5th Annual 2005 Entrepreneur Venture Conference

The WTC is seeking technology-driven, women-led companies to apply to present at the 5th Annual 2005 Entrepreneur Venture Conference on November 1, 2005 at Microsoft Silicon Valley Conference Center. Applicants will be reviewed based on the following criteria: * An innovative technology * credible team and business plan * strong and profitable market opportunity * defendable competitive advantage * completed seed round or customer beta * seeking Series A or B Round * and a woman in a leadership role (at least at C level) or position of equity Download and fill-out Application ($75 Applicant fee applies) http://www.wtc-sf.org/vc_applicant_deadline.htm For more information, contact applicant@wtc-sf.org. Deadline for applicants is August 15, 2005. "The WTC Springboard conference in June of 2004 was instrumental in helping us secure our Series A round. When we decided to seek funding, I made up a wish list of Board members and investors. Mitchell Kertzman and Hummer Winblad were at the top of the list. Through the conference, we were introduced to Mitchell and Hummer who in turn introduced us to Matt Miller and WaldenVC. Palamida is extremely fortunate to have two such incredible and experienced Board members for our company. I am grateful to the WTC team for helping us reach such world-class investors." Theresa Bui Friday, Founder & 2004 Venture Conference Presenter 2005 Venture Partners Asset Management Company Cargill Ventures Hummer Winblad Venture Partners Opportunity Capital Partners

The Ultimate Goal-Predictive, Preventative, and Personalized Medicine By G. Steven Burrill, CEO of Burrill & Company G. Steven Burrill is CEO of Burrill & Company, a San Francisco-based life sciences merchant bank with over $500 million under management. In 2002, Mr. Burrill was recognized as the biotech investment visionary by the prestigious Scientific American magazine (The Scientific American 50). He currently serves on the Boards of Directors of Catalyst Biosciences, DepoMed (Amex: DMI), Galapagos Genomics, Pharmasset, Targacept, and Third Wave Technologies (NASDAQ: TWTI), and is Chairman of the Boards of Icoria (NASDAQ: ICOR) and Pyxis Genomics. Prior to founding Burrill & Company in 1994, he spent 28 years with Ernst & Young, directing and coordinating the firm’s services to clients in the biotechnology/life sciences/high technology/manufacturing industries worldwide.

Personalized medicine-getting the right drug to the right patient—has been gaining momentum steadily over the last several years. While three years ago, the concept was just emerging the promise has evolved into a reality with the advent of a growing list of targeted cancer therapies including Genentech’s Herceptin, Millennium’s Velcade, and ImClone’s Erbitux. (See Figure entitled, "Targeted Cancer Therapies Approved and Experimental"). Targeted cancer drugs are thought to have fewer side effects than traditional chemotherapy drugs because they go after cancerous cells, leaving the healthy cells intact. Many of these drugs are also designed to hone in on specific proteins or treat a form of cancer that’s identified by the presence of a certain gene. That’s certainly the case with Genentech’s Herceptin, which is only effective in women who have multiple copies of the HER-2/neu gene—approximately 25% of all breast cancer patients. It’s also the case with ImClone’s Erbitux, which only works on cancers that are dependent on epidermal growth factor receptors (EGFR) for tumor growth. Cancer Management Greatly Facilitated With a prevalence rate of between 1% and 1.5% in the developed world, cancer represents a huge opportunity for a more predictive and personalized approach to therapy. Herceptin, posted sales in 2003 of $424.8 million—a level of popularity that might not have been achieved without an accompanying diagnostic such as HercepTest ™ to identify HER-2 positive women responders to the drug. Today, HER-2 over-expression is a requirement in Herceptin’s label. Erbitux, which was developed by ImClone Systems and Bristol-Myers Squibb, is a monoclonal antibody that binds specifically to epidermal growth factor receptors on both normal and tumor cells and competitively inhibits the binding of those factors and other ligands such as transforming