Dutch microRNA drug developer InteRNA Technologies this month announced that it has received a notice of allowance from the US Patent and Trademark Office for a patent application covering a number of novel microRNA sequences, including one that forms the basis of the company's lead drug candidate.
With the intellectual property in hand, InteRNA has now set its sights on raising additional capital and advancing at least one therapeutic into human testing by the end of 2013, a company official told Gene Silencing News this week.
The allowed patent application, No. 20100035760, is entitled “Nucleic Acid Molecules and Collections Thereof, Their Application, and Modification” and claims a variety of miRNA sequences identified through the deep sequencing of different mouse, non-human primate, and human samples, including tumor samples, InteRNA said.
According to the patent application's abstract, it also claims the use of these sequences for therapeutic and diagnostic applications.
Among the miRNAs covered by the IP is miR-3157, which InteRNA CEO Roel Schaapveld said was identified in a melanoma screen and has been validated in vitro for its ability to inhibit proliferation and induce apoptosis in tumor cells.
Specifically, the miRNA appears to counteract the effects of BRAF, a protein kinase that regulates cell growth and proliferation but which is mutated in about half of patients with melanoma. As such, it is a key target for a number of different therapeutics including Genentech's Zelboraf.
““The microRNA itself doesn't regulate BRAF,” Schaapveld noted, “but initiates certain pathways and regulates certain proteins” that are dysregulated by the mutated gene. He added that a second patent application covering miR-3157's function has already been filed.
Currently, InteRNA is conducting in vivo studies in a xenograft model with a miR-3157 mimic formulated with an undisclosed delivery vehicle for intravenous delivery, he said. The company then aims to test the compound in a human transplant model.
Assuming all proceeds as expected, InteRNA expects to file for regulatory clearance to begin human testing of the melanoma drug around the end of 2013. A decision on where the trial will be run has not been finalized, but Schaapveld said he expects it to be in Europe given the limited resources of the company.
Depending on InteRNA's financial position, however, it is possible that a second drug candidate could also move into clinical trials next year.
Also in InterRNA's pipeline are anti-angiogenic miRNA mimics being developed to combat solid tumors and, in an earlier stage effort, eye diseases associated with excessive blood vessel growth.
Schaapveld declined to specifically name the miRNAs under evaluation in this program, but a published World Intellectual Property Organization patent application — No. WO 2012/096573 — points to miR-9, miR-574, miR-7, miR- 190b, and miR-142 as the top candidates. That application is entitled “miRNA for Treating Disease and Conditions Associated with Neo-Angiogenesis,” and claims the diagnostic and therapeutic use of the miRNA molecules.
Schaapveld said that InteRNA has already obtained in vivo proof of concept for the use of these anti-angiogenic miRNAs in cancer, again with an undisclosed IV delivery technology, and could be in a position to file an investigational new drug application for the compound around the end of next year.
Moving two drugs toward the clinic simultaneously, he stressed, “may be a little too much.” However, it is possible should a planned financing round, which is expected to pull in between €8 million and €10 million ($10.4 million and $13 million), be successful.
Regardless, InteRNA is focused on moving at least one drug through phase I testing on its own, which Schaapveld said will help generate the data needed to woo a potential big pharma partner.
Despite the high-profile departures of Roche and Pfizer from the oligonucleotide drugs space in 2010, he said, “there is interest by pharma.”
Also in the Pipeline
In addition to the melanoma and anti-angiogenesis programs, InteRNA has a preclinical program in head and neck cancer. Few details are available about this effort, which is also centered around intravenously delivered miRNA mimics, but Schaapveld said that preliminary data suggests that the company's compounds are able to selectively target cancer cells while leaving normal cells untouched.
The firm also has discovery-stage programs underway with a variety of miRNA inhibitors, but no details about these efforts have been made public.