Oryzon Genomics Sa · BME:ORY
Oryzon Genomics Sa — Investor Presentation (July 2024)
55 slides from Oryzon Genomics Sa's investor presentation, July 2024
Slide 1: Pioneering personalized medicine in epigenetics
Pioneering personalized medicine in epigenetics Corporate Presentation July 2024 ORY:SM / ORY.MC1 Corporate deck – July 2024 I
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: Epigenetic champion developing new therapies in CNS and Oncology
Epigenetic champion developing new therapies in CNS and Oncology with an advanced pipeline Growing epigenetic platform Developing highly potent and Listed in Europe (Madrid) with an expanding pipeline to selective drugs against LSD1 MK Cap $150M bring treatments to high unmet medical needs in CNS a
Slide 4: Oryzon investment thesis
A unique dual EPIGENETIC approach A Phase II molecule in A Phase II molecule with psychiatry (BPD and SCZ) promising clinical data in AML and SCLC Oryzon Area of great interest for Pharma (M&A and licensing) Endorsed by the NCI-NIH investment CRADA Agreement In conversations with FDA to thesis agree
Slide 5: LSD1 inhibition is a validated epigenetic approach for targeted therapies
LSD1 inhibition is a validated epigenetic approach for targeted therapies in Oncology and CNS Lysine specific histone demethylase 1 (LSD1): removes methyl groups from histones and scaffolds key TFs in enhancer & promoter regions LSD1 expression and activity can block LSD1 plays an important role in
Slide 6: Multiple Shots on goal & main investment thesis in the short-mid term
Multiple Shots on goal & main investment thesis in the short-mid term Two main catalysts in 2024: PORTICO in BPD and FRIDA in AML Note: Other finalized clinical trials for iadademstat and vafidemstat are not shown. See www.oryzon.com for more details AML: acute myeloid leukemia; SCLC: small cell lu
Slide 7: ORYZON, the only company developing epigenetic drugs in CNS
ORYZON, the only company developing epigenetic drugs in CNS VAFIDEMSTAT A Phase II LSD1 inhibitor for CNS diseases Corporate deck – July 2024 I 7
Slide 8: Two main catalysts in 2024
Two main catalysts in 2024 Phase I Phase II Preclinical Program Study Status Expected Milestone(s) Phase Phase Ia Phase Ib Phase IIa Phase IIb CNS: Vafidemstat (ORY-2001) – CNS optimized LSD1 inhibitor Borderline personality disorder Completed Top line data in January 2024 Agitation / Aggression & O
Slide 9: Vafidemstat is safe and well tolerated drug
Vafidemstat is safe and well tolerated drug A very robust safety package. +430 treated subjects Brain Penetrant Safe, No DDIs No side effects An optimal Comparable SARs between No weight gain CSF: plasma placebo and vafidemstat arms No sedation / somnolence ratio of 0.9 in 6 Phase II trials: No sexu
Slide 10: Borderline personality disorder: an unmet medical need & vast commercial opportunity
Borderline personality disorder: an unmet medical need & vast commercial opportunity Prevalent & impairing disease Two main types of symptoms No approved drugs yet 9 million in US & EU Psychiatric symptoms Patients on off-label anti-psychotics + Agitation/Aggression Vafi improves these symptoms in:
Slide 11: PORTICO: A Global Phase IIb randomized, placebo-controlled trial in BPD
PORTICO: A Global Phase IIb randomized, placebo-controlled, double blinded trial in BPD Key inclusion criteria Endpoints N=210 Men and women 18-65 years of age Primary: Randomized DSM-5 BPD diagnostic criteria, at least 3 months before the 1:1 Agitation/Aggression (CGI-S A/A) from baseline to weeks
Slide 12: TLD ANALYSIS
TLD ANALYSIS* Phase IIb PORTICO study Efficacy of vafidemstat in Borderline Personality Disorder * FINAL DATA AVAILABLE UNDER CDA Corporate deck – July 2024 I 12
Slide 13: Agitation/Aggression
TLD ANALYSIS Phase IIb PORTICO study Efficacy of vafidemstat in No statistical significance in the two primary endpoints: BPDCL and Borderline Personality Disorder CGI-S A/A placebo vafidemstat placebo vafidemstat 0 0,0 W EEK 2 WEEK 4 WEEK 6 W EEK 8 W EEK 10 W EEK 12 WEEK 2 WEEK 4 WEEK 6 WEEK 8 WEE
Slide 14: BEST-Total Score
