First-In-Class Semi-Allosteric PI3Kδ Inhibitor

iOnctura Provides Development Update on PI3Kδ Inhibitor


Updated clinical data demonstrates a prolonged and sustained favorable safety profile for roginolisib (IOA-244). Clinical data shows a comparable safety profile in both solid and hematologic malignancies. Clinical responses seen in both solid and hematologic malignancies. US FDA grants Orphan Drug Designation for IOA-244 in uveal melanoma.

iOnctura, a clinical-stage biotech developing selective cancer therapies against targets that play critical roles in multiple tumor survival pathways, today provides an update on IOA-244, its lead cancer drug, which is in development for solid and hematologic malignancies including uveal melanoma, a rare cancer arising within the uveal tract of the eye.

After assessing the novel chemical and biological properties of IOA-244, and the promising signals of clinical activity seen to date in patients with uveal melanoma, the US FDA granted Orphan Drug Status for IOA-244. This grants certain benefits during development and commercialization. Uveal melanoma is a disease in which cancer originates in the tissues of the eye, causing symptoms such as blurred vision or a dark spot on the iris. When the cancer metastases, which it does in approximately 50% of patients, there are limited treatment options and projected overall survival is only a year.

iOnctura’ sPI3Kδ inhibitor, IOA-244

A PI3Kδ inhibitor, IOA-244 recently received the proposed name roginolisib and is being investigated in  the DIONE-01 trial, a two-part, first-in-human Phase I study (, identifier NCT04328844). Part A of the study investigated the safety and pharmacokinetics of continuous daily dosing of IOA-244 at 10, 20, 40 and 80mg. Part B is an ongoing cohort-expansion of the biologically effective dose (BED) of 80mg in solid and hematologic malignancies including a recently opened non-Hodgkin´s lymphoma cohort.

These  data demonstrate for the first time that a semi-allosteric inhibitor of PI3Kδ can be given to patients safely for long durations.

Catherine Pickering, CEO of iOnctura

Promising effects of IOA-244

As of December 2022, 38 patients (including 23 with metastatic uveal melanoma and eight patients with follicular lymphoma) have been treated with IOA-244. Across all patients treated to date, roginolisib given at the BED showed less than 5% Grade 3 or Grade 4 toxicities, with these toxicities being transient in nature. There have been no dose-limiting drug reductions or interruptions and longterm (over six months) administration of IOA-244 is well tolerated. 

Clinical activity, including partial and complete responses, are being seen in patients with both solid and hematologic malignancies. Further details on clinical responses will be released at a future international clinical conference in 2023. Fourteen of 38 patients (including 11 of 23 uveal melanoma patients) are still on treatment, with two patients having been on treatment for more than two years. The one-year OS rate is currently 70%; median OS has not been reached.

38 Patients treated in Phase 1 study