PRESS RELEASE
AB SCIENCE PRESENTS ITS FINANCIAL RESULTS FOR THE FIRST HALF OF 2024 AND THE KEY EVENTS OF THE PERIOD
Clinical development Masitinib platform: Ongoing re-examination by EMA and Health Canada of the marketing authorisation application for masitinib in amyotrophic lateral sclerosis (ALS)Update on the development of masitinib in progressive forms of multiple sclerosis following the ECTRIMS 2024 conferencePositive results from the phase 2 study of masitinib in Covid-19Strengthening the intellectual property of masitinib in mastocytosis Microtubule platform: Update on the AB8939 microtubule program and in in particular on the ability of AB8939 to generate a response on MECOM rearrangement Financial and corporate situation Operating deficit of 3.6 million euros as of June 30, 2024, down 59.5% compared to the first half of 2023Cash position of 9.1 million euros as of June 30, 2023, to which is added 5 million euros from the capital increase by private placement announced in September 2024Completion of the settlement and delivery of the 5 million euros capital increase Paris, October 10, 2024, 8.30am CET
AB Science SA (Euronext – FR0010557264 – AB) today announces its half-year financial results as of June 30, 2024 and provides an update on its activities.
KEY EVENTS RELATED TO CLINICAL DEVELOPMENT DURING THE FIRST HALF OF 2024 AND SINCE JUNE 30, 204
EMA negative opinion on the marketing authorisation application for masitinib in amyotrophic lateral sclerosis and ongoing re-examination of the dossier by EMA
AB Science announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted, in line with the trend vote, a negative opinion on the application for conditional marketing authorization of masitinib in the treatment of amyotrophic lateral sclerosis (ALS).
AB Science requested a re-examination on the basis of:
First and foremost, the urgent need for patients to have early access to a promising treatment.The opportunity of having the dossier re-examined by new rapporteurs and by a Scientific Advisory Board. AB Science highlights the difficulty of a conditional marketing authorization in ALS and cannot guarantee a positive outcome following this re-examination.
The reasons which nevertheless led AB Science to request a re-examination of the file are as follows:
Acceptable masitinib safety: First, the CHMP confirmed that the safety of masitinib is deemed acceptable, which is a key consideration in the context of a conditional marketing authorization where confirmatory evidence of efficacy is required.Objection concerning deviations from Good Clinical Practice: As per EMA guidance (EMA/868942/2011), impact analyses of all protocol deviations that could not be corrected were performed and showed no impact, resolving Good Clinical Practice issues as per guideline.Objection concerning the exclusion of fast progressors: The amendment transitioning from phase 2 to phase 3 excluding fast progressors from the primary analysis population was necessary and well justified, in order to have a more homogenous population with greater chance of reaching week 48 time point and minimizing missing data. Furthermore, the amendment was implemented early enough and while the study was blinded, removing any methodological issues.Objection concerning the treatment of missing data in the primary analysis: Multiple sensitivity analysis of the primary analysis; using non LOCF (Last Observation Carried Forward) methods for imputation of missing data, are positive and consistent, including two analyses previously recommended by the CHMP, demonstrating the robustness of the primary analysis, thus resolving the objection concerning the treatment of missing data.Objection on the subgroup data: There was an important imbalance in a subset of patients experiencing complete loss of function (i.e., ALSFRS-R score of zero) in one or more of the item scores (20% in the masitinib arm versus 8% in the placebo arm), because ALSFRS-R score was minimized but not stratified by category of severity. The subgroup defined as patients prior to any complete loss of function (i.e. excluding the overmentioned biased subset) accounted for 86% of the population and showed extremely compelling results, including a significant 12 months survival benefit. The subgroup analysis is the strict application of EMA guidance (EMA/CHMP/539146/2013), which is applicable to post hoc analysis and to registration with single pivotal study, thus resolving the objection regarding subgroup data. The re-examination of the dossier by EMA is ongoing.
Notice of Deficiency-Withdrawal (NOD/w) regarding the New Drug Submission (NDS) for masitinib in the treatment of amyotrophic lateral sclerosis (ALS) in Canada and ongoing re-examination of the dossier by Health Canada
AB Science announced in February 2024 that Health Canada issued a Notice of Deficiency-Withdrawal (NOD/w) regarding the New Drug Submission (NDS) for masitinib in the treatment of ALS and indicated its intention to submit a reconsideration request.
In April 2024, AB Science announced that Health Canada had granted eligibility for reconsideration request. The reconsideration process will re-examine, with new assessors, the decision based on information that was included in the original submission.
The re-examination is ongoing by Health Canada.
Update on the AB8939 microtubule program and in particular on the ability of AB8939 to generate a response on MECOM rearrangement
AB Science provided an update on the microtubule program AB8939 and in particular the ability of AB8939 to generate response on MECOM rearrangement.
AB8939 is a novel microtubule destabilizer currently evaluated in phase 1 clinical trial (study AB18001, NCT05211570) in patients with refractory and relapsed acute myeloid leukemia (AML).
