Newron Pharmaceuticals S.p.a. · SIX:NWRN

Newron Pharmaceuticals — WCBP Berlin (September 2025)

17 slides from Newron Pharmaceuticals's conference presentation, Sep 10, 2025

  1. Slide 1: Glutamate Modulation as Adjunctive Therapy in Patients with Schizophrenia

    GLUTAMATE MODULATION AS ADJUNCTIVE THERAPY IN PATIENTS WITH SCHIZOPHRENIA NOT ADEQUATELY RESPONDING TO SECOND-GENERATION ANTIPSYCHOTICS Clinical benefits of evenamide in a phase 3, international, randomized, double-blind, placebo-controlled trial Ravi Anand, MD Chief Medical Officer - Newron Pharmac

  2. Slide 2: Neurochemical Changes in APs Responders, TRS, and Healthy Controls

    NEUROCHEMICAL CHANGES IN APS RESPONDERS, TRS, AND HEALTHY CONTROLS Dopamine synthesis capacity (whole striatum)1 • Patients with TRS and non-responders from Striatal dopamine synthesis 0.016 p=0.02 first episode have a normal dopamine capacity (Kicer), per min 0.015 synthesis capacity1,3 0.014 Mean

  3. Slide 3: Evenamide's efficacy and attenuation of vHipp hyperexcitability

    Evenamide's efficacy in downregulating the hyperdopaminergic state, social deficits, and recognition memory impairment may result from its ability to attenuate vHipp hyperexcitability Evenamide is capable of addressing positive, cognitive, and negative symptoms of schizophrenia Sustained effects of

  4. Slide 4: Antipsychotic Drug Action

    ANTIPSYCHOTIC DRUG ACTION PFC Hippocampus Dopamine cognition-no impact Receptor Amygdala – Only effective if negative elevated DA activity symptoms- no impact Site of Action of Current Antipsychotic Site of VTA Ventral Drugs Deficit Dopamine Ventral Striatum Pallidum A better approach would be to tr

  5. Slide 5: Ketamine-Induced Deterioration of PPI Rescued by Clozapine and Evenamide Combination

    KETAMINE-INDUCED DETERIORATION OF PPI IS RESCUED BY A COMBINATION OF INEFFECTIVE DOSES OF CLOZAPINE AND EVENAMIDE 80 Impairment “Full reversal” 60 P<0.001 ^^^ *** Evenamide FGAs/SGAs %PPI Average 40 *** ns ns Combination of ineffective doses of evenamide with 1 20 antipsychotics (APs) was associated

  6. Slide 6: Studies with Evenamide in Human Subjects

    STUDIES WITH EVENAMIDE IN HUMAN SUBJECTS Phase 1 Phase 2 Phase 3 001, 007, 010, 011 002 008 014 - TRS 008A 015 - TRS (OLE) N=115 N=89 N=138 N=161 N=291 EU; LATAM; Asia US, UK, GER US; India US; India India; Sri Lanka; Italy 11 countries Randomized Double-blind Double blind Open label Double-blind Pl

  7. Slide 7: Study 008A – Outpatient Study in Inadequately Responding Patients

    STUDY 008A – OUTPATIENT STUDY IN INADEQUATELY RESPONDING PATIENTS WITH CHRONIC SCHIZOPHRENIA Day 29 Safety Day 0/1 Endpoint Follow up Day 8 Day 15 Day 22 (+ 30 days) 21-day Screening Period Antipsychotic plasma levels to confirm adherence RANDOMIZATION Evenamide (30 mg bid) Eligibility Process Place

  8. Slide 8: Summary of Disposition and Adverse Events

    SUMMARY OF DISPOSITION AND ADVERSE EVENTS Evenamide Placebo 30 mg bid n (%) n (%) Screened - - Randomized 132 159 Completed Day 29 126 (95.5) 154 (96.9) Adverse dropout* 2 (1.5) 1 (0.6) Withdrawal of consent 4 (3.0) 4 (2.5) Most frequent adverse events Nasopharyngitis 3 (2.3) 1 (0.6) Headache 3 (2.3

