Salarius' lead molecule, Seclidemstat, is scheduled to begin enrollment for a Phase 1 trial in Ewing sarcoma in 2017. Ewing sarcoma is a devastating pediatric illness and represents a major unmet clinical need. Currently, chemotherapy, radiation and tumor resection surgery are the only options for patients, and in many cases the tumors reoccur or is in too delicate of a location to risk surgery. There is a 90% five-year mortality rate for patients whose tumors recur after treatment or who are initially diagnosed with metastatic disease. Translocations in the EWS protein are the sole driver for over 85% of Ewing sarcoma, and EWS must complex with LSD1 to induce a cancer phenotype. Seclidemstat blocks this LSD1 interaction to reverse cancer pathology resulting in cures in animal models.
Salarius plans to begin enrolling for a phase 1 trial in prostate cancer in 2018. Prostate cancers generally initiate via dependence on the androgen receptor, and can be controlled for a short time with the hormonal therapies like abiraterone and enzalutamide. However, the cancer can progress to gain independence from the androgen receptor, and in these cases, will no longer respond to standard of care treatments. These advanced cancers show constitutive androgen receptor signaling in the absence of androgen ligands. LSD1 complexes with the androgen receptor, and Seclidemstat blocks this interaction to reduce tumor burden and re-sensitize tumors to standard of care hormonal therapies.
In a separate phase 1 trial sponsored by the Huntsman Cancer Institute, Seclidemstat will be evaluated in combination with carboplatin for the treatment of late stage triple negative breast cancer (TNBC) and ovarian cancer. TNBC is missing the cell components targeted by common hormonal therapies, so it is untreatable and often more aggressive than other forms of breast cancer. No targeted therapies currently exist for late stage ovarian cancer, and carboplatin is the chemotherapy of choice. LSD1 is connected to proteins that drive both of these cancers, and preliminary data suggests Seclidemstat may represent a better treatment option.