FDA grants permission for clinical investigations into iOnctura's roginolisib

31-Oct-2023 - Last updated on 31-Oct-2023 at 10:20 GMT

It was announced today (October 31), that the US Food and Drug Administration (FDA) has granted permission to proceed with clinical investigations of small molecule treatment, roginolisib.

iOnctura is a clinical-stage biotech that develops selective cancer therapies, including roginolisib, against targets that play critical roles in multiple tumor survival pathways.

Roginolisib (IOA-244) is in development for solid and hematologic malignancies including uveal melanoma, a rare cancer in which malignant (cancer) cells form in the uveal tract of the eye. When the cancer metastases, which it does in approximately 50% of patients, there are limited treatment options, and the projected overall survival is only a year.

As the first novel allosteric modulator of PI3Kδ, roginolisib marks a new era in drug development within the class. The unique binding mode, combined with high selectivity for PI3Kδ, is expected to translate to an improved safety and tolerability profile relative to that of earlier-generation inhibitors.

Commitment to driving roginolisib

Catherine Pickering, chief executive officer of iOnctura, said: “As we remain on track to deliver final clinical data from the initial patients treated with roginolisib in 2024, the clearance of our IND application demonstrates our commitment to driving roginolisib through the clinic.

“We believe roginolisib has the potential to slow or halt the progression of uveal melanoma, so providing an important treatment option for patients who currently have no approved therapeutic options after they progress on their first-line therapy.”

Roginolisib is being investigated in the DIONE-01 trial, a two-part, first-in-human phase 1 study. The study is fully enrolled with final data expected in the first quarter of 2024. Across all patients treated to date, roginolisib monotherapy has shown 7% grade 3/4 toxicities, with no dose-limiting toxicities, drug-related serious adverse event (SAE), or drug-related adverse event (AE) leading to dose interruption or discontinuation. Whilst median overall survival has not yet been reached, 62% of patients were alive at 12 months, which compares favorably to historical controls of 34% in the same setting.

Oncogenic role in many tumor types

Long-term administration of roginolisib is well tolerated and patients have been treated for up to 40 months in the study. Promising clinical activity has been observed across patients with both solid and hematological cancers.

Roginolisib’s unique structural and selectivity features drive a unique way of inhibiting PI3Kδ which translates into a highly beneficial tolerability and clinical benefit profile. PI3Kδ over-expression stimulates multiple cancer mechanisms and has an oncogenic role in many tumor types.

It has a multi-modal effect on cancer; directly preventing cancer cell proliferation, harnessing an anti-tumor immune response via an effect on regulatory T-cells and cytotoxic T cells, and potentiating the effect of immunotherapy.