PRT543 / Prelude Therap 
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  • ||||||||||  PRT811 / Prelude Therap, Lenvima (lenvatinib) / Eisai, Merck (MSD), PRT543 / Prelude Therap
    PRMT5 inhibition has a potent anti-tumor activity against adenoid cystic carcinoma of salivary glands (Grand Ballroom GHIJ) -  Mar 5, 2024 - Abstract #AHNSCOSM2024AHNS_COSM_59;    
    Identifying PRMT5 as a putative candidate, we next determined the applicability of PRMT5 inhibitors (PRT543 and PRT811) using ACC cell lines, organoids, and patient derived xenograft (PDX) models. Our study underscores the role of PRMT5 in ACC and supports PRMT5 blockade as a promising strategy for treating this rare disease.
  • ||||||||||  Lynparza (olaparib) / Merck (MSD), AstraZeneca, PRT543 / Prelude Therap
    Journal, BRCA Biomarker, PARP Biomarker:  PRMT5 Inhibitors Regulate DNA Damage Repair Pathways in Cancer Cells and Improve Response to PARP Inhibition and Chemotherapies. (Pubmed Central) -  Nov 8, 2023   
    Furthermore, PRT543 treatment significantly inhibits growth of Olaparib resistant tumors in vivo. These studies reveal a novel mechanism of PRMT5 inhibition and suggest beneficial combinatorial effects with other therapies, particularly in patients with tumors that are resistant to therapies dependent on DNA damage as their mechanism of action.
  • ||||||||||  PRT543 / Prelude Therap
    PRT543, a methyl transferase inhibitor, has potent anti-tumor activity against adenoid cystic carcinoma of salivary glands (Section 14; Poster Board #8) -  Mar 14, 2023 - Abstract #AACR2023AACR_7241;    
    Further, based on these observations, we have sequenced a collection of 50 ACC tumor samples to identify the subset of patients who may potentially benefit from PRT543 treatment based on their underlying genetic signatures. This study provides evidence underscoring the role of PRMT5 signaling in ACC and supports the clinical development of PRMT5 inhibitors for this indication.
  • ||||||||||  PRT543 / Prelude Therap
    Trial completion, Metastases:  A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies (clinicaltrials.gov) -  Nov 25, 2022   
    P1,  N=232, Completed, 
    This study provides evidence underscoring the role of PRMT5 signaling in ACC and supports the clinical development of PRMT5 inhibitors for this indication. Active, not recruiting --> Completed
  • ||||||||||  PRT1419 / Prelude Therap, navitoclax (ABT 263) / AbbVie, PRT543 / Prelude Therap
    PRMT5 Inhibition Alters Mitochondrial Dynamics in Mantle Cell Lymphoma Creating Vulnerability to BH3 Mimetic Compounds (ENMCC - Hall D) -  Nov 4, 2022 - Abstract #ASH2022ASH_2182;    
    Selectively inhibiting PRMT5 has shown significant anti-tumor activity in preclinical MCL models, and a Phase 1 clinical trial with PRT543 (Prelude), a novel PRMT5 inhibitor, is underway...Combinatorial treatment was tested in vivo using the PDX.AA.MCL model of ibrutinib resistant MCL...Navitoclax and PRT808 single agent as well as PRT808+PRT1419 regimens significantly slowed disease progression...Of note, navitoclax dosing alone or in combination did not induce additional platelet loss. Our results provide rationale for combining BH3 mimetics and PRMT5 inhibition in clinical trials as a novel treatment strategy for MCL.
  • ||||||||||  PRT543 / Prelude Therap
    Trial primary completion date, Metastases:  A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies (clinicaltrials.gov) -  Sep 2, 2022   
    P1,  N=227, Active, not recruiting, 
    Our results provide rationale for combining BH3 mimetics and PRMT5 inhibition in clinical trials as a novel treatment strategy for MCL. Trial primary completion date: Aug 2022 --> Dec 2022
  • ||||||||||  Review, Journal, IO biomarker:  Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors in Oncology Clinical Trials: A review. (Pubmed Central) -  Aug 30, 2022   
    Highly significant is a durable complete response in isocitrate dehydrogenase 1-mutated glioblastoma multiforme with PRT811...Further studies are warranted, and there are clinical trials to come whose data will be telling of the efficacy of PRMT5 inhibitors in both hematologic and solid malignancies. The aim of this study is to compile available results of PRMT5 inhibitors in oncology clinical trials.
  • ||||||||||  PRT543 / Prelude Therap
    Enrollment closed, Trial completion date, Trial primary completion date, Metastases:  A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies (clinicaltrials.gov) -  May 5, 2022   
    P1,  N=227, Active, not recruiting, 
    The aim of this study is to compile available results of PRMT5 inhibitors in oncology clinical trials. Recruiting --> Active, not recruiting | Trial completion date: Aug 2022 --> Dec 2022 | Trial primary completion date: Apr 2022 --> Aug 2022
  • ||||||||||  navitoclax (ABT 263) / AbbVie, tapotoclax (AMG 176) / Amgen, Roche, AbbVie, PRT543 / Prelude Therap
    PRMT5 inhibition alters mitochondrial dynamics in mantle cell lymphoma, creating vulnerability to BH3 mimetic compounds (Section 20) -  Mar 9, 2022 - Abstract #AACR2022AACR_3324;    
    Selectively inhibiting PRMT5 has shown significant anti-tumor activity in preclinical MCL models, and a Phase 1 clinical trial with PRT543 (Prelude), a novel PRMT5 inhibitor, is underway...BH3 mimetics navitoclax (BCL2, BCLXL, and BCLw inhibitor), A852 (BCLXL inhibitor), and AMG176 (MCL1 inhibitor) were found to have IC50s below 1uM in five, two, and four of the nine cell lines respectively...iBH3 flow-based analysis revealed increased sensitivity of ex vivo PDX cells to pan BCL2, BCLXL, and MCL1 inhibition. These results provide rationale for combining BH3 mimetics and PRMT5 inhibition in clinical trials as a novel treatment strategy for MCL.
  • ||||||||||  PRT543 / Prelude Therap
    Trial primary completion date, Metastases:  A Study of PRT543 in Participants With Advanced Solid Tumors and Hematologic Malignancies (clinicaltrials.gov) -  Aug 18, 2021   
    P1,  N=227, Recruiting, 
    We are currently exploring novel combinations to maximize the therapeutic potential of PRMT5 inhibition in this disease. Trial primary completion date: Aug 2021 --> Apr 2022
  • ||||||||||  PRT543 / Prelude Therap
    PRMT5 Inhibition Modulates E2F1 Methylation and Gene Regulatory Networks Leading to Therapeutic Efficacy in JAK2VF Mutant MPN (W308, Level 3 (Orange County Convention Center)) -  Nov 7, 2019 - Abstract #ASH2019ASH_3281;    
    P1
    These data demonstrate a novel link between PRMT5, E2F1 gene regulatory function, and the survival of MPN cells and provide a strong mechanism-based rationale for therapeutic studies of PRMT5 inhibitors in MPN . Based on these studies and others, PRT543, a novel and selective PRMT5 inhibitor, is currently being evaluated in a Phase I clinical trial in advanced cancers, including myelofibrosis (NCT03886831).