; OXFORD
Documents
Resources
Learning Center
Upload
Plans & pricing Sign in
Sign Out
Your Federal Quarterly Tax Payments are due April 15th Get Help Now >>

OXFORD

VIEWS: 36 PAGES: 8

  • pg 1
									Q1

2006

OXFORD
n ISSUE 1 page 2

Q S C E W S L N T E S B I O U A RI T EN C Y NP A R T E TE R R E R L E
NEWSLETTER

W H AT ’ S I N S I D E
DEVICES Saving Heart Failure Patients’ Lives, Reducing the Need for Open-Heart Surgery THERAPEUTICS Preparing for a Flu Pandemic TOOLS & INSTRUMENTS Affordable, Fast Genome Sequencing: A Dream Becomes Reality
page 4

Seeing Beyond the Curve to Identify Market-Transforming Technologies
OBP has built its reputation by working closely with each portfolio company’s scientific and executive leadership to help them develop corporate strategies that will move products swiftly forward and position the businesses to bring optimal rewards for investors’ willingness

page 3

to take risk. OBP has made its mark throughout the bioscience field. For instance, OBP’s patient, over-the-horizon perspective made it a leading early investor in genomics and gene-driven technologies, which have now transformed the process by which disease targets are identified and drugs developed. Many of those genomics Since the creation of its first fund in 1993, Oxford Bioscience Partners (OBP) has strived to identify the technologies that will not simply lead to novel products but will actually transform entire markets. As a result, OBP has been a driving force in the bioscience revolution. As their technologies develop, many of these The companies described in this issue— PowderMed and VaxInnate, Solexa, Mitralign and Circulite, and Sirna—represent a new companies prove highly valuable, either to public markets, such as Memory Pharmaceuticals and Geron, or for merger and acquisition, such as Corixa, now part of Glaxo SmithKline, and CombiChem, acquired by DuPont. With more than $900 million under management, OBP continues to draw on its exceptional in-house scientific, information technology and medical expertise, as well as teams of outside consultants with specialized knowledge, to build companies that will revolutionize the marketplaces of the future. companies, such as Human Genome Sciences, Exelixis, and Gene Logic, have moved successfully to convert their proprietary intellectual property into the development of pharmaceutical products.

BREAKTHROUGH TECHNOLOGIES Sirna Therapeutics Re-Invents the Drug VENTURE AHEAD 2006 Biomedical Executive Summit: Evaluating Risk in Decision-Making

page 5

page 6

generation of OBP investments that have the potential to transform the pharmaceutical and medical device industries and, by doing so, benefit public health. These companies possess technologies that may replace outmoded vaccine technologies and prepare for possible pandemic influenza; they will soon bring to market genetic sequencers that could make the promise of the low-cost human genome for personalized medicine real; they may create an entirely new type of therapeutic agent that opens new avenues for treating diseases; and they may herald the end of the need for open heart surgery for many of the 25 million heart failure patients worldwide.

OXFORD TEAM

page 7

W W W. OX B I O . C O M

OXFORD

Q S C E W S L N T E S B I O U A RI T EN C Y NP A R T E TE R R E R L E

Saving Heart Failure Patients’ Lives, Reducing the Need for Open-Heart Surgery
Heart Failure (HF) patients who undergo open heart surgery to repair the progressively accumulating damage to their hearts face long, expensive operations that require lengthy hospitalization and all too often lead to complications and even death. Many more HF patients, however, are not candidates for surgery at all because of existing complications, resulting in suffering and early death. Through Accelerated Technologies, Inc., (ATI), a unique device “accelerator” for interventional cardiology ventures developing minimally invasive technologies, OBP has been founding and investing in companies that may one day end the need for many of today’s open heart surgeries and also make lifesaving procedures more widely available for the world’s 25 million HF patients. Operating since 2001, ATI (www.acctec.net) utilizes cardiology, managerial and venture expertise to identify breakthrough product opportunities and then develops and commercializes these products within standalone companies. Two recently founded ATI ventures, Mitralign and CircuLite, exemplify ATI’s ongoing program. The novel Mitralign system is being developed to treat Mitral Regurgitation (MR), a leak in the mitral valve that, when healthy, keeps oxygenated blood flowing in the proper direction inside the heart. MR robs the heart of pumping ability and the body of needed blood, significantly increasing the risk of mortality in HF patients. The minimally invasive Mitralign system resembles surgical annuloplasty during which a dysfunctional, dilated mitral valve opening is reduced to a functional size. Instead of opening the heart to repair the faulty mitral valve, the Mitralign procedure utilizes catheters to deliver a series of sutures which are cinched together, reducing the circumference of the dilated valve

