Due 5/30 Solicitation for submission of Pre-LOIs for Iadademstat
May 09, 2025
As part of the iadademstat (ORY-1001) clinical development program, CTEP would like to request presolicitation applications from all interested UM1 investigators for a very limited number of new iadademstat CTEP studies.
Iadademstat is an oral small-molecule inhibitor of lysine-specific demethylase 1 (LSD1) and has been granted FDA Orphan Drug Designation for the treatment of acute myeloid leukemia (AML) and small cell lung cancer (SCLC). LSD1 modulates gene expression via demethylation of histone H3 lysine 4 (H3K4) and 9 (H3K9), plus non-histone targets such as p53 (Lynch et al., 2012. Expert Opin Ther Targets. 16(12):1239-1249). LSD1 also provides a scaffold for assembly of the GFI1/CoREST transcriptional repressor complex, which regulates hematopoietic differentiation (Maiques-Diaz et al., 2018. Cell Rep. 22(13):3641-3659). Overexpression of LSD1 has been detected in hematological malignancies such as AML (Niebel et al., 2014. Blood. 124(1):151-152) along with solid tumors such as bladder, lung, and colorectal carcinomas (Hayami et al., 2011. Int J Cancer. 128(3):574-586). In cell lines and mouse models of AML driven by mixed-lineage leukemia gene (MLL) rearrangements, LSD1 inhibition resulted in impairment of the oncogenic transcriptional program and induction of the differentiation program (Harris et al., 2012. Cancer Cell. 21(4):473-487). Gene expression shifting from a proliferation to a differentiation signature has also been preclinically characterized in other AML subtypes (McGrath et al., 2016. Cancer Res. 76(7):1975-1988) and SCLC (Mohammad et al., 2015. Cancer Cell. 28(1):57-69) in response to LSD1 blockade.
If you are interested in conducting a trial with iadademstat in any of the above-described settings, please contact Dr. Geoffrey Shapiro (geoffrey_shapiro@dfci.harvard.edu).
Please see the Pre-LOI form for your submission. Please complete and submit it to PreLOIs@tech-res.com and CC' Dr. Geoffrey Shapiro (geoffrey_shapiro@dfci.harvard.edu) by COB May 30, 2025. Please note that in the case of an ECI application, the ECI-PI’s curriculum vitae and letters of mentorship and institutional commitment must be submitted together with the Pre-LOI application via e-mail. The Investigational Drug Branch will review the submissions and make a formal request for a full LOI on or around June 27, 2025.
Should you have questions or concerns regarding this process or the solicited iadademstat trials, please contact Dr. Lorraine Pelosof at 240-276-6281 or lorraine.pelosof@nih.gov.