R&D: The NGP Head-to-Head

To find out more about the cost of cutting costs, innovation and opportunity in R&D, NGP spoke with two leading experts, R. Richard L. Hamer, Ph.D., Head of Business Development for OriGene Technologies and James Laveglia, Ph.D., Executive Vice President and Director of Research for MPI Research.

NGP. While there is the need to discover new drugs and to implement new technologies, analysts say that in order to save costs, companies may have to face right-sizing, which implies either trimming R&D or, at least, investigating whether it should be trimmed. What is your company doing to make drug discovery and development more efficient?

JL. Patent expirations and a lack of pipeline productivity have certainly created significant challenges for pharmaceutical companies. Many within the industry are now recognising that internal resources are best focused on improving their drug discovery engine rather than drug development, manufacturing and sales.

As a contract research organisation, MPI Research offers comprehensive nonclinical and early clinical drug development services to assist pharmaceutical companies with their drug development needs. Our sponsors often realise efficiencies and cost savings by placing single studies or entire nonclincial development programs with us. Without bearing the significant fixed costs associated with nonclinical drug development, our sponsors are able to focus internal resources on drug discovery while at the same time efficiently and cost effectively moving their drug development projects forward. By providing comprehensive nonclinical drug development service offerings, MPI Research reduces the need to utilise multiple service providers, resulting in an additional savings of time and money for our sponsors.

RH. OriGene’s business model is to develop and provide new research tools and reagents to the bio-pharmaceutical market. OriGene’s TrueClone collection of over 30,000 expression-ready full-length cDNAs is a powerful tool for pharmaceutical companies to discover new gene targets. Individually, these clones have been widely used by the research communities. By switching from de novo cloning to commercial clones, the pharmaceutical companies not only cut down R&D costs and but also accelerate their research. The availability of a wide breadth of human full-length cDNA clones (covering majority of the human genome) makes it possible to screen for novel targets on a global scale.

Novartis has successfully used OriGene’s collection to identify novel activators in PGC-1? induced mitochondrial biogenesis. The newly launched GFC (Genome wide-Full length-cDNA) Transfection Array enables researchers to conduct similar studies without the difficult process of obtaining the clones and preparing the DNA for analysis. The scientists can fully focus on their science while OriGene provides the content for their screen.

NGP. The ultimate goal of the pharmaceutical and biotechnology industries is to bring innovative medicines to the marketplace. Is innovation vital to your company?

RH. OriGene’s reagent based product business is entirely dependent upon the introduction of new products to the drug discovery and development market. We innovate by constantly interviewing researchers in the field to provide input to our internal development and in-licensing teams in their creation and launching of useful tools.

JL. As a contract research organisation, innovation takes on a different context at MPI Research. Our innovation is focused on meeting our sponsors’ needs in the timeliest, most efficient and cost effective manner possible. We invest heavily in facilities, technology and people. Our recently completed US$65 million toxicology expansion project allows our sponsors to quickly initiate studies to meet their nonclinical safety evaluation milestones. Our investment in Provantis, an integrated electronic data capture and management system, provides our sponsors with consistent, high quality data and accelerated reporting times.

However, the most modern facilities and technology are meaningless without quality people. In 2006 we invested over US$4 million on recruiting and training efforts. As result we’ve been able to attract some of the best up and coming talent from leading universities as well as experienced professionals from companies such as Pfizer, Eli Lilly, Bristol Myers Squib and Wyeth.

NGP. With no new antibacterial drugs expected to reach the market any time soon, immediate action is needed to avert a looming healthcare disaster. But antibacterial discovery faces immense scientific and business challenges. Where will the next generation of antibiotics come from?

RH. Antibacterial drug development has been driven to date using tried and true models for the inhibition of basic cellular processes. We strongly feel there are whole arenas of potential targets awaiting discovery through data-driven discovery tools such as genome-wide scanning for anti-bacterial phenotypes. Such tools are just making themselves available to the research community and OriGene is proud to be one of the leaders (along with its partners in the biopharmaceutical industry) in this field with its GFC Transfection Arrays.

JL. Overly judicious prescription of antibiotics, patient compliance and other factors has helped contribute to the evolution of multi-drug resistant bacteria. Market pressures, discovery engine failures, increased clinical trial complexity requirements and generics have pushed many large pharmaceutical companies to reduce R&D investments in anti-bacterial programs or eliminate them entirely.

It’s a complex problem but in the short term the best hope for new antibacterial drugs will likely come from small pharmaceutical and biotechnology companies; either through novel programs of their own or via a continuation of programs abandoned by larger competitors. Increased incentives from government agencies in the form of funding and patent extensions would help drive future investment in anti-bacterial research. However, a better fundamental understanding of bacterial physiology from academia combined with improved pharmaceutical discovery engines is the key to solving the problem long term.

NGP. The world's largest drug company, Pfizer, was forced to terminate the trial of its eagerly anticipated cholesterol-lowering drug torcetrapib. The compound was found to be associated with unacceptably high death rates in a late-stage clinical trial involving 15,000 people. Should a government initiative like the FDA’s Critical Path have prevented this from happening? Do you think we need a similar government initiative in Europe?

