pipeline of Ontario-based biotech innovations

TORONTO, ON (September 13, 2018) – With an expanding portfolio of breakthrough innovations, FACIT is committed to supporting Ontario entrepreneurs through the latest round of its Prospects Oncology Fund. FACIT has selected three novel cancer therapeutic discoveries to receive early-stage capital – biotechnology start-up Talon Pharmaceuticals (“Talon”), the Drug Discovery team at the Ontario Institute for Cancer Research (“OICR”) and CCRM. The Prospects Fund provides entrepreneurial scientists with the capital resources necessary to achieve critical proof-of-principle studies for their cutting-edge breakthroughs aiming to benefit future patients.

Continue reading – FACIT invests in three top Ontario entrepreneur-teams from near record pool of applicants

September 4, 2018

Meet our students – 2018

Meet Dike Aduluso-Nwaobasi, Sarah Donald and Benson Wan. Find out how summer co-op positions affected their career and educational journeys.

August 22, 2018

Meet the researchers: Ratheesh Subramaniam

Ratheesh Subramaniam talks about his work in OICR’s Drug Discovery team and how it could help doctors make a difference in treating cancer patients.

July 31, 2018

Can an open drug discovery model find a solution for rare brain cancers in children?

Dr. Aled Edwards

Dr. Aled Edwards

OICR-funded drug discovery project’s unique ‘open science’ business model is accelerating the search for a solution to lethal pediatric brain cancers

Diffuse intrinsic pontine glioma (DIPG) is a lethal and inoperable brain cancer with a median survival of less than a year from diagnosis. Finding solutions to this disease is challenging due to its rarity, scientific complexity and its presentation in pediatric populations. An OICR-funded team of researchers, led by Dr. Aled Edwards from M4K Pharma, have developed new potential drug candidates for DIPG that they will test in animal models in the coming months. They’ve reached this milestone ahead of schedule, with fewer resources required than anticipated, by using an ‘open drug discovery’ approach – sharing their methods and data with the greater research community to streamline the drug discovery process.

Continue reading – Can an open drug discovery model find a solution for rare brain cancers in children?

December 4, 2017

OICR launches groundbreaking Cancer Therapeutics Innovation Pipeline to drive cutting-edge therapies to the clinic

Ten new projects were selected in the pipeline’s inaugural funding round, highlighting Ontario’s strengths in collaboration and drug discovery.

Toronto (December 4, 2017) – The Ontario Institute for Cancer Research (OICR) today announced the Cancer Therapeutics Innovation Pipeline (CTIP) initiative and the first 10 projects selected in CTIP’s inaugural round of funding. CTIP aims to support the local translation of Ontario discoveries into therapies with the potential for improving the lives of cancer patients. The funding will create a new pipeline of promising drugs in development, and attract the partnerships and investment to the province necessary for further clinical development and testing.

“Ontario congratulates OICR on this innovative approach to driving the development of new cancer therapies,” says Reza Moridi, Ontario’s Minister of Research, Innovation and Science. “The Cancer Therapeutics Innovation Pipeline will help ensure that promising discoveries get the support they need to move from lab bench to commercialization, and get to patients faster.”

Continue reading – OICR launches groundbreaking Cancer Therapeutics Innovation Pipeline to drive cutting-edge therapies to the clinic

March 22, 2017

FACIT Announces Investment in Propellon Therapeutics

Seed financing of CAD$3.0M positions first-in-class WDR5 cancer therapy for clinical development

TORONTO, March 22, 2017 /CNW/ – FACIT announced a seed stage investment in Propellon Therapeutics (the “Company” or “Propellon”), a start-up created by FACIT focused on developing a portfolio of WDR5-targeted anti-cancer therapeutics. FACIT’s investment, combined with non-dilutive capital, achieves a targeted $3.0M financing for the lead program. The seed funding enables Propellon to accelerate the nomination of a candidate drug and position the Company for financing and/or entering a strategic partnership for clinical trials in patients with haematological cancers.

Continue reading – FACIT Announces Investment in Propellon Therapeutics

February 10, 2017

How chemical probes can boost cancer research

Dr. David Uehling in the Lab.

Guest post by David Uehling, PhD, Ontario Institute for Cancer Research, on behalf of the Chemistry In Cancer Research Working Group, part of the American Association for Cancer Research (AACR).

The quest for a new cancer drug often begins when a protein target is implicated as an important driver in tumourigenesis. For cancer researchers, small molecules that block or stimulate such proteins can be valuable tools in research. Not only do they help us understand the role that the protein plays in cancer biology, but they also enable researchers to demonstrate which tumours are sensitive toward inhibition or stimulation with that protein target of interest, providing early clues as for patient selection and biomarker identification. Moreover, the knowledge that a small molecule can bind to such a protein builds confidence that this target is indeed “druggable,” which can provide a powerful stimulus to initiate a sustained effort to find medicines for that target.

Continue reading – How chemical probes can boost cancer research

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