ROCKVILLE, Md.—There are smiles to be had over BiTEantibodies for Micromet Inc. with the recent signing of a collaborationagreement with Amgen Inc. for research directed at using such antibodiesagainst three undisclosed solid tumor targets. With the promise of some $14million upfront and a maximum deal value of around $976.3 million, plusroyalties and development cost reimbursement, the deal could mean as much as$1.01 billion for Micromet over the long run.
Under the terms of the agreement, Amgen will have the rightto pursue development and commercialization based on Micromet's proprietaryBiTE technology for as many as two of the three targets, to be selected byAmgen.
For one of the programs, Micromet could receive roughly$480.2 million in clinical and commercial milestone payments if various goalsin indications and tumor type are achieved, and Micromet would also be eligibleto receive up to double-digit royalties on worldwide net sales.
For the second BiTE program, Micromet is eligible to receivean additional cash payment upon initiation of the program, as well asmilestones, royalties and development funding that would be more or lesscomparable to the first program.
The initial development plan assumes about $35 million infunding of Micromet research and development activities if two BiTE antibodiesare advanced to the (Investigational New Drug) IND stage. All expected costsassociated with the research, development and commercialization of the BiTEantibodies will be borne by Amgen. Micromet will be primarily responsible forthe discovery and preclinical development of the BiTE antibodies. Amgen willlead the clinical development, manufacturing and commercialization of anyproducts resulting from the collaboration.
"The BiTE antibody provides an innovative approach to cancertherapy," said Dr. Roger M. Perlmutter, executive vice president of researchand development at Amgen, in a press release about the deal, noting that theantibodies are designed to direct the body's cytotoxic, or cell-destroying, Tcells against tumor cells.
Typically, antibodies cannot engage T cells because T cellslack the appropriate receptors for binding antibodies. BiTE antibodiesreportedly can bind T cells to tumor cells, ultimately inducing aself-destruction process in the tumor cells referred to as apoptosis, orprogrammed cell death. In the presence of BiTE antibodies, T cells have shownevidence of the potential to serially eliminate tumor cells, which thecompanies say explains the activity of BiTE antibodies at very lowconcentrations. Through the killing process, T cells start to proliferate,which leads to an increased number of T cells at the site of attack.
Although Micromet declined to share any details about theorigin of the relationship between the two companies nor the process of thedeal coming together, Jennifer Neiman, director of corporate communications,tells ddn, "from a strategic standpoint, this deal enables us to gainentrée into additional large solid tumor indications with support from apartner while also generating substantial non-dilutive capital for thecompany."
This echoes the comments of Dr. Christian Itin, Micromet'spresident and CEO, in the news release about the deal, who called Amgen "anindustry leader with a proven track record of success in oncology andbiologics" and noted that this collaboration "aligns well with our strategy toexpand development of BiTE antibodies into solid tumor indications."
Micromet has ongoing collaborations with a number of leadingpharmaceutical and biotechnology companies other than Amgen, including BayerHealthcare Pharmaceuticals, Boehringer Ingelheim, MedImmune, Merck Serono,Nycomed and Sanofi, and Neiman adds that "the growing number of partnered BiTEsis adding significant long-term value in future milestones and royalties withno investment required by Micromet."
The company generated approximately $141.4 million in cashfrom 2006 to the first quarter of 2011 from corporate partnerships, she notes,including five BiTE antibody collaborations now in place, and points out that"Amgen has long been a leader in the development and marketing of antibodies,making them an ideal collaboration partner."
Amgen likewise had no further comment on the details of thedeal itself or its genesis, but Kristen Davis of the company's corporatecommunications department notes that Amgen is keenly focused on developinginnovative cancer therapies and adds that the BiTE antibody technology willexplore new targets for treating solid tumors.
"BiTEs are an extension of antibody technology and are anexcellent fit with Amgen's expertise," she adds.
Micromet focuses on antibody-based therapies for thetreatment of cancer, and its product development pipeline includes novelantibodies generated with its BiTE technology as well as conventionalmonoclonal antibodies. The company's lead product candidate blinatumomab(MT103) is currently the subject of a pivotal European trial in patients withminimal residual disease positive acute lymphoblastic leukemia.