- |||||||||| GYY4137 / National University of Singapore, Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Review, Journal: Investigating the impact of protein S-sulfhydration modification on vascular diseases: A comprehensive review. (Pubmed Central) - Feb 19, 2024 The review also emphasizes the antithrombotic effects of HS in regulating platelet aggregation and thrombosis. The aim of this review is to enhance our understanding of the function and mechanism of protein S-sulfhydration modification in vascular diseases, and to provide new insights into the clinical application of this modification.
- |||||||||| axatilimab (SNDX-6352) / Syndax Pharma, Incyte
AXATILIMAB FOR CHRONIC GRAFT-VERSUS-HOST DISEASE: RESPONSES IN FIBROSIS-DOMINANT ORGANS IN AGAVE-201 (Hall 5) - Feb 14, 2024 - Abstract #EBMT2024EBMT_1019; P2 In AGAVE-201, clinical activity in fibrosis-dominant organs is supported by clinician-reported changes in the majority of patients and patient-reported reductions in organ-specific symptom burden. Axatilimab had a generally well-tolerated safety profile; opportunistic infections, which are typically common in patients with cGVHD under heavy immunosuppression, were infrequent with axatilimab
- |||||||||| Beleodaq (belinostat) / Aurobindo, Assertio, Farydak (panobinostat) / Secura Bio, Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Journal: Dysregulated Forkhead Box (FOX) Genes Association with Survival Prognosis, Anti-tumor Immunity, and Key Targeting Drugs in Colon Adenocarcinoma. (Pubmed Central) - Feb 4, 2024 Axatilimab had a generally well-tolerated safety profile; opportunistic infections, which are typically common in patients with cGVHD under heavy immunosuppression, were infrequent with axatilimab The FOX genes have a strong correlation with the poor prognosis for survival, tumor immunity, cancer-associated pathways, and biochemical processes that cause the pathogenesis of COAD.
- |||||||||| Niktimvo (axatilimab-csfr) / Syndax Pharma, Incyte
Enrollment open: MAXPIRe: Study to Evaluate Axatilimab in Participants With Idiopathic Pulmonary Fibrosis (IPF) (clinicaltrials.gov) - Jan 25, 2024 P2, N=135, Recruiting, Our study unveils a direct impact of HDAC-1/2 in the regulation of MC/EOC adhesion and highlights the regulation of MC plasticity by epigenetic inhibition as a potential target for therapeutic intervention in EOC peritoneal metastasis. Not yet recruiting --> Recruiting
- |||||||||| Journal, Epigenetic controller: Novel combination of imipridones and histone deacetylase inhibitors demonstrate cytotoxic effect through integrated stress response in pediatric solid tumors. (Pubmed Central) - Jan 8, 2024
ONC201, ONC206, and ONC212 are imipridones showing pro-apoptotic anti-cancer response...Additionally, pediatric solid tumor cells were treated with single-agent therapy with histone deacetylase inhibitors (HDACi) vorinostat, entinostat, and panobinostat, showing cell killing with all 3 HDACi drugs, with panobinostat showing the greatest potency...Our results introduce a novel class of small molecules to treat pediatric solid tumors in a precision medicine framework. Use of impridones in pediatric oncology is novel and shows promising pre-clinical efficacy in pediatric solid tumors, including in combination with HDAC inhibitors.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Journal: HDAC1-3 inhibition increases SARS-CoV-2 replication and productive infection in lung mesothelial and epithelial cells. (Pubmed Central) - Jan 6, 2024 We focused our analysis on the most potent ACE2/TMPRSS2 inducer among the inhibitors analysed, MS-275, a HDAC1-3 inhibitor...This study highlights a previously unrecognized effect of HDAC1-3 inhibition in increasing SARS-CoV-2 cell entry, replication and productive infection correlating with increased expression of ACE2 and TMPRSS2. These data, while adding basic insight into COVID-19 pathogenesis, warn for the use of HDAC inhibitors in SARS-CoV-2 patients.
- |||||||||| Zolinza (vorinostat) / Merck (MSD), tefinostat (CHR-2845) / Chroma Therap, Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Journal: Efficacy of HDAC Inhibitors in Driving Peroxisomal ?-Oxidation and Immune Responses in Human Macrophages: Implications for Neuroinflammatory Disorders. (Pubmed Central) - Dec 27, 2023 Our results revealed the significant stimulation of VLCFA degradation with the upregulation of genes involved in peroxisomal ?-oxidation and interference with immune cell recruitment; however, tefinostat was less potent than the class I HDAC-selective inhibitor entinostat in promoting a regenerative macrophage phenotype. Further research is needed to fully explore the potential of class I HDAC inhibition and downstream targets in the context of neuroinflammation.
- |||||||||| revumenib (SNDX-5613) / Syndax Pharma
Journal: Menin Inhibitors Trigger Leukemia Remissions. (Pubmed Central) - Dec 14, 2023 A phase II study of revumenib yielded a response rate of 63% in patients with relapsed or refractory disease and KMT2A rearrangements; a phase I trial combining the drug with three chemotherapies also yielded complete remissions in patients with acute myeloid leukemia. A phase I study of a different menin inhibitor detected responses in 63% of patients with acute leukemia and certain gene alterations.
- |||||||||| mezigdomide (CC-92480) / BMS
Preclinical, Journal, Combination therapy: Mezigdomide is effective alone and in combination with Menin inhibition in pre-clinical models of KMT2A-r and NPM1c AML. (Pubmed Central) - Dec 14, 2023 The combination of mezigdomide with the Menin inhibitor VTP-50469 increased survival and prevented and overcame MEN1 mutations that mediate resistance in patients receiving Menin inhibitor monotherapy. These results support prioritization of mezigdomide for early phase clinical trials in KMT2A-r and NPM1c AML, either as a single-agent or in combination with Menin inhibitors.
