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How Does Biomarker Stratification Affect Drug Development Cost? It Depends. #BIO2010

Posted by Mary Canady May 5th, 2010 .
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bio_conf-logo1-300x218_2On the San Diego Biotechnology Network LinkedIn group, we asked you what you wanted to hear about from the BIO Convention in Chicago, and you requested to hear about Biomarkers. Tuesday I attended a breakout session titled ‘Impact of Biomarkers on Drug Development Complexity and Cost,’ and it described a study done by panel members Federico Goodsaid of the FDA, Michael Palmer of Adaptive Pharmacogenomics, Mark Trusheim of MIT, Steven Averbuch of BMS, Theresa Long of the Van Andel Institute. The study modeled different scenarios utilizing biomarker information and the financial impact on estimated net present value (eNPV) of developed drugs. The group was truly interdisciplinary, and it was clear from the quality of the presentations that they likely worked well together due to their communication skills.
The session described a workshop held in October of 2009 in which case studies on oncology and alzheimers were discussed (featured in Nature Reviews Drug Discovery as well–requires login).
MIT economist Mark Trusheim began by describing the ‘pharmaeconomics’ of choosing patient populations for clinical trials. There are obvious benefits to using biomarkers to enrich populations, but there are many factors which need to be considered, and ultimately it depends on the science behind the drug and the market. The group determined three factors to be the most important: variability in the therapeutic effectiveness of the drug, prevalence of the biomarker, and the quality of companion diagnostics. Trusheim also described modeling different long term scenarios ranging from Phase II extending through to the end of market exclusivity, from the perfect ‘Nirvana’ situation, where everything goes perfectly, to ‘pharmageddon’ where it goes bad at every turn. Trusheim indicated that in both the oncology and Alzheimer’s study, a very significant increase in eNPV could be achieved by utilizing biomarker information.
Steven Averbuch, VP of Oncology at BMS, covered the study results for Herceptin and Vectibix for oncology indications. In the case of Herceptin, it had a large effect on a small population, saving money and adding to the eNPV by allowing a smaller clinical trial, but perhaps precluding the discovery of other biomarkers or indications for the drug, as was found to be important for drugs such as Gleevec. Vectibix had a large effect on a large population, obviating the need for biomarker stratification but giving the drug a higher eNPV because of a larger market size. Averbuch reiterated Trusheim’s three important factors, and the need for increased communication between all the stakeholders to utilize biomarker information to help move from the ‘pharmageddon’ to nirvana drug development situation.
Theresa Long, presented the study on the Alzheimer’s drug Bapineuzumab, and the effect of biomarker stratification on a chronic condition. They used the ApoE4 biomarker and started with data past Phase 2. Three different scenarios were modeled, from an all-inclusive to stratified, with an 80% increase in eNPV in the biomarker study. Long stressed the importance of knowing the prevalence of the biomarker in the population, even for chronic conditions such as Alzheimer’s which has blockbuster potential.
This session was inspiring as it showed how science can drive drug development and how biomarker stratification could lead pharma and healthcare towards a path of increased communication resulting in lower costs. The study has been submitted for publication and the modeling tools that were used will be available. Federico Goodsaid indicated that the tool could be made available to those who contact him.


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Translational Research Forum at #BIO2010: Learning From the Land of Lincoln

Posted by Mary Canady May 4th, 2010 .
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I attended the translational research forum Monday morning at the BIO 2010 convention in Chicago. The morning started with Congressman Dan Lipinski from Illinois, who was a great choice as he is a member of the House Committee for Science and Technology, as well as the House Committee on Small Business. He is sponsoring the NSF Reauthorization Bill, which will increase the NSF budget to $20B by 2015 and include funding for higher risk/reward projects. The bill will also have provisions for research infrastructure and education. This bill is slated to be brought to the House in the Memorial Day work period, and its passage will of course be beneficial to academic researchers, key to translational research efforts.
Congressman Lipinski also discussed the status of SBIR/STTR reauthorization, which is currently in limbo as there are House and Senate bills which must be reconciled. I did not realize that these programs are currently in a temporary extension and thus vulnerable to be no longer available for small businesses. One of the issues plaguing the reauthorization is the disagreement about whether venture capital (VC) funded companies should be eligible. Lipinski was vague as to the future of this bill, but assured us that these business grants are a high priority, especially since they will help to create jobs in this down economy.
The forum continued with a panel themed ‘From Science to Invention’ containing mostly academic panelists from Illinois, with a representative from Pfizer St. Louis (on the Missouri-Illinois border). Ted Mazzone of University of Illinois Chicago explained the organization of their CTSA (Clinical and Translational Science Awards) center, which has sophisticated infrastructure to support collaboration and commercialization across a ‘mini consortium’ that exists within the CTSAs in Illinois. Stephen Kent from the University of Chicago talked about his experience with translational research from early challenges in vaccine research to studies of the decreasing chiralty of drugs and its affects on NCE approvals. David McCormick from the IIT Research Institute talked about the importance of bioinformatics and stratification of patients.
Dean Welsch, Research Fellow at Pfizer, described his work in the Indications Discovery Unit, where drugs are being repurposed to treat new indications. Efforts to streamline internal information around compounds has been key to making these efforts successful. Pfizer is also looking externally, including a pharma portal within the CTSA to exchange materials or information. He also described how they find new partners and technologies, including utilization of resources such as this web-based network of research centers for Idiopathic Pulmonary Fibrosis. Pfizer also creating a model which they hope will also be adopted more universally called Foci of Expertise, in which CTSA experts can be found and connect. In Welsch’s three years using these methodologies, their modestly sized group has moved 5 compounds into the clinic, which is impressive. Welsch also hinted that a ‘creative’ collaboration between Pfizer and Washington University in St. Louis will be announced soon.
The panel discussed the future of translational research as well. Access to biobanking information, software and informatics challenges, and the traversing the ‘valley of death’ appeared to be the common thread among the discussions. The question that kept nagging me revolves around which entity is ultimately responsible for funding translational research, if any. Government initiatives such as CTSA and NIH Roadmap are certainly important, but are they enough to stimulate the level of collaboration needed? I was encouraged by the level of creativity demonstrated by Pfizer, and I’m guessing this has been driven by the need to economize. Hopefully, lessons that are learned will be applicable more generally. Interesting that I had never heard of a CTSA until today–they seem to be more prevalent in the midwest/east coast, but the Scripps Translational Science Institute is a CTSA. How could we apply these lessons in translational research collaboration in Illinois/Missouri to San Diego biotech?


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#EB10 Conference Report: Lee Hood – A Systems Biology approach to prion disease

Posted by Dr. Gunn April 26th, 2010 .
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This is a post from the 2010 Experimental Biology meeting in Anaheim, part of the SDBN conference reporting channel.

Leroy Hood probably doesn’t need any introduction here, but for those who don’t know, he’s a leader in using a systems biology to address large, complex medical problems. One such problem is prion disease, a disorder caused by a proteinaceous infectious agent which results in neurodegenerative symptoms as the proteins accumulate in the brain. After decreasing in recent years subsequent to the slaughter of 4.4 million potentially prion-bearing cattle in the UK and establishment of new industry practices, deaths due to prion disease are now as high as they were at their height in 2003.

As prion proteins accumulate and physiology is disturbed, there’s a change in gene expression of over 7400 genes. using 8 mouse strains, Dr. Hood used subtractive biology techniques to narrow the list of relevant genes to 333. Of this number, 2/3 were already known to be involved from previous work. An additional 100+ genes discovered were newly implicated. To study the dynamics of accumulation co-occurring with prion accumulation, Hood developed a massive dataset consisting of transcriptme analysis, histopathological studies, and tissue distribution studied, combining these data with known protein interaction data and clinical signs of disease. This massive analysis identified the accumulation networks and revealed the dynamics of the process as it happens over 20 weeks. In the human, prion disease can gestate for 4 years, so 20 weeks is a reasonable time for a mouse model.
One of the neatest things to come out of this work was a a means of predicting the cell type involved, based on the differential expression of the genes. All the novel prion-associated genes were correctly predicted this way. From within this dataset, they further identified 15 proteins found in the blood which track the clinical course of the disease. Instead of a definitive diagnosis only being possible upon autopsy, now the disease state can be monitored via blood markers, resulting in much easier monitoring of at risk populations and a far safer food supply.
Dr. Hood took a few moments to mention that he’s founded a company, Integrated Diagnostics, which is undertaking some fascinating projects. Among these are creation of a human proteome atlas, which will yield a quantitative assay for every known human protein, and a microfluidic chip platform with some impressive stats. He said the chip would be able to assay 50 proteins in 5 minutes using a volume of 300nL of serum (not whole blood, I assume) at attomolar sensitivities. With that level of sensitivity, they’re well within clinically significant ranges for most proteins.
To do this, they invented a novel protein capture technique that used a combination of low-affinity 6mers and click chemistry to create highly stable chips with antibody-like specificity. he cited 5 years until their availability.
In 10 years, he expects genome sequencing to be routinely done as part of medical practice, costing no more than a couple hundred dollars (as the inventer of automated DNA sequencing, I’d believe him). What this would allow, for example, is capturing of an individuals MHC locus during allergy testing and identification of specific auto-antibodies.

Update: The slides for this talk (PDF) are now available, as gave the same presentation at the SAGE Congress.


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San Diego Biotechnology Network Partner Event May 27th: Rondaxe Drug Development Symposium

Posted by Mary Canady April 22nd, 2010 .
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san diego drug development workshopDrug development is an area that, according to our 2010 poll, you are interested in, and in previous meetings we’ve discussed that San Diego biotech could grow if we would better complement our drug discovery capabilities with drug development. The SDBN was approached by Rondaxe, a drug development services company, with an idea for an event which will highlight companies they work with from outside the San Diego region. The event will be held May 27th, from 9:00 a.m. to 2:15 p.m., and a light breakfast and lunch will be provided. Please join us, the full description and agenda follows, and you can register here.
In coordination with one major consulting firm and one important CRO in the Pharma arena (Rondaxe and TD2), Helsinn Advanced Synthesis is organizing a drug development symposium. Three major companies involved in API Manufacturing, CMC Services/Consulting and Clinical Development will give a short technical and educational presentation related to their expertise.
The symposium will also offer the opportunity to share your ideas with other participants. At the end of this event, the organizers cordially invite you to join them for lunch.

Rondaxe Drug Development Workshop


Helsinn Advanced Synthesis: The choice of the right CMO to avoid pitfalls by successfully transferring your API / HPAI process. Implementing a roadmap to avoid potential problems and extra costs.

TD 2: Integrates world-class preclinical, clinical and regulatory expertise with “-omic” science and provides unique drug development strategies and services aimed at minimizing the risk for clients in the oncology drug development industry.

Rondaxe: De-risking CMC through experience, project and knowledge management; utilizing virtual business development expertise to maximize value realization


9:00 AM Check-in, Continental Breakfast Helsinn_logo



10:15 AM Welcome Speech
Pierre Vitaloni, Manager Business Development Helsinn Advanced Synthesis
10:30 AM Helsinn: Supply chain challenges for the Biotech / Pharma Industry
Dr. Waldo Mossi, Senior Director
Sandra Moro, Deputy Director Business Development
11:15 AM TD2: Innovation and Precision – The future of oncology clinical development
Linda Vocila, Director of Clinical Operations
12:15 PM Rondaxe: Improving value realization with de-risked CMC and virtual business development
Jeffrey Evans, Rondaxe Managing Member
12:40 PM Rondaxe: How to stay compliant in the currently changing regulatory environment
Karl Hofmann, Rondaxe Quality, President
1:00 PM Participants’ Discussion & Closing Speech
1:15 PM Lunch

Event Details

Who: Biotechnology professionals in the greater San Diego area
What: San Diego Biotechnology Network Partner Event May 27th Rondaxe Drug Development Symposium
When: Thursday, May 27th, 9:00-2:15 p.m.
Where: Tango Del Rey, 3567 Del Rey Street, San Diego 92109 (Directions below)
Cost: $20/$15 Academic, +$5 at the door (cash/check only)
For more information about the event:

Directions: From the North: South on Interstate 5, Exit Balboa Ave, Straight to 4th Traffic Light then left on Bunker Hill St. Building directly ahead 3 blks. From the South: North on Interstate 5, Exit Grand/ Garnet Ave, Straight to 3rd Traffic Light then right on Bunker Hill St. Building directly ahead 3 blks. Park on the street or in the structure just past Tango del Rey.


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#SBS10 Day 3 – Smart mice and blowing House, M.D.’s mind: Drug discovery in epigenetics

Posted by Dr. Gunn April 14th, 2010 .
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At the afternoon session of the Society for Biomolecular Science in Phoenix, it’s all about epigenetics, the study of heritable changes that don’t involve changes in genetic sequence.  Epigenetics explains why identical twins turn out a little different and even clones won’t be exactly identical.

Manfred Jung from Freiberg kicked off the session giving an overview of recent developments in epigenetics and presented what would become the central theme of the afternoon: Here are some diseases which haven’t received the amount of attention they deserve, here are some enzymes and proteins that cause the diseases when there’s something wrong with them, here’s how to target those enzymes. Go get ‘em, boys! (more…)