MRG004A / Lepu Med - LARVOL DELTA

Tissue factor promotes TREX1 protein stability to evade cGAS-STING innate immune response in pancreatic ductal adenocarcinoma. (PubMed, Oncogene) - "While a novel TF-ADC (MRG004A) demonstrated efficacy for PDAC and TNBC in a Phase I/II trial [Ref...Thus, TF-inhibition reshapes an "immune hot" tumor environment. TF-targeted therapy warrants clinical investigation as a single agent or in combination with immunotherapy for treating TF-positive PDAC and TNBC."

IO biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Triple Negative Breast Cancer • CXCL9 • STING • TREX1

Lepu Biopharma's TF-targeted ADC receives FDA fast track designation for the treatment of pancreatic cancer (bydrug.pharmcube.com) - "On March 11, Lepu Biopharma announced that its drug candidate MRG004A (a novel specific antibody-drug conjugate targeting tissue factor) was granted Fast Track Designation (FTD) by the U.S. FDA for the treatment of pancreatic cancer."

Fast track • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

OneOncology Highlights Research Contributions at 2024 ASCO Annual Meeting (PRNewswire) - "OneOncology, the fastest growing platform for independent oncology practices, is pleased to highlight the groundbreaking research efforts of investigators at OneOncology partner practices through 13 oral and poster presentations at the 2024 ASCO Annual Meeting May 31-June 4, 2024."

P2 data • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

2024ASCO｜Memorial Sloan Kettering Cancer Center (MSK)'s Prof. Wungki Park Unveils Precision Targeting of TF in Pancreatic Cancer, Signaling ADC Drug Innovations (PRNewswire) - P1/2 | N=108 | NCT03941574 | Sponsor: Shanghai Henlius Biotech | "Significant anti-tumor activity of MRG004A was observed in pts with PC. Among 12 evaluable pts with PC in the 2.0mg/kg cohort, who have received median 3 lines of prior therapy, there were 4 PR and 6 SD. ORR was 33.3% (4/12) and DCR was 83.3% (10/12). Among them, 5 pts with PC of TF expression ≥50% and 3+ intensity and ≤2 prior lines of therapy received MRG004A at 2mg/kg. 4 of 5 TF-overexpressed PC achieved PR and 1 SD. Also, MRG004A showed efficacy in other cancers. In 4 pts with heavily-treated triple-negative breast cancer (TNBC), ORR and DCR were 25% (1/4) and 50% (2/4), respectively. In 2 pts with cervical cancer with four prior therapy lines, 1 PR and 1 SD."

P2 data • Breast Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Phase I/II first-in-human study to evaluate the safety and efficacy of tissue factor-ADC MRG004A in patients with solid tumors. (ASCO 2024) - P2 | "MRG004A demonstrated a manageable toxicity and a striking antitumor activity across multiple tumor types with high TF expression in heavily pretreated setting, including pancreatic cancers. These encouraging findings warrant further evaluation of MRG004A, particularly in the context of TF-overexpressed solid tumors."

Clinical • P1/2 data • Anemia • Breast Cancer • Cardiovascular • Cervical Cancer • Conjunctivitis • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Ocular Infections • Ocular Inflammation • Oncology • Ophthalmology • Pancreatic Cancer • Solid Tumor • Steven-Johnson Syndrome • Thrombosis • Triple Negative Breast Cancer

Lepu Biopharma Co, Ltd. Announces Results of Three Clinical Trials Presented at 2024 Asco Meeting Announces Presentation of Three Clinical Trial Results at 2024 Asco Annual Meeting [Google translation] (Zonebourse) - P1/2 | N= 181 | NCT04843709 | Sponsor: Shanghai Miracogen Inc. | "The Company will orally present preliminary safety and efficacy results from the Phase I/II MRG004A study in patients with advanced solid tumors at the 2024 ASCO Annual Meeting, which are summarized as follows: 63 Patients were recruited, including 43 patients in the dose escalation phase (across 8 dose levels 0.3-2.6mg/kg) and 20 patients in the dose expansion phase (15 patients at 2, 0mg/kg and 5 patients at 2.4mg/kg). Significant antitumor activity of MRG004A was observed in patients with pancreatic cancer (PC). Among the 12 evaluable pancreatic cancer patients in the 2.0 mg/kg cohort, who had previously received three lines of therapy, there were 4 partial responses (PR) and 6 cases of stable disease (MS). ), the objective response rate (ORR) was therefore 33.3% (4/12) and the disease control rate (DCR) was 83.3% (10/12)."

