Masitinib in Alzheimer’s Disease Webcast Presentation

AB SCIENCE WEBCONFERENCE MASITINIB IN ALZHEIMER’S DISEASE 17 December 2020 2 Disclaimer This presentation, together with the material set forth herein, does not constitute an offer of securities for sale nor the solicitation of an offer to purchase securities in any jurisdiction. Distribution of such presentation in certain jurisdiction may constitute a breach of applicable laws and regulation. This document is solely for your information on a confidential basis and may not be reproduced, redistributed or sent, in whole or in part, to any other person, including by email or by any other means of electronic communication. In particular, neither this document nor any copy of it may be taken, transmitted or distributed, directly or indirectly, in the United States, Canada, Japan or Australia. The distribution of this document in other jurisdictions may be restricted by law and persons into whose possession this document comes should make themselves aware of the existence of, and observe, any such restrictions. Neither the Company, nor any of its advisors and representatives may accept any responsibility for any loss or damage incurred by the use of this document or the information set forth herein. Neither the Company, nor any of its advisors and representatives takes any undertaking nor guarantees, whether explicitly or tacitly, the accuracy or the completeness of the information set forth herein. Neither this document, nor any part of it, shall form the basis of, or be relied upon in connection with, any contract or commitment whatsoever. In particular, in France, any decision to purchase such securities shall rely solely on the documents that have been reviewed by the Autorité des Marchés Financiers (the “AMF”) and/or published by the Company. This document does not constitute an offer to purchase any financial instruments in the United States. Securities mentioned in this document have not been and will not be registered under the Securities Act of 1933, as amended (the “Securities Act”) and may not be offered or sold in the United States absent registration or an exemption from the registration requirements of the Securities Act. The Company does not intend to register any offering in all or in part or to make a public offer of securities in the United States. This document contains information on the objectives of the Company along with some projections and forward-looking statements. The reader’s attention is drawn to the fact that these objectives may not be fulfilled, and the forecasts or information provided may prove erroneous, and the Company is not required to update such information. Past performance is no guide to future performance and persons needing advice should consult an independent financial adviser. Participants 3 Alain MOUSSY , MBA Co-founder and Chief Executive Officer. Laurent GUY , MBA Chief Financial Officer Olivier HERMINE, MD, PhD Chief Scientific Officer and Chaiman of Scientific Committee AB Science Management and Chairman of Scientific Committee Bruno Dubois, MD Professor of Neurology at the Neurological Institute of the Salpétrière University Hospital, Paris Philip Scheltens, MD, PhD Professor of Cognitive Neurology and Director of the Alzheimer Center at the VU University Medical Center, Amsterdam Jeffrey L. Cummings, MD Director of the Chamber-Grundy Center for Transformative Neuroscience at UNLV, Las Vegas Alzheimer’s Disease Experts Masitinib Profile and Mechanism of Action 4 Orally-administered kinase inhibitor selectively targeting mast cells and microglia Dubreuil 2009, PLoSONE.4(9):e7258; AB Science. Davis 