Published Preclinical Study Shows Receptor BioLogix's Pan-HER Ligand Trap Has Broad Anti-Cancer Activity

Main Category: Cancer / Oncology
Also Included In: Clinical Trials / Drug Trials
Article Date: 29 Oct 2008 - 9:00 PDT

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Receptor BioLogix, Inc., today announced that a new publication in the journal Molecular Cancer Therapeutics1 confirms the broad anti-cancer potential of its pan-HER (human EGF receptor) ligand traps, which are novel fusion proteins designed to significantly improve the response rate and increase the survival of patients with HER-related cancers. These preclinical studies confirm that the company's pan-HER ligand traps can successfully sequester multiple tumor promoting HER ligands and achieve a range of anti-tumor effects. Based on these positive results, Receptor BioLogix researchers have developed optimized pan-HER ligand traps that are now in pre-IND development.

"This new scientific publication illustrates why we are so enthusiastic about our pan-HER ligand traps," said Dale R. Pfost, Ph.D., chief executive officer of Receptor BioLogix. "In diverse preclinical studies, our first-generation molecule met or exceeded our high expectations, demonstrating that it can sequester a large number of HER ligands and generate promising anti-tumor effects on its own and synergistically with other cancer drugs. We believe our pan-HER ligand traps have the potential to transform the treatment of HER-related cancers and we are committed to their rapid development."

The complex HER system, comprised of four receptors and 11 known receptor-activating ligands, is dysregulated in about half of all solid cancers. It includes validated cancer targets - both Herceptin® and Erbitux® target HER family members. These drugs represent advances in cancer treatment, but many patients receiving them develop resistance and eventually relapse. This reflects the fact that tumor growth in these cancers is affected by complex compensatory signaling networks among the HER family members and their ligands, so the inhibition of any one family member can lead to the upregulation of others, increasing production of the growth factors that stimulate the growth and spread of tumors. Receptor BioLogix's unique pan-HER ligand traps, also known as HermodulinsTM, are novel fusion proteins that broadly target these tumor-promoting ligands, thereby effectively blocking the compensatory mechanisms of the HER system.

"These new studies indicate that our better understanding of the HER system is now making possible the design of drugs with the potential to improve on single-targeted anti-HER therapies," said H. Michael Shepard, Ph.D., president and CSO of Receptor BioLogix and a leader of the team at Genentech that developed Herceptin®. "They confirm that our strategy of targeting HER family ligands is both feasible and capable of producing significant anti-cancer effects. Our researchers have developed optimized second generation pan-HER ligand traps with improved characteristics, and we look forward to advancing a clinical candidate through pre-IND development over the next year."

In the new publication, Receptor BioLogix researchers and colleagues describe how they designed RBLX-200, a heterodimeric chimeric protein, by fusing the extracellular domain of the HER-1 and HER-3 receptors with the Fc domain of human IgG1. A wide variety of in vitro and in vivo studies were conducted to assess the activity and potential therapeutic utility of RBLX-200. The researchers concluded that RBLX-200:

- Specifically binds to multiple HER-1 and HER-3 ligands with high affinity
- Blocks ligand-induced receptor tyrosine phosphorylation of HER family proteins
- Inhibits the growth of multiple tumor cell types in vitro
- Is synergistic with tyrosine kinase inhibitors in inhibiting tumor cell proliferation in vitro
- Demonstrates significant in vivo anti-tumor activity in animal xenograft models.

1. "Human epidermal growth factor receptor (HER-1:HER-3) Fc-mediated heterodimer has broad antiproliferative activity in vitro and in human tumor xenografts"
Jay Sarup, Pei Jin, Lisa Turin, Xiaomei Bai, Malgorzata Beryt, Cathleen Brdlik, Jeffrey N. Higaki, Brett Jorgensen, Francis W. Lau, Peter Lindley, Jim Liu, Irene Ni, James Rozzelle, Rajendra Kumari, Susan A. Watson, Juan Zhang, and H. Michael Shepard
Mol Cancer Ther 2008;7(10): 3223-36, October 2008

About Receptor BioLogix

Receptor BioLogix is applying its expertise in human EGF receptor (HER) pathways and receptor-based biologics to develop novel pan-HER ligand traps for cancer and other diseases. The company's pan-HER ligand traps are designed to inhibit the compensatory feedback mechanisms that limit the efficacy and durability of many cancer drugs. In preclinical studies, Receptor BioLogix's pan-HER ligand traps have demonstrated promising anti-cancer potential. The company also is developing its Intron Fusion Protein platform for the discovery of novel, naturally occurring alternative forms - splice variants - of human proteins with therapeutic potential.

Receptor BioLogix