P1/2, N=158, Recruiting, iOmx Therapeutics AG | Phase classification: P1 --> P1/2 | N=30 --> 158 | Trial completion date: May 2025 --> Apr 2026 | Trial primary completion date: Aug 2024 --> Mar 2026

P2, N=40, Recruiting, Rhizen Pharmaceuticals SA | Not yet recruiting --> Recruiting

P2, N=40, Not yet recruiting, Rhizen Pharmaceuticals SA

Coadministration of tenalisib and romidepsin did not significantly alter the pharmacokinetics of romidepsin. Overall, tenalisib and romidepsin combination demonstrated a favorable safety and efficacy profile supporting its further development for relapsed/refractory TCL.

P1/2, N=17, Completed, Rhizen Pharmaceuticals SA | Trial primary completion date: Mar 2022 --> Mar 2023

P2, N=40, Completed, Rhizen Pharmaceuticals SA | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Mar 2023 | Trial primary completion date: Dec 2022 --> Mar 2023

By screening sensitive and non-sensitive tumor cell lines and PDX models, we identified a response-prediction biomarker signature. In upcoming clinical studies, this predictive biomarker signature will be evaluated for it’s potential to enrich for patients highly responsive to OMX-0407 therapy.

P2, N=0, Withdrawn, Rhizen Pharmaceuticals SA | N=40 --> 0 | Not yet recruiting --> Withdrawn

P2, N=40, Not yet recruiting, Rhizen Pharmaceuticals SA | Initiation date: May 2022 --> Jan 2023

For clinical indications, dietary nutrients (such as curcumin) as an adjuvant to chemotherapy should be helpful to TNBC patients because the current trend is to shrink the tumor with preoperative chemotherapy and then perform surgery. In addition, from the perspective of chemoprevention, curcumin has excellent clinical application value.

We have identified salt-inducible kinase 2 (SIK2) inhibitors, ARN3236 and ARN3261, which decreased DNA double-strand break (DSB) repair functions and produced synthetic lethality with multiple PARP inhibitors in both homologous recombination DNA repair deficiency and proficiency cancer cells. Furthermore, SIK2 inhibitors abolished class-IIa HDAC4/5/7-associated transcriptional activity of myocyte enhancer factor-2D (MEF2D), decreasing MEF2D binding to regulatory regions with high chromatin accessibility in FANCD2, EXO1, and XRCC4 genes, resulting in repression of their functions in the DNA DSB repair pathway. The combination of PARP inhibitors and SIK2 inhibitors provides a therapeutic strategy to enhance PARP inhibitor sensitivity for ovarian cancer and TNBC.

In summary, OMX-0407, a first-in-class oral SIK3 inhibitor, demonstrates potent monotherapy efficacy in a pro-inflammatory tumor setting by reshaping the immune compartment and accelerating tumor cell death. The ability of OMX-0407 to remodel an immunosuppressed TME in a generally cold tumor setting, harbors great clinical potential for OMX-0407 combination therapy with anti-PD-1/PD-L1 immune checkpoint blockade, specifically in patients with high unmet medical need who are resistant to current immune checkpoint inhibitor monotherapy.

P2, N=40, Not yet recruiting, Rhizen Pharmaceuticals SA

CD, fluorescence, and NMR examined models of i-motif and G-quadruplex sequences present in the n-myc gene and the c-kit gene. We provide evidence that escholidine does not induce stabilization of the i-motif sequences, while the interaction with G-quadruplex structures appears to be more significant.