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Increasing the precision of cancer medicine

Norway’s strengths in immunology and cancer R&D have probably not gone unnoticed by anyone within the Nordic life science industry, and perhaps also beyond. Next in a line of promising Norwegian spin-outs is Oncosyne – with a quest to become a leading provider of cell-based cancer diagnostics.

Cancer is the second leading cause of death globally and accounted for nearly ten million deaths in 2020 according to statistics from the WHO (nearly one in six deaths). Despite these dark numbers, great progress is being made, including groundbreaking new treatments and approved new medicines, also from the Nordic region. Promising approaches and solutions are also being developed within cancer diagnostics, which is the area that Oslo-based Oncosyne is focusing on.

Often the oncologists are forced to take a one-size-fits all approach. This is wasteful for society and detrimental for all the patients who only get the side-effects and lose valuable time.”

“We and others believe there is a huge potential in increasing the precision of cancer medicine. Our vision is to provide world-leading diagnostic tools that give cancer patients significantly longer and better lives,” describes Jarle Bruun, CEO and co-founder of Oncosyne. “Currently, the clinicians have hundreds of anti-cancer drugs potentially available, but they lack accurate tools to identify for whom these drugs work and do not work. Often the oncologists are forced to take a one-size-fits all approach. This is wasteful for society and detrimental for all the patients who only get the side-effects and lose valuable time.”

Overall, most cancer patients receive limited clinical benefit from their cancer drugs, elaborates Bruun.

“Case in point, work published from Professor Vinay Prasad’s lab shows that the objective response rate of chemotherapy across advanced cancers is less than 50%. Furthermore, the majority of patients are currently ineligible for targeted therapy. Even for patients with “actionable” mutations such as BRAFV600E, the response rate of targeted treatment is often disappointingly low, in colorectal cancer for instance, about 30%,” he says.

Breakthroughs in stem cell biology over the past 10-15 years have made it possible to relatively rapidly and reliably establish long-term cultures of individual patient tumors. This combined with advances in robotics, microfluidics, and machine learning has made it feasible to develop personalized in vitro diagnostic drug testing, explains Bruun. Pre-company, Bruun and his co-founder Peter W. Eide were central in building a research platform to test this concept on patients with colorectal cancer liver metastases. The first paper coming out of this work (Bruun et al., 2020) showed that, in terms of drug response, different hepatic lesions from the same patient were highly similar.

“From a clinical perspective, this is extremely important, as it would be unfeasible to get a viable sample from all lesions (not to mention occult micrometastases…),” emphasizes Bruun.

Encouraged by these results and with a strong passion to develop new technology for better patient treatments, Bruun and Eide decided that this concept needed to be turned into a diagnostic product.

A functional precision medicine approach

Currently, the state-of-the-art is to detect a limited set of predictive mutations in the patient’s cancer by DNA-sequencing. Importantly, DNA-sequencing has been unable to identify clinically useful biomarkers for response to chemotherapy, which constitutes the bulk of prescribed – and least expensive – anti-cancer drugs.

Our own research shows that this functional precision medicine approach can identify potentially effective drugs for more than 80% of patients with metastatic colorectal cancer.”

“Most drug effects cannot be predicted simply by static genomic information alone because the biology and functional responses of cancer cells are determined by non-genetic mechanisms in a dynamic living system. With our technology, the effect of the drug is directly tested in vitro on the patient’s own living cancer cells,” says Bruun. “Our own research shows that this functional precision medicine approach can identify potentially effective drugs for more than 80% of patients with metastatic colorectal cancer, including standard-of-care generic anti-cancer therapies, and independent early studies show that the technology may achieve a predictive accuracy of over more than 80%.”

Compared to their competitors’ platforms for cell-based in vitro diagnostic screening, he believes that Oncosyne is well-positioned. “Our technology stack is state-of-the-art, the analytical performance validation has been very good, and the clinical performance study is designed to show signals of clinical benefit – the key factor that will determine market success,” he says.

