purinostat / Baoling Bio - LARVOL DELTA

High HDAC I/IIb selective inhibitor purinostat mesylate in relapsed and refractory peripheral T-cell lymphoma: A single-agent phase IIa study (ASH 2025) - P2 | "Current monotherapies yieldonly modest overall response rates (ORR) ranging from 22% to 38%, except for brentuximab vedotin inCD30-positive anaplastic large cell lymphoma (ALCL). The most common grade ≥3 treatment-related adverse eventsincluded neutropenia (83.3%), thrombocytopenia (75.0%), leukocytopenia (50.0%), lymphocytopenia(41.7%), anemia (20.8%), infectious pneumonia (16.7%), bacterial pneumonia (12.5%), and hypokalemia(12.5%). There was one treatment-related death due to infection.ConclusionPreliminary results from this phase IIa study indicate that PM administered in 21-day cycles demonstratespromising efficacy compared with currently available single agents, with a manageable safety profile inpatients with R/R PTCL."

P2a data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • Pneumonia • Respiratory Diseases • Systemic Anaplastic Large Cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia

An exploratory clinical study evaluating the safety, tolerability, and efficacy of the combination of purinostat mesylate, sintilimab, and apatinib in the treatment of advanced/metastatic gastric cancer (ChiCTR) - P1 | N=18 | Not yet recruiting | Sponsor: West China Hospital, Sichuan University; West China Hospital, Sichuan University

New P1 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor

Study of Purinostat Mesylate for Injection in the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL) (clinicaltrials.gov) - P2 | N=74 | Active, not recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | Recruiting ➔ Active, not recruiting | N=120 ➔ 74 | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Oct 2025 ➔ Dec 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Phase III Clinical Study of Purinostat Mesylate for Injection in Patients With Diffuse Large B-cell Lymphoma (clinicaltrials.gov) - P3 | N=390 | Recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A STUDY ON THE MECHANISM OF THE NOVEL HIGHLY SELECTIVE HDAC INHIBITOR PURINOSTAT MESYLATE IN DOUBLE-HIT LYMPHOMA AND ITS THERAPEUTIC POTENTIAL COMBINATION WITH VENETOCLAX (ICML 2025) - "Introduction: In Double-hit lymphoma (DHL), high expression of BCL-2 and MYC leads to poor response to R-CHOP and resistance to venetoclax. PM may inhibit MYC expression by regulating histone methylation. In the DHL PDX mouse model, the combination of PM and venetoclax significantly reduced tumor volume and prolonged survival time. These findings lay the foundation for and provide new insights into the development of more effective therapeutic strategies for DHL."

IO biomarker • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Oncology • BCL2 • MYC • NSD2

Preclinical and first-in-human of purinostat mesylate, a novel selective HDAC I/IIb inhibitor, in relapsed/refractory multiple myeloma and lymphoma. (PubMed, Signal Transduct Target Ther) - P1 | "Purinostat mesylate (PM), a highly selective HDAC I/II binhibitor, exhibits excellent antitumor activity in MM and lymphoma cell lines and mouse models, outperforming the pan-HDAC inhibitor panobinostat or first-line/second-line multi-drug combinations. Additionally, PM combined with pomalidomide and dexamethasone showed strong synergistic activity in r/r MM treatment. These findings support further open-label, multicenter phase Ib/IIa trials of PM combination therapy with immunomodulators for r/r MM, as well as phase II monotherapy trials for r/r DLBCL and r/r T-cell lymphoma."

Journal • P1 data • Preclinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Leukopenia • Lymphoma • Multiple Myeloma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • CD8 • CXCL10 • IFNG

EXPLORING THE IMPACT OF DIFFERENT TREATMENT REGIMENS ON MINIMAL RESIDUAL DISEASE MONITORING IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: AN ANALYSIS BASED ON NEXT-GENERATION SEQUENCING OF IMMUNOGLOBULIN GENE REARRANGEMENT (EHA 2025) - "Patients with R/R DLBCL were enrolled to receive either monotherapy with Purinostat Mesylate (PM) or the conventional salvage chemotherapy regimen R-MINE (rituximab, ifosfamide, mitoxantrone, and etoposide). The monitoring of MRD in patients with R/R DLBCL is relatively complex, and different treatment strategies, such as PM or R-MINE, have varying impacts on MRD. Future research will need to expand the sample size, extend the follow-up time, and track clonal changes to provide a basis for accurately assessing prognosis and optimizing clinical treatment."

