The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Monthly Archives: January 2011

Monday Biotech Deal Review: January 31, 2011

Welcome to your Monday Biotech Deal Review for January 31, 2011.  Angiotech has voluntarily entered into CCAA proceedings and will continue its restructuring efforts there.  There was also some investment activity involving government agencies in Ontario, Quebec and Prince Edward Island.  Read on to learn more, as well as the usual assortment of biotech news reviews from the past week.  Read more of this post

Friday Science Review: January 28, 2011

Cancer’s Byzantine Architecture – The Plot Thickens

Campbell Family Institute for Cancer Research ♦ Ontario Cancer Institute ♦ University of Toronto

Published in Nature, 20 Jan., 2011

In the mid 90s one of Canada’s foremost stem cell researchers, John Dick, made the rather shocking discovery that not all cancer cells are equivalent. Based on his eloquent work we were able to formulate our current thinking on cancer biology, which has it that only a small sub-population of cells within tumours support malignant expansion, while the majority of cancer cells — although dividing — can only divide so many times before they hit cell cycle arrest and begin to senesce. Therefore, to completely eradicate a population of cancer cells, this minority of “cancer stem cells” must be targeted and destroyed. Our historical view on transformation was that single cells accumulate mutations over time, and in a step-wise fashion their genetic contents slowly mutates to the point that the cell itself loses control over its proliferation. Under this model each clone, or descendant of the original transformant, is linearly related. However, recent genomic work in the area indicates that this view is all too simple. It is now apparent that the architecture, the “framework” upon which cancer supports itself, is in fact a complex and branching network of sub-clones that each have the capacity to support tumour growth. Working with human BCR-ABL lymphoblastic leukemia cell lines, John Dick and his colleagues found that many diagnostic patient samples had several genetically distinct leukemia-initiating clones. DNA copy number alteration (CNA) profiling allowed them to reconstruct an evolutionary map of these clones. Transplantation of clones into xenograft models revealed that the predominant diagnostic clone, sometimes, but not always, was associated with the most aggressive growth properties. In some cases, interestingly, minor subclones proved to be the most potent leukemia-initiating cells. Next generation cancer therapeutics are being targeted to cancer stem cells, but now it appears — for these to be effective — they must target not only the dominant cancer stem cell clone, but all of the minor subclones that may be equally, if not more, vicious.

Freeing Systems Biology Data from the Shackles of the 2D Realm

University of Toronto ♦ Published in PLoS ONE, Jan. 10, 2011

One of the great challenges of systems biology will be to integrate multiple data sets, of widely differing scales, into an interactive and visual interface for human interpretation. Visualization is an important element in elucidating the connections between diverse data sets. Only in recent times have platforms existed that have the capacity to weave together large quantities of data into meaningful 3D representations. Historically, visualizations of biological data have been limited to 2D outputs that fail to do justice to the underlying connections between different biological processes. The need for 3D visualization tools is essential. We as humans have lived and evolved in a 3D environment and as a result have adapted a profound capacity to reason and conceptualize along three axes. In addition, biological processes occur within 3D environments, so carrying out analysis of biological data sets in three dimensions is logical. As a solution to this challenge, a group of researchers at the University of Toronto led by Dr. Nicholas Provart have created an open-source template that integrates and visualizes systems biology data as  interactive 3D representations on the world wide web. The group applied their template to the model plant organism Aribidopsis thaliana and have dubbed it ePlant. The platform incorporates proteome-scale protein structure prediction and annotation along with existing -omics scale data, and allows users to evaluate protein structure and function, protein-protein interactions, protein subcellular locations (great visual display here), gene expression patterns, and genetic variation. The result is a program that integrates systems biology data found on the nanoscale with genetic variation found on the kilometer-scale. The open-source nature and flexibility of the ePlant framework circumvents one of the major limitations of current computational systems biology tools — accessibility. ePlant does not require users to download specific data visualization and analysis software to their specific operating system, reducing the learning curve required to grasp the program. Software development on the world wide web also allows for community-driven expansion of systems biology software like that of ePlant, allowing for continued growth and refinement.

