Oryzon Genomics Sa · BME:ORY
Oryzon Genomics Sa — ECNP 2024
21 slides from Oryzon Genomics Sa's conference presentation, Sep 23, 2024
Slide 1: Final Results Phase 2b PORTICO study
Final Results Phase 2b PORTICO study Efficacy of vafidemstat in Borderline Personality Disorde Pioneering personalized medicine ECNP, Milan, Italy in epigenetics September 23, 2024 1
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: 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
Slide 4: LSD1 an epigenetic key enzyme in CNS
4 Vafidemstat is a highly selective LSD1 inhibitor with a new MoA, and whose LSD1 an epigenetic pharmacology supports use in different mental diseases key enzyme in CNS Vafidemstat (aka ORY-2001) and other LSD1i induce expression of genes involved in neuronal plasticity, restoring neuronal morpholog
Slide 5: Vafidemstat is safe and well tolerated
Vafidemstat is safe and well tolerated 10 clinical trials with vafidemstat in adult populations including 7 Phase 2 clinical trials in different neuro- degenerative and neuropsychiatric indications. As of April 2024, 423 subjects have been exposed to vafidemstat (87 subjects in a Phase 1 clinical tr
Slide 6: Excellent pharmacology & established RP2D from previous trials
Vafidemstat: Excellent pharmacology & established RP2D from previous trials Oral, once a day *** *** *** *** 100 *** Vafidemstat Ctrough,ss (pg/mL) 25,000 *** 80 20,000 LSD1-TE (%) 60 15,000 10,000 40 5,000 20 0 0 Placebo 0.6 mg 1.2 mg Placebo 0.6 mg 1.2 mg Dose Dose PK data supports once daily dosi
Slide 7: PORTICO: Global Phase IIb double blind, randomized, placebo-controlled trial
PORTICO: Global Phase IIb double blind, randomized, placebo-controlled, adaptive 14-week, trial to evaluate the efficacy and safety of vafidemstat in an adult BPD population Endpoints N=211 Primary (Multiple, Not Co-Primary): Considering there is no ‘gold standard’ measure of Randomized 1:1 Agitatio
Slide 8: PORTICO: Study design
PORTICO: Study design Subject-blind Placebo Run- Screening Double-blind Placebo-controlled Treatment Period out Period Safety Follow-up 1 week 12 Weeks 2 weeks Vafidemstat, 1.2mg Once daily (5 days on/2 days off1) N=106 N=211 Randomized Placebo 1:1 Placebo Once daily (5 days on/2 days off1) N=105 V1
Slide 9: Demographics
Vafidemstat Placebo (n = 106) (n = 104) Psychotherapy at Baseline: 84/22 82/22 No (n) / Yes (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 10: 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) There were no statistically significant BEST Total 39.9 (10.06) 39.6 (10.02) group differences across endpoints STAX
Slide 11: CGI-Severity A/A
Improvement in agitation/aggression measured by CGI-S A/A. Yet, no statistical significance CGI-Severity A/A Across weeks 8-12 LS Means Estimate (SE) CGI-Severity A/A LS Means Estimate (SE) PBO VAFI 0,0 -0,2 -0,4 -0,6 -0,8 -1,0 -1,2 -1,4 Full Analysis Set Model Estimates -1,6 -1,8 p=0.2266 -12.2%
Slide 12: BPDCL-Total Score
Overall disease improvement measured by the BPDCL scale. Yet, no statistical significance placebo vafidemstat BPDCL-Total Score Across weeks 8-12 LS Means Estimate (SE) BPDCL-Total Score LS Means Estimate (SE) PBO VAFI 0 -5 -10 -15 -20 -25 -30 -35 -40 Full Analysis Set Model Estimates p=0.3839 -11.2
Slide 13: STAXI-2 Trait Anger Scale
Nominal statistical significance in secondary endpoint: improvement in STAXI-2 Trait Anger across weeks 8-12 placebo vafidemstat 0 WEEK 2 WEEK 4 WEEK 6 WEEK 8 WEEK 10 WEEK 12 -1 STAXI-2 Trait Anger STAXI-2 Trait Anger Scale -2 Across weeks 8-12 LS Means Estimate (SE) LS Means Estimate (SE) -3 PBO VA
Slide 14: Improvement in BEST across weeks 8-12
Nominal statistical significance in secondary endpoint: improvement in BEST across weeks 8-12 placebo vafidemstat 0 WEEK 2 WEEK 4 WEEK 6 WEEK 8 WEEK 10 WEEK 12 -2 BEST-Total Score -4 Across weeks 8-12 LS Means Estimate (SE) LS Means Estimate (SE) BEST Total Score PBO VAFI -6 0 -2 -8 -4 -6 -10 -8 -10
Slide 15: BDI-II Total Score trend
A trend in secondary endpoint: improvement in depression by BDI-II Total Score by weeks 8-12 LS Means Estimate (SE) BDI-II Total Score 15
Slide 16: All primary and secondary efficacy endpoints favored vafidemstat
PORTICO: all primary and secondary efficacy endpoints consistently favored vafidemstat Favors Vafidemstat Favors Placebo * P-values are uncorrected for multiplicity 16
Slide 17: Cumulative Global Statistical Test (GST)
PORTICO: Cumulative Global Statistical Test (GST) using the pre-specified hierarchy is 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
Slide 18: PORTICO safety: vafidemstat was safe and well tolerated
PORTICO safety: vafidemstat was safe and well tolerated • Treatment Emergent Adverse Events (TEAEs) were slightly lower for those receiving vafidemstat Placebo Vafidemstat (N=104) (N=106) • Treatment-Related TEAEs were similar between n (%), e n (%), e groups Treatment Emergent AEs (TEAEs) 68
Slide 19: Reduced inclination towards self-harm
PORTICO safety: vafidemstat-treated patients showed a reduced inclination towards self-harm Treatment-Emergent Adverse Events by Preferred Term Occurring in > 5% of Subjects Placebo Vafidemstat (N=104) (N=106) N (%), e N (%), e TEAEs by Preferred Term 68 (65.4%), 214 61 (57.5%), 192 Headache 17 (16.
Slide 20: PORTICO: final summary
PORTICO: final summary • Primary endpoints not met by FAS. Yet, a trend by PPA in CGI-S A/A was detected • Four important pre-specified secondary endpoints reached nominal statistical significance by FAS, with clinically meaningful value reductions compared to placebo Primary Endpoints (p-values) FA
Slide 21: Thank you!
Thank you! Pioneering personalized medicine in epigenetics 21