Slide 1: Efficacy and safety of roluperidone for the treatment of negative symptoms of schizophrenia
3 Authors: Michael Davidson1,2 MD, Jay Saoud1 PhD, Corinne Staner3 MD, Nadine Noel3 PhD, Sandra Werner3 PhD, Elisabeth Luthringer3 RN, Philip Harvey PhD, Gregory Strauss PhD, Mark Weiser4MD, Remy Luthringer1 PhD Efficacy and safety of roluperidone for the treatment of negative symptoms of schizophr
Slide 2: Abstract
Abstract Objective: In a previous large multi-national trial, roluperidone (MIN-101) a compound with antagonistic properties for 5‑HT2A, sigma2 and α1A-adrenergic receptors demonstrated statistically significant efficacy in reducing negative symptoms and good tolerability in stable schizophrenia pat
Slide 3: Roluperidone
Roluperidone Receptor subtypes _ Materials Ki values, nmol/L Rat, cerebral cortex 7.5 Serotonin 5-HT: esealiieralen Human binant 5.2 Sigma, Guinea pig, brain 8.2 Sigma, Guinea pig, brain 253.8 A, adrenergic Rat, brain 14.4 v Specific Affinity for 5-HT2, 02, and o.,-adrenergic receptors Y No affinity
Slide 4: Trial design and patient population
Trial design and patient population 12 weeks double blind 32 mg/day, 64 mg/day or placebo in 1/1/1 ratio, followed by 9 months open label phase DSM-5 schizophrenia Baseline score ≥ 20 on the PANSS negative symptoms subscale Symptomatically stable for 6 months A score <4 on the PANSS P-4excitement/hy
Slide 5: PANSS Negative Symptoms Factor Score (Marder) Change from Baseline (MMRM)
PANSS Negative Symptoms Factor Score (Marder) Change from Baseline (MMRM) (ITT Population) WEEK 0 2 4 6 8 10 12 1.0 2 00 £ seting Mean (SD) Fa Placebo MI. mg MIN-101 64 mg 3 24.3 (3.0) M24) 25.4 (3.2) —€ 1.0 2 8 § -2.0 s i 2 - & 3.9 Improvement 4 © 5 8 = -4.0 p<0.259 | p<0.064 5.0 —Placebo = - -MIN-
Slide 6: NSFS Score – Double-Blind Primary Endpoint, mITT
NSFS Score – Double-Blind Primary Endpoint , mITT Improvement Decision to exclude one site because of questionable data quality was taken before the data blinding was removed
Slide 7: PSP Total Score Change from Baseline (MMRM)
LS Mean + SEM Change from Baseline PSP Total Score Change from Baseline (MMRM) (ITT Population) WEEK 0 2 4 6 8 10 12 Baseline Mean (SD) Placebo MIN-10132 mg — MIN-10164 mg 52.6(11.0) 52.5(12.2) 52.6 (10.5) ps0.021) Improvement —Placebo ---MIN-101 64 mg = -MIN-101 32 mg Note: MINERVA
Slide 8: Mean±SEM Change from Study Baseline in Marder NSFS by Visit
MeansSEM Change from Study! Baseline in Marder NSFS by Visit [ Desbcmia Pine [indo Pi Open Lab NV do nd nan ana Ticetteamentt | a So & Baseline Week? Weeks Weeks Week 12 R14 Wis wre waa we wees Wes? Wk sues > MIN-101 32mg —*=-MIN-101 64mg -* Placebo 9 MINERVA
Slide 9: Mean±SEM Change from Study Baseline in PSP Total Score by Visit
Mean+SEM Change from Study! Baseline in PSP Total Score by Visit ¢ L__Damvic nina ane Teac ore Pha “Open: Label: MIN-TOI dove Dinded to mvestgators and patents Tend of treatment |] 1 — Improvement 14 Gn 510 8 a 6 g Bs to) 2 ° = LJ Baseline Week d Week Week 12 Week 16 Week 24 Week 32 Week 0 Week ae W
Slide 10: Other key efficacy parameters
Other key efficacy parameters The relapse rate during the OLE, defined as patients being withdrawn from the trial due to worsening of symptoms of psychosis, was 15 patients out of 166 patients (9%) in the 32 mg arm and 10 patients out of 167 patients (6%) in the 64 mg arm. Over the one-year duration
Slide 11: Phase 2b study showed improvements in negative symptoms
Phase 2b study showed improvements in NS over 12 weeks and 36 weeks in both doses and stable positive symptoms Core 12-week phase: Statistically significant improvements in the primary endpoint 12-Week DB & 24-week extension phase Core Phase Extension Phase Source: Davidson et al., 2017
Slide 12: Roluperidone showing improvement in both Experience & Expression of Negative Symptoms
Roluperidone showing improvement in both “Experience” & “Expression” of Negative Symptoms These results are consistent with improvements observed in other scales such as PSP (Personal & Social Performance Scale)
Slide 13: How much does the assessment instrument matter?
How much does the assessment instrument matter?
Slide 14: Discussion
Discussion Roluperidone administered as monotherapy may improve negative symptoms and social functioning in patients suffering from schizophrenia and moderate to severe negative symptoms. Monotherapy, rather than add-on to antipsychotics, design was selected for two trials because: antipsychotics ma