Clinical-stage biopharmaceutical company Salarius Pharmaceuticals (which specializes in potential new medicines to treat sarcomas, pediatric cancers, and other hematologic and solid tumors) has announced the formation of a research partnership with the Cancer Epigenetics Institute at Fox Chase Cancer Center in Houston. Research carried out by the laboratory of institute director Johnathan Whetstine reportedly will be aimed at identifying new indications and potential biomarkers for Salarius’ drug candidate seclidemstat.
“We are excited to be working with Salarius to further explore the potential of seclidemstat and LSD1 inhibition in new indications,” Whetstine said. “Overexpression of the LSD1 enzyme is associated with poor prognosis across a variety of cancer types; building on our prior research expertise and knowledge, we will explore the impact of LSD1 depletion and LSD1 catalytic inhibition on the transcriptome in order to better understand the enzyme’s catalytic and non-catalytic functions and the impact of seclidemstat on those functions.”
Seclidemstat (SP-2577) is a novel, oral, reversible inhibitor of lysine-specific histone demethylase 1 (also referred to as LSD1, an enzyme with a key role in the development and progression of several cancers.). A number of therapies intended to inhibit LSD1’s cancer-promoting activity have been in development recently.
According to Salarius, seclidemstat takes a different approach than other LSD1 inhibitors now in development. It simultaneously targets LSD1’s enzymatic activity and its scaffolding properties, creating a dual mechanism of action with the potential to offer differential therapeutic activity in various cancer types (including solid tumors). Up to this point, therapeutic activity of LSD1 inhibitors in clinical development has for the most part been limited to hematological cancers and myeloproliferative neoplasms.
“Seclidemstat’s ability to target the scaffolding property of the LSD1 enzyme has high relevance in several cancer types and could lead to potent inhibition with advantageous therapeutic properties,” Whetstine commented. “Insights into these aspects of LSD1 regulation could significantly impact our understanding about LSD1 function and therapeutic intervention.”
A Phase I/II clinical trial is now underway exploring seclidemstat as a treatment for sarcomas; the trial reportedly is treating patients with myxoid liposarcoma and other FET-rearranged sarcomas with single-agent seclidemstat and evaluating seclidemstat in combination with the chemotherapy agents topotecan and cyclophosphamide as a potential second- and third-line therapy for Ewing sarcoma, a deadly pediatric bone cancer. Fox Chase is among the nine clinical trial sites now enrolling patients.
“This is an exciting opportunity to advance our development of seclidemstat by harnessing the scientific expertise of a renowned cancer research center and one of the rising stars in the field of LSD1 inhibition,” said Salarius CEO David Arthur “To have Fox Chase and a scientist of Dr. Johnathan Whetstine’s caliber involved in this project is a strong validation of our work with seclidemstat. With the help of Fox Chase Cancer Center and Dr. Whetstine, our ultimate aim is to bring new treatment options and hope to more patients and their families fighting hard-to-treat cancers.”
Salarius recently expanded its seclidemstat clinical program into hematologic cancers, with the MD Anderson Cancer Center in Houston initiating a Phase I/II clinical trial to evaluate seclidemstat in combination with azacytidine in myelodysplastic syndromes and chronic myelomonocytic leukemia.