Quark Biotech announced this week that it has landed the world’s biggest pharmaceutical firm as a partner, exclusively licensing its proprietary human gene target RTP-801 to Pfizer for certain indications including age-related macular degeneration.
Under the deal, Pfizer also has acquired RTP-801i, an siRNA-based molecule that silences RTP-801 and which Quark expects to move into phase I testing before the end of the year.
Financial terms of the deal were not disclosed. However, an announcement by SR Pharma subsidiary Atugen, which licensed RTP-801i to Quark last year (see RNAi News, 3/18/2005), indicates that the Pfizer deal is worth well in excess of $100 million to Quark.
Although the RNAi-for-AMD field is a crowded one, with Sirna Therapeutics and Acuity Pharmaceuticals having already moved siRNA-based treatments for the disease into human trials (see RNAi News, 8/10/2006 and 9/14/2006), Quark has set itself apart by aiming at a novel target in its program.
Sirna and Acuity’s drugs target either vascular endothelial growth factor or a VEGF receptor, but Quark’s drug silences RTP-801. According to Quark CEO Daniel Zurr, this gene has been found to play a role in the three major hallmarks of AMD: angiogenesis, vascular permeability, and retinal neuron death.
By targeting RTP-801, Quark’s drug goes two steps beyond VEGF inhibitors, he said.
VEGF suppression “gives you anti-angiogenesis effect, but [inhibition of vascular] leakiness and stoppage of apoptosis of retinal neurons is something that VEGF certainly is not giving you,” Zurr said, although a number of studies have linked VEGF with enhanced vascular permeability.
“This is one of the reasons Pfizer was very interested in” RTP-801i and approached Quark about a licensing deal, he added.
Although the specifics of Quark’s arrangement with Pfizer remain undisclosed, Zurr said that his company would handle development of RTP-801i at least through phase I testing — which will begin at five clinical centers in the US before the end of 2006 — under Pfizer’s “guidance.”
“Slowly, they will take over” after that, he said, although in certain territories Quark “will continue [development of the drug] even into phase III.”
Ultimately, however, “Pfizer is in the driver’s seat,” Zurr added.
Separately this week, SR Pharma unit Atugen said that it stands to receive up to $95 million in milestones, as well as royalties, from Quark pursuant to its 2005 licensing deal for RTP-801i as a result of the Pfizer arrangement. Atugen also said that it will receive an upfront payment of $2 million from Quark, and that its first milestone payment, which will be triggered by the initiation of phase I testing of RTP-801i, will be worth $1.5 million.
Zurr said that Atugen’s announcement, which was made independently of both Quark and Pfizer, gives an indication of what the Pfizer deal is worth.
“Their numbers are correct numbers,” he said. “We have to pay [Atugen up to] $95 million, so we have to get much more than that [from Pfizer] of course. This is not a small deal — we are not getting $96 million and using $95 million to pay them.”
Although AMD is central to Quark’s deal with Pfizer, the agreement also gives the big pharma the right to develop drugs against the gene for other indications, both in and out of ophthalmology.
Zurr declined to specify which other diseases are covered under the deal, but noted that Atugen has waived its right to pursue development of RTP-801i for cancer since RTP-801 has proven to be a poor oncology target.
Officials from Pfizer were not available for comment by press time.
Aside from RTP-801i, Quark is developing an siRNA-based drug, also licensed from Atugen, that targets p53, a transcription factor associated with DNA repair and apoptosis, for acute renal failure.
“We have to pay [Atugen up to] $95 million, so we have to get much more than that [from Pfizer] of course. This is not a small deal — we are not getting $96 million and using $95 million to pay them.”
Last summer, Quark announced that the US Patent and Trademark Office had issued the company a notice of allowance for a US patent entitled “p53 Inhibitors and Therapeutic Use of the Same.” The patent — No. 7,008,956 — was issued earlier this year.
Licensed by Quark from the University of Illinois at Chicago, the patent covers “the therapeutic use of temporary p53 inhibitors in the treatment of p53-mediated diseases, conditions, and injuries” such as cancer.
Quark has already filed an investigational new drug application for its p53-targeting siRNA, and earlier this year Atugen announced that it had been informed by Quark that it planned to begin phase I studies later this year (see RNAi News, 4/6/2006).
But before human testing begins, Quark is hoping to strike its second drug-development deal, Zurr hinted.
“There will be shortly another very big announcement” involving “a kind of partnership” for Quark’s p53 program, he said, declining to comment further.