InteRNA is building a diversified oncology product pipeline with a focus on lead drug candidate INT-1B3. Beyond oncology, we employed our miRNA discovery and functional validation technology platform also in neuroscience with a focus on our furthest advanced CNS program on Epilepsy.

INT-1B3 is a LNP-formulated, chemically-modified mimic of a tumor suppressor miRNA (miR-193a-3p) with a unique MoA addressing multiple hallmarks of cancer simultaneously. It directly targets tumor cells and the tumor microenvironment by specific modulation of multiple signaling pathway components across the PTEN tumor suppressor pathway and the oncogenic PI3K/Akt and Ras/MAPK pathways resulting in inhibition of proliferation and migration, and induction of cell cycle arrest and apoptosis. The triggering of the immunogenic tumor cell death (ICD) process as well as downregulation of the adenosine-A2A receptor pathway through inhibition of CD39/CD73 leads to a decrease in immunosuppressive FoxP3/Lag3 regulatory T cells and monocytic myeloid-derived suppressor cells (mMDSCs), and maturation of dendritic cells. As a result, the immune system is activated, and long-term immunity is triggered by recruitment of CD8+ effector T cells leading to decreased metastasis development and improved animal survival compared to anti-PD1 treatment in pre-clinical tumor models.

INT-1B3 triggers the transition from ‘cold-to-hot (immunoreactive)’ tumor, and activates the adaptive immune response.

In 2021, InteRNA Technologies initiated an open-label, multi-center, Phase 1a (dose escalation) clinical trial of INT-1B3 in ‘all-comer’ cancer patients with advanced solid tumors. The trial is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of INT-1B3, to help defining the Recommended Phase 2 Dose (RP2D).

Click here to learn more about the Phase 1a (dose escalation) trial (INT1B3-CLIN-101).

In our second independent oncology development program, INT-5A2 is a LNP-formulated, chemically-modified mimic of a tumor suppressor miRNA, comprising anti-proliferative and anti-angiogenic properties and serves as potential back-up compound for INT-1B3 in hepatocellular carcinoma (HCC), with in addition pre-clinical proof-of-concept in highly vascularized tumors like glioblastoma (GBM).

Yet, based on its MoA, targeting the pathways involved in the resistance to crizotinib (Xalkori®), we foresee initial straightforward clinical development in crizotinib-resistant ALK+ non-small cell lung cancer (NSCLC).

INT-2H10 represents our furthest advanced CNS program in which we obtained pre-clinical proof of concept in an established Kainate model for mesial Temporal Lobe Epilepsy (mTLE), the most common form of Epilepsy which is highly resistant and refractory to current treatments. INT-2H10 is an antimiR that knocks down a miRNA that is overexpressed in the brain of mTLE patients and thereby reducing the number, duration, and severity of spontaneous recurrent seizures at the chronic stage.

In addition to the above-mentioned programs, we are advancing a portfolio of early-stage programs.