• CLL
• Multiple Myeloma

Description

In 2004 XOMA and Chiron entered into a worldwide, multi-product, cost and profit sharing collaborative agreement for the development and commercialization of antibody products for the treatment of cancer. In April of 2006, Novartis acquired Chiron and the corresponding collaborative agreement. HCD122 (formerly known as CHIR-12.12) is the first lead product candidate to come out of the collaboration.

HCD122 is a fully human, antagonist antibody that targets the CD40 antigen. As shown in vitro in cell lines, in vivo in animal models and ex vivo in patient cells, HCD122 binds to tumor cells that express CD40 and antagonizes (prevents) CD40 ligand-mediated growth and survival of malignant B cells. Based on preclinical data, HCD122 also induces antibody-dependent cellular cytotoxicity (ADCC), killing CD40 expressing tumor cells by immune effector cells. This dual mechanism of action makes HCD122 a drug candidate with potential for the treatment of B-cell malignancies. HCD122 is an investigational drug candidate and has not been approved by the U.S. Food and Drug Administration.

Mechanism of Action

Indications

• Chronic Lymphocytic Leukemia
• Multiple Myeloma

Development Status

The first Investigational New Drug (IND) application submission took place in December of 2004. In April of 2005, XOMA and Chiron announced the initiation of Phase I clinical testing of HCD122, a fully human, antagonist antibody that targets the CD40 antigen, with patients with advanced chronic lymphocytic leukemia. In October 2005, the clinical program was extended to a Phase I trial in patients with multiple myeloma.

Publications and Presentations

• "In Vitro Activity of a Novel Fully Human Anti-CD40 Antibody CHIR-12.12 in Chronic Lymphocytic Leukemia: Blockade of CD40 Activation and Induction of ADCC" (PDF), Xia Tong, et. al, American Society of Hematology Meeting, 2004.
• "Safety Evaluation of a Fully Antagonist Anti-CD40 Antibody, CHIR-12.12, in a Dose Range-Finding Study in Cynomulgus Monkeys" (PDF), Ursula Jeffry, et. al, American Society of Hematology Meeting, 2004.
• "Antagonist Anti-CD40 Monoclonal Activity, CHIR-12.12, Inhibits Growth of a Rituximab-resistant NHL Xenograft Model and Archives Synergistic Activity when Combined with Ineffective Rituximab" (PDF), Li Long, Ph.D., et. al. American Society of Hematology Meeting, 2004.
• "Human Anti-CD40 Antagonist Activity Triggers Significant Antitumor Activity Against Human Multiple Myelomas" (PDF), Yu-Tzu-Tai, et. al, American Society of Hematology Meeting, 2004.
• "A Fully Human Anti-CD40 Antagonist Antibody, CHIR-12.12, Inhibits the Proliferation of Human B Cell in Non-Hodgkin's Lymphoma" (PDF), Wen-Kai Weng, et. al, American Society of Hematology Meeting, 2004.