- |||||||||| Clinical, Review, Journal: Novel Pharmacological Treatment Options of Steroid-Refractory Graft-versus-Host Disease. (Pubmed Central) - Dec 14, 2023
Meanwhile, emerging treatments include tyrosine kinase inhibitors such as nilotinib, rituximab, and low-dose IL-2, as well as axatilimab and pomalidomide. While their efficacy needs to be better evaluated through large-scale, multicenter, randomized clinical trials, these novel agents show potential and could provide a better alternative for SR-GVHD treatment in the future.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Journal, Stroma: Inhibiting stromal Class I HDACs curbs pancreatic cancer progression. (Pubmed Central) - Dec 11, 2023 Notably, HDAC inhibition (HDACi) enriches a lipogenic fibroblast subpopulation, a potential precursor for myofibroblasts in the PDAC stroma. Overall, our study reveals the stromal targeting potential of HDACi, highlighting the utility of this epigenetic modulating approach in PDAC therapeutics.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD)
Enrollment closed, Trial completion date: WOOPS: Window of Opportunity Study of Pembrolizumab Alone and in Combinations in Bladder Cancer (clinicaltrials.gov) - Dec 8, 2023 P2, N=20, Active, not recruiting, Overall, our study reveals the stromal targeting potential of HDACi, highlighting the utility of this epigenetic modulating approach in PDAC therapeutics. Recruiting --> Active, not recruiting | Trial completion date: Jun 2024 --> Oct 2026
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Trial completion, Trial completion date, Trial primary completion date, Metastases: PEMDAC: Efficacy Study of Pembrolizumab With Entinostat to Treat Metastatic Melanoma of the Eye (clinicaltrials.gov) - Dec 8, 2023 P2, N=29, Completed, Recruiting --> Active, not recruiting | Trial completion date: Jun 2024 --> Oct 2026 Active, not recruiting --> Completed | Trial completion date: Aug 2023 --> Jan 2023 | Trial primary completion date: Aug 2021 --> Jan 2023
- |||||||||| revumenib (SNDX-5613) / Syndax Pharma
Phase 1/2 evaluation of revumenib in patients with advanced colorectal cancer and other solid tumors. (Level 1, West Hall; Poster Bd # N15) - Dec 6, 2023 - Abstract #ASCOGI2024ASCO_GI_640; P1/2 Active, not recruiting --> Completed | Trial completion date: Aug 2023 --> Jan 2023 | Trial primary completion date: Aug 2021 --> Jan 2023 Patients with CRC must be unable to receive or have disease that progressed on oxaliplatin, irinotecan, and bevacizumab; if left-sided RAS wild-type CRC, the patient must have received anti
- |||||||||| axatilimab (SNDX-6352) / Syndax Pharma, Incyte
Safety and Efficacy of Axatilimab in Patients with Chronic Graft-Versus-Host Disease (AGAVE-201) (Stars at Night B1 (Ballroom Level, Henry B. Gonzalez Convention Center); in-person) - Dec 5, 2023 - Abstract #TCTASTCTCIBMTR2024TCT_ASTCT_CIBMTR_675; P2 Patients with CRC must be unable to receive or have disease that progressed on oxaliplatin, irinotecan, and bevacizumab; if left-sided RAS wild-type CRC, the patient must have received anti The ORR (95% CI) by Cycle 7 was 73.8% (62.7
- |||||||||| mocetinostat (MGCD0103) / Mirati, Otsuka, Farydak (panobinostat) / Secura Bio, Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Preclinical, Journal: Applying HDACis to increase SSTR2 expression and radiolabeled DOTA-TATE uptake: From cells to mice. (Pubmed Central) - Nov 27, 2023 Not yet recruiting --> Recruiting To conclude, tumoral uptake levels of radiolabeled DOTA-TATE were not enhanced after HDACi treatment in vivo, but, depending on the applied inhibitor, increased SSTR2 expression levels were observed.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Journal: S100PBP is regulated by mutated KRAS and plays a tumour suppressor role in pancreatic cancer. (Pubmed Central) - Nov 13, 2023 This indicates Kras as an upstream epigenetic regulator of S100PBP. Finally, analysis of TCGA PanCancer Atlas PDAC datasets demonstrated poor prognosis in patients with high S100P and low S100PBP expression, suggesting that S100PBP is a novel tumour suppressor gene with potential clinical utility.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Tecentriq (atezolizumab) / Roche
P1 data, Journal, PD(L)-1 Biomarker: Phase I Study of Entinostat, Atezolizumab, Carboplatin, and Etoposide in Previously Untreated Extensive-Stage Small Cell Lung Cancer, ETCTN 10399. (Pubmed Central) - Nov 8, 2023 P1 Further exploration of entinostat with carboplatin, etoposide, and atezolizumab should not be explored. (ClinicalTrials.gov Identifier: NCT04631029).
- |||||||||| revumenib (SNDX-5613) / Syndax Pharma
Revumenib Maintenance Therapy Following Revumenib-Induced Remission and Transplant (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6412; P1/2 With 3 patients on revumenib maintenance therapy for more than a year, long-term responses, including conversion to MRD-negative status, were seen in these heavily pretreated patients with AML. Resuming revumenib post HSCT had a tolerable safety profile consistent with that previously reported for the AUGMENT-101 study.
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