Quark Files IND for Kidney Failure Drug, Aims for Second IND in Hearing Loss this Year
Quark Biotech has recently completed an investigational new drug application for its siRNA-based acute renal failure drug AKli-5.
The drug, which was licensed from SR Pharma subsidiary Atugen, is designed to temporarily inhibit the expression of the transcription factor human p53, which is associated with DNA repair and apoptosis, Quark said.
“In acute settings such as in [acute kidney injury], the temporary inhibition of p53 at the time of injury delays the induction of cell death, thereby allowing natural repair mechanisms to restore normal DNA and cellular integrity,” the company said.
SR Pharma said that it expects clinical trials of AKli-5 to begin later this year, triggering a milestone payment from Quark.
Quark also said that it is preparing to file an IND this year on another of its RNAi drugs, AHLi-11, which is being developed to treat acute hearing loss associated with acoustic trauma or ototoxic drugs such as aminoglycoside antibiotics.
According to Quark, acoustic trauma and ototoxic agents are believed to trigger cochlear hair cell apoptosis through a p53 dependent stress response. AHLi-11 designed to inhibit p53 expression.
Benitec HIV Drug to Enter Phase I Testing ‘Soon,’ Stock Rights Issue Plan Falls Short
Benitec last week said that a phase I study of an AIDS lymphoma therapy incorporating the company’s expressed RNAi technology is expected to commence shortly.
Though Benitec has recently shut down its in-house drug-development programs (see RNAi News, 6/29/2006), the therapy’s development is being funded by strategic partner City of Hope.
The AIDS treatment involves using granulocyte colony stimulating factor to mobilize stem cells in AIDS lymphoma patients.
Once the stem cells begin circulating peripherally, they can be collected, isolated, and genetically modified with a lentiviral vector containing three therapeutic genes: DNA that encodes for shRNAs targeting the tat-rev exon, a ribozyme that cleaves the mRNA for CCR5, and a nucleolar-localizing TAR decoy.
The patients undergo full chemoablation, which kills both the regenerative cells of the bone marrow and lymphoma cells, and then the stem cells are infused back into their bloodstreams so that they can migrate to, and engraft in, the marrow.
Benitec said that an investigational new drug application for the therapy was filed in January with US regulators, who asked for an additional safety test and additional information regarding reagents used in the treatment’s manufacture.
The test is expected to take four weeks to complete, Benitec said. “Pending final submission of these results … and approval to proceed, we expect recruitment [in the study] to commence soon,” the company added.
Benitec also had some bad news to report last week, announcing that a fund-raising effort failed to pull in as much as expected.
Last month, the company announced a stock rights issue plan designed to raise as much as Aus$6.5 million ($5.1 million), which it planned to use to support its efforts to fend off ongoing litigation and continue a corporate reorganization. Cash raised would also more than compensate for a share-purchase plan that would have brought in Aus$500,000 but failed to its meet minimum investment level last year.
Under the rights issue plan, Benitec shareholders had the right to participate in a non-transferable rights issue of one new share for every 4.4 shares held at an issue price of Aus$0.10, and one new option for every new share subscribed for at an exercise price of Aus$0.15, he said.
However, Benitec said last week that subscription levels under the plan were less than half of what had been expected.
Agilent to Introduce microRNA Microarray Assay
Agilent is planning on introducing a microarray-based microRNA assay later this month, RNAi News has learned.
According to the company, the assay enables miRNA expression profiling with total RNA samples as small as 100 nanograms. The assays, which will be available in a multipack format with eight microrarrays printed on a standard slide, are processed using the standard Agilent microarray platform, including hardware and software required for hybridization, scanning, feature extraction, and data analysis.
Technology used in the assays was recently detailed in the January issue of RNA. According to that paper, the assay is based on a novel probe that provides “both sequence and size discrimination, yielding in most cases highly specific detection of closely related mature miRNAs. Using a simple, single-vial experimental protocol, 120 ng of total RNA is directly labeled using Cy3 or Cy5, without fractionation or amplification, to produce precise and accurate measurements that span a linear dynamic range from 0.2 amol to 2 fmol of input miRNA,” the paper adds.
The initial assay will include probes for 474 human miRNAs in the Sanger miRBase 9.1.
CytRx 2006 Net Loss Rises on Higher Expenses
CytRx this week reported its financial results for 2006, posting a higher net loss on greater expenses.
For the year, the company’s net loss rose to $17.2 million, or $0.25 per share, from $16.2 million, or $0.28 per share, the year before.
Driving the increased net loss was a jump in research and development spending to $9.8 million from $9.1 million in 2005, and surging general and administrative expenses, which climbed to $9.7 million in 2006 from $6.4 million the year before.
As of Dec. 31, 2006, CytRx had cash and cash equivalents totaling $30.4 million.
Alnylam Grants Non-Exclusive IP License to Bio-Rad
Alnylam Pharmaceuticals last week said that it has granted Bio-Rad a non-exclusive license to sell RNAi research products under Alnylam’s Kreutzer-Limmer family of European patents.
The intellectual property, according to Alnylam, covers siRNAs and their use to mediate RNAi in mammalian cells. Last year, the European Patent Office upheld an amended version of Alnylam’s core Kreutzer-Limmer patent, which ended a long-standing dispute over the validity of the patent (see RNAi News, 6/29/2006).
However, some industry players at the time questioned whether the amended claims in the patent still have commercial utility.
Calando Publishes Data Showing Lead Drug Has Anti-Cancer Effect
Researchers from Calando Pharmaceuticals this week published data showing its lead drug candidate, CALAA-01, was able to reducethe growth potential of cancer cells both in vitro and in vivo.
CALAA-01 targets the M2 subunit of ribonucleotide reductase, an enzyme that catalyzes the formation of the deoxyribonucleotide precursors required for DNA synthesis.
In experiments published in Clinical Cancer Research, Calando researchers showed that the drug silenced RRM2 and reduced cell proliferation across multiple species and cancer types, both in cell culture and in whole animals, the company said.
Last month, Calando published data showing that the drug can be systemically administered to non-human primates with no adverse effects (see RNAi News, 3/22/2007).