GSK Bolsters Orphan Drug Discovery By Signing Antisense Deal With Isis

Under the deal, which has all the hallmarks of a GSK option-based alliance, Isis gets $35 million upfront, and will deliver five drugs through PoC.

In another partnership that signals GlaxoSmithKline's affection for option-based deals and growing interest in the orphan disease market, the company announced an alliance with the drug discovery firm Isis on March 31. Under the arrangement, GSK will apply Isis' antisense drug discovery platform to develop new drugs against five targets for rare and serious diseases (with the potential to add one additional program), including infectious diseases and conditions causing blindness.

Under the terms, Isis will receive $35 million up front to develop the drugs through Phase II proof of concept, at which point GSK will have an option to license the compounds and become responsible for future development and commercialization. Isis also is eligible to receive an average of up to $20 million in development milestones per program up to PoC.

Those milestones are different for each candidate but are slated for transitional events like demonstration of efficacy in animals, selection of development candidate and initiation of Phase II, according to Isis. The total value of the deal, though heavily risk-weighted, is $1.5 billion, including licensing and milestone payments in the event that all six programs are successfully developed.

Option-based deals have been growing in the industry, but GSK has mastered the deal structure, signing more such alliances than any other big pharma. And this latest deal provides GSK with a low-risk opportunity in an emerging area of science, antisense-based drugs. Antisense therapies target the proteins involved in disease processes through the RNA that builds the proteins. Antisense drugs represent a potential new class of drugs beyond small molecules and biologics.

Isis' discovery platform develops therapies that bind to messenger RNA and inhibit the production of disease-causing proteins. GSK has completed several deals in the RNA market, including deals with Sirna (now part of Merck & Co) for respiratory disease; with Santaris for RNA antagonists to treat viral diseases, and with Regulus (a joint venture between Alnylam and Isis) for anti-inflammatory microRNA antagonists. GSK was the first partner signed by Regulus in 2008, and the two firms recently announced an expansion of the partnership to include a new collaboration to co-develop drugs targeting micro-RNA-122 in hepatitis C (Also see "GSK Doubles Up With Regulus, Signing New Collaboration For HCV Therapeutics" - Pink Sheet, 25 Feb, 2010.).

"The discovery of RNA interference led to a resurgence in this whole area of antisense, and it felt like the right time to invest because it is a new area of science," a spokesperson for GSK said in a follow-up interview.

Option-Based Deals Are Of Interest To Isis, CEO Says

For Isis, the arrangement marks the company's first option-based deal. The drug developer typically has either completed outright licensing deals like its transformative 2008 partnership with Genzyme for the cholesterol drug mipomersen - a deal and drug that is widely linked to validation of the antisense platform - and with Bristol-Myers Squibb for the PCSK9 inhibitor for cholesterol or created satellite companies for non-core assets, as it did with Regulus.

"This is the sort of deal we are willing to do now," CEO Stanley Crooke said in an interview. "By taking an option, GSK gets access to our technology, but in the meantime, we stay in control, moving through drug discovery in a much more expeditious way." The option-based deal is a transaction style Isis is discussing with other companies as well, he added.

Four of the five targets are completely new targets, the exec said, but the company expects to move a first drug into clinical development this year, and have one to "several" drugs reach Phase II PoC within three to five years.

As for what happens if GSK chooses not to exercise its option on a drug candidate, Crooke said that is not a concern. "In partnering, most drugs are returned at least once. We assume there will be changes in appetite and interest at GSK over time, and if that's the case, then we've got a drug to develop."

The deal with GSK returns Isis to a therapeutic area it has worked in before, eye disease. The company's only antisense drug on the market is Vitravene (fomivirsen), an earlier-generation antisense drug approved in 1998 for cytomegalovirus retinitis in AIDS patients.

Needham & Co. analyst Mark Monane applauded the deal in a same-day research report. "We believe this collaboration represents another example of the value of Isis' core technology for the potential treatment of hard-to-treat illnesses," he said.

GSK is among several big pharmas that have expressed growing interest in the orphan disease area. Last year, the company signed a deal with Prosensa to focus on the development of four RNA-based compounds for the treatment of Duchenne muscular dystrophy, and then in February, GSK announced the formation of a specialist unit to explore the development of drugs for orphan diseases. The trend is one other big pharmas, like Novartis and Pfizer, also are getting involved in (Also see "Orphaned No Longer: Big Pharma Embraces Drugs for Niche Markets" - In Vivo, 1 Feb, 2010.).

The five targets included in the deal with Isis were brought into the collaboration by GSK, Isis Chief Financial Officer Lynne Parshall said in a same-day conference call. "These programs allow us to extend and expand our therapeutic focus in ways that we think play to our strengths and capitalize on the ability of our technology to approach targets not druggable using traditional methods," she said.

-Jessica Merrill ([email protected])