Skip to Content for BioOncology Pipeline Menu for BioOncology Pipeline About Us Menu Research Menu Development Menu Medicines Menu Investors Menu Media Menu Careers Menu
Banner Image

BioOncology Pipeline

Printer Friendly Version Printer Friendly Version

Genentech BioOncology Pipeline Fact Sheet

Pipeline: Insight and Innovation from Genentech BioOncology As a result of our commitment to basic research, Genentech BioOncology has a robust product pipeline, with innovative compounds designed to target cancer via specific molecular processes. We believe that studying the biological pathways involved in cancer development, progression and metastasis holds the key to identifying promising molecular targets.

Genentech BioOncology also supports the development of clinical diagnostics to identify patients most likely to benefit from treatment with our medicines. Scientists at Genentech are investigating potential diagnostic markers, including HER receptors, that may aid selection of the patients most likely to benefit from our targeted therapies.

Through our current research focus, including anti-angiogenesis, cell signaling (HER signaling, apoptosis and B-cell signaling) and arming antibodies, we approach cancer research from multiple pathways, helping us to unravel the complexity of cancer treatment and positively impact the lives of patients.

Genentech BioOncology's pipeline includes both new molecular entities and the development of existing products in new therapeutic areas. While we are studying Avastin®, Herceptin®, Rituxan® and Tarceva® in numerous tumor types, as well as conducting combination trials, we are also investigating several new molecules as cancer therapies, including:

  • Apomab
  • RhApo2L/TRAIL (recombinant human Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand), in collaboration with Amgen
  • ABT-263, in collaboration with Abbott Laboratories
  • GDC-0449, in collaboration with Curis, Inc.
  • Anti-CD40, in collaboration with Seattle Genetics
  • Pertuzumab
  • Trastuzumab-DM1 (T-DM1)
  • ABT-869, in collaboration with Abbott Laboratories

Apomab, RhApo2L/TRAIL and ABT-263: Cell Signaling/Apoptosis Apoptosis, or "programmed cell death," is a process by which cells in the body, both normal and abnormal, self-destruct. Under normal conditions, apoptosis eliminates damaged or unneeded cells.1 However, many cancer cells evade apoptosis, allowing tumors to survive and grow.2 Therefore, developing therapies that can activate — or induce — apoptosis may have the potential for treating a variety of cancers.3

Apomab Apomab is a fully human antibody discovered by Genentech scientists that is designed to specifically bind to and activate an important receptor, called pro-apoptotic Death Receptor (DR) 5, which is found on the surface of various types of cancer cells.4

Binding of Apomab to DR5 may directly activate the extrinsic apoptosis pathway, may also indirectly induce the intrinsic apoptosis pathway in cancer cells.5 In preclinical models, Apomab selectively induced apoptosis in cancer cells.5,6

Genentech scientists are currently studying Apomab in early-stage clinical trials in a variety of solid tumors and blood cancers. In April 2007, Genentech announced the initiation of two Apomab Phase II clinical studies — one in non-small cell lung cancer and the other in non-Hodgkin's lymphoma (NHL).

Recombinant Human (rh)Apo2L/TRAIL Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/ TRAIL) is a recombinant (engineered) human protein designed to activate two pro-apoptotic receptors, DR4 and DR5.4

Binding of rhApo2L/TRAIL to DR4 and DR5 may directly activate the extrinsic apoptosis pathway may also indirectly induce the intrinsic apoptosis pathway in cancer cells.7-9 In preclinical models, rhApo2L/TRAIL selectively induced apoptosis in cancer cells, while sparing normal cells.8

Genentech BioOncology, in collaboration with Amgen, is studying rhApo2L/TRAIL, the first dual pro-apoptotic receptor agonist, in early-stage clinical trials in a variety of solid tumors and blood cancers, including a Phase II study in NHL.

ABT-263 ABT-263 is a small-molecule agent designed to restore apoptosis in cancer cells. ABT-263 inhibits members of a group of related proteins called the Bcl-2 family of proteins.10 Bcl-2 family proteins are expressed at high levels in many tumors and play a central role in regulating apoptosis and, consequently, tumor formation and growth. Some of these proteins promote apoptosis and some promote survival by acting as "stop signs" to intrinsic apoptotic signals.11 ABT-263 blocks the activity of pro-survival Bcl-2 family proteins.10

Genentech BioOncology, in collaboration with Abbott Laboratories, is studying ABT-263 in Phase I/II clinical trials as a single agent for relapsed or refractory chronic lymphocytic leukemia, relapsed or refractory lymphoid malignancies and advanced small cell lung cancer.

Pertuzumab: Cell-Signaling/HER Pathway Pertuzumab, a humanized monoclonal antibody, represents the first in a new class of investigational agents known as HER (human epidermal growth factor receptor) dimerization inhibitors (HDIs).12

Pertuzumab is designed to bind to the HER2 receptor — a protein found on the surface of epithelial cells — and inhibits the ability of HER2 to interact with other HER family members (HER1/EGFR, HER2, HER3 and HER4).13,14 HER dimerization (receptor pairing) is believed to play an important role in the growth and formation of several different cancer types.12

Pertuzumab binds to a different part of the HER2 receptor than other approved products, known as the dimerization domain.

Based on results from Phase II trials of pertuzumab and Herceptin, Genentech BioOncology and Roche have initiated a Phase III clinical trial (CLEOPATRA) investigating pertuzumab in combination with Herceptin for the treatment of first-line, HER2-positive metastatic breast cancer.

