Tuesday, July 22, 2008

Roche Nabs Mirus Bio’s RNAi Therapeutics Delivery Technology

Roche again...before this week will have come to an end, Roche has drastically changed the RNAi Therapeutics playing field leaving many heads in the RNAi space spinning.

You may think it is because I live in an RNAi Therapeutics bubble, but the Roche-Genentech press release and conference call to me clearly shows that a major motivation for the proposed taking private of Genentech was to broaden their RNAi Therapeutics efforts by bringing in a company with deep immunology and personalized cancer know-how, as well as being able to leverage Genentech’s monoclonal antibody capabilities for targeted RNAi Therapeutics delivery.

To this they now add for $125M, a sum that makes related companies look very cheap in comparison, the privately held Madison, Wisconsin, nucleic acid delivery company Mirus Bio. The jewel of Mirus Bio is their Dynamic PolyConjugates (DPCs), small, flexible designer particles for the targeted systemic delivery of siRNAs. Although the technology is relatively young and data scarce, from the PNAS publication last year (reviewed here in the RNAi Therapeutics blog) and conference presentations, DPCs are very competitive with liposomal technologies for delivery to the liver. Also very attractive from a safety and efficacy point-of-view is their apparent ability to selectively target silencing either to hepatocytes or Kupffer cells in the liver, depending on whether glucose or galactose-derivatives were attached. Although I haven’t seen data beyond the liver, the small size and modularity suggests that with the appropriate pharmacology it could well have applications for a number of other tissue types and organs and nicely complement larger nanoparticle delivery technologies.

It’s unlikely to be a coincidence that Roche is making all these moves in such short order. What has started with an IP license from Alnylam for basic access to RNAi mechanism of action, within 2 days they have now added to that one of the most coveted delivery technologies and scientific depth. The rapid moves by Roche means that fellow Big Pharmas like Pfizer, which had a non-exclusive license to DPCs, and Merck which had probably also been very interested in DPCs, now risk falling behind on delivery while their core RNAi IP has either not been secured yet (Pfizer) or is at best uncertain (Sirna Therapeutics/Merck). From a strategic perspective, it will be interesting whether due to their close relationships there will be any sharing/coordination of DPC technology with Alnylam and Tekmira, and for which indications Roche will employ the two leading delivery technologies (DPCs and SNALPs) both of which it has now immediate access to.

Today's acquisition is yet another piece of evidence that Roche is building their future on RNAi Therapeutics in a big and bold way. It's also encouraging that this comes a year after the Alnylam platform licensing agreement and suggests that they must have been pleased with what they have seen since.

7 comments:

Anonymous said...

"it will be interesting whether due to their close relationships there will be any sharing/coordination of DPC technology with Alnylam and Tekmira"

I wonder how the present moves by Roche will affect this relationship...

Looking forward to ALNY's 2Q confcall. Perhaps we will get some flavor on this.

Martin

Dirk Haussecker said...

Martin- How about the following time-line: Roche makes deal with Alnylam. Alnylam scientists know of Mirus’ very promising delivery technology, but too expensive for Alnylam to buy. Since Pfizer and Merck may take out Mirus and risk depriving Alnylam of access to that technology, Alnylam asks for a favor. Due diligence initiated after DPC paper comes out. Deal takes a year to wrap up, announcement today. I guess the comments section is the place for such wild speculations.

Anonymous said...

Wild speculations are fun, so don't lets hold back on them.

I like the notion that the Mirus deal was in fact made in concert with ALNY. This could also help explain the apparently less than enthusiastic extension of the cooperation by Novartis - Novartis would have no reason to celebrate if the ALNY-Roche relationship in fact ran as deep as this speculation would imply.

On the other hand, if ALNY had no hand in or prior knowledge of the Mirus deal, one could interpret this as macchiavelian play by Roche in trying to secure a better future bargaining position vis-a-vis ALNY.

Naturally, I hope the former rather than the latter is closer to the truth.

Possibly related: there have been speculations that a deal of some sort might be brewing between ISIS and Novartis. Note the recent appointment of Dr. Bedigian to ISIS from Novartis and the departure of Dr. Jonas from ISIS as well as the historic relationship going back to vitravene and the run up in ISIS pps. Although this may be, and probably is, dead wrong, I would not be surprised if we saw some aggressive response to Roche from Novartis in due course.

Martin

GS said...

All very interesting.

Also, that Pfizer has a license to Mirus' technology, but doesnt yet have rights to any further trigger IP.

So, my suspicion is that they're working on a deal with Alnylam? They're opposing Tuschl II in the EU - perhaps to help get better terms from Alnylam?

Anonymous said...

Where does all of this leave Merck, Pfizer and Eli Lilly?

The whole industry is being taken over by Roche and Novartis.

Even Takeda have done a deal with Alnylam but none of the US guys.

Dirk Haussecker said...

Martin, GS, Anonymous- We've seen patent oppositions before, particularly in Europe, and then have them drop as they join Alnylam in a deal. Wouldn't be surprised to see that with Pfizer as well. Remember, Pfizer insisted Quark to take an InterfeRx license from Alnylam for the wet AMD/DME candidate that has just entered phase II. On the other hand, Pfizer's RNAi Therapeutics efforts have seen dramatic changes in the last couple of months and one has to wait for them to declare their new stance on RNAi IP. Quark is also an interesting case. Making all that noise about their new proprietary breakthrough siRNA chemistry. I thought we had covered all the lengths, modifications, overhangs/blunt, gaps, and 2-3-4 strandedness.

GS said...

" I thought we had covered all the lengths, modifications, overhangs/blunt, gaps, and 2-3-4 strandedness"

Yes, will be interesting to see what, if anything, they come up with!?

Out of interest, with Mirus gone, who do you think has fundamental IP in the lipid-based delivery space?

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