Oryzon Genomics Sa · BME:ORY
Oryzon Genomics Sa — Technical Presentation (January 2024)
23 slides from Oryzon Genomics Sa's technical presentation, Jan 7, 2024
Slide 1: Topline Results Phase 2b PORTICO study
Topline Results Phase 2b PORTICO study Efficacy of vafidemstat in Borderline Personality Disorder Pioneering personalized medicine January 7, 2024 in epigenetics
Slide 2: Legal Notice
Legal Notice DISCLAMER This document has been prepared by Oryzon Genomics, S.A. exclusively for use during the presentation. Oryzon Genomics, S.A. does not assume liability for this document if it is used with a purpose other than the above. The information and any opinions or statements made in thi
Slide 3: Topline Results of Vafidemstat's Phase 2b PORTICO trial in BPD
❖ The primary endpoints improvement in Borderline Personality Disorder Checklist (BPDCL) and in aggression by CGI-S A/A did not reach statistical significance. ❖ Nominal statistically significant, and clinically meaningful, reduction was achieved in the secondary endpoint Borderline Topline Results
Slide 4: Borderline personality disorder: a serious and prevalent disease with no approved drugs
Borderline personality disorder: A serious and prevalent disease with no approved drugs Two main types of symptoms • Frantic efforts to avoid real or imagined abandonment Unstable-extreme • Pattern of unstable and intense interpersonal relationships alternating between extremes of idealization inter
Slide 5: Borderline Personality Disorder (BPD). Multifactorial etiology
Borderline Personality Disorder (BPD). Multifactorial etiology BPD etiology is multifactorial, but LSD1i effects are coherent with a potential therapeutic benefit. • A growing body of data indicates that the glutamatergic system, particularly the N-methyl-D-aspartate (NMDA) subtype receptor, plays a
Slide 6: Vafidemstat's unique MoA and pharmacology supports use in different mental diseases
Vafidemstat’s unique MoA and pharmacology supports use in different mental diseases Aggression Vafidemstat (aka ORY-2001) and other LSD1i induce NMDAR rescue expression of genes involved in neuronal plasticity, restoring neuronal morphology, branching and axonal navigation Vafidemstat restores the r
Slide 7: Vafidemstat is safe and well tolerated
Vafidemstat is safe and well tolerated A very robust safety package. +430 treated subjects Brain Penetrant Safe, No DDIs No side effects ❖ No weight gain ❖ No sedation / somnolence ❖ No sexual dysfunction Comparable SARs between An optimal ❖ No extrapyramidal placebo and vafidemstat CSF : plasma sig
Slide 8: Vafidemstat: Excellent pharmacology & established RP2D in previous trials
Vafidemstat: Excellent pharmacology & established RP2D in previous trials Oral, once a day PK data supports once daily dosing in both adult and Full LSD1 occupancy elder subjects at 1.2 mg/day 8
Slide 9: Multiple shots on goal & main investment thesis in the short-mid term
Multiple Shots on goal & main investment thesis in the short-mid term Phase I Phase II Preclinical Expected Program Study Status Phase Phase Ia Phase Ib Phase IIa Phase IIb Milestone(s) CNS: Vafidemstat (ORY-2001) - CNS optimized LSD1 inhibitor Completed. Study has Top line data in January BPD PORTI
Slide 10: EVOLUTION, an ongoing PoC schizophrenia study with vafidemstat
EVOLUTION, an ongoing PoC schizophrenia study with vafidemstat EVOLUTION: An adaptative randomized double blind, placebo-controlled Phase IIb trial with vafidemstat in schizophrenia patients • Strong rationale: LSD1i restores phenotypes in various SCZ mice models • High Unmet Need: No drugs approved
Slide 11: PORTICO: Phase IIb randomized, placebo-controlled, double blinded trial in BPD
PORTICO: Phase IIb randomized, placebo-controlled, double blinded trial in BPD Primary Endpoints Key Inclusion criteria Improvement in Clinical Global Impression-Severity by Agitation/Aggression (CGI-S A/A) from baseline to weeks 8-12 Men and women 18-65 years of age Improvement in Borderline Person
Slide 12: Demographics