2011, Nat Biotechnol; 29(11):1046 Masitinib targets mast cells • Masitinib is a selective inhibitor of c-Kit, Lyn, and Fyn kinases • These kinases play critical roles in the activation of mast cells Masitinib targets macrophages/microglia • Masitinib is a potent and selective inhibitor of MCSFR-1 • This kinase plays critical roles in the modulation of microglia Masitinib is a tablet • Oral route • Morning and evening Kinase inhibition profile of masitinib Cellular Target Molecular Target IC50 [nM] Kd [µM] Mast cells KIT wild-type (WT) 20 0.008 FYN 240 0.14 LYN 225 0.061 Microglia MCSFR-1 90 0.0076 Scientific Rationale in Alzheimer’s disease (AD) 5 The mode of action of masitinib in AD is based on four targets, which may have a synergistic effect Control of Mast Cell (MCs) activity Modulation of Microglia Protection of Synapses Inhibition of Tau protein ▪ Microglia is involved in the neuro- inflammation in AD ▪ Masitinib promotes recovery of synaptic markers in mice model of AD▪ Synapses are altered in AD ▪ Tau protein aggregates in the physiopathology of AD ▪ Masitinib inhibits FYN kinase, a kinase that is phosphorylasing Tau ▪ Masitinib prevent the accumulation of amyloid fibrillin hippocampus of young mice model of AD ▪ Mice depleted from MCs do not develop symptoms of AD ▪ Masitinib blocks MCs activation through inhibition of c-Kit, LYN, and FYN kinases ▪ eta-amyloid plaques activate mast cells ▪ Transgenic AD mice treated by masitinib are protected for cognition impairment ▪ Masitinib blocks microglia through inhibition of MCSFR-1 kinase Pharmacology 6 In a transgenic mouse model of AD, masitinib could restore/protect completely cognitive impairment References : Courtesy from B Delatour. ICM – Brain Institute - France Cognitive evaluation in a curative setting (APPXPS1DE9 mouse model) During learning End of learning period Hidden platform (target) ❖ Blinded study ❖ Masitinib was evaluated for its effect on memory deficit in AD mice (Tg) versus using the Morris Water Maze (MWM) in a curative setting (mice aged 12-14 months) ❖ The MWM test evaluates hippocampal-dependent learning, including acquisition of spatial memory and long-term spatial memory, which is often affected in AD. Morris Water Maze (MWM) – Improvement in Acquisition Phase Control group (Veh) Masitinib Group (Mas) Tg Veh (n=8) WT Veh (n=8) Tg Mas(n=9) WT Mas (n=9) AD mice (Tg) have longer distance and no spatial memory improvement as compared with control mice (WT=wild-type) AD mice (Tg) treated with masitinib improve cognitive function, with spatial memory returning to normal levels Pharmacology 7 In a transgenic mouse model of AD, masitinib could completely protect/restore the ability to perform navigation strategy References : Courtesy from B Delatour. ICM – Brain Institute - France Morris Water Maze (MWM) – Improvement in Spatial Strategy * p<0.05. WT = wild-type mice. Tg = APPxPS1dE9 mice. M = masitinib treatment. Veh = vehicle treatment. Group p-value Test Tg Veh vs. Tg M 0.034 Treatment effect Pharmacology 8 In a transgenic mouse model of AD, masitinib could protect through mast cell inhibition against synaptic loss/destruction B Delatour. Effects of Chronic Masitinib Treatment in APPswe/PSEN1dE9 Transgenic Mice Modeling Alzheimer's Disease. J Alzheimers Dis. 2020;76(4):1339-1345. doi: 10.3233/JAD-200466. WT = Wild-type mice. Wsh = Wild-type mice depleted in mast cells. TgAD = mice model of AD. TgAD-Wsh = mice model of AD depleted in mast cells. Veh= Vehicule Data expressed as mean±SEM.