In the news this week, the launch of NeuroCDRD – a new initiative to accelerate development of treatments for neuro diseases; OICR researchers invent a new molecular barcode technology; and Aurinia Phramceuticals prices a US$150.5 million public offering of common shares. We have all this and more coming up on Biotechnology Focus Radio.

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Our first story this week highlights Calgary, AB’s Oncolytics Biotech® Inc. The company has entered into a collaborative research project  with cancer charity Myeloma UK and multi-national biotech firm, Celgene.  In the joint initiative Myeloma UK has launched MUK eleven, a first-of-its-kind immunotherapy trial that aims to modulate the immune system to target myeloma. The Phase 1b trial will study Oncolytics immuno-viral therapy and lead product REOLYSIN®, in combination with Celgene Corporation's immunomodulatory drugs (IMiDs), Imnovid® (pomalidomide) or Revlimid® (lenalidomide), as a rescue treatment in relapsing myeloma patients. MUK eleven’s chief investigator Gordon Cook, Consultant Haematologist at Leeds Teaching Hospitals Trust  says this trial is about taking a new approach of activating a patient's own immune system to target their myeloma (immunotherapy) using a natural virus and lenalidomide or pomalidomide. REOLYSIN will be combined with Celgene's Imnovid® or Revlimid® in patients whose myeloma is progressing while on these IMiD treatments. The dose escalation trial will look at the safety and tolerability of these combinations, and will investigate whether the addition of REOLYSIN extends disease control in this patient group.

This clinical study expands on earlier pre-clinical work by Professor Cook that demonstrated that REOLYSIN has dual modes of action against multiple myeloma; being both directly cytotoxic and also activating immune effector cells to target and destroy cancer cells. Further, this immune-mediated activity can be enhanced by immunomodulatory agents to eliminate disease.

The trial will aim to recruit 44 patients across up to six Myeloma UK Clinical Trial Network centres in the UK. MUK eleven is part of the Myeloma UK Clinical Trial Network, a portfolio of early stage trials coordinated by the Clinical Trials Research Unit at the University of Leeds, focused on testing and speeding up access to promising new treatments for patients.

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In a unique public-private partnership, Montreal’s Cyclenium Pharma Inc. and Toronto’s Hospital for Sick Children (SickKids) have entered into a research agreement designed to facilitate the discovery of novel modulators for multiple new and existing biological targets of pharmacological interest across a variety of disease areas, including cardiovascular, immunology and oncology.  Cylenium is a company focused on discovery and development of novel drug candidates through the use of its proprietary macrocyclic chemistry. The collaboration will give SickKids researchers immediate access to the company’s QUEST Library™ of next generation macrocyclic molecules and associated chemical hit and lead optimization capabilities. The initial objective of the partnership is to identify compounds capable of interacting with specific therapeutic targets being studied at SickKids, thereby providing tools to improve the understanding of their involvement in the pathophysiology of specific diseases, with the ultimate goal of discovering novel therapeutic or diagnostic agents.

Cyclenium president, CSO and CEO Dr. Helmut Thomas.adds that his company’s library will be made available to researchers through the SickKids Proteomics, Analytics, Robotics & Chemical Biology Centre (SPARC BioCentre). The SPARC BioCentre is a high-throughput drug screening facility at SickKids. One of the first studies to be initiated involves targets implicated for the treatment of cancer and immune disorders.

For Cyclenium, this is the latest in an extensive series of international discovery collaborations established with prominent companies and research institutions to explore the exciting potential of its unique macrocycle chemistry technology, including Astellas Pharma, Haplogen GmbH, Fundación MEDINA, German Cancer Research Center (DKFZ), McGill University/Goodman Cancer Research Centre, Institute for Research in Immunology and Cancer (IRIC)/Université de Montréal, and Southern Research Institute.

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Clinical-stage drug developer Aurinia Pharmaceuticals last week announced the pricing of secondary public offering for gross proceeds of approximately $150.5 million US. As part of the offereing the company is selling 22.3 million shares at $6.75 per share. Leerink Partners LLC and Cantor Fitzgerald & Co. are acting as joint book-running managers for the Offering, that is expected to close March 20th. The cash will be very beneficial as the Victoria-based company intends to initiate a Phase 3 trial for its lead drug candidate, voclosporin, in treating lupus nephritis. The trial will commence in the second quarter. The drug successfully went through a positive 48-week data phase 2b trial in 2016 and 2017, and seems on track to becoming the first drug to demonstrate a clear benefit for the disease.

As an aside, Aurinia’s stock had hit an all-time high of $10.50 per share on March 13, the eve of the public offering announcement. By offering its shares at $6.75 the next day, new investors received a 36 percent discount. Canada’s Motley Fool reported that while it may seem as if investors are getting a raw deal, it should be noted that the stock began 2017 at just $2 per share. Motley Fool further commented that there are only 53.45 million shares outstanding today, and the company ended 2016 with less than $40 million in cash. In other words, while the number of shares will be diluted by 41.7%, the company will more than quadruple its cash.

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In Toronto,  a team of cancer researchers have identified a protein biomarker expressed on the surface of tumour cells in high-grade serous ovarian cancer, the most common and lethal subtype of the disease.

