DRUG DISCOVERY AND DEVELOPMENT SESSIONS
Sponsored by Astellas Pharma US

Monday, 2 May 2010
2:00–3:30 PM
Due Diligence: It's NOT Just the Science
4:00–5:30 PM
Reengineering the Clinical Trials Contracting Process

Tuesday, 4 May 2010
8:00–9:00 AM
Dual-Specific Antibody Approaches to Cancer Therapy
9:30–10:30 AM
Building Co-discovery Collaborations to Sustain Pipelines: Executive Perspectives on Models That Work
2:00–3:30 PM
Realization of the Promise of Antibody–Drug Conjugates (ADCs)
4:00–5:30 PM
Is Big Pharma Outsourcing Discovery Research to Academia?

Wednesday, 5 May 2010
8:00–9:30 AM
Where Are the Drugs to Stop Bad Bugs?
10:00–11:30 AM
High-Hanging Fruit: Drugging the “Undruggable” Targets
2:00–3:30 PM
Can We Reverse Memory Loss During Aging?
4:00–5:30 PM
Challenging the Conventional Wisdom: Reemergence of Innovative Chemistry for Breakthrough Drugs

Thursday, 6 May 2010
10:00–11:30 AM
Cardiovascular Drug Development: In or Out?

Dummit went on, “So we'll open this forum where Andrea can pose some of those difficult questions to these computational experts. We hope to start with a dialogue about the reality and then conclude by identifying some areas for future collaboration to further product development.”

Dummitt says this panel will be interactive following brief presentations by speakers who were asked to use layman's terms for a general audience rather than one specializing in information technology. “Thom Dunning will discuss Blue Waters, which is 100 times more powerful than today's general purpose supercomputers but dramatically simpler to use. Then Emad Tajkhorshid (professor of medical pharmacology at UL Urbana–Champagne's college of medicine and the Beckman Institute) will talk about the role of the computational microscope in describing biomolecular behavior and how that will affect the development of new treatments. Rick Stevens (from Argonne National Laboratory and the University of Chicago) will speak on computational tools for genomics and metagenomics, genome annotation and reconstruction, and metabolic modeling. Then Andrea will ask some tough questions about computation and its potential. I think she will represent the biotech industry very well.”

Oncology: Despite some clinical and commercial success, MAbs for cancer treatment often have limited efficacy, and patients can develop immune resistance to them. Combining multiple cancer-fighting agents is becoming an important aspect of cancer therapy. Novel concepts have emerged including antibody fragments, bifunctional MAbs, and T cell–engaging antibodies that redirect cytotoxic lymphocytes to cancer cells. MAbs are also used as vehicles to deliver cytotoxic drugs to tumor cells in so-called conjugate therapies. Recent advances in linker stability, drug potency, and target selection have increased clinical efficacy and safety in several different indications. Antibody–drug conjugates are emerging as a prominent therapeutic modality.

Many researchers have tried to unravel the mechanisms of anticancer immunity, and recent progress has led to significant clinical success for some cancer vaccines. Both patient-individualized approaches and recombinant therapeutic vaccines are in phase 3 clinical trials for diseases such as prostate cancer, breast cancer, and non–small-cell lung cancer. Many industry insiders expect to see therapeutic vaccines approved during the next few years.

Vaccines: In 2004, the World Health Organization (WHO) published a top-10 list of diseases with inadequate near-term therapeutic outlooks, and infection by antibiotic-resistant bacteria topped that list. Every year in the United States alone, methicillin-resistant Staphylococcus aureus (MRSA) infects >94,000 people and kills ~19,000 — more than emphysema (12,551), HIV/AIDS (14,016), Parkinson's disease (14,593), and homicide (18,573). The drug resistance trend shows no sign of abating. Where will drugs come from to combat these killers?

