Slide 1: Evenamide TRS Study 014/015: 6-month results
COMMITTED TO CNS DRUG DEVELOPMENT INNOVATIVE TREATMENTS TO IMPROVE QUALITY OF LIFE Evenamide TRS Study 014/015: 6-month results Stefan Weber, CEO Ravi Anand, CMO January 3, 2023
Slide 2: Disclaimer
DISCLAIMER RESTRICTED SCOPE; EXCLUSION OF LIABILITY; CONFIDENTIALITY This document has been prepared by Newron Pharmaceuticals S.p.A. ("Newron") solely for your information. The information contained herein has not been independently verified. No representation or warranty, express or implied, is ma
Slide 3: Company Highlights
COMPANY HIGHLIGHTS Unique portfolio of innovative Management team with extensive CNS product candidates experience and proven track record Xadago® for Parkinson’s disease – Global in drug development and approvals validate Newron’s development commercialization capabilities from research to market
Slide 4: Innovative Clinical Pipeline with Near-Term Catalysts
INNOVATIVE CLINICAL PIPELINE WITH NEAR-TERM CATALYSTS PRODUCTS PHASE I PHASE II PHASE III MARKET COMMERCIAL RIGHTS Adjunctive therapy in PD Zambon Xadago® Adjunctive therapy in PD Zambon/Supernus (safinamide)1 Adjunctive therapy in PD Meiji Seika/Eisai Levodopa Induced Dyskinesia (PD LID) Zambon/Sup
Slide 5: Differentiation of Evenamide in Schizophrenia
DIFFERENTIATION OF EVENAMIDE IN SCHIZOPHRENIA Large market Positive results from phase II Study 002 in non- Unique MoA and positioning TRS patients − First add-on drug 1 of 2 pivotal studies (non-TRS) ongoing − Change a non-responder into a responder Pilot study in TRS patients ongoing, 4
Slide 6: Enormous Medical Need for 20 Million Patients Worldwide
ENORMOUS MEDICAL NEED FOR 20 MILLION PATIENTS WORLDWIDE Over 30 antipsychotics available, but all provide short-term and insufficient relief of some of the symptoms VAST MARKET OPPORTUNITY Most patients with schizophrenia demonstrate reduced control of positive (anti-psychotics symptoms by typical a
Slide 7: Evenamide – The Commercial Opportunity
EVENAMIDE – THE COMMERCIAL OPPORTUNITY • Large Market Opportunity • NO direct competition as evenamide can be added to all antipsychotics • Promise to change treatment management paradigm in schizophrenia First add-on antipsychotic to be approved for inadequately responding patients − Up to 70% of
Slide 8: Evenamide's Unique MoA Demonstrated
EVENAMIDE’S UNIQUE MOA DEMONSTRATED Selectively blocks native sodium channels, showing no off-target effect on >130 other CNS receptors, enzymes, transporters, etc. Modulates sustained repetitive firing Selectively blocks VGSCs in a Inhibits without inducing impairment of voltage-and use-dependent m
Slide 9: Monotherapy and Add-On Effect of Evenamide in Animal Models Relevant to Schizophrenia
MONOTHERAPY AND ADD-ON EFFECT OF EVENAMIDE DEMONSTRATED IN ANIMAL MODELS RELEVANT TO SCHIZOPHRENIA MONOTHERAPY ADD-ON Information Pre-pulse inhibition (PPI) disrupted by dopamine activation (amphetamine -rat) Processing Pre-pulse inhibition (PPI) disrupted by NMDA antagonists (MK-801, PCP, -rat)
Slide 10: Disposition of Subjects Exposed to Evenamide and Most Frequent Adverse Events
DISPOSITION OF SUBJECTS EXPOSED TO EVENAMIDE AND MOST FREQUENT (>3%) TREATMENT EMERGENT ADVERSE EVENTS ~ 430 human subjects 275 completed patients in 9 studies (~95% completed) ~ 130 patients in ongoing studies (including extension) 24 Discontinued 4 for Adverse Events (Seizure, Atrial ~ 270 patie
Slide 11: Conclusions on Safety
CONCLUSIONS ON SAFETY Single doses of 60 mg of evenamide in healthy To date, >400 subjects have been treated in volunteers, and multiple doses of 7.5 to 30 mg Phase I-III trials without any evidence of EPS, bid in patients with schizophrenia receiving metabolic syndrome, sexual disfunction, antipsyc
Slide 12: Evenamide: Efficacy Demonstrated in Patients with Schizophrenia (Non-TRS, Study 002)
EVENAMIDE: EFFICACY DEMONSTRATED IN PATIENTS WITH SCHIZOPHRENIA (NON-TRS, STUDY 002) 4-week, placebo-controlled, add-on study of evenamide (15-25mg BID/day) in 89 patients on stable doses of aripiprazole or risperidone showing signs of worsening when compared to standard of care, at every assessme
