The Cross-Border Biotech Blog

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

Monthly Archives: February 2010

This Week in the Twitterverse: Weekend Reading

Here are some good tidbits to catch up on over the weekend in case you missed them the first time around on @crossborderbio:

Friday Science Review: February 26, 2010

A few medical research applications this week…

Personalized Medicine – for Lung Cancer: To develop a personalized medicine approach to treating non-small cell lung cancer (NSCLC), researchers generated a xenograft model where they implant human tumour tissue into the renal capsule of a host mouse.  As the tumour establishes itself, the mouse then becomes the platform for testing various chemotherapy regimes (cisplatin+vinorelbine; cisplatin+docetaxel; cisplatin+gemcitabine) to determine which one or combination therapy is the most effective against each of the different tumours.  They compared the results of the treatments in mice to retrospective patient outcomes and found significant correlation to consider the xenograft model a success.  Although it takes about 6-8 weeks for the results, they believe that it is quick enough to gain an insightful preliminary assessment of the potential therapeutic outcome.  Dr. Yuzhuo Wang led his team at the BC Cancer Agency and reports their work in Clinical Cancer Research.

HIV-1 Molecular Manipulations: HIV-1 infected patients exhibit a loss of CD4+ T cells, which are essential players in the defense against viral infections.  A new study reveals how the HIV-1 protein, Vpr, activates the Natural Killer (NK) cells by inducing the expression of stress-related proteins at the cell surface of CD4+ T cells.  The NK cells recognize the stress signals on CD4+ T cells and attacks and destroy these cells, leaving the patient with severely reduced CD4+ T cells.  Researchers also noticed that the continuous activation of NK cells eventually desensitizes them and they eventually lose their ability to perform their normal duties in attacking infected cells.  The molecular mechanisms of Vpr discovered in this study should help in future research leading to new therapeutic strategies.  Dr. Éric Cohen and his team at the Institut de recherches cliniques de Montréal describe their research in last week’s issue of Blood.

Protecting Your Heart: The blood pressure cuff you see in every doctor’s office can be used to limit the severity of heart attacks by triggering a molecular response in the body that protects the heart during an attack.  It is called remote ischemic preconditioning where the blood pressure cuff is used to intermittently cut off blood flow to the arm during an attack.  This triggers an innate response warning message throughout the body to release molecules to protect itself from the lack of blood flow.  In this particular study, the size of the heart attacks were reduced by 30-50% compared to control groups.  It is one of the most effective treatments and is relatively simple to administer.  Dr. Andrew Redington at The Hospital for Sick Children led the international study and is published in the The Lancet.

Cephalon-Ception’s Canadian Connection: Great News for Lumira Capital and McMaster in $250 million Option Deal

At the beginning of 2009, when Ception Therapeutics was working on mid-stage trials of its lead compound, it struck an option deal with Cephalon (NASDAQ: CEPH): $100 million up-front, and an option to acquire the rest of Ception for $250 million more. 

This week, Cephalon exercised the option after taking a look at Phase II results for Cinquil (reslizumab), a novel biologic that could potentially be used to treat asthma and Pediatric Eosinophilic Esophagitis. 

Among many other beneficiaries, foremost among them hopefully being patients, this deal is great news for Canadian-based VC firm Lumira Capital*, which co-led the deal, and for McMaster University, which did some of the clinical work on the drug. 

According to FierceBiotech, the $350 million paid so far is not the end of the story either, as Ception shareholders will benefit from future clinical and regulatory milestones.

Bookmark and Share

* occasional contributors to this publication.

