At “BIO 2007” in Boston, keynote speaker, actor Michael J. Fox, threw down a drug development gauntlet to the biotech industry: “innovate and accelerate the translation of basic science into improved therapies for patients,” he said. More than 200 breakout sessions told attendees how they could do just that.
In “Do’s and Don’ts of Biotech Start-ups,” panelists discussed the financial, legal, and practical aspects of starting a company in the biotech and biomedical device arena. They talked about obtaining and arranging financing, intellectual property (IP) law strategies, personnel issues, partnering with other companies, and outlined simple steps and missteps that can help make or break a new company.
J. Peter Fasse, principal of Fish & Richardson, moderated the panel, which included Elizabeth Douville, Ph.D., vp of GeneChem Management (www.genechem.com), Douglas Fambrough, Ph.D., partner of Oxford Bioscience Partners (www.oxbio.com), Harry H. Penner, chairman and CEO of Marinus Pharmaceuticals (www.marinuspharma.com), and Stephen Bloch, M.D., venture partner with Canaan Partners (www.canaan.com).
Key points of the panel discussion included not assuming a company’s technology will determine its best business model, not starting before a company is ready, involving IP counsel early, not looking for money too soon, developing an IP strategy, hiring a good CEO, and not skimping on a company’s IP budget. “Building a business model around your assets that maximizes ROI is a key decision and laden with assumptions, some of which may be testable given resources, for example, real market research,” Dr. Fambrough said.
Panelists discussed the timing for spinning out of a university, the role of that university, the definition of the market opportunity, the company leadership (scientist founder vs. experienced executive), initial financing, staking out IP, and recruitment procedures for start-up companies. They suggested hiring an IP attorney prior to launching a product or offering public disclosure of a company’s technology in order to protect IP rights. They also discussed working with legal counsel on the development of an IP strategy that identifies the technologies to be protected and that best protects the company’s products.
Another aspect of the panel discussion was looking for money. Panelists agreed that a company that looks for investors before the story is in order is less likely to be financed, and after a failed fundraising attempt, a company may find it harder to be financed. However, getting venture capital input early can help in refining the business model and recruiting the right team. Dr. Fambrough talked about how to decide when it is the right time to start talking to investors, and Dr. Douville offered opinions on when a start-up should raise money and from what sources.
“At a time in which drug development costs are rising, when resources are limited, and big science is increasingly the norm, interdisciplinary and interinstitutional partnerships provide an opportunity for synergy and the leveraging of resources,” reported Anna Z. Amar, technology development associate at the extramural technology development and transfer branch of the NIAID, who chaired a panel called “Partnering with the NIH: We’ve Got More for You Than Money.” The panel session was designed to let BIO participants know about the wealth of resources available to them through NIH that are not related to the more familiar grant and contract mechanisms, Amar said.
Amar concentrated on educating the audience on the ways and means of harnessing NIH resources that are not being well utilized: the publicly available scientific resources useful in both the lab and clinic. The objective was to tell the audience what resources are available and, even more importantly, how to access them.
The first speaker, Bonny Harbinger, Ph.D., deputy director, office of technology transfer at NIH, presented a new text-mining application developed at NIH that makes it possible to match a company’s research interests with NIH and FDA funded inventions. The tool aggregates information from a variety of sources, including the U.S. Patent and Trademark Office, NIH CRISP (database of federally funded extramural biomedical research projects), PubMed, and news articles.
Barbara B. Mittleman, M.D., director, program on public private partnerships, at the office of science policy and office of science policy analysis at the NIH, presented information on public-private partnerships that allow the private sector and academic institutions to partner with NIH for the more rapid and effective achievement of common goals and objectives.
To provide an industry perspective on all of the above, Alan Naidoff, associate director of external scientific affairs for Merck & Co. (www.merck.com), provided examples of Merck’s success stories with NIH interactions. Finally, Gregory Curt, M.D., U.S. senior medical lead, AstraZeneca (www.astrazeneca.com), used his experiences with the NCI as an example of successful industry collaborations with the NIH.
Alfred Yen, professor of law at Boston College Law School, chaired the panel for “Challenges in Reviving/Repositioning Old Compounds to Address Unmet Medical Needs.” As biotech and biopharmaceutical companies explore alternative means to accelerate pipeline building, previously abandoned drug candidates or new combinations of existing drugs may be worth examining when they match an unmet medical need or fit into a therapeutic parameter, according to the panelists. The discussion, which addressed challenges, lessons, and cautions, revolved around two issues.
