LB-100 / NOMAD Power Solutions, National Institute of Health and Medical Research - LARVOL DELTA

PP2Acα regulates the Hippo-YAP signaling axis to promote cardiac regeneration and alleviate myocardial infarction. (PubMed, J Mol Cell Cardiol) - "Conversely, LB-100 increased YAP phosphorylation without altering its mRNA expression, indicating regulation dependent on phosphatase activity. Collectively, these findings identify PP2Acα as a critical phosphatase that promotes neonatal cardiac regeneration by directly dephosphorylating YAP and activating the Hippo-YAP signaling axis, uncovering a previously unrecognized regulatory mechanism controlling cardiomyocyte proliferation and highlighting a potential therapeutic target for cardiac repair."

Journal • Cardiovascular • Fibrosis • Immunology • Myocardial Infarction • PPP2CA

Development of glutamatergic antipsychotics requires efficient synaptic glutamatergic transmission while preventing NMDA receptor down-regulation and overactivation of extrasynaptic transmission. (PubMed, Br J Pharmacol) - "These results suggest that potentiation of the NMDA receptor is involved in improving negative symptoms, but down-regulating NMDA receptor and enhanced extrasynaptic-NMDA receptor conversely contribute to the aggravation of negative symptoms."

Journal • CNS Disorders • Psychiatry • Schizophrenia • GRIN2A • GRIN2B

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 | Trial completion date: Jul 2026 ➔ Jul 2028 | Trial primary completion date: Jul 2026 ➔ Jul 2028

Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor • CD4

Lactic acid bacterial strains isolated from Attiéké (semolina cassava): bio-tools for combating emergent pathogens in the context of climate change. (PubMed, Front Microbiol) - "All strains were sensitive to amikacin, minocycline, penicillin, erythromycin, and streptomycin...LB strains isolated from Attiéké demonstrated promising biopreservation properties at elevated temperatures. Among these strains, Enterococcus faecalis LB 95 exhibited the strongest antimicrobial activity and safety-associated traits, highlighting its potential as a bioprotective culture in a warming climate."

Journal • Hematological Disorders • Infectious Disease

The Protein Phosphatase Inhibitor LB100 Targets the Mesenchymal Lineage of Pancreatic Ductal Adenocarcinoma. (PubMed, MedComm (2020)) - "Our findings support a reciprocal regulatory relationship between PP2A and CDK9 that connects to the activation of ER stress response factors, including activating transcription factor 4 (ATF4). These results establish PP2A as a druggable target in mesenchymal PDAC cells and reveal a role of LB100-induced transcriptional elongation and splicing, providing a mechanistic basis to guide future therapy development."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ATF4 • CDK9 • PPM1A • PPP2CA • TCF4

Phase I trial of LB-100 plus doxorubicin as first-line of advanced soft tissue sarcomas: A Spanish Sarcoma Group (GEIS) study. (ASCO 2026) - P1/2 | "The RP2D is L1.75 and D 75 based on tolerance and activity, and it deserves to be tested in phase II trials."

Clinical • Metastases • P1 data • Febrile Neutropenia • Hematological Disorders • Neutropenia • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Polystyrene nanoplastics drive neuronal senescence via PP2A-B56γ-targeted p-Ebp1Ser335 dephosphorylation-mediated ribosome biogenesis dysfunction. (PubMed, Free Radic Biol Med) - "This is the first study to identify the PP2A-B56γ-p-Ebp1Ser335-ribosome biogenesis axis as a novel cascade mechanism driving PS-NP-induced neuronal senescence. Our findings offer a targetable strategy to mitigate nanoplastics-associated neurodegeneration."

Journal • CNS Disorders • Cognitive Disorders • ERBB3 • PPP2R5C

Protein phosphatase 2A regulates senescence and immunogenicity in medulloblastoma models. (PubMed, J Clin Invest) - "LNP-siPP2Ac efficiently silenced PP2Ac in vitro and, when delivered locally in vivo, prolonged survival in a CD8+ T cell-dependent manner. Together, these findings identify PP2A as a regulator of immunogenic senescence in MB and support PP2Ac targeting as a therapeutic strategy."

