GS Report: Medarex, Inc. Healthcare
In-line rating and Neutral coverage view.
I. Pipeline review
Medarex is gradually building out its proprietary and out licensed pipeline. Five proprietary candidates are in clinical studies and the company also has a number of candidates being developed by private French company Immuno Designed Molecules, S.A. (IDM) and Genmab SA, where Medarex has equity positions. Medarex has stablished "cash and carry" type agreements with more than 20 companies, including several large pharmaceutical and biotechnology companies.
Three candidates are in Phase I clinical studies at Johnson & Johnson. Two undisclosed antibodies are also being developed by Novartis. In addition, Medarex has stablished a similar number of 50/50 development agreements with biotechnology companies. Two candidates have been identified for development from these programs.
** Multiple MDX-010 trials underway - plans for pivotal studies described **
MDX-010 is a fully human monoclonal antibody that blocks CTLA-4, a T cell receptor target with immunosuppressive properties which was in-licensed from the University of California, Berkeley.
Medarex currently has six ongoing Phase I/II or Phase II trials with MDX-010 for the treatment of melanoma, hormone refractory prostate cancer and metastatic breast cancer. In addition, the company has begun a Phase I study in up to 18 patients with HIV/AIDS. At its R&D day, management updated clinical data from these programs. While the reported responses are encouraging, we are cautious on this program, as immune boosting approaches toward the treatment of cancer have not had much success historically.
Medarex unveiled plans to conduct potentially pivotal studies for the second-line treatment of melanoma in patients who have failed prior chemotherapy. Management indicated they are currently in discussions with the FDA regarding the potential for the future studies to be submitted under an accelerated approval filing, and that a strategy for pivotal trials would be further elucidated subject to further discussions. The company plans to initiate the first study in 1Q04, and expects to have interim data in 1H05 and final data in 4Q05 or 1Q06. As presently envisioned, the first study will include four arms and will be designed to test for a benefit of MDX-010 in combination with the gp100 vaccine, compared to either agent alone. Management expects the four arms to consist of gp100 vaccine alone, MDX-010 alone, combination treatment at a dose of 3mg/kg MDX-010, and combination treatment with a slightly lower dose of MDX-010. It is
thought that approximately 45 patients would be encluded in each arm. An interim analysis is planned in order to confirm efficacy and confirm the optimal dose. Following the interim analysis, the company plans to drop the less effective dosing arm of combination treatment, and increase
enrollment to 200 patients in the remaining 3 arms.
Medarex also discussed some new data from a Phase II study with MDX-010 with or without the chemotherapy agent dacarbazine (DTIC). While some patients demonstrated responses and stable disease, all responses have not yet been confirmed, and the response rate did not appear as robust as the high dose cohort in the MDX-010 plus gp100 trial. Management expects to continue to evaluate the response rates from this trial through 1H04. Pending these results, a potential second pivotal trial with MDX-010 could be conducted in combination with dacarbazine. The study would likely also be in patients with metastatic melanoma who had failed prior chemotherapy and endpoints would include overall response rate and duration of response and survival.
In June, at ASCO, Medarex presented Phase II interim data on 14 patients with metastatic melanoma treated with MDX-010 in conjunction with gp100, a melanoma associated antigen. In the high-dose cohort of 14 patients, who were treated with gp100 and 3mg/kg of MDX-010 every 3 weeks, three patients (21.4%) demonstrated objective responses including two complete and one partial responder. Clinical responses appear to correlate with autoimmune reactions, as 43% of the patients experienced Grade III/IV autoimmune responses, including all three patients with tumor
responses. In the low-dose cohort, 27 patients were treated with gp100 and 3mg/kg of MDX-010 once, followed by 1mg/kg every 3 weeks. Three patients demonstrated partial responses (11.4%), two of which also experienced autoimmune reactions. We believe that additional data will be required to assess the relationship between immune response and clinical response
Recently, at the American Society of Hematology meeting, Dec 4-9 2003, Medarex presented early stage data from a pilot study on 11 patients with a variety of cancers including prostate cancer, colon cancer and non-Hodgkin's lymphoma. The patients had previously failed treatment with a variety of cancer vaccines. Patients received an initial dose of 3.0 mg/kg followed by monthly doses of 1.5 mg/kg for three additional months. Tumor regression was observed in two patients, including a partial response in one patient with follicular lymphoma. The company plans to initiate a Phase II trial in patients with follicular lymphoma.
