Pfizer

Oncology Research and Development Postdoctoral Program

ORD: In Depth

Pfizer’s Oncology Research and Development (ORD) Group is at the forefront of Pfizer’s Precision Medicine R&D effort designed to develop the right drug, for the right target and right patient groups. The ORD is advancing a diverse portfolio of differentiated and targeted cancer therapies based on a comprehensive understanding of the underlying biological mechanisms and the patient populations most likely to benefit from treatment. The ORD focuses on established areas such as cell signaling, and emerging areas of cancer biology, including antibody-drug conjugates (ADCs), a highly promising therapeutic modality that provides targeted delivery of an antibody drug linked to chemotherapy.

Industry Context

Oncology research is the largest and most competitive field in biopharmaceutical R&D. Many companies are pursuing various forms of targeted therapy, which in contrast to traditional chemotherapy allow for specific targeting of proteins or pathways found in certain cancers. The application of Precision Medicine to patient selection for clinical trials is embedded extensively into oncology R&D, and increasing number of our cancer medicines will be marketed in conjunction with tailored diagnostics. Pfizer’s Xalkori (crizotinib) is an example of the application of Precision Medicine early on in the development process, indicated for a specific subset of non-small cell lung cancer patients bearing the oncogenic EML4-ALK tyrosine kinase oncoprotein. ADCs are an increasingly important area with deep investment from various pharmaceutical and biotechnology companies.

Core Focus Areas

Translating Emerging Biology into Novel Cancer Drugs: Pfizer is developing world-class capabilities that will help ensure leadership in current areas of focus for cancer drug discovery, including oncogenic drivers and cell signaling mechanisms. These efforts are complemented by growing research interest in cancer cell metabolism and epigenetics, or how cancer can be caused by modifications to DNA and histones that regulate gene expression. The ORD also proactively addresses mechanisms of resistance to protein kinase inhibitors and other agents in the oncology portfolio. Programs focus on a range of solid tumor and blood cancers based on the underlying biology of each disease.

Building a Leadership Platform in ADCs: the ORD, in collaboration with Pfizer’s biologic partner lines, is focused on leadership in ADC-based therapies, building on Pfizer’s strong expertise in large and small molecule development. ADCs are comprised of an antibody, linker, and a cytotoxic payload. Importantly, Pfizer has comprehensive in-house capabilities across all three facets of this promising platform. Our efforts focus on building innovative second- and third-generation ADC therapies to offer safer and more effective medicines for patients. Some of our innovative ADCs target the most dangerous subpopulations of cancer cells – those that exhibit tumor-initiating capacity (often called cancer stem cells) and those that are tolerant of or wholly refractory to chemotherapy.

Scientific Platforms


Signal Transduction

Signal transduction refers to a process by which signals are moved from outside to inside a cell, thereby eliciting a physiological response.

Pfizer has leading expertise in signal transduction, with multiple therapies, including Sutent and, most recently, Xalkori, on the market. The ORRD continues to leverage this knowledge to increase the availability of differentiated biomarker-based cancer treatments.

Antibody Drug Conjugates (ADCs)

ADC's are a type of targeted therapy combining therapeutically potent and highly selective antibodies with a payload drug to target a tumor-associated antigen. These ADC platforms enhance the anti-tumor activity of an antibody while reducing the toxicity of cytotoxic drugs that would be experienced if administered systemically.

ADC exploration is focused on: Solid tumors, Blood cancers, Cancer stem cells, Vascular biology

Epigenetics

The study of epigenetics helps build an understanding of how cancer can be caused by modifications to DNA and histones that regulate gene expression during normal development and cell differentiation.

  1. Identifying new epigenetic drug targets: bioinformatic and genomic technologies, functional screens using chemogenomic and shRNA libraries.
  2. Discovering new small-molecule inhibitors of the cancer epigenome: focused chemical libraries designed to identify proprietary investigational agents, robust biochemical assays for measuring activity of epigenetic enzymes, and cell-based assays for analyzing histone modifications

Cancer Metabolism

Pfizer is exploring targets related to the reprogramming of intermediate metabolism in cancer cells. This strategy includes blocking metabolic targets upregulated in therapy-resistant cells and interfering with the metabolic coupling between tumor epithelial and stromal cell compartments.

Capitalizing on untapped opportunities using different targets and approaches: genomics, proteomics, and metabolomics to identify key notes in pathological metabolic networks and metabolite biomarkers; flexible target-based modalities, including antibody- and small-molecule-based therapeutics.

Oncology Target Discovery (OTD)

The OTD organization applies capabilities in integrated computational biology, proteomics, functional genomics, transcriptomics, and Phage Display selection to contribute to the discovery of breakthrough cancer therapies.