LB-100 / Lixte Biotech, National Institute of Health and Medical Research - LARVOL DELTA

On the history, synthesis, and medicinal use of cantharidin, LB-100, and their analogs. (PubMed, RSC Med Chem) - "From its notorious use as the aphrodisiac "Spanish fly" to its modern FDA approval as YCANTH™ for molluscum contagiosum, this small yet complex molecule has inspired both infamy and innovation...Despite inconsistencies in the literature, ranging from pharmacological selectivity to reproducibility of assay data, recent advances in structural biology, computational modeling, and medicinal chemistry have opened new opportunities to refine potency, selectivity, and stability of cantharidin-derived therapeutic molecules. This review critically examines the historical, chemical, and biomedical landscape of cantharidin and its derivatives, clarifies longstanding ambiguities, and highlights future opportunities to develop phosphatase-targeting therapies for cancer, autoimmune, and inflammatory disease."

Journal • Review • Dermatology • Immunology • Oncology

Safety and Efficacy of Targeting PP2A in Ovarian Clear Cell Carcinoma Using Dostarlimab and LB-100 (clinicaltrials.gov) - P1/2 | N=21 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Jan 2026 ➔ Oct 2027 | Trial primary completion date: Jan 2026 ➔ Oct 2027

Platinum resistant • Trial completion date • Trial primary completion date • Clear Cell Carcinoma • Oncology • Ovarian Cancer • CD4

LIXTE and its Collaborators Expand Clear Cell Ovarian Cancer Trial (GlobeNewswire) - "A second trial site was added earlier this year at the Robert H. Lurie Comprehensive Cancer Center (Lurie Cancer Center) of Northwestern University, led by Emily M. Hinchcliff, MD, MPH...MD Anderson and Northwestern Medical Center plan to double the number of enrollments in the trial to 42 patients, after successfully attaining its initial target of 21 patients earlier this year. The Company also announced that it expects data to be presented from the trial on the initial 21 patients in the first half of 2026."

P1/2 data • Trial status • Ovarian Clear Cell Cancer

PP2A Promotes Epithelial-Mesenchymal Transition in Chronic Rhinosinusitis with Nasal Polyps via Wnt/β-Catenin Pathway: A Novel Insight. (PubMed, J Asthma Allergy) - "The rhWNT3A-induced EMT cell model using BEAS-2B cell line was established in vitro and treated with either LB-100 or the PP2A agonist DT-061...PP2A exerts a positive regulatory effect on the modulation of Wnt signaling in CRSwNP. Targeting PP2A might represent a viable therapeutic option for treating CRSwNP."

Journal • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Inflammation • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis • WNT3A

LIXTE’s Phase 1B/2 study evaluates LB-100 in combination with doxorubicin, the current standard of care, in patients with advanced STS. (The Manila Times) - "Status: Dose escalation completed; Upcoming Milestone: Safety report Q4 2025"

P1/2 data • Soft Tissue Sarcoma

A Phase 0 Window of Opportunity Trial of LB100, a Protein Phosphatase 2A Inhibitor, in Patients with Recurrent Gliomas. (PubMed, medRxiv) - "The IC50 of PP2A is 0.2-0.4 uM; showing drug penetration was inadequate. In this first PK analysis of LB100 in human gliomas there was poor penetration of LB100 into glial tumors."

Journal • Astrocytoma • Brain Cancer • Glioblastoma • Glioma • Oligodendroglioma • Oncology • Solid Tumor

Synergistic Efficacy of Chidamide and LB100 in Sézary Syndrome via TNC Downregulation and PI3K/AKT/mTOR Dephosphorylation. (PubMed, Cancer Sci) - "This study also preliminarily validated the effect of the combination of the two drugs on other subtypes of CTCL. Overall, these findings provide potential new therapeutic strategies for CTCL (especially SS), although further clinical evaluation is required to validate these results."

Journal • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • ANXA5

New Clinical Findings Published in Scientific Journal Nature Validate LIXTE’s Ongoing Ovarian and Colorectal Cancer Trials (GlobeNewswire) - "LIXTE Biotechnology Holdings, Inc...announced that the medical journal Nature has published findings by a team of physician-scientists that validate LIXTE’s ongoing clinical trials with its proprietary compound LB100 for Ovarian and Colorectal cancers....The study showed that patients having tumors with inactivating mutations in PPP2R1A - the major scaffold subunit of protein phosphatase 2A (PP2A) - had significantly better overall survival, compared with patients who did not have this mutation in their tumors."

Clinical data • Colorectal Cancer • Ovarian Cancer

PTPA Governs Stress-Responsive Differentiation and Metabolic Homeostasis in Toxoplasma gondii. (PubMed, Cells) - "TgPTPA emerges as a linchpin coordinating PP2A activity, metabolic flux, and lifecycle transitions. Its dual roles in acute virulence and chronic persistence, combined with LB-100's efficacy, position the PTPA-PP2A axis as a promising target for antitoxoplasmosis strategies."

