Medarex issued their 10K today. Their pipeline starts to look quite impressive.
Medarex Product Candidates in Clinical Development
MDX-33 (Anti-CD64 Antibody)--Idiopathic Thrombocytopenia Purpura (ITP). MDX-33 is a humanized antibody that targets CD64 (the immunoglobulin receptor Fc gammaR1) that is expressed on myeloid progenitor cells, monocytes, macrophages, human cytotoxic effector cells, activated neutrophils and dendritic cells. MDX-33 is designed for the treatment of ITP, an autoimmune condition in which patients' platelets are destroyed by their own immune system. Conventional treatments include steroids, removal of the spleen and high doses of intravenous IgG. In a Phase II clinical study, administration of MDX-33 appeared to substantially elevate platelet counts in patients treated with the highest dose. Further development is under evaluation.
MDX-010 (Anti-CTLA-4 Antibody)--Prostate Cancer, Malignant Melanoma, Melanoma Vaccines. MDX-010 is a fully human antibody that targets an immune receptor known as CTLA-4. This receptor, which is a protein found on the surface of T-cells, normally functions to suppress the immune response to tumors or infectious agents. By using a fully human antibody to block the activity of CTLA-4, we believe that patients' immune systems may be able to mount a stronger immune response against foreign pathogens and cancers. We initially focused on the use of this antibody in the treatment of prostate cancer and malignant melanoma. In January 2002, we expanded our focus and announced plans for a multi-pronged tumor vaccine clinical program employing different melanoma vaccines used in conjunction with MDX-010. Preclinical data suggests that MDX-010, when combined with certain tumor vaccines, may enhance the anti-tumor effects of such vaccines. We are conducting the following trials for this product:
Prostate Cancer; Malignant Melanoma: We began Phase I/II clinical trials of MDX-010 in patients with prostate cancer and melanoma, respectively, during 2000. Interim findings indicated that MDX-010 was generally well tolerated with evidence of immunologic and antitumor activity. Based on these results, we intend to initiate further trials to test repeated dosing of the antibody used alone and in combination with other anti-cancer therapies.
Melanoma Vaccines: As part of our tumor vaccine program, three separate Phase I/II clinical trials of MDX-010 are currently underway. Additional vaccines coupled with MDX-010 are expected to enter clinical trials during 2002.
MDX-44 (Anti-CD64 + Toxin Antibody)--Psoriasis, other dermatological disorders. MDX-44 is a humanized antibody that targets CD64 (see discussion of MDX-33 above) that has been conjugated to a toxin. Application of MDX-44 will target for destruction macrophages and other CD64 expressing effector cells that play key roles in psoriasis and other dermatologic disorders. An investigator initiated Phase I study of MDX-44 in atopic dermatitis was completed in 2001.
Out-Licensed Product Candidates in Clinical Development
IDM-1* (Anti-Her2 & CD64 Antibody)--Ovarian Cancer. IDM-1, currently being developed by our partner, IDM, is a humanized, bispecific antibody-based Cell Drug(TM) for the treatment of ovarian cancer. Phase III trials for IDM-1 targeting patients with Stage III ovarian cancer began in Europe in early 2000, and additional trials in Australia and Canada were added in 2001. IDM has reported that the aim of the Phase III studies is to prolong remission of Stage III ovarian cancer after a positive response to a standard protocol consisting of surgery, followed by two chemotherapies.
HuMax-CD4** (Anti-CD4 Antibody)--Rheumatoid Arthritis; Psoriasis. HuMax-CD4, being developed by our partner, Genmab, is a high affinity, fully human antibody that targets the CD4 receptor on cells known as T-cells, which are believed to be involved in promoting autoimmune disease. Preclinical and clinical studies to date suggest that an antibody that targets CD4 may be useful for the treatment of several inflammatory diseases including rheumatoid arthritis and psoriasis. HuMax-CD4 has been designated a "Fast Track" product by the FDA, potentially accelerating its development and FDA review. The following clinical trials are being conducted by Genmab for this product:
Rheumatoid Arthritis: In December 2001, Genmab announced the initiation of a Phase III clinical trial with HuMax-CD4 to treat patients with active rheumatoid arthritis who have failed to respond to treatment with methotrexate and TNF-a blocking agents. This trial is expected to involve approximately 400 patients at 50 sites in the United States and Europe. Genmab is also currently conducting a Phase II trial for HuMax-CD4 in a broader arthritis population consisting of patients with moderate to severe arthritis undergoing methotrexate therapy. Genmab reported that blinded safety data from this study was presented to the FDA prior to its approval of the Phase III trial.
