Kinaction (masitinib) / AB Science - LARVOL DELTA

AB Science announces new publication on Medrxiv highlighting clinical benefit with masitinib in Amyotrophic Lateral Sclerosis patients prior any complete loss of function (GlobeNewswire) - "A significant improvement in functional decline was measured by the ALSFRS-R score, with a 4.04-point difference favoring masitinib over placebo (p=0.0065), surpassing the 3.39-point difference observed in the AB10015 trial population; A significant benefit in CAFS with a relative change versus placebo of +20.2% (p=0.029), above the +13.8% relative benefit observed in the AB10015 trial population. CAFS is the preferred endpoint for the FDA; The median progression-free survival (PFS) was extended by 9 months (p=0.0057), and the median overall survival (OS) increased by 12 months (p=0.0192) compared to the placebo, and both improvements were more pronounced than those in the primary analysis....Safety outcomes improved in this subgroup, with a reduction in serious adverse events from 27.6% to 22.6% in masitinib-treated patients."

P3 data • Amyotrophic Lateral Sclerosis

Masitinib in Patients With Mild Alzheimer's Disease (clinicaltrials.gov) - P3 | N=600 | Not yet recruiting | Sponsor: AB Science | Trial completion date: Dec 2026 ➔ Dec 2029 | Trial primary completion date: Dec 2026 ➔ Dec 2028

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders

Masitinib in Combination With Standard of Care in the Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P3 | N=412 | Not yet recruiting | Sponsor: AB Science

New P3 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients (clinicaltrials.gov) - P3 | N=495 | Recruiting | Sponsor: AB Science | Trial completion date: Dec 2023 ➔ Dec 2027 | Trial primary completion date: Dec 2023 ➔ Dec 2027

Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

MASIMS: Masitinib in the Treatment of Patients With Primary Progressive or Non-active Secondary Progressive Multiple Sclerosis (clinicaltrials.gov) - P3 | N=800 | Active, not recruiting | Sponsor: AB Science | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Dec 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2028

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor After Imatinib Resistance. (PubMed, Pharmaceutics) - "Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents-such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib-have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs...Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options,..."

Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

Baseline sample characteristics for the BackInAction pragmatic trial of acupuncture for chronic low back pain in older adults. (PubMed, Contemp Clin Trials) - P=N/A | "Findings suggest that FQHC populations have higher-than-average social and clinical risks, illustrating the complexity of delivering treatment for cLBP and the urgency to ensure such clinical environments are included in trials."

Journal • Back Pain • Infectious Disease • Lumbar Back Pain • Musculoskeletal Pain • Novel Coronavirus Disease • Pain

Understanding the degradation behavior of masitinib by Stress testing, UHPLC, HRMS, NMR, APCI-MS, DFT and prediction of toxicity using in silico tools. (PubMed, J Pharm Sci) - "DP6, a mutagenic DP, was further evaluated for genotoxicity using molecular docking. Considering masitinib's clinical relevance, this study highlights the importance of correlating degradation products with known human metabolites and assessing their potential toxicological impact in long-term therapeutic use and environmental exposure."

Journal • Oncology

In this subgroup, defined as patients before complete loss of function and with normal disease progression, which corresponds to the optimal population of best responders to masitinib that is targeted in study AB23005 (AB Science Press Release) - P2/3 | N=394 | NCT02588677 | Sponsor: AB Science | "the AB10015 study generated extremely robust results, with a median survival increase of +12 months. This optimal population represents approximately 75% of the total patient population...The optimal population included approximately 90 patients per treatment group in the AB10015 study. The effect of masitinib was statistically significant (p=0.0290) on the CAFS endpoint, which is the endpoint recognized by the FDA...Based on the results of the AB10015 study, AB Science has filed a patent application for methods of treating ALS (i.e., a secondary medical use patent) with its lead molecule, masitinib, and this patent has been granted in all jurisdictions where it has been filed. This patent provides strong protection for masitinib in the treatment of ALS until 2037..."

P2/3 data • Patent • Amyotrophic Lateral Sclerosis

Tyrosine Kinase Inhibitors for the Treatment of Mast Cell Diseases: Review and Update. (PubMed, J Investig Allergol Clin Immunol) - "TKIs represent a major advance in the management of MCDs, with more patients being able to benefit from a treatment that addresses pathophysiology. We review the main TKIs currently available for SM, their indications, and their safety and effectiveness."

Journal • Review • Bone Marrow Transplantation • Transplantation • KIT

Masitinib attenuates neuropathological changes in acrolein-induced sAD mouse model via NF-κB/NLRP3/Caspase-1 signaling pathway. (PubMed, Neurosci Lett) - "These findings demonstrate that masitinib, for the first time, attenuates sAD pathology through dual mechanisms of cognitive enhancement and neuroprotection. Our study provides strong preclinical evidence to support further clinical development of masitinib as a disease-modifying therapy for sAD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Mood Disorders • Oncology • Psychiatry • DLG4 • NLRP3

Intellectual property protection until 2037 or even 2042 and Orphan Drug Designation (AB Science Press Release) - "...masitinib has been designated as an orphan drug for ALS by both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). This orphan drug designation confers 10 and 7 years of marketing exclusivity in Europe and the United States, respectively, from the date of product registration. Such status may also be sought in Japan. If granted, the period of commercial exclusivity is extended to 10 years (compared with 4 to 6 years for conventional drugs)."

