Antibiotic resistance could exist before the drug is dosed!

Both the antibiotics we use to fight infection, and the genes that the pathogens use to avoid being killed by the antibiotics, generally have their origins in the natural environment.  Antibiotics are frequently produced by microorganisms in the soil.  At high concentrations, the microorganisms may use the antibiotics to inhibit the growth of competitors; at lower concentrations these antibiotics have signaling roles independent of bacterial stress pathways. 

The huge number of antibiotic resistance genes in the environment may arise because bacteria also have genes that enable them to metabolize the antibiotic structures as nutrients.  The microorganisms also have developed systems to avoid being harmed by the action of antibiotics they themselves produce.  It also seems that many of the components of antibiotic resistance, like the MDR (MultiDrug Resistance) pumps, have other roles beyond dealing with antibiotics.  Unrecognized antibiotic resistance genes may already exist in many organisms in the natural environment.   With contamination of the environment from waste water bearing human pathogens, these unrecognized antibiotic resistance genes have the potential to jump into pathogen species, making it possible to have resistance in pathogens even without human exposure to the new antibiotic.  (J.L. Martinez, Science 321: 365-367, 2008). 

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Factors driving success in specialty pharma?

A new McKinsey study of 143 specialty drugs launched from 1994-2004 concluded that the primary driver for specialty drug market success is differentiation versus the standard of care.   The second most important factor driving market success is market size at time of launch (meaning it is easier to launch a product into a large existing market than to create a new market).  The third factor is the growth rate of the market over the first five years after the drug is launched.  The authors concluded a novel mechanism was not a major driver, although novel mechanism drugs win most often if they have improvements in efficacy against the standard of care.  (Nature Reviews: Drug Discovery 7: 563-567, 2008)

Given that the degree of differentiation was scored by physicians looking back on successful and less successful drugs, I think a more accurate interpretation of the data might be that physicians perceive successful drugs as more differentiated against the standard of care, and that they value differentiation.  I also think interpreting the growth of the market as driving the drug success might be confounded.   It seems to me that a growing market will make drug success more likely, but also that the successful drugs will grow the market.  Despite these caveats on the interpretation of this study, it seems logical that drug developers would do well to aim for a differentiated product in a large and growing market. 

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Picking biopartnering meetings to attend

The Partnering Forum at BIO was a great partnering event, because everyone seemed to be there.  But one of the best features of the smaller partnering meetings is the chance to discover the unexpected possible mutual interests by chance meetings.  At smaller partnering events, you meet people more than once and get to know their interests.   I also like the chance to hear a few talks and panels without skipping possible partnering meetings.   I don’t like it when the big companies have private rooms away from the main partnering floors (sorry, BPE) as that reduces the chance interactions.  Varying the location of the meetings helps draw a somewhat different mix of attendees.  This year, I can’t make the upcoming Atlanta Biopharm meeting (http://www.ebdgroup.com/ebd/conferences/biopharmamerica.htm), but I plan to make BioEurope in November (http://www.ebdgroup.com/ebd/conferences/bio-europe.htm).  See you there?  

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Patient-sponsored drug research and development

Virtual biotech companies are increasingly common, pulling together academic researchers and consultants to advance drug discovery with the fewest possible resources.  Now patient groups see they can do it, too (Amy Dockser Marcus, Wall St. Journal, July 29, 2008, p.  D1-D2.) 

The Myelin Repair Foundation (www.myelinrepair.org), founded by a patient with multiple sclerosis, set up a team of researchers and provided them $13 million over four years.  They are now ready to present their two best targets to drug companies in hopes of partnering for further development by July 2009. 

The Cystic Fibrosis Foundation (www.cff.org) in 2003 supported the determination of the crystal structure of CFTR protein by Structural GenomiX, Inc.   Then an affiliate of the Cystic Fibrosis Foundation funded work by Vertex Pharmaceuticals, Inc., which has developed an oral small molecule potentiator of that CFTR protein.   VX-770 is in a Phase II trial, with positive interim results (PharmaProjects).

Now CollabRX (www.collabrx.com) plans to expand patient-funded research by providing project managers, working on a strategic plan, and offering an internet platform for sharing information, in exchange for a 10% management fee and a 20% share of the IP.  Dr. Tennebaum of CollabRx says patients can get started with as little as $50,000 to $100,000 to support tasks such as molecular profiling of a tumor, which if results are promising, might lead to creation or involvement of a biotech company.  The current roster of clients includes the Bonnie J. Addario Lung Cancer Foundation sharing annotated specimens from a biobank; a melanoma collaboration funded by a grant from the Melanoma Research Alliance to genotype melanoma tumors for drug sensitivities in subsets of patients;  and  Support of Accelerated Research for Niemann-Pick disease type C, a group looking to identify a combination therapy (presumably of existing drugs) within three years to delay the onset and progression  of Niemann-Pick, a lysosomal storage disease.  CollabRx is also looking to create Health Commons, a non-profit marketplace for data, materials, resources and services needed for studying and treating disease.  Biotech companies and patients who want to pursue research and drug development could find information and services on the site. 

Patient group involvement may spur innovations that might not be supported by other types of funding. 

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Pullan Consulting

Linda M. Pullan, Ph.D.

Biotech Business Development

www.pullanconsulting.com and www.lindapullan.com

e-mail: lpullan@msn.com

805-558-0361

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