Roche, the world's largest biotechnology company and Isis Pharmaceuticals, Inc. have formed an alliance to develop treatments for Huntington's disease (HD) based on Isis' antisense oligonucleotide (ASO) technology. This alliance combines Isis' antisense expertise with Roche's scientific expertise in developing neurodegenerative therapeutics.

In addition, Isis and Roche will be collaborating to combine Isis' ASOs and Roche's proprietary "brain shuttle" programme with the objective of increasing the brain penetration of ASOs with systemic administration.

Initially, research will focus on Isis' lead drug candidate that blocks production of all forms of the huntingtin (HTT) protein, the protein responsible for HD and thus has the potential to treat all HD patients. Isis is also conducting research into treatments that specifically block production of the disease-causing forms of the HTT protein which has the potential to treat subsets of HD patients. In parallel, Roche will combine its proprietary brain shuttle technology with Isis ASO technology that, if successful, will also allow systemic administration of antisense drugs to treat asymptomatic patients.

Under the terms of the agreement, Roche will make an upfront payment of $30 million to Isis, with total payments related to license fee and pre- and post-licensing milestone payments reaching potentially $362 million, including up to $80 million in potential commercial milestone payments. In addition, Isis will receive tiered royalties on sales of the drugs. Roche has the option to license the drugs from Isis through the completion of the first phase I trial. Prior to option exercise, Isis is responsible for the discovery and development of an antisense drug targeting HTT protein. Roche and Isis will work collaboratively on the discovery of an antisense drug utilizing Roche's "brain shuttle" programme. If Roche exercises its option, it will be responsible for global development, regulatory and commercialisation activities for all drugs arising out of the collaboration.

Commenting on the deal, Luca Santarelli, head of Neuroscience and Small Molecules Research at Roche, said, "Huntington's is a severely debilitating neurodegenerative disease and a large unmet medical need. Patients experience gradually worsening motor function and psychological disturbances, with a significant shortening of life expectancy after the disease is diagnosed. Treatments are urgently needed, and we believe that the Isis approach in combination with Roche's brain shuttle represent one of the most advanced programmes targeting the cause of HD with the aim of slowing down or halting the progression of this disease."

Shafique Virani, Global Head Neuroscience, Cardiovascular & Metabolism at Roche Partnering, added, "Central to the partnership is Roche's brain shuttle programme, which we see as highly complementary to Isis' drug development work. This dual track development programme ensures whichever candidate compound proves to be most promising -- Isis' lead target or Roche's brain shuttle version -- can be taken forward to pivotal clinical trials."

B Lynne Parshall, chief operating officer of Isis said, "We are pleased to be working with Roche, a global leader in drug development with significant experience in developing and commercialising drugs to treat neurological diseases. We believe that Roche's expertise in developing CNS drugs, along with their clinical development experience, will greatly enhance our development efforts for this programme and allow us to move forward more rapidly. In addition, by utilizing Roche's brain shuttle technology with our antisense drug discovery capabilities, we have the potential to significantly improve the therapeutic potential for this programme."

Parshal further added, "By partnering our more complex and nuanced research and development programmes earlier in development, like our Huntington's disease CNS programme, we add value and resources with partners that bring unique benefits."

"We are excited to be working with Roche," said Frank Bennett, senior vice president of Research at Isis. "We believe our mature antisense drug discovery platform is a perfect fit for Roche's neuroscience franchise, and we anticipate a fruitful collaboration to advance our pre-clinical compounds."

Isis also recognizes the tremendous benefit provided to its HD programme by its academic collaborators, Drs Don Cleveland at the Ludwig Institute, University of California San Diego and David Corey at University of Texas Southwestern. These collaborators have been instrumental in Isis' early preclinical work demonstrating that antisense drugs can inhibit the HTT protein and produce activity in animal models of disease.

Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. The company is working on new molecular entities in neuroscience that could become the next generation of medicines for a range of diseases including schizophrenia, multiple sclerosis, depression, neurodevelopmental disorders, Parkinson's disease and Alzheimer's disease.