P1/2 data • Oncology • Solid Tumor

Lepu Biotech (02157.HK) MRG004A received FDA orphan drug designation for the treatment of pancreatic cancer [Google translation] (Yahoo Sports) - "Lepu Biologics (02157.HK) announced that its drug candidate MRG004A, used to treat pancreatic cancer, has recently been granted orphan drug designation by the U.S. Food and Drug Administration (FDA)."

Orphan drug • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Tissue factor overexpression in triple-negative breast cancer promotes immune evasion by impeding T-cell infiltration and effector function. (PubMed, Cancer Lett) - P1/2 | "Tissue factor (TF) is the target of the FDA-approved ADC Tivdak. HuSC1-39 is the parent antibody of MRG004A, a clinical stage TF-ADC (NCT04843709)...Treatment of TF-high TNBC cells with anti-TF or TF-knockout all stimulated CXCL9/10/11 production, promoted T cell migration and effector function. Thus, we have identified a new mechanism of TF in TNBC tumor progression and therapy resistance."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CXCL9 • TGFB1

Generation of DAR1 Antibody-Drug Conjugates for Ultrapotent Payloads Using Tailored GlycoConnect Technology. (PubMed, Bioconjug Chem) - "GlycoConnect technology can be readily adapted to provide different drug-to-antibody ratios (DARs) and is currently also evaluated in various clinical programs, including ADCT-601 (DAR2), MRG004a (DAR4), and XMT-1660 (DAR6). In a follow-up experiment, HCC-1954 tumor spheroids were treated with either an AlexaFluor647-labeled DAR1 or DAR2 PBD-based ADC to study the effect on tumor penetration. Significant improvement of tumor spheroid penetration was observed for the DAR1 ADC compared to the DAR2 ADC at an equal payload dose, underlining the potential of a lower DAR for ADCs bearing ultrapotent payloads."

Journal • Oncology

Third ADC with Synaffix’s Technology Enters Clinical Development (PRNewswire) - “Synaffix B.V….announces that its partner Shanghai Miracogen has commenced a Phase I trial in the US with MRG004A, an ADC designed to treat solid tumors. This is the 3rd ADC built with GlycoConnect™ ADC technology to enter the clinic.”

Trial status • Oncology • Solid Tumor

[VIRTUAL] MRG004A, a Tissue Factor Targeted ADC Using GlycoConnectTM Technology: Process Optimization & Impurity Controls (ADC-USA 2021) - "GlycoConnect is a site-specific conjugation technology which offers improved linkage stability and homogeneity of payload distribution; Examine how Miracogen has adopted the GlycoConnect technology and optimized it for the production of MRG004A ADC with high purity and yield, leading to a successful IND approval in the US."

[VIRTUAL] MRG004A, a Tissue Factor Targeted ADC Using GlycoConnectTM Technology: Process Optimization & Impurity Controls (ADC-USA 2021) - "GlycoConnect is a site-specific conjugation technology which offers improved linkage stability and homogeneity of payload distribution; Examine how Miracogen has adopted the GlycoConnect technology and optimized it for the production of MRG004A ADC with high purity and yield, leading to a successful IND approval in the US."

A Study of MRG004A in Patients With Tissue Factor Positive Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2; N=181; Recruiting; Sponsor: Shanghai Miracogen Inc.; Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor

A Study of MRG004A in Patients With Tissue Factor Positive Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1/2; N=181; Not yet recruiting; Sponsor: Shanghai Miracogen Inc.

New P1/2 trial • Oncology • Solid Tumor