***p < 0.0001, **p < 0.01, *p < 0.05. B. Relative optical density of synaptophys in immunoreactivity in the hippocampus of WT and TgAD mice with or without mast cells depletion induced by the Wsh mutation (left part) and representative microphotographs illustrating synaptophys in immunoreactivity levels in the four studied groups (right part). Mast cell-deficient transgenic AD mice show a recovery of synaptic markers A. Relative optical density of synaptophys in immunoreactivity in the hippocampus of WT and TgAD mice treated with Vehicle or masitinib (left part) and representative microphotographs illustrating synaptophys in immunoreactivity levels in the four studied groups (right part). Likewise, masitinib induces a recovery of synaptic markers in transgenic mice model of AD Masitinib Clinical Development Plan in AD .9 The development program in Alzheimer’s disease is comprised of AB04024 proof of concept study (published), and AB09004 phase 2B/3 study Phase Study code Design Population Primary endpoint Patient target Related publications 2a AB04024 (NCT00976118) Double-blind, placebo- controlled, parallel-group study Patients with mild to moderate Alzheimer Disease Change on ADAS-Cog 34 Piette, 2011 2B/3 AB09004 (NCT01872598) Prospective, double-blind, placebo-controlled, parallel groups study Patients with mild to moderate Alzheimer Disease Change on ADCS-ADL or Change on ADAS-Cog 720 Positioning in AD .10 Masitinib is positioned in patients with mild and moderate dementia, which is different from other compounds Disease severity MMSE Score (mini mental state examination) Prodromal > 25 Mild [21 – 25] Moderate [12 – 20] Severe < 12 Aducanumab Masitinib Prodromal AD > 22 / > 24 Mild & Moderate AD [ 12 – 25] Standard of care in AD .11 There are currently four drugs used in the treatment of mild and moderate AD and approved 20 years ago Year of approval Drug Class 1996 Doneprazil Cholinesterase inhibitors 2000 Rivastigmine Cholinesterase inhibitors 2001 Galantamine Cholinesterase inhibitors 2003 Memantine NMDA Antagonist Masitinib is used in add-on to Standard of Care Primary clinical endpoints .12 Evaluation of efficacy is based on two clinical endpoints Clinical endpoint Objective Assessment Measurement Outcome ADAS-Cog Measure the effect on cognition and memory By patient 11 Questions Maximum 70 points The lower the better ADCS-ADL Measure self-care and activities of daily living By caregiver 23 Questions Maximum 70 Points The higher the better 13 A proof of concept study was published in 2011 AB04024 study results in Alzheimer’s disease Positive effect detected on Daily activityPositive effect detected on cognitive function Piette et al., Alzheimers Res Ther. 2011 Apr 19;3(2):16. doi: 10.1186/alzrt75. Change in ADAS-Cog Change in ADCS-ADL Masitinib Placebo Phase 2a (n=34) -8 -6 -4 -2 0 2 4 6 8 10 12 Week 0 Week 12 p=0.035 Week 24 p=0.128 Mean change from baseline ± standard error ADAS-ADL Masitinib Placebo worsening - improvement -6 -4 -2 0 2 4 6 8 10 Week 0 Week 12 p=0.016 Week 24 p=0.030 Mean change from baseline ± standard error ADAS-Cog Masitinib Placebo worsening - improvement AB09004 – Study Design .14 Study AB09004 evaluated, in add-on to standard of care, three doses of masitinib, each dose having its own placebo control Main inclusion criteriaDesign Design: Double-blind, Placebo-controlled, Randomized, Parallel-group Phase 3 Study to Evaluate the Safety and Efficacy of Masitinib in Patients With Mild to Moderate Alzheimer's Disease (AD), in add-on to Standard of Care Standard of Care (SoC): Cholinesterase inhibitors, memantine Doses tested: ▪ Masitinib 3 mg/kg/day (stopped early based on IDMC recommendation) ▪ Masitinib 4.5 mg/kg/day, randomisation 1:1 ▪ Masitinib titration 4.5 to 6.0 mg/kg/day, randomisation 2:1 