Acetylon Pharmaceuticals announced the publication of two abstracts describing preclinical trials that demonstrated the potential of ricolinostat (ACY-1215), a HDAC6 inhibitor, to augment immunotherapies used to treat melanoma, and plans to start clinical testing in patients. The abstracts were published in conjunction with the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, in a special edition of the Journal of Clinical Oncology.
The studies, titled “In vitro and in vivo anti-melanoma activity of ricolinostat, a selective HDAC6 inhibitor with immunomodulatory properties” and “Selective histone deacetylase inhibition augments melanoma immunotherapy,” were conducted in collaboration with the labs of Jeffrey S. Weber, MD, PhD, at the NYU Langone Medical Center, and Eduardo Sotomayor, MD, at the George Washington University School of Medicine and Health Sciences.
Results revealed that treatment with ricolinostat increased in vitro melanoma immunotherapy in experiments conducted with patient-derived T-cells.
Rocilinostat is a selective inhibitor of HDAC6 (histone deacetylase 6), an enzyme encoded by the HDAC6 gene that plays an important role in translational regulation, cell cycle progression, and developmental events. HDAC6 overexpression is correlated with tumorigenesis, cell survival, and metastasis.
Evidence from previous studies demonstrated that pan-HDAC inhibitors induce apoptosis and, through HDAC6, regulate melanoma cells’ immunogenicity. Other studies have shown that the progression of melanoma cells that lack HDAC6 is delayed in comparison with wild-type cells.
Selective HDAC inhibition is expected to reduce or eliminate the severe side effects related with non-selective HDAC inhibition.
“The anti-tumor activity of ricolinostat observed in a preclinical model of melanoma, in addition to its positive effects on the proliferation and function of melanoma patient-derived T-cells during ex vivo expansion, provide a solid rationale for further development,” Simon S. Jones, PhD, senior vice president, Preclinical Development at Acetylon, said in a press release. “Based on these exciting results, clinical trials with ACY-241, a selective HDAC6 inhibitor in tablet form, will be initiated in melanoma and non-small cell lung cancer in combination with the immune checkpoint inhibitors Opdivo® alone or in combination with Yervoy®.
“We are currently evaluating the safety and antitumor activity of ACY-241 in multiple myeloma and ricolinostat in lymphoma, and these new preclinical data in melanoma highlight the broad versatility and immunomodulatory capability of selective HDAC6 inhibitors across multiple oncology indications,” Dr. Jones said.