Monday Biotech Deal Review: February 22, 2010

There was a lot of follow-up among Canadian biotech deals this week: letters of intent turning into definitive agreements, merged companies turning to consolidation, bids launched on schedule and wrapped up; as well as an average crop of new M&Eh and securities.  Start things off with an interesting (cross-border!) twist to the SIFT/SR&ED deals we’ve seen after the jump…

This Week in the Twitterverse: Weekend Reading

Here are some good tidbits to catch up on over the weekend in case you missed them the first time around on @crossborderbio:

Friday Science Review: February 19, 2010

Hunks and pigs highlight this week’s research wrap-up…

HUNKs Stop Cancer Metastasis: Researchers screening tumour cells found that expression of the enzyme HUNK (Hormonally Up-regulated Neu-associated Kinase) is significantly lower in cancers.  When they reconstituted HUNK into metastatic cancer cells, it decreased their metastastic potential when tested in mouse cancer models.  Its actions block the association of PP2A and cofilin-1 and prevent the formation of actin filaments, which are key skeletal proteins involved in the cell migration process.  Dr. Tak Mak led the research team at the Campbell Family Institute for Breast Cancer Research and published the study in the Proceedings of the National Academy of Sciences.

Malaria Research Gets Genomic Help: A genome-wide study on the parasite Plasmodium falciparum should help researchers in the hunt for new drugs against malaria.  The genome of 189 malaria samples from around the world were decoded and analyzed to try to identify key genes that are responsible for the parasite’s propensity to evolve and become resistant to currently available drug treatments.  These data are invaluable for the design of future therapeutic approaches.  An international team was co-led by Dr. Philip Awadalla at the Université de Montréal and reports their work in the current issue of Nature Genetics.

Genetic Clues to Diabetes: Using a genome-wide association approach, 13 SNPs concentrated in 4 genetic regions were identified to be strongly correlated with glycemic control in type 1 diabetes.  For example, SORCS1 is strongly associated with hypoglycemia (low blood glucose) and BNC2 is correlated with eye and kidney complications.  This study is a first for suggesting that there may be a genetic contribution to the individual’s ability to control blood glucose levels.  The Hospital for Sick Children’s Dr. Andrew Paterson led the study, which appears in the journal Diabetes.

Porky Pig to the Rescue: Scientists revealed a significant advantage to transplanting porcine pancreatic islet cells as a therapeutic for diabetes.  In contrast to using human islet cells, porcine derived cells do not result in the formation of islet amyloids, which allows them to continue functioning properly for the long term.  They attribute this porcine advantage to differences in the sequences of islet amyloid polypeptide (IAPP).  Dr. Bruce Verchere’s team at the University of British Columbia describes their work in the Proceedings of the National Academy of Sciences.

In (un)related news, Guelph University’s genetically engineered pigs or “Enviropigs” were given the OK by Environment Canada as being non-toxic to the environment.  Now they await Health Canada’s nod before they appear in your local supermarket.

Stem Cells Don’t Mind DNA Damage: Canadian scientists have discovered that stem cells intentionally damage their own DNA in order to regulate development… continue reading the rest of the story here at the Stem Cell Network Blog.

Bookmark and Share

Biotech Trends Update — Personalized Medicine: The Limits of Genomic Analysis

A great report on GenomeWeb yesterday by Andrea Anderson reviews two JAMA papers that failed to show a clinically useful role for SNP genetic testing in predicting heart disease risk.  Instead,

“traditional risk information based on factors such as family history and plasma biomarker levels were better for predicting heart disease.”

Anderson ties these results back to a January paper in the British Medical Journal that found that

“non-genetic factors were more useful for predicting type 2 diabetes than a set of 20 SNPs.”

The GenomeWeb article quotes the lead author of one JAMA paper as finding the results “surprising and a little disappointing;” but I am inclined to think some context is missing, since only the most die-hard genetic determinist should be either surprised or disappointed. 

Two factors suggest that these conditions, and many others, will resist accurate prediction based on genomic sequence analysis:

  1. They are genetically complex.  The prospective studies looked at data sets with between 12 and 101 SNPs.  Simple calculations suggest that the number of genetic permutations is itself staggering, never mind the physiological complexity of multigenic interactions.
  2. There are massive environmental components. Diet and exercise, among many other factors, will have a tremendous impact on clinical outcomes.  These habits are learned, not inherited, and are even “contagious” within social groupings.

My bottom line: In an age when genomic sequences are becoming increasingly accessible, it should be reassuring to know that even your medical future is not written in stone.  We always suspected as much. Now we have the genetic data to prove it.

