Pfizer to present data on ADCs at AACR 2012

Pfizer Oncology will present data from a variety of preclinical and clinical studies of Pfizer's early-stage compounds, including data from Pfizer's investigational antibody-drug conjugate (ADC) portfolio and research evaluating several molecules targeting novel pathways that play a crucial role in basic cellular functions, at the American Association for Cancer Research (AACR) Annual Meeting 2012 in Chicago, IL, from March 31-April 4.

“The data being presented at this meeting highlight preclinical research that has helped to shape our clinical development strategies.”

"The data we will present at AACR are representative of our continued commitment to emerging science and to advancing research and development in the area of antibody-drug conjugates," said Bob Abraham, PhD, senior vice president and chief scientific officer, Oncology Research Unit. "With expert scientists and complete in-house capabilities in this unique targeted therapy platform, our goal is to discover and develop the next generation of ADCs that may provide improved treatment options for patients with cancer."

ADC-based cancer therapies use a targeted antibody to deliver a cytotoxin directly to specific tumor cells, with the goal of enhancing the anti-tumor activity of an antibody while reducing the toxicity of the cytotoxin on healthy cells. At the meeting, Pfizer will present data on several of the ADCs in its portfolio, including an analysis from an ongoing Phase 2 study (Study 2001) of inotuzumab ozogamicin in patients with refractory or relapsed indolent B-cell Non-Hodgkin's lymphomas (Abstract #3776, April 3).

The following data evaluating ADCs will also be featured:

• The use of pharmacokinetic-pharmacodynamic modeling to characterize platelet response following inotuzumab ozogamicin treatment in patients with follicular or diffuse large B-cell NHL (Abstract #3767, April 3)
• Long-term tumor regression induced by a novel ADC that targets 5T4, an oncofetal antigen expressed on tumor-initiating cells (Abstract #2530, April 2)
• Novel site-specific ADCs based on novel amino acid incorporation technology have improved pharmaceutical properties over conventional ADCs (Abstract #5691, April 4)

Additional Research Reflects Emerging Science

Pfizer will present further data relating to its pipeline and preclinical studies in emerging areas of cancer research.

"Over the past 12 months, Pfizer has launched two new oncology drugs in the U.S., filed a third for review, and focused our early portfolio on the development of innovative compounds that hold the greatest potential in areas of unmet need," said Mace Rothenberg, MD, senior vice president of clinical development and medical affairs for Pfizer's Oncology Business Unit. "The data being presented at this meeting highlight preclinical research that has helped to shape our clinical development strategies."

Data being presented from Pfizer's early development portfolio include:

• PF-04691502 and PF-05212384 (PI3K/mTOR Inhibitors)
  The PI3K signaling pathway has been shown to play a critical role in regulating basic cellular functions including growth, proliferation and survival, and its dysregulation is a common event in human cancer that may contribute to uncontrolled growth in cancer cells, metastases and resistance to therapy. Research indicates that dual inhibition of PI3K and mTOR may provide benefit beyond that seen from mTOR inhibition alone.
  • Preclinical studies of the PI3K/mTOR dual inhibitors in endometrial cancer cell lines (Abstract #2871, April 2).
• PF-04605412 (α5β1 Inhibitor)
  α5β1 may play an important role in cancer progression through the promotion of cancer cell migration, proliferation, survival and metastasis. Elevated expression of α5β1 has been observed in several types of cancer including colorectal, glioma, pancreatic, renal, liver, ovarian, bladder and lung.
  • PF-04605412 induces cytokine activation and marginalization of NK cells and macrophages in patients with solid tumor (Abstract #2512, April 2).
• PF-05082566 (4-1BB Inhibitor)
  The 4-1BB (CD137) molecule is a member of the tumor necrosis factor (TNF) receptor gene family, proteins of which are involved in the regulation of cell proliferation, differentiation and cell death.
  • Targeting 4-1BB by mAb PF-05082566 to enhance T cell function and promote antitumor activity (Abstract #4384, April 3)
• PF-03084014 (Gamma Secretase/Notch Pathway Inhibitor)
  The Notch pathway is an important developmental signaling pathway, which is aberrantly activated in tumor angiogenesis. Activation of Notch receptors is mediated through gamma secretase, a target amenable to inhibition with small molecules.
  
  • Gamma secretase inhibitor PF-03084014 diminishes the tumor-initiating cells and demonstrates synergy with docetaxel in breast cancer xenograft models (Abstract #3492, April 3)
  • Inhibition of Notch signaling enhances the antitumor efficacy of chemotherapy in triple negative breast cancer through reduction of cancer stem cells (Abstract #3485, April 3)

Additionally, Pfizer will present data evaluating marketed and late-stage compounds crizotinib, a first-in-class compound that inhibits the anaplastic lymphoma kinase (ALK), dacomitinib (PF-00299804), an investigational, irreversible pan-HER inhibitor, and sunitinib, a small molecule that inhibits multiple receptor tyrosine kinases (RTKs).

Source Pfizer Oncology