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.
In addition, 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.
According to iOnctura, IOA-289 is a novel ATX inhibitor with a unique chemical structure, excellent potency and an attractive non-clinical safety profile.
The company said IOA-289 has a unique binding mode that places it in an inhibitor "class of its own". Further, the avoidance of interaction with the catalytic site contributes to the improved safety profile of IOA-289 compared to other ATX inhibitors, avoiding toxicities seen with first-generation entities.
“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,” said Michael Lahn, chief medical officer of iOnctura.
“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, published in ESMO journal Immuno-Oncology and Technology (IOTECH), IOA-289 demonstrated positive effects in highly fibrotic cancer models, preventing metastasis and tumor outgrowth.
In iOnctura’s phase 1b 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.
iOnctura said that the results from the ongoing phase 1b study will be disclosed at a future medical meeting.