Saturday, April 19, 2008

Lost in Translation? Financial Express Report Says Multiple Merck RNAi Therapeutics Candidates in Clinical Development

[Update 23 April, 2008: added "multiple" to the title to emphasize potential clinical candidates in addition to the widely known wet AMD RNAi trial by Merck/Allergan]

This week I escaped from the lab to step into the warm and sunny California spring weather to see what was going on at Stanford’s Biotechnology job fair on the lawn of the Medical School. The first booth that I encountered was that by Sirna Therapeutics, the RNAi Therapeutics subsidiary of Merck. Strangely enough, when I started asking what kind of jobs they were offering, they suggested me to sign a non-disclosure agreement before saying anything more. Go figure, how do you intend to recruit the right people if you can’t properly tell them what jobs you are trying to fill?

I think this is somewhat symptomatic of Merck’s secretive attitude towards their RNAi Therapeutics development efforts. Following the Sirna acquisition, essentially nothing specifically has been disclosed about the stage of their development programs, one for wet AMD already in the clinic and others that were were close to IND filings as of before the Sirna takeover.

A February 7 interview of the Financial Express of India with Sirna Therapeutics’ Bharatt Chowrira, responsible for Merck’s Asian licensing and collaboration activities ex-Japan, could shed astounding light on Merck’s recent RNAi Therapeutics activities and have significant repercussions for the competitive landscape of RNAi Therapeutics.

Not only is it notable that while the interview was predicated on Merck’s general collaboration activities in India, most of Dr. Chowrira’s comments were geared towards RNAi Therapeutics, even more tantalizing, intended or not, was the following section:

“''We are serious about the R&D relationships in Asia in areas such as contract research and clincical trials and will be embracing partnerships,'' he said adding that Merck is building a virtual laboratory by mounting best scientific programs and there is more of external research conducted by partners. The company is searching for partners with a true collaboration mindset and the ability to deliver compounds against novel targets.

On the research front, the company is working towards providing personalized medicine. It has screened over six lakh RNAi, out of which two to three are in clinical trials and 10-20 are candidates for in pre-clinical trials. For starters, RNA interference (RNAi) is a mechanism that inhibits gene expression at the stage of translation or by hindering the transcription of specific genes. RNAi targets include RNA from virus [DH: HCV?] and play a role in regulating development and genome maintenance [DH: cancer?].”

It is known that Allergan is responsible for the development of one Sirna Therapeutics-derived product candidate, but is it really true that Merck has another one or two RNAi Therapeutics programs in the clinic (and 10-20! in pre-clinical studies)? Unlike development-stage biotechs for which making scientific progress public is an essential element in attracting investor interest, Big Pharma often likes to be secretive about their research programs, particularly in areas that here highly competitive.

If true, this would cast events in the past several months going back to Merck’s acquisition of Sirna in a completely different light. Much has been made of the $1.1billion price-tag, particularly as the impression was growing that Merck’s efforts to moving RNAi into the clinic were stalling. However, this equation would change dramatically from a discounted cash flow perspective if they were actually conducting RNAi Therapeutics trials right now in India. As such, Merck could gain valuable early insights into the safety and efficacy of SNALP-RNAi in man, for example by targeting ApoB or PCSK9 and measuring protein levels in the blood early on in phase I. That information could then either be used to progress these drug candidates further or to optimize the formulations. In addition to the competitive advantage, the secretive nature of these studies would also spare them the public humiliation that any failure would bring with it.

As the involvement of Tekmira, Protiva, Roche, Merck, Alnylam, and four as yet undisclosed Big Pharma/biotech companies document, the interest and potential competition for gene targets that can be addressed by SNALP-RNAi could be considerable. Could therefore say a conflict between Merck and Alnylam or one of Alnylam’s partners (e.g. Novartis) for the same gene targets have contributed to the break-up of Alnylam and Merck in the fall of last year? Did the court injunction forbidding Merck to further develop SNALP-based programs force them into the Protiva settlement, because otherwise it would have imperiled their clinical development activities? Does the possibility that Merck may have more than one additional RNAi clinical trial on top of wet AMD ongoing mean that the initial experience was positive so that they could rapidly expand the technology towards targeting multiple genes as is the promise of RNAi?

Maybe everything here is a misunderstanding and the truth was lost in translation, but in any case such a scenario certainly makes for an interesting exercise in game theory.

1 comment:

Peter said...

Hi Dirk, This is Peter Parker - we corresponded a bit before and you met my CTO Johannes Fruehauf out there several months ago. I need to be in Palo Alto on the evening of May 20 and am curious if you are free for a few minutes either on the evening of the 20th or AM on the 21st. I am staying at the Garden Court and we could have a drink at Il Fornaio at say 6pm on the 20th or else breakfast on the 21st. You can email me at

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