The Cross-Border Biotech Blog

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

Monthly Archives: October 2010

This Week in the Twitterverse

If you’re not following our Twitter stream @crossborderbio, here’s what you missed this week:

Friday Science Review: October 29, 2010

One announcement to make this week before delving into the FSR – Gordon Ramsay and a handful of well known Canadian chefs, including Toronto’s Mark McEwan, Jamie Kennedy, and Lynn Crawford, will be attending Mount Sinai Hospital on November 20th for the Chef’s Challenge. Participants must raise $2500 to attend the event and the top 50 fundraisers get to go head to head with Ramsay in a kitchen battle. Proceeds raised will go towards funding breast and ovarian cancer research at the Samuel Lunenfeld Research Institute and the Marvelle Koffler Breast Centre both of Mount Sinai Hospital. Check it out.

Oxygen Sensors Down: Preeclampsia is a serious pregnancy disorder, affecting 5-10% of all pregnancies, and results from the dysregulation of oxygen sensing mechanisms during early formation of the placenta. Ultimately, this defective development leads to hypertension and drastic increases in urinary protein that can damage the kidney and liver of women who suffer from the disorder. The Hypoxia Inducible Factor (HIF) family transcription factors have a key role in physiological response to acute and chronic hypoxia. One member of this family, HIF-1, is important for healthy placental development and is found in abnormally high concentrations in preeclamptic placental tissue. By establishing cultures of villous explants derived from human placental tissue and growing them under varying oxygen tensions, researchers at the Samuel Lunenfeld Research Institute were able to demonstrate that HIF-1 accumulation results from the diminished function of the oxygen sensing molecules PHD2, FIH, and the SIAHs. Under normal circumstances, PHD2 controls the abundance of HIF-1 by marking it for degradation. In the absence of a functional oxygen sensing mechanism, HIF-1 accumulates beyond normal levels and alters the expression of molecules necessary for proper modeling of maternal arteries at the maternal-placental interface, leading to preeclamptic symptoms. The study was led by Dr. Isabella Caniggia, and is published in PloS ONE.

Microsatellites Need Repair: In a large-scale multi-center study, published in PLoS ONE, researchers describe how single nucleotide polymorphisms contribute to colorectal cancer (CRC).  Typically CRC arises either through abnormalities in the APC/wingless signaling pathway causing somatic mutations in oncogenes (~80% of the time), or results from deficiencies in a mismatch-repair (MMR) system causing genome-wide microsatellite instability (~20% of the time). Building on their previous work which identified several single nucleotide polymorphisms (SNPs) associated with microsatellite instability-colorectal cancer (MSI-CRC), researchers have elucidated a mechanism that explains how these SNPs contribute to the onset and formation of the disease. After removing lymphocytes from the blood of patients, researchers genotyped SNPs located in a specific region of chromosome 3 surrounding the mismatch repair gene MLH1. They were then able to use logistical regression to test for the association between these SNPs and MLH1 gene expression in CRC, and DNA methylation in CRC. Results of this analysis suggest that SNPs near or in the promoter of the MLH1 gene make this segment of DNA more susceptible to methylation, which reduces its expression causing mismatch-repair deficiency and eventually genome-wide instability. This study, led by Dr. Bharati Bapat of the Samuel Lunenfeld Research Institute, included large patient samples from Ontario, Newfoundland, and the Seattle metropolitan area.

Death by Synergy: Researchers have discovered yet another way to sensitize drug resistant cancer cells to chemotherapeutics. A group at the University of Ottawa, led by Dr. Mary-Ellen Harper, has found that a molecule known as genipin can sensitize drug-resistant cancer cells (MX2) to a number of cancer fighting small molecule drugs including menadione, doxorubicin, and epirubicin. How does it do this? Drug resistant cancer cells respond to oxidative stresses by activating uncoupling protein-2 (UCP2). This protein, a component of the mitochondrial membrane, is responsible for ushering reactive oxygen species (ROS) from the cytoplasm into the matrix of the mitochondria. By activating UCP2, drug-resistant cancer cells have a way of evading oxidative damage to essential cellular macromolecules by storing these ROS in the mitochondria. Genipin happens to be an inhibitor of UCP2 and its presence increases the concentration of ROS in the cytoplasm leading to increased cell death in the presence of cytotoxic drugs. Find the study in PLoS ONE.

Technology Transfer at Canadian Universities

The technology transfer office (TTO) lies at the interface between university researchers and the university’s external environment, including industry and government. The presumed role of the TTO has been to mobilize knowledge and foster research relationships between academia and industry, and in doing so support the commercialization agenda of the university by monetizing its innovations and technological assets. It is becoming more and more evident, however, that there is a misalignment in the expectations that the government has of the TTO and the role that the TTO actually fulfills.

