DUBLIN – Interna Technologies BV closed out its series A round with funding from two new co-lead investors, Inkef Capital and Aglaia Oncology, which takes the final tally to $10.5 million. That's enough cash to take the company's two lead micro-RNA (mi-RNA) programs up to investigational new drug (IND) filings in or around 2017.

The new funding will enable the company to generate more in vivo data, as well as entering formal, IND-enabling preclinical research.

The company is not divulging details on the programs as yet. INT-5A2 is in development for liver cancer, while INT-1B3 is in development for BRaf600-positive melanoma. Each comprises a single miRNA that can hit several targets and, hence, several pathways, within a given cancer. Even as standalone therapies, they have the potential to overcome the resistance that typically emerges with targeted therapies, such as tyrosine kinase inhibitors. But the company also aims to explore their potential in drug combinations.

RNA-based therapies, in various guises, have enjoyed a resurgence in the past couple of years, as companies have started to iron out some of the initial wrinkles in the technology that caused the likes of Merck & Co. Inc. to exit the field while it was still in a nascent stage of development. Roche Holding AG's acquisition last year of antisense drug developer Santaris Pharmaceuticals A/S, for $250 million up front plus up to $200 million in milestones, and Sanofi SA's $700 million investment in RNAi stalwart Alnylam Pharmaceuticals Inc. both heralded the renaissance. Curevac GmbH also has found takers for its mRNA-based therapeutic and prophylactic vaccines, signing deals with Sanofi AG and with Boehringer Ingelheim GmbH.

Interna, based in Nijmegen, the Netherlands, has already served its time in the trenches. It was established back in 2008 to bring forward research performed at the Hubrecht Institute in Utrecht, and it has raised cash on a phased basis since then. Its scientific founders are Edwin Cuppen, a principal investigator at the institute and Eugene Berezikov, formerly at Hubrecht and now at the European Institute for the Biology of Ageing, in Groningen.

The company has taken a distinctive approach to identifying novel miRNA molecules – and to identifying novel functions for molecules already annotated in publicly accessible databases. Most firms in this area, CEO Roel Schaapveld told BioWorld Today, have focused on differential expression profiling – that is comparing the differing patterns of expression of particular miRNA molecules in healthy and in diseased cells. But that approach does not address a fundamental issue – whether the observed differences are causal or consequential, in terms of their relationship to a disease pathology.

"We took an agnostic approach," Schaapveld said. The company built a lentiviral expression library containing novel and known miRNAs and tested their effects on cancer signaling pathways, cell proliferation, apoptosis, epithelial-to-mesenchymal transition, invasion and migration, and angiogenesis. "We looked at all cancer-related parameters," he said. As well as validating its proprietary molecules, it also identified novel functions for previously known molecules, all with a relatively clean profile. "They don't show the same effect on normal cells," Schaapveld said. "We expect a good therapeutic window."

Delivering RNA-based therapies to target tissues has been one of the major challenges for the entire field. Here, too, Interna is not yet showing its hand, but it is working with proprietary technologies – and is not reliant on just one. "We don't believe in just one drug delivery technology to address different types of tumors," Schaapveld said. Delivery alone is necessary but not sufficient for drug activity. "There are technologies that do proper delivery, but if the molecule gets trapped in the endosome you lose activity," he said. "It needs to be released from the endosome to become active in the cytoplasm."

The company named Hans Schikan as its new chairman last week, although he actually stepped into the role several months ago, not long after completing the sale of the company he led, Prosensa Holding NV, to Biomarin Pharmaceutical Inc., for $680 million up front plus up $160 million in milestones.