- |||||||||| bintrafusp alfa (M7824) / EMD Serono, PDS01ADC / PDS Biotech, Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Trial completion date, Metastases: A Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers (clinicaltrials.gov) - Apr 18, 2024 P1/2, N=107, Recruiting, These findings further support entinostat as an effective and safe treatment option for the specific patient population. Trial completion date: Dec 2024 --> Dec 2025
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Journal: Inhibition of HDAC1 and 3 in the Presence of Systemic Inflammation Reduces Retinal Degeneration in a Model of Dry Age-Related Macular Degeneration. (Pubmed Central) - Apr 12, 2024 Mice were treated with a selective HDAC class I inhibitor, MS-275, and retinal structure [optical coherence tomography (OCT)], function (electroretinography), and molecular changes quantitative real-time polymerase chain reaction (RT-qPCR, Western Blot) were assessed...In addition, HDAC inhibition in CIA + NaIO3 treated mice resulted in reduced cytokine production. These findings are highly innovative and provide additional support to the therapeutic potential of HDAC inhibitors for dry AMD treatment.
- |||||||||| Keytruda (pembrolizumab) / Merck (MSD), Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Phase classification, Trial completion date, Combination therapy, Epigenetic controller: Testing the Safety and Efficacy of the Combination of the Antibody Pembrolizumab and Entinostat in Patients With Myelodysplastic Syndrome Who Are Not Responding to Hypomethylating Agents (clinicaltrials.gov) - Mar 25, 2024 P1, N=28, Active, not recruiting, Not yet recruiting --> Recruiting Phase classification: P1b --> P1 | Trial completion date: Jun 2023 --> Mar 2025
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, Istodax (romidepsin) / Astellas, BMS
Preclinical, Journal, Epigenetic controller: Systemic histone deacetylase inhibition ameliorates the aberrant responses to acute stress in socially isolated male mice. (Pubmed Central) - Mar 19, 2024 Treatment with class I histone deacetylase (HDAC) inhibitors ameliorates the aggressive behaviour and social interaction deficits of SIRS males, and normalizes glutamatergic currents in PFC neurons. It provides an epigenetic mechanism and intervention avenue for aberrant stress responses induced by chronic social isolation.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Journal, IO biomarker: Mechanisms of mesothelial cell response to viral infections: HDAC1-3 inhibition blocks poly(I:C)-induced type I interferon response and modulates the mesenchymal/inflammatory phenotype. (Pubmed Central) - Mar 17, 2024 A quantitative proteomic analysis of MCs treated with MS-275, an HDAC1-3 inhibitor, unveiled altered expression of several proteins, including inflammatory cytokines/chemokines and interferon-stimulated genes (ISGs)...Collectively, our findings underline the significance of viral infections in acquiring a mesenchymal-like phenotype by MCs and the potential consequences of virus-associated peritonitis episodes for PD patients. The observed promotion of MMT reversal and interferon response inhibition by an HDAC1-3 inhibitor, albeit without a general impact on inflammatory cytokine production, has translational implications deserving further analysis.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
INTRATUMORAL IMMUNE MODULATION FOR HEPATOCELLULAR CARCINOMA (Hall A, Poster Hall - Walter E. Washington Convention Center) - Mar 14, 2024 - Abstract #DDW2024DDW_7971; A novel microparticle formulation that composed of a PBAE and PLGA was developed to enable co-delivery of small molecule drug Entinostat and immunomodulatory cytokine IL-12. The new microparticles achieved high loading of Entinostat and IL-12 and enabled inhibition of orthotopic HCC growth.
- |||||||||| LOW DOSE DOUBLE EPIGENETIC THERAPY IMPROVES IMMUNOTHERAPY RESPONSE AND PROLONGS SURVIVAL IN PANCREATIC CANCER. (103AB - Walter E. Washington Convention Center) - Mar 14, 2024 - Abstract #DDW2024DDW_2386;
We previously showed, using the KPC (Kras LSL G12D/+; p53 r172H/+; Pdx1-Cre) mouse model of pancreatic cancer (PDAC), that sequential treatment with the DNA hypomethylating agent (HMA) decitabine (DAC) followed by aPD-1 initially enhanced anti-tumor effects, yet tumors developed resistance linked to a unique M2-polarized Chil3+ myeloid subtype...We then evaluated four different HDAC inhibitors with reported immunomodulatory effects and non-overlapping HDAC isoform specificities: Romidepsin (RM), Domatinostat (DM), Pracinostat (PR) and Entinostat (EN)...Our findings identify a functionally immune suppressive HMA specific myeloid effect. The addition of a second epigenetic agent enhances the therapeutic efficacy resulting in prolonged survival and reverses the suppressive myeloid cell related effects of DAC + aPD1.
