Kinaction (masitinib) / AB Science - LARVOL DELTA

Progression-Free Survival With Second, Third, and Fourth Line Tyrosine Kinase Inhibitors After Imatinib Failure in Gastrointestinal Stromal Tumors: A Genetic Mutation-Stratified Systematic Review and Meta-Analysis (ACG 2026) - "Masitinib did not improve PFS versus sunitinib. In the VOYAGER trial, avapritinib did not improve progression-free survival compared with regorafenib in the overall study population, but it showed activity in patients with PDGFRA D842V mutations... 11 randomized trials including 2,181 patients with advanced gastrointestinal stromal tumors after imatinib failure were included. Overall, active TKIs significantly improved progression-free survival (PFS) compared with placebo or best supportive care (HR 0.32, 95% CI 0.21â0.51) although heterogeneity was substantial. Sunitinib, regorafenib, ripretinib, pazopanib, and imatinib rechallenge showed benefit in delaying disease progression compared with placebo or best supportive care, whereas Nilotinib did not with best supportive care, with or without imatinib or sunitinib."

Retrospective data • Review • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

AB Science announces today the successful completion of capital increases of a total gross amount of EUR 14.2 million (GlobeNewswire) - "Use of proceeds..The Company intends to use the net proceeds from the Private Placement to fund its research and development programs, with primary focus on: AB8939 development in acute myeloid leukemia; Masitinib development in amyotrophic lateral sclerosis; and Nearer-term value-creation projects that are expected to be finalized and disclosed in September....This transaction strengthens the Company’s cash position and enables it to cover its financing needs beyond the next 12 months."

Financing • Acute Myelogenous Leukemia • Amyotrophic Lateral Sclerosis

Identification of molecular subtypes in clear cell renal cell carcinoma based on chromatin regulators and tumor immune microenvironment profiling. (PubMed, Biochem Biophys Res Commun) - "Drug-sensitivity analyses nominated several candidate agents, and SMARCD3 knockdown in 786-O cells inhibited proliferation and migration and reduced sensitivity to masitinib. Collectively, these findings support the prognostic and therapeutic relevance of CR-related states in ccRCC and provide a framework for future experimental validation of chromatin-regulated tumor-immune interactions."

IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • SMARCD3

Repurposing Masitinib Mesylate as a Novel FOXM1 Inhibitor for the Treatment of Aggressive Solid Tumors: Preclinical Validation in Human Breast and Oral Cancer Cells and Organotypic Tumor Slice Culture. (PubMed, ACS Omega) - "Our findings establish a novel mechanistic link between masitinib mesylate and FOXM1 inhibition by DNA binding, providing a compelling rationale for drug repurposing, offering a targeted therapeutic strategy to disrupt the FOXM1-driven regulatory network in aggressive, therapy-resistant cancers. In silico analyses predict a potential interaction of masitinib with the FOXM1 DNA-binding domain (DBD); however, further experimental validation is required to confirm direct binding."

Journal • Preclinical • Breast Cancer • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Triple Negative Breast Cancer • FOXM1 • LYN • PDGFRA • PDGFRB

Repurposed anticancer drugs disrupt cancer-like traits of Theileria annulata and suppress Leishmania donovani. (PubMed, Cell Commun Signal) - "Notably, floxuridine, masitinib, paclitaxel, cabazitaxel, vinorelbine, maytansine, and bortezomib also suppressed L. donovani, highlighting cross-species efficacy. Target mapping revealed that the majority of active molecules disrupt hallmarks of cancer and parasite-transformed cells, including metabolic reprogramming, genome instability, and invasive phenotypes. Collectively, these findings underscore the value of oncology-derived drug libraries for antiparasitic discovery and identify promising candidates for further evaluation against T. annulata and L. donovani."