TLD ANALYSIS Phase IIb PORTICO study Efficacy of vafidemstat in Nominal statistical significance in secondary endpoint: Borderline Personality Disorder Improvement in BEST across weeks 8-12 placebo vafidemstat 0 W EEK 2 W EEK 4 W EEK 6 W EEK 8 W EEK 10 W EEK 12 -2 BEST-Total Score Across weeks 8-12
Slide 15: STAXI-Trait Anger Scale
TLD ANALYSIS Phase IIb PORTICO study Efficacy of vafidemstat in Nominal statistical significance in secondary endpoint: Borderline Personality Disorder Improvement in STAXI Trait Anger across weeks 8-12 placebo vafidemstat 0 W EEK 2 W EEK 4 W EEK 6 W EEK 8 W EEK 10 W EEK 12 -1 STAXI-Trait Anger Acro
Slide 16: PORTICO: All primary and secondary efficacy endpoints consistently favored vafidemstat
TLD ANALYSIS Phase IIb PORTICO study Efficacy of vafidemstat in PORTICO: All primary and secondary efficacy endpoints Borderline Personality Disorder consistently favored vafidemstat over placebo Favors Vafidemstat Favors Placebo BEST01-Total Score 0.0423 -2.05 0.0799 -1.76 STAXI1-Trait Anger Scale
Slide 17: Global statistical test (GST) consistent with a global treatment effect
TLD ANALYSIS Phase IIb PORTICO study Efficacy of vafidemstat in Global statistical test (GST) consistent with a global treatment effect Borderline Personality Disorder favoring vafidemstat BPD is a multisymptomatic disease with psychiatric, behavioral, and functional outcomes. GST is designed to add
Slide 18: Topline safety: reduced inclination towards self-harm
Topline 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 19: PORTICO: Final summary of TLD
PORTICO: Final summary of TLD • 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 placebo • Improvement
Slide 20: PORTICO's efficacy and safety results support further clinical development
PORTICO: Final PORTICO’s efficacy and safety results support Summary of TLD further clinical development Oryzon has requested an end-of-Phase 2 meeting with the FDA to discuss plans for a registrational BPD Phase III trial Corporate deck – July 2024 I 20
Slide 21: Vafidemstat in Schizophrenia
Vafidemstat in Schizophrenia Genetic and physiological connections between LSD1 and schizophrenia pathology Corporate deck – July 2024 I 21
Slide 22: Vafidemstat in Schizophrenia
Vafidemstat in Schizophrenia Genetic link Preclinical data in No approved drugs Strong market between LSD1 and in- vitro and in yet in negative interest & huge SCZ animal models symptoms or M&A activity supporting LSD1 Cognitive inhibition as a new Impairment MoA in SCZ symptoms Corporate deck – Jul
Slide 23: EVOLUTION: an ongoing schizophrenia PoC study with vafidemstat
EVOLUTION: an ongoing schizophrenia PoC study with vafidemstat An adaptative randomized double blind, placebo-controlled Phase IIb trial with vafidemstat in schizophrenia patients • Expected recruitment: A prevalent & impairing Three main types of No approved drugs disease 20 million ww. symptoms ye
Slide 24: IADADEMSTAT
IADADEMSTAT A Phase II LSD1 inhibitor for oncological diseases Corporate deck – July 2024 I 24
Slide 25: Iadademstat: first and potentially best-in-class LSD1 inhibitor in oncology
Iadademstat: first and potentially best-in-class LSD1 inhibitor in oncology • A unique asset to address specific cancers (rare or orphan designations) • Focusing on clinical execution in hemato-oncology ODD AML ODD AML and solid tumors with a registrational plan ODD SCLC • Reinforcing institutional
Slide 26: LSD1i in clinical development
LSD1i in clinical development • In AML o Leukemic Stem Cells are forced to differentiate by LSD1i o LSD1i synergizes with other agents in AML as azacitidine, gilteritinib, and venetoclax amongst others o Clinical evidence of benefits in diverse AML patients • In SCLC and other Neuroendocrine tumors
Slide 27: Multiple Shots on goal in Oncology & leverage on CRADA-NCI agreement
Multiple Shots on goal in Oncology & leverage on CRADA-NCI agreement Phase I Phase II Preclinical Program Study Status Expected Milestone(s) Phase Phase Ia Phase Ib Phase IIa Phase IIb Oncology: Iadademstat (ORY-1001) – Selective LSD1 inhibitor AML 1L Unfit Patients Final positive results Completed
Slide 28: AML Program: ALICE and FRIDA trials
AML Program: ALICE and FRIDA trials Corporate deck – July 2024 I 28
Slide 29: Iadademstat with Azacitidine in First Line AML: ALICE Final Results
