The role of CD40L in ALS

CAMBRIDGE, Mass.—The ALS Therapy Development Institute (ALSTDI) has teamed with Biogen Idec of Weston, Mass., and UCB Pharma SA ofBrussels, Belgium to investigate the use of an anti-CD40L antibody as apotential therapy for amyotrophic lateral sclerosis (ALS), also known as LouGehrig's or motor neuron disease. Financial terms of the agreement were notdisclosed.

Under the terms of a pre-existing collaboration betweenBiogen Idec and UCB, UCB is currently developing an anti-CD40L monovalent pegylatedFab antibody fragment (CDP7657) in a Phase I clinical trial of patients withsystemic lupus erythematosus.

From research already conducted, ALS TDI believes thattargeting CD40L is a promising potential therapeutic approach for ALS. ALS TDIhas studied a commercially available research reagent that targets CD40L in apreclinical disease model of ALS (known as SOD1). The results, which werepublished in Nature Genetics in 2010,showed that the anti-CD40L research reagent slowed paralysis and improvedsurvival in the preclinical SOD1 mouse model. The researchers concluded that"our studies with anti-CD40L therapy in the SOD1G93A model of ALS show thatblocking CD40L interactions is therapeutically beneficial in slowing weightloss, delaying paralysis and extending survival. This work exemplifies theutility of genome-wide expression profiling as a tool to drive theidentification, prioritization and rapid validation of preclinical therapeuticsin neurodegenerative disorders such as ALS."

Under the terms of this agreement, ALS TDI will test amurine surrogate of CDP7657 in the SOD1 model. On conclusion of the study,Biogen Idec and UCB will have the option to license global rights to developand commercialize compounds targeting the CD40L pathway in ALS.

"This relationship validates the approach taken by ALS TDIto bridge the gap between basic science and drug development for ALS," says Dr.Steve Perrin, CEO & chief scientific officer of ALS TDI.

He notes that the antibody used in mice in the Nature Genetics study couldn't be usedin humans, and that the Biogen-UCB team already has a program in Phase I trialsin humans. If the mouse data look good, "the humanized version could possiblygo right into Phase II," he says, and adds that the U.S. Food and DrugAdministration is usually pretty liberal with orphan diseases.

"By partnering with Biogen and UCB, we could save three tofive years off of ALS TDI going it alone," he says. "There is great hope thatthis project will be a successful one and lead to additional therapeuticoptions for people living with ALS."

"ALS is a devastating and deadly disease, and Biogen Idecand UCB are both committed to finding therapies for severe neurologicaldiseases with high unmet medical need. We are excited about this project andlook forward to working with ALS TDI in this investigation," says Dr. DouglasKerr, director of medical research at Biogen Idec.

"By combining ALS TDI's innovative approach to bridging thetranslational research gap with our companies' strengths in developing andcommercializing novel therapies, we hope to advance this promising compound forALS patients," adds Neil Weir, senior vice president of discovery research atUCB.

ALS TDI was founded in 1999 as a nonprofit biotech by theJohn Haywood family, whose son Stephen had been diagnosed with ALS (he lost hisbattle with the disease in 2006). Over time, the research group moved from theHaywood's basement to the garage, then occupied a couple of small labs, Perrinrecounts. Today, ALS TDI occupies a 15,000 square-foot facility and has plans to move up to 26,000 square feet inthe near future. Focused on meeting this urgent unmet medical need, ALS TDIexecutes a robust target discovery program, while simultaneously operating theworld's largest efforts to preclinically validate potential therapeutics,including a pipeline of dozens of small molecules, protein biologics, genetherapies and cell-based constructs. Believed to be the world's first nonprofitbiotech, ALS TDI has developed an industrial-scale platform that allows for thedevelopment and testing of dozens of potential therapeutics each year. Withmore than 30 professional scientists, the research Institute collaborates withleaders in both academia and industry to accelerate ALS therapeutic development.

Biogen Idec and IsisPharmaceuticals partner on antisense program targeting SMA

WESTON, Mass.—Biogen Idec also announced in early Januarythat it has entered into an exclusive, worldwide option and collaborationagreement with Isis Pharmaceuticals Inc. under which the companies will developand commercialize Isis' antisense investigational drug, ISIS-SMNRx, for thetreatment of spinal muscular atrophy (SMA).

Under the terms of the agreement, Isis will receive anupfront payment of $29 million and is eligible to receive up to $45 million inmilestone payments associated with the clinical development of ISIS-SMNRx priorto licensing. Biogen Idec has the option to license ISIS-SMNRx until completionof the first successful Phase II/III trial. Isis could receive up to another$225 million in a license fee and regulatory milestone payments. In addition,Isis will receive double-digit royalties on sales of ISIS-SMNRx.

Isis will be responsible for global development ofISIS-SMNRx through the completion of Phase II/III clinical trials, with BiogenIdec providing advice on the clinical trial design and regulatory strategy. IfBiogen Idec exercises its option, it will assume global development, regulatoryand commercialization responsibilities.