Slide 13: Evenamide: Regulatory Interactions
EVENAMIDE: REGULATORY INTERACTIONS Health Authorities (Spain, Denmark, Sweden, Germany, UK, CHMP, US, Canada) consulted on Phase III plan Newron providing additional informative studies suggested by the FDA prior to allowing Newron to initiating its Phase III development program Preclinical part o
Slide 14: Ongoing Phase II Exploratory Safety and Efficacy Study in TRS Patients
ONGOING PHASE II EXPLORATORY SAFETY AND EFFICACY STUDY IN TRS PATIENTS Six-week, open-label, randomized, rater-blinded, parallel group study, option to enter extension up to 12 months PHASE II To evaluate tolerability and preliminary efficacy of adjunctive 7.5, 15, 30 mg BID TRS patients with
Slide 15: Ongoing Exploratory Study in TRS Patients (Study 014) Interim Assessment
ONGOING EXPLORATORY STUDY IN TRS PATIENTS (STUDY 014) INTERIM ASSESSMENT OBJECTIVE Provide data on safety and preliminary evidence of benefit to Independent Safety Monitoring Board to allow assessment of risk-benefit for evenamide ANALYSIS POPULATION First 100 patients randomized completing 6-we
Slide 16: Efficacy: PANSS Total Score by Visit and Change from Baseline
EFFICACY: PANSS TOTAL SCORE BY VISIT AND CHANGE FROM BASELINE PANSS TOTAL SCORE CHANGE FROM BASELINE 82 0% 0 79.7 80 78.2 -2% Effect further -1,6 Effect further 78 (2.0%) improved -4% improved 76 75.5 by > 30% by > 30% -4,1 74 72.8 -6% (5.1%) 72 70,4 -8% 70 -6,9 -10% (8.7%) 68 -12% -9,4 66 (11.8%) 6
Slide 17: Efficacy: PANSS Total Score Responder Rate
EFFICACY: PANSS TOTAL SCORE RESPONDER RATE 100% 90% 80% Responders more 70% than doubled 60% 50% 40% 30% 20% 16% 10% 5% 0% 1% 0% Day 8 Day 15 Day 29 Day 43 Week 30 Responders: Improvement ≥20% on PANSS total score 17
Slide 18: Efficacy: CGI-S & CGI-C Over Time
EFFICACY: CGI-S & CGI-C OVER TIME CGI-S CGI-C Visit Mean Rating Mean Change from Baseline Mean Rating Baseline 4.6 – – Day 8 4.5 -0.1 3.8 Day 15 4.3 -0.3 3.5 Day 29 4.0 -0.5 3.2 Day 43 3.9 -0.7 3.0 6-Month Change further improved by > 25% Rating further improved by ~10% 18
Slide 19: Efficacy: CGI-C Responder Rate
EFFICACY: CGI-C RESPONDER RATE 100 80 Responders further improved by > 10% 60 40 27% 20 10% 1% 0% 0 Day 8 Day 15 Day 29 Day 43 Week 30 Responders: Very much improved | Much improved Non-Responders: Minimally improved | No change | Minimally worse | Much worse | Very much worse 19
Slide 20: Efficacy: CGI-S Responder Rate
EFFICACY: CGI-S RESPONDER RATE 100% 90% Responders 80% further increased 70% by ~20% 59% 60% 47% 50% 40% 30% 25% 20% 8% 10% 0% Day 8 Day 15 Day 29 Day 43 Week 30 Responders: Any improvement on CGI-S 20
Slide 21: Interim Efficacy Assessment – 6-Month versus 6 Weeks
INTERIM EFFICACY ASSESSMENT – 6-MONTH VERSUS 6 WEEKS FIRST 100 PATIENTS RANDOMIZED IN STUDY 014 FOLLOWED OVER TIME Item 6-week 30-week** (compared to 6 weeks) Completers 97 85 Adverse Drop-Outs 1 2 (+1) PANSS Total – Mean change from baseline -9.4 Further improved by > 30% PANSS Total – Responders r
Slide 22: Conclusions
CONCLUSIONS Add-on of evenamide to all 97% completed 6-week treatment antipsychotics was well tolerated with period with 90% continuing in few new adverse events extension study PANSS total, CGI-S, LOF, and MSQ show This indicates the treating psychiatrists gradual improvement over time at doses rat
Slide 23: Newron Has Initiated the First of Two Pivotal Studies
NEWRON HAS INITIATED THE FIRST OF TWO PIVOTAL STUDIES PHASE IIB/III PHASE III Safety and efficacy study (study 008A, Safety and efficacy study in TRS patients non-TRS), started Sept 6th, 2021 to start in 2023 (study 003) Four-week, randomized, double-blind, placebo- Ten-week, randomized, double-
Slide 24: Contact Details
CONTACT DETAILS NEWRON Stefan Weber – CEO +39 02 6103 46 26 pr@newron.com UK/Europe Germany/Europe Simon Conway, Ciara Martin Anne Hennecke/Caroline Bergmann, FTI Consulting MC Services +44 20 3727 1000 +49 211 52925220 SCnewron@fticonsulting.com newron@mc-services.eu Switzerland USA Valentin Handsc