Bookmark and Share

Biotech Trends Update — Commercialization by Foundations: $500k to AVI BioPharma from DMD Organizations

Continuing a trend by nonprofits to invest directly in commercialization of relevant products, CureDuchenne and the Foundation to Eradicate Duchenne each awarded grants of $250,000 to AVI BioPharma, Inc. (NASDAQ: AVII) to support continued research and development of the Company’s drug candidates for the treatment of Duchenne Muscular Dystrophy (DMD).

One interesting note here is the collaboration between foundations, something we also saw in an ALS project in December.   This is a great way for smaller foundations to maximize their impact on the (expensive!) drug development process.

Both foundations, run by parents of kids with DMD, are focused on commercial products:

“CureDuchenne is very happy to support AVI BioPharma as it advances these treatments to boys with DMD as soon as possible.”

“The exon-skipping strategies being developed by AVI offer the greatest prospect for meaningful clinical therapies.”

Bookmark and Share

Monday Biotech Deal Review: February 15, 2010

A busy Monday Deal Review is headlined by Labopharm and ProMetric on the securities front, MDS’ final divestiture on the M&Eh front and Biovail and Bioniche on the licensing front, and there’s lots more activity behind those for over $100 million of deals.  Check out all the details (and the witty headlines) after the jump…

This Week in the Twitterverse: Weekend Reading

Here are some good tidbits to catch up on over the weekend in case you missed them the first time around on @crossborderbio:

Friday Science Review: February 12, 2010

New Discovery for Neonatal Diabetes: Researchers uncovered an important role for the Rfx6 gene.  Its integrity is required for normal development of the islets of Langerhans cells in the pancreas that produces important hormones including insulin.  Genetic mutations found in Rfx6 are the cause of severe neonatal diabetes where there are no insulin producing islets of Langerhans cells.  To prove the critical role of Rfx6 in directing the differentiation of early pancreatic cells, researchers disrupted the gene in mice and observed the development of an identical disorder as displayed in humans.   Identifying the gene is a key piece of the puzzle and will lead to new avenues to find treatments for all types of diabetes.  Dr. Constantin Polychronakos and his team at McGill University collaborated with researchers from UCSF and report their study in the on-line edition of Nature.

Controlling Stem Cell Fate: A genome-wide screen identified the PCL2 (polycomb-like 2) gene as a key decision maker in determining the fate of stem cells.  This is an important area of research because stem cell based therapies in regenerative medicine are on the rise but more thorough understanding of stem cell control is necessary for safety reasons.  In the absence of PCL2, stem cells can no longer differentiate into specialized cells regardless of adding stimulating factors to try to push it to differentiate.  Once they re-introduced PCL2 into the stem cells, they were able to drive differentiation again.  By mapping the network of genes that PCL2 regulates, they can trace the steps in the path of a stem cell in becoming one of the many cell types in our body.  University of Toronto scientist, Dr. William Stanford and his team describe their research in the journal Cell Stem Cell.

Stem Cell Prediction: This is a neat study.  Researchers generated an algorithm to predict the future of a stem cell – whether it divides and self-renew as stem cells or produce alternate cell types.  They recorded video of retinal progenitor cells under the microscope to ‘observe’ the cell’s characteristic dynamic behaviour and movements just prior to dividing.  This information was computed to generate a predictive algorithm that was tested to be (amazingly!) 99% accurate in identifying cells that will self-renew as stem cells and 87% correct in predicting a differentiation cell fate.  This may lead to new tools to help scientists isolate pure populations of stem cells for their future studies.  Dr. Michel Cayouette’s group at the Institut de Recherches Cliniques de Montréal presents their work in this week’s edition of Nature Methods.

Genomics of Flesh-eating Disease: The genomic sequences of Streptococcus bacterial strains from past epidemics in Ontario were determined in a study involving Canadian and US researchers.  They identified and compared single nucleotide polymorphisms (SNPs) between the strains and found that they were different by an average of only 49 SNPs.  Each strain, however, also contained unique sequences that could be used for tracking purposes in future outbreaks.  Some genes were highly variable, which is information that they can use to try to understand the bacterial virulence factors at play in gaining an advantage over the infected person.  These comparative pathogenomic studies are invaluable for microbial epidemiology research and for shedding light on new potential targets for antibiotic drugs.  Drs. Donald Low and Allison McGeer at Mount Sinai Hospital participated in the research that is reported in this week’s edition of the Proceedings of The National Academy of Sciences.