Iadademstat Combination with Azacitidine is a Safe and Effective Treatment in First Line Acute Myeloid Leukemia. Final Results of the ALICE Trial. Summary of Responses Rapid, deep, and durable responses n = 27 n % ORR CR 9 33% (CR+CRi+PR) CR/CRi DoR (on CR/CRi) CRi 5 19% PD 4% PR 8 30% NR 15% PR 36%
Slide 30: ALICE results published in Lancet Haematology in May 2024
ALICE results published in Lancet Haematology in May 2024 One of the most influential scientific journals in the field of oncology This notable publication is a continuation of Oryzon’s previous pioneering research featured in the Journal of Clinical Oncology (First-in-Human study in AML with iadade
Slide 31: IIS-X002 Program continues to explore iadademstat potential in 1L AML
IIS-X002 Program continues to explore iadademstat potential in 1L AML A Phase Ib Investigation of the LSD1 Inhibitor Iadademstat (ORY-1001) in Combination With Azacitidine and Venetoclax in Newly Diagnosed AML Dr. Curtis Lachowiecz, OHSU Knight Cancer Institute • Sponsor: OHSU Knight Cancer Institut
Slide 32: FLT3mut+ R/R AML, the best and shortest market opportunity for iadademstat
• In a competitive market, R/R AML is an underserved population: Majority of AML patients relapse after 1L treatment and require further treatment • FLT3 is the most common mutation in AML (30-40%) FLT3mut+ R/R • These patients are now treated with gilteritinib, yet there is a high medical need (mEF
Slide 33: FRIDA: a Phase Ib trial in R/R AML
FRIDA: a Phase Ib trial in R/R AML as a foundation for an accelerated development Inclusion Escalation Expansion Criteria Up to ~6 pts/dose level Up to ~ 14 pts/dose cohort Adult pts with Relapsed/ Refractory FLT3m+ AML Iadademstat Gilteritinib • Refractory or relapsed to PO PO first- or second-line
Slide 34: FRIDA follows FDA's Project Optimus
FRIDA follows FDA’s Project Optimus, requiring identification of the lowest possible effective dose • Initial preliminary data presented at EHA-2024 • First two cohorts completed (13 patients). All but 2 patients were refractory to prior standard regimens including venetoclax, 7+3 and midostaurin •
Slide 35: Neuroendocrine Program
Neuroendocrine Program Corporate deck – July 2024 I 35
Slide 36: Iadademstat in SCLC and other Neuroendocrine tumors
Iadademstat: potentially first and best-in-class LSD1 inhibitor in SCLC and other Neuroendocrine tumors Mechanism of Action LSD1 is required for survival & proliferation of neuroendocrine/SCLC tumor cells Iadademstat induces Notch, a well characterized tumor suppressor in SCLC and represses ASCL1 Ia
Slide 37: Iadademstat and anti-PD-L1 combination inhibits SCLC progression
Iadademstat and anti-PD-L1 combination inhibits SCLC progression Analysis of epigenetic determinants of antigen presentation identified LSD1 gene expression as a correlate of worse survival outcomes for patients treated with either nivolumab or the combination of nivolumab and ipilimumab Nguyen et a
Slide 38: NEXT-CTEP-NCI Program – CRADA: new SCLC trial in combination with ICI
NEXT-CTEP-NCI Program – CRADA: new SCLC trial in combination with ICI Testing the Combination of an Anti-cancer Drug, Iadademstat, With Other Anti-cancer Drugs (Atezolizumab or Durvalumab) at Led by Dr. Noura Choudhury Improving Outcomes for Small Cell Lung Cancer ClinicalTrials.gov ID: NCT06287775
Slide 39: ED-SCLC, an interesting market opportunity
ED-SCLC, an interesting market opportunity Best route to Market: Combo with IO, 1L ED-SCLC in maintenance SCLC MARKET 4000 Tolerability profile of both drugs suggesting high compatibility 3500 320 The global market for small-cell lung cancer drugs expected to reach 3000 +$3.4 billion by 2027, expand
Slide 40: Neuroendocrine Tumors: a Collaborative PoC basket trial with iadademstat
Neuroendocrine Tumors: a Collaborative PoC basket trial in NETs with iadademstat NET: PI: Dr. Namrata Vijayvergia A Phase II study of iadademstat in Assistant Chief, Gastrointestinal Medical combination with paclitaxel in Oncology Associate Professor, Department of Hematology/Oncology platinum-R/R S
Slide 41: ORY-3001
ORY-3001 A refined LSD1 inhibitor for hematological disorders Corporate deck – July 2024 I 41