Journal • Infectious Disease • Oncology

AB Science provides an update on its clinical program, suspending some non-priority clinical trials to focus on two clinical programs (Yahoo Finance) - "AB Science...to focus on two clinical programs, the AB8939 program for acute myeloid leukemia and the masitinib program for amyotrophic lateral sclerosis....three clinical studies—which the company currently considers non-priority and for which patient enrollment had been suspended—are being discontinued, namely: Phase 2 study (AB20006) of masitinib in mast cell activation syndrome; Phase 3 study (AB15003) of masitinib in mastocytosis; Phase 3 study (AB20009) of masitinib in progressive forms of multiple sclerosis....The discontinuation of these studies is not related to any safety concerns regarding masitinib. The company intends to complete these clinical studies in accordance with applicable regulations...The next step is to seek authorization from health authorities—based on a preliminary favorable opinion from the study's Independent Data Monitoring Committee (IDMC)—to initiate Phase 4 of the study, which will evaluate the triple combination of AB8939..."

New P4 trial • Trial suspension • Acute Myelogenous Leukemia • Amyotrophic Lateral Sclerosis • Hematological Malignancies • Immunology • Multiple Sclerosis

AB Science announces the successful completion of a EUR 2.3 million private placement (GlobeNewswire) - "The Company intends to use the net proceeds of the Private Placement to finance research and development programs of the Company, the priority being the...masitinib in amyotrophic lateral sclerosis. This transaction strengthens the Company’s cash position and enables it to cover its financing needs beyond the next 12 months."

Financing • Amyotrophic Lateral Sclerosis

Feline Asthma-Update on Diagnosis and Treatment Recommendations. (PubMed, Vet Clin North Am Small Anim Pract) - "Main treatment includes inhaled corticosteroids, often combined with bronchodilators. Additional options like cyclosporine, inhaled lidocaine, masitinib, and allergen-specific immunotherapy are available but mostly supported by limited studies."

Journal • Review • Allergy • Asthma • Chronic Cough • Cough • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Five-Year Survival Of 42% In ALS Patients Treated With Masitinib: Long-Term Outcomes From AB10015 Trial (ENCALS 2026) - "Objectives This post-hoc analysis evaluated long-term survival outcomes (>5 years from symptom onset) in patients treated with oral masitinib as an add-on therapy to riluzole in the phase 2b/3 study, AB10015...AMX0035 currently lacks established long-term survival data for ALS patients beyond 2 years, with 51.6% versus 89.2% for masitinib (4.5 mg/kg/day).Conclusion These findings underscore masitinib's potential to improve outcomes for patients with ALS. The greatest survival benefit is associated with starting treatment early (i.e., prior to severe functional impairment). A recently identified biomarker detecting masitinib's effect on pathological pro-inflammatory microglia may help identify responsive patients."

Clinical

AB Science SA…announced that the United States Patent Office has formally granted a patent for methods of treating metastatic castrate resistant prostate cancer (mCRPC) with its lead compound masitinib (GlobeNewswire) - "This new US patent (US 12,648,944) ensures intellectual property protection for masitinib until May 2042. This new US patent adds to the IP coverage already granted in Europe (EP4175639). Counterpart patent applications have also been filed in other major international markets."

Patent • Castration-Resistant Prostate Cancer

AB Science SA...announced that new analyses from its phase 3 trial in amyotrophic lateral sclerosis (AB10015) have been accepted for poster presentation at the ENCALS annual meeting (June 24-26, 2026, Madrid, Spain). (GlobeNewswire) - "The survival benefit was even more pronounced in enriched patient populations...A 50% five-year survival rate in patients with slower disease progression (ALSFRS-R progression rate ΔFS < 1.1 points/month) at baseline, the primary efficacy population of study AB10015; A 53% five-year survival rate in patients with baseline ΔFS < 1.1 points/month and no complete loss of functionality at baseline (i.e., a score ≥1 on all ALSFRS-R items); Masitinib's five-year survival rates substantially exceed registry-based benchmarks ranging from 7% to 27.8% (weighted average ~24%), and compare favorably against large retrospective analyses of riluzole-treated and untreated cohorts (~24% and ~15-17% from diagnosis, respectively)."