and treating the MR. Many patients who currently are not candidates for open heart surgery due to their HF condition will benefit from this less invasive procedure. CircuLite is also seeking to expand the number of HF patients whose condition can be improved by developing the world’s smallest minimally invasive micro-assist device for chronic HF. Many chronic HF patients have failed conventional medical therapy, but are not sick enough to justify undergoing a surgical implantation of a mechanical support device to sustain life. Currently, these patients have no other option except to wait for their HF condition to deteriorate while their quality of life declines. The Circulite technology will offer these patients a new, minimally invasive option to increase their heart’s output, thus improving their quality of life. CircuLite’s heart assist device, no bigger than an AA battery, allows subcutaneous placement and endovascular delivery. The miniature size and minimally invasive delivery of the CircuLite device reduce the complications associated with mechanical circulatory support and enable implantation in a catheterization lab by an interventional cardiologist. The device requires only a pocketsize battery pack to operate. These key benefits will allow many more chronic heart failure patients earlier access to mechanical support. Currently some 1 million patients worldwide are candidates for implantation of a mechanical-assist device. That number could double with CircuLite’s technology. Through ATI, OBP anticipates developing other technologies that will transform the lives of millions of people with heart disease and the interventional cardiology industry.

2

DEVICES

OXFORD
Preparing for a Flu Pandemic
The risk of a global influenza pandemic currently facing the world is unprecedented. A virulent strain of H5N1 influenza has reached epidemic proportions in wild and domesticated birds. The best documented avian epidemic of this scale immediately preceded, and ultimately precipitated, the deadly 1918 influenza that killed 100 million people worldwide. The US and other countries are unprepared for a pandemic; the US currently has manufacturing capacity for only 50 million vaccine doses per year and other developed nations are similarly constrained, while the developing world has no reasonable access to flu vaccines and would be devastated by a pandemic. Production shortages of seasonal flu vaccines have added to public anxiety and increased government scrutiny concerning the lack of readiness. Flu vaccines are currently produced using chicken eggs; a fifty-year-old approach with significant problems, including the risk of bacterial contamination, long lead times in the production cycle (nine months from strain identification to vaccine availability), lack of scalability, and the high expense of adding new manufacturing capacity.

Q S C E W S E Q U AB I T E R RI T EN C Y W P A E T E TE R R R O U A L Y R LE E N S L R L T ET R S E N N

VaxInnate seeks to put the power of the innate immune system—the immune response with which we are born—to work. The company’s technology uses the innate response to activate the adaptive portion of our immune system—the “learned” response that defends against repeat invaders—to recognize even mutant strains of a virus such as avian flu. Moreover, the vaccine can be produced out of e. coli culture far faster, less expensively and with less risk of contamination than the current process of growing vaccines in eggs. VaxInnate’s first flu vaccine should enter human testing at the beginning of next year. Based in Oxford, UK, PowderMed already has four clinical and three preclinical programs. Its programs target influenza, chronic viral diseases and cancer, and are all based on its DNA particle-mediated epidermal delivery (PMED™) technology. PMED™ coats gold particles with DNA, which are thrust into the skin of a patient using a helium-powered device. These gold particles are small enough to deliver DNA directly to the nucleus of antigen-presenting dendritic cells in the skin. The cells’ machinery translates the DNA into its corresponding cell surface protein causing the immune system to recognize the cells as foreign, thus evoking an immune response. Successful completion of Phase I trials of the company’s influenza vaccine in the past quarter has paved the way for a larger Phase II study to begin later this year. The PowderMed DNA vaccine will offer many advantages, including faster production and the ability to store inventories in dry form for stockpiling, thus reducing the possibility of supply shortfalls in the event of pandemic outbreaks of flu or other diseases.

THERAPEUTICS

Two OBP portfolio companies, VaxInnate, Inc., and PowderMed, Inc., are developing new vaccine technology to replace this outmoded vaccine production method, which will permit the preparation of a stockpile of readily available vaccine with cross-strain immunity in the event of an avian flu outbreak. Their technologies also offer the potential for new immunotherapeutics for cancer, HIV and other diseases.

