pseudo, here's a little hype on imcl
Imclone Systems, Inc.
Nasdaq: IMCL
180 Varick Street
New York, NY 10014
Tel: (212) 645-1405
Fax: (212) 645-2054
Andrea F. Rabney
Director, Corporate Development & Investor Relations
Investor Relations: ir@imclone.com
Company Description
ImClone Systems Incorporated is a New York City based biotechnology company (with manufacturing facilities in New Jersey) focused on the development of novel therapeutic products for the treatment of cancer and cancer-related disorders. The company is working on three distinct development programs; cancer therapeutics, cancer vaccines and anti-angiogenesis agents. The firm is developing chimerized monoclonal antibodies (part mouse and part human) as cancer therapeutics, vaccines for small-cell lung carcinoma and melanoma as well as endothelial stem cells to deliver gene therapies. ImClone has products in clinical trials, as well as candidates approaching the clinical stage. They recently signed an agreement with Merck KgaA for the development and commercialization of ImClone's lead anti-cancer product, C225. ImClone conducts much of its research with partners, including CombiChem and Memorial Sloan-Kettering Cancer Center.
Technology
ImClone's efforts are directed at the research and development of new drugs to treat cancer. Imclone has decided to take a three pronged approach to the attack on cancer. They are developing monoclonal antibodies to tumor cell receptors. They are also developing vaccines to specific cancer antigens. The third approach they are exploring is the use of angiogenesis inhibitors to stop blood vessel formation in tumors.
One of ImCIone's overlying technologies is the use of chimeric monoclonal antibodies to target cancer cell receptors. An antibody is a protein that specifically recognizes foreign substances in the body. A monoclonal antibody means that the antibody is derived from a single antibody-producing cell called a hybridoma. Monoclonal antibodies can be directed at a specific target called an antigen.
ImClone is developing inhibitors of tyrosine kinase receptors, a type of growth factor receptor. Tumor cells rely on growth factors to grow. The growth factor binds to the receptor, inducing enzyme activity, which initiates cell division. IMCL has inhibited tyrosine kinase receptors with antibodies that block the binding of growth factors to the receptors. Examples include C225, which blocks the binding of EGF to its receptor, EGFr and c-p1C11, which blocks the binding of VEGF to its receptor, KDR. The company is also working on a program to identify small molecules that inhibit the enzyme portion of growth factor receptors. They are working with CombiChem, Inc. to use CombiChem's library of chemical compounds to help identify candidates that interfere with the function of growth factor receptors. CombiChem will also synthesize novel molecules to act as inhibitors of growth factor receptors. IMCL also has an agreement with the Institute for Molecular Medicine in Freiburg, Germany to test small molecules for effectiveness in inhibiting various tyrosine kinase receptors.
ImClone is also studying the use of antibody inhibition of vascular-specific cadherin (VE cadherin) to inhibit angiogenesis. Cadherins are cell surface molecules that help organize tissue structures. Vascular-specific cadherin is thought to play a role in angiogenesis by organizing the assembly of endothelial cells into vascular tubes in the formation of new blood vessels. The company hopes the inhibition of VE cadherin will inhibit capillary formation thus starving the tumor. The company is also using CombiChem's libraries to identify small molecules that inhibit VE cadherin. IMCL has been assigned the exclusive rights to VE cadherin-2, a recently developed form of vascular-specific cadherin and to antibodies that inhibit VE-cadherin.
ImClone is also researching cancer vaccines. The company believes they can use the immune system to attack cancer. They hope to activate the immune system to recognize tumor specific antigens and stop a tumors local spread, metastases and recurrence. IMCL has BEC2 in clinical trials for small cell lung cancer. The company is also researching a vaccine using the melanoma antigen gp75. In preclinical studies, a gp75 vaccine has shown promise inhibiting melanoma growth.
ImClone has developed the technology needed to isolate endothelial stem cells. These stem cells are involved in the development of blood vessels. The company hopes to use the stem cells in the development of new blood vessels throughout the body. They plan to study these stem cells to generate new vessels in ischemia, burns and wound healing.
ImClone is also studying the use of endothelial stem cells in gene therapy to treat cancer. Tumors attract endothelial stem cells for use in angiogenesis. The company believes they can genetically alter endothelial stem cells to express tumor-destroying molecules thus delivering the deadly molecule directly to the tumor. ImClone's wholly-owned subsidiary EndoClone Incorporated is conducting this research.
The company is studying hematopoiesis in hopes of using the stem cells to regenerate blood cells after chemotherapy and/or radiation. The company is hoping to remove the stem cells from the patient prior to treatment and return them to the patient afterwards. IMCL is studying factors to control the proliferation, differentiation and functional deterioration of stem cells. They hope to develop technology to allow them to be maintained in culture outside of the body. ImClone has an exclusive license from The National Institutes of Health to the delta-like protein (DLK) in studies involving stem cells. DLK is a protein that helps maintain stem cells in their undifferentiated state while outside the patient's body. They are also hoping to use DLK to maintain undifferentiated stem cells while genetically manipulating them outside of the body. The company also discovered the FLK-2/FLT-3 receptor. The FLK-2/FLT-3 ligand binds and activates the receptor inducing the growth of the hematopoietic stem cells. The ligand may help stem cells reproduce outside of the body.
Products
The company currently has no products on the market. They have two drugs in late stage clinical trials, C225 and BEC2. The company derives what revenue they currently receive from a few different sources. They have licensed the rights to diagnostic products and vaccines for infectious diseases (such as gonorrhea and chlamydia) to corporate partners. They also derive revenue from contract research and development fees. Another source of funding is the licensing, research support, milestone payments and royalty fee revenues received from corporate partners.
Pipeline
ImClone Systems, Inc. has a number of products in clinical and preclinical trials. The most promising is their lead cancer therapeutic C225, a chimerized monoclonal antibody that blocks the Epidermal Growth Factor receptor (EGFr). EGFr is overexpressed on the cells of over one-third of all solid tumors, including bladder, breast, colon, ovarian, prostate, pancreatic, renal cell and squamous cell (non-small cell lung and head & neck) carcinomas. In cancer, specific growth factors act to trigger tumor cell growth and division through interaction with surface receptors (such as EGFr) on tumor cells. In animal studies, C225 in combination with chemotherapeutic agents or radiation increased the ability to kill tumor cells. In some of these studies, the human tumors established in these animals were eliminated and the animals survived tumor-free for a significant period of time. C225 used alone has also helped reduce implanted renal cell carcinoma and pancreatic carcinoma tumors in animals. As we know, animal studies are great (there are a lot of ecstatic mice with cancer dancing in the streets) but the "proof is in the pudding" (or in this case human clinical trials). Clinical trials are underway for a number of indications (various solid cancers, such as breast, prostate, head, and neck and renal cancers) either alone and in combination with chemotherapeutic drugs or radiotherapeutic agents. The studies have shown C225 to be generally well tolerated. C225 recently had positive results from a Phase Ib/IIa study. The study had 15 patients with unresponsive head and neck tumors. The patients were given C225 in conjunction with radiation. The results were quite impressive showing 100% resolution in 13 of the patients and 50% in the other two patients. Based on these results, the FDA granted approval to begin pivotal Phase III trials in head and neck cancers. One group will receive C225 plus radiation and the other will get radiation alone. A second trial with head and neck cancers will compare cisplatin to cisplatin plus C225. A third trial in squamous cell head and neck cancers that have failed chemotherapy will involve combining chemotherapy with C225. The company is planning to begin additional Phase II clinical trials to determine the type of tumors in which C225 is most effective. In these trials, they plan to use C225 in combination with chemotherapeutic agents or cytokines. ImClone recently presented preclinical results of C225 in combination with the anti-cancer drug gemcitabine in a mouse model of pancreatic cancer. Combined administration of C225 plus gemcitabine caused a 90% reduction in pancreatic tumors, compared with a 27% response rate using gemcitabine alone. ImClone has entered into an agreement to grant Merck KGaA the right to market C225 outside of North America. The two companies will co-develop C225 in Japan. ImClone retained the rights to North America.
Another promising product is the BEC2 cancer vaccine. BEC2 is a monoclonal anti-idiotypic antibody. An anti-idiotypic antibody is an antibody to another antibody's antigen binding site. The theory is that the anti-idiotypic antibodies mimic a specific antigen. This induces the body to produce an immune response to the chosen specific antigen. The anti-idiotypic antibody seems to stimulate a stronger immune response than the antigen itself. The BEC2 vaccine is given to the patient after the initial treatment of the tumor. The BEC2 vaccine resembles an antigen (GD3 ganglioside) on the tumor thus inducing the immune system to attack the cancer cells. GD3 is overexpressed on a number of cancers including small cell lung carcinoma, melanoma and soft tissue sarcomas. In preclinical studies BEC2 was shown to eliminate tumor metastases and prevent cancer reoccurrence. The vaccine has been in clinical trials since 1991. A trial of 15 patients with small cell lung cancer showed significantly increased survival. Median survival was 20.5 months versus a reference group with median survival of 17.9 months. A significant difference in survival curves was demonstrated (p = 0.03). BEC2 is currently in a Phase III clinical trial for the treatment of limited disease in small cell lung carcinoma. The trial will evaluate the effect in approximately 800 patients with small cell lung carcinoma. ImClone has entered into an agreement with Merck KGaA to develop and commercialize BEC2. Merck was granted the exclusive rights to manufacture and market BEC2 worldwide excluding North America. In North America the companies will co-market BEC2.
Merck will be responsible for the clinical development outside the United States, for development costs of the small cell lung cancer trial worldwide, milestone payments and royalties. ImClone will be the bulk product manufacturer of BEC2 to support worldwide sales.
Vascular Endothelial Growth Factor (VEGF) is a growth factor produced by tumor cells. VEGF induces angiogenesis (the growth of new blood vessels) via binding of the KDR receptor on endothelial cells (the cells that line blood vessels). Angiogenesis ensures an adequate blood supply for continued tumor growth. ImClone's angiogenesis inhibitor is c-p1C11. C-p1C11 is a chimeric monoclonal antibody that binds to the KDR receptor for VEGF. This prevents VEGF from binding thus inhibiting angiogenesis. C-p1C11 is currently in pre-clinical studies that have shown angiogenesis inhibition in animal studies. A recent presentation of preclinical results of in vivo findings demonstrated that administration of the anti-VEGFR-2 antibody resulted in a reduction of new blood vessel formation in tumors by as much as 80% and a decrease of existing blood vessel structures. Additionally, administration of anti-VEGFR-2 antibody significantly reduced or completely halted growth of established tumors. Examination of treated tumors showed evidence of tumor necrosis, decreased vascular permeability, decreased endothelial cell division and decreased microvessel density. IMCL is also working with MRC Collaborative Center in England, preparing a humanized form of c-p1C11. This would be a human antibody that contains only the minimal amount of mouse components necessary for the antibody to have therapeutic value.
Management
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