Should FDA Special Protocol Assessments be Public?

A provocative post by Matthew Herper at Forbes’ The Science Business Blog this week argues that special protocol assessments (SPAs) should be public.  SPAs are the FDA’s way of pre-approving a clinical trial design, so that a company can conduct its trials secure in the knowledge that the FDA won’t later withhold approval based on a design flaw.

SPAs are currently “confidential communications” not subject to public disclosure, but Herper argues for congressional action to put them into the public record:

“It might take an act of Congress to allow the FDA to make SPAs public, but that should happen. This would increase their value to biotechnology firms who are trying to raise money and prevent run-of-the-mill stock buyers from getting fleeced.”

The event that triggered Herper’s call for new legislation is yesterday’s revelation that Seattle-based Cell Therapeutics deviated from an agreed protocol in 2008.  Herper characterizes this mainly as the FDA’s failure for leaving SPA disclosures “entirely up to the company” and says the confidentiality protection “represents one way in which the regulator fails to  make sure investors have information they need.”

However, as much as I’m a fan of government transparency, the responsibility to investors lies with the company not with the FDA.  To the extent details of an SPA are material, they should be disclosed.  Ongoing developments with respect to clinical trials should likewise be assessed as part of a company’s disclosure controls and procedures and disclosed as necessary.

Did Cell Therapeutics fail in this duty?  Unclear.  As an article by Adam Feuerstein pointed out on Feb. 1, Cell Therapeutics did disclose that they halted enrollment in the trial early.  However, the company did continue to reference the SPA in subsequent press releases.

Would FDA publication of the SPA have helped?  Also unclear.  The FDA’s guidance on SPAs (pdf) says, clearly:

“Failure of a sponsor to follow a protocol that was agreed upon with the Agency will be interpreted as the sponsor’s understanding that the protocol assessment is no longer binding on the review division.”

So I’m not sure what would have been added by having the SPA available.

My bottom line: Companies that fail to disclose material developments or that misrepresent material facts will subject themselves to liability to their shareholders.  Herper’s hope is that disclosure by the FDA would “prevent run-of-the-mill stock buyers from getting fleeced,” but absent evidence that securities laws are failing to provide adequate incentives or remedies, I’m not convinced that forcing these confidential FDA communications open to public scrutiny would help investors or patients.

Bookmark and Share

If You License IP in Canada, You Need to Know About Recent BIA/CCAA Amendments

Adapted from a bulletin by my colleagues Evan Cobb and Brad Newman:

In the U.S., Section 365(n) of the bankruptcy code provides protection to licensees in the event their licensor becomes insolvent.  Canadian law has not historically had that protection, forcing licensors to set up dedicated IP holding companies or other bankruptcy-remote structures to protect their licensees.  However, recent amendments to Canada’s insolvency legislation provide a solution for licensees, at least in the case of intellectual property licensors that are restructuring under the Companies’ Creditors Arrangement Act (“CCAA”) or Bankruptcy and Insolvency Act  (“BIA”) proposal regime.

Under the amendments, even if an intellectual property license has been successfully disclaimed by an insolvent licensor, the licensee’s right to use, or its ability to enforce a right of exclusive use of, the licensed intellectual property is not affected for the duration of the license agreement (which includes any rights of renewal).  The right to continued use is conditional upon the licensee’s continued performance of its obligations under the license agreement in relation to that usage.