Read more of this post

Ten Business Law Tips for Startups

There are lots of collections of tips for startups that have excellent business advice on building your team, hitting product milestones and pitching to VCs; but not that many that give a corporate lawyer’s perspective. So here’s mine:*

  1. You May be a Genius, but You Are Not a Lawyer
    • Your idea is brilliant and you have what it takes to be a CEO, but you are still not a lawyer (or an accountant).
    • Hire professionals and use them to help you figure out what you need and when.
    • This doesn’t have to be expensive. Figuring out priorities isn’t billable work – executing them is.
  2. Even Though You’re Not a Lawyer, It’s Still Your Job to Read Everything
    • When it comes to your business the buck stops with you
    • You need to read and understand everything you sign
    • Your lawyers’ and accountants’ job includes explaining things you don’t understand
  3. If You Don’t Incorporate, You’re Personally Liable
    • Unless you’ve incorporated (or formed an LP , LLP, S.a.r.l, etc.), you’re personally liable for everything done in the name of the company or by any of your partners
    • One you have a corporate entity, issue shares (or units, etc.) to yourself and your partners – they are the legal basis for corporate power
  4. A Shareholders Agreement is Cheaper than a Lawsuit
    • Unless you’re the only founder, you need to align everyone’s expectations
    • Drafting a shareholders agreement will help you address key controversies in advance
    • Waiting until there’s a dispute is too late
  5. Be Greedy With Your Equity
    • Once you have a shareholder, they are hard to get rid of
    • It’s tempting to use shares for compensation, advisory boards, etc.
    • Try to use non-dilutive cash or options instead
    • Make sure when you do issue equity that it doesn’t constrain your next steps
  6. Pay Your Taxes
    • There are lots of taxes that apply at early stages
    • Payroll taxes, HST, VAT, sales taxes, etc.
    • You can be personally liable if your company doesn’t pay
    • Ignoring taxes only makes it worse
  7. Protect Your IP
    • Get assignments from your inventors or institutions
    • Get signed development agreements before the work starts
    • Talk to an IP lawyer about appropriate patent filings and permissible disclosures
    • Separate your current job from your startup. If you use time, facilities or equipment that belong to your current employer, they could end up owning your new company’s IP.
  8. An NDA May Ruin First Impressions
    • Don’t drive away potential partners or investors with premature or paranoid NDAs
    • Give potential investors and partners enough non-proprietary information to generate interest
    • If in doubt, run planned disclosures by your lawyers and existing investors
  9. Be Honest With Your Customers
    • Make sure your terms of use and policies are clear, but comprehensive
    • If you’re collecting personal information, you need to comply with privacy law
  10. Talk to Your Investors
    • Let them know about progress and challenges
    • Give them advance notice of future financing rounds

* This is not legal advice (duh, it’s a blog), just my thoughts (not my firm’s – see previous) on how to use legal services efficiently when your business is new. I presented a version of these as part of Ogilvy’s How to Draft a Patent seminar at MaRS yesterday.

Two MaRS Innovation Transactions Take Off

MaRS Innovation, the “integrated commercialization platform” responsible for commercializing inventions from 16 Toronto academic institutions, announced two deals last week. One spin-out and one out-license (pdf links).

The spin-out: MI put $500,000 into Prof. Shana Kelley‘s new company, Xagenic, alongside a $300,000 loan from HTX; $200,000 from the Ontario Institute for Cancer Research; and $40,000 from the OCE Centre for Commercialization of Research. The notable part of this transaction is the launch of a University spin-out with pre-built seed funding. The structure of MI’s “investment” was not disclosed.

The out-license: A sustained‐release form of nitric oxide (NO) from Prof. Ping Lee’s lab at U of T was out-licensed to San Diego-based Cardium Therapeutics (AMEX: CXM), which will pay undisclosed amounts for the technology. One form of consideration that is disclosed: a nice endorsement for MI from Cardium’s CEO, Christoper J. Reinhard, who said “MI brought great business understanding to the process. The team understood our needs quickly and they worked efficiently to get the deal done.”

The bottom line: These are two interesting and positive deals from MI, executed in pretty short order for a new organization, that deserve congratulations. We look forward to future MI deals that disclose more some detail on business terms and valuations.

