minnelide / Minneamrita Therap - LARVOL DELTA

Phase II study of Minnelide for patients with adenosquamous carcinoma of the pancreas (ASCP) (AACR 2025) - "Abstract is embargoed at this time."

Clinical • P2 data • Oncology • Pancreatic Cancer

Minnelide as a potential treatment strategy for CIC::DUX4 sarcoma (AACR 2025) - "Therapeutic advancements for CIC::DUX4 sarcoma have been limited to date, and there are currently no clinical trials available for CDS patients. Our findings demonstrate that Minnelide effectively reduces CDS cell viability and xenograft growth, while downregulating key CIC::DUX4 target genes. Given the role of CIC::DUX4 as a potent transcriptional activator, Minnelide's disruption of this activation may offer a promising therapeutic approach for CDS."

Ewing Sarcoma • Gastric Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • DUSP6 • DUX4 • ETV1

Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP) (clinicaltrials.gov) - P2 | N=15 | Completed | Sponsor: National Cancer Institute (NCI) | Trial completion date: Sep 2026 ➔ Mar 2025 | Active, not recruiting ➔ Completed | Trial primary completion date: Sep 2026 ➔ Mar 2025

Trial completion • Trial completion date • Trial primary completion date • Hepatology • Oncology • Pancreatic Cancer

Anti-SARS-CoV-2 and anticancer properties of triptolide and its derived carbonized nanomaterials. (PubMed, Cancer Lett) - "Finally, we showed that triptolide-derived carbonized materials excelled in their anticancer properties compared to triptolide and Minnelide, a water-soluble analog of triptolide. Together, our results provide a rationale for the potential development of triptolide-carbonized derivatives as a promising antiviral candidate for the current pandemic and future outbreaks, as well as anticancer agents."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Ophthalmology • Respiratory Diseases

NCI-2021-12558: Minnelide and Osimertinib for the Treatment of Advanced EGFR Mutated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Oct 2026 ➔ Oct 2027 | Trial primary completion date: Oct 2026 ➔ Oct 2027

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP) (clinicaltrials.gov) - P2 | N=15 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=11 ➔ 15

Enrollment change • Hepatology • Oncology • Pancreatic Cancer

Superenhancer Inhibitor Minnelide in Advanced Refractory Adenosquamous Carcinoma of the Pancreas (ASCP) (clinicaltrials.gov) - P2 | N=11 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting | N=55 ➔ 11

Enrollment change • Enrollment closed • Hepatology • Oncology • Pancreatic Cancer

Super-enhancers and efficacy of triptolide in small cell carcinoma of the ovary hypercalcemic type. (PubMed, iScience) - "In patient-derived xenograft models, triptolide and prodrug minnelide effectively inhibit tumor growth. These results reveal unique features of super-enhancers in SCCOHT, which may be one mechanism through which triptolide has high activity in these tumors."

Journal • Oncology • Ovarian Cancer • Solid Tumor • SALL4 • SMARCA2 • SMARCA4

Pharmacological, computational, and mechanistic insights into triptolide's role in targeting drug-resistant cancers. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Early-phase clinical trials of Minnelide, a water-soluble derivative of triptolide, are promising, but additional work is necessary to optimize dosing, delivery, and safety. This comprehensive analysis demonstrates that triptolide may constitute a repurposed precision medicine tool to overcome tolerance in cancer therapy."

Journal • Review • Breast Cancer • Lung Cancer • Oncology • Ophthalmology • Pancreatic Cancer • Solid Tumor • CDC37 • HSP90AA1 • PARP1

INVESTIGATING THE THERAPEUTIC POTENTIAL OF TRIPTOLIDE PRODRUG, MINNELIDE, AS A TREATMENT ALTERNATIVE FOR CIC-DUX4 SARCOMA (CTOS 2024) - "To date, therapeutic advancements for CIC::DUX4 sarcoma have been limited. Utilizing a high-throughput approach, we screened the effects of 160 epigenetic compounds on human CDS cells and identified triptolide as a top candidate. Our studies demonstrate that treatment with the Triptolide prodrug, Minnelide, significantly reduces CDS cell viability and CDS xenograft growth."

