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Quark Aims for Five Clinical Indications, New IND in 2010

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By Doug Macron

With the completion of enrollment in a phase II study of its siRNA-based treatment for diabetic macular edema, which was exclusively licensed to Pfizer, Quark Pharmaceuticals said earlier this month that it is on track to have three drugs in the clinic for five indications next year.

At the same time, the company anticipates that at least one of its drugs will move into phase III testing by the end of 2010 and that it will file an investigational new drug application for an additional drug. Both would be milestones that could put the company in a position to make a second attempt at going public, Quark President and CEO Daniel Zurr told RNAi News last week.

According to Quark, Pfizer recently completed enrollment in a phase II study of PF-4523655, formerly RTP-801i, in DME, while a separate phase II study examining the drug in patients with wet age-related macular degeneration continues. Designed to inhibit the proprietary gene RTP-801, the drug was acquired by Pfizer in 2006 (see RNAi News, 9/28/2006).

Meanwhile, enrollment in two studies of Quark's p53-targeting agent QPI-1002 has been completed.

The first is a phase I trial examining whether the drug can prevent acute kidney injury in patients undergoing cardiovascular surgery. According to Quark, temporary inhibition of the stress-response gene p53 a few hours after a patient has been taken off a cardiopulmonary bypass pump can prevent ischemia-reperfusion-induced kidney injury by delaying apoptosis and allowing “natural repair mechanisms to restore normal DNA and cellular integrity.”

Based on the positive results observed thus far in the trial, Quark has already been cleared by US regulators to start enrollment in a phase II study of QPI-1002 for acute kidney injury prevention, which is expected to begin early next year.

The planned study will enroll "two to three hundred patients" and have three arms, with patients in the first two receiving one of two doses of the drug and those in the third receiving a placebo, Zurr said.

Importantly, the phase II trial will test QPI-1002 in patients at high risk for acute kidney injury, which should allow Quark to make determinations of the drug's efficacy. Indications of efficacy were not measurable in the phase I study since it focused on patients at low risk for the complication and therefore not likely to experience it with or without treatment.

Quark did, however, observe some level of efficacy with QPI-1002 in the first part of a phase I/II trial of the drug in the prevention of delayed graft function in patients undergoing kidney transplant surgery, Zurr indicated.

In this setting, QPI-1002 is designed to function in the same way as it does in patients at risk for acute kidney injury, only with the ischemia-reperfusion injury occurring during the time the kidney is removed from the donor and placed into the transplant recipient.

In part A of the phase I/II trial, "we saw some evidence of efficacy … in the first 40 patients we dosed," Zurr said, adding that Quark will likely make an announcement about the findings "sometime early next year."

With these "very encouraging results … we can now seamlessly move into part B, where we are planning to dose about 180 patients."

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Both trials of QPI-1002 — the phase II in acute kidney injury and part B of the phase I/II study in delayed graft function — are expected to begin next year.

Also on track to move into human testing early next year is Quark's ocular neuroprotective drug QPI-1007.

As RNAi News reported in July, Quark hopes to ultimately develop the drug as a treatment for glaucoma, but will first examine it in a separate but related indication: non-arteritic anterior ischemic optic neuropathy (see RNAi News, 7/30/2009).

NAION, a rare condition that can lead to permanent blindness, is characterized by the death of retinal ganglion cells — the same cause of glaucoma-related blindness. However, whereas glaucoma is a slow, progressive disease, NAION has a rapid onset and reaches its end stage within 30 days.

As a small company with limited resources, Quark is not in a position to conduct the lengthy clinical testing required for a glaucoma treatment, Zurr explained. "What we thought is to use something that mimics glaucoma, but in an acute situation. We have consulted with … leaders of glaucoma and they say that [NAION] is the best model [with which] to move forward."

"Of course, our real interest is to go to glaucoma," he said. "But if the drug is approved [for NAION, potentially with orphan drug status] … I believe it will first start to be used off-label. Then we will move into glaucoma studies," potentially with a larger partner that can lend a financial hand.

The US Food and Drug Administration has approved the company's IND for a phase I/II study of QPI-1007 in NAION, "and we will start dosing patients in the first quarter," with data available before the end of 2010, Zurr said.

Phase III and an IND

During the coming year, Quark also expects one of its clinical programs could move into phase III development, although it is not clear which would be the most likely to do so.

"If the results of the DME [study] are really good, [Pfizer] will certainly move into phase III," Zurr said. At the same time, "we will move very quickly" with QPI-1002 for delayed graft function, he added.

Meanwhile, Quark remains on track to file an IND on a drug for lung injury, having "previously demonstrated [the drug's efficacy] in several models of lung injury [associated] with lung transplantation," he said.

The target of that drug has not been disclosed, but Zurr said that it may be more than one gene.

"In injury, you have a combination of inflammation and apoptosis," he explained. "So you need a gene … or more than one gene, that work on inflammation and apoptosis in concert. We will announce this sometime in the first quarter or second quarter of next year."

In light of all this clinical activity, Quark is also on the lookout for additional capital, Zurr said, and is currently in discussions with "some big pharmas" about potential deals.

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"I would love not to partner, quite frankly, but as a small company, we need to do some partnerships," he said. The top candidates for partnering remain QPI-1002 in kidney injury and QPI-1007, Zurr noted, although he added that he would prefer striking a deal for only one of the candidates and keeping the other in-house.

At the same time, "you can think seriously about going public … even in today's financial situation," he said.

Quark had previously filed to float its shares in mid-2007 at between $12 and $14 each (see RNAi News, 7/7/2007), but dropped its bid to go public shortly thereafter amid unfavorable market conditions and an unwillingness to lower the stock's bid price.

Although it toyed with the idea of an initial public offering in 2008, the company never followed through.

Noting that Wall Street views positive clinical data as a key metric when determining the value of a biopharmaceutical company and that Quark leads the field when it comes to moving RNAi drugs into human trials, Zurr said that another IPO bid is under consideration.

Still, the company has no immediate plans to make a move for the public markets.

"On one hand … it's an easy way to quickly raise money," he said. "On the other hand, looking at the economy, it would be kind of a drag on us. [By not] spending money [for] promotion and PR, et cetera, we are making better use of our money in trying to push more products into the clinic."

But "at the end of the day, the more products you have in the clinic … the more money" you need, he said.

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