Monday Biotech Deal Review: October 25, 2010

Welcome to your weekly review of Canadian biotech deals for October 25, 2010.  Last week’s notable transactions included the Qualifying Transaction of TSXV CPC company CCS Capital Inc. (now known as China Health Labs & Diagnostics Ltd.) and ProMetic’s strategic agreement with Allist Pharmaceuticals Inc., for the commercialization in China of two of ProMetic’s drug candidates.  Read on to learn more about these transactions, as well as the usual assortment of Canadian biotech news. Read more of this post

This Week in the Twitterverse

Some weekend reading from our Twitter stream on @crossborderbio:

Friday Science Review: October 22, 2010

Some great research to touch on this week in top-notch journals including Science, Cell, and NEJM. The first publication really emphasizes the strength of collaborative research projects around the globe.

Understanding Endometriosis: Ovarian clear-cell carcinomas are less common than high-grade serous carcinomas (12% and 70% of total respectively), but still remain the second leading cause of death from ovarian cancer. It is important that the mechanisms behind the formation of this rare subtype are elucidated because it is not responsive to conventional platinum-taxane chemotherapeutic regimes that are currently the first-line treatment for ovarian cancer. In a comprehensive study published in The New England Journal of Medicine, researchers sequence the entire transcriptomes of 18 ovarian clear-cell carcinomas  and identify frequent somatic mutations in the tumor suppressor gene ARID1A (the AT-rich interactive domain 1A). ARID1A encodes the protein BAF250a which in turn is part of the chromatin remodeling complex SWI-SNF that regulates a diversity of cellular processes including DNA repair and tumor suppression. Interestingly, the mutation appears specific to the clear-cell and endometrioid subtypes. After identifying the ARID1A mutation, researchers carried out targeted re-sequencing in a mutation-validation cohort consisting of an additional 210 carcinoma samples from all subtypes. Combining the discovery cohort and validation cohort, the ARID1A mutation was found in 55 of 119 clear cell carcinomas (46%), 10 of 33 endometrioid  carcinomas (30%), but not one of 76 high-grade serous ovarian carcinomas. These findings strongly implicate ARID1A mutation in the early transformation of endometriosis into cancer and the genesis of clear-cell and endometrioid ovarian carcinomas. This exhaustive work was carried out by some 45 researchers in a dozen or so institutions found in Canada, the United States, and Australia.

Danger Signaling: Physical injury to tissue leads to cell necrosis and the release of special patterning molecules, including proteins, nucleic acids, extra-cellular matrix proteins, and various lipids as a complex milieu of chemotaxic signals. Neutrophils are able to use these unique signals to guide themselves to the site of a wound, and play an important role in recycling debris from dying cells. In a study published in Science, led by Dr. Paul Kubes of the Immunology Research Group at the University of Calgary, researchers used a mouse model of sterile injury and an in vivo imaging technique known as spinning disk confocal microscopy to observe the kinetics of eGFP-expressing neutrophils in response to thermal induced necrotic injury. Experiments revealed that necrotic cells activated a multistep hierarchy of cues that lured neutrophils to the site of danger. Another interesting finding of the study is that neutrophils appear to travel to the site of injury intravascularly as opposed to taking the most direct route through tissue. The group proposes that danger sensing and recruitment mechanisms may have evolved to prioritize intravascular travel in order to reduce the collateral damage incurred if neutrophils were to migrate directly through healthy tissue.

In Pursuit of Perfection: The fundamental limit of minimally invasive surgery is at the level of the single cell. In principal, lasers are capable of operating at this spatial resolution however efforts to achieve this have been limited by thermal and shock wave induced collateral damage to surrounding tissue. The long-held promise of a fine surgical laser has been delivered by two investigators in the Toronto research community with the creation of a novel laser source – the Picosecond IR Laser (PIRL). As a cutting modality the PIRL has a shorter pulse duration than conventional surgical lasers, vaporizing tissue on the picosecond timescale rather than burning on the nanosecond, and exploits a new cutting mechanism that selectively energizes water molecules. Researchers created full thickness wounds in CD1 mice using PIRL to demonstrate that it caused neither cavitation or any associated shock wave induced damage, and also showed that PIRL greatly reduced scar formation by comparison to conventional surgical laser or scalpel. The technology is expected to be useful in surgical procedures where scarring is particularly debilitating. Dr. Benjamin Alman, Head of the Division of Orthopedic Surgery at Sick Kids, and Dr. Dwayne Miller, in the Department of Chemistry at the University of Toronto, were co-principal investigators in this study published in PloS ONE.