 

Patient-derived tumoroids from colorectal cancer stained with fluorescent markers. Photo: Oncosyne

 

Both stressful and rewarding

That being said, history has shown that turning promising research into clinical benefit is exceedingly difficult. Still, this has always been the key driver, says Bruun. “For us, it started in the cell lab more than 15 years ago, where my co-founder Peter W. Eide and I became friends through our shared passions for science and technology. We are both former cancer researchers at the Radium Hospital in Oslo and were searching for the most promising technologies to fight the disease.”

High-throughput drug screening was of particular interest and they were given unique opportunities by their former group leader, Professor Ragnhild A. Lothe, to build large pharmacological databases on cancer cell lines in collaboration with the Institute for Molecular Medicine in Finland, and subsequently to establish a translational research platform for pharmacogenomic analysis of patient-derived organoids from metastatic colorectal cancer, the initial key result mentioned earlier.

The four key challenges we saw were related to improving accuracy, precision, scalability, and reproducibility.”

“For us, the question was how to bring this technology further, faster, into a robust diagnostic product. The four key challenges we saw were related to improving accuracy, precision, scalability, and reproducibility,” says Bruun.

Narrowingly focusing on these was not easy to reconcile with priorities of academic research, he adds. “To go all-in on building a scalable platform for in vitro diagnostics, we quit our jobs and put our savings into starting Oncosyne. The second year we recruited a talented product developer, Christer A. Andreassen, to speed things up in the lab. We’re still unsure whether we were lucky or unlucky with the timing; building the lab in a pandemic lockdown with a plastic supply crisis superseded by strong macroeconomic headwinds. The first three years have been both stressful and rewarding, but we believe we are very well positioned for the next phase of clinical validation.”

In 2021 the company became part of the Oslo Cancer Cluster Incubator’s (OCCI) dynamic growth environment and in January 2023 the team moved its pipeline into a dedicated laboratory space there.

“We came into this field from academic research with an entrepreneurial mindset and a plan to build a diagnostic technology platform. To turn this plan into reality, coaching from Oslo Cancer Cluster Incubator’s (OCCI) experienced advisors, Dr. Thomas Andersson and Dr. Janne Nestvold, has been invaluable,” says Bruun.

The incubator also offers top lab facilities with flexibility to adapt to the individual company’s needs and this has been very valuable for us when gradually building up the platform.”

Concretely, Bruun and his team were for example put in touch with world-leading expertise in IP, medical device regulation, and clinical advisors. “The incubator also offers top lab facilities with flexibility to adapt to the individual company’s needs and this has been very valuable for us when gradually building up the platform,” Bruun adds.

He believes there are a lot of opportunities for support in Norway for a company like Oncosyne. Specifically, OCCI and the collaboration with Akershus University Hospital have been invaluable. “We have also been fortunate to receive considerable project support from Norway Health Tech, Innovation Norway, Regional Research Fund-Oslo, and Eurostars/Norwegian Research Council,” he adds.

Key challenges however are limited access to competence in the in vitro diagnostic business development area, regulatory certification processes and patenting within biotech.”

Key challenges however are limited access to competence in the in vitro diagnostic business development area, regulatory certification processes and patenting within biotech, says Bruun. “However, we have access to this competence in Sweden and the UK through the OCCI network.”

Huge potential

Since the inception of Oncosyne the company has tested and verified the platform’s technical performance in a clinical observational study, TargetCRC, where more than 40 patients with primary colorectal cancer have been included. In the verification phase, it has had a 80% culture success-rate and is now finalizing documentation for a follow-up clinical performance study.

“In this study, the target population is patients with progressing metastatic colorectal cancer that have exhausted standard-of-care options. The aim is to document clinical feasibility and detect signals of clinical benefit,” says Bruun.

Personalized drug screening can make clinical trials much more efficient and has huge potential as companion diagnostics.”

So what does the future hold?

“The aim is to provide diagnostic drug screening as a service for hospitals and healthcare systems. When the clinical performance study starts early next year, we will start exploring the drug development market. Already, we have a research collaboration with Isofol Medical. Personalized drug screening can make clinical trials much more efficient and has huge potential as companion diagnostics. Long-term, we aim for Oncosyne to become a global, leading provider of cell-based cancer diagnostics,” concludes Jarle Bruun.

Featured photo of Peter W. Eide, Christer A. Andreassen and Jarle Bruun. Photo: Xuan Jiang

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