The clinical stage biotech specializes in developing therapies for cancer patients. The research has been published in the AACR journal, Cancer Research Communications. It says roginolisib can prevent tumor proliferation and breaks immune tolerance in this patient group.
Researchers say that PI3Kδ inhibition in solid tumors has recently emerged as a new 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.
Favorable toxicity profile
They also said that patients with solid malignancies where a rapid onset of toxicities has been seen are particularly vulnerable to safety concerns. Roginolisib’s favorable toxicity profile has less than five per cent grade three or four toxicities at the biologically effective dose. Importantly, these toxicities were transient in nature without the need for dose reductions.
The published research, iOnctura says, 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, 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.”
Immune modulatory properties
iOnctura explained that 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.
The mechanism 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 1b/2 investigation in solid and hematological tumors.
Catherine Pickering, CEO at 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 toolboxes for hematological cancers as well as offering new value for patients with solid tumors.”