At the Junction: The RAS/MAPK signaling pathway contributes to a number of important cellular processes including proliferation, differentiation, and survival. In its most basic form the pathway is regulated by the small GTPase RAS, and the three core kinases RAF, MEK, and ERK/MAPK. Like most signaling pathways, the RAS/MAPK pathway is controlled by a diversity of post-translational modifications but much less is known about regulation of its core protein components at the mRNA stage. Using a genome-wide RNAi screen in Drosophila S2 cells, researchers set out to identify other proteins involved in the pathway that could modulate MAPK protein levels. In doing so they identified the Exon Junction Complex (EJC) as a regulator of mapk transcripts. The complex is believed to contribute to the regulation of exon definition and suggests that the EJC has a key role in early regulation the RAS/MAPK pathway. This study, published in Cell, was led by Dr. Marc Therrien at the University of Montreal.


Biotech Trends Update — Biosimilars Blur IP Constituencies: Novartis and Pfizer-Biocon are Featured in the Economist

Two 9-figure announcements this week mark a turning point for the biosimilars market, and one highlights the increasingly important role India plays in innovation.

  1. Pfizer linked up with India’s Biocon in a deal that will see Biocon take the lead in development of four biosimilar insulin products that gives Biocon $200 million up front. Coverage of the deal in the Business Standard highlights the country’s overall strength in biosimilars, which fall midway between new molecule development and small molecule generics in terms of the R&D and manufacturing sophistication required. Biocon cites the deal as proof that India can move up the value chain, doing for biosimilars what it did for generics. This is especially true if they continue to attract backing and partnerships from the Pfizers of the world.
  2. Novartis’ generics unit, Sandoz, reported Q3 revenues of $292 million from a single biosimilar product — enoxaparin, a copy of Sanofi-Aventis’ anticoagulant Lovenox — which is not expected to hit blockbuster status in its own right. As we have noted before, the high level of expertise required to make biosimilars creates a high barrier to entry and contributes to the field’s attractiveness to traditional pharmas (e.g., Pfizer, above) as well as to the major generics players. FierceBiotech notes further growth is expected as the first biosimilar antibodies hit the market in 2014-2015.

The Economist picked up the relevant trends in an article today entitled “Attack of the Biosimilars“:

1) “Innovator” pharmas are moving into the biosimilars business, reversing their recent role as the predominant plaintiffs in IP litigation:

“…it is ironic that the next great opportunity for traditional drugs firms is to do to the biotechnology interlopers exactly what the generics firms have done to them: shred their profit margins with cheaper copies…”

2) India in moving up the innovation value chain, increasing that country’s incentive to protect IP more forcefully:

“And as if to remind the world that new ideas don’t all come from America, it is the Indian firm that will design and manufacture the original drugs; Pfizer will only market them.”

Bottom line: biosimilars are at least as big a business as predicted. This success is another challenge to the concept that pharma’s patent cliff challenge will be met by more in-licensing from small biotechs or by increased R&D spending. Revenue is revenue, and biosimilars are poised to generate lots more of it.

Monday Biotech Deal Review: October 18, 2010

Despite the short week, it was a busy one in the Canadian biotech sector. Read on to learn about the Labopharm / Paladin licensing deal, Ondine’s new facelift (and 15:1 equity liposuction), and various other biotech updates and news. 

Read more of this post

This Week in the Twitterverse

Lots of great weekend reading from our Twitter stream on @crossborderbio, including news and commentary on the latest in personalized medicine and the Canadian VC landscape:

 

Friday Science Review: October 15, 2010

A world first

It has been almost 12 years since James Thomson published his groundbreaking paper in Science providing details on how he and his colleagues had managed to isolate embryonic stem cells from human blastocysts, and maintain them indefinitely in culture. This work provided the foundation upon which future therapies could be built. Stem cells are once again in the spotlight as we begin to transcend conventional medical therapies into unchartered waters. Earlier this week, Geron Corp. initiated the world’s first embryonic stem cell-based clinical trial in patients suffering spinal cord injury. In this phase 1 study, oligodendrocyte progenitor cells (GRNOPC1) derived from human embryonic stem cells will be investigated for their safety, and potentially for their ability to remyelinate neurons and stimulate nerve growth in the spinal column of patients.

The stem cell community is no doubt experiencing a whirlwind of conflicting emotions in the face of this progress – excitement and relief, that a new milestone in stem cell-based therapy has been reached; hope, that the patients may indeed benefit from the treatment; and fear, that the study may have arrived too early and could prove unsafe in its course. While the outcome of the study remains uncertain, what is more clear is that its results will have far reaching effects and set the tone for stem cell transplantation therapy for years to come. No doubt, the study will agitate the already heated interchange between stem cell proponents (researchers, advocates, and otherwise) and those staunchly opposed due to ethical and moral objections. It seems it may not be long before one side or the other has new material to buoy its argument.