- |||||||||| revumenib (SNDX-5613) / Syndax Pharma
Enrollment open, Trial completion date, Trial initiation date, Trial primary completion date, Combination therapy: Testing the Addition of an Anti-cancer Drug, SNDX-5613, to the Standard Chemotherapy Treatment (Daunorubicin and Cytarabine) for Newly Diagnosed Patients With Acute Myeloid Leukemia That Has Changes in NPM1 or MLL/KMT2A Gene (clinicaltrials.gov) - Mar 12, 2024 P1, N=28, Recruiting, The addition of a second epigenetic agent enhances the therapeutic efficacy resulting in prolonged survival and reverses the suppressive myeloid cell related effects of DAC + aPD1. Not yet recruiting --> Recruiting | Trial completion date: Feb 2024 --> Dec 2027 | Initiation date: Feb 2024 --> Nov 2024 | Trial primary completion date: Feb 2024 --> Dec 2027
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Entinostat alters cell cycle in ovarian cancer cells (Section 52) - Mar 5, 2024 - Abstract #AACR2024AACR_8936; Not yet recruiting --> Recruiting | Trial completion date: Feb 2024 --> Dec 2027 | Initiation date: Feb 2024 --> Nov 2024 | Trial primary completion date: Feb 2024 --> Dec 2027 Abstract is embargoed at this time.
- |||||||||| VTP-50469 / Syndax Pharma
Menin drives oncogenesis in Ewing sarcoma cells by activating transcription of key metastatic factors (Room 31 - Upper Level - Convention Center) - Mar 5, 2024 - Abstract #AACR2024AACR_8849; To determine if genes altered in MEN1-KO cells were dependent on the role of Menin in Menin/MLL methyltransferase complexes, we analyzed transcriptomes of EwS cells that had been exposed to the Menin/MLL interaction inhibitor, VTP-50469...Finally, we found that Menin and EWS::FLI1 co-immunoprecipitate in EwS nuclear extracts suggesting that they may exist in complex with one another at sites of shared gene regulation. Taken together, these data indicate that Menin promotes EwS metastasis and that this is achieved by its function as a scaffolding protein that augments the transcriptional activity of EWS::FLI1 at intragenic enhancers of pro-metastasis genes.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm, ANK-101 / Ankyra Therap
Anchored IL-12 synergizes with an epigenetic modulator to promote immune remodeling and overcome anti-PD1-refractory murine tumors (Section 4) - Mar 5, 2024 - Abstract #AACR2024AACR_7010; Significant decrease in CD4+ Tregs and increased CD8/Treg ratio were also observed. Ongoing functional studies, proteomic and immune cell analysis at the tumor site, tdLN, and periphery, including single cell transcriptomics and epigenetic studies, will allow for a deeper understanding of the synergistic effect of mANK-101 with the epigenetic modulator Entinostat.Conclusions Collectively, these findings form a rationale for the clinical combination of intralesional delivery of ANK-101 with entinostat for patients with ICB-refractory malignancies, including colorectal and HPV16neg head and neck cancers.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
From tumor progression to therapeutic control: Combinatorial targeting of immune vulnerabilities in TNBC (Section 3) - Mar 5, 2024 - Abstract #AACR2024AACR_6902; Preliminary data has revealed that immune-competent mammary tumor-bearing MMTV-PyMT transgenic mice have slowed tumor progression following sequential combination of a microtubule poison (paclitaxel; PTX) to enhance tumor immunogenicity, plus a macrophage-depleting/reprogramming agent such as a colony-stimulating factor 1 receptor blocking antibody (?CSF1R), and undergo primary tumor regression in 60% of transgenic mice when an ICI targeting PD-1 is applied (3x therapy) by a CD8+ T cell-dependent mechanism...Using a class 1 benzamide histone deacetylase (HDAC) inhibitor (e.g., entinostat) sequentially added to PTX/?CSF1R/?PD-1 therapy (4x) resulted in primary tumor stasis in 100% of mice, and significantly enhanced overall survival, in two transgenic mouse models of breast cancer (MMTV-PyMT and C3-(1)-TAg)...Adoptive serum transfer (AST) from 4x-treated MMTV-PyMT mice into either 3x-treated or untreated MMTV-PyMT mice elicited tumor stasis and control. These preclinical studies indicate the complexity of myeloid, B cell and T cell interactions that are co-opted by tumors, and identify novel paths to therapeutic tumor control by targeting vulnerable immune communication programs.
