T cell targets

BOSTON—A three-year researchcollaboration between global pharmaceutical company Sanofi andBrigham and Women's Hospital, a teaching and research affiliate ofHarvard Medical School, will focus on the immunology of type 1diabetes in an attempt to analyze and develop new drug targets.

"Because diabetes is a major focus ofour company, we are always seeking opportunities to develop newmedicines for both type I and type 2 varieties of the disease,"explains Dr. Srideran Natesan, scientific site head of research anddevelopment at Sanofi in Cambridge, Mass., and head of externalinnovation and partnering for the U.S. northeast region. "Now thatwe have become a significant presence in the Cambridge area, we arelooking for ways to collaborate with top researchers and invite themto make presentations to our diabetes management team."

Sanofi was impressed with the work ofDr. Vijay Kuchroo, a veterinarian and pathologist who serves asprofessor of neurology at the Harvard Medical School and Wasserstromprofessor of neurology and associate immunologist at the Brigham andWomen's Hospital, according to Natesan.

"Vijay is a key leader in immunologyin type 1 diabetes and has validated several targets in hislaboratory," Natesan says. "Eventually, through thiscollaboration, we will look for new targets and develop them."

Kuchroo's laboratory has made severaltransgenic mice that serve as animal models for human disease. Themajor focus of research in the laboratory is to study the autoimmuneT cell response, role of costimulatory molecules and their receptorsin the induction and differentiation of T cells and identification ofcell surface molecules differentially expressed on T cell subsets.Kuchroo's research interests are studying the autoimmune diseases,particularly the role of costimulation, the genetic basis ofexperimental autoimmune encephalomyelitis or experimental allergicencephalomyelitis, an animal model of brain inflammation and type 1diabetes and cell surface molecules and regulatory factors thatcontribute to susceptibility and resistance to autoimmune diseases.

"Brigham and Women's Hospital isexcited to engage in this important research collaboration," saidDr. Barbara Bierer, the hospital's senior vice president ofresearch, in a press release. "This strategic collaboration bringsfurther recognition to the outstanding research of Dr. Kuchroo andhis colleagues, including Drs. Terry Strom and Maria Koulmanda fromBeth Israel Deaconess Medical Center, and the importance of thetranslation of fundamental discoveries into routine clinicalpractice."

According to the terms of thecollaboration, Sanofi and Brigham and Women's Hospital will shareknowledge and apply their respective expertise in basic and appliedresearch regarding diabetes and drug target and candidatedevelopment. Researchers from both organizations will undertakeproof-of-concept, safety and functional studies for a novelimmunomodulatory approach to treat type 1 diabetes, and Sanofi willhave an option to exclusively license intellectual property emergingfrom the collaboration. There will be "milestones on one or twotargets" and then "a decision on whether to expand the program,"Natesan says.

Internationally acclaimed for itspatient care, biomedical research and healthcare professionalteaching capabilities, Brigham and Women's Hospital is a 793-bedteaching affiliate of Harvard Medical School. With roots dating backto 1832, the hospital formed in 1980 with the merger of three Harvardteaching hospitals.

Sanofi, which discovers, develops anddistributes therapeutic solutions, has established a number ofpartnerships to offer diagnostics, therapies, services and devicesfor the prevention and cure of diabetes. After two years ofdiscussions with leaders in universities and research institutions,Sanofi has made plans to ally with other researchers to enhance itsown offerings of insulin products. The global and diversifiedhealthcare company recently announced a collaboration with the JoslinDiabetes Center, a clinical, teaching and research affiliate ofHarvard Medical School that has 47 affiliated clinics in the UnitedStates.

Natesan believes that diabetes ismoving toward more personalized medicine and hopes the collaborationbetween Sanofi and Brigham and Women's Hospital will bring about "acomprehensive strategy to address immunomodulation, which we believeto have a lot of value."

PARIS—Sanofi also announced lastmonth, along with partner Regeneron Pharmaceuticals Inc., thatseveral trials within ODYSSEY, the Phase III clinical program ofSAR236553/REGN727, have initiated patient enrollment.

SAR236553/REGN727 is a potentialfirst-in-class, subcutaneously administered, fully human antibodythat lowers low-density lipoprotein (LDL) cholesterol by targetingproprotein convertase subtilisin/kexin type 9 (PCSK9), an enzymewhich binds LDL receptors, leading to their accelerated degradationand increased LDL-cholesterol levels.

ODYSSEY, a global program to evaluateSAR236553/REGN727, will consist of more than 10 clinical trials andwill include more than 22,000 patients. The studies will be conductedin clinical centers around the world, including the United States,Canada, Western and Eastern Europe, South America, Australia andAsia.

SAR236553/REGN727 is administered as asingle injection every two weeks in multiple treatment strategies andpatient types, such as those who are at elevated cardiovascular risk,are unable to tolerate statin therapy or have familialhypercholesterolemia.