Vafidemstat Placebo (n = 106) (n = 104) Psychotherapy at Baseline: No (n) / Yes 84/22 82/22 (n) DEMOGRAPHICS Age (years, Mean (SD)) 32.4 (10.68) 31.8 (10.89) PORTICO enrolled a representative Female n (%) 78 (73.6) 79 (76.0%) real-world BPD population allowing Male n (%) 28 (26.4%) 25 (24.0%) common
Slide 13: Baseline characteristics
Vafidemstat Placebo (n = 106) (n = 104) AAPI-CR Total 74.1 (22.51) 78.0 (22.30) BASELINE CHARACTERISTICS BPDCL Total 141.7 (36.96) 144.6 (34.08) CGI-Severity A/A 4.8 (0.82) 4.7 (0.82) BEST Total 39.9 (10.06) 39.6 (10.02) There were no statistically significant group differences across endpoints STAX
Slide 14: No statistical significance in the two primary endpoints: BPDCL and CGI-S A/A
No Statistical Significance in the two Primary Endpoints: BPDCL and CGI-S A/A CGI-Severity A/A Across weeks 8-12 LS Means Estimate (SE) Pcbo Vafi Pcbo Vafi 0 -0,2 -0,4 -0,6 -0,8 -1 -1,2 -1,4 -1,6 p=0.412 p=0.254 14
Slide 15: Nominal statistical significance in secondary endpoint: improvement in BEST
Nominal Statistical Significance in Secondary endpoint: Improvement in BEST across weeks 8-12 BASELINE BEST-Total Score LS Means Estimate (SE) BEST-Total Score Across weeks 8-12 LS Means Estimate (SE) 0 Pcbo Vafi -2 -4 -6 -8 -10 -12 * -14 p=0.1823 p=0.0152 p=0.0799 p=0.0423 22.1% 38.3% 27.5% 28.9% 1
Slide 16: Nominal statistical significance in secondary endpoint: STAXI Trait Anger
Nominal Statistical Significance in Secondary endpoint: Improvement in STAXI Trait Anger across weeks 8-12 BASELINE STAXI-Trait Anger STAXI-Trait Anger Scale Across weeks 8-12 LS Means Estimate (SE) LS Means Estimate (SE) Pcbo Vafi ** p=0.2753 p=0.0016 p=0.0778 p=0.0259 23.9% 80.8% 40.2% 46.7% 16
Slide 17: All efficacy endpoints consistently favored vafidemstat over placebo
PORTICO: All efficacy endpoints consistently favored vafidemstat over placebo BEST01-Total Score 0.0423 -2.05 0.0799 -1.76 STAXI1-Trait Anger Scale Raw Score 0.0259 -2.25 0.0778 -1.77 *P-values are uncorrected for multiplicity Favors Vafidemstat Favors Placebo 17
Slide 18: Global statistical test consistent with a global treatment effect favoring vafidemstat
Global statistical test (GST) consistent with a global treatment effect favoring vafidemstat BPD is a multisymptomatic disease with psychiatric, behavioral, and functional outcomes. GST is designed to address whether a treatment is efficacious across different aspects of a condition. GST efficiently
Slide 19: Topline Safety: vafidemstat was safe and well tolerated
Topline Safety: vafidemstat was safe and well tolerated • Treatment Emergent Adverse Events (TEAEs) were slightly lower for those receiving vafidemstat Placebo Vafidemstat • Treatment-Related TEAEs were similar between (N=104) (N=106) n (%), e n (%), e groups Treatment Emergent AEs (TEAEs) 68 ( 65.
Slide 20: PORTICO: Topline Safety – Treatment Emergent & Serious AEs
PORTICO: Topline Safety – Treatment Emergent & Serious AEs Treatment-Emergent Adverse Events by Preferred Term Occurring in > 5% of Subjects Serious Adverse Events ❖ There was 1 serious AE, a kidney infection, in a vafidemstat treated subject •Case was independently judged by the PI as ‘Unlikely Rel
Slide 21: PORTICO will explore biomarker correlatives
PORTICO will explore biomarker correlatives (as will also do EVOLUTION trial in SCZ) Cytokine alterations in Schizophrenia domains Increasing evidence suggests that inflammatory responses have an important role in (Positive correlation in black, negative in red) the pathophysiology of neurological d
Slide 22: PORTICO: Final Summary
PORTICO: Final Summary as of January 7th, 2023 • Primary endpoints not met. • Two important pre-specified secondary endpoints reached statistical significance: • Overall improvement in BPD disease severity, measured by BEST across weeks 8-12 (p=0.042). Clinically meaningful reduction compared to pla
Slide 23: Pioneering personalized medicine in epigenetics
Pioneering personalized medicine in epigenetics
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