Sanofi-aventis boosts oncology pipeline in deals with Oncodesign, Micromet

Deals aimed at boosting the French drug company’s pipeline and profile in cancer therapy market

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PARIS—French pharma sanofi-aventis has once again capturedcenter-stage in the global cancer market with two signed oncology-focused dealsaimed at boosting the French drug company's pipeline and profile.


The first, with Dijon, France-based Oncodesign, is atwo-year service contract targeted toward developing exclusive, experimentalmodels in different types of cancer. Unlike traditional models which arederived from cultured cell lines, Oncodesign is developing models based ontumor tissue taken directly from patients, enabling more customized evaluationsof new therapies while remaining as close as possible to clinical reality. Thefinancial terms of the contract were not disclosed.


The second partnership is with Bethesda, Md.-basedbiopharmaceutical Micromet Inc., for the licensing of Micromet's BiTE antibodyagainst an antigen present at the surface of carcinoma cells. Under the termsof the agreement, sanofi-aventis will pay Micromet an upfront cash payment of$12 million, plus development and regulatory milestone payments of up to $241million, as well as performance-based sales milestones of up to $224 millionand royalties on worldwide product sales.


The collaborations, announced in late October, reflectsanofi-aventis' plans to position itself as a major player in the estimated $48billion global oncology market.


"These strategic partnerships are aimed at providing accessto diverse forms of external innovation into our search for new anti-tumordrugs, expand our product portfolio and support our new strategy, which isfocused firmly on targeted therapies and biotherapies," says Christopher A.Viehbacher, the company's CEO.


Viehbacher has had his eye on the oncology market sincecoming over to sanofi-aventis from GlaxoSmithKline PLC in December 2008. InApril, sanofi-aventis acquired BiPar Sciences, a biopharmaceutical company,developing novel tumor selective-approaches for the treatment of differenttypes of cancers including triple-negative breast cancer. In May,sanofi-aventis and Exelixis, a biotechnology enterprise, announced a globallicense agreement for XL147 and XL765 and an exclusive collaboration for thediscovery of inhibitors of phosphoinositide-3 kinase (PI3K) for the managementof solid malignancies.


Christoph Lengauer, head of Oncology Research atsanofi-aventis, says Oncodesign's "specific logistics of enabling usable modelsto be developed with only a few grafts, was a decisive factor in pursuing thepartnership."


Philippe Genne, CEO of Oncodesign, says, "To our knowledge,this contract is a first for a service company, since it is a long-termcollaboration that calls for us to supply experimental models tosanofi-aventis. We are working to develop our design and validation capabilityso we can make ready-to-use models available to our customers and partners."


Oncodesign and sanofi-aventis worked together on the CReMECprogram, which started in 2005 under the sponsorship of the Medicen ParisRegion competition pole and entailed the development and characterization ofexperimental models of colon cancer. The work involved evaluating new therapiesin the most relevant models, the ones that most resemble the clinical realityin histological, molecular and pharmacological terms. The participants in thisprogram may also have access to models of tumors taken from patients who havealready undergone treatments and/or have developed resistance to them.


"Oncodesign has been the leader of the CReMEC consortium,"says Cyril Berthet, the company's associate director of scientific relations. "Throughthis leadership, Oncodesign has shown its capacity to manage complex projectswith more than 10 partners, from academia to pharma, over a long period of time(2005-2009). Since sanofi-aventis trusts Oncodesign in such expertise, we hopeto build on this new relationship and work with sanofi-aventis on otherpotential long-term collaborations, such as a lead optimization program or biomarkerdevelopment that we now offer."


Oncodesign's programs are bound to enhance sanofi-aventis'goals and existing oncology pipeline because "compared to standard xenographs,patient-derived tumor models are more suitable to evaluate targeted therapies sincethey match clinical samples on histological, molecular and pharmacologicalaspects," Berthet says.


Oncodesign is seeking other pharma partners, and "developingour platform for integrated discovery and building strong partnerships on thelead optimization of therapeutic drugs," he says.


The sanofi-aventis-Micromet agreement stipulates thatMicromet will be mainly responsible for the discovery, research and developmentof the BiTE antibody through the completion of Phase I clinical trials, whilesanofi-aventis works on the further development and worldwide commercializationof the BiTE antibody, which has the potential to significantly expand thetreatment options to cancer patients in the future, says Marc Cluzel, executivevice-president of R&D at sanofi-aventis.


Micromet CEO Christian Itin says the collaboration "furthervalidates the BiTE antibody technology and creates the opportunity to expandthe pipeline of BiTE antibodies for the treatment of solid tumors."


BiTE antibodies activate a patient's T-cells to seek out anddestroy cancer cells, representing a new therapeutic approach to cancertherapy. Typically, antibodies cannot engage T-cells because they lack theappropriate receptors for binding antibodies. BiTE antibodies have been shownto bind T-cells to tumor cells, ultimately inducing a self-destruction processin the tumor cells referred to as apoptosis, or programmed cell death.
In the presence of BiTE antibodies, T-cells have seriallyeliminated tumor cells, Mircomet reports. Through the killing process, T-cellsstart to proliferate, which leads to an increased number of T-cells at the siteof attack.


On Nov. 5, Micromet also announced that it signed an agreement withMedImmune LLC to buy out MedImmune's rights to blinatumomab in North America,and to terminate the collaboration agreement signed in 2003 under whichMedImmune had been granted the right to develop and commericalize blinatumomabin North America. As a result of this transaction, Micromet now controls globalrights to develop and commercialize blinatumomab, a novel therapeutic antibodythat activates a patient's T cells to seek out and destroy lymphoma andleukemia cells. 

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