Commercial • Orphan drug • Amyotrophic Lateral Sclerosis

AB Science has received approval from several European countries to initiate the confirmatory phase 3 study of masitinib in ALS (The Manila Times) - "AB Science SA...announced that the confirmatory Phase 3 study with masitinib in amyotrophic lateral sclerosis (ALS), study AB23005, has been authorized by the first set of European countries (Spain, Greece, Slovenia) in Step 2 of the Clinical Trials Information System (CTIS) procedure. This authorization follows EMA's validation of the harmonized protocol, approved at the end of Step 1 of the CTIS procedure, and followed the authorization from the FDA. Consequently, AB Science can now initiate this registration study in Europe and the United States...Study AB23005 is a prospective, multicenter, randomized, double-blind, placebo-controlled, two-arm study in patients with amyotrophic lateral sclerosis (ALS), to confirm the efficacy and safety of masitinib (at a dose of 4.5 mg/kg/day in combination with riluzole) as compared against riluzole in combination with placebo after 48 weeks of treatment."

Clinical protocol • New P3 trial • Amyotrophic Lateral Sclerosis

Structure-activity relationship studies of thiazole-based derivatives leading to the identification of novel and potent SARS-CoV-2 main protease inhibitors. (PubMed, Eur J Med Chem) - "Using Masitinib and MAC-5576 as leads, we designed 29 compounds featuring a pyridinyl ester for covalent binding to Cys145 and a thiazole core for S2 subsite interaction...Compound MC12 (IC50 = 77.7 ± 14.1 nM) demonstrated inhibitory activities comparable to Nirmatrelvir (IC50 = 58.4 ± 8.6 nM)...These compounds also showed low cytotoxicity and dual inhibition of SARS-CoV and SARS-CoV-2 Mpro. Thiazole-based compounds thus emerge as promising leads for developing potent and safe SARS-CoV-2 Mpro inhibitors."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

AB Science: Masitinib receives FDA and EMA authorization for confirmatory phase 3 trial in metastatic castrate-resistant prostate cancer (The Manila Times) - "AB Science SA...announced that a confirmatory phase 3 trial of masitinib in metastatic castrate resistant prostate cancer (study AB22007) has been authorized by FDA and EMA (harmonized protocol approved through step 1 of Clinical Trials Information System), with a biomarker that targets patients with less advanced metastatic disease."

Clinical protocol • New P3 trial • Castration-Resistant Prostate Cancer

AB Science - New peer-reviewed data provide strong evidence supporting masitinib potential for the treatment of Alzheimer’s disease (GlobeNewswire) - "AB Science...announced that a new peer-reviewed study from an independent research team based in China (Guangdong Pharmaceutical University and Sun Yat-sen University) presents new evidence showing that masitinib offers a promising new approach to treating Alzheimer’s disease, specifically the most common form, sporadic Alzheimer’s disease (sAD), which accounts for over 95% of all cases...The research also revealed that masitinib: Reduced toxic brain proteins such as hyperphosphorylated Tau; Alleviated synaptic dysfunction and morphological damage, i.e., it protected synapses, which are essential for brain cell communication; Suppressed microglial activation, which in turn inhibited the NF-κB/NLRP3/caspase-1 signaling axis, a key inflammatory signaling cascade linked to Alzheimer’s disease, thereby suppressing inflammation in the brain of sAD mice."

Preclinical • Alzheimer's Disease

TARGETING MYH9-PRC1 AXIS EXERTS ANTI-TUMOR EFFECTS IN DIFFUSE LARGE B-CELL LYMPHOMA BY REGULATING PINK1/PARKIN-MEDIATED MITOPHAGY (EHA 2025) - "In summary, we found the prognostic value of PRC1 and the regulatory mechanism of the MYH9-PRC1 axis on PINK1/Parkin-mediated mitophagy in DLBCL, highlighted the potential of Masitinib as a novel therapeutic strategy for DLBCL."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Metabolic Disorders • Non-Hodgkin’s Lymphoma • Oncology • Targeted Protein Degradation • PRC1

Dibutyl phthalate promotes central precocious puberty through primordial follicle activation by downregulating BMP15. (PubMed, Ecotoxicol Environ Saf) - "To investigate the role of primordial follicle activation in CPP development, masitinib was used to establish a model of primordial follicle silencing...In vitro culture of neonatal ovaries revealed that DBP downregulates AMH expression via the BMP15/p38-MAPK pathway. In conclusion, our study firstly demonstrates that the activation of primordial follicles is essential for CPP development, and DBP contributes to CPP by accelerating primordial follicle activation through the BMP15/p38-MAPK/AMH pathway."