Journal • Metabolic Disorders • PTPA

A potential therapeutic target at Connexin 43 serine phosphorylation against ischaemia/reperfusion arrhythmia. (PubMed, Br J Pharmacol) - "Cx43-S282 dephosphorylation can trigger reperfusion arrhythmias by impairing gap junction intercellular communication while favouring hemichannel permeability. An up-regulated intramolecular interaction between L2 and Cx43-carboxyl-terminus is associated with this arrhythmogenicity, providing a novel and targetable mechanism to preserve the heart from ischaemia/reperfusion arrhythmias."

Journal • Cardiovascular • Reperfusion Injury • Ventricular Tachycardia

Retraction: Inhibition of protein phosphatase 2A with a small molecule LB100 radiosensitizes nasopharyngeal carcinoma xenografts by inducing mitotic catastrophe and blocking DNA damage repair. (PubMed, Oncotarget) - No abstract available

Journal • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

A PP2A-mtATR-tBid axis links DNA damage-induced CIP2A degradation to apoptotic dormancy and therapeutic resistance in PDAC. (PubMed, Cancer Lett) - "We found that in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) cells, CIP2A degradation via ubiquitination enhanced PP2A phosphatase activity, leading to the dephosphorylation of ATR at Ser428 in the cytoplasm...These findings reveal a novel mechanism of resistance to DNA damage-based cancer drugs and introduce a new action mechanism of LB-100, which works through mtATR-tBid complex-mediated apoptotic dormancy triggered by CIP2A degradation-mediated PP2A activation. Disrupting the mtATR-tBid complex may represent a promising strategy to restore or sensitize resistant cancer cells to apoptosis."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Targeted Protein Degradation • CIP2A

LIXTE Launches New Study to Determine if Certain Pre-Cancerous Cells Found in an Aging Population Can Be Eliminated by LB-100 (GlobeNewswire) - "LIXTE Biotechnology Holdings...announced it will conduct a new pre-clinical study in collaboration with Netherlands Cancer Institute (NKI) to test whether 'initiated' cells that carry mutations found in cancer cells can be eliminated by treatment with LIXTE’s proprietary compound LB-100....Recent data from LIXTE’s ongoing clinical collaboration with NKI shows that LB-100 activates oncogenic signaling and that this is detrimental to cancer cells. The new study in animal models will investigate whether 'initiated' cells, harboring a mutant RAS oncogene, can be eliminated with LB-100. If successful, LB-100 could have a significant role in the elimination of initiated cells in aged individuals and could reduce the risk of developing a wide range of cancers as a person ages."

Preclinical • Oncology

LIXTE Biotechnology Provides Update On Progress with Proprietary Compound, LB-100, to Treat Ovarian and Colorectal Cancer (GlobeNewswire) - "Further bolstering of LIXTE’s intellectual property portfolio, with receipt of a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for U.S. Patent application number 16/467,721...for combining the Company’s LB-100 compound with various innovative cancer immunotherapies."

Patent • Colorectal Cancer • Ovarian Cancer

Enhancer: Phase I/II of LB-100 Plus Doxorubicin Vs. Doxorubicin Alone in First Line of Advanced Soft Tissue Sarcomas (clinicaltrials.gov) - P1/2 | N=152 | Active, not recruiting | Sponsor: Grupo Espanol de Investigacion en Sarcomas | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

NLRP4 unlocks an NK/macrophages-centered ecosystem to suppress non-small cell lung cancer. (PubMed, Biomark Res) - "Altogether, we delineated NLRP4's unexplored facets and discovered an NLRP4-driven anti-tumor ecosystem composed of TIGIT+TNFA+ NK and iNOS+ M1. Finally, targeting PP2A by its inhibitor successfully mimicked the anti-tumor capacity of the overexpression of NLRP4."

IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CXCR2 • LRP4 • TIGIT • TNFA

New Findings Show how LIXTE’s Lead Clinical Compound, LB-100, is Metabolized to its Active Form (GlobeNewswire) - "As published in BioXriv, scientists at the Netherlands Cancer Institute have discovered an enzyme that mediates the conversion of LB-100 into the active metabolite endothall. Accordingly, this protein represents a potential biomarker to identify patients who are most likely to respond to LB-100. The biomarker discovery study was performed in the laboratories of Professor Rene Bernards, group leader at the Netherlands Cancer Institute and LIXTE board member....As published in the International Journal of Pharmaceutics, Dr. Hans Rollema and colleagues, medicinal chemists and biochemists at BioPharmaWorks LLC, a consultant to LIXTE, studied how LB-100 can spontaneously convert into the active metabolite endothall by hydrolysis. Their data indicate that this conversion is slow under physiological conditions. The enzymatic conversion of LB-100 identified by the Bernards laboratory expedites the activation of LB-100 inside the cell."