Monday Biotech Deal Review: January 24, 2010

Welcome to your Monday Biotech Deal Review for January 24, 2010.  Despite a slow financing week, there were a few operational announcements as well as awards granted to Canadian biotech companies by the NIH and the UK’s Medical Research Council.  Read on to learn more.  Read more of this post

Friday Science Review: January 21, 2011

How to Build a Retina — Hope for the Three Blind Mice

Ottawa Hospital Research Institute ♦ Review Published in Stem Cells, Jan. 14, 2011

There have been waves of progress in the stem cell world and regenerative medicine is a field that continues to amaze. In a recently published review, Dr. Valerie Wallace underlines the anatomy and developmental sequence of the retina and provides insight into the biological pathways that can be exploited to re-create retinal cells in the lab. The retina is a light-sensitive tissue found at the back of the eye that contains specialized photoreceptor cells known as cones and rods. After light passes through the lens into the eye it travels through a jelly-like substance in the middle to reach the retina. The retina then converts these photons of energy to a signal that the brain can register as an image. The key to producing functional retinal cells is in exploiting the signaling pathways and chemical cues that lead to their natural formation in the body. In 2009 a paper published in Cell Stem Cell provided evidence that human embryonic stem cell-derived photoreceptors could integrate into the retina and partially repair vision loss in blind mice. This was a pivotal study demonstrating that cell types derived in vitro can potentially be used to rescue vision. There are hopes that similar techniques will be able to treat patients suffering from a variety of retinal diseases, including glaucoma, retinitis pigmentosa, age-related macular degeneration, and diabetic neuropathy. However, as is the case with all prospective transplantation therapies, producing pure, safe, and functional populations of relevant cell types in the lab will be a difficult hurdle to jump — but certainly not one that is impossible to jump. Protocols for the derivation and identification of photoreceptor cells are currently being honed and as we continue to learn more about the developmental pathways that contribute to their formation, these cell populations will move closer to being implemented in the clinic.

Genomic Signature Cracks the Case

Pacific Biological Station ♦ Published in Science, Jan. 14, 2011

In a nice bit of detective work researchers at the Pacific Biological Station in Nanaimo, BC, have figured out the probable cause of the precipitous decline in Canada’s stock of wild salmon. Historically, as many as 8 million sockeye salmon return annually from the Pacific Ocean to spawn in the Fraser River basin. However over the past two decades these numbers have dropped rapidly as salmon die en route to their destination. In 2009 the returns to the river were less than the replacement rate, a finding that spurred a judicial inquiry into the matter. Investigators were able to correlate physiological profiles with failed migration and reproduction by taking non-lethal biopsies of gill tissue from salmon caught in the ocean and tracking salmon with radio transmitters. The gene expression profiles of fish that were successful in making the journey back to the Fraser were then compared with those that perished en route. Researchers found several genes that were associated with survivorship and noted that 60% of fish contained a gene expression signature that was predictive of in-river fate when they were greater than 200km from the mouth of the river. Several genes in the mortality-related signature had known linkages to viral activity, consistent with the finding that fish with this signature also exhibited an up-regulation in inflammatory and apoptotic processes. Researchers attribute the increased mortality of sockeye salmon to viral infection, being exacerbated by the physiological demands placed on salmon as they return from a salt water environment to a fresh water environment and begin their long journey upstream.

The Genome, The Proteome, How About the Tyrosine Phosphatome?

