pulrodemstat (CC-90011)

Combined inhibition of class I HDACs and LSD1 potently increases SSTR2 expression and consequently radioligand binding and might thus be a putative strategy to improve the outcome of PRRT therapy in patients with NETs.

Pulrodemstat is an effective therapeutic drug for HNSCC. Thus, the TET3/KDM1A axis may account for the malignant phenotype of HNSCC.

P1, N=90, Completed, Celgene | Active, not recruiting --> Completed

P1, N=90, Active, not recruiting, Celgene | Phase classification: P1b --> P1 | Trial completion date: Feb 2024 --> Jun 2024 | Trial primary completion date: Feb 2024 --> Jun 2024

P1, N=75, Terminated, Celgene | Trial completion date: Sep 2025 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2025 --> Mar 2024; Business objectives have changed

Pulrodemstat synergized with Lenvatinib based on suppression of PI3K-AKT signaling and activation of apoptotic signaling.

P2, N=92, Completed, Celgene | Active, not recruiting --> Completed

P1, N=91, Active, not recruiting, Celgene | Trial primary completion date: Aug 2023 --> Sep 2025

The advent of LSD1 inhibitor-based clinical utility began with tranylcypromine, and it is now considered an inevitable scaffold in the search for other irreversible novel LSD1 inhibitors (IMG-7289 or bomedemstat, ORY1001 or iadademstat, ORY-2001 or vafidemstat, GSK2879552, and INCB059872). Moreover, numerous reversible inhibitors for LSD1 have been reported in the literature, including clinical candidates CC-90011 (pulrodemstat) and SP-2577 (seclidemstat)...For the first time, we comprehensively organized the peptide-based LSD1 inhibitors from the design strategy. Peptide inhibitors of LSD1 are classified as H3 peptide and SNAIL1 peptide derivatives, along with miscellaneous peptides that include naturally occurring LSD1 inhibitors.

P1, N=6, Completed, Celgene | Active, not recruiting --> Completed | N=10 --> 6 | Trial completion date: Mar 2025 --> May 2023

The present study preclinically demonstrated that LSD1 inhibition could provide a valuable strategy to enhance PI sensitivity and overcome drug resistance in MM patients and that this combination might be exploited for the treatment of other B-cell malignancies, thus extending the therapeutic impact of the project.

Overall, clinical activity was limited in this pre-treated patient population. No new safety signals emerged, and CC-90011 was well-tolerated in combination with nivolumab. Select biomarker data will be presented.