Welcome to your Monday Biotech Deal Review for June 25, 2012. Highlights from the previous week include the closing of the second tranche of Medifocus’ private placement for gross proceeds of $3.3 million. Read on to learn more. Read more of this post
On the heels of the U.S. government’s recent report: National Bioeconomy Blueprint , Battelle and BIO have released: State Bioscience Industry Development 2012.
The report highlights how the bioscience industry has excelled in terms of job growth. Even during tough economic times and an uneven recovery of the global economy, the industry has generally been an employment generator, well above the U.S. national average.
The report goes on to examine the bioscience industry by state. To read the report, click here
The Dick lab at the Campbell Family Institute of the Ontario Cancer Institute has been instrumental in the field of cancer stem cells. The central tenet of the cancer stem cell hypothesis is that there is a small population of cells within a tumour that are able to self-renew and also differentiate into the full range of cell types found within that tumour. In addition to their role at the head of the tumour cell hierarchy, these cancer stem cells (also known as cancer initiating cells, or tumour initiating cells) have increased resistance to chemotherapeutics, leading to an unfortunate ability to cause both relapse and metastasis.
In their Cancer Cell paper, the Dick lab and collaborators investigated the genes that are involved in controlling this combination of abilities. They determined that the proteins ID1 and ID3 were responsible for controlling the self-renewal of colon cancer stem cells. ID1 and ID3 are members of the DNA-binding protein inhibitor family of proteins that heterodimerize with basic helix-loop-helix transcription factors to prevent their ability to bind DNA. ID1 and ID3 appeared to be exerting their effect by increasing levels of p21, a cell-cycle inhibitor and regulator of self-renewal. p21 itself has previously been linked to protecting cancer cells from stress and DNA damage and it was also found that knocking down ID1 and ID3 led to increased sensitivity to oxaliplatin, thereby linking the phenomenon of increased resistance to chemotherapy and self-renewal.
As an official blog site for BIO 2012, Cross Border Biotech had the opportunity to participate in a fantastic new program known as the “BIO Buzz Center” which enables official bloggers to do webcasts over BIO’s website. During the convention, traffic to BIO’s websites surges – with the audience increasing by 2-3 times the normal size therefore increasing visibility.
Not being shy of the camera I jumped at the opportunity and had the privilege of interviewing Mr. Sanj Singh, President and CEO of Ade Therapeutics
Aside from the fact that my mike level was a bit low and I probably should have hit the makeup chair before taping, the 4 minute interview went very well.
A big thank-you to Sanj, Tracy Wemett and Gayle Kansagor for making this happen.
In light of the Canadian government’s review of the R+D tax credit regime in Canada and the hand wringing around the fallout should the recommendations from the Jenkins report be implented, it was refreshing to hear about the State of Maryland’s approach.
The Maryland government decided to create a unique approach to tax credits for early stage bio and tech companies resulting in “InvestMaryland”. The program has been highlighted in the “BIOtechNOW” event daily : BIOtech_Issue1_17 (2) from the BIO 2o12 convention.
The state program has been well received and local governments like Montgomery county have stepped up to provide additional support .
Welcome to your Monday Biotech Deal Review for June 18, 2012. Highlights from the previous week include the $10 million subscription receipt financing by Allon Therapeutics, the elimination of $11.8 million in debt by MedMira and the syndication of $600 million in debt by Valeant under its existing senior secured credit facilities. Read on to learn more. Read more of this post
BIO 2012 has officially kicked off in the beautiful city of Boston.
Social Media has moved front and centre during the convention with a full range of bloggers and tweeters. This year BIO is re-broadcasting blog posts via: http://convention.bio.org/ . Cross Border Biotech is listed as an official blog site so please check back for the latest updates and news from the convention floor. Speaking of convention floor, the Canadian Pavilion (booth 735) occupies a very large piece of real estate (7200 sq. ft.) and although not officially open is attracting a steady flow of people. The Pavilion houses companies from every province looking to promote, connect and partner.
[Ed. This is the nineteenth part in Wayne's series. You can access the whole thing by clicking here. Please leave comments or questions on the blog and Wayne will address them in future posts in this series.]
The deal structure as outlined in Part 18 of this blog series is not meant to be a perfect, detailed model, or even realistic. However, this is a model which can be easily used to change assumptions and see what the impact is on the cash flow and NPV. Here are two examples.
Cisplatin was the first platinum based chemotherapy and remains the most widely used. Through an alkylating-like mechanism of action, cisplatin kills cells by binding, cross linking and damaging their DNA, thereby stimulating apoptosis through failed DNA repair attempts.
