Cash round sets up trial of InteRNA’s microRNA for cancer

Dutch biotech InteRNA Technologies has raised €18.5 million ($22 million) in second-round financing as it prepares to start clinical trials of its lead drug candidate INT-1B3 for solid tumours.

The Series B funding has come more than five years after InteRNA’s first-round, which raised just over $10 million in 2015, and nine months after the biotech was cleared to start trials of INT-1B3 in the Netherlands and Belgium.

The start of dosing in the phase 1/1b trial of the drug has been delayed by the COVID-19 pandemic, but recruitment of the target 80 participants with advanced solid tumours is reported to be ongoing.

InteRNA is focusing on the development of gene-silencing drugs based on microRNA, naturally occurring, non-coding strands of RNA that are thought to regulate gene expression in cells.

MicroRNAs are smaller than the small interfering RNA (siRNA) drugs now reaching the market, such as Alnylam’s Onpattro (patisiran), Givlaari (givosiran) and Oxlumo (lumasiran) for rare diseases.

The major difference between siRNAs and microRNAs is that the former are very specific to one messenger RNA target, while the latter can have multiple targets.

INT-1B3 is a chemically modified mimic of a microRNA called miR-193a-3p that is formulated in lipid nanoparticles (LNPs) and is delivered by intravenous infusion.

Preclinical research suggests that the microRNA has multiple effects on solid tumours by attacking malignant cells directly as well as altering the microenvironment around them – hitting multiple cancer-related targets simultaneously, according to InteRNA.

It interacts with signalling pathways involved in the proliferation of cancer cells and impairs their ability to spread, whilst driving them into programmed cell death (apoptosis) and encouraging a T cell-mediated immune response.

InteRNA’s clinical trial will start with a dose-escalation phase in which subjects with advance cancer will receive a 60-minute infusion twice a week in 21-day cycles.

InteRNA is one of a growing number of biotech companies focusing on microRNA drug pipelines, along with the likes of miRagen, MiRNA Therapeutics, and Regulus Therapeutics.

While InteRNA has taken longer to get its project off the ground, the early movers have suffered a series of mishaps that have stripped away their lead – and in some cases taken them out of the running altogether.

miRagen changed its direction last year by buying antibody specialist Viridian, taking its name and putting its microRNA pipeline out for licensing, while MiRNA was hit by the failure of its lead cancer programme and merged with Synlogic in 2017, diverting its cash reserves to microbiome candidates.

Regulus meanwhile remains a microRNA player, but has suffered a number of setbacks. It lost AstraZeneca as a partner for a non-alcoholic steatohepatitis (NASH) drug in 2017 and selling its lead candidate for rare disease Alport syndrome to Sanofi at a knockdown price the following year.

InteRNA’s chief executive Dr Roel Schaapveld said the latest fundraising – led by Italian biotech investment company Aurora Science – validates the potential that microRNAs have for hard-to-treat cancers.

He said the company is now looking forward to evaluating INT-1B3’s “unique mode of action, targeting not only the tumour cells themselves but also the disease-promoting tumour microenvironment.”