PHILADELPHIA (November 17, 2022)—Fox Chase Cancer Center and Oryzon Genomics S.A. will work together to test the safety and efficacy of the drug iadademstat in patients with pulmonary and extrapulmonary neuroendocrine carcinomas (NECs), which are rare and heterogeneous cancers arising from neuroendocrine cells, and small cell lung cancer (SCLC).
“NECs are difficult to diagnose and treat because these types of carcinomas behave differently depending on where they grow in the body. There are very few treatment options for these patients and even fewer trials, which makes this effort even more important,” said Namrata “Neena” Vijayvergia, MD, principal investigator on the study.
Vijayvergia is a member of the Cancer Epigenetics Institute (CEI), associate professor in the Department of Hematology/Oncology, and a member of the Nuclear Dynamics and Cancer research program at Fox Chase.
Hossein Borghaei, DO, MS, the Gloria and Edmund M. Dunn Chair in Thoracic Surgical Oncology and chief of the Division of Thoracic Medical Oncology at Fox Chase, will be a co-principal investigator for the trial. “We are excited to explore the therapeutic potential of iadademstat in patients with small cell lung cancer where better treatment options are needed,” he said.
Fox Chase will be conducting different collaborative combination clinical trials with iadademstat, for which Oryzon will provide funding, the drug, and technical expertise. The first collaborative Phase II trial will be an open-label basket study to be conducted by Fox Chase as sponsor.
“The approval of iadademstat for research studies represents a new paradigm and option for patients. I am excited about the collaboration between the CEI at Fox Chase and with Oryzon in this important scientific endeavor,” said Vijayvergia.
Iadademstat is an orally available, highly potent, and selective inhibitor of the epigenetic enzyme lysine-specific histone demethylase 1 (LSD1). The discovery of LSD1 put an end to the long-held idea that histone methylation could not be reversed. Histone methylation is a process in which amino acids in a histone protein are modified, leading to the increase or decrease of gene transcription.
LSD1 was first discovered in the lab of Yang Shi, PhD, at Harvard Medical School. At the time it was discovered, Johnathan Whetstine, PhD, director of the CEI and co-leader of the Nuclear Dynamics and Cancer research program at Fox Chase, was a postdoctoral fellow who was part of the discovery in Yang’s lab. He is now a co-investigator on this trial and playing a role in the research for this novel basket trial at Fox Chase.
“It is so gratifying to be part of a trial born from discoveries I was part of from the very beginning and be in an institution where I can facilitate clinical application,” Whetstine said.
The CEI is a national hub for epigenetics study and collaboration that is focused on mechanisms promoting cancer and therapeutic resistance. It seeks to promote fundamental discovery in cancer epigenetics while identifying novel biomarkers and therapeutic targets.
This collaboration between Oryzon, Fox Chase, and the CEI is an example of the type of bench-to-bedside discoveries CEI hopes to foster with industry partners leveraging epigenetic therapies.
“NECs and small cell carcinomas have been shown to be dependent upon LSD1 for their growth and the survival of the tumor stem cells,” said Douglas V. Faller, MD, PhD, Oryzon’s Global Chief Medical Officer. “We believe that our epigenetic therapeutic drug, iadademstat, in combination with selected other agents which have shown activity in these malignancies, represents a new approach to the treatment of SCLC and NECs, with the potential to provide meaningful benefit to these patients.”