abexinostat (CG-781) / Xynomic Pharmaceuticals, AbbVie - LARVOL DELTA

Abexinostat attenuates temozolomide-resistant glioma stem cells. (PubMed, Neuro Oncol) - "Abx reduced both DNA repair machinery and GSC markers by decreasing chromatin accessibility. Abx reduced tumor growth and mesenchymal GSCs in vitro and in vivo in GBM PDC and PDX models, supporting Abx's potential to prevent GSC-mediated therapy resistance and improve patient survival."

Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • ALDH1A1 • ALDH1A3 • BMI1 • BRCA1 • CD44 • CHEK1 • KLF4 • MYC • RAD51

A Study of Temodar With Abexinostat (PCI-24781) for Patients With Recurrent Glioma (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: University of Nebraska | Trial completion date: Jul 2029 ➔ Jul 2027

Trial completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Gliosarcoma • High Grade Glioma • Oligodendroglioma • Oncology • Sarcoma • Solid Tumor

Mapping Non-Homologous Pocket Compatibilities to Identify Hidden Drug-Target Relationships: A Pocket Hopping Framework. (PubMed, J Med Chem) - "In two case studies, pocket hopping demonstrates broad utility in drug discovery by enabling de novo hit identification and mechanistic interpretation, identifying fedratinib and its analogues as helicase WRN inhibitors. The model also identified the clinical-stage HDAC inhibitor abexinostat as a direct ENPP1 binder and inhibitor, and cellular assays showed enhanced cGAMP-STING signaling under cGAMP stimulation. Together, these results indicate that pocket-level compatibility can complement existing approaches for target identification, hit discovery, and polypharmacology analysis."

Journal • ENPP1 • WRN

Abexinostat, a histone deacetylases inhibitor, for patients with relapsed or refractory follicular lymphoma: a multi-center, single-arm phase 2 study. (PubMed, Signal Transduct Target Ther) - P2 | "The most common treatment-emergent adverse events were thrombocytopenia (77/90, 85.6%), neutropenia (53/90, 58.9%), and leukopenia (47/90, 52.2%). The results of this study demonstrated that abexinostat had promising efficacy and manageable safety profile, supporting abexinostat as a new treatment option for the third-line or later-line treatment of r/r FL."

Journal • P2 data • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Oncology • Thrombocytopenia

A Study of Temodar With Abexinostat (PCI-24781) for Patients With Recurrent Glioma (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: University of Nebraska | Trial completion date: Mar 2027 ➔ Jul 2029 | Trial primary completion date: Mar 2026 ➔ Jul 2027

Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Gliosarcoma • High Grade Glioma • Oligodendroglioma • Oncology • Sarcoma • Solid Tumor

Drug Development. (PubMed, Alzheimers Dement) - "Abexinostat demonstrates potential as a dual-target therapeutic for AD, inhibiting Aβ aggregation and improving cognitive function by modulating oxidative stress and Aβ metabolism. Further investigation is needed to explore its clinical applications."

Journal • Alzheimer's Disease • CNS Disorders • Aβ42 • BACE1 • CAT

Survival and response rates of histone deacetylase inhibitors in peripheral T-cell lymphoma: A comprehensive systematic review and meta-analysis of 67 studies. (ASH 2025) - "It has high relapses and unfavorable prognoses with first-line chemotherapy regimens (cyclophosphamide, doxorubicin, vincristine, and prednisone)...Currently, romidepsin, vorinostat, and belinostat have US FDA approval for the treatment of relapsed/refractory PTCL, while chidamide is approved in China but is not approved in the US...HDACi monotherapy in patients with R/R T cell lymphoma, demonstrated an ORR, with chidamide [42%; 95% CI: (0.148, 0.57), p-value = <0.00001, I2=85%] followed by romidepsin [30%; 95% CI: (0.25, 0.35), p-value = <0.00001, I2=35%], abexinostat [28%; 95% CI: (0.19, 0.37), p-value = <0.00001], belinostat [26%; 95% CI: (0.19, 0.33), p-value = <0.00001, I2=0%]... This meta-analysis demonstrates that HDACi has shown overall improved response rates and survival in PTCL patients. However, chidamide has higher response rates than romidepsin in previously treated (UT) patients. In R/R patients, complete remission is higher with romidepsin;..."