Planned Enrolment: 720 patients Primary endpoint: ▪ Change in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) ▪ Change in the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Duration: 24 weeks 1) Patient with dementia of Alzheimer's type, according to the Diagnostic and Statistical Manual of Mental Disorders criteria (DSM-IV) 2) Patient with probable Alzheimer' disease according to the NINCDS-ADRDA criteria (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) 3) Patient with MMSE ≥ 12 and ≤ 25 at baseline 4) Patient treated for a minimum of 6 months with a stable dose of cholinesterase inhibitors and/or a stable dose of memantine, with no changes foreseen in therapy throughout the study. ClinicalTrials.gov Identifier: NCT01872598 AB09004 – Study Design .15 The study was successful if a significant improvement was reached on either ADAS-Cog or ADCS-ADL at a 2.5% level of statistical significance Statistical analysis: ▪ Statistical risk Alpha (chance finding) splited between ADAS-COG (2.5%) and ADCS-ADL (2.5%). ▪ Study is successful if the treatment effect is established in at least one of the two primary endpoints Stratification factors ▪ MMSE score at baseline ▪ Age at baseline ▪ ADCS-ADL total score at baseline ▪ ADAS-COG total score at baseline Populations analysed ▪ Primary analysis : FAS (Full Analysis Set) Type I error was controlled at interim by the Haybittle-Peto alpha spending method The efficacy criteria was tested at a significance level which defined as follows – ▪ Stop at interim and reject null hypothesis on primary endpoint if p-value < 0.001 ▪ If at interim p-value > 0.001, continue to final analysis and efficacy criteria at final analysis is tested at 2.499% level for each of the primary endpoints AB09004 – Population analyzed .16 The study was comprised of two independent sub-studies testing two distinct dosing regimens ITT population N=370 (M=185 ; P=185) Safety population N=368 (M=185 ; P=183) Full Analysis Set N=358 (M=182 ; P=176) Dosing Masitinib 4.5 mg/kg/day vs matching placebo Dosing Masitinib 4.5 to 6.0 mg/kg/day titration vs matching placebo ITT population N=278 (M=186 ; P=92) Safety population N=278 (M=186 ; P=92) Full Analysis Set N=277 (M=186 ; P=91) Study AB09004 : N = 718 from 118 sites in 21 countries, 51.5% of patients enrolled in EU countries Dosing 3.0 mg/kg/day N=58 Stopped early in the study upon IDMC recommendation. Data not analyzed N= 58 is masitinib treated patients. Placebo treated patients are analyzed as part of the placebo arm versus masitinib 4.5 mg/kg/day Dosing 6.0 mg/kg/day N=12 Stopped early in the study by Sponsor decision and replaced with Masitinib 4.5 to 6.0 mg/kg/day titration. Data not analyzed As a result, Group 4.5 mg/kg/day and Group titration up to 6.0 mg/kg/day were not conducted at the same time nor in the same centers Full Analysis Set : Exclusion from ITT population of 13 patients - Patients from sites with critical GCP violations at 2 sites as highlighted by audit report and internal report (n=6) - Patients with no treatment intake (n=2) - Patients with baseline Adl or Cog scores that do not correspond to the medical history, with documented letter from investigator to exclude them from primary analysis, validated by steering committee (n=3) - Patients with caregiver that changed during the main period, with documented letter from investigator to exclude them from primary analysis, validated by steering committee (n=2) AB09004 – Baseline Characteristics .17 Baseline characteristics were balanced FAS Masitinib + SoC (N = 182) Placebo + SoC (N = 176) Age (Years) Mean (std) 71.9 (8.28) 71.7 (8.21) Median 73.0 73.0 >=50 - <60 [n (%)] 19 (10.4) 17 (9.4) >=60 - <70 [n (%)] 44 (24.0) 52 (28.9) >=70 - <80 [n (%)] 82 (44.8) 76 (42.2) ≥ 80 [n (%)] 38 (20.8) 35 (19.4) Sex [n (%)] Female 114 (62.6) 98 (55.7) MMSE 12-20 119 (65.4) 115 (65.3) 21-25 63 (34.6) 61 (34.7) Mean 18.8 (3.73) 18.6 (3.76) Median 19.0 19.0 ADCS-ADL Mean (std) 51.8 (15.13) 51.4 (14.95) Median 55.0 53.5 ADAS-COG Mean (std) 26.1 (10.13) 25.9 (9.67) Median 25.5 24.8 Masitinib 4.5 mg/kg/day vs matching placebo Masitinib 4.5 to 6.0 mg/kg/day titration vs matching placebo FAS Masitinib + SoC (N = 186) Placebo + SoC (N = 91) Age (Years) Mean (std) 71.9 (8.29) 71.2 (8.11) Median 72.0 72.0 >=50 - <60 [n (%)] 14 (7.5) 10 (11.0) >=60 - <70 [n (%)] 54 (29.0) 26 (28.6) >=70 - <80 [n (%)] 78 (41.9) 41 (45.1) ≥ 80 [n (%)] 40 (21.5) 14 (15.4) Sex [n (%)] Female 118 (63.4) 57 (62.6) MMSE 12-20 123 (66.1) 57 (62.6) 21-25 63 (33.9) 34 (37.4) Mean 18.8 (3.62) 18.7 (3.71) Median 19.0 19.0 ADCS-ADL Mean (std) 52.4 (14.76) 53.2 (13.65) Median 54.0 57.0 ADAS-COG Mean (std) 24.9 (10.08) 26.2 (10.64) Median 24.3 24.3 AB09004 – Primary analysis - Cog - 4.5 mg/kg/day .18 The study met its primary analysis, demonstrating a statistically significant reduction in Cognitive impairment based on ADAS-COG (p=0.0003) Significant effect on cognitive function after 24 weeks of treatment Descriptive Statistics Model Summary - LSM Difference Treatment n Mean (SD) LS Mean 95% CI LS Mean (SE) 97.51% CI p-value Masitinib 4.5 mg/kg/day + SoC 182 -1.51 (5.81) -1.46 (-2.46, -0.45) -2.15 (0.59) (-3.48, -0.81) 0.0003 Placebo + SoC 176 0.63 (5.35) 0.69 (-0.36, 1.75) Change in ADAS-Cog - ANCOVA Analysis (Full Analysis Set) - M4.5 vs Placebo Imputation Model for missing Data For the primary analysis, missing values are imputed by using the patient’s previous non-missing score and data from other similar patients (same cluster) that have continued treatment. AB09004 – Cog J2R sensitivity analysis - 4.5 mg/kg/day .19 Cog sensitivity analysis based on Jump to reference imputation method remained positive, demonstrating a robust treatment effect Significant effect on cognitive function confirmed based on Jump to Reference analysis Descriptive Statistics Model Summary - LSM Difference Treatment n Mean (SD) LS Mean 95% CI LS Mean (SE) 95% CI p-value Masitinib 4.5 mg/kg/day + SoC 182 -1.24 (5.86) -1.04 (-2.06, -0.03) -1.89 (0.60) (-3.06, -0.72) 0.0016 Placebo + SoC 176 0.63 (5.35) 0.85 (-0.21, 1.91) Change in ADAS-Cog - ANCOVA Analysis (Jump to Reference) - M4.5 vs Placebo The Jump to Reference (J2R) approach The Jump to Reference, which is the most conservation approach, imputes the Placebo estimates for all patients who prematurely discontinue due to lack of efficacy and toxicity (related TEAE) in the treatment arm. AB09004 – Adl - 4.5 mg/kg/day .20 The study demonstrated a statistically significant improvement on daily activity based on ADCS-ADL (p=0.0381) Significant effect on daily activity after 24 weeks of treatment Change in ADCS-Adl - ANCOVA Analysis (Full Analysis Set) - M4.5 vs Placebo Descriptive Statistics Model Summary - LSM Difference Treatment n Mean (SD) LS Mean 95% CI LS Mean (SE) 97.51% CI p-value Masitinib 4.5 mg/kg/day + SoC 182 0.51 (7.78) 1.01 (-0.48, 2.50) 1.82 (0.87) (-0.15, 3.79) 0.0381 Placebo + SoC 176 -1.09 (9.17) -0.81 (-2.36, 0.74) Imputation Model for missing Data For the primary analysis, missing values are imputed by using the patient’s previous non-missing score and data from other similar patients (same cluster) that have continued treatment. AB09004 – Adl J2R sensitivity analysis - 4.5 mg/kg/day .21 Adl sensitivity analysis based on Jump to reference imputation method