GENEVA, Switzerland I December 09, 2021 I iOnctura SA, a clinical stage oncology company targeting core resistance and relapse mechanisms at the tumor-stroma-immune interface, is presenting clinical data confirming the mode of action of its autotaxin inhibitor IOA-289 and showing preclinical evidence of the role of autotaxin inhibition in breaking down tumor resistance mechanisms. IOA-289 will be the first autotaxin inhibitor to be clinically investigated in oncology. The data will be presented as a poster at the European Society of Medical Oncology’s Immuno-Oncology Congress (ESMO-IO) taking place on December 8–11, 2021 as a virtual meeting.

The randomized, double-blind, placebo-controlled study of single ascending doses of IOA-289 showed that IOA-289 lowered circulating levels of LPA in a dose-dependent manner. LPA is a blood-based biomarker of autotaxin inhibition; importantly, LPA levels have been shown to correlate with circulating CA19-9, a clinical biomarker of pancreatic cancer progression, providing a strong rationale for a biomarker-evaluable-response in this study. A Phase I clinical study of IOA-289 in pancreatic cancer, a malignancy typically characterized by a fibrotic and immune excluded phenotype, is in preparation.

Further compelling preclinical data show IOA-289 reduces tumor burden in mouse pancreatic cancer models. The experimental results support the role of cancer-associated fibroblasts (CAFs) in promoting pancreatic adenocarcinoma cells (PDAC) growth. Additionally in preclinical models iOnctura has demonstrated that blocking autotaxin reduces fibrosis and enhances recruitment of T effector cells, two key mechanisms driving tumor mediated resistance to cancer therapy.

The poster presentation at ESMO-IO is entitled “Translating a novel autotaxin inhibitor from preclinical proof of concept in pancreatic cancer to a biomarker response in human subjects” (P131).

The e-poster presentation is available on the ESMO-IO virtual meeting platform and iOnctura’s website.

iOnctura SA is clinical stage oncology company targeting core resistance and relapse mechanisms at the tumor-stroma-immune interface. iOnctura’s best-in-class drug development programs combine immune-mediated and direct anti-tumor activity to deliver molecules with superior clinical efficacy and safety in oncology. Its lead program, IOA-244 is the only semi-allosteric PI3Kdelta specific, orally dosed, small molecule inhibitor that is being developed in solid and hematological malignancies to address tumor and stroma induced immune suppression. IOA-244 is currently in Part B of a Phase 1 study. iOnctura’s second program, IOA-289, is an oral small molecule that inhibits the cross-talk between the tumor and its stroma and is in a Phase 1 clinical study. iOnctura is backed by blue chip investors including M Ventures, Inkef Capital, VI Partners, Schroders Capital, and 3B Future Health Fund. For more information, please visit iOnctura’s website.

IOA-289, originally licensed from Cancer Research UK, is iOnctura’s second clinical compound, a next generation oral small molecule autotaxin inhibitor that is currently being investigated in the healthy volunteer stage of the AION 01 trial ( Identifier: NCT05027568). A phase 1 clinical study in pancreatic cancer patients is in preparation. iOnctura has undertaken extensive validation of the autotaxin inhibition mechanism in multiple solid tumor preclinical models.

Pancreatic cancer (PDAC): Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer accounting for approximately 90% of cases. PDAC has a poor prognosis, with less than 5% of patients surviving beyond five years after diagnosis.   Pancreatic cancer accounts for about 3% of all cancers in the US and about 7% of all cancer deaths, with 60,430 diagnoses each year in the United States and 48,220 deaths.

SOURCE: iOnctura