- |||||||||| Lynparza (olaparib) / Merck (MSD), AstraZeneca
Selective HDAC3 inhibition e-sensitizes PARPi-resistant ovarian cancer cells to olaparib (Section 24) - Mar 5, 2024 - Abstract #AACR2024AACR_6880; Interestingly, BRD3308 alone reduced colony formation in the ID8_OR cells, but not in the ID8 cells. In conclusion, selective HDAC3 inhibition in combination with olaparib may be an effective therapy in the treatment of acquired PARPi resistant ovarian cancers.
- |||||||||| revumenib (SNDX-5613) / Syndax Pharma, FHD-286 / Foghorn Therap, birabresib (OTX015) / Merck (MSD)
Novel combination therapies to overcome non-genetic/adaptive menin inhibitor resistance in AML with MLL1r or mtNPM1 (Ballroom 6 B - Upper Level - Convention Center) - Mar 5, 2024 - Abstract #AACR2024AACR_3342; In vivo treatment with FHD-286 and OTX015 or SNDX-5613 significantly reduced the AML burden in mice bearing OCI-AML3-MITR xenografts. These findings underscore preclinical activity of epigenetically-targeted agent-based combinations and highlight their promise in overcoming MI resistance in AML with MLL1r or mtNPM1.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
HDAC3 sustains resistance to hypofractionated radiotherapy in fusion positve rhabdomyosarcoma cells (Section 28) - Mar 5, 2024 - Abstract #AACR2024AACR_2682; Recently, we reported that MS-275, a Class I and IV HDACi, in combination with RT affected cell survival, reduced colony formation ability, increased DNA damage repair inhibition and reactive oxygen species formation in FP-RMS cells...The new HDAC3i is highly specific in targeting FP-RMS cell growth in vitro while no effects have been observed in normal cells such as myoblasts and lung fibroblast. Moreover, the drug treatment in combination with radiotherapy phenotypically and molecularly recapitulated what observed in HDAC3 depleted cells.The study has been founded by Italian Association for Cancer Research (AIRC) to FM.
- |||||||||| revumenib (SNDX-5613) / Syndax Pharma
Deciphering the mechanism of the menin-MLL complex dependency in HCC (Section 23) - Mar 5, 2024 - Abstract #AACR2024AACR_2658; Moreover, treatment of HCC cell lines (HLF, PLC/PRF5, HepG2) with recently developed menin inhibitor SNDX-5613 (revumenib) revealed a dose-dependent reduction in cell proliferation...Integration of our genomics data revealed a list of 30 genes, which are downregulated upon menin inhibition in both HLF and PLC/PRF5 cells (FC?1.5) and the direct targets of the menin-MLL complex in HLF cells, suggesting their potential role in HCC cell survival. Altogether, we anticipate that menin and ASH2L serve as promising targets and represent an appealing therapeutic strategy for HCC treatment.
- |||||||||| Biomarker, Trial completion date, Trial primary completion date: Beat AML: Study of Biomarker-Based Treatment of Acute Myeloid Leukemia (clinicaltrials.gov) - Feb 21, 2024
P1/2, N=2000, Recruiting, Taken together, this study demonstrates that formulating these agents within a single nanoparticle delivery platform may provide clinical utility beyond use as nonencapsulated agents. Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026
- |||||||||| 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.
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