The phase 1 clinical trial of AB8939 completed its first step, consisting in determining the maximum tolerated dose following 3 consecutive days of AB8939 treatment, and was authorized to proceed with the next step, consisting in determining the maximum tolerated dose following 14 consecutive days of AB8939 treatment.
The phase 1 clinical trial continues to determine MTD and the study is now at the last cycle of the 14 days evaluation. The next step will be to determine the MTD in the combination of AB8939 with Vidaza® (azacitidine).
AB Science previously reported a case of complete bone marrow response in an AML patient in failure to prior treatment with azacitidine and presenting with a MECOM gene rearrangement, which consists of chromosomic aberrations of EVI1 oncogene, leading to one of the worst prognostics in AML and is associated with lack of response and resistance to conventional chemotherapy.
New data confirm that there is a signal of activity against MECOM, with AB8939 generating a complete response in combination with Vidaza, as evidenced by a synergistic effect in a patient-derived xenograft (PDX) mouse model bearing the MECOM rearrangement. PDX are cell lines coming from patients that are grafted to immune deficient mice to mimic as closely as possible the human disease.
AB8939 was able to generate 50% response when used as a single agent on MECOM cell lines ex vivo in a non-clinical setting.In the phase 1 trial, 4 patients bore the MECOM rearrangement and 50% responded to AB8939 when used as a single agent.In phase 1, so far, AB8939 does not appear to be toxic to bone marrow, avoiding severe neutropenia and suggesting the possibility to use the drug for long-term treatment.
These data taken together confirm the opportunity to develop AB8939 in phase 2 clinical trial in MECOM as a single agent or in combination with Vidaza.
The advantage is that a small study could be sufficient to comply with FDA guideline on accelerated approval.
Update on the development of masitinib in progressive forms of multiple sclerosis following the ECTRIMS 2024 conference
AB Science provided an update on the development of masitinib in progressive forms of multiple sclerosis (MS), following the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2024 conference.
The development of masitinib in progressive forms of multiple sclerosis is based on the MAXIMS study (AB20009), a randomized, double-blind, phase 3 study of masitinib 4.5 mg/kg/day in patients with primary progressive multiple sclerosis (PPMS) and non-active secondary progressive multiple sclerosis (nSPMS).
The recent results of tolebrutinib in non-active secondary progressive MS presented at the ECTRIMS 2024 conference, reinforce the scientific hypothesis that targeting microglia in nSPMS is a valid approach. Tolebrutinib belongs to a class of drugs that target microglia through an enzymatic target called BTK (Bruton Tyrosine Kinase).
Masitinib also targets microglia but through a different enzymatic target called M-CSFR1 (Macrophage Colony Stimulating Factor Receptor-1) and generated positive results in phase 2B (AB07002), which are consistent with tolebrutinib data.
EDSS progression confirmed at 3 months was reduced by 37% with masitinib in study AB07002 and by 23% with tolebrutinib in the Hercules study (although the reduction in study AB07002 did not reach the conventional 5% p-value since the study was not powered to detect a significant effect in this secondary endpoint, having 300 patients in the masitinib 4.5 or placebo arms as compared with 1100 patients in the Hercules trial).EDSS progression confirmed at 6 months was reduced by 32% with masitinib and by 31% with tolebrutinib. Importantly,
Masitinib significantly improved manual dexterity measured by 9-hole Peg test, in study AB07002 (-4,28 ; p=0,0388).Masitinib has shown the ability to decrease serum neurofilament light chain (NfL) concentration in an animal model of MS, and by extension therefore, possibly neuronal damage.Masitinib not only targets microglia but also mast cells, which play a crucial role in progressive MS and in the experimental autoimmune encephalomyelitis (EAE) model of MS, as shown by numerous publications.
Masitinib benefits from a large safety database with long-term exposure across various indications. In non-oncology indications, around 2,200 patients have received at least one dose of masitinib, more than 1,300 patients have received masitinib for more than six months and close to 1,000 patients have received masitinib for more than one year.
BTK safety profiles shows increase in liver injury, hypertension and infections which seem to be a class effect, leaving room for alternative drugs.
As a conclusion, masitinib represents a potential credible alternative to BTK inhibitors in the development of new drugs both in primary and non-active secondary progressive MS.
Positive results from the phase 2 study of masitinib in Covid-19
AB Science announced the results of a Phase 2 study evaluating masitinib in COVID-19. This Phase 2 study (AB20001) was designed to evaluate the safety and efficacy of masitinib plus isoquercetin in hospitalized patients with moderate COVID-19 (WHO 7-point ordinal scale level 4) or severe COVID-19 (level 5). The study initially planned to recruit 200 patients (over 18 years of age with no upper age limit). The primary objective was to improve the clinical status of patients after 15 days of treatment, as measured by the WHO 7-point ordinal scale. Following a DSMB recommendation, decision was taken to continue the study only in level 4 patients (i.e. hospitalized patients with oxygen supply