Biomarker • Clinical • Minimal residual disease • Next-generation sequencing • Residual disease • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A STUDY ON THE MECHANISM OF ACTION OF THE NOVEL HIGHLY SELECTIVE HDAC INHIBITOR PURINOSTAT MESYLATE IN DOUBLE-HIT LYMPHOMA AND ITS THERAPEUTIC POTENTIAL IN COMBINATION WITH VENETOCLAX (EHA 2025) - "Additionally, compared with the combination of Venetoclax and R-CHOP, the combination of PM and Venetoclax significantly reduced tumor volume and prolonged survival time (P=0.005) .Drug administration was discontinued on day 35 of treatment, and tumor recurrence was monitored. PM may inhibit MYC expression by regulating histone methylation. In the DHL PDX mouse model, the combination of PM and Venetoclax significantly reduced tumor volume and prolonged survival time. These findings lay the foundation for and provide new insights into the development of more effective therapeutic strategies for DHL."

Combination therapy • IO biomarker • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Oncology • MYC • NSD2

A Phase III Clinical Study of Purinostat Mesylate for Injection in Patients With Diffuse Large B-cell Lymphoma (clinicaltrials.gov) - P3 | N=390 | Not yet recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd

New P3 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

High HDAC I/IIb selective inhibitor purinostat mesylate in relapsed and refractory diffuse large B-cell lymphoma: A single agent phase IIb study. (ASCO 2025) - P2 | "This ongoing study showed 11.2mg/m2 PM in 21-day-cycle achieved remarkable efficacy in r/r DLBCL and acceptable safety profile. The strategy for pivotal study of PM in r/r DLBCL is discussed with NMPA."

P2b data • Anemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Dyslipidemia • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Leukopenia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • TP53

An open, multicenter Phase Ib/IIa study to evaluate the safety, tolerability, pharmacokinetics, and initial efficacy of combination purinostat mesylate for injection in advanced solid tumors (ChiCTR) - P=N/A | N=132 | Recruiting | Sponsor: Sun Yat-sen Memorial Hospital,Sun Yat-sen University/West China Hospital of Sichuan University; Chengdu Zenitar Biomedical Technology Co., Ltd.

New trial • Breast Cancer • Colorectal Cancer • Esophageal Cancer • Head and Neck Cancer • Hepatocellular Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ALK • BRAF • EGFR • ER • FGFR2 • HER-2 • MSI • PD-L1 • PGR • ROS1 • TMB

A Phase IIa Clinical Study of Purinostat Mesylate for Injection in Patients With Peripheral T-Cell Lymphoma and Cutaneous T-Cell Lymphoma (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | Initiation date: Nov 2023 ➔ Apr 2024

Trial initiation date • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Phase Ib/IIa clinical study of purinostat mesylate for injection in combination with To determine the maximum tolerated dose (MTD) and phase IIa recommended dose (RP2D) of pomalidomide mesylate for injection in combination with fixed-dose pomalidomide capsules and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM). capsule and low-dose dexamethasone in patients with... (ChiCTR) - P1/2 | N=123 | Recruiting | Sponsor: West China Hospital of Sichuan University/Peking University People's Hospital; Chengdu Zenitar Biomedical Technology Co., Ltd.

New P1/2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Phase II clinical study of purinostat mesylate for injection in the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (ChiCTR) - P2 | N=120 | Completed | Sponsor: West China Hospital of Sichuan University/Ruijin Hospital of Shanghai Jiao Tong University School of Medicine; Chengdu Zenitar Biomedical Technology C

New P2 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Purinostat Mesylate Combined With Pomalidomide Capsules and Low-dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=144 | Recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | Initiation date: Jun 2024 ➔ Mar 2024

Trial initiation date • Hematological Malignancies • Multiple Myeloma • Oncology

Distribution, metabolism, and excretion of [14C] purinostat mesylate, a novel selective HDAC I/IIb inhibitor, in rats analyzed by high-performance liquid chromatography coupled with LTQ orbitrap mass spectrometry/radioactivity monitoring. (PubMed, J Pharm Biomed Anal) - "Concomitantly, the primary phase II metabolic routes involved acetylation and glucuronic acid conjugation. This study was the first comprehensive PM pharmacokinetic study utilizing [14C] isotope labeling technology."