Journal • Brain Cancer • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • CD8 • PPM1A • PPP2CA • TP53

Data Mining for Identification of Targets and Repurposed Drugs to Eliminate Persistent Chronic Myeloid Leukaemia Stem Cells: Targeting RAS/RAF Signalling. (PubMed, Oncol Res) - "Variation in experimental platforms, sample representation, and data integration across public datasets is a recognised study limitation. Nonetheless, LB-100 may provide a novel therapeutic avenue in CML, provided further preclinical functional and clinical validation is performed in patient-derived samples to confirm translational applicability of the findings."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • BRAF • PPM1A • PPP2CA

A microRNA expression signature in infant t(4;11) KMT2A::AFF1+ BCP-ALL uncovers novel therapeutic targets. (PubMed, Hemasphere) - "Importantly, using a drug-repurposing approach, we found that inhibition of CA5B, PPP3CA, and PP2A by acetazolamide, tacrolimus, and LB-100, respectively, showed high toxicity toward KMT2A::AFF1+ leukemic blasts and reduced leukemia burden in vivo...This study highlights how the unique microRNA expression signature of patients with KMT2A::AFF1+ BCP-ALL can be used to uncover novel therapeutic avenues and accelerate drug repurposing. It also indicates potential new drug combinations for less toxic chemotherapy."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Transplantation • AFF1 • KMT2A • MIR125A • MIR194 • MIR99B • PPP2R5C • PPP3CA

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 | Trial completion date: Mar 2026 ➔ Jan 2027 | Trial primary completion date: Mar 2026 ➔ Jan 2027

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

LIXTE Biotechnology Holdings, Inc…announced the presentation of preliminary results for a clinical trial testing the combination of Lixte’s proprietary compound LB100 in combination with Dostarlimab at the 2026 Conference of the Society of Gynecological Cancer, April 10-13, in San Juan, Puerto Rico. (GlobeNewswire) - "At a median follow-up length of 12 months (range 1.4-22), median OS has not been reached. However, OS probability was 0.84 (95%CI 0.64-0.94) at 6 months and 0.69 (95% CI 0.44-0.84) at 12 months. The Disease Control Rate was 40% (8/20, 95% CI 19.1-63.9%)."

P1/2 data • Ovarian Clear Cell Cancer

LIXTE Biotechnology…Positions LB-100 to Expand Effectiveness of Standard Cancer Treatment (Digital Journal) - "'Instead of developing standalone cancer drugs, the company is adopting a different strategy aimed at enhancing the overall effectiveness of existing immunotherapy and chemotherapy regimens through a novel biological target,' reads a recent article. "LIXTE's platform is built on its proprietary LB-100 compound, a one-of-a-kind inhibitor of Protein Phosphatase 2A ('PP2A'). PP2A is a critical enzyme involved in various cellular processes, including cell growth regulation, DNA repair, and modulation of the immune response. Through the selective inhibition of PP2A, LB-100 is strategically designed to make cancer cells more treatable while also boosting the body's immunity to tumors."

Clinical • Solid Tumor

PP2A dysfunction mediated by PPP2R1A deficiency drives cGAS-STING-dependent hyperinflammation in SLE CD14+ monocytes. (PubMed, Clin Rheumatol) - "These findings position PP2A hypofunction as a critical pathogenic driver in SLE and highlight the therapeutic potential of targeting this phosphatase. The restoration of PP2A activity mitigates dysregulated innate immune responses, presenting a promising strategy for immunomodulation in SLE. Key Points • The downregulation of PPP2R1A expression and the concomitant reduction in PP2A phosphatase activity constitute a pathological mechanism in SLE monocytes. • PP2A agonist FTY720 reverses cGAS-STING pathway activation in SLE monocytes."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD14 • CGAS • IFNA1 • IL1B • IL6 • ISG15 • PPM1A • PPM1B • PPP2CA • PPP2R1A • STING

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