growth factor-alpha. EGFR is expressed in a number of cancers including lung, breast, pancreatic, bladder, prostate, kidney, and in cancers of the head and neck. In fact, up to 77% of colorectal cancer tumors express EGFR. Two days after the approval of Erbitux on February 12, 2004, the FDA also gave the green light to market a diagnostic kit called EGFR-pharmDx™, which helps to identify patient eligible for treatment with Erbitux. Made by DakoCytomation, the same company that produces HercepTest, EGFR-pharmDx was submitted for approval in parallel with Erbitux. Other companies are following suit. Roche and Epigenomics are collaborating to develop molecular diagnostic and pharmacogenomic cancer products based on Epigenomics’ DNA-methylation technologies. The two companies are creating diagnostic products for use in early detection of cancers, their characterization, and prediction of treatment response to particular anti-cancer drugs. Early detection can make a tremendous difference to a patient’s outcome. For example, when ovarian cancer is detected before metastasis, surgery has proven curative in 90% of the cases. Prognosis for this cancer is very poor otherwise. Biotech firm Immunicon is developing technology to automatically collect, identify and analyze rare cells from whole blood, which is being used to create products that will focus on cancer diagnostics based on the analysis of circulating tumor cells. In early studies, Immunicon found that breast cancer patients with even a few tumor cells circulating in the blood had reduced survival compared to those who had none. This kind of information is valuable for tailoring care as patients with circulating tumor cells might signal more aggressive cancer, requiring more radical treatment. Other firms such as Genomic Health in the U.S. and Dutch firm, Agendia, began marketing genomic tests for breast cancer earlier this year. Massachusetts General Hospital has been using its own test to measure the activity of two particular genes in breast cancer tumor tissue. The test provides clues as to whether patients are likely to respond to the widely used breast cancer treatment, tamoxifen. To date, scientists have identified molecular markers for breast cancer, lung cancer, and various blood cancers.

Keeping Track of Treatment Outcomes Theranostics, the combination of drug therapy and diagnostics, enables two important goals of personalized medicine—the identification of patients most likely to respond to a given medicine and the ability to monitor the biological effects of the drug as therapy progresses. This targeted approach to treatment improves patient outcomes by helping doctors make more effective use of various therapeutic agents. In addition, theranostics can dramatically reduce adverse drug reactions (ADRs), which cost the U.S. healthcare system $15 billion annually and are responsible for more than 100,000 deaths. Advances in molecular diagnostics are enabling more precise clinical diagnosis earlier in the disease process. Some tests are able to determine predisposition and susceptibility while others help to determine if a particular therapeutic is working as anticipated. Dr. George Poste, former SmithKline Beecham CSO and current head of The Biodesign Institute of Arizona State University, is a strong advocate for the link between diagnostics and therapeutics. He believes that as we learn more about the correlation of the specific patterns of altered gene and protein expression in different subtypes of disease with variable responsiveness to treatments, we’ll be in a better position to develop medicines that act only on specific subtypes of disease and only on patients with the relevant molecular pathology. While the use of biomarkers to measure drug induced changes in a patient’s blood or tissue is growing, this technology is still in its infancy. Biomarkers are used primarily as prognostic markers or as pharmacodynamic markers. Prognostic markers are able, for instance, to match a novel cancer drug to the molecular profile of an individual tumor. Pharmacodynamic markers are able to confirm whether or not the desired biological effect has been achieved. Using molecular markers, scientists also are able to create more targeted therapeutics (See Figure 2 entitled "The Discovery Process