P3 data • Amyotrophic Lateral Sclerosis

CREB–mediated pharmacologic antagonism is associated with adaptive escape from MAPK inhibition in melanoma (SID 2026) - "To identify antagonistic compounds, we subjected 5 BRAF* melanoma lines to a high-throughput screen of 1,600 broad-spectrum FDA-approved and advanced preclinical drugs, co-administered with dabrafenib + trametinib (D+T; 4.0/0.4 nM)...The top 5 ranking antagonistic drugs were Mocetinostat (E=0.92), CP673451 (E=0.88), Axitinib (E=0.76), Amuvatinib (E=0.74), and BX-795 (E=0.74)...Notably, this subset included 14 mechanistically related platelet-derived growth factor receptor inhibitors (PDGFRI: CP673451, Amavadin, Axitinib, Crenolanib, Nintedanib, Sorafenib, Linifanib, Tivozanib, Imatinib, Masitinib, Pazopanib, Motesanib, Sunitinib)...Comparative phosphokinome profiling across the 3 cell lines identified CREB phosphorylation at S133 as a conserved event, robustly suppressed by D+T but selectively rescued by PDGFRi co-treatment. Together, these data identify PDGFR inhibitors as a reproducible source of antagonism to BRAF+MEK-targeted therapy and nominate CREB phosphorylation..."

Melanoma • Solid Tumor

Efficacy and safety of pharmacological and biological therapies for amyotrophic lateral sclerosis: a network meta-analysis. (PubMed, Front Neurol) - "Within-class subgroup analyses further identified several specific agents, such as masitinib, talampanel, and EH301, as demonstrating relatively consistent efficacy, although substantial heterogeneity remained among enzyme inhibitors...Survival benefits remain inconclusive, underscoring the continued importance of comprehensive supportive care. https://www.crd.york.ac.uk/PROSPERO/view/CRD420251000672, identifier CRD420251000672."

Journal • Retrospective data • Review • Amyotrophic Lateral Sclerosis • CNS Disorders

Macrophage-Derived PDGF-BB and GDF-15 Promote Drug Resistance in KRAS-Mutant Colorectal Cancer. (PubMed, bioRxiv) - "In contrast, macrophage-conditioned medium had little effect on regorafenib and increased sensitivity to dabrafenib, suggesting that resistance depends on the inhibitory profile of each drug. The multi-kinase inhibitor masitinib-which targets several kinases along this resistance network-strongly restored sensitivity to trametinib and RMC-6236. Together, these data define a macrophage-driven resistance network in KRAS-mutant colorectal cancer organoids and support combined inhibition of RAS-pathway and tyrosine kinase signalling."

Journal • Colorectal Cancer • Oncology • Solid Tumor • GDF15 • KRAS • TP53

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

Trial suspension • CNS Disorders • Multiple Sclerosis

AB Science SA...announces today that a final agreement has been reached with its financial creditors for the 24-month deferral of repayment of its bank debt (for a total amount of approximately €3.7 million) and the 12-month deferral of repayment of a loan subscribed with the EIB (for a total principal amount of €12 million, initially repayable in January and December 2028). (Yahoo Finance UK) - "AB Science has reached a final agreement with its financial creditors; This agreement provides for a two-year deferral of repayment of the State-Guaranteed Loans and a 12-month deferral of the repayment date of the EIB Covid credit; The savings over the period will be invested in R&D...'Having secured insurance for its Phase III clinical trial, AB Science is honored to receive the confidence of its banking partners, who are extending the maturity of their loans. AB Science will now focus on its Phase III study in amyotrophic lateral sclerosis and its AB8939 program.'"

Financing • Acute Myelogenous Leukemia • Amyotrophic Lateral Sclerosis • Myelodysplastic Syndrome

Lysosomal accumulation of Masitinib alters autophagy via pH-dependent trapping. (PubMed, Eur J Pharmacol) - "Across multiple cell lines, masitinib suppresses mTORC1 signaling while paradoxically inducing AKT phosphorylation through a VPS34 and rapamycin-sensitive pathway independent of class I PI3K. This lysosomal accumulation impairs lysosomal acidification and disrupts autophagic flux, providing a mechanistic link between the physicochemical properties of masitinib and its downstream signaling effects. Together, our findings highlight lysosomal sequestration as a key determinant of kinase inhibitor behavior and underlie the importance of subcellular drug distribution in modulating cellular responses."

Journal

AB Science: New publication on medrxiv demonstrating substantial survival benefits and preserved quality of life with masitinib in ALS patients (GlobeNewswire) - "The 5-year survival rate from disease onset reached 42.3% across all 130 patients receiving masitinib 4.5mg/kg/day, increasing to 50% in patients with slower disease progression (ALSFRS-R progression rate <1.1 points/month) and 52.9% in those without complete loss of functionality at baseline. This surpasses the historical benchmarks ranging from 7% to 27.8% (weighted average approximately 23.5%)...Among long-term masitinib-treated survivors (n=55), the median overall survival was 121 months compared to 42 months predicted by the ENCALS model, representing a 79-month residual median survival gain."