Breast Cancer • Ewing Sarcoma • Gastric Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • CHEK2 • DUSP6 • DUX4 • ETV1 • EWSR1

The Yin and Yang of the Natural Product Triptolide and Its Interactions with XPB, an Essential Protein for Gene Expression and DNA Repair. (PubMed, Genes (Basel)) - "Recent developments, including triptolide prodrugs such as Minnelide and derivatives like glutriptolides, aim to enhance its pharmacokinetic properties and reduce toxicity. This review critically examines triptolide's chemical structure, therapeutic applications, toxicological profile, and molecular interactions with XPB and other protein targets to inform future strategies that maximize therapeutic efficacy while minimizing adverse effects."

Journal • Review • Cardiovascular • Hepatology • Immunology • Oncology • Ophthalmology

Dual activity of Minnelide chemosensitize basal/triple negative breast cancer stem cells and reprograms immunosuppressive tumor microenvironment. (PubMed, Sci Rep) - "We provide evidence that Minnelide targets tumor intrinsic pathways and reprograms the immune suppressive microenvironment. Our studies also suggest that Minnelide in combination with cyclophosphamide may lead to durable responses in patients with basal/TNBC subtype warranting its clinical investigation."

Biomarker • Cancer stem • Journal • Tumor microenvironment • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Water-soluble and predictable-release triptolide prodrugs block bleomycin-induced pulmonary fibrosis in mice. (PubMed, Eur J Med Chem) - "Two soluble TP prodrugs (PG490-88 and Minnelide) have entered clinical research. In vivo, TP-DEA2 transformed into TP, effectively inhibiting fibrosis in the bleomycin group without observed toxicity. Importantly, positive outcomes when administering TP-DEA2 at a later stage post-bleomycin exposure suggest its potential role in treating IPF."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • ADAM10 • TGFB1

NCI-2021-12558: Minnelide and Osimertinib for the Treatment of Advanced EGFR Mutated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: City of Hope Medical Center | Phase classification: P1b ➔ P1 | Trial completion date: Dec 2024 ➔ Oct 2026 | Trial primary completion date: Dec 2024 ➔ Oct 2026

Combination therapy • Metastases • Phase classification • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Research Progress of Triptolide Against Fibrosis. (PubMed, Drug Des Devel Ther) - "Triptolide and its derivatives (Omtriptolide, Minnelide, (5R)-5-hydroxytriptolide) have been proven to have a variety of pharmacological effects. Under pathological conditions, a toxic dose of TPL has a protective effect on organs. The emergence of TPL derivatives (especially Minnelide) and NPs drug delivery systems promotes the anti-fibrosis effect of TPL and reduces its toxicity, which may be the main direction of anti-fibrosis research in the future."

Journal • Review • Fibrosis • Immunology • Inflammation • Ophthalmology

Triptolide and its pro-drug Minnelide target high-risk MYC amplified medulloblastoma in preclinical models. (PubMed, J Clin Invest) - "Importantly, Minnelide acted on MYC to reduce tumor growth and leptomeningeal spread, which resulted in improved survival of G3 MB animal models. Moreover, Minnelide improved the efficacy of adjuvant chemotherapy, further highlighting its potential for the treatment of MYC-driven G3 MB patients."

Journal • Preclinical • Brain Cancer • Colorectal Cancer • Medulloblastoma • Oncology • Solid Tumor • MYC

The safety and efficacy outcomes of Minnelide given alone or in combination with paclitaxel in advanced gastric cancer: a Phase I trial. (PubMed, Cancer Lett) - P1 | "The combination of Minnelide plus paclitaxel as salvage treatment in AGC patients showed meaningful clinical activity with a manageable safety profile. Based on these encouraging results, a phase II study is being initiated to test the effectiveness of the combination regimen in patients with advanced gastric cancer."

Combination therapy • Journal • Metastases • P1 data • Gastric Cancer • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Pain • Solid Tumor

A phase 1 study to evaluate the safety and preliminary efficacy of minnelide given alone or in combination with paclitaxel in advanced gastric cancer. (ASCO 2024) - P1 | "The combination of Minnelide plus paclitaxel as salvage treatment in AGC patients showed meaningful clinical activity with a manageable safety profile. Based on this Phase I experience a Phase II will be initiated in AGC patients."