Some cautionary notes regarding the Canadian amendments:

  1. The amendments do not provide protection to licensees in a standard bankruptcy or receivership scenario. If a receiver or bankruptcy trustee of the licensor were to sell the licensed intellectual property and terminate the license associated therewith, licensees would generally be left only with an unsecured claim against the assets of the licensor. 
  2. The exact definition of “intellectual property” is uncertain.  Under the U.S. Bankruptcy Code, “intellectual property” is defined specifically (and excludes trademarks).  A similar definition may be adopted in Canada, but at the moment the application could be quite broad.
  3. Obligations “in relation to” use of the intellectual property that the licensee has to comply with may be uncertain in some circumstances.  License fees that aggregate payments for all usage, exclusivity rights and maintenance services may be problematic in light of the amendments. Precise delineation of obligations under a license agreement that are attributable to use of the licensed intellectual property would be a prudent drafting response to the amendments.

Read the whole bulletin for more analysis of the amendments’ implications for IP licensors and licensees.

Bookmark and Share

Monday Biotech Deal Review: February 8, 2010

This week’s Canadian biotech deals feature a new private placement, two medical device acquisitions, a truly dedicated CEO, some HIV funding from Merck. Seeking redemption?   Read more of this post

This Week in the Twitterverse: Weekend Reading

Here are some good tidbits to catch up on over the weekend in case you missed them the first time around on @crossborderbio:

Friday Science Review: February 5, 2010

Several neurological related stories this week and quantum biology?

Glial Cells – They’ll turn against you: An unusual molecule can turn glial cells, which normally surround neurons, into killer cells that attack the neurons they are suppose to protect.  Researchers made the surprising discovery of proNGF’s role while trying to figure out its function in the eye.  They found that it can activate glial cells to turn against retinal neurons and potentially cause vision impairment or loss.  Some of the molecular details were also worked out and they describe the significance of TNFalpha and p75NTR proteins in this cell death process.  These results shed light on potential routes for therapeutic targets to prevent certain cases of vision loss.  The study, published in the early on-line edition of the Proceedings of the National Academy of Sciences, is a collaboration involving Dr. Adriana Di Polo at Université de Montreal and Dr. Philip Barker at the Montreal Neurological Institute.

Unexpected Heart Failure and Treatment: Researchers studying mouse models for neuronal diseases, such as Alzheimer’s, noticed progressive abnormalities in the rodent’s heart function.  The mice had slower heart rates (as expected) but they also had difficulty pumping blood and researchers soon realized that they may have stumbled upon a possible mechanism of human heart failure.  The genetic modification in these mice resulted in decreased levels of the neurotransmitter, acetylcholine.  In contrast to previous reports on heart failure, this is the first study suggesting that slower heart rates may lead to cardiac dysfunction.  Furthermore, the administration of the drug Pyridostigmine, which increases acetylcholine levels and is approved for treating muscle weakness, corrected the cardiac dysfunction.  The research team of Drs. Marco Prado and Vania Prado at the Robarts Research Institute at The University of Western Ontario describe their findings in the latest edition of Molecular and Cellular Biology.

Early Stages of Huntington’s: Insight into the cellular mechanisms in the brain that causes Huntington’s disease is described in this article appearing in the journal Neuron.  Using mouse models expressing the gene mutations causing the disease, scientists discovered increased numbers of NMDA receptors surrounding the synaptic connections between neurons.  The increased NMDA receptor activity also diminishes survival signals leading to brain cell death.  In other words, the neurons become confused and triggers cell death (excitotoxicity).  Although it is not known why the receptors accumulate outside of the neuron, a therapeutic drug is already available (for Alzheimer’s) to treat the early stages of the disease.  Memantine can control the abnormal NMDA receptor signaling specifically outside the synapses and not disrupt the normal activity within the synapse, thereby reducing side effects.  Clinical trials are underway.  Dr. Lynn Raymond at the University of British Columbia led the research team.

Algae + Quantum Biology?: It appears that algae, a very simple organism, figured out quantum mechanics nearly two billion years ago.  During the process of photosynthesis, antenna proteins in the light-harvesting complexes absorb light and transmit the energy between molecules to proteins in the reaction centre.  Researchers at the University of Toronto decided to study this energy transfer and discovered quantum mechanics at play in this photosynthetic process.  This is just a bit beyond the scope of our blog but you can read Drs. Greg Scholes and Paul Brumer’s commentary here or enrich yourself with the detailed study here in the journal Nature.

