frenlosirsen (ION251)

So far, pre-clinical and clinical studies showed promising results when Bcl-2 (Genasense), Mcl-1 (ISIS2048), STAT3 (ISIS345794) and IRF4 (ION251) were targeted using ASOs-based formulations. The relevant genetic targets in ASOs-based MM therapies were described, and the research results obtained in the studies conducted so far were analyzed, with a focus on the ASOs formulations that were already included in clinical trials. In the end, current challenges, and future perspectives of antisense therapy for MM were also discussed.

P1, N=23, Completed, Ionis Pharmaceuticals, Inc. | Active, not recruiting --> Completed | Trial completion date: Jan 2024 --> Sep 2024 | Trial primary completion date: Jan 2024 --> Sep 2024

P1, N=23, Active, not recruiting, Ionis Pharmaceuticals, Inc. | Recruiting --> Active, not recruiting | N=80 --> 23

In a patient-derived xenograft model that recapitulates IRF4 pathway activation in human myeloma, we test the effects of IRF4 antisense oligonucleotides (ASOs) and identify a lead agent for clinical development (ION251)...Mechanistically, IRF4 inhibition disrupts cell cycle progression, downregulates stem cell and cell adhesion transcript expression, and promotes sensitivity to myeloma drugs. These findings will enable rapid clinical development of selective IRF4 inhibitors to prevent myeloma progenitor-driven relapse.