showed a numerical advantage close to statistical significance in favor of masitinib Numerical advantage close to statistical significance on daily activity based on sensitivity analyses Descriptive Statistics Model Summary - LSM Difference Treatment n Mean (SD) LS Mean 95% CI LS Mean (SE) 95% CI p-value Masitinib 4.5 mg/kg/day + SoC 182 0.39 (7.79) 0.81 (0.76) (-0.68, 2.30) 1.71 (0.87) (-0.01, 3.43) 0.0512 Placebo + SoC 176 -1.09 (9.17) -0.90 (0.79) (-2.46, 0.65) Change in ADCS-Adl - ANCOVA Analysis (Jump to Reference) - M4.5 vs Placebo The Jump to Reference (J2R) approach The Jump to Reference, which is the most conservation approach, imputes the Placebo estimates for all patients who prematurely discontinue due to lack of efficacy and toxicity (related TEAE) in the treatment arm. AB09004 – Cog and Adl analysis in mITT - 4.5 mg/kg/day .22 mITT analysis shows that the Cog analysis remained positive and Adl analysis lost statistical significance Descriptive Statistics Model Summary - LSM Difference Treatment n Mean (SD) LS Mean 95% CI LS Mean (SE) 95% CI p-value Change in ADAS-Cog Masitinib 4.5 mg/kg/day + SoC 183 -1.49 (5.81) -1.45 (0.51) (-2.45, -0.45) -2.10 (0.59) (-3.25, -0.95) 0.0004 Placebo + SoC 180 0.61 (5.30) 0.65 (0.53) (-0.39, 1.69) Change in ADCS-Adl Masitinib 4.5 mg/kg/day + SoC 183 0.57 (7.79) 1.09 (0.76) (-0.41, 2.59) 1.58 (0.88) (-0.16, 3.31) 0.07426 Placebo + SoC 180 -0.76 (9.35) -0.49 (0.79) (-2.05, 1.08) Post-Hoc Analysis (ANCOVA) in mITT - M4.5 vs Placebo mITT population : - Exclude 8 patients from sites with critical GCP violations at 2 sites as highlighted by audit report and internal report (n=6) and with no treatment intake (n=2) - Retain patients with baseline Adl or Cog scores that do not correspond to the medical history, with documented letter from investigator to exclude them from primary analysis, validated by steering committee (n=3), and patients with caregiver that changed during the main period, with documented letter from investigator to exclude them from primary analysis, validated by steering committee (n=2) AB09004 – CIBIC - 4.5 mg/kg/day .23 CIBIC (Improve) - Logistic Regression Analysis (Full Analysis Set) - M4.5 vs Placebo The study demonstrated a 71% improvement on CIBIC as compared with placebo, statistically significant (p=0.040) Descriptive Statistics Count (percentage) Statistic Treatment n Improvement Worsening/No Change OR (95% CI) p-value Masitinib 4.5 mg/kg/day + SoC 182 47 (25.82) 91 (50.00) 1.71 (1.02, 2.85) 0.0400 Placebo + SoC 176 36 (20.45) 119 (67.61) Modified Last Observation Carried Forward (mLOCF) Comparison between treatment groups performed on the difference between improvement [1-3] and worsening [5-7] CIBIC-plus classes (improvement minus worsening) at Week 24 by using a chi square test for proportions comparison, using Modified Last Observation Carried Forward (mLOCF) methods for the management of missing data. The mLOCF approach carries forward the last observed value for patients who prematurely discontinue due to lack of efficacy and toxicity (related TEAE). AB09004 – MMSE / CDR / NPI - 4.5 mg/kg/day .24 The study showed a numerical advantage non statistically significant in favor of masitinib on MMSE, CDR, and NPI Parameter Treatment Statistics Week 8 Week 12 Week 24 Mini-Mental State Examination (MMSE) Masitinib + SoC n 156 149 139 Mean (SD) 0.49 ( 2.67) 0.79 ( 2.89) 0.35 ( 3.04) Placebo + SoC n 170 163 155 Mean (SD) 0.09 ( 2.52) 0.66 ( 2.77) 0.22 ( 3.02) Diff. of M-P 0.40 0.12 0.13 Clinical Dementia Rating (CDR) Masitinib + SoC n 123 146 136 Mean (SD) -0.05 ( 0.42) -0.03 ( 0.41) -0.01 ( 0.49) Placebo + SoC n 116 162 155 Mean (SD) -0.01 ( 0.41) 0.06 ( 0.48) 0.01 ( 0.55) Diff. of M-P -0.04 -0.09 -0.02 Caregiver Distress (NPI) Masitinib + SoC n 87 103 95 Mean (SD) -1.08 ( 3.58) -0.50 ( 4.62) 0.61 ( 4.88) Placebo + SoC n 77 120 108 Mean (SD) -0.66 ( 3.05) -0.13 ( 3.73) 0.85 ( 4.64) Diff. of M-P -0.42 -0.38 -0.24 Frequency and Severity (NPI) Masitinib + SoC n 87 103 95 Mean (SD) -2.06 ( 7.51) -0.72 ( 9.12) 1.18 (10.20) Placebo + SoC n 77 120 108 Mean (SD) -0.66 ( 5.58) -0.11 ( 7.81) 2.19 ( 8.70) Diff. of M-P -1.40 -0.61 -1.01 Summary of change from baseline (mLOCF) of All Secondary Endpoints Over Time by Treatment - Full Analysis Set - M4.5 vs Placebo AB09004 – Cog and Adl analysis – titration 6.0 mg/kg/day .25 No significant treatment-effect was observed either on Cog or Adl for high-dose masitinib (titration up to 6.0 mg/kg/day) Descriptive Statistics Model Summary - LSM Difference Treatment n Mean (SD) LS Mean 95% CI LS Mean (SE) 95% CI p-value Change in ADAS-Cog Masitinib 4.5 to 6.0 mg/kg/day + SoC 186 -0.54 (4.50) -0.18 (0.47) (-1.10, 0.73) -0.43 (0.61) (-1.81, 0.95) 0.4828 Placebo + SoC 91 -0.26 (5.46) 0.25 (0.60) (-0.94, 1.43) Change in ADCS-Adl Masitinib 4.5 to 6.0 mg/kg/day + SoC 186 0.53 (6.15) 0.57 (0.62) (-0.69, 1.80) 0.20 (0.82) (-1.64, 2.04) 0.8073 Placebo + SoC 91 0.25 (6.98) 0.37 (0.81) (-1.22, 1.96) ANCOVA Analysis (Full Analysis Set) - M4.5 up to 6.0 vs Placebo Improvement in mean Cog (Mean = - 0.26) Improvement in mean daily activity (Mean = 0.25) Improvement under placebo possibly influenced by low number for placebo (n<100) No higher efficacy with masitinib titration to 6.0 vs 4.5 mg/kg/day Cognitive function (Mean = - 0.54 with M6 vs -1.51 with M4.5) Daily activity (Mean = 0.53 with M6 vs 0.51 with M4.5) We can conclude that the effective dose in Alzheimer’s disease for masitinib is 4.5 mg/kg/day AB09004 – 4.5 mg/kg/day vs combined placebo .26 In order to assess the impact of the divergent placebo effect, masitinib 4.5 mg/kg/day was compared with the pooled placebo arms and Cog analysis remained significant Descriptive Statistics Model Summary - LSM Difference Treatment n Mean LS Mean 95% CI LS Mean (SE) 95% CI p-value Change in ADAS-Cog Masitinib 4.5 mg/kg/day + SoC 182 -1.51 (5.81) -1.16 (-2.12, -0.19) -1.90 (0.53) (-2.95, -0.85) 0.0004 Combined Placebo + SoC 267 0.33 (5.40) 0.74 (-0.15, 1.63) Change in ADCS-Adl Masitinib 4.5 tmg/kg/day + SoC 182 0.51 (7.78) 1.00 (-0.39, 2.39) 1.33 (0.77) (-0.18, 2.84) 0.0838 Combined Placebo + SoC 267 -0.64 (8.50) -0.33 (-1.61, 0.95) Significant effect on Cog with masitinib 4.5 versus combined placebo ANCOVA Analysis (Full Analysis Set) - M4.5 vs Combined Placebo AB09004 – Severe Dementia - 4.5 mg/kg/day vs combined placebo .27 There were significantly fewer patients reaching severe dementia stage (MMSE<10) and a significant decrease in time to severe dementia with masitinib 4.5 mg/kg/day compared with the pooled placebo arms Significant effect on severe dementia (MMSE<10) with masitinib 4.5 versus combined placebo Dementia- M4.5 vs Placebo Pooled (FAS) p-value Hazard Treatment group Total No. of Events Percentage Events No. Censored Percentage censored Median [95% CI] KM p- Value Log Rank Ratio (95% CI) p-Value Masitinib 4.5 mg/kg/day 182 2 1.10 180 98.90 Not reached [ ; ] 0.0446 0.0403 0.19 (0.0,0.8) 0.0276 Pooled Placebo 267 15 5.62 252 94.38 6.3 [5.9;6.3 ] Baseline MMSE (FAS) Masitinib + SoC (N = 182) Pooled Placebo + SoC (N =267) < 14 18 (9.9) 30 (11.2) < 17 54 (29.7) 81 (30.3) AB09004 – Safety Overview .28 The safety of masitinib consistent with its known tolerability profile Masitinib 3.0 + SoC (N = 58) n (%) Masitinib 4.5 + SoC (N = 185) n (%) Masitinib 4.5 to 