Biotech Trends Update: Costs Savings from Personalized Medicine Sought by PBMs, Employers, Pharma Face Legal and Privacy Hurdles

When AstraZeneca announced a companion diagnostics collaboration recently, their head of oncology development said the goal was to get “the right treatment, to the right patient, the first time,” a nice turn of phrase* that is becoming a chorus in the healthcare industry.

This week, giant PBM Medco purchased DNA Direct, saying “[o]ur whole thing at Medco is to get people on the right drug the first time.”  DNA Direct uses its research on 2,000 available tests to help physicians, health insurance companies and patients understand how to use personalized medicine.  This is a good move — we said last month that education is key to expanding the personalized medicine market

AstraZeneca, Medco and other providers, employers and insurers would all like to use information on individuals’ health risks in order to reduce their costs, and as the Wall Street Journal reports, they are willing to provide incentives to their employees to mitigate those risks.  However, some of these efforts conflict with barriers put in place by the Genetic Information Nondiscrimination Act (GINA), which prohibits the intentional acquisition of genetic information about applicants and employees, and imposes strict confidentiality requirements on data that is acquired. (H/T @genomicslawyer)

In addition to legal barriers (some still being erected), AMA and other advocacy groups have also reportedly expressed concern.  I agree there is risk inherent in putting the decision of what the “right drug” is in the hands of manufacturers or payors, neither of whom is neutral in the outcome.  Medco, in particular, does not seem a neutral player here (at least based on their approach to Plavix and Effient, though I invite comments if I’m misinterpreting that study).

Still, a solution is required.  As I have been saying for over a year, personalized approaches to treatment have the potential to benefit all participants in the healthcare system, as the KRAS-Erbitux story has proven.  As Procter & Gamble said when investing in Navigenics’ funding round this week, “Personalized genetic testing can have significant meaning in helping consumers focused on prevention and wellness live better, healthier lives.” 

My bottom line:  A large part of the problem here is the low level of trust from the public, which even limits governments’ ability to act.  That’s particularly unfortunate, because government is the closest thing we have to a neutral funding source for comparative effectiveness and personalized medicine research (despite also being a payor). This is a problem much bigger than just personalized medicine, but until trust is restored, valuable cost savings and health benefits will go unrealized.

Bookmark and Share

* A concept I’ve been trying to call “personalized effectiveness” — tell your friends.

Biotech Trends Update: Teva’s BLA for Neupoval is Accepted at the FDA

Teva’s decision last year to submit a full biologic license application (BLA) for Neupoval looks positively prescient today.  Teva’s product is already sold in the EU as a biosimilar to Amgen’s Neupogen, but a U.S. biosimilars pathway is stalled along with the rest of health reform and today, the FDA accepted Teva’s BLA, clearing the way for a review of Teva’s clinical data and potentially for approval of the product.

FDA approval isn’t Teva’s only hurdle, though.  Amgen’s U.S. patents on Neupogen don’t expire until 2013, and the two companies are currently litigating the issue of whether Teva’s product infringes those patents.  Furthermore, the Dow Jones article quotes Credit Suisse analyst Michael Aberman who points out that in the EU Teva’s product only has 5% market share, competing against both the original Neupogen and Amgen’s longer-acting Neulasta.

Investors’ reaction? Teva shares were up 1.4 percent, Amgen shares were off minutely.

My bottom line: If you want to read tea-leaves to predict the approach other biosimilar products will take (and I do), watch the Neupoval BLA closely.  The calculus undertaken by other potential market entrants will weigh Teva’s success and costs with this approach against the costs of any Congressional requirement for data exclusivity period and any FDA requirement for clinical trials in an eventual biosimilars regime.

Follow our coverage of North American biosimilars news on this Biotech Trends in 2010 page.

Bookmark and Share

Monday Biotech Deal Review: February 1, 2010

Canadian biotech companies were busy making and closing deals this week, with $44 million raised, four new licensing and collaboration deals, and particularly big weeks for Ospens and the MDS/Dahaner transaction. Read more of this post

Follow

Get every new post delivered to your Inbox.

Join 126 other followers