** MDX-060 - Early data presented at ASH **
In May, Medarex filed an IND to begin clinical studies with MDX-060 and is currently in Phase I/II trials. MDX-060 is a fully human antibody to CD30, a receptor found on activated lymphocytes, and believed to play a role in the development of lymphomas, including Hodgkin's disease (HD) and Anaplastic Large Cell Lymphoma (ALCL). Medarex is currently enrolling an expected 30 patients in the Phase II portion of the trial, and the company expects to have data in mid-2004.
At the ASH meeting, the company presented Phase I/II data on 29 evaluable patients (of 31 enrolled) with relapsed or refractory Hodgkin's disease, ALCL, or other CD30-positive
lymphomas. The patients had received and failed multiple prior treatments, and most had also failed bone marrow transplantation. Patient received weekly infusions of MDX-060 at doses of 0.1, 1.0, 5.0 or 10.0 mg/kg for four weeks.
One complete response and two partial responses were observed. The complete response was seen in a patient with ALCL who received a dose of 1.0mg/kg for four months. The first partial response was observed in a patient with HD who was treated with 5.0mg/kg who had an ongoing response at 4 months. The second partial response was seen in a patient with HD who was treated with 10.0mg/kg for three months.
The company reported 2 possible drug-related adverse events, which included one patient who developed Grade 3 liver transaminase levels. The patient had a history of Graft versus Host Disease, and the effect resolved after treatment with steroids. A second patient developed elevated
Grade 2 liver transaminase levels who was treated with 0.1 mg/kg of MDX-060. Medarex has not yet identified a maximum tolerated dose.
** MDX-070 - Phase I/II enrollment ongoing **
Medarex is developing MDX-070, a fully human antibody that targets Prostate Specific Membrane Antigen (PSMA). Management expects to have data in mid-2004. The primary
target is prostate cancer, but the antibody could have applications in other cancers where antiangiogenic characteristics are desirable. In January, the company announced it had filed an IND for Phase I/II trials in up to 40 patients with metastatic prostate cancer. The trial will investigate the safety of MDX-070 in addition to efficacy which will be based on objective tumor response and decreases in prostate specific antigen (PSA) levels.
In December 2002, Medarex acquired full therapeutic development and commercialization rights for MDX-070 as well as certain patents related to anti-PSMA antibodies from Northwest Biotherapeutics. Medarex also entered into a royalty-free, worldwide, non-exclusive cross-license
agreement with Millennium Pharmaceuticals for certain patents related to antibodies against PSMA.
** MDX-214 - Phase I/II enrollment underway **
In November, Medarex announced FDA approval to initiate Phase I/II studies with MDX-214, to treat patients with cancers that overexpress the epidermal growth factor receptor (EGFr). MDX-214 is a fusion of recombinant epidermal growth factor (EGF) to a fully human antibody fragment that is designed to activate cytotoxic killing of cancer cells by immune effector cells. The fusion protein is expected to kill cancer cells by inhibiting tumor cell growth and by mediating antibody-dependent cellular cytotoxicity (ADCC). The company expects to enroll up to 48 patients with refractory or relapsed EGFr-expressing cancers, including cancers of the head and neck, breast, colon, prostate, lung and ovary. Management expects to have data in 2005.
** Preclinical pipeline discussed **
Management reviewed some of the antibodies in the preclinical pipeline. One potential IND, expected in 1H05, is MDX-1100 which is directed at IP-10 for the treatment of multiple sclerosis and other inflammatory disorders. Other candidates include MDX-1185, which acts on IFNAR,
and MDX-1103, which acts on IFN alpha, could have INDs in 2H04 and 1H05, respectively, and could be used for the treatment of Systemic Lupus Erythematosus (SLE). Management also discussed a potential cytotoxic drug-conjugate of an antibody directed at PSMA for the potential treatment of prostate cancer.
Milestones H2 2003
Present data at ASH on:
* MDX-010 in patients with colon cancer, prostate cancer and NHL
* MDX-060 in patients with lymphoma
* Dec 11 - R&D Day to review pipeline and update on clinical trials
File IND's for:
* MDX-214 EGF inhibitor
2004 Milestones
- Initiation of pivotal study with MDX-010 and gp100 in 1Q04
- Phase II data with MDX-060 in lymphomas in mid-04
- Phase II data with MDX-010 in prostate cancer in 2H04
- Phase II data with MDX-010 in breast cancer in 2H04
- Potential data from multiple MDX-010 cancer studies with NCI and CTEP
* completed
I, Meg Malloy, hereby certify that all |