The avian and swine flus added urgency to a rising demand for effective vaccines worldwide, and WHO is calling for increased capacity to discover, test, manufacture, and deliver such products. Several major infectious diseases also consistently plague developing countries, affecting billions of people. New scientific discoveries and innovative public–private partnerships increase research and investment in vaccines to combat these diseases. Innovative technologies are attacking deadly pathogens as well as cancerous tumors. In addition to various influenzas, MRSA, enteric Escherichia coli (ETEC), shigella, salmonella, and other infections may be treatable using new vaccines. And existing vaccines for anthrax, rabies, and typhoid could be improved. But many technical, business, regulatory, intellectual property, and policy hurdles stand in the way of vaccine development and technology transfer.

Inducing effective immune responses is a key challenge in developing new vaccines. Adjuvants are often used to boost immune response or reduce the amount of antigen needed. Advancing scientific understanding of immune responses has led to new adjuvants, including toll-like receptor agonists, tumor necrosis factor receptor ligands, cytokines, and liposomes — although alum remains the only one widely used and approved for human use. Some others are approved for limited use.

Diseases of Aging: As early as age 20, the mental performance (memory, comprehension, and cognitive speed/function) of normal healthy adults begins to slowly deteriorate. A census report from the National Institute on Aging predicted that the world's 65-and-older population will hit 1.3 billion by 2040. A major research goal is to develop treatments that promote healthy aging by delaying or mitigating diseases such as Alzheimer's and Parkinson's diseases. Cognitive decline similar to human dementia and healthy aging is seen in laboratory rodent models, which provide important insights into brain mechanisms that underlie age-related memory loss. Changes in multiple-organ contributions to brain functions that make and maintain new memories are a recent discovery. Several sessions at the 2010 BIO International Convention will cover these topics.

Despite advancing scientific understanding of Alzheimer's disease, a clear path to identifying treatments remains elusive. Patient selection and validating early drug responses or appropriate outcome measures are two difficulties companies need to overcome in working on this difficult therapeutic problem. One session brings together experts from academia and industry to discuss the strategic use of biomarkers in Alzheimer's disease clinical trials. Another will revisit a recent joint meeting of the New York Academy of Sciences and the Alzheimer's Drug Discovery Foundation that explored the neurobiology of cognitive aging and how it relates to neurodegenerative disorders.

Practical Matters: Clinical studies present numerous legal challenges across the range of therapeutic areas, and those difficulties become even more complicated when trials are conducted abroad or involve contract research organizations (CROs). Clinical trial delays can cost ≤$35,000/day, with a typical cost overrun costing >$5 million. They also shorten the period during which a product can be commercialized before its patent protection expires. In a recessive economy, biotech companies feel pressured to increase the value obtained from each dollar they spend and maximize returns to their investors. By following big pharma's lead in reengineering the clinical trials contracting process, the industry should be able to reduce overall costs and increase the value of its products.

Of course, pharmaceutical companies outsource many routine aspects of preclinical drug development, as well. But they have long maintained their grip on the earliest steps of drug discovery, characterized by biological experimentation to identify drug targets. Now they're looking for help from smaller companies and from academic laboratories. They aim to populate pipelines depleted by patent erosion and competition, and some want to find ways to modulate known drug targets that have been historically intractable: e.g., peptide transmitters, stapled peptides, and glial cell therapies. Featured companies in one convention session believe they may have the tools to reach those targets.

The biotherapeutics industry is evolving from a model of vertical integration and internally developed pipelines to one of distributed resources and externally derived pipelines. This distributive model requires judicious partnering during drug discovery between traditional large pharma/biotech companies and innovative-rich small partners. Joan Lau (CEO of Locus Pharmaceuticals) organized a session for the 2010 BIO International Convention's drug discovery and development track called “Building Codiscovery Collaborations to Sustain Pipelines: Executive Perspectives on Models that Work” to explore multiple facets of successful codiscovery collaborations and what partners do to nurture scientific innovation while meeting investor and customer expectations. Panelists will provide executive perspectives from both sides and give concrete examples of successes and failures to help attendees understand how partners can best work together in discovery collaborations, what big pharma seeks in discovery partnerships, what small discovery partners can offer — and why they can more effectively deliver drug discovery innovations.

INNOVATIONS IN VACCINES SESSIONS AT THE CONVENTION