Journal • Endocrine Disorders • Oncology

New treatments for systemic mastocytosis in 2025. (PubMed, Curr Opin Allergy Clin Immunol) - "Despite the considerable therapeutic progress in recent years, systemic mastocytosis is an incurable disease. In the last 20 years, the management of systemic mastocytosis has transformed from a one-size-fits-all approach, characterized by nonspecific cytoreductive drugs, to a tailored strategy focused on increasingly precise molecular targets, with the most notable example being the KIT inhibitors. Recently, the FDA and EMA have approved two drugs for treating systemic mastocytosis: avapritinib and midostaurin. Moreover, numerous trials are currently assessing the efficacy of new molecules: most are testing new-generation KIT inhibitors (ripretinib, bezuclastinib, elenestinib, masitinib, nintedanib), others focusing on Bruton's kinase (TL-895), interleukin-6 (sarilumab), sialic acid-binding immunoglobulin-like lectin-8 (lirentelimab), mTOR and CD33, among others. Real-life data are needed to confirm preliminary preclinical results."

Journal • Aggressive Systemic Mastocytosis • CD33 • IL6

Evaluating the efficacy of tyrosine kinase inhibitors and other targeted therapies in imatinib-resistant gastrointestinal stromal tumors: A comprehensive Bayesian network meta-analysis. (ASCO 2025) - "Imatinib has transformed GIST treatment; however, resistance typically emerges within 20–24 months, necessitating effective second-line therapies such as sunitinib, regorafenib, ripretinib, and masitinib. Masitinib and regorafenib demonstrate the most promising efficacy for improving survival and treatment response in imatinib-resistant GIST patients. These findings emphasize the importance of tailored therapeutic strategies for advanced GIST management."

Retrospective data • Stroma • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

The role of microglia in multiple sclerosis: implications for treatment with Bruton's tyrosine kinase inhibitors. (PubMed, Front Immunol) - "BTK inhibitors and other novel treatments for MS, including masitinib and frexalimab, show promise in modulating microglial function and influencing the disease progression rate. The multifaceted roles of microglia in CNS development, immune surveillance, and particularly in the pathogenesis of MS highlight the potential of targeting microglial functions in MS treatment. Emerging research on the involvement of microglia in MS pathophysiology offers promising avenues for developing novel therapies, especially for progressive MS, potentially improving patient outcomes in this debilitating disease."

Journal • Review • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis

AB Science announces the settlement delivery of its latest capital increase for €1.8 million (GlobeNewswire) - "This transaction strengthens the Company's cash position and enables it to cover its financing needs in 2025 and beyond the next 12 months, taking into account the explanations set out in section 5.2.1.5 (note 2) of the 2024 financial report."

Commercial • Acute Myelogenous Leukemia • Alzheimer's Disease • Chronic Obstructive Pulmonary Disease • Immunology • Melanoma • Myelodysplastic Syndrome • Oncology • Parkinson's Disease • Rheumatoid Arthritis

AB Science receives Chinese patent protecting masitinib in the treatment of Covid-19 until 2041, adding one more indication with long term intellectual property protection (GlobeNewswire) - "AB Science SA...announced that the Chinese Patent Office has issued a patent relating to methods of treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing COVID-19 (i.e. a medical use patent) with its lead compound masitinib. This new Chinese patent provides intellectual property protection for masitinib in this indication until April 2041...The patent is based in part on preclinical data that has been published in the world-renowned journal Science, and which identified masitinib as a broad antiviral agent capable of treating SARS-CoV-2 (the virus that causes COVID-19), including demonstration of in vivo activity in mice, with efficacy maintained, in vitro, against SARS-CoV-2 variants of concern."

Patent • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

AB Science today reports a new publication in the scientific journal PLOS One, showing promising neuroprotective effects of masitinib (GlobeNewswire) - "Masitinib significantly reduced serum neurofilament light chain (NfL) levels, indicating its neuroprotective effects in a neuroimmune-driven neurodegenerative disease model. Reduction in relative NfL Levels: At Day 8, masitinib treatment reduced the relative increase in serum NfL levels as compared with the EAE control group. Specifically: Masitinib 50 mg/kg/day reduced NfL levels by 43%. Masitinib 100 mg/kg/day reduced NfL levels by 60%....Masitinib treatment significantly reduced the levels of several pro-inflammatory cytokine biomarkers in the EAE mouse model, indicating its anti-inflammatory effects."

Preclinical • CNS Disorders • Immunology

Tyrosine kinase inhibitor, masitinib, limits neuronal damage, as measured by serum neurofilament light chain concentration in a model of neuroimmune-driven neurodegenerative disease. (PubMed, PLoS One) - "This study is the first demonstration that masitinib, a drug that targets the innate as opposed to the adaptive neuroimmune system, can lower serum NfL levels, and by extension therefore, neuronal damage, in a neuroimmune-driven neurodegenerative disease model. Overall, findings indicate that masitinib has a neuroprotective effect under conditions of chronic neuroinflammation and therefore plausible disease-modifying activity across a broad range of neurodegenerative diseases."

Journal • CNS Disorders • Immunology • Inflammation • NEFL