GDC-0449: Cell-Signaling/Hedgehog Pathway Genentech BioOncology, under a collaboration agreement with Curis, Inc., is currently investigating GDC-0449, a novel small molecule antagonist of the Hedgehog signaling pathway. Abnormal activation of the Hedgehog signaling pathway appears to be an important mechanism for tumors to survive and grow and has been implicated in the development of basal cell carcinoma (BCC), as well as in the progression of several solid tumor cancers.15

Genentech BioOncology has initiated a Phase II study evaluating GDC-0449 in first-line metastatic colorectal cancer and is planning to initiate two additional Phase II studies in the second half of 2008 in advanced BCC and an advanced epithelial tumor.

Anti-CD40: Cell-Signaling/B-Cell Signaling Genentech BioOncology, in collaboration with Seattle Genetics, is currently investigating Anti-CD40, a humanized monoclonal antibody that targets the CD40 antigen. CD40 is highly expressed on most B cell blood cancers.16

Several Phase I and II clinical trials evaluating Anti-CD40 are ongoing or planned, including:

  • as a single agent for relapsed multiple myeloma and relapsed diffuse large B-cell lymphoma (DLBCL) are ongoing
  • in combination with other therapies, including Rituxan, for relapsed multiple myeloma, relapsed follicular NHL, and relapsed and second-line DLBCL.

Trastuzumab-DM1 (T-DM1): Armed Antibody T-DM1 is an investigational HER2 antibody drug conjugate that builds on the science of Herceptin by combining two therapeutic strategies for HER2-positive breast cancer: Herceptin (trastuzumab) biologic activity and targeted intracellular delivery of a potent anti-microtubule (cancer killing) agent. T-DM1 is being developed in collaboration with Roche and Immunogen, Inc.

T-DM1 is currently being evaluated in Phase II trials in patients with locally advanced or metastatic HER2-positive breast cancer who have progressed on a chemotherapy regimen containing Herceptin.

ABT-869: Anti-Angiogenesis Genentech is building upon the scientific breakthroughs of Avastin by co-developing ABT-869, a small molecule inhibitor of angiogenesis, with Abbott Laboratories. ABT-869 is designed to selectively inhibit vascular endothelial growth factor (VEGF) receptors.

The molecule is in Phase II trials for hepatocellular (liver) carcinoma, non-small cell lung cancer and renal cell carcinoma. Phase II trials evaluating the compound in metastatic breast cancer will be initiated in the second half of 2008.

View full prescribing information and Boxed Warnings for Avastin, Rituxan, Herceptin, and Tarceva.

References

  1. Lodish H., D. Baltimore, A. Berk, S.L. Zipursky, P. Matsudaria, and J. Darnell. 2003. Molecular Cell Biology, Fifth Edition, Scientific American Books.
  2. Kelley SK, Ashkenazi A. Targeting death receptors in cancer with Apo2L/TRAIL. Curr Opin Pharmacol. 2004; 4:333-339.
  3. Jin Z, El-Diery WS. Overview of cell death signaling pathways. Cancer Biol Ther. 2005; 4:139-163.
  4. Spierings DCJ, de Vries EGE, Timens W, Groen HJM et al. Expression of TRAIL and TRAIL death receptors in stage III non-small cell lung cancer tumors. Clin Cancer Res. 2003;9:3397-3405.
  5. Fesik SW. Promoting apoptosis as a strategy for cancer drug discovery. Nat Rev Cancer. 2005;5:876-885.
  6. Ichikawa K, Liu W, Zhao L, et al. Tumoricidal activity of a novel anti-human DR5 monoclonal antibody without hepatocyte cytotoxicity. Nat Med. 2001;7:954-960.
  7. Ashkenazi A. Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nature. 2002;2:420-430.
  8. Ashkenazi A, Pai RC, Fong S, et al. Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 1999;104:155-162.
  9. Kischkel RC, Lawrence DA, Chuntharapai A, et al. Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity. 2000;12:611-620.
  10. Genentech press release. June 26, 2007.
  11. Youle RJ, Strasser A. The Bcl-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Bio. 2008; 9:47-59
  12. Adams CW, Allison DE, Flagella K, et al. Humanization of a recombinant monoclonal antibody to produce a therapeutic HER dimerization inhibitor, pertuzumab. Cancer Immunol Immunother. 2006;55:717-727.
  13. Franklin MC, Carey KD, Vajdos FF, et al. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004; 5:317-328.
  14. Agus DB, Akita RW, Fox WD, et al. Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth. Cancer Cell. 2002; 2:127-137.
  15. Rubin LL, Sauvage FJ. Targeting the hedgehog pathway in cancer. Nat Rev Drug Disc. 2006;5:1026-1033
  16. Vonderheide RH. Prospect of targeting the CD40 pathway in cancer cells. Clin Cancer Res. 2007;13:1083-1088.
  17. DiJoseph F, Goad ME, Dougher MM, et al. Potent and specific antitumour efficacy of CMC-544, a CD22-targeted immunoconjugate of calicheamicin, against systemically disseminated B cell lymphoma. Clin Cancer Res. 2004; 10:8620-8629.
  18. Hamann PR. Monoclonal antibody-drug conjugates. Expert Opin Ther Patents. 2005;15:1087-1103.