Cytune Pharma SAS, a French biotech company focused on research and development of novel immunotherapies for cancer treatment, has secured a 6 million euro financing upgrade from existing investors.
The money will be used to advance Cytune’s lead product candidate RLI15 to Phase 1 clinical trials. The company’s key investor PPF Group and founding shareholder partners have also agreed to a full buyout of the remaining shares at the start of Phase 1.
Recombinant human interleukin-15 (rhIL-15) is an immunostimulatory cytokine naturally produced in the human body, and its properties can increase the activity and strength of the body’s natural immune system. However, IL-15 has been shown to have limited efficacy mostly because the alpha chain receptor is usually cleaved from the presenting cells in pathological situations, which prevents IL-15 from activating its target cells.
The RLI15 drug and its platform, based on a modified and improved IL-15, allow for its use in combination therapies along with other immunotherapy strategies, such as checkpoint inhibitors. Cytune explains that due to its unique mode of action, RLI15 has been proven to stimulate immune effector cells such as cytotoxic and helper T-cells and NK (natural killer) cells, but RLI15 does not stimulate immune-inhibitory regulatory T-cells or other cells.
Cytune reports that in preclinical experiments, RLI15 is shown to be more potent and better-tolerated compared to normal IL15 or IL2.
In a paper recently published online in The Journal of Immunology, titled “IL-15 Trans-Signaling with the Superagonist RLI Promotes Effector/Memory CD8+ T Cell Responses and Enhances Antitumor Activity of PD-1 Antagonists,“ a team of scientists from several French research institutions and Cytune Pharma note that tumors enlist help from the surrounding environment to facilitate immune suppression, and immunotherapy can counteract this inhibition.
Among immunotherapeutic strategies, they observe that IL-15 might be assumed to represent a serious candidate for the reactivation of antitumor immunity. However, exogenous IL-15 (originating outside the body) may have a limited impact on patients with cancer due to its dependency on IL-15R, which is frequently downregulated in cancer patients.
In this investigation, researchers studied antitumor activity of the IL-15 superagonist receptor-linkerIL-15 (RLI).
The scientists report that in a mouse model of colorectal carcinoma, it was observed that RLI as a standalone treatment could only limit tumor outgrowth when initiated at an early stage of tumor development. Later commencement of RLI therapy was ineffective, coinciding with strong accumulation of terminally exhausted programmed cell death, suggesting that RLI was incapable of reactivating terminally exhausted CD8+ T-cells.
However, RLI in combination with programmed cell death-1 (PD-1) blocking antibody showed synergistic activity with RLI, but not with IL-15, and RLI could induce a greater accumulation of memory CD8+ T-cells and a stronger effector function compared to IL-15.
The investigators conclude that this study provides evidence that the sushi IL-15R/IL-15 fusion protein RLI enhances antitumor activity of anti-PD-1 treatment and represents a promising approach to stimulating host immunity.
The new funding will enable Cytune to advance the RLI15 candidate to Phase 1 clinical trials in 2017 and broaden its RLI15-based immunocytokine product pipeline. Cytune Pharma will partner with 
PPF Group member SOTIO, a biotechnology company developing a proprietary active cellular immunotherapy platform based on dendritic cells, and which is experienced in clinical development of oncology products, to closely collaborate with Cytune on additional developments in its pipeline.
“Our innovative products have the potential to provide more efficacious and safer treatments to cancer patients, when used either as monotherapy or for augmenting immunotherapies currently on the market,” Cytune Pharma President and CEO Dr. David Bechard said in a press release. “We are very grateful for the continuous and strong support of our shareholders.”
PPF shareholder and SOTIO CEO Ladislav Bartonicek said they are pleased not only with Cytune projects, but also the diligence of the team advancing RLI15 toward clincial trials.
“We are looking forward to moving RLI15 through clinical development to be able to offer superior alternative treatments to cancer patients,” he said.
