Medarex Announces Efficacy Data in Cancer Patients Treated with Investigational Anti-PD-1 Antibody at American Society of Clinical Oncology Annual Meeting

-Phase 1 Single-Dose and Phase 1b Multi-Dose Data Presented-

PRINCETON, N.J.--(BUSINESS WIRE)--Jun 1, 2009 - Medarex, Inc. (NASDAQ: MEDX) today announced anti-tumor activity and efficacy data for MDX-1106 (also known as ONO-4538), a fully human anti-PD-1 antibody that Medarex is co-developing with Ono Pharmaceutical Co. Ltd. for the treatment of recurrent or treatment-refractory cancers, including malignant melanoma, renal cell carcinoma, colorectal carcinoma, non-small cell lung cancer, and castrate resistant prostate carcinoma. Results presented at the annual meeting of the American Society of Clinical Oncology (ASCO) showed:


  • Durable anti-tumor activity in patients treated with intermittent 10 mg/kg dosing of MDX-1106 in the 21-patient expansion cohort from the Phase 1 trial, including one patient with renal cell cancer experiencing an ongoing objective partial response of over 9 months and one patient with melanoma experiencing ongoing stable disease with marked clinical improvement for over 19 months and 9 doses of MDX-1106. One patient with colorectal carcinoma treated with five doses at the earlier 3 mg/kg cohort has also maintained a partial response for over 20 months;
     
  • All patients showing clinical benefit with MDX-1106 had previously progressed after prior chemotherapies;
     
  • None of the patients treated at 10 mg/kg have developed any significant drug-related adverse events. MDX-1106 appeared to be well-tolerated at the 10 mg/kg dose, including those patients in the cohort eligible to receive between two and nine doses of 10mg/kg MDX-1106; and
     
  • No dose-limiting toxicities have been reached.
     

These data focused on the experience of an expansion cohort of 21 patients dosed at 10 mg/kg of MDX-1106 from the single-dose Phase 1 trial and were presented by investigator Julie Brahmer, M.D., Assistant Professor of Oncology from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University (Abstract #3018). The complete study was designed to examine the safety, tolerability and pharmacokinetic profile of single-dose MDX-1106 (0.3, 1, 3 or 10 mg/kg) in patients with recurrent or treatment-refractory cancers. However, per protocol, patients demonstrating clinical benefit could receive additional intermittent doses (up to nine doses of 10 mg/kg MDX-1106) until an objective response was obtained. In addition to the durable responses outlined above, lesional regressions were observed in two additional patients, including one with non-small cell lung cancer, and one with melanoma. Enrollment in the single-dose Phase 1 trial is complete with 39 patients.

Also presented were preliminary data from an ongoing multi-dose, dose escalating Phase 1b monotherapy study of MDX-1106. One patient with melanoma in the first treatment cohort of 4 patients has demonstrated marked tumor regression of liver and lung lesions after receiving four doses of 1 mg/kg of MDX-1106. The tumors have continued to shrink after additional cycles of four doses, and the patient continues to tolerate the treatment without adverse events. Additional anti-tumor activity has been observed with lung lesion regression in a patient with renal cell cancer. Subsequently observed in the second dose level cohort, one patient with non-small cell lung cancer has demonstrated regression of a solitary adrenal metastasis after the first 4 doses of 3 mg/kg of MDX-1106. The trial is designed to examine the safety and activity in patients treated with multiple doses of MDX-1106 (1, 3 and 10 mg/kg) administered every two weeks until a confirmed complete response, clear progression or serious adverse event emerges. This multi-center, open label study is expected to enroll up to 76 patients in the United States.

“We are encouraged by both the safety profile and the initial anti-tumor activity that included durable responses in several cancer indications for patients treated intermittently with MDX-1106 up to the 10 mg/kg dose. We are also pleased by our ongoing Phase 1b study of repeated doses of the antibody which has also shown early evidence of activity at a repeated dose of 1 or 3 mg/kg,” said Geoffrey M. Nichol, MBChB, Senior Vice President of Product Development at Medarex. “While we are still in early stages of development, it is also exciting that these treatments continue to be generally well tolerated.”