McGill University ♦ Review Published in Nature Reviews Cancer, Jan. 2011

We’re in the era of “-omics” and as we continue to explore the microscopic world within us we find more and more families to apply the suffix to. Protein tyrosine phosphatases (PTPs) play an important role in the regulation of numerable biological processes that are intertwined in the development of cancer. Dr. Sofi Julien and her colleagues at the Goodman Cancer Research Centre and Department of Biochemistry at McGill University have prepared an impressive review on the “human cancer tyrosine phosphatome”. The work focuses on the genetic and epigenetic alterations that may lead to loss or gain in function of PTPs that are involved in cancer formation, and provides figures illustrating such things as the location of PTP genes on chromosomes, the location of mutations in PTPs, and proposed mechanisms of both oncogenic and tumour suppressor functions. Interestingly, PTPs have modes of action that can both cause and prevent cancers depending on the cellular context. PTPs exert their effects by removing phosphate groups from target proteins, and depending on the type of protein that becomes dephosphorylated, the resulting signaling cascade can promote or suppress tumour formation. PTPs counter the effects of protein tyrosine kinases (PTKs) which add phosphate groups to target proteins as opposed to removing them. The activity of PTPs and PTKs exist in a sort of equilibrium within the body and shifts in this balance can have detrimental effects. Generally speaking members of the kinase family are considered to be oncogenic because overzealous phosphorylation activity, particularly activation of growth receptors on the extremity of cells, can lead to rapid and uncontrolled cell proliferation. Since the late 1980s, when the first true phosphatase was discovered, more than 100 have been identified by scientists. PTPs have the potential to be used as prognostic indicators for different cancer types. Investigators are also hoping that PTPs may prove to be effective drug targets for cancers where PTP hyperactivity is known to contribute to formation and onset of disease. PTP inhibitors, including natural compounds, small molecules, silencing RNAs, and anti-sense molecules are all under development. The only advanced clinical trial of an anti-PTP therapeutic is ISIS’s 113715 which targets PTPN1. The antisense molecule successfully made its way through a phase II clinical trial for diabetes. PTPN1 has been identified as an oncoprotein in a mouse model of breast cancer suggesting that it may also have utility in an oncology setting.

Biotech Trends in 2011: Biosimilars

In our original post on biosimilars, Lumira Capital’s Beni Rovinski set out the business opportunities, the technical challenges and the regulatory hurdles facing follow-on biologics in 2009. Since then, as Beni predicted, a series of pharma deals have followed Merck’s Insimed acquisition, and the regulatory framework in North America has been clarified substantially, with final Health Canada guidance having been issued and the the U.S. BCPI Act working its way through the FDA’s rule-making process.

The biosimilars market has also evolved in a couple of unexpected ways: 

  1. Teva decided not to wait for a distinct U.S. biosimilars pathway, and instead submitted a full BLA for Neupoval (which was accepted). Although Neupoval’s approval is now delayed, with the 12-year exclusivity period in the BCPI Act far exceeding similar periods in the EU and Canada, more companies may follow Teva’s approach instead of navigating the U.S. biosimilar regime.
  2. At the JP Morgan conference last week, the CEO’s of Amgen and Biogen Idec, two companies that have been built on innovator biologics, both openly discussed their own plans to produce biosimilars. Although Amgen’s Sharer said the company “should participate in an intelligent way without disturbing the core business,” and was looking to Asian and Latin American markets, Biogen Idec’s Scangos said flatly that “[t]he next decade will be about access and cost as much as it is about innovation,” and that biosimilars are “a low risk way to generate substantial revenue.”

As the regulatory and business environments continue to evolve, we’ll continue to keep an eye on the latest developments.

This post is the fourth in a series briefly outlining the biotech industry trends we’ve been following on the blog and noting some recent developments, plus directions for 2011.

Monday Biotech Deal Review: January 17, 2011

Welcome to your Monday Biotech Deal Review for January 17, 2011.  Among other things, the past week saw a third extension of deadlines for Angiotech’s debt restructuring efforts, a management-approved take-over bid of WEX Pharmaceuticals, and American DARPA money being spent on Medicago for the development of a H5N1 vaccine.  Read on to learn more.   Read more of this post

Weekend Reading: This Week in the Twitterverse

Catch up on the week’s biotech developments and news from our Twitter stream @crossborderbio:

Friday Science Review: January 14, 2011

The Eukaryotic Tree of Life Expands

Dalhousie University ♦ Published in PNAS, Jan. 4, 2011

Photosynthetic marine organisms carry out roughly half of the primary production on the planet today. Tracing the lineages of these tiny creatures has helped us document eukaryotic evolution and draw conclusions on the events that led to their current distribution and the distribution of the genetic content hidden within them. A new lineage of photosynthetic algae, being referred to as rappemonads, has been discovered by Dr. John Archibald’s lab group in the Department of Biochemistry and Molecular Biology at Dalhousie University. Phylogenetic analysis using operons from plastid ribosomal DNA indicates that this new group is indeed evolutionarily distinct. Furthermore, scientists revealed that the habitat distribution of rappemonads is wide; environmental DNA sequencing in the North Atlantic, North Pacific, and at European fresh water sites suggests an extensive diversity. Although flare-ups of this new species are rare, they are believed to be able to form transient blooms. Quantitative PCR analysis was able to detect large quantities of rappemonads rRNA in the Sargasso Sea. Discoveries of this nature bring to mind the Sorcerer II expedition — launched by Craig Venter in 2004 — where researchers traveled the world’s oceans to discover new microbial species. The field of environmental genomics is in its infancy, and has the potential to help us alleviate some of our environmental issues and elucidate many aspects of biodiversity and evolution.

Novel Vaccine Delivery Formulation Protects Against Respiratory Pathogen Challenge

Institute for Biological Sciences, NRCC ♦ Published in PLoS ONE, Dec. 29, 2011

Mucosal surfaces represent an excellent opportunity for microbial pathogens to invade the body and give rise to infections. Currently many systemic vaccines targeting these pathogens fail to elicit adequate mucosal immunity in the host. It is for these reasons that Dr. Wangxue Chen and his colleagues at the NRCC are developing mucosal vaccines that specifically target these entry points. Creating long lasting and memory boostable immune responses has proven difficult with mucosal vaccines however, and they typically require an adjuvant, or delivery vehicle, to be successful.  The team at NRCC has found that intranasal immunization of mice with a cell free extract of Fransicella tularensis has much more pronounced effects when it is paired with archael lipid mucosal vaccine adjuvant and delivery (AMVAD). The technology incorporates cell free extract, from the organism against which immunity is desired, into liposomes which can then be delivered as a vaccine. Mice receiving the AMVAD/extract preparation had lower pathogen burden in the lungs and spleen, longer mean time to death, and significantly greater overall survival than mice that received just the cell free extract or naive mice receiving no vaccination.

Oxidative Stress of Surrogate Tissues Mirrors that of the Prostate

McMaster University ♦ University of Toronto ♦ Published in PLoS ONE, Dec. 28, 2011

Researchers believe that surrogate androgen regulated tissues from the same host can be used to determine the oxidative stress (OS) status of the prostate. Androgens have long been known to drive the formation of prostate cancer. Oxidative stress is regulated by androgens, so reducing OS is a key target in the prevention of prostate cancer. Using a mouse model researchers show that the level of prostatic OS is correlated with the OS of Dermal Papillary Cells, a cell type found in hair follicles, and also the salivary glands – two exocrine glands that express the androgen receptor and are morphologically similar to the prostate. Determining the OS status of the prostate and patient response to prevention strategies directly, would require taking a biopsy sample from the prostate itself. Thus, the findings of Dr. Jehonathan Pinthus and his team at McMaster University could have great implications for the non-invasive and indirect evaluation of prostate OS status and patient response to prevention strategies.

Biotech Trends in 2011: Transgenics

As our ability to manipulate the genomes of plants and animals grows, we can increase crop yields, reduce environmental impact, improve nutrition and turn barren land arable.  Canada, in particular, has been at the forefront of much of this technology:

  • The Enviropig, developed in Guelph, Ontario, in 1999, produces phytase, an enzyme regular pigs lack, which helps it digest naturally occurring plant phosphorous in its feed more efficiently, which reduces feed costs and decreases the amount of phosphorus that winds up in pigs’ waste – making it less polluting. Recent coverage, from specialty (GenOmics video) to national to international (BBC video) highlights the animals’ great potential.
  • AquaBounty’s AcqAdvantage salmon, developed in Prince Edward Island, is even closer to approval. Although the FDA panel assigned to review the fish decided not to reach a conclusion this past Fall, they are still likely to be the first GM animal to be widely consumed by humans.  The AcqAdvantage salmon grow much more quickly than their non-GM peers and are farmed under close scrutiny, thereby improving environmental impact and reducing costs and overfishing.