A recently published letter in Cell Stem Cell, focusing on induced pluripotent stem (iPS) cells, discusses a transplantation approach that may help the scientific and medical communities maximize the value of early stem cell transplantation studies in humans, like that of Geron’s.

Moving iPS cells to the clinic: It has been well established in the scientific community that if induced pluripotent stem (iPS) cells are to be of therapeutic value in the clinic they must be free of any genetic factors used in the reprogramming process. If left behind, reactivation of any of these ‘stem cell’ genes could result in tumor formation following transplantation. In line with this goal, the Canadian research community was taken aback last year when Dr. Andras Nagy of Mount Sinai Hospital in Toronto managed to create human iPS cells using a jumping gene which allowed for complete excision of reprogramming factors (this was also some of the first work illustrating that iPS cells could be generated without viruses, find it here).

In a recent letter in Cell Stem Cell, James Ellis of the Ontario Human iPS Cell Facility reinforces the importance of transgene-free iPS cell lines like Nagy’s for future therapeutic use. In addition, Ellis points out that in the absence of cell tracking technology in early autologous transplantation procedures in humans we will have difficulty in knowing whether transplanted cells survive, localize to pathological sites, or exert positive or negative effects on the recipient. Gene therapy is an example of a field that would have benefited early on from basic information related to clinical outcome. An NIH review of gene therapy trials published in the mid-90′s noted that of over 100 approved clinical protocols virtually none had demonstrated definitive clinical efficacy.  To ensure that stem cell transplantation protocols do not meet the same end, Ellis proposes that transgenes be investigated for their ability to act as reporters to facilitate monitoring of therapeutic cells following transplantation. It’s only early days, but this is excellent foresight.

In other Canadian research news we find therapeutic value in natural compounds..

It’s in the skin: Studies show that a ‘Mediterranean diet’ reduces the incidence of certain age-related diseases such as heart disease, cancer, and dementia. Efforts to deconstruct this effect have put scientists on to polyphenols, a class of compounds found in abundance in Mediterranean foods with pronounced anti-oxidant and protective activity. One highly potent polyphenol, resveratrol, happens to be found in the skins of grapes (another reason to enjoy wine). Dr. Remi Quirion and his colleagues at McGill University previously showed that polyphenols bind receptors in the brain. This observation led them to believe that resveratrol may exert positive effects on the skin. Indeed, experiments revealed that resveratrol has specific binding sites in human skin tissue and is able to reduce the incidence of apoptosis in toxicity models. The molecule is currently being investigated by many groups around the globe for use in life extension, prevention of cancer, and a number of other disease-related applications.

Extracts for insulin: After scanning a library of 1319 marine invertebrate extracts using a high-throughput platform, researchers identified a number of compounds that modulate insulin and pdx1 expression in human pancreatic islet cells. In order to confirm up-regulation of relevant genes, pancreatic islet cells were transfected with a dual-reporter lentivirus containing eGFP driven by the insulin promoter and mRFP driven by the pdx1 promoter. Each compound was examined for four parameters, including insulin promoter activity, pdx1 promoter activity, nuclear morphology, and cell number. Bivittoside D was identified as a positive regulator of insulin gene expression. This study is the first example of a high-throughput, high-content, multi-parameter screen in living pancreatic beta-cells, and was led by Dr. James Johnson of the Department of Cellular and Physiological Sciences at the University of British Columbia.

Biotech Trends Update — Personalized Medicine: Duncan’s Personalized Health Manifesto is Primarily Preventative

Image from flickr user Steve Rhodes. Some rights reserved.Journalist David Ewing Duncan’sPersonalized Health Manifesto” was published this week by the Ewing Marion Kauffman Foundation. The most interesting thing about the manifesto* is that it assumes that the technical hurdles to generating and understading a full set of personalized health data have been overcome, and focuses on how that information can be deployed most effectively.  Duncan says that “a widening gap exists in integrating and implementing this promising new epoch of personalized health.” There are two main themes in the manifesto: integration and prevention.

Integration comes from Duncan’s view about how the flood of personalized data should be analyzed by researchers and physicians:

“A balance between specialization and integration needs to be restored,with an emphasis on the whole human organism as much as its parts…”

Prevention is, for Duncan, the natural best use of personalized data:

“Shifting to a health care system based as much on healthy wellness as illness is achievable…”

Both are laudable long-term goals, but I am not convinced of the need for urgent action on either point.