Preclinical • Colorectal Cancer • Oncology • Ovarian Cancer

LB-100 Enhances Drugs Efficacy Through Inhibition of P-Glycoprotein Expression in Multidrug-Resistant Glioblastoma and Non-Small Cell Lung Carcinoma Cellular Models. (PubMed, Pharmaceutics) - "Background/Objectives: This study explores the potential of LB-100 (a protein phosphatase 2A-PP2A inhibitor) combined with adavosertib (a WEE1 kinase inhibitor) and doxorubicin (DOX), to overcome multidrug resistance (MDR) in cancer cells and enhance treatment efficacy...Additionally, LB-100 reduces P-gp expression in MDR glioblastoma and NSCLCs, sensitizing them to DOX and increasing its accumulation. LB-100 enhances the effectiveness of drugs against MDR cancer cells, presenting a promising strategy to overcome drug resistance in glioblastoma and NSCLCs through P-gp modulation."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

LIXTE Adds Northwestern University’s Lurie Cancer Center as Second Site in Ongoing Clinical Trial for Ovarian Clear Cell Cancer (GlobeNewswire) - "LIXTE Biotechnology Holdings...announced it has added the Robert H. Lurie Comprehensive Cancer Center (Lurie Cancer Center) of Northwestern University as a second site in a clinical trial combining the Company’s proprietary compound LB-100 with GSK’s Dostarlimab to treat ovarian clear cell cancer....Emily M. Hinchcliff, MD, MPH, will lead the clinical trial at Lurie Cancer Center, a renown Chicago-based National Cancer Institute-designated Comprehensive Cancer Center, which is located at Northwestern Memorial Hospital’s downtown medical campus. Patient recruitment is underway, and the first patient has been dosed."

Trial status • Ovarian Clear Cell Cancer

In vitro studies on stability and phosphatase activity of the anticancer agent LB-100 and its active hydrolysis product endothall. (PubMed, Int J Pharm) - "Endothall concentrations present in LB-100 assays can account for the observed PP2A inhibition, indicating that inhibitory activity measured in LB-100 assays is mainly due to endothall. These data suggest that LB-100 is a prodrug that acts as a PP2A inhibitor through hydrolysis to endothall, which is ultimately responsible for PP2A inhibition and LB-100's pharmacological activity."

Journal • Preclinical • Oncology

LB-100, Carboplatin, Etoposide, and Atezolizumab for the Treatment of Untreated Extensive-Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=3 | Active, not recruiting | Sponsor: City of Hope Medical Center | Recruiting ➔ Active, not recruiting | N=21 ➔ 3

Combination therapy • Enrollment change • Enrollment closed • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

PTGER4 signaling regulates class IIa HDAC function and SPINK4 mRNA levels in rectal epithelial cells. (PubMed, Cell Commun Signal) - "These findings suggest a mechanism during mucosal injury whereby MSC production of PGE2 increases HDAC4, 5, and 7 activities in epithelial cells by upregulating PTGER4 signaling, ultimately increasing SPINK4 mRNA levels and extracellular release of SPINK4."

Journal • Crohn's disease • Gastroenterology • Immunology • Inflammatory Bowel Disease • HDAC4 • PTGER4

LIXTE Receives U.S. Patent Issue Notification for Immune Oncology (GlobeNewswire) - "LIXTE Biotechnology Holdings, Inc...announced it has received a Notice of Allowance from the United States Patent and Trademark Office (USPTO) for U.S. Patent application number 16/467,721, titled, 'Oxabicycloheptanes for Modulation of Immune Response,' for combining the Company’s LB-100 compound with various innovative cancer immunotherapies....The new patent award follows the signing of an exclusive patent license agreement earlier this year between LIXTE and the National Institute of Neurological Disorders and Stroke (NINDS) and National Cancer Institute (NCI), each a component of the National Institute of Health (NIH)."

Patent • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

CoLBAt: LB-100 (PP2A Inhibitor) and Atezolizumab (PD-L1 Inhibitor) in Metastatic Colorectal Cancer Patients (clinicaltrials.gov) - P1 | N=37 | Recruiting | Sponsor: The Netherlands Cancer Institute | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4

The cellular protein phosphatase 2A is a crucial host factor for Marburg virus transcription. (PubMed, J Virol) - "The regulatory subunit B56 of PP2A facilitates VP30 dephosphorylation, and hence transcription activation, via binding to NP. Our results, together with previous data, reveal a conserved mechanism of filovirus VP30 dephosphorylation by host factor PP2A at the NP interface and provide novel insights into potential pan-filovirus therapies."

Journal • Ebola Virus Disease • Infectious Disease