Roche and Isis Pharmaceuticals form $392 million alliance against Huntington's disease

In addition, the companies will work to combine Isis' antisense oligonucleotide technology and Roche's proprietary ‘brain shuttle’ program in hopes of increasing the brain penetration of antisense oligonucleotides with systemic administration

| 4 min read

Jeffrey Bouley

BASEL, Switzerland, and CARLSBAD, Calif.—Roche andIsis Pharmaceuticals Inc. formed an alliance this week to develop treatmentsfor Huntington's disease (HD) based on Isis' antisense oligonucleotide (ASO)technology—the idea being to combine Isis' antisense expertise with Roche'sscientific expertise in developing neurodegenerative therapeutics and centralnervous system (CNS) research in general.

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In addition to the goal of finding therapies forHD, Isis and Roche also will be collaborating to combine Isis' ASOs and Roche'sproprietary "brain shuttle" program, the objective being to increase the brainpenetration of ASOs with systemic administration.

Under the terms of the agreement, Roche will makean upfront payment of $30 million to Isis, with total payments related tolicense fee and pre- and post-licensing milestone payments reaching as much as$362 million. In addition, Isis will receive tiered royalties on sales of thedrugs should they reach the market.

Roche has the option to license the drugs fromIsis through the completion of the first Phase I trial. Prior to any exerciseof that option, Isis is responsible for the discovery and development of anantisense drug targeting the huntingtin (HTT) protein. Roche and Isis will workcollaboratively on the discovery of an antisense drug utilizing Roche's brainshuttle program. If Roche exercises its option, it will be responsible forglobal development, regulatory and commercialization activities for all drugsarising out of the collaboration.

Initial research will focus on Isis' lead drugcandidate that blocks production of all forms of the HTT protein, the proteinresponsible for HD, which offers the potential to treat all HD patients if itworks. But there is also the potential for treating subsets of HD patients, as Isisis also conducting research into treatments that specifically block productionof the disease-causing forms of the HTT protein.

In parallel, Roche will combine its proprietarybrain shuttle technology with Isis ASO technology and, if that is successful,it should allow systemic administration of antisense drugs to treatasymptomatic patients.

"Huntington's is a severely debilitatingneurodegenerative disease and a large unmet medical need," said LucaSantarelli, head of Neuroscience and Small Molecules Research at Roche. "Treatmentsare urgently needed, and we believe that the Isis approach in combination withRoche's brain shuttle represent one of the most advanced programs targeting thecause of HD with the aim of slowing down or halting the progression of thisdisease."

"Central to the partnership is Roche's brainshuttle program, which we see as highly complementary to Isis' drug developmentwork," added Shafique Virani, global head of Neuroscience, Cardiovascular &Metabolism at Roche Partnering. "This dual track development program ensureswhichever candidate compound proves to be most promising—Isis' lead target orRoche's brain shuttle version—can be taken forward to pivotal clinical trials."

"We believe that Roche's expertise in developingCNS drugs, along with their clinical development experience, will greatlyenhance our development efforts for this program and allow us to move forwardmore rapidly," noted B. Lynne Parshall, chief operating officer of Isis. "Bypartnering our more complex and nuanced research and development programsearlier in development, like our Huntington's disease CNS program, we add valueand resources with partners that bring unique benefits."

In a different therapeutic area, Isis recentlyscored a victory with orphan drug Kynamro (mipomersen sodium), an injection tobe used with lipid-lowering medications and diet to treat patients with a raretype of high cholesterol called homozygous familial hypercholesterolemia.However, that was a bittersweet victory given that the drug got approval in theUnited States but was denied in Europe, and some market-watchers are noting thatcompeting drug Juxtapid, with its better safety profile, might be the winnerfor an already niche patient population.

So, as Brandy Betz noted April 8 at The MotleyFool, Isis needs "to keep moving to bring something else to market," addingthat the company does benefit from being a "little friend" to Big Pharma, as Isishas more than 20 projects in its pipeline and many of those are with partners likeAstraZeneca, GlaxoSmithKline and Sanofi—and now Roche with the HD deal—and thatgives Isis some breathing room by reducing its risk.

There is enormous revenue potential, as Betznotes, should Roche and Isis even manage to get a therapy approved to simply toslow the progression of HD. But the opinion over at The Motley Fool is not to gettoo optimistic unless and until mid-stage and late-stage trials show somepromising data.

Huntington's disease is an inherited genetic braindisorder that results in the progressive loss of both mental faculties andphysical control. Symptoms usually appear between the ages of 30 to 50, andworsen over a 10- to 25-year period. Ultimately, the weakened individualsuccumbs to pneumonia, heart failure or other complications. There is noeffective treatment or cure as yet for the disease, and current treatmentsfocus on reducing the severity of some disease symptoms.

Because financial and scientific support from the CHDIFoundation, a non-profit foundation exclusively dedicated to the development oftherapies that slow the progression of HD, has played a significant role inIsis' progress with HD research, that foundation will also benefit from theRoche deal.

"Together, Isis and CHDI demonstrated thatantisense compounds can be used to inhibit the production of HTT protein inboth brain and peripheral tissues," notes Isis in the news release about theRoche deal, "and that the inhibition of normal HTT protein was well tolerated."

Over time, CHDI will be reimbursed for its supportof Isis' program out of the milestone payments received by Isis, and thefoundation will receive $1.5 million in the short run associated with thesigning of the Roche agreement. CHDI reportedly will continue to provide adviceto Isis and Roche on the development of antisense drugs to treat patients withHD.

Roche and Isis Pharmaceuticals form $392 million alliance against Huntington's disease

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Jeffrey Bouley

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