Oryzon Genomics Sa · BME:ORY
Oryzon Genomics Sa — Investor Presentation (January 2024)
46 slides from Oryzon Genomics Sa's investor presentation, January 2024
Slide 1: Pioneering personalized medicine in epigenetics
Pioneering personalized medicine in epigenetics C OR P O R AT E P R E S E N TAT I O N JANUARY 2024 ORY:SM / ORY.MC
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 Growing epigenetic Focus on developing 2 Programs in Phase II Listed in Europe (Madrid) platform with an highly potent and selective with well-defined MK Cap $150M expanding pipeline to bring epigenetic drugs against registrational pa
Slide 4: A Management Team with Proven Drug Development and Operational Capabilities
A Management Team with Proven Drug Development and Operational Capabilities Carlos Buesa Douglas Faller Michael Ropacki Ana Limon Jordi Xaus Sonia Gutierrez Enric Rello PhD MD, PhD PhD PhD PhD MS JD; PhD CEO Global CMO CMO for CNS SVP Clinical Dev & CSO Chief of Clinical CFO-COO Medical Affairs Oper
Slide 5: LSD1 inhibition is a validated epigenetic approach for targeted therapies in Oncology and CNS
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 • 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 LSD 1 inhibitor for CNS diseases
Slide 8: Vafidemstat: an LSD1 inhibitor to treat large multifactorial CNS indications
Vafidemstat: an LSD1 inhibitor to treat large multifactorial CNS indications including borderline personality disorder (BPD) and schizophrenia (SCZ) • LSD1i induces neuronal plasticity & downregulates neuroinflammation Mechanism • Modulates the glutamatergic signal of Action • LSD1i modulates the re
Slide 9: 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 10: Borderline personality disorder: an unmet medical need & a vast commercial opportunity
Borderline personality disorder: an unmet medical need & a vast commercial opportunity A Prevalent & impairing disease Two main types of symptoms No approved drugs yet 9 million in US & EU Unstable-extreme Patients in off-label anti- interpersonal relationships psychotics + Aggression & self-aggress
Slide 11: PORTICO: A Global Phase IIb randomized, placebo-controlled, double blinded trial in BPD
PORTICO: A Global 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 Borderli
Slide 12: 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 13: 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 13
Slide 14: 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 15: 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% 15
Slide 16: PORTICO: 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 16
Slide 17: Global statistical test (GST) 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 18: PORTICO: Final Summary of TLD
PORTICO: Final Summary of TLD as of January 7th, 2023 • Primary endpoints not met. Two important pre-specified secondary endpoints reached nominal statistical significance: • Overall improvement in BPD disease severity, measured by BEST across weeks 8-12 (p=0.042). Clinically meaningful reduction co
Slide 19: ORYZON has an ambitious epigenetic program in Oncology
ORYZON has an ambitious epigenetic program in Oncology IADADEMSTAT A Phase II LSD 1 inhibitor in Oncology
Slide 20: AML Program: ALICE and FRIDA trials
AML Program: ALICE and FRIDA trials
Slide 21: Iadademstat: first and potentially best-in-class LSD1 inhibitor in AML
Iadademstat: first and potentially best-in-class LSD1 inhibitor in AML • LSD1 is required for leukemic stem cell survival and blocking leukemic cell