Slide 42: Sickle cell disease (SCD)
Sickle cell disease (SCD) Patients suffer anemia, pain, progressive organ damage, early mortality SCD is an inherited autosomal recessive disorder resulting in mutation of the hemoglobin (Hb) structure in red blood cells. The mutation of normal hemoglobin A Dactylitis (α2ß2) to hemoglobin S (α2ß26 V
Slide 43: ORY-3001 is a therapeutic option for SCD
ORY-3001 is a therapeutic option for SCD • ORY-3001 is a highly potent and selective oral LSD1 inhibitor with a very good pharmacology • It has completed the IND enabling toxicology • Its action over SCD is based on two distinct mechanisms: • one addresses sickle hemoglobin (HbS) polymerization-medi
Slide 44: ORY-3001 Efficacy in SCD models
ORY-3001 Efficacy in SCD models PoC demonstrated in: • SCD Townes mouse model • SCD non-anemic baboon model • SCD anemic-bled baboons LSD1 occupancy confirmed by target engagement analysis and platelet reduction In these models, ORY-3001 increased: • Expression of γ-globin mRNA • Fetal reticulocytes
Slide 45: Sickle cell disease prevalence
Sickle cell disease prevalence Around 20-25 million people are living with SCD across the globe and the number is anticipated to increase by 30% by 2050. SCD accounts for approximately 305,773 births per year worldwide Number of Sickle Cell Births Per Year Europe No. of SCD Prevalence of Sickle Cell
Slide 46: ORY-3001 is available for partnering in non-oncological indications
ORY-3001 is available for partnering in non-oncological indications Non-malignant Immune-mediated disease: Viral Infections hematological diseases Psoriasis Sickle Cell disease, Viral infections caused by a Inhibits CCL2 release in Polycythemia vera, etc… variety of viruses cultured keratinocytes Co
Slide 47: ORY-4001
ORY-4001 A selective HDAC6 inhibitor for CMT, ALS and other CNS diseases Corporate deck – July 2024 I 47
Slide 48: ORY-4001 is a highly potent and selective HDAC6 inhibitor
ORY-4001 is a highly potent and selective HDAC6 inhibitor HDAC-6 has been suggested as a therapeutic target in Charcot-Marie-Tooth (CMT), ALS, and other Mean Relative Ac.H3 EC50 CNS diseases % Relative Ac. Tubulin (%) 150 Relative Ac. Tubulin (%) Relative Ac.H3 (%) 150150 150 Relative Ac.H3 (%) vo
Slide 49: Charcot-Marie-Tooth disease
Charcot-Marie-Tooth disease A medical need and a market opportunity Corporate deck – July 2024 I 49
Slide 50: VAFIDEMSTAT Personalized medicine in CNS
VAFIDEMSTAT Personalized medicine in CNS Corporate deck – July 2024 I 50
Slide 51: LSD1i, a precision medicine therapeutic option in CNS
LSD1i, a precision medicine therapeutic option in CNS to rescue deficits caused by mutations in key genes COMPASS Pathologies: H3K4-met related indications • KMT2D (MLL2) – Kabuki Syndrome • KMT2F (SetD1a) - Schizophrenia susceptibility • KMT2A - Wiedemann–Steiner syndrome • KMT2B - Dystonia 28, Chi
Slide 52: Methylation is involved in Kabuki Syndrome and LSD1 inhibition rescues phenotypes
Methylation is involved in Kabuki Syndrome and LSD1 inhibition rescues phenotypes in a genetic model • Kabuki syndrome is a congenital disorder characterized by intellectual disability, growth retardation, dysmorphic facial features and immune defects • Mutations of MLL2 (KMT2D) cause Kabuki syndrom
Slide 53: Methylation is involved in Kabuki Syndrome and LSD1 inhibition rescues phenotypes
Methylation is involved in Kabuki Syndrome and LSD1 inhibition rescues phenotypes in a genetic model Effects of LSD1i in the phenotype of a KO Kabuki mice* LSD1i rescues neurogenesis defects in hippocampus of Kmt2d+/bGeo mice • LSD1i restores methylation balance in the hippocampus • LSD1i rescues ad
Slide 54: HOPE: a Phase Ib/II trial in Kabuki syndrome patients
HOPE: a Phase Ib/II trial in Kabuki syndrome patients • Kabuki syndrome (KS) is caused by mutations in the HOPE: KMT2D/MLL2 gene (KS Type 1, about 70% of cases) An adaptative randomized or the KDM6A gene (KS Type 2) double blind Phase I/II trial • KS is a congenital, rare, multisystem disorder with
Slide 55: Pioneering personalized medicine in epigenetics
Pioneering personalized medicine in epigenetics Corporate deck – July 2024 I 55