Specialization is (as Duncan acknowledges) what has enabled us to discover personalized markers and to analyze them on a allele-by-allele basis. We are a long way from making meaningful predictions about systemic effects on complex traits based on the available information. A shift too early away from specialization could prevent us from ever developing the underlying science sufficiently to make reliable predictions.

And shifting to a preventative healthcare system is not a goal I view as being unique to personalized medicine. As genomic testing becomes widely available, and patients begin to process their data, complex traits continue to present a challenge for them and their doctors — now that I know I have an increased risk of heart disease, I should shift my diet and increase my exercise. But these are things preventative healthcare advocates have been recommending for decades; and there is no evidence that I’ve seen that suggests the genetic information about increased risk is more motivational than family history, or peer behaviour, or any other non-personalized factor.

Bottom line: I’m no expert on manifestos, but while there’s nothing in this one I feel strongly opposed to, it doesn’t move me to action either. Read the whole thing (it’s not very long) and form your own (personalized) view.

* Other than his decision to call it a manifesto.
Image from flickr user  Steve RhodesSome rights reserved.

Monday Biotech Deal Review: October 11, 2010

Happy (Canadian) Thanksgiving!  This Monday Biotech Deal Review reports that it was a bad week for turkeys and a bit of a slow week on the biotech front, but read on to learn about some interesting collaborations, allegations and corporate immigrations. Read more of this post

Friday Science Review: October 8, 2010

This week I’ll take the opportunity to discuss a Nature Biotechnology commentary that has generated a little buzz in the health-biotech community, in addition to a recent publication in Science that is particularly impressive.

Making the Invisible “Visible”: The elucidation of protein structure is essential for our understanding of protein function. Despite having sound methods for the determination of protein structure in the native folded state, thus far it has been particularly challenging to determine the structure of transient intermediates along the protein folding pathway. Now researchers have developed a protocol combining a unique form of nuclear magnetic resonance (NMR) with chemical shift-based methodology (CS-Rosetta) allowing for structural determination of “invisible” metastable intermediates. These rare conformational states form rapidly and last only for microseconds before folding to the native state. The methodology, published in Science, can also be used for the determination of excited states crucial to function, for example enzyme catalysis and ligand bonding, and is expected to provide a wealth of data on conformational states that so far have proven highly elusive. The study was led by Dr. Lewis Kay of the Department of Molecular Genetics at the University of Toronto.

A fine balance

Peter A. Singer and Rahim Rezaie, both of the McLaughlin-Rotman Centre for Global Health at the University of Toronto, bring an interesting debate to the table in a recent Nature Biotechnology commentary:

“As health biotech enterprises in emerging economies move from imitation to innovation, will they become less relevant to local global health priorities?”

Countries such as China, India, and Brazil have played a pivotal role in supporting local and global health priorities through the production of low-cost health products. Now it seems we may begin to see more and more integration of health-biotech companies in the developing world into the global product development value-chain. The concern, however, is that a movement towards more costly innovative products and lucrative markets may lead to the neglect of poorer market segments that health-biotech firms in the developing world have traditionally focused on. Rezaie and Singer pose an eloquent question:

“..as enterprises in the emerging markets take on more costly innovative projects, would they be compelled to choose between global health and global wealth?”

A force driving integration is the exchange of service-provision arrangements between health-biotech enterprises in emerging economies and large multinational pharmaceutical companies (MNCs). For example, China’s Wuxi PharmaTech and India’s Advinus Therapeutics have entered service-provision arrangements with MNCs. The movement is further supported by an increase in collaborative development between firms in developing countries and MNCs, as they work together to produce innovative health products.

Despite the “innovative” interests of health-biotech firms in emerging economies, data suggests the priorities of global health may continue to be met. Growth in pharmaceutical markets in emerging economies has risen sharply over the last several years. India and Brazil have seen average annual growth rates of 10% in their pharma markets, and China even greater at 21%, suggesting the interests of MNCs may be shifting from developed to developing markets. Hence, the global integration of health-biotech firms operating in the developing world may in part be balanced by the evolving mindset of multinationals towards less developed markets.

Rezaie and Singer believe that the objectives of global health and global wealth can be satisfied simultaneously. Providing the proper support mechanisms are put in place, they argue, development of health products for poor market segments can be secured. An interesting instrument discussed is an orphan drug-like legislation plan for emerging economies, where the intended purpose is to incentivize products for diseases of the poor rather than diseases of low prevalence. The Global Health Accelerator platform, health funds directed at emerging economies (see NY-based Acumen Fund, Ventureast Biotechnology Fund in India, Bioveda China Fund, among others), and tactics such as public-private partnerships, advance market commitments, and patent pools to share intellectual property are also posed as mechanisms for bolstering interest and investment in global health challenges.