About MDX-1106/ONO-4538

MDX-1106/ONO-4538 is a novel fully human antibody designed to target and inhibit the function of PD-1 (programmed cell death 1), a receptor expressed on the surface of activated lymphocytes (T-cells). The binding of PD-1 with one of two ligands (PD-L1 or PD-L2) is an important negative regulation pathway that suppresses or inhibits activated lymphocytes. Recent research has noted increased PD-1 expression levels on antigen specific T-cells in both the oncology and chronic infectious disease settings, as well as a strong correlation between increased PD-L1 expression on tumors and a negative survival prognosis in cancer patients. Preclinical studies indicate that antibodies targeting the PD-1 signaling pathway reinvigorate antigen-specific T-cell responses and promote an immune response to fight tumors and infectious diseases.

MDX-1106/ONO-4538 is being investigated in both the oncology and infectious disease settings. In addition to the Phase 1b study in cancer, a Phase 1 trial is ongoing for the treatment of hepatitis C. In September 2008, Ono initiated a single and multi-dose Phase 1 clinical study in patients with advanced solid malignancies in Japan. MDX-1106/ONO-4538 may also have the potential to be used synergistically in combination with other treatment modalities, including with anti-CTLA-4 blockade.

In May 2005, Ono entered into a collaboration agreement with Medarex to research and develop a fully human anti-PD-1 antibody for the treatment of cancer. The two companies plan to share the costs and responsibilities of research and product development up to the completion of a Phase 2 clinical study in each party's territory. Thereafter, each company will be fully responsible for any continued development and any commercialization in its exclusive territory; Medarex's exclusive territory is North America, and Ono's exclusive territory is all areas outside of North America.

About Medarex

Medarex is a biopharmaceutical company focused on the discovery, development and potential commercialization of fully human antibody-based therapeutics to treat life-threatening and debilitating diseases, including cancer, inflammation, autoimmune disorders and infectious diseases. Medarex applies its UltiMAb® technology and product development and clinical manufacturing experience to generate, support and potentially commercialize a broad range of fully human antibody product candidates for itself and its partners. Over forty of these therapeutic product candidates derived from Medarex technology are in human clinical testing or have had INDs submitted for such trials, with the most advanced product candidates currently approved for commercial sale, the subject of regulatory applications for marketing authorization or in Phase 3 clinical trials. Medarex is committed to building value by developing a diverse pipeline of antibody products to address the world's unmet healthcare needs. For more information about Medarex, visit its website at www.medarex.com.

Medarex Statement on Cautionary Factors

Except for the historical information presented herein, the statements relating to MDX-1106 in this press release may constitute forward-looking statements, as defined in the Private Securities Litigation Reform Act of 1995, that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Medarex disclaims, however, any intent or obligation to update these forward-looking statements. Risks and uncertainties include risks associated with product discovery and development of MDX-1106, as well as risks detailed from time to time in Medarex's public disclosure filings with the U.S. Securities and Exchange Commission (SEC), including its Annual Report on Form 10-K for the fiscal year ended December 31, 2008 and its quarterly reports on Form 10-Q. There can be no assurance that such development efforts will succeed or that developed products will receive required regulatory clearance or that, even if such regulatory clearance were received, such products would ultimately achieve commercial success. Copies of Medarex's public disclosure filings are available from its investor relations department.

Medarex®, the Medarex logo and UltiMAb® are registered trademarks of Medarex, Inc. All rights are reserved.

Contact: Medarex, Inc.
Laura S. Choi
Investor Relations
Phone: 609-430-2880, x2216

or
Nichol Ochsner
Corporate Communications (media)
Phone: 609-430-2880, x2214

Posted: June 2009

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