P2/3 data • Amyotrophic Lateral Sclerosis

Voluntary temporary halt of clinical trials in Europe (Yahoo Finance) - "The recruitment of new patients in AB Science studies has been voluntarily halted while AB Science was negotiating with the insurer and was having on-going exchanges with European health authorities...AB Science submitted detailed responses to the agencies and is reviewing its strategic priorities, namely:To deprioritize development in mastocytosis and mast cell activation program...To pursue the phase 3 clinical development in multiple sclerosis and Alzheimer’s disease through partnerships...To prioritize AB Science clinical development program on the masitinib phase 3 in amyotrophic Lateral Sclerosis (ALS) and AB8939 phase 1 in acute myeloid leukemia (AML)."

Discontinued • New P3 trial • Trial status • Trial suspension • Acute Myelogenous Leukemia • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • Multiple Sclerosis • Rare Diseases

AB Science secures EUR 25 million clinical trial insurance fr its phase III trial in amyotrophic lateral sclerosis (Yahoo Finance) - "The CTFI will become effective (and the premium will be payable) when AB Science are ready to initiate its ALS Phase III clinical trial, and when AB Science will have mobilized the necessary financing for such study and the payment of the premium. The CFTI offer received is binding and may be activated until December 31st, 2026...This covers the following situations: Efficacy Failure: the phase 3 fails to meet the FDA or the EMA criteria of success, defined by the policy; Safety Failure: the drug raises unacceptable safety concerns in the ALS patient population; Recruitment Failure: inability to enroll or retain the required number of patients within the policy period; Regulatory Action (Clinical Hold): the FDA or an equivalent authority suspends or terminates the trial."

Financing • Amyotrophic Lateral Sclerosis

Masitinib for the Treatment of Severe Mast Cell Activation Syndrome (clinicaltrials.gov) - P2 | N=72 | Active, not recruiting | Sponsor: AB Science | Not yet recruiting ➔ Active, not recruiting

Enrollment closed

Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment (clinicaltrials.gov) - P3 | N=140 | Active, not recruiting | Sponsor: AB Science | Not yet recruiting ➔ Active, not recruiting

Enrollment closed

AB20009: A 96-Week, Prospective, Multicenter, Randomised, Double-Blind, Placebo-Controlled, Phase 3 Study to Compare Efficacy and Safety of Masitinib Dose Titration to 4.5 mg/kg/day versus Placebo in the Treatment of Patients with Primary Progressive or Secondary Progressive Multiple Sclerosis Without Relapse (clinicaltrialsregister.eu) - P2/3 | N=145 | Active, not recruiting | Sponsor: Ab Science | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis

AB23005: A prospective, multicenter, randomised, double-blind, placebo-controlled, parallel groups, phase 3 Trial to compare the efficacy and safety of masitinib in combination with standard of care versus placebo in combination with standard of care in the treatment of patients suffering from Amyotrophic Lateral Sclerosis (ALS) (clinicaltrialsregister.eu) - P2/3 | N=135 | Not yet recruiting | Sponsor: Ab Science

New P2/3 trial • Amyotrophic Lateral Sclerosis • CNS Disorders • Neutropenia

AB Science announces the identification of a plasma biomarker that indicates the activity of masitinib in treating ALS (GlobeNewswire) - "The key characteristics of this newly identified biomarker are as follows: It is a blood-based (plasmatic) biomarker, which has the advantages of being easy to collect and accurately evaluated using ELISA...It is produced by proinflammatory microglia; It activates microglia and astrocytes and is therefore an activator contributing to a vicious neuroinflammation feedback loop; It is also released by mast cells, establishing a link between mast cells and microglia, which are two major cellular targets of masitinib....This biomarker will be introduced in the phase 3 program of masitinib in ALS, as well as in progressive MS and Alzheimer’s disease, to validate the mechanism of action of masitinib in humans and its clinical relevance."

Biomarker • New P3 trial • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • Multiple Sclerosis