3

OXFORD

Q S C E W S L N T E S B I O U A RI T EN C Y NP A R T E TE R R E R L E

Affordable, Fast Genome Sequencing: A Dream Becomes Reality
The completion of the 13-year, $3 billion Human Genome Project (HGP) in 2003 was an epochal event that promised to change the nature of biomedical science, drug development, clinical diagnostics and patient care. However, at present sequencing each additional human genome still costs around $20 million, making it unaffordable and impractical to sequence the hundreds of additional human genomes required to do statistically valid genome comparisons. In the past quarter, OBP portfolio company Solexa, Inc. began delivering the first-generation of the Solexa Genome Analysis System that will enable whole genome sequencing for less than $100,000 for the first time. This represents a milestone as important in its way as the HGP itself, allowing scientists to do the genomic comparisons necessary to move genome-scale science into the clinic. The Solexa System comprises the 1G Genetic Analyzer, Cluster Station and associated reagents, consumables and software. The System’s Sequencing-By-Synthesis process breaks the genome into millions of small, fluorescently labeled pieces read out by high speed laser readers. At full capacity it can generate a billion bases of sequence per day, compared to half a million bases per day for current instruments. Solexa System users should experience dramatic increases in productivity while reducing costs by over two orders of magnitude relative to current state-of-the-art DNA sequencing technologies. To screen a single gene today costs about $1,000. Solexa’s longer-term goal is to reduce the cost to $1,000 for all 30,000 genes. That will make the dream of the HGP real. Sequencing of individual genomes will then be practical for use in a wide range of applications from basic research through clinical diagnostics, and an

affordable part of health care. The ultimate goal of personalized medicine to which the HGP pointed—prescribing the right treatment for the right patient at the right time—will finally be realized. In its initial step toward making that dream a commercial reality, Solexa is delivering its initial “early-access” Systems to launch customers, including several major genomics centers, starting in the second quarter of this year. Potentially more than a dozen Solexa Systems - with a list price of nearly $400,000 for a full-specification instrument, plus $100,000 to $200,000 in Solexa reagents per instrument per year - could be in operation before the end of the current year. The company expects its instrument to be adopted as the standard platform for those centers and eventually to become a core research tool in biotechnology and pharmaceutical laboratories and biomedical research centers throughout the world. OBP enabled Solexa to advance its technology to its present commercial product stage by leading the financing and guiding its purchase of Lynx, a publicly traded instrument maker. This merged Solexa’s technology with Lynx’s instrumentmaking expertise and enabled the new Solexa to complete two successful public offerings. Highlighting Tools & Instruments ExonHit Therapeutics entered its 50th SpliceArray™ commercial project one year after the launch of the service. SpliceArray enables the identification of new therapeutic targets or diagnostic markers based on alternative RNA splicing using the leading microarray technologies. BioProcessors sold its SimCell™ system to NovoNordisk. SimCell is the first fully-integrated cell culture experiment management system for bioprocess development capable of generating data scalable to large-scale bioreactors.

4

TOOLS & INSTRUMENTS

OXFORD
In the entire history of the pharmaceutical industry there have been only two types of therapeutics: small molecule chemicals and protein-based drugs. Sirna Therapeutics, Inc. has moved rapidly ahead to create an entirely novel type of therapeutic agent that may lead to new and better treatments for a wide range of important diseases. With the progress of its lead program into advanced clinical trials this year and a second program about to begin human testing, the entire industry will be watching to learn whether Sirna is on the brink of changing the pharmaceutical world.

Q S C E W S E Q U AB I T E R RI T EN C Y W P A E T E TE R R R O U A L Y R LE E N S L R L T ET R S E N N

Sirna Therapeutics Re-Invents the Drug

BREAKTHROUGH TECHNOLOGIES

In the past few years it has become apparent that short interfering RNA, or siRNA, plays a critical role in almost all aspects of gene regulation in higher cells. The possibility exists for disease-treatment purposes that chemically synthesized siRNAs can be specifically designed to travel into a cell and prevent the production of virtually any disease-causing protein or virus, including proteins and viruses that other types of drugs have never been able to reach. The opportunity to treat previously incurable or incompletely treated diseases with siRNA drugs has led Sirna to ramp up drug discovery and development programs in age-related macular degeneration (AMD), hepatitis C, dermatology, asthma, Huntington’s disease, diabetes and oncology. OBP was part of a high-level syndicate which enabled publicly traded Sirna to become the siRNA technology leader and to capture nearly all the intellectual property in the field. The company has a leading intellectual property portfolio covering over 250 mammalian gene and viral targets and over 175 issued or pending patents covering other major aspects of RNAi technology. Alliances with several strategic partners have affirmed the company’s leadership in this potentially revolutionary technology.