6.0 + SoC (N = 186) n (%) Placebo + SoC (N = 280) n (%) At least one AE 53 ( 91.4) 161 ( 87.0) 160 ( 86.0) 217 ( 77.5) At least one serious AE (non-fatal) 6 ( 10.3) 24 ( 13.0) 25 ( 13.4) 15 ( 5.4) At least one severe AE 9 ( 15.5) 49 ( 26.5) 47 ( 25.3) 54 ( 19.3) Summary of Adverse Events – Safety population - [W0-W24] period Among the 13% and 13.4% SAEs with masitinib (M4.5 and M6), 4.8% and 4.9 % were associated with mild or moderate adverse events, respectively AB09004 – Safety Overview .29 The increase in Serious adverse events was equally distributed across all organ classes Masitinib 3.0 + SoC (N = 58) n (%) Masitinib 4.5 + SoC (N = 185) n (%) Masitinib 4.5 to 6.0 + SoC (N = 186) n (%) Placebo + SoC (N = 280) n (%) At least one Serious Adverse Event 6 ( 10.3) 24 ( 13.0) 25 ( 13.4) 15 ( 5.4) Skin and subcutaneous tissue disorders 1 ( 1.7) 3 ( 1.6) 9 ( 4.8) 0 ( 0.0) Infections and infestations 0 ( 0.0) 6 ( 3.2) 3 ( 1.6) 3 ( 1.1) Blood and lymphatic system disorders 3 ( 5.2) 4 ( 2.2) 4 ( 2.2) 0 ( 0.0) Gastrointestinal disorders 0 ( 0.0) 4 ( 2.2) 1 ( 0.5) 1 ( 0.4) Neoplasms benign, malignant and unspecified 0 ( 0.0) 3 ( 1.6) 1 ( 0.5) 2 ( 0.7) Cardiac disorders 0 ( 0.0) 4 ( 2.2) 1 ( 0.5) 0 ( 0.0) Injury, poisoning and procedural complications 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 5 ( 1.8) Investigations 1 ( 1.7) 1 ( 0.5) 2 ( 1.1) 1 ( 0.4) Hepatobiliary disorders 0 ( 0.0) 1 ( 0.5) 1 ( 0.5) 2 ( 0.7) Nervous system disorders 1 ( 1.7) 1 ( 0.5) 2 ( 1.1) 0 ( 0.0) General disorders and administration site conditions 0 ( 0.0) 0 ( 0.0) 3 ( 1.6) 0 ( 0.0) Renal and urinary disorders 0 ( 0.0) 3 ( 1.6) 0 ( 0.0) 0 ( 0.0) Respiratory, thoracic and mediastinal disorders 0 ( 0.0) 2 ( 1.1) 1 ( 0.5) 0 ( 0.0) Immune system disorders 0 ( 0.0) 1 ( 0.5) 0 ( 0.0) 0 ( 0.0) Metabolism and nutrition disorders 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 1 ( 0.4) Musculoskeletal and connective tissue disorders 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) 1 ( 0.4) Reproductive system and breast disorders 0 ( 0.0) 1 ( 0.5) 0 ( 0.0) 0 ( 0.0) Non - Fatal Serious Adverse Events by System Organ Class – Safety population - [W0-W24] period Intellectual Property 30 A new patent was filed based on results from study AB09004, which would permit AB Science to retain exclusive rights on the use of masitinib in Alzheimer’s disease until 2041. Protection Item Duration of protection Status Patent on composition of matter and PTE Patent on composition of matter has been filed and delivered. It will be further extended until 2028 through patent term extension (PTE) Until 2028 Delivered Synthesis process patent A further protection until 2028 has been achieved through synthesis ‘process’ patent Until 2028 Delivered Phase 2/3 ‘Method of use’ patents New patent based on results from study AB09004 Until 2041 Filed Market potential 31 Indication Prevalence Alzheimer’s Disease 1,000 / 100,0001 Mild and moderate forms of Alzheimer’s Disease* 60%2 Source : Population : https://data.worldbank.org/indicator/SP.POP.TOTL and https://ec.europa.eu/eurostat/web/population-demography-migration-projections/population-data/main-tables 1. Weili Xu et al. Epidemiology of Alzheimer’s Disease. 2013.doi: 10.5772/54398 2. https://www.j-alz.com/editors-blog/posts/when-do-we-diagnose-severe-alzheimers-disease * : expressed as percentage of Alzheimer’s Disease Annual cost of drugs registered in the indication No approved drug as an add-on to cholinesterase inhibitors or memantine Estimated number of potential eligible patients US Patients EU Patients 2,000,000 3,000,000 Q&A

The release as fetched from its publisher. ab-science.com ↗