of the Future will Begin with an Understanding of Disease at the Molecular Level"; Source: IBM Life Sciences). In the future, companies will define the different disease pathologies and molecular mechanisms in a particular disease family and use emerging techniques to identify targets and test them against various biologically based molecules that have been designed to interact with them. At the same time, companies can design diagnostics based on biomarkers in tandem. FDA Embraces Pharmacogenomics The FDA has already given the green light to several diagnostic products that link the "Dx" to the "Rx" by identifying patients that are genetically inclined to be the best responders to a particular medication. Last November, for example, the FDA approved labeling for an Eli Lilly drug, Strattera (for attention deficit disorder), which said on its label that a genetic test is available to show if the patient can metabolize the drug properly. In 2003, the FDA also issued draft guidelines on pharmacogenomics, asking for voluntary submissions of genomic research to help the agency gain experience in this arena—a move that many took as an endorsement of the personalized medicine paradigm. Indeed, when making the announcement, then FDA Commissioner Mark McClellan noted, "Pharmacogenomics holds great promise to shed scientific light on the often risky and costly process of drug development and to provide greater confidence about the risks and benefits of drugs in specific populations. Pharmacogenomics is a new field, but we intend to do all we can to use it to promote the development of medicines. By providing practical guidance on how to turn the explosion of pharmacogenomic information into real evidence on new drugs, we are taking an important step toward that goal." Under the new draft guidance, if a drug company wants to include such information on a label, it will need to share test results with the FDA. The agency also wants to review pharmacogenomic data if the drug developer used such information to determine which patients should receive the drug in clinical trails. Although the FDA is unlikely to see a full submission of a pharmacogenomics-based drug until 2005 and probably later, a number of biotech firms are already forging the process along side the agency. There’s likely to be plenty to contemplate as the industry and the FDA explore the various implications for pharmacogenomics-based drugs, including the predictive power of the accompanying molecular diagnostics and making sure that the genetic markers are prevalent enough in the population to make the drug worth releasing. Ethics Abound, but the Gains Are Worthwhile As myriad ethical questions continue to surround this area of research—including whether or not diagnostics should be available for diseases for which there is no known cure, or whether employers or insurers will use genetic information in a discriminatory fashion—patient security will play a big role in the future viability of this approach. So, too, will the answers to the ethical questions themselves, which may yet take years to discover. While skeptics are worried about privacy issues and the ultimate medical benefits, advocates of this approach are excited about the potential correlations yet to be unearthed. We’re already seeing dramatic changes in the way that cancer is being addressed, moving from a more acute setting to chronic care. In the future we’ll see more progress with other diseases that are difficult to manage, such as Alzheimer’s and Parkinson's. We’ll also see the predictive, preventative, and personalized paradigm applied to conditions that are becoming chronic and acute such as cardiovascular disease and obesity. *Please reference or credit any material, article or figure cited from http://www.medicineandbiotech.com as: Copyright 2004. MedicineandBiotech.com, http://www.medicineandbiotech.com/ Disclaimer: MedicineandBiotech.com is managed by AstraGen LLC. Please re-distribute this e-magazine. AstraGen LLC and MedicineandBiotech.com do not assume, and hereby disclaim, any liability for any loss or damage caused by errors or omissions in any material published at the web-site http://www.medicineandbiotech.com, whether such errors or omissions resulted from negligence, misstatements or other oversights.

