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Single cell diversity - wow! we are so complex!
Sequencing of the genomes of single cells reveals so much complexity. In tumors, single cell genome sequencing revealed that 4 individual cells had "hundreds of additional mutations, many of which where un ique or 'private' to that individual cell". In neurons, each  human neuron probably has between 80 and 300 unique insertions of long interspersed nuclear elements or "jumping genes", differences that could affect a person's susceptibility to neurological disorders, or provide the brain with a reservoir of diversity with which to respond to challenges. single cell genomics
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What targets for a platform technology?
Every platform company must wrestle with the best application to balance risk and reward. The first application can be a modest differentiation but the value in the long run will be if real differentiation can be shown.
Bruce Booth's analysis of targets for macrocyclics lays out a matrix of extracellular versus intracellular and oral versus injectable. Intracellular targets with oral delivery is clearly high rew  ard, but for many platforms, challenging. Within the crowded space of extracellular targets and injectables, other dimensions of differentiation (agonist, bispecifics, good tumor penetration) are necessary. Demonstrating differentiation early and convincingly is key. Cost of goods differentiation does not meet that test for early demonstration; nor would convenience.
Bruce Booth's macrocyclic target analysis
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DEALS: Top Licensing and JV deal makers
Who spent the most in deals in the first half of 2012? Fierce Biotech tallied the big spenders.
1. Roche Genentech $1.37B in neurology, infection, small molecules
2. Abbott $1.37B in Autoimmune/inflammatory and genitourinary, small molecules
3. Merck $1.3B in Cancer, small molecules and antibodies
4. Boehringer Ingelheim $0.81B in Cancer discovery, small molecules
5. J&J $0.5B in Cancer discovery, small molecules
Fierce Biotech on top licensing and JV deals 1st Half 2012
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$$$: VC investments down, but returns in biotech not worse than internet
The VC investment in life science (biotech and med devices) of $1.4 billion in 174 deals in the 2nd quarter of 2012 dropped 9 percent in dollars and 6 percent in deals from the prior quarter. In biotechnology, $697 million went into 90 deals, representing the lowest quarterly total for the industry since the first quarter of 2003. 2nd quarter VC investments by PWC
Bruce Booth, citing data from Adams Street Partners, looked at VC returns for biotech and came to some interesting conclusions.
1. The decreased returns lately come from the reduction in the numbers of a few out-sized winners at exit.
2. Winners don't get more capital than the average company.
3. VCs are not worse at picking winners than in past decades with about 55% of dollars going to losing exits.
4. While over 30 years the aggregate biotech sector returns are similar to internet deals (~2x), the dollar-weighted loss ratio in biotech is significantly less: ~36% vs ~59%, respectively, over the past 30 years. More on VC returns
A great analysis shows that later funds by the same firm have higher returns, consistent with the value of partner experience. Smaller funds do better than the big ones. However, even the top tercile of VC fund managers have only a 48% chance of being in the top tercile of fund performance on their next fund. It is a tough business!
Felda Hardymon analysis of VC fund performance
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Patterns of innovation and challenges of partnering early
Thanks to Mike Boss for sharing a link to the interesting work of Bentley University's Center for Integration of Science and Industry. In a recent article in Nature Biotechnology, they looked at the patterns of biotech innovation for gene therapy, oligonucleotides and monoclonal antibodies, and found them consistent with the patterns of sustaining and disruptive technologies in other areas.
Nature Biotech article
I think the article is great. It shows the long time n eeded for products to be derived from true scientific innovation. I've marked up a figure as an illustration of the challenges of partnering early and rewarding innovation. Pharma partners want mature technology in practical products which are YEARS away from the time when so much of the innovation is done.
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Bacteria cells signal and human epithelial cells listen
Bacteria sense bacterial population density with short fatty acids (acylhomoserine lactones or AHLs) as quorum sensors. When  a threshold of bacterial population is reached, gene expression in the bacteria is changed to regulate biofilms and virulence. Recently, it has been shown that human epithelial cells respond to these bacterial quorum sensor signals and change the integrity of the gut barrier and change epithelial cell migration. More new biology in that microbiome in us! publication on quorum sensor and response
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Pricing Problems all over the place!
Sanofi cut the price of Zaltrap, the VEGF trap for cancer, after doctors at Memorial Sloan Kettering published an op-ed criticizing the high price, saying it was twice as expensive as Avastin and no more effective. But the reduction is really a discount for oncologists, not a change in list price or a change in the patient co-pays.  Sanofi price reduction
Can Merck succeed in bring a somewhat safer sleep aid to the market in the face of generics and cost containment pressure? Most pharma companies are focusing on specialty markets such as cancer rather than these huge primary care markets, where the pressures for safety and price are so large.
Safer ambien?
282 drugs are hard to find, including lidocaine, morphine and other standards, especially injectables. Nearly a third of the industry's manufacturing capacity is not running because of plant closings or shutdowns to fix serious quality issues. Drug Shortages
Health care is far from an efficient market - prices don't reflect the needs of the consumer. Demand does not result in supply because the prices aren't tied directly to patient demand.
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Update:
Yeah! 11 deals that I helped negotiate were signed this year for my clients. ImmunGene put 3 of its antibody interferon fusions in a JV (named Valor Biotherapeutics) with Caliber Biotherapeutics . ImmunGene seeks partners for other antibody interferon fusions or to apply the technology to your antibodies.
Links for webinars and free stuff on my webpage. www. PullanConsulting. com
I hope to see you at
- Biotech Showcase during JPM in San Francisco, Jan 7-9th. Several clients will present at Biotech Showcase and I'll be working to line up meetings for some clients.
- BioEurope Spring, March 11-13th in Barcelona. The BioEurope meeting in the fall was great, with 50+ meetings with potential partners for clients.
See you there!
Sincerely,
Linda
Linda Pullan
1-805-558-0361
www.PullanConsulting.com
lpullan@msn.com
linda@pullanconsulting.com
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