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

AMSTERDAM and GENEVA, May 16, 2023 /PRNewswire/ -- 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.

About iOnctura

iOnctura is a clinical-stage biotech developing selective cancer therapies against targets that play critical roles in multiple tumor survival pathways such as cellular proliferation; escape from immune detection; and drug resistance. iOnctura's pioneering approach to drug development is expected to offer significant clinical benefits over the traditional approach of targeting a single pathway alone. iOnctura has progressed two therapeutic candidates into mid-stage clinical development: IOA-244 (proposed name roginolisib), a first-in-class allosteric modulator of PI3Kδ; and IOA-289, a highly selective, non-competitive autotaxin (ATX) inhibitor. iOnctura is backed by specialist institutional investors including M Ventures, Inkef Capital, VI Partners, Schroders Capital, and 3B Future Health Fund. iOnctura BV is headquartered in Amsterdam, The Netherlands with its wholly owned Swiss subsidiary, iOnctura SA, located in Geneva, Switzerland.

About IOA-289

IOA-289 is an orally dosed molecule that has shown preclinically to inhibit the growth and proliferation of cancer cells, stimulate immune cell infiltration into tumors and inhibit the development of fibrosis. IOA-289 is being developed as a first-in-class therapy for highly fibrotic cancer indications that overexpress ATX including pancreatic, liver, colorectal, ovarian and breast cancers. A Phase 1b study of IOA-289 in combination with chemotherapy in metastatic pancreatic cancer started in Q4 2022 (NCT05586516).