Date: 2013-04-08
Type of information: Development agreement
Compound: antisense oligonucleotide (ASO) technology
Company: Isis Pharmaceuticals (USA - CA) Roche (Switzerland)
Therapeutic area: Genetic diseases - Neurodegenerative diseases - Rare diseases
Type agreement: development
Action mechanism: antisense oligonucleotide.
Disease: Huntington's disease
Details:
* On April 8, 2013, Roche and Isis Pharmaceuticals 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\" program 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 1 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\" program. If Roche exercises its option, it will be responsible for global development, regulatory and commercialization activities for all drugs arising out of the collaboration. CHDI Foundation, a non-profit foundation exclusively dedicated to the development of therapies that slow the progression of HD, provided financial and scientific support to Isis\' HD drug discovery program through a development collaboration with Isis. CHDI\'s support has enabled Isis to make significant progress in discovering a drug to treat HD. Together Isis and CHDI demonstrated that antisense compounds can be used to inhibit the production of HTT protein in both brain and peripheral tissues, and that the inhibition of normal HTT protein was well tolerated. Over time, CHDI will be reimbursed for its support of Isis\' program out of the milestone payments received by Isis. CHDI will receive $1.5 million associated with the signing of the Roche agreement. CHDI will continue to provide advice to Isis and Roche on the development of antisense drugs to treat patients with HD. Isis also recognizes the tremendous benefit provided to its HD program 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.
Financial terms:
Latest news: * On July 21, 2015, Isis Pharmaceuticals announced that it has initiated a Phase 1/2a clinical study of ISIS-HTTRx in patients with Huntington's disease (HD). ISIS-HTTRx is the first therapy to enter clinical development that is designed to directly target the cause of the disease by reducing the production of the protein responsible for HD. Presently, there are no disease-modifying treatments for HD, with current therapies focused only on treating disease symptoms. The randomized, placebo-controlled, dose escalation Phase 1/2a clinical study will evaluate the safety and activity of ISIS-HTTRx in patients with early stage HD. In this study, ISIS-HTTRx will be administered intrathecally as an injection directly into the cerebral spinal fluid. Intrathecal administration of antisense drugs has been shown to be well tolerated in multiple clinical studies in patients.