Nevertheless, much of Europe continues to resist growing or importing GM strains, and the U.S., traditionally a strong supported of GM crops, seems to be wavering:

We will continue to follow these important legal, regulatory and scientific developments.

This post is the third in a series briefly outlining the biotech industry trends we’ve been following on the blog and noting some recent developments, plus directions for 2011.

Biotech Trends in 2011: Commercialization by Non-Profit Foundations

Financing for biotech companies is a major part of my work at my real job, and the horrible financing environment in the wake of 2008′s financial crisis was one of the motivators for starting this blog. So, when nonprofit foundations started financing commercialization and product development in addition to their traditional role in financing research, it was a trend this blog was quick to note.

In the years since, a steady stream of new entrants have financed a wide variety of companies and projects, and the trend has appeared in the last year as a panel and the BIO convention and in E&Y’s annual biotech industry report.

Most recently, the Canadian Cystic Fibrosis Foundation gave a $750,000 grant to a new Cystic Fibrosis Technology Initiative (CFTI) which was launched in partnership with the University of British Columbia and the Centre for Drug Research and Development (CDRD). The CFTI will “assemble researchers and identify promising discoveries from across Canada to create new medicines” for CF. Selected promising new drug candidates will be developed with CDRD. The initial application deadline is January 28th and details are available here.

With MJFF and Gates leading the way and with a continued shortage of traditional development and commercialization funding for the industry, expect to see lots more of these deals in Canada and internationally in the coming year.

This post is the third in a series briefly outlining the biotech industry trends we’ve been following on the blog and noting some recent developments, plus directions for 2011.

Biotech Financings: Preview of 2010 Data Shows Momentum for 2011

The ‘2010 Canadian Healthcare Review’, which I co-author with James Smith, Vice President Healthcare at The Equicom Group, will be published in about two weeks. One of the components of this review is a summary of the financings by public Canadian healthcare companies.

Equity and convertible debt financings by public Canadian healthcare companies totaled $866.9 million in 2010. This financing number does not include debt, warrant exercises, license fees and milestones, and government grants. When financings by larger profitable companies are subtracted from this amount, financings by development stage companies in 2010 totaled $529.7 million, slightly higher than the $498.2 million raised during 2009.

The Q4 total of $259.3 million was almost half of the total raised in 2010, providing some momentum going into 2011.

Monday Biotech Deal Review: January 10, 2011

Welcome to your Monday Biotech Deal Review.  2011 is off to a fast start in Canadian biotech!  Among other things, last week’s highlights included some interesting licensing activity, the completion by Bioniche of its A$12.5 million Australian offering, a $200k SEDA draw-down by Allon Therapeutics, Futuremed’s conversion to a corporation, and some regulatory and litigation updates as well.  Read on to learn more.

Weekend Reading: This Week in the Twitterverse

Catch up on the week’s biotech developments and news from our Twitter stream @crossborderbio:

Friday Science Review: January 7, 2011

Symmetry Saves the Day

University of Toronto ♦ Published in Stem Cells, Dec. 29, 2010

One of the hallmarks of stem cells is their ability to maintain the stem cell pool indefinitely through the process of asymmetric division. When they divide they give rise to one slightly more differentiated cell and one daughter stem cell identical to the original. By carrying out cell division in this manner, stem cell populations, at least in theory, are capable of living indefinitely. David Piccin and Cindi Morshead — researchers at the Donnelly Centre for Cellular and Biomolecular Research — discovered that the Wnt (pronounced ‘wint’) signaling pathway is involved in damage response in neural stem cells found in the brain. Using a mouse model Piccin and Morshead show that when neural stem cells sense it is time to replenish the stem cell population, for example during the period following a stroke, Wnt signaling contributes to a signaling cascade that promotes symmetric division. When stem cells divide symmetrically they produce two identical daughter stem cells rather than one daughter stem cell and a differentiated progenitor, ensuring that the stem cell pool does not become depleted.