Sirna’s powerful technology lends itself to extremely fast drug development. Sirna is the first company to enter human clinical trials with a chemically optimized siRNA and demonstrate its biological activity in humans. Sirna is also the first company to demonstrate efficacy of a systemically delivered siRNA in multiple pre-clinical models at therapeutically relevant doses. In a period of just 18 months, Sirna moved its first therapeutic candidate, a treatment for AMD, from discovery into human testing. The successful Phase 1 clinical trial for the drug was completed in 2005 and, with strategic partner Allergan, Phase 2 clinical trials will commence in the next few months. Sirna has also selected a clinical compound for hepatitis C virus, which the company plans to bring into Phase 1 clinical trials before the end of this year. In addition, Sirna has established an exclusive multi-year strategic alliance with GlaxoSmithKline for the development of siRNA compounds for the treatment of respiratory diseases.

5

OXFORD

Q S C E W S L N T E S B I O U A RI T EN C Y NP A R T E TE R R E R L E

2006 Biomedical Executive Summit: Evaluating Risk in Decision-Making
Each year OBP brings together its portfolio company executives along with senior executives of pharmaceutical and medical device companies for its annual Biomedical Executive Summit. This year, the theme of the Summit, held May 31-June 2 on Cape Cod, was the evaluation of risk in decision-making. The goal of the Summit was to help the executives improve their ability to evaluate the relative risk of competing alternative courses of action, such as the decision whether to continue a clinical development program or whether to enter into a corporate partnership to transfer risk to a larger company. Estimating risk should be a rational process, relying upon methodologies such as risk-adjusted net present value analysis, real option analysis, and probability assessment. But as attendees discovered, biases inevitably creep into human judgments, leading to faulty forecasts characterized most often by excessive optimism. Successful executives must learn to spot these biases, according to Summit keynote speaker, Nobel Laureate in Economics Daniel Kahneman, Princeton University Professor of Psychology. Professor Kahneman described some of the most persistent psychological errors in the judgment of risk which he has found to afflict even highly experienced executives. Among the biases Kahneman identified were those he termed the “availability heuristic,” in which executives assess risk based on the ease with which analogous situations come quickly to mind rather than relying on

VENTURE AHEAD

the proper evaluation of data. He also pointed to judgments driven by “representativeness” bias, in which evidence based on only partially comparable information can lead to flawed outcome predictions; he also discussed “anchoring” in which executives estimate value based upon an initial baseline number derived from irrelevant past events and from which they then make insufficient adjustment in arriving at a final estimate. Above all, he said, “Over-optimism is the most prevalent bias.” This bias leads to overconfidence and harms predictive ability. Kahneman urged the audience to be vigilant against psychological biases in evaluating risk. He suggested that organizations build discipline into their decision-making processes to free them of over-reliance on intuition and personal experiences, and to look to more objective external evidence to counter the inherent optimism of the wholly “inside” viewpoint. The meeting also featured a presentation by Professor David Scharfstein of Harvard Business School on the risks of clinical trial failure and how successful large and small companies are, comparatively, in managing these risks. Scharfstein presented illuminating and provocative data on the effect of corporate alliances and financial resources on success in the clinic with a particular program. The Summit also included as panelists numerous heads of R&D and business development of major pharmaceutical, biotechnology and medical device companies.

6

OXFORD
Oxford Team

Q S C E W S E Q U AB I T E R RI T EN C Y W P A E T E TE R R R O U A L Y R LE E N S L R L T ET R S E N N

Jonathan J. Fleming Managing General Partner Boston, MA

Alan G. Walton, Ph.D., D.Sc. Senior General Partner Westport, CT

Jeffrey T. Barnes General Partner Boston, MA

Mark P. Carthy General Partner Boston, MA

OXFORD TEAM

Matthew A. Gibbs General Partner Boston, MA

Michael Lytton, J.D., M.Sc. General Partner Boston, MA

Ellen S. Baron, Ph.D. Partner Boston, MA

Douglas M. Fambrough, Ph.D. Partner Boston, MA

Oxford Bioscience Partners (OBP) is a life science venture capital firm that provides equity financing and management assistance to advanced-stage start-ups and later-stage commercially oriented organizations. The General Partners of OBP currently manage
Edmund M. Olivier Founding General Partner Costa Mesa, CA Cornelius T. Ryan Founding General Partner Westport, CT

venture funds with combined committed capital of more than $900 million.

7

222 Berkeley Street, Suite 1650 Boston, MA 02116 Tel: (617) 357-7474 Fax: (617) 357-7476 315 Post Road West Westport, CT 06880 Tel: (203) 341-3300 Fax: (203) 341-3309 650 Town Center Drive, Suite 810 Costa Mesa, CA 92626 Tel: (714) 754-5719 Fax: (714) 754-6802

w

w

w

.

o

x

b

i

o

.

c

o

m


								
To top