iOnctura announces publication of pioneering research describing the unique biological features of roginolisib

iOnctura announces publication of pioneering research describing the unique biological features of roginolisib

Preclinical data on roginolisib, an oral first-in-class non-ATP competitive allosteric modulator of PI3Kδ, for the potential treatment of solid and hematological tumors

Geneva, Switzerland and Amsterdam, The Netherlands, 16 March - iOnctura, a clinical stage biotechnology company developing breakthrough therapies for patients suffering with cancer, today announces the publication of non-clinical research on roginolisib in the AACR journal Cancer Research Communications. Roginolisib is a first-in-class, non-ATP-competitive, allosteric modulator of PI3Kd which prevents tumor proliferation and breaks immune tolerance in patients with solid and hematological tumors. 

PI3Kδ inhibition in solid tumors has recently emerged as a novel approach to treating cancer because of its potential in targeting multiple tumor survival pathways. First-generation PI3Kδ inhibitors are used to treat hematological tumors, but safety concerns and limited target selectivity have curbed their clinical usefulness.  Safety concerns are even more aggravated in patients with solid malignancies where rapid onset of toxicities have been observed. Conversely, roginolisib has a favorable toxicity profile with less than 5% Grade 3/4 toxicities at the biologically effective dose. Importantly, these toxicities were transient in nature without the need for dose reductions.

The research published in Cancer Research Communications reinforces the conclusion that roginolisib inhibits regulatory T cell proliferation while having limited anti-proliferative effects on conventional CD4+ T cells and no effect on CD8+ T cells.  This process unveils the tumor to the immune system whilst retaining normal immune function. Importantly, treatment of CD8+ T cells with roginolisib during activation favors the differentiation of memory-like, long-lived CD8+ T cells, known to have increased antitumor capacity.  Consistent with first-generation PI3Kd inhibitors, roginolisib inhibits the in vitro growth of lymphoma cells.  In contrast to these other PI3Kd inhibitors, roginolisib activity is correlated with the expression levels of PIK3CD, suggesting cancer cell-intrinsic effects of the drug.

Professor Francesco Bertoni, Head of the Lymphoma Genomics group at Institute of Oncology Research in Bellinzona, Switzerland, said: “This research differentiates roginolisib from other PI3Kd inhibitors and adds to the growing body of nonclinical and clinical evidence that modulation of PI3Kd through an allosteric non-ATP competitive mechanism can be achieved safely and effectively.”

The research also highlights roginolisib has immune-modulatory properties that can be exploited in solid tumors. In CT26 colorectal and LLC lung cancer models, roginolisib sensitized the tumors to anti-PD-1 (Programmed cell death protein 1) treatment, with similar activity in the Pan-02 pancreatic and A20 lymphoma syngeneic mouse models. Roginolisib reshaped the balance of tumor infiltrating cells, favoring infiltration of CD8+ and NK cells, while decreasing suppressive immune cells. Roginolisib presented no safety concerns in animal studies, or in Phase I human studies, and is currently in clinical Phase Ib/II investigation in solid and hematological tumors.

Catherine Pickering, Chief Executive Officer of iOnctura, said: “We are excited that our ground-breaking research has been published by Cancer Research Communications highlighting the potential of our lead clinical program, roginolisib in both solid and hematological cancers. We anticipate returning this key anti-tumor mechanism to physician’s tool-boxes for hematological cancers as well as offering new value for patients with solid tumors.”

The research was published in the open access peer-reviewed journal Cancer Research Communications, part of the prestigious AACR stable of journals, which aims to accelerate the pace of discovery and stimulate innovation in cancer science, by giving rapid open publication of hypotheses, methods, results, data resources and cutting-edge knowledge.

For more information contact:

iOnctura

Catherine Pickering

Chief Executive Officer

T : +41 79 952 72 52

E: c.pickering@iOnctura.com