Wednesday, May 2, 2012

Pfizer Gives Quark another Chance to Prove Worth of Ophthalmic RNAi Drug Candidate


Quark announced on Tuesday that it reached an agreement with Pfizer to test PF-04523655 (‘655), a drug that has already undergone phase II studies in diabetic macular edema (DME) and wet AMD, in yet a third indication: open-angle glaucoma

‘655 is an Atu-siRNA that Quark had licensed from Silence Therapeutics and in turn sublicensed to Pfizer.  Based on mixed phase II results which included a dose-dependent improvement in visual acuity, Quark and Pfizer had decided that Quark will run a phase IIb study in DME (testing higher dosages of the drug in a head-to-head with Lucentis) on its own dime with Pfizer retaining an opt-in.  The wet AMD indication meanwhile seems to be off the table now entirely, finding no mention in the latest press release. 

Testing the intravitreally injected ‘655 for open-angle glaucoma (OAG) is based on the relatively novel mechanism of action of targeting the apoptosis stress-response gene RTP801/REDD1 which should be neuroprotective and, according to preclinical studies, apparently also neuroregenerative.  OAG is a neuropathy characterized by retinal ganglion cell death and consequent optic nerve damage and is often caused by elevated intraocular pressure.  Because of this, most drugs, such as topical beta blockers, aim at reducing intraocular pressure.  In addition to unmet efficacy needs and partly because of side effects, demand for new agents remains strong.  Quark’s very own QPI-1007 RNAi Therapeutics candidate for example is being developed for related conditions (also based on neuroprotection), as is one from Spanish RNAi Therapeutics company Sylentis (SYL040012 which aims at reducing intraocular pressure, but with hopefully less side effects than competing agents).

Added motivation for testing ‘655 in OAG comes from the phase IIa results in DME which showed the dose-dependent improvement in visual acuity without the concomitant decrease in retinal thickness as is the case for the angiogenesis inhibitors such as Lucentis and is in line with the hypothesized neuroprotective mechanism of ’655.


Financials

The revision of the agreement does not seem to be associated with an immediate financial benefit to Quark Pharmaceuticals, a company which has long been struggling to become a publicly traded company (in my opinion, a reverse takeover with Silence Therapeutics may be their best hope- although it would ‘only’ land them on the AIM public market in the UK).  Similar to the case with DME, it seems that the phase IIa trial of ‘655 in OAG will be run (and paid for) by Quark, and should the results please Pfizer, the Big Pharma company may opt into further development through the payment of an exercise fee.

Similarly, it does not seem to be the case that Silence Therapeutics will have any immediate windfall from the deal amendement.  As the co-inventor of ‘655 and licensor of key patents covering ‘655, Silence Therapeutics stands to collect a mid-teens percentage of the milestone payments that Quark receives from Pfizer.  The potential earn-out from those, however, have increased from $95M to $120M according to the press release that was just issued by Silence Therapeutics.  

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By Dirk Haussecker. All rights reserved.

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