Journal • Preclinical • B Cell Lymphoma • Cholangiocarcinoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

A Clinical Study of Purinostat Mesylate for Injection in Patients with Solid Tumors (clinicaltrials.gov) - P1/2 | N=120 | Recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

Purinostat Mesylate Combined with Pomalidomide Capsules and Low-dose Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=126 | Recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

Study of Purinostat Mesylate for Injection in the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL) (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd | N=30 ➔ 120 | Trial completion date: May 2025 ➔ Dec 2025 | Trial primary completion date: Oct 2024 ➔ Oct 2025

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

A Phase IIa Clinical Study of Puesta Mesylate for Injection in Patients With T-Cell Lymphoma and Cutaneous T-Cell Lymphoma (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd

New P2 trial • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Puesta Mesylate Combined With Pomalidomide Capsules and Low-dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=126 | Not yet recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd

Combination therapy • New P1/2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

HDAC I/IIb selective inhibitor purinostat mesylate in relapsed and refractory diffuse large B-cell lymphoma: A single agent phase IIa trial. (ASCO 2024) - P2 | "PM monotherapy showed stronger and superior antitumor effects in DE DLBCL and TP53 mutations PDX models than selinexor and R-CHOP. This study further supports the recommended dose 11.2 mg/m 2 PM as the phase 2b for r/r DLBCL. Currently, the phase 2b, open-label, multicenter study has enrolled in 37 sites in China."

Late-breaking abstract • P2a data • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • MYC • TP53

A Clinical Study of Puesta Mesylate for Injection in Patients With Solid Tumors (clinicaltrials.gov) - P1/2 | N=120 | Not yet recruiting | Sponsor: Chengdu Zenitar Biomedical Technology Co., Ltd

New P1/2 trial • Oncology • Solid Tumor

PRECLINICAL AND A PHASE 1 STUDY OF PURINOSTAT MESYLATE, A NOVEL HDAC I/IIB SELECTIVE INHIBITOR, FOR THE TREATMENT OF RELAPSED OR REFRACTORY MULTIPLE MYELOMA (ICML 2023) - "In vivo studies demonstrated that PM alone was better than LBH589, or lenalidomide, bortezomib, and dexamethasone (DXM) triple-drug combinations in treating multiple MM mouse models...In mouse models, this combination treatment is more effective than PM alone and other triple-drug combination therapies (selinexor, pomalidomide, and DXM, and daratumumab, pomalidomide, and DXM) without significant toxicity. PM showed low toxicity and potent efficacy in R/R MM by downregulating key proteins for MM survival and activating immunity in preclinical and phase 1 studies. The triple-drug combination of PM, pomalidomide and DXM has demonstrated strong synergistic anti-tumor activity, laying the foundation for phase 2 clinical trials."

P1 data • Preclinical • Hematological Malignancies • Lymphoma • Oncology • IKZF1 • IKZF3 • IRF4 • MYC

ACTIVITY AND SAFETY OF PRECLINICAL AND A PHASE 1 STUDY OF PURINOSTAT MESYLATE, A UNIQUELY POTENT AND SELECTIVE HDAC I/IIB INHIBITOR IN RELAPSED OR REFRACTORY LYMPHOMA (ICML 2023) - "In vitro, PM had better inhibitory activity against DLBCL cell lines than other HDAC inhibitors, such as chidamide and panobinostat. In several PDX models of DLBCL, the tumors of the PM-treated mice completely regressed, and the activity was significantly superior to selinexor, R-CHOP, and chidamide combined with R-CHOP, with controlled toxicity... PMdemonstrated promising clinical activity and an acceptable safety profile in R/R lymphoma, especially good objective response in patients with DLBCL. Preclinical studies have also confirmed the potent anti-tumor activity of PM in DLBCL."

P1 data • Preclinical • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • MYC