This article, published in Nature, is well worth a read for any interested in the evolving trajectories of the healthcare and biotech sectors, and the implications these changes will have on global health.

Biotech Trends Update — Biosimilars: FDA Meeting Formally Announced, EMA Working on Rules for (a few) Antibody Biosimilars

Reuters reports that the European Medicines Agency (EMA), which has already approved 13 biosimilars, is expecting to publish guidelines in November on biosimilar antibody therapeutics. EMA Executive Director Thomas Lonngren said that clinical trials will be required for antibody biosimilars (as they are for the products EMA has approved to date), but that requirements were likely to be less onerous than in the United States.

Reuters says that the small number of requests (six) received by EMA so far “reflects the difficulties of making such copycat medicines [antibodies]” but with the earliest therapeutic antibodies coming off patent (in Europe) in 2014, I expect these initial inquiries are just the tip of the iceberg. Of couse, biosimilars are hard (as we’ve noted); but a lucrative opportunity of that scale will not go untapped.

Meanwhile, as expected based on the draft notice leaked in September, the FDA is holding public meetings on the implementation of the Biologics Price Competition and Innovation Act (i.e., the biosimilars legislation). The full Federal Register notice (pdf) is up, and Mark Sernak at eyeonfda.com has extracted the questions posted for comment.

In addition to a long list of scientific and technical questions, there are a couple of inquiries that I’d highlight from a corporate law perspective:

  1. Which types of related entities may be ineligible for a period of 12-year exclusivity for a subsequent BLA, given the “potential transfer of BLAs from one corporate entity to another and the complexities of corporate and business relationships”; and
  2. Whether the existing fee structure under the Prescription Drug User Fee Act (PDUFA) should be considered as a model in establishing a user fee structure for biosimilar applications.

Interested in attending or in submitting a comment? The FDA’s meeting information page is here, and it includes webcast access for November 2 and November 3.

Canadian Venture Capital Data from Q2 2010 Shows Big Jump From Q2 2009 but Only Moderate Increase for Biotech

The Q2 issue of Industry Canada’s Venture Capital Monitor is up, and it shows “the highest level of VC activity since Q3 2008,” though that is still “significantly lower than the quarterly average of $440M recorded over the previous five years before the downturn.”

A couple of (particularly) parochial notes:

  1. First-time deals at the seed and start-up stages of development were hurt by a decline in first-time, early-stage investments in Ontario, which recorded only one new deal at the seed or start-up stage in Q2 2010.
  2. Biotech investment saw a 13% increase to $91 million, but it paled in comparison to the 71% increase for IT (to $149 million) and the 377% increase (to $56 million) for “energy and environmental technologies.”

How does the future look? Steady overall. Canadian VC fundraising was down a bit (7% from Q2 2009), totalling only $255 million; but for the year ended June 30, 2010, the total raised was “roughly the same as the annual average from 2005 to 2008.” There is no sector breakdown, though, and everyone our neck of the woods knows we’re due for a turnaround in in Canadian life sciences VC fundraising.

Monday Biotech Deal Review: October 4, 2010

This week’s Monday Deal Review brings you the usual assortment of biotech wheelings and dealings from the past week, including a summary of the newly completed Valeant / Biovail merger.  Read more of this post

This Week in the Twitterverse

Here’s some weekend reading from our Twitter stream on @crossborderbio …

  • Friday Science Review is back, thx to Mark Curtis! Today’s cool Canadian science = tomorrow’s cool startups… http://ow.ly/19f2te1
  • DTC genetics link in last tweet is from @CMAJ_News – also contrasts Class III regulation of companion diagnostics. I.e. DTC is non-clinical?
  • MT @genomicslawyer: …Health Canada is taking a “far more relaxed approach” than U.S. regulators to DTC genetics http://bit.ly/bX3Il7
  • RT @JohnCFierce: Covance is buying 3 R&D facilities from sanofi and inked a 10-yr research contract worth up to $2.2B http://reut.rs/dBbQ7F
  • RT @MSBiV: Leap Medical completes second tranche of financing http://bit.ly/dl7KbL a @McGillU spin-off and @MSBiV investee
  • Planning to! RT @robannan: I’m going – anyone else? RT @JVPLS @sciencepolicy Canadian Science Policy Conf Mtl Oct.20-22 http://ow.ly/2KpWG
  • Biovail, Valeant shareholders vote to approve merger, expected to close tomorrow. http://bit.ly/aAstb0
  • RT @MaRSDD: Blog – Got a management challenge? Win a ticket to see Malcolm Gladwell! … http://bit.ly/cdQkDv
  • RT @genomicslawyer: BGI as one of China’s multiple “moon shots”, as told by Thomas Friedman of NYT: http://nyti.ms/aJlNvY H/T @phylogenomics
  • Happy Bday! RT @IlseTreurnicht: Birthday cake @MaRSDD: 5 years since opening of the MaRS Centre today…
  • Healthcare giving down in the U.S. and up in Canada (2008 vs 2009, tho 2009 in Canada just = recovery to 2006 levels) http://bit.ly/aaENDU