Platinum based chemotherapy is a standard first line therapy following surgery for many of the most common cancers (e.g. lung, ovarian, cervical). While cisplatin is able to produce positive responses in many patients, with time many will suffer from disease progression due to the development chemoresistance. While targeting cancer stem cells may prove to be a successful (and topical) approach, other approaches that seek to overcome the mechanisms of chemoresistance are important. These mechanisms will depend upon the agent to which resistance is conferred, but include increased efflux, mutation in the therapeutically target enzyme, decreased drug activation, increased drug metabolism, drug inactivation, enhanced DNA repair and mutation of the apoptosis pathway.
In this weeks post, the Lu lab at the University of Waterloo sought to boost the DNA-damaging activity of cisplatin. Based upon the authors’ previous studies, where they demonstrated the importance of a dissociative electron-transfer mechanism for reductive DNA damage by cisplatin, the authors proposed that addition of a biological electron donor to cisplatin treatment would increase its activity and potentially overcome resistance. N,N,N’,N’-tetramethyl-p-phenlenediamine (TMPD) is one such donor and in combination with cisplatin it was shown to increase plasmid DNA double strand breaks (a simple measure for DNA-damage activity); increase cisplatin sensitivity in both HeLa cells and in the cisplatin resistant ovarian cancer cell line NIH:OVCAR-3. A key feature of the combination is that it led to synergistic rather than additive effects. Furthermore, the authors proposed that the presence of TMPD actually suppressed the mechanism conferring cisplatin resistance to the NIH:OVCAR-3 cells, however, demonstration of that will require further work.
Indeed, much remains to be done to demonstrate the broad applicability and robustness of the results, but cisplatin’s immense importance in the formulary and its frontline use in a wide range of cancers means that the rapid development of a TMPD adjunctive therapy is one to be hoped for.
Welcome to your Monday Biotech Deal Review for June 11, 2012. The Monday Biotech Deal Review is back with Norton Rose Canada summer law student Jennifer Ng, who has agreed to assist with the deal review over the summer months. A very warm thanks to Keldeagh Lindsay for his dedication and contribution to the blog! The below covers transactions in the biotech space since since May 14, 2012. Highlights include the closing of the first tranche of Stellar Pharmaceuticals’ debt financing, as well as private placements each worth approximately $6 million closed for each of MedMira Inc. and Lorus Therapeutics. Read on to learn more. Read more of this post
The cancer stem cell (CSC) hypothesis – the concept that a small population of stem cell-like transformed cells is important for cancer initiation, progression and relapse – has gained quite a bit of attention in both academia and industry. It is proposed that these populations of cells have the unfortunate combination of being able to reinitiate tumour growth following treatment, as well as being more resistant to treatment, which explains the development of therapy resistance, minimal residual disease and tumour recurrence.
An attractive therapeutic rationale is therefore to develop drugs that either selectively target the cancer stem cells. However, any such treatment would need to have a therapeutic window between killing the cancer stem cells and killing an individual’s healthy stem cells, a population of cells that play important roles in tissue maintenance and repair. One approach is to discourage the proliferative self-renewal role that CSC’s favour and encourage their differentiation, thereby reducing their tumour growth potential. However, despite exactly this mechanism being used by Vesanoid, a treatment for acute promyelocytic leukemias developed over 20 years ago, no similar treatments for other cancers exist. However, the research by the Bhatia lab and collaborators at McMaster University is aimed at reinvigorating this approach.
They developed a discovery platform that can be used to screen molecules for their ability to induce the differentiation of a model of human CSC’s (a variant human pluripotent stem cell line) and but not normal pluripotent human stem cells. Applying their platform in a proof-of-concept screen, initially with well established, annotated compounds from the NIH Clinical and Canadian Compound collections they identified several candidates that induced morphological changes in the CSC model cells, but had no effect on normal stem cells. Unexpectedly a compelling hit arose from the antipsychotic drug thioridazine, with the apparent activity arising from the molecules action as a dopamine receptor antagonist.
With a paper that presents both a powerful screening tool, a potential repurposing of an approved molecule and a new potential target for the selective treatment of CSC’s, there is certainly no shortage of avenues to pursue and hopefully it will not be another 20 years before the we see the addition of another cancer therapy using the differentiation approach.
Divergent Genomic and Epigenomic Landscapes of Lung Cancer Subtypes Underscore the Selection of Different Oncogenic Pathways during Tumor Development. PLoS One. British Columbia Cancer Research Centre
Inhibition of Serine Palmitoyl Transferase I Reduces Cardiac Ceramide Levels and Increases Glycolysis Rates following Diet-Induced Insulin Resistance. PLoS One. University of Alberta
Assessment and implication of prognostic imbalance in randomized controlled trials with a binary outcome – a simulation study. PLoS One. McMaster University
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