  9. Slide 9: PANSS Total Score to Day 29; ITT Population

    PANSS TOTAL SCORE TO DAY 29; ITT POPULATION PRIMARY ESTIMAND - TREATMENT POLICY; MMRM 0 Evenamide 30 mg bid N=132 -2 Placebo -4 * N=159 -6 * Drug-Placebo Difference: -8 -7.6 (0.7) LS mean (SE) = -2.5 (0.9) -10 p-value: 0.006 -10.2 (0.7) Cohen’s d= 0.33 -12 CI: -4.3, -0.7 Baseline Day 8 Day 15 Day 22

  10. Slide 10: Primary and Key Secondary Efficacy Endpoints Mean Change from Baseline to Day 29

    PRIMARY AND KEY SECONDARY EFFICACY ENDPOINTS MEAN CHANGE FROM BASELINE TO DAY 29 - ITT POPULATION - PRIMARY ESTIMAND - TREATMENT POLICY; MMRM Evenamide Placebo LS mean difference (SE) Scale Visit 30 mg bid N=159 p-value [CI] N=132 Baseline – mean (SD) 4.4 (0.6) 4.5 (0.6) -0.16 (0.08)* CGI of Severit

  11. Slide 11: Responder Analyses - Proportion of Patients

    RESPONDER ANALYSES - PROPORTION OF PATIENTS (%) - MITT; OC PANSS improving ≥20% from baseline CGI-C rating of at least “much improved” p-value = 0.037 p-value = 0.006 Evenamide Placebo Evenamide Placebo OR 2.18 N=131 N=156 OR 1.99 N=131 N=156 CI (1.0, 3.8) CI (1.2, 3.8) * 31.3 * 20.6 19.8 17.3 12.2

  12. Slide 12: Evaluation of Primary and Key Secondary Efficacy Endpoints Sensitivity Analyses

    EVALUATION OF PRIMARY AND KEY SECONDARY EFFICACY ENDPOINTS SENSITIVITY ANALYSES Endpoint Analysis Model p-value Measure Primary Estimand Treatment Policy MMRM 0.006 Supportive Estimand Hypothetical 0.002 Primary PANSS Total score WOCF ANCOVA 0.008 MI ANCOVA 0.006 Tipping point ANCOVA 0.004 Key secon

  13. Slide 13: PANSS Mean Change from Baseline by Current Antipsychotic Medication

    PANSS MEAN CHANGE FROM BASELINE BY CURRENT ANTIPSYCHOTIC MEDICATION; ITT; OC Evenamide 30 mg bid Placebo N=132 N=159 Antipsychotic PANSS change from PANSS change from n (%) n (%) baseline (SD) baseline (SD) Risperidone 51 (38.6) -8.8 (6.5) 63 (39.6) -7.3 (7.4) Olanzapine 32 (24.2) -13.4 (8.6) 32 (20

  14. Slide 14: PANSS Response of Patients Who Failed 1 vs ≥2 Antipsychotics

    PANSS RESPONSE OF PATIENTS WHO FAILED 1 VS ≥2 ANTIPSYCHOTICS - (ITT; OC) PANSS Change Day 29 Antipsychotic Mean (SD) Stat attempts* Evenamide Placebo EVE-PBO N=127 N=154 p-value n (%) 38 (29.9) 50 (32.5) -4.1 1 Mean change (SD) -8.9 (6.5) -4.8 (6.4) 0.0122# n (%) 89 (70.1) 104 (67.5) -2.4 ≥2 Mean ch

  15. Slide 15: Evenamide Study NW-3509/023/III/2024 (ENIGMA-TRS 1)

    Evenamide Study NW-3509/023/III/2024 (ENIGMA-TRS 1) A Phase III, 52-week, prospective, randomized, double-blind, placebo-controlled, parallel-group, multi-center study, with a primary efficacy endpoint at 12 weeks, to determine the efficacy, safety, and tolerability of fixed doses of 15 mg bid and 3

  16. Slide 16: Evenamide Phase 3 TRS Study – ENIGMA-TRS 1

    Evenamide Phase 3 TRS Study – ENIGMA-TRS 1 12-Week 26-Week 52-Week ICF Baseline Day 0 Eligibility Randomization Screening – 42 days Double-blind treatment of 52 weeks Confirmation of Pivotal study endpoint Maintenance endpoint Long-Term Efficacy treatment resistance TRRIP criteria* Third (1-year) Ef

  17. Slide 17: Thank you

    Thank you CY)

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