Epigenetic controller • Retrospective data • Review • Adult T-Cell Leukemia-Lymphoma • Extranodal Natural Killer/T-cell Lymphoma • Hematological Malignancies • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK

Identifying Novel Drug Vulnerabilities in Specified Molecular Subsets of Chronic Lymphocytic Leukemia (ASH 2024) - "Supporting the clinical and biological relevance of our results, venetoclax and ibrutinib were highly effective across CLL, nutlin-3 was ineffective in p53 mutant CLL. Novel drugs with the greatest pan-CLL effects include abexinostat, navitoclax, cerdulatinib, gandotinib and nutlin-3...We found many such associations including high sensitivity of IGHV-mutated CLL (M-CLL) to nutlin-3, IGHV-unmutated CLL (U-CLL) to Onalespib (MWU test, q<0.1), the intermediate epigenetic subtype (i-CLL) to Rapamycin (ANOVA, q<0.1). RNA subtype EC-m4 (TNF- and IFN- high M-CLLs) was specifically sensitive to nutlin-3 and onalespib; and EC-m2 (trisomy 12 enriched M-CLLs) demonstrated resistance to venetoclax and sensitivity to abexinostat (MWU test, p<0.05). Response to lenalidomide was associated with trisomy 12 (MWU, p=0.002)...In summary, we present an experimental strategy to rapidly prioritize novel treatments for CLL patients and a computational framework to inform precision..."

IO biomarker • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • CD5 • IGH • TP53

The role of SLC22A4 in Acute Myeloid Leukaemia. (PubMed, Mediterr J Hematol Infect Dis) - "Drug-sensitivity analysis showed positive correlations with cyclobenzaprine, hydrochloride, SGX-523, and simvastatin, and negative correlations with fluorouracil, abexinostat, EMD-534085, hypothemycin, tamoxifen, and sunitinib. SLC22A4 may be useful as a potent molecular-targeted agent in AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Safety, pharmacokinetics, and efficacy of abexinostat, an novel histone deacetylase inhibitor, in Chinese patients with relapsed/refractory B cell non-Hodgkin lymphoma: a Phase 1 study. (PubMed, BMC Cancer) - P1/2 | "Abexinostat showed favorable tolerability with no DLT in Chinese patients with r/r B cell NHL. The RP2D was 80 mg BID. The plasma concentration was dose-proportional manner. The PK result demonstrated that BID "one week on, one week off" administration is reasonable. Promising anti-tumor activity were seen in these patients population. This result support further investigation."

Journal • P1 data • PK/PD data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Dyslipidemia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia

A Study of Temodar With Abexinostat (PCI-24781) for Patients With Recurrent Glioma (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: University of Nebraska | N=18 ➔ 24

Enrollment change • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Gliosarcoma • Malignant Glioma • Oligodendroglioma • Oncology • Sarcoma • Solid Tumor

Identification and evaluation of Pharmacological enhancers of the factor VII p.Q160R variant. (PubMed, Sci Rep) - "Both drugs showed a dose-response effect on FVII antigen and activity levels in conditioned cell medium and on FVII activity in patients' plasma. In conclusion, the efficacy of the FDA-approved drugs abexinostat and tyloxapol in enhancing FVII variant activity constitute a proof of principle for high-throughput identification of drugs that may be feasible for novel treatment of FVII deficiency."

Journal

Abexinostat and Ibrutinib in Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Memorial Sloan Kettering Cancer Center | Active, not recruiting ➔ Completed

Trial completion • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL6 • IRF4 • MME

A Study of Pazopanib With or Without Abexinostat in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma (RENAVIV) (clinicaltrials.gov) - P3 | N=413 | Recruiting | Sponsor: Xynomic Pharmaceuticals, Inc. | Trial completion date: Jun 2025 ➔ Jun 2028 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Trial completion date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Study to Evaluate Efficacy and Safety of Oral Abexinostat in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL) (clinicaltrials.gov) - P2 | N=170 | Recruiting | Sponsor: Xynomic Pharmaceuticals, Inc. | Trial completion date: May 2025 ➔ Aug 2027 | Trial primary completion date: Dec 2024 ➔ Jul 2026

