Alkermes and Clovis Oncology collaborate on combination cancer therapies
DUBLIN and BOULDER, Colo.—Alkermes plc and Clovis Oncology, Inc. have entered into a research collaboration to evaluate ALKS 4230, Alkermes’s investigational engineered interleukin-2 (IL-2) variant immunotherapy, in combination with rucaparib, Clovis’s PARP inhibitor, and lucitanib, Clovis’s investigational tyrosine kinase inhibitor. The collaboration plans to explore the potential anti-cancer effects of both treatment combinations in preclinical models across multiple tumor types. Results of this research may form the basis for potential future clinical studies of the novel combinations of ALKS 4230 with rucaparib and/or lucitanib.
ALKS 4230 is an engineered fusion protein designed to selectively activate tumor-killing immune cells, while avoiding the expansion of immunosuppressive cells by preferentially binding to the intermediate-affinity interleukin-2 (IL-2) receptor complex. The selectivity of ALKS 4230 is reportedly designed to leverage the proven anti-tumor effects of existing IL-2 therapy while mitigating certain limitations.
“Our preclinical partnership with Clovis reflects our ongoing efforts to explore the numerous combination options afforded to ALKS 4230. The collaboration will allow us to examine combinations in two areas of keen interest, PARP and tyrosine kinase inhibition pathways,” said Mark Namchuk, Ph.D., senior vice president, research, pharmaceutical and non-clinical development at Alkermes. “Evidence of combined benefit of ALKS 4230 with rucaparib and/or lucitanib from these preclinical studies may provide a strong rationale to advance into clinical development.”
Rucaparib is an oral, small molecule inhibitor of the poly (ADP-ribose) polymerase (PARP) enzymes PARP-1, PARP-2, and PARP-3, which play a role in DNA repair. Rucaparib stimulates an anti-tumor immune response through the activation of the stimulator of interferon (STING) pathway and tumor cell death, resulting in the infiltration of multiple immune subsets including CD8 positive T-cells. Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDFGRα/β), and fibroblast growth factor receptors 1 through 3 (FGFR1-3).
Under this collaboration agreement, Alkermes and Clovis will perform preclinical studies to examine the mechanism of action and efficacy of the combinations of ALKS 4230 with rucaparib and ALKS 4230 with lucitanib in multiple tumor models. Under the terms of the agreement, the companies will share costs related to the preclinical studies, and each will contribute their respective compounds to the research collaboration.
“The unique profiles of rucaparib, lucitanib and ALKS 4230 may offer the potential for complementary therapies that could represent a meaningful opportunity for the development of new anti-cancer combination treatment options,” added Patrick J. Mahaffy, president and CEO of Clovis Oncology. “We are committed to exploring combinations such as these with Alkermes in order to bring improved therapeutic outcomes to patients with multiple tumor types.”