How can companies discover existing compounds that can be repositioned for commercial success? Three general methods were discussed—fortuity, personal knowledge of scientific literature, and technological approaches. The panelists—Robert Zerbe, M.D., CEO and founder of QuatRx Pharmaceuticals (www.quatrx.com); Michael Bonney, president and CEO, Cubist Pharmaceuticals (www.cubist.com); James Czaban, partner, at WilmerHale (www.wilmerhale.com); and Alexis Borisy, president, CEO, and founder, Combinatorix (www.combinatorix.com)—related experiences their companies and clients have had with these approaches.
Once a compound has been identified, what challenges will companies face in bringing them to market? The panelists divided these challenges into marketing/ public perception, regulatory, IP, and financial issues, based on their experiences. They also discussed future uncertainties that may present new challenges, as much is changing on the IP and regulatory fronts in particular. Panelists outlined the costs and benefits to consider upfront, discussed relevant case studies demonstrating both success and failure, and presented specific problem-solving techniques for acquisition of external compounds, IP, and the regulatory path forward.
Cell Cycle Inhibitors
At a session entitled “Around They Go, and Where They Stop, Only the Inhibitors Know,” panelists discussed cell-cycle inhibitors that may represent an important change in the field of drug discovery and ultimately in the treatment of cancer and other diseases, according to Neil W. Gibson, Ph.D., CSO at OSI Pharmaceuticals (www.osip.com), who chaired the panel. Panelists attempted to answer the following questions:
• Do we understand which proteins we should be targeting?
• Do we understand the PK/PD requirements needed to help guide development?
• Do we have appropriate biomarkers to measure efficacy?
• Do we think we will see an acceptable therapeutic index?
• Do we need to combine cell-cycle inhibitors with existing chemotherapy and do we understand how to combine such agents?
• Do we know which diseases and which patients should be targeted?
• How do we select those patients most likely to benefit?
While cell-cycle inhibitors offer promising opportunities in targeting cancer cell cycles, specifically in the areas of interactions and pathways altered, there are some bottlenecks in this area of research, according to Spiro Rombotis, president and CEO of Cyclacel Pharmaceuticals (www.cyclacel.com), who discussed CDK inhibitors. “For instance, there is no broad agreement about the target profile,” he explained. “People tried to generalize inhibitors that targeted single enzymes, but cancer cells get around this. We need multikinase drugs and ways to optimize them.”
Rombotis added that there was a lack of predictable value from experiments, because animal models could not predict how humans would respond to cell-cycle inhibitors. Finally, according to Rombotis, we are still in the embryonic stages of the biomarker era when we are getting real samples from patients, not lab samples, as an alternative to animal studies.
Proteomics and Cancer
In a session called “Proteomics: A Strategy for Translating Discoveries to the Cancer Clinic,” panelists outlined a strategy for the advancement of clinical proteomic technologies that perform consistently across platforms as well as describing instruments and laboratories to facilitate biomarker discovery. Highlights of the session, chaired by Henry Rodriguez, Ph.D., director of clinical proteomic technologies for cancer at the NCI, and including Steven A. Carr, Ph.D., director of proteomics at the Broad Institute, were identifying the major instruments and technologies used in proteomic research and clinical proteomic applications, identifying cellular and molecular pathways linked to tumorigenesis, describing proteomic alterations that may reflect the onset of these pathways and be measured within the serum/plasma proteome, and describing and comparing proteomic data representation, including qualitative measurements from technologies such as LC-MS/MS.
Fred E. Regnier, Ph.D., Law distinguished professor in the department of chemistry at Purdue University, gave a presentation directed toward conducting immunological assays on multiple antigens in 100–300 patients at a time, which will be needed in translational medicine to validate cancer markers in large numbers of patients. The system is automated and has a detection sensitivity of 1–10 pg/mL, according to Dr. Regnier.
Working in collaboration with Biosystems, Barry Karger, Ph.D., director of the Barnett Institute, presented a global approach to the large-scale generation of disease-specific mAbs to native proteins in blood. “A robust screening method, developed by Biosystems (www.biosystems.com), discovers discriminating monoclonals that are then available for validation studies using microarrays,” Dr. Karger explained. “The identity of the antigens to these biomarkers is determined by antibody enrichment and mass spectrometry. The methodology can generate monoclonal libraries for screening for disease-specific biomarkers.”
Amanda Paulovich, M.D., Ph.D., director of the Fred Hutchinson Cancer Research Center’s Early Detection and Intervention Initiative, explained how she is working with high-tech mass spectrometers to search for biomarkers that may indicate cancer long before a tumor is detected. “For many common cancers, when the disease is caught early enough, nine out of 10 people can be saved,” Dr. Paulovich said. “But the sad truth is that tens of thousands of people each year are diagnosed too late. I am looking ahead to the day when we change all that.”