Salarius Pharmaceuticals, Inc. announced that Daniela Santiesteban, Ph.D., Salarius’ director of targeted protein degradation development, presented positive SP-3164 preclinical data at the 64thAmerican Society of Hematology (ASH) Annual Meeting and Exposition underway in New Orleans and virtually. SP-3164 is an oral, next-generation molecular glue that uses deuterium to stabilize the preferred (S)-enantiomer of avadomide and thereby prevents interconversion into the unwanted (R)-enantiomer of avadomide. Avadomide is an extensively studied clinical compound that has demonstrated encouraging single-agent and combination-therapy efficacy in non-Hodgkin’s lymphomas (NHL) and other hematologic malignancies. In addition, published DLBCL avadomide clinical data showed patients with an identifiable gene signature had clinically meaningful improvements in overall response rates, suggesting that Salarius may be able to select patients more likely to respond to SP-3164 treatment. This, along with the data presented at ASH showing compelling SP-3164 activity in lymphoma models, supports SP-3164’s potential in NHL for the clinical trial planned for 2023. The poster – titled “SP-3164, a Novel Cereblon-Binding Protein Degrader, Shows Activity in Preclinical Lymphoma Models” – demonstrated that in lymphoma cells, SP-3164 interacts with the cereblon component of a CRL4 E3 ligase, inducing recruitment and subsequent degradation of the hematological transcription factors Ikaros and Aiolos, which play a critical role in regulating B and T cell development. Like other Ikaros and Aiolos degraders such as lenalidomide and avadomide, SP-3164 demonstrates compelling activity in NHL and may have potential safety and efficacy advantages over other molecular glues.
Data highlights included in the poster, available here, include: SP-3164 induced rapid and efficient Ikaros degradation compared to other studied molecular glues, SP-3164 exhibited antiproliferative effects across several NHL cell lines, SP-3164 pharmacokinetics showed exclusive exposure to the preferred (S)-enantiomer, SP-3164 demonstrated single-agent activity in DLBCL mouse model and superiority to lenalidomide, SP-3164 resulted in complete regressions in 50% of mice when treated in combination with rituximab in a DLBCL mouse model and performed significantly better than the approved regimen of lenalidomide and rituximab.