JL. Terminating a late-stage clinical trial is always disappointing. Although Pfizer stood to gain substantially had torcetrapib moved forward and eventually received marketing approval, they acted responsibly based on the data available.

The Critical Path initiative has underscored the urgency of translating scientific discoveries more rapidly into new and better medical treatments. Although by applying new and existing technologies we hope to more rapidly and safely meet unmet medical needs, no existing technologies are completely predictive of human efficacy and safety. As the science evolves and the Critical Path initiative matures, I think we’ll start to see more success stories but it’s still very early. It’s something the European community should definitely examine and consider.

RH. Most examples of high levels of either toxicity or of efficacy are driven by the personal phenotypes of the individual patients or, the collective phenotypes of groups of individual patients and their reaction to particular drug regimens. Scanning of patients using broadly applied phenotype analysis tools (HER2 for example) would help identify those patients at risk or those most likely to benefit prior to access to the drug regimen. These “personalised medicine” diagnostics can be developed more efficiently through data-driven genome-wide discovery tools as described above (vide infra: GFC Transfection Arrays).

NGP. The possible on ban stem cell research using animal eggs will jeopardize finding treatment and cures for degenerative diseases such as Alzheimer’s and spinal muscular atrophy. In your opinion, just how useful are animal experiments in predicting the outcome of human trials of new medicines?

JL. The current stem cell controversy in the UK regarding the use of animal eggs involves the creation of hybrid embryos that combine human and animal genetic material, and that issue is currently unresolved. However, the use of animal models in general as a predictive tool for human clinical trials, although imperfect, is critically important. The two main areas of interest are safety and efficacy. The availability of in-silico, in vitro and other non-animal models that consistently and reliably predict these endpoints is severely limited. Although animal models also have limitations they’re some of the most important predictive tools we have available and their judicious use is critical to discovering and developing new therapies that address unmet medical needs. Through experience and advances in science and technology, predicting human safety and efficacy has improved. However, until large human populations are exposed a drugs true safety and efficacy profile can’t be determined.

RH. In the field of neurodegenerative diseases, the link between animal experiments and human response in clinical trials is very limited.

NGP. Do you see an opportunity in biomarker research tools?

RH. OriGene sees a clear trend toward personalised medicine as represented by biomarkers. Any company developing biomarker research tools or useful tools that aid in the discovery of biomarkers will have a very clear market opportunity. OriGene feels it has positioned itself well through its contributions to the research community of the Genome-Wide Transfection Arrays and is proud to be one of the leaders in this field.

JL. Over the past decade biomarkers have been utilised extensively in clinical research. Many diseases states are often accompanied by abnormal levels of unique chemicals in the blood stream. By identifying how these chemicals relate to a given disease state and developing robust analytical techniques to quantify them, clinicians are better able to evaluate therapeutic responses via simple blood tests.

This same concept can be applied to nonclinical drug development. During the drug candidate selection process, the application of toxicogenomics can aid in the early identification of biomarkers. These biomarkers can then be monitored as part of future animal studies, much the same way they are clinically. By applying biomarkers and other data generated from toxicogenomics, pharmaceutical companies are able to make earlier more informed decisions saving significant time and money. Resources can then be focused on expeditiously bringing the most promising candidates forward for development in order to meet unmet medical needs.

R. Richard L. Hamer, Ph.D.: “There are whole arenas of potential targets awaiting discovery through data-driven discovery tools”

James Laveglia, Ph.D.: “The best hope for new antibacterial drugs will likely come from small pharmaceutical and biotechnology companies”

R. Richard L. Hamer, Ph.D. is the Head of Business Development for OriGene Technologies, Inc.

Dr Hamer has a 20-year background covering all aspects of pharmaceutical research and development. He founded Cayenne, a contract venture management firm after leaving Viaken Systems where he was the Chief Science Officer and VP of Research & Development. Dr Hamer spent much of his career with the Hoechst /Aventis Group initially working on their US Central Nervous Systems Disorders synthesis program and later an inflammatory research program. He initiated the US computational chemistry group for Hoechst, and created their US-based automated screening facility and research informatics group to capture and integrate the screening data flow with a new chemical informatics system. Dr Hamer founded the global bioinformatics group for Hoechst Marion Roussel, and co-founded a biotechnology joint venture, Hoechst-ARIAD Genomics Center. He has been awarded over 42 US patents and has produced 28 publications and presentations.

James Laveglia, Ph.D. is Executive Vice President and Director of Research for MPI Research.

MPI Research is a leading global provider of nonclinical and early clinical research and development services headquartered in Mattawan, Michigan, USA. Dr Laveglia also serves on the company’s Corporate Management Team and Board of Directors. He has over 30 years of experience as a toxicologist and responsibility for the direction of all scientific studies conducted at MPI Research. Prior to joining the company in 1996, Dr Laveglia held numerous senior level positions within the chemical and contract toxicology industries, including the Monsanto Company, Diamond Shamrock Corporation, WIL Research Laboratories, Food and Drug Research Laboratories and Ricerca, Inc. Dr Laveglia earned his Bachelors and Masters Degrees in Biology at Bowling Green State University, Ohio and his Ph.D. at Iowa State University. He has authored numerous toxicology publications, abstracts and presentations and is a member of the Society of Toxicology and American College of Toxicology.