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Pharmaceutical Drug Development

The Critical Path from Bench to Bedside

According to an analysis conducted by Tufts University, it requires 11 years and nearly $1 billion to take a drug from concept to FDA approval.1 A substantial portion of these expenses occurs in late stage development, during Phase II and III clinical trials. Yet, half of the new drugs that show evidence of activity and safety in earlier phases fail at the Phase III clinical trial level.2

In response, the pharmaceutical industry has dedicated hundreds of millions of dollars to study human biology and personalized medicine. Yet, virtually all of these resources are being expended in the field of genomics. While the analysis of gene expression, mutation, amplification and SNPs can provide useful information and prognostic tools, virtually no gene expression profile can connect an individual patient to an active treatment. Genomic platforms cannot adequately interrogate the complexity, redundancy and indiscriminant nature of human tumor biology.

To address these needs, we have applied “functional profiling,” a platform that captures the complexities of human tumor biology at the level of the cellular phenotype.

Functional profiling conducted on human tumor samples utilizes native microspheroids replete with vascular, stromal and inflammatory cells to analyze cellular responses in the context of the tumor microenvironment. This snapshot of cellular response recapitulates patient response to cytotoxic compounds, signal transduction inhibitors and growth factor antagonists in real time.

Having proven the capacity of this platform to predict the activity of drugs like 2-CDA,3 the Gemcitabine plus CDDP combination4 and the EGFr antagonists,5 Rational Therapeutics is actively engaged in the study of the newest classes of compounds, which target a wide variety of cellular signaling pathways.

The Rational Therapeutics Ex-Vivo Analysis – Programmed Cell Death (EVA-PCD) platform offers the pharmaceutical industry the opportunity to conduct Phase II trials in the laboratory. By streamlining the path from promising compound to clinically active therapy, the EVA-PCD platform has the capacity to substantially reduce the cost of drug development and shorten the development cycle by years. Our most precious resource ­— our patients — should never be exposed to drugs and combinations until they have been thoroughly vetted in the laboratory setting. With almost 20 years experience we are qualified and well-positioned to explore novel uses of the newest agents.

  1. Tufts University, Drug Development Cost Analysis, 2001
  2. Roberts TG, The Phase III Trial in the Era of Targeted Therapy: Unraveling the “Go or No Go” Decision, J Clin Oncol 21 (19), 2003
  3. Nagourney RA et al, British  Journal of Cancer, 1993
  4. Nagourney RA, Deoxynucleoside Analogs In Cancer Therapy, (ed) G Peters, Human Press, 2006
  5. Nagourney, RA, et al Functional Profiling of Human Tumors In Primary Culture: A Platform for Drug Discovery and Therapy Selection: Proc AACR, 2008


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