Friday Science Review: October 1, 2010

I am pleased to see the Friday Science Review back online, and very much look forward to contributing to the Cross-Border Biotech Blog. This week I will play a little catch up and provide details on a number of publications from the Canadian research realm spanning the last month or so. Future posts will of course focus on weekly hits. So without further delay..

Early Epigenetic Experience: Some of the earliest adverse events humans experience may occur even before we are born. Roughly 15% of mothers suffer mood disturbances while pregnant, and an increasing amount of evidence is implicating maternal depression and anxiety in the development of neurobehavioural disturbances during childhood. A reduced concentration of the neurotransmitter serotonin (5-HT) in the brain has long been associated with depression, and can be directly linked to weak expression of the transmembrane serotonin transporter 5-HTT. A study led by Dr. Tim Oberlander of the Department of Pediatrics at the University of British Columbia shows that maternal depression during the 2nd trimester is associated with a decrease in both maternal and neonatal methylation in the 5-HTT promoter region. These findings suggest that maternal mood can alter epigenetic patterns in newborns, and may to some extent “program” infant and childhood behaviour.

A Sensitive Subject: As male fertility in the human population continues to decline, researchers are pressed to investigate links between environmental factors and the development of spermatozoa. New findings implicate environmental-epigenetic modification in the regulation of two key stem cell genes involved in spermatogenesis. Using the chromatin modifying drugs tranylcypromine and trichostatin, researchers were able to show that increases in histone H3 methylation and acetylation led to activation of the genes Pou51 and Gfra1. Chemicals with chromatin modifying capabilities may be able to influence the expression of genes necessary for normal and healthy spermatogenesis, and illustrates the sensitivity of these precious cells to chemical cues in our environment. The study was led by Dr. Sarah Kimmins from the Department of Animal Science at McGill University.

One Gene, Many Proteins: The lethality of different cancer cell types is often directly related to their ability to metastasize, or move from their place of origin to distant sites in the body.  A study led by Dr. Jacek Majewski from the Department of Human Genetics at McGill University, suggests there could be an intimate relationship between alternative splicing and the metastatic abilities of breast cancer cells. Using splicing-sensitive microarray technology (Affymetrix Exon Microarrays), researchers analyzed genome-wide mRNA isoforms derived from three mouse mammary carcinoma cell lines with varying propensities to metastasize. What they found was a large  group of genes, 2623 to be exact, that underwent gene expression variations specific to metastatic characteristics. This research, published in PLoS, suggests that metastasis of breast cancer cells may be facilitated by splicing variations or splicing defects that affect a number of biological processes including cell adhesion, migration, apoptosis, and proliferation.

Biomimicry: The transcriptional and translational factor YB-1 (Y-box binding protein-1) has been known to exacerbate breast cancer by binding DNA and enhancing the expression of several genes related to drug resistance and tumour growth including EGFR and HER-2. Dr. Sandra Dunn and her colleagues in the Laboratory for Oncogenic Research at UBC recently identified a kinase, RSK, that activates YB-1 by phosphorylation allowing it to bind DNA. Their solution? A molecular decoy protein. In this recent study in PLoS, researchers design a cell permeable peptide (CPP) that mimics the activation site of YB-1, thus competing for RSK’s attention. The result was a drastic reduction in phosphorylation of YB-1 and concomitant reduction in the expression of EGFR and HER-2. The beauty of this approach is that YB-1 has been broadly implicated in cancers including those of the bone, lung, colon, and brain. The findings also give hope to patients with the most aggressive form of breast cancer that fail to respond to other therapeutics such as trastuzumab; the decoy protein was found to reduce growth in a dose-dependent manner in an incurable model of breast cancer (triple-negative, HER-2+).

Follow

Get every new post delivered to your Inbox.

Join 130 other followers