Monotherapy • Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

FORERUNNER: Study of Abexinostat in Patients With Relapsed or Refractory Follicular Lymphoma (clinicaltrials.gov) - P2 | N=139 | Active, not recruiting | Sponsor: Xynomic Pharmaceuticals, Inc. | Trial completion date: Dec 2025 ➔ Dec 2029 | Trial primary completion date: Dec 2024 ➔ Dec 2027

Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

A Clinical Study to Evaluate Pharmacokinetics, Safety, and Tolerability of Abexinostat in Chinese Patients (clinicaltrials.gov) - P1/2 | N=12 | Active, not recruiting | Sponsor: Xynomic Pharmaceuticals, Inc. | Trial completion date: Jun 2024 ➔ Nov 2025 | Trial primary completion date: Feb 2024 ➔ Dec 2024

Monotherapy • Trial completion date • Trial primary completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Multi-Center Phase 2 Study to Evaluate Efficacy and Safety of Oral Abexinostat as Monotherapy in Patients With Relapsed or Refractory Follicular Lymphoma (clinicaltrials.gov) - P2 | N=87 | Active, not recruiting | Sponsor: Xynomic Pharmaceuticals, Inc. | Trial completion date: Sep 2024 ➔ Oct 2025 | Trial primary completion date: Feb 2024 ➔ Jan 2025 | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Pazopanib in Combination with PCI-24781 in Patients with Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=90 | Completed | Sponsor: Pamela Munster | Active, not recruiting ➔ Completed

Trial completion • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Thyroid Gland Carcinoma

Three novel epigenetic-modifying compounds identified as HIV latency-reversing agents in Ghana (ASTMH 2024) - "The lead compounds were further screened in CD4+ T cells of four individuals living with HIV on suppressive ART.We identified five positive hits (MC1568, Abexinostat, Pracinostat, EPZ2015666, CXC6258-HCL) from the J.LAT 10.6 cell culture system with GFP-positive cells (20-91%). These compounds effectively reactivated latent HIV-1 in vitro and induced HIV expression ex vivo. Our findings suggest that these LRAs hold promise for reactivating latent HIV in individuals living with the virus."

Human Immunodeficiency Virus • Infectious Disease • CD4

A phase 1 trial of abexinostat with ibrutinib in relapsed/refractory mantle cell lymphoma and non-germinal center diffuse large B cell lymphoma. (PubMed, Leuk Lymphoma) - No abstract available

Journal • P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

The Bioequivalence of Abexinostat (CRA-024781) Tosylate Tablet (20 mg) in Chinese Healthy Subjects Under Fasting Conditions. (PubMed, Clin Pharmacol Drug Dev) - "The 90% confidence intervals (CIs) for the Cmax, AUC0-t, and AUC0-∞ of CRA-024781 and its 2 major metabolites (PCI-27789 and PCI-27887, both metabolites are pharmacologically inactive on HDAC1) fell within the acceptable range of 80%-125%. The results suggest that the CRA-024781 test preparation (Test [T1]) is bioequivalent to the reference preparation (Reference [T2]) in healthy Chinese subjects under fasting conditions."

Journal • HDAC1

A Study of Temodar With Abexinostat (PCI-24781) for Patients With Recurrent Glioma (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: University of Nebraska | Trial completion date: Jun 2027 ➔ Mar 2027 | Trial primary completion date: Feb 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Gliosarcoma • Oligodendroglioma • Oncology • Sarcoma • Solid Tumor

Chromatin context-dependent effects of epigenetic drugs on CRISPR-Cas9 editing. (PubMed, Nucleic Acids Res) - "For example, we find a subset of histone deacetylase inhibitors that improve Cas9 editing efficiency throughout all types of heterochromatin (e.g. PCI-24781), while others were only effective in euchromatin and H3K27me3-marked regions (e.g. apicidin). In summary, this study reveals that most epigenetic drugs alter CRISPR editing in a chromatin-dependent manner, and provides a resource to improve Cas9 editing more selectively at the desired location."

Journal

A phase II multicenter study of abexinostat, an oral histone deacetylase inhibitor, in patients with relapsed/refractory follicular lymphoma. (ASCO 2024) - P2 | "Abx was well tolerated at dose of 80 mg BID as monotherapy, and demonstrated a significant response in pts with heavily pretreated R/R FL."

Clinical • Epigenetic controller • P2 data • Anemia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Neutropenia • Oncology • Thrombocytopenia • CREBBP • EP300