The findings, featured on the cover of the March 7 issue of Cell Reports, show that patients with high levels of the biomarker, CD151, have a poor prognosis, says lead author Mauricio Medrano, a molecular biologist and research associate at Princess Margaret Cancer Centre, University Health Network.

“Ovarian cancer is many diseases,” says Dr. Medrano. “By identifying CD151 and its underlying role in cancer cell survival, we hope to develop a therapy to target it. As a marker for poor prognosis, with further research, there is the potential to develop a clinical screening tool to help personalize cancer treatment for patients.”

The research was led by principal investigator Dr. Robert Rottapel, senior scientist and Professor, Departments of Medical Biophysics and Immunology, University of Toronto.

In lab experiments, the research team used cell lines derived from 40 patient tumour samples to identify that CD151 contributes to the survival of cells of high-grade serous ovarian cancer origin. The team further analysed tissue samples from a cohort of approximately 1,000 patients to establish the correlation of high levels of CD151 to poor prognosis.

Dr. Medrano says the study provides a lot of new information about other possible targets, not only CD151, that could be important and can provide new ideas for how to target ovarian cancer.”

The research was supported by the Ontario Institute for Cancer Research, Ovarian Cancer Canada, the Canadian Ovarian Cancer Research Consortium’s biobank funded by the Terry Fox Research Institute, and The Princess Margaret Cancer Foundation.

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Also In Toronto, Researchers at the Ontario Institute for Cancer Research (OICR), together with international collaborators, have invented a technique to avoid a major problem with common laboratory techniques and improve the sensitivity of important cancer tests. The findings, recently published in the journal Nature Protocols, describe a process by which the sensitivity of DNA sequencing can be improved. The technology, called SiMSen-Seq, could aid in detecting the recurrence of cancers, catching possible disease relapses faster than current methods and improving patient outcomes.

Essentially the scientists have created a DNA barcode with a hairpin structure that as Dr. Paul Krzyzanowski, Program Manager of OICR’s Genome Technologies Program explains opens up to be read when heated and contracts when cooled. This allows researchers to ‘hide’ the barcode and analyze more patient DNA fragments in a single reaction he says.

Cirrently, for DNA sequencing, scientists often use a technique called polymerase chain reaction (PCR) to increase the amount of DNA available from a sample. However, PCR can introduce mistakes that can limit researchers’ ability to detect real mutations in the original DNA molecules. To track the original molecules in a sample, molecular tags called DNA barcodes are added. This technique is essential for sensitive detection of mutations but can lead to other errors, as components of the tags can interfere with each other and affect the final results.

Dr. Krzyzanowski led the development of analysis pipeline software used in SiMSen-Seq which flags errors in sequencing results and corrects them computationally. Current genome sequencing technologies return results with error rates of about one per cent, meaning that for researchers to be certain that a mutation exists it has to be detected in a sample at a rate of greater than one per cent. Dr. Krzyanowski says that the SimSen-Seq technology has lowered this error rate 100-fold, meaning that the recurrence of cancers could be detected at lower levels and earlier than before, allowing patients to receive additional treatment sooner.

His team has already patented the technique, and while it can conceivably be performed in any molecular biology lab, the group also hopes to make their expertise in using the method available to the research community. Those interested in accessing this service can do so through OICR’s Collaborative Research Resources directory.

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In our final story, three leading players in Canada’s health sciences sector are joining forces to create a novel drug development platform that will help advance new therapeutics for some of the most debilitating conditions such as amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, and Parkinson’s disease.

The initiative, under the banner of ‘NeuroCDRD’, is jointly led by The Centre for Drug Research and Development (CDRD), the Montreal Neurological Institute and Hospital at McGill University (MNI), and Merck. Its initial focus is the creation of a high-content hiPSC (human-induced pluripotent stem cell) screening platform that will help researchers better model neurological disease.

Development of new drugs for neurological diseases has long been hampered by the lack of predictive humanized models, and many treatments that have looked promising in animal studies have in turn failed in subsequent human clinical trials. To mitigate this challenge, this new collaboration will use the MNI’s renowned hiPSC platform and bring together experts from MNI’s neurological and CDRD’s drug screening and assay development teams to develop a new generation of disease-specific research models using patient-derived hiPSCs. The idea is to significantly reduce research timelines and costs, making it possible to develop future hiPSC models for neurological diseases with smaller patient populations.

As Gordon McCauley, President and CEO of CDRD explains this collaborative initiative not only combines the cutting-edge science of academia, that it will also benefit from CDRD’s translational abilities, and the commercial resources of a top industry partner like Merck. “By working together, we are a catalyst for Canadian life sciences leading the world,” he said.

And that wraps up another weekly episode of the Biotechnology Focus RADIO. A special shout out to Laskey Hart who works tirelessly to produce each weeks show, and to the Biotechnology Focus research team for tracking this weeks stories.  As we’re always on the lookout for your story ideas and podcast suggestions we’d love to hear from you our listeners, to let us know what’s hot on the Canadian biotech scene.  Be sure reach out to us via twitter @biotechfocus, or by email at  [email protected] with your suggestions. And of course, you can also catch up on past episodes online via our podcast portal at www.biotechnologyfocus.ca .