INGELHEIM, Germany—Boehringer Ingelheim (BI) and Bethesda,Md.-based biopharmaceutical Micromet Inc. have joined forces for the research,development and commercialization of a new BiTE antibody for the treatment ofmultiple myeloma, a blood cancer disease that is largely incurable.
In the United States, Micromet and BI will jointlyco-promote the BiTE antibody with commercial terms commensurate with a profitsplit, according to the joint company announcement on May 5.
Micromet will be responsible for discovery of the BiTEantibody and will jointly conduct with BI further preclinical studies, while BIwill be responsible for all manufacturing activities, clinical development andworldwide commercialization subject to Micromet's co-promotion right in theUnited States.
Micromet will bear the costs up to a pre-defined amount forits preclinical activities.
During commercialization, Micromet will solely bear thecosts for its sales force in the United States. All other costs for research,development, manufacturing and commercialization of the BiTE antibody will beborne by BI.
Under the terms of the agreement, BI will pay Micromet anupfront cash payment of approximately $6.6 million. Micromet is eligible toreceive development and regulatory milestone payments of up to approximately$66 million and tiered low double-digit royalties on product sales outside theUnited States.
Wolfgang Rettig, head of corporate research at BI, says thecompany recognizes the advantage of combining Micromet's BiTE antibody platformwith BI's target identification and development expertise. Kate O'Connor,executive director of public relations at BI's Ridgefield, Conn. facility, saysthe companies have a "long-standing relationship" on a senior management level.
"The respective projects that resulted in the collaborationrepresent a perfect fit of BI's interest in developing innovative approaches totarget specific biologically relevant structures in the area of multiplemyeloma and BI's expertise in the central nervous system research field."
Myeloma is a tumor involving specialized white blood cellsin the bone marrow. The cells that are affected are plasma cells, which are ourantibody-producing cells. The disease myeloma is called "multiple"since there frequently are multiple patches or areas in bone where tumors orlesions have developed.
The commercial opportunity for treatments for multiplemyeloma is reflected in the growing numbers of mostly elderly adults worldwideinflicted with the disease. The American Cancer Society estimates that about20,580 new cases of multiple myeloma were diagnosed during 2009 in the UnitedStates, where the lifetime risk of getting multiple myeloma is one in 161. Morethan 14,000 new cases a year are expected in the United States alone.
Despite recent advances in the treatment of multiplemyeloma, the disease remains largely incurable, O'Connor says. While themajority of patients initially respond to treatment, almost all will eventuallyrelapse. The five-year relative survival rate for multiple myeloma is around 35percent.
BI and Micromet believe BiTE antibodies will help moreindividuals survive longer since the antibodies are designed to direct thebody's cytotoxic, or cell-destroying, T cells against tumor cells, thusrepresenting a new and more powerful therapeutic approach to cancer therapy.
Jennifer Neiman, Micromet's director of corporatecommunications, says that typically, antibodies cannot engage T cells because Tcells lack the appropriate receptors for binding antibodies. However, BiTEantibodies have been shown to bind T cells to tumor cells, ultimately inducinga self-destruction process in the tumor cells referred to as apoptosis orprogrammed cell death. In the presence of BiTE antibodies, T cells have beendemonstrated to serially eliminate tumor cells, which explains the need forBiTE antibodies at very low concentrations, Neiman explains.
The BiTE antibodies actually represent a new class ofantibodies that activate the T cells of a patient's immune system to eliminatecancer cells, she said. T cells are considered the most powerful '"killercells'" of the human immune system.
"We believe that treating multiple myeloma represents apotentially meaningful future revenue stream for the company," Neiman says."Based on our understanding of the target for this BiTE antibody, we believethat it has the potential to offer an improvement over existing treatmentoptions."
Christian Itin, Micromet's president and CEO, says he is"very pleased to collaborate with Boehringer Ingelheim, an industry leader witha proven track record of successful partnerships."
In line with the strategic importance of hemato-oncology forMicromet, "we have retained U.S. co-promotion rights for this product candidateconsistent with our goal of building a commercial hematology franchise in theUnited States," Itin says.
The deal with BI was timely. In announcing Micromet'sfinancial results for the first quarter ending March 31, 2010, Itin said: "Withthe proceeds from our recent financing, we are well-positioned to conduct theplanned European pivotal study of blinatumomab in patients with acute lymphoblasticleukemia and other studies intended to support its use as a key component ofthe standard of care in this indication."
"Our new collaboration with Boehringer Ingelheim is animportant step toward our goal to develop a hemato-oncology franchise, with nowthree BiTE antibodies in research and development that have the potential toaddress the majority of hematological cancers," he now adds.