Peer-reviewed translational research paves the way for first-in-class autotaxin inhibitor IOA-289 in cancer

Amsterdam, The Netherlands and Geneva, Switzerland, 16 May 2023 - iOnctura, a clinical stage biotechnology company developing breakthrough therapies for patients suffering with cancer, today announces the peer-reviewed publication of comprehensive translational research on the novel autotaxin (ATX) inhibitor IOA-289 in the ESMO journal Immuno-Oncology and Technology (IOTECH).

Inhibition of ATX is a novel treatment strategy for cancer that offers a three-pronged attack on the tumor through cancer cell inhibition, immune system stimulation and inhibition of fibrotic processes. ATX-mediated lysophosphatidic acid (LPA) signalling directly encourages tumor cell proliferation and inhibits anti-tumor immune responses via a direct effect on T cells. Further, it has a predominant role in fibrotic processes, including those important in cancer propagation, metastasis and resistance to therapy. Cancers surrounded by scar tissue (fibrotic tissue) and without markers visible to the immune system are tough to treat with existing therapies.

IOA-289 is a novel ATX inhibitor with a unique chemical structure, excellent potency and an attractive non-clinical safety profile. It has a unique binding mode that places it in an inhibitor class of its own. Avoidance of interaction with the catalytic site likely contributes to the improved safety profile of IOA-289 compared to other ATX inhibitors, avoiding toxicities seen with first-generation entities. 

Michael Lahn, Chief Medical Officer of iOnctura commented: “Despite the advances in the treatment of cancer in the last few decades, a large proportion of tumors are resistant to current treatments such as chemotherapy, immunotherapy and radiotherapy. Based on this translational research, we are excited to be investigating the safety and mode of action of IOA-289 in pancreatic cancer patients, where ATX signalling plays a central role.”

In this translational research, IOA-289 demonstrates positive effects in highly fibrotic cancer models, preventing metastasis and tumor outgrowth. In iOnctura´s Phase Ib clinical study, IOA-289 is being combined with standard of care nab-paclitaxel and gemcitabine.  While assessing the safety of an ATX inhibitor in cancer patients for the first time, a broad biomarker program will investigate the translation of the non-clinical observations to clinical application. As demonstrated in healthy volunteers in this research, single ascending doses of IOA-289 were safe, tolerable and blood exposure showed a reduction of the pharmacologic marker circulating LPA. Disclosure of results of the ongoing Phase 1b study will be released at a future medical meeting.