Proteomic Bailout: The end of Gene Prot

By Dr. K. Maggon, PhD, Pharma Advisor, Geneva, Switzerland; email: kmaggon@yahoo.com March 2005. Volume 7. By the end of March 2005, GeneProt (initially Geneva Proteomics) a proteomics company in Geneva ends its operations and terminates remaining 53 staff on its payroll. Gene Prot was founded in March 2000 during the period of biotech genomic and proteomic gold rush era by five professors from University of Geneva (Profs RE Offord, D. Hochstrasser, R. Appel, A. Bairoch and K. Rose) with experience in protein chemistry, mass spectrometry, clinical chemistry and bioinformatics. All the founders except Prof Offord, who left in early 2002, were members of the advisory board or as chief scientific officer (K. Rose). It had two Nobel Prize winners on its scientific advisory board (Profs A. Klug and EM Fischer) and was able to attract top talented staff and employed 120 persons in 200. The company was able to raise $150 million in three financial rounds within the next two years and attracted investors like Fidelity, Compaq Computers and Novartis. At its peak period of glory in 2001, the company was valued at $200 million. The state of New Jersey in 2001, awarded GeneProt numerous incentives, including a generous construction allowance in excess of $6 million.and a state Business Employment Incentive Program grant with an estimated value of $3.27 million over a 10-year span to open an R&D/production facility and locate its headquarters in New Brusnwick. and to create150 high-end jobs. The North Brunswick site was aselected because of its close proximity to current and prospective partners, mainly pharmaceutical companies, and the area's access to leading academic institutions. Fifteen of the world's 20 largest drug companies have major facilities in New Jersey; and Bristol-Myers Squibb, Johnson & Johnson, Merck, are headquartered in the state. Novartis, has its Consumer Health Division headquartered in Summit, N.J., only 28 miles (47.6 km.) from New Brunswick. Another major location factor was the New Brunswick site's access to the high-powered academic cluster along Route 1, stretching between Rutgers University and Princeton University. This site was closed within a year after opening. By the end of 2004, 150 biological products (proteins, peptides, vaccines) were approved by FDA, are marketed and another 370 are in clinical trials for over 200 diseases and indications. In 2003, sales of biotechnology products were $46 billion, a ten percent share of the global pharmaceutical markets. Erythropoietin, sold under different brands by Amgen, Johnson & Johnson, Roche, Kirin and Sankyo has been the best selling medicine with sales of $11.8 billion in 2004, followed by human insulin brands at $5.6 billion and interferon brands at $4.6 billion. Some recently introduced biological products like Rituxan (Roche, $2.8 billion), Enbrel (Amgen, Wyeth, $2.6 billion), Remicade (Johnson & Johnson, $2.1 billion), GCSF (Amgen, Roche $1.8 billion) and Hereceptin (Roche $1.3 billion) have reached the billion dollar sales in 2004. Comprehensive analysis of biological systems or molecular profiling of DNA, RNA, proteins, lipids, carbohydrates, and metabolism is an important tool for discovering and developing therapeutic proteins, drug targets and diagnostics. The proteomic era started on the promise that since proteins mediate most biological events and drug effects, know-how in protein research is a central part of modern drug discovery and development. The elucidation of the human proteome will provide a better understanding of the physiological functions of various proteins in cells, tissues and body fluids. Mass spectrometry based methods for screening linked with affinity or size based separation of proteins permit analysis of thousands of proteins. Proteomic companies with industrial scale integration of protein separation, analysis and identification by mass spectrometry and computing and bioinformatics were to identify unique proteins involved in human diseases by comparing diseased tissues or fluids with normal healthy tissues. Potentially interesting proteins or peptides can thus be selected for further research and development. Of interest are molecules with therapeutic potential as well as novel targets to be used in lead discovery and characterization process and biomarkers which can be measured directly and could be correlated either to disease state or to efficacy and side effects of therapies. The biological function of the unique protein in human disease is elucidated through appropriate bioassays and chemical protein synthesis process used to make sufficient quantities available for preclinical and clinical testing. The advantage of the proteomic over genomic include the ability to measure posttranslational modifications (glycosylation), screening of cells (platelets) and fluids (plasma, synovial and cerebrospinal fluids). GeneProt gained immediate endorsement from the industry. In 2000, Novartis and GeneProt signed the World's largest ever proteomics collaboration, within 6 months after its formation. In 2002, GeneProt and Serono signed a Collaboration Agreement whereby Serono received synthetic proteins from GeneProt for screening into their biological assay platform and with Lundbeck for neurological diseases. GeneProt had collaboration with the Swiss Institute of Bioinformatics, and with Geneva University Hospital. The company had several active technology