Clinical • Combination therapy • Metastases • P1 data • Gastric Cancer • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Neutropenia • Oncology • Pain • Pancreatic Cancer • Solid Tumor

Minnelide exhibits antileukemic activity by targeting the Ars2/miR-190a-3p axis. (PubMed, Phytomedicine) - "Our findings demonstrate that targeting Ars2/miR-190a-3p signaling using minnelide could represent a novel chemotherapeutic strategy for AL treatment and support the evaluation of minnelide for the treatment of AL in clinical trials."

Journal • Hematological Malignancies • Leukemia • Oncology

Phase II open label trial of Minnelide™ in patients with chemotherapy refractory metastatic pancreatic cancer (AACR 2024) - "The study identified a tolerable drug dose and evidence of activity in a highly chemotherapy-refractory population which provides encouraging proof for the principle of targeting TFIIH in human PDAC."

Clinical • Metastases • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CA 19-9 • MYC

Designing targeted approaches for recurrent medulloblastoma (AACR 2024) - "Additionally, to further support the translational relevance of our data, Minnelide increased the efficacy of adjuvant therapeutics used in the clinical management of MB. Our findings not only highlight the potential for repurposing Minnelide to treat children with recurrent MB, but also the potential of our research approaches aimed at identifying novel therapeutics for relapsed cancers."

Brain Cancer • Medulloblastoma • Oncology • Solid Tumor

Minnelide suppresses GVHD and enhances survival while maintaining GVT responses. (PubMed, JCI Insight) - "Here, we tested the effectiveness of Minnelide in preventing acute GVHD as compared to cyclophosphamide post-aHSCT (PTCy). Importantly, Minnelide GVHD prevention was accompanied by preservation of graft-versus-tumor (GVT) activity. As Minnelide possesses anti-AML activity and is being applied in clinical trials, together with the present findings, we conclude that this compound might provide a new approach for AML patients undergoing aHSCT."

Journal • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Gastrointestinal Cancer • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Oncology • Transplantation

Therapeutic Targeting of Hypoxia-Inducible Factors in Cancer. (PubMed, Int J Mol Sci) - "Findings showcase the efficacy of agents like EZN-2968, Minnelide, and Acriflavine in modulating HIF-1α protein synthesis and destabilizing HIF-1, providing preliminary proof of HIF-1α mRNA modulation and antitumor activity. However, challenges, including toxicity, necessitate continued exploration and development, as exemplified by ongoing clinical trials. This article concludes by emphasizing the potential of targeted HIF therapies in disrupting cancer-related signaling pathways."

Journal • Review • Oncology • Von Hippel-Lindau Syndrome • HIF1A

Mechanisms of cancer cell death induction by triptolide: A comprehensive overview. (PubMed, Heliyon) - "In addition, several triptolide moieties, including minnelide and LLDT8, have progressed in investigations on humans for the treatment of cancer. Targeted strategies, such as triptolide conjugation with ligands or triptolide loaded nano-carriers, are efficient techniques to confront toxicities associated with triptolide. We expect and anticipate that advances in near future, regarding combination therapies of triptolide, might be beneficial against cancerous cells."

Journal • Review • Genetic Disorders • Oncology • Ophthalmology • ADAM10 • CDKN1A • ERCC3

First-in-Human Phase I Study of Minnelide in Patients With Advanced Gastrointestinal Cancers: Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity. (PubMed, Oncologist) - "This first-in-human, phase I clinical study identified a dose and schedule of Minnelide in patients with refractory GI cancers. The primary toxicity experienced was hematologic. Evidence of efficacy of Minnelide treatment in this group of patients was observed. The DCR ranged from ~2 to 6 months in 14/28 (50%) of evaluable patients. Studies in monotherapy and combination treatments are underway."

Journal • Metastases • P1 data • PK/PD data • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Hepatology • Neutropenia • Oncology • Pancreatic Cancer • Solid Tumor