Circio Holding ASA announced that it has entered into a collaboration with Georgetown University as part of a collaborative research support agreement with Janssen Scientific Affairs, LLC (Janssen) and a drug supply agreement with Bristol Myers Squibb (BMS) to test its drug candidate TG01 in combination with daratumumab (anti -CD38) and nivolumab (anti-PD1) in patients with RAS-mutated pancreatic cancer and patients with non-small cell lung cancer (NSCLC). Mutations in the RAS family of genes are a major cause of cancer and are found in over 90% of pancreatic and 30% of NSCLC cancer patients. RAS-mutated cancers typically have poor prognosis, and few targeted treatment options exist.

The only approved RAS-targeting pharmaceuticals are small molecule inhibitors of the specific G12C KRAS mutation, which covers around 40% of RAS-mutated lung cancers, and the medical need for novel treatment alternatives for mutant RAS cancer remains high. Furthermore, anti-PD1 resistance is emerging as a major problem in immunotherapy, and more than 80% of patients with advanced tumors still do not respond to such treatment. To further study this unmet medical need, Georgetown University is pursuing a phase 2 study to test the combination of daratumumab provided by Janssen, nivolumab provided by BMS, and TG01 provided by Circio in immunotherapy-naïve pancreatic cancer and in anti-PD1 resistant NSCLC.

The scientific hypothesis behind the study is based on ground-breaking research led and published by Prof. Samir Khleif and colleagues, demonstrating that elimination of dysfunctional CD8 T-cells by anti-CD38, followed by priming of new effector T-cells by a cancer vaccine, reinstated and strengthened efficacy of PD1 checkpoint blockade in pre-clinical models.