By Doug Macron
MDRNA officials this week said that it remains on track to filing an investigational new drug application for its bladder cancer therapy by the end of the year, and disclosed that it has chosen the non-muscle-invasive form of the disease as the first indication pursued under the program.
Additionally, the RNAi drugs shop said it still expects to fulfill its goal of forging two major research and development alliances with big pharma or biotech partners, potentially ones with which MDRNA already has ongoing early-stage collaborations, the officials said.
Separately this week, MDRNA also announced that it has acquired from Valeant Pharmaceuticals North America an intellectual property estate covering bridged nucleic acids, a move that it expects will enhance its ability to develop RNAi and, potentially, non-RNAi therapeutics.
During a conference call held to discuss the company's newly released fourth-quarter financial results, CSO Barry Polisky said that the bladder cancer indication was selected based on discussions with key clinicians regarding which patients with the disease were most "under-served" by existing treatments.
He added that MDRNA is currently conducting non-human primate safety and tolerability studies with its bladder cancer candidate, and thus far, "direct installation of our lead formulation into [the] non-human bladder, followed by a two-hour retention time, was observed to be well-tolerated with no signs of toxicity."
Additionally, "urinalysis and serum chemistry and hematology values were normal," he said. "Tissue histology is underway and will be completed very soon."
Meanwhile, efforts to ramp up manufacturing of the drug to meet both clinical and commercial requirements are underway in collaboration with an undisclosed "leading contract manufacturing organization," Polisky noted.
In regards to the BNA technology, he said that the acquisition "further increases the versatility of [MDRNA's proprietary] UsiRNA and meroduplex [siRNA] constructs."
According to MDRNA, BNAs are "novel nucleoside analogs in which the flexible ribose sugar is locked into a rigid conformation by a small chemical linker. When included in single- or double-stranded oligonucleotides, the highly stable A-form of RNA or DNA is favored, resulting in increased thermal stability of a duplex or higher affinity of a single strand for its complementary target," such as mRNA.
"In addition, BNAs provide resistance to nuclease degradation," MDRNA added.
The technology "provides us with the ability to pursue single-stranded constructs with non-RNAi mechanisms of action," Polisky noted. However, he stressed that its near-term importance for MDRNA lies in its ability to help the company develop "novel siRNA constructs" by enhancing the "structural versatility and [tuning] the details of the double-stranded molecules in the RNAi pathways.
"For the foreseeable future, our focus is on siRNA and the applications that BNA will provide in the work we've already done," he explained. "The extent to which we will go beyond RNAi mechanism is under discussion … and in the early stages. We don't have a specific program in mind here."
MDRNA President and CEO Michael French added during the call that "we are still siRNA-focused. We think this [technology] brings some additional capability to looking at [RNAi] constructs and making sure that we can apply constructs effectively as therapeutic modalities."
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As for the company's partnering efforts, June Ameen, MDRNA's vice president of corporate development, said that the firm is still focused on establishing "two target- and/or therapeutic-based research and development collaborations." She said they will likely be outgrowths from two of the companies' three early-stage collaborative efforts but may result from "ongoing discussions with … other large, international pharmaceutical companies."
MDRNA has not disclosed the names of the first two partners, but last week announced that the third is with AstraZeneca's Innovation Center in China.
That deal centers around using MDRNA's so-called DiLA2 delivery technology in hepatocellular carcinoma, an indication that is the focus of the company's second pipeline program.
French noted that the arrangement does not provide AstraZeneca with rights to MDRNA's liver cancer program, but that the partner may, down the road, opt to in-license it.
"I don't see [the AstraZeneca deal] becoming a licensing transaction solely around hepatacellular carcinoma," he said. "Our hope … is that this grows into one of these larger multi-year, multi-target R&D collaborations where perhaps [our partner] says, 'Oh, by the way, I like this program so I'll take it where it is today.'"
For the three-month period ended Dec. 31, MDRNA posted a sharp decrease in its net loss, which fell to $800,000, or $0.02 per share, from $12.3 million, or $0.39 per share, the year before.
Revenue in the quarter was flat with the same period a year earlier at $200,000.
R&D spending, meanwhile, dropped 68 percent to $3.1 million from $9.7 million, reflecting the discontinuation of legacy intranasal drug-delivery programs from before MDRNA shifted its focus entirely onto RNAi therapeutics. This move, the company noted, "resulted in lower headcount, facilities, and stock compensation expenses in 2009 compared to 2008."
Selling, general, and administrative expenses slipped to $2.3 million from $2.5 million in the quarter.
At the end of 2009, MDRNA had cash and cash equivalents totaling $1.7 million. The company said that it expects its current resources to be "sufficient to fund our planned operations well into the second quarter of 2010."
Earlier this year, French had told RNAi News that in addition to funding from possible partnerships, MDRNA could potentially generate additional capital through the sale of non-core assets and technology-licensing deals (see RNAi News, 2/11/2010).