H5N1 Vaccine Derived from Tobacco Plants Shows Results in the Clinic

Medicago Inc. ♦ Published in PLoS ONE, Dec. 22, 2010

Egg-based vaccine manufacturing failed to live up to its promise of rapidly producing large quantities of live vaccine for control of viral outbreaks. During the recent H1N1 influenza pandemic only 3 million doses of live vaccine had been produced by the 5 month mark, when 60 million had been expected. Canadian biotechnology company Medicago Inc. has come up with an all together different approach that could make fast and efficient vaccine production a reality — a plant-based manufacturing technology that produces influenza vaccines using Nicotiana benthamiana. At the core of the vaccine technology is something known as a “Virus-Like Particle” (VLP). VLPs are small entities containing the hemagglutinin protein of H5N1, and are produced by infecting tobacco plants with an Agrobacterium inoculum containing an H5 expression cassette. VLPs are then harvested from the aerial portions of the plant. Although a VLP resembles a viral particle, it lacks the genetic content within, thus is replication defective and non-infectious. Another aspect differentiating Medicago’s approach is that the technology only requires the genetic sequence of the virus, not an actual sample, as is the case with technologies using inactivated virus in vaccines. In a preclinical study led by Medicago’s Dr. Louis Vezina, researchers show that a VLP vaccine could induce cross-reactive antibodies in ferrets. After challenging the animals with lethal doses of H5N1 researchers observed reduced pathology and suppressed viral loads in vaccinated animals. The paper also reports on clinical results: a phase 1 trial of the H5 VLP vaccine in healthy adults between the ages of 18 and 60 revealed that the plant-derived vaccine was tolerated well at all doses and had strong immunogenicity as detected by microneutralization assays. These results taken together hold promise for Medicago’s plant-based manufacturing technology. Another plus? The vaccine can be produced in 3 weeks of sequence release! This is no doubt why DARPA made a non-repayable contribution of $21 million to Medicago back in August to build a 90,000 square foot cGMP facility in North Carolina for VLP vaccine production.

Biotech Trends in 2011: Comparative Effectiveness and Personalized Medicine

When this blog was launched in 2009, comparative effectiveness and personalized medicine were fairly new features in the North American landscape. Our initial argument that they were related topics — determining which treatment is best depends on which patient is being treated – was soon bolstered by the comparative effectiveness provisions in the U.S. stimulus bill and new personalized medicine data via the FDA.

The proposition has since become common knowledge, culminating in statements by Francis Collins and at BIO 2010 and discussed in the New York Times. Personalized medicine is now a key strategy for 12-50% of current drug pipelines, according to a recent Tufts study, and is a significant driver for DNA sequencing technology companies. If anything, the pendulum has swung a bit too far towards ‘hype,’ and as Matthew Herper reminds us, there are still non-personalized potential blockbusters in the pipeline.

The two concepts have even merged in a motto:

“the right drug to the right patient at the right time,”

which I still don’t like as much as “Personalized Effectiveness” (my neologized mash-up), but seems to be sticking. We’re just going to call it “Personalized Medicine” for now and will continue to follow major developments. You can too, on this page.

This post is the second in a series briefly outlining the biotech industry trends we’ve been following on the blog and noting some recent developments, plus directions for 2011.

Biotech Trends in 2011: Social Media in Biotech and Healthcare

Use of social media by pharmaceutical companies, biotechs, and industry observers will continue to grow in scale, value and importance this year. The emergence of Twitter as a public health surveillance tool and the pending (still pending…) release of the FDA’s social media guidelines will contribute to this growth in the short term, and we’ll continue to keep an eye on novel developments.

This post is the first in a series briefly outlining the biotech industry trends we’ve been following on the blog and noting some recent developments, plus directions for 2011.

Monday Biotech Deal Review: January 3, 2011

Happy New Year, and welcome to the first Monday Biotech Deal Review of 2011!  There were only a handful of items to report on from last week, as the holiday season brought the usual corporate slow-down.  Nevertheless, the week saw the completion of a couple of private placements (CardioComm and Ondine Biomedical), along with the expansion of the previously announced Theralase private placement.  Read on to learn more.   Read more of this post

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