collaborations and partnerships to maintain state-of-the-art technology processes for application to customer projects and our own internal programs. Partners include HP for computing power, Bruker for Ion Trap and MALDI TOF/TOF (Matrix assisted laser desorption ionization, time of flight) mass spectrometry, Waters Micromass for Q-tof mass spectrometry, Waters for protein separation technologies and Gryphon Therapeutics for chemical protein synthesis. Within a year after its debut, GeneProt started the world’s first large-scale proteomic discovery center in Geneva, Switzerland with 51 advanced Mass spectrometers working 20 hours a day. The new center was managed by a world-class team of proteomic and bioinformatics pioneers working in three shifts, and used the supercomputing capabilities of HP’s AlphaServer systems, Tru64 UNIX software and StorageWorks systems to capture, store and analyze the huge volumes of data generated by GeneProt’s proteome analyses. HP’s equity investment in GeneProt was managed as part of US$100 million Genomics Investment Program. The supercomputing technology includes 1,420 HP Alpha-based, Tru64 UNIX computer processors, each of which is capable of performing more than a billion sequence comparisons per hour, while offering increased sensitivity and performance in sequence similarity analysis and it helped map the human genome. GeneProt's Geneva facility, for example, was ranked as the world's 16th most powerful computing site by Gunter Ahrendt Purchasing Consulting. The facility was designed to identify and select for clinical study large numbers of previously unidentified proteins that are potential drugs, targets for drug development or markers that can be used to diagnose or prevent diseases. GeneProt had plans to obtain the total protein profile of healthy and diseased fluids or tissues during the development of an organism, maturation of cell types and tissues and progression of diseases as they vary over time. The partnership with Novartis was for the protein profile (proteome) of three human diseased tissues or body fluids and their healthy counterparts. Under the terms of the agreement, Novartis will also pay defined proteome fees of USD 41 million over the course of four years. Further license fees, milestone payments and reimbursements are possible for GeneProt subject to outcomes according to predefined criteria. Novartis will gain exclusivity for three years or longer for several hundred molecules and information on expression patterns studied in the alliance. For proteomics of the coronary heart disease, subjects were enrolled through the Duke Databank for Cardiovascular Disease, the worlds largest and longest running cardiac catheterization-based database. From the tens of thousands of patients in the database, 241 carefully selected patients consisting of a population with coronary artery disease and a control population with no disease were sampled. After matching of gender, age, and ethnicity, and excluding patients with obvious plasma protein abnormalities, 6 liters of pooled plasma from a set of 53 patients and from a set of 53 control subjects were established. Large volumes of fluids are required in order to have sufficient quantities of those proteins present at very low concentration; this involves pooling, which also serves to dilute normal differences, which occur between individuals unrelated to the disease process. More than 12 liters of plasma was collected by investigators at Duke University Medical Center, for plasma proteomic analysis by GeneProt for a study sponsored by Novartis. GeneProt met its internal delivered six synthetic proteins to Novartis for consideration as potential leads for pharmaceutical or diagnostic development in 2002. Of the six candidates, Novartis selected three for further investigation. And took options for licensing of only one product in 2003. However all the projects were discontinued at the preclinical stage and none of these progressed to clinical trials. Local papers in Geneva mentioned some of the reasons for the failure of the company to take off in spite of attracting industry veterans and respected financial experts in its management team. Non-renewal of the Novartis deal which terminated in December 2004 and inability to attract other partners from the Industry with similar deals was the main reason. The laboratory in the USA, which was closed after a very short duration, was a total waste. The high cash burn rate was reduced very late and if steps had been taken earlier, it could have survived for 10 years just based on the Novartis deal. Local press highlighted other wasteful practices like very high salaries and bonuses for the management team and founders. There were some press reports that the founders received $2 million each and additional bonuses after Novartis deal. *Please reference or credit any material, article or figure cited from http://www.medicineandbiotech.com as: Copyright 2004. MedicineandBiotech.com, http://www.medicineandbiotech.com/ Disclaimer: MedicineandBiotech.com is managed by AstraGen LLC. Please re-distribute this e-magazine. AstraGen LLC and MedicineandBiotech.com do not assume, and hereby disclaim, any liability for any loss or damage caused by errors or omissions in any material published at the web-site http://www.medicineandbiotech.com, whether such errors or omissions resulted from negligence, misstatements or other oversights.

StockConsultant.com Enter Symbol