Skip to main content
Premium Trial:

Request an Annual Quote

Roche Aims to Move First RNAi Drug into Clinic in 2010; Keeps Eye on miRNA Space

Premium
Less than a year after it picked up non-exclusive access to Alnylam Pharmaceuticals’ portfolio of RNAi-related intellectual property and acquired the RNAi-drug developer’s German subsidiary, Roche is on track to move its first RNAi-based drug candidates into the clinic in 2010, according to a senior company official.
 
“We are moving forward and investing very significantly … to drive [our RNAi] compounds into the clinic … with the goal of doing our first clinical studies … in about two years,” Lee Babiss, head of global pharma research at Roche, told RNAi News last week.
 
The Swiss biopharmaceuticals giant is developing RNAi drugs in the fields of liver-associated metabolic disorders, respiratory diseases, and cancer, but Babiss declined to name specific targets or indications the company is pursuing.
 
To meet its two-year timeline, Babiss said Roche has begun investing heavily in Alnylam’s former German operations, which have become Roche’s Center of Excellence for RNAi therapeutics discovery, and plans to double the unit’s headcount to approximately 90 staffers “over the next couple of years.”
 
Mindful that delivery remains a key hurdle for all RNAi drug developers, Roche is also looking outside of its own labs for potential solutions to that problem, he noted.
 
“We never take just an insular view of our science,” he said. “We have a great deal of respect for our scientists but we also know that the world of science is a lot bigger than Roche. We have done deals already and will continue to do deals, not only with biotech but [with] academia, to get our hands on every type of delivery approach that could be viable.”
 
Babiss noted that Roche has already forged RNAi drug-delivery collaborations with “some [undisclosed research] institutes in China,” but has yet to enter an arrangement with an industry partner.
 
As it advances its RNAi work, the company is also keeping a close eye on the emerging microRNA field. Although its in-house research into miRNA therapeutics is “very preliminary,” Roche is moving the work forward and is already in talks with an undisclosed industry player about a possible miRNA drugs collaboration, Babiss said.
 
At the same time, Roche has at least two research groups examining the diagnostic potential of the small, non-coding RNAs, he added. “As the largest diagnostics company in the world, we don’t have a deaf ear” to miRNA-based diagnostics, he said.
 
As such, Roche has not ruled out the possibility of using acquisitions to give a boost to its miRNA diagnostics research, Babiss said. 
 
Citing Roche’s 1991 buyout of PCR-developer Cetus and its 1999 acquisition of Genentech, Babiss noted that his company has “a long history of taking a longer-term view of science and investing in it at an earlier stage.”
 
“There are different ways of doing [this]: one is to jumpstart it internally and the other way is to go out there and buy what you might need,” he added. Roche’s diagnostics group “knows how to do that work very well. They’re on top of it.”
 
Eyeing RNA
 
Roche first began pursuing the RNAi drugs field in earnest around mid-2006 under an initiative set in motion by former Roche CEO Franz Humer, according to Babiss. “We began … [by asking] a very simple question: ‘We’re strong in small-molecule drug discovery and we’re the largest biotech, if you want to consider us that, [so] what’s next?’”
 
He said that in trying to answer that question, Roche evaluated a wide variety of therapeutic modalities including stem cells, vaccines, and RNA drugs in general. “We came away with the conclusion that the success we were having with RNAi in the laboratory setting preclinically really suggested that there was an opportunity to take this technology to the next level” — meaning human therapeutics.
 
But before it could try to reach that level, Roche had to secure the freedom to operate in RNAi therapeutics. Already, a handful of big pharmas had moved in to secure the field’s fundamental IP: Merck had begun collaborating with Alnylam in 2003 (see RNAi News, 9/12/2003), although that relationship fell apart after Merck acquired Alnylam’s chief rival Sirna Therapeutics about a year ago (see RNAi News, 9/20/2007).
 
More significantly, in 2005 Novartis Pharmaceuticals formed a broad drug-discovery and -development alliance with Alnylam that gives Novartis the right of first offer on targets Alnylam may wish to partner with third parties (see RNAi News, 9/9/2005).
 

“Kudos to Novartis for going first; certainly they got [access to Alnylam’s IP] for a lot less, but they took a much greater risk in investing in the technology at that time. We were very comfortable with the price we paid.”

According to Babiss, despite having begun IP-licensing talks with Sirna before the Merck acquisition, “we felt that from an intellectual property perspective, Alnylam had the [best] package overall to allow freedom to operate,” Babiss said. In January 2007, Roche began negotiating for access to Alnylam’s IP estate. Seven months later, the deal was done (see RNAi News, 7/12/2007).
 
Under the terms of the arrangement, Roche paid Alnylam $274 million in upfront IP license fees and $15 million to acquire the RNAi shop’s facilities in Kulmbach, Germany. Roche also made a $42 million equity investment in Alnylam.
 
Despite Roche paying what some industry-watchers consider a high price for the Alnylam IP and being subject to Novartis’ right of first offer on RNAi drug targets it wishes to pursue, Babiss said that the deal was a good one for Roche and not an instance of his company playing catch-up.
 
“I don’t feel that our hands were on the coals,” he said. “In the end, we decided what the fair price was and that’s what we went with.
 
“Kudos to Novartis for going first; certainly they got [access to Alnylam’s IP] for a lot less, but they took a much greater risk in investing in the technology at that time,” Babiss added. “We were very comfortable with the price we paid … [and] we’re very comfortable with the IP position that we have; we do not feel there is any IP out there that does not allow us freedom to operate.”
 
Babiss also said that the Kulmbach acquisition was a major victory for his company. “I didn’t want to have to take one or two years to build up the scientific capabilities within Roche to begin to take advantage of the IP we had just acquired,” he said.
 
In acquiring the Kulmbach site, where Alnylam had been conducting chemistry and lead-generation and -optimization work, “we overnight became fully enabled.”
 
Delivery Options
 
Before inking its deal with Alnylam, Babiss said, Roche also considered the various RNAi alternatives to delivered synthetic siRNAs including expressed RNAi, but ultimately decided against pursuing them — at least for now.
 
For expressed RNAi, “the hurdle will be a little higher because of the complexity of the overall approach,” he said. “Conceptually and in a laboratory, [the technology] can work. But when you start thinking gene therapy approaches, it raises different issues. I would have some concerns about it as it stands today.”
 
That said, the RNAi field continues to grow and expand, he added. “The rest of the world is not standing still and saying, ‘There is no more hope for getting into [the RNAi] space.’ There are a lot of creative people out there and we certainly are watching the field as it continues to evolve.”

The Scan

Study Finds Few FDA Post-Market Regulatory Actions Backed by Research, Public Assessments

A Yale University-led team examines in The BMJ safety signals from the US FDA Adverse Event Reporting System and whether they led to regulatory action.

Duke University Team Develops Programmable RNA Tool for Cell Editing

Researchers have developed an RNA-based editing tool that can target specific cells, as they describe in Nature.

Novel Gene Editing Approach for Treating Cystic Fibrosis

Researchers in Science Advances report on their development of a non-nuclease-based gene editing approach they hope to apply to treat cystic fibrosis.

Study Tracks Responses in Patients Pursuing Polygenic Risk Score Profiling

Using interviews, researchers in the European Journal of Human Genetics qualitatively assess individuals' motivations for, and experiences with, direct-to-consumer polygenic risk score testing.