Psoriasis: Genmab initiated a Phase II clinical trial of HuMax-CD4 in January 2001 for the treatment of moderate to severe psoriasis. Genmab reported that the HuMax-CD4 appeared to be safe and well tolerated and that mean Psoriasis Area Severity Index was reduced in all treatment groups. Genmab has reported further that it intends to proceed to Phase IIb trials of HuMax-CD4 in psoriasis in the second half of 2002. HuMax-IL15** (Anti-IL-15 Antibody)--
Rheumatoid Arthritis. HuMax-IL15 is a high affinity, fully human antibody against Interleukin-15 (IL-15) being developed by Genmab through a collaboration with Immunex. IL-15 is a cytokine, an immune system signaling molecule that appears early in the cascade of events that ultimately lead to inflammatory disease. Genmab initiated Phase I/II trials of HuMax-IL15 to investigate its utility for the treatment of patients with active rheumatoid arthritis. Genmab has stated that this multi-center, placebo-controlled study will test up to six dose levels and include approximately 30 patients.
Centocor/J&J Antibody--Anti-inflammatory diseases. Centocor is developing a high affinity, fully human antibody for an anti-inflammatory application. Phase I trials are currently underway.
Antibody Product Candidates in Pre-Clinical Development:
MDX-070 (Anti-PSMA Antibody)--Prostate Cancer. MDX-070 is a fully human antibody, developed in collaboration with Northwest Biotherapeutics, Inc. that targets Prostate Specific Membrane Antigen, or PSMA. PSMA is a cell surface marker that is preferentially expressed on normal prostate tissue on malignant prostate tissues, and also on blood vessels in other tumors. Preclinical data suggests that the antibody will target live prostate tumor cells. MDX-060 (Anti-CD30 Antibody)--Lymphoma. MDX-060 is a fully human antibody that targets CD30, which is a marker for activated lymphocytes and is present on the malignant cells of Hodgkin's Disease and anaplastic large cell lymphoma. Through its ability to target CD30 expressing tumor cells, MDX-060 may facilitate the elimination of such cells by the human immune system. Preclinical studies are ongoing with respect to this antibody.
HuMax-EGFr** (Anti-EGFr Antibody)--Cancer. HuMax-EGFr, being developed by Genmab, is a fully human antibody targeting the Epidermal Growth Factor receptor, or EGFr. EGFr is a receptor molecule that has been found in excess on many tumor cells, including carcinoma of the head and neck, breast, colon, prostate, lung and ovary. Preclinical studies have indicated that blocking the interaction between EGFr and its ligands has the potential to inhibit tumor growth leading to cell death.
Anti-heparanase I--Breast and Other Cancers. We are working with Oxford GlycoSciences plc, or OGS, to create human antibody therapeutics and/or tumor vaccines based on an initial set of disease targets. The first product candidate emerging from the program is a fully human antibody that binds to and neutralizes the heparanase I enzyme, which is involved in invasion and metastasis in many tumor types, including breast cancer nd other common cancers. Preclinical testing suggests that this antibody has the potential to prevent tumor growth and to reduce metastasis to limit the spread of the disease.
Others -- We have an active clinical and preclinical development program, which includes identified projects that we anticipate will lead to new antibodies and novel combinations with antibodies currently in development, such as additional candidates for our MDX-010 tumor vaccine program. We expect these development efforts to lead to additional clinical candidates in the near and long term.
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* Formerly referred to by us as MDX-210.
** We received equity interests in these partners in exchange for licenses of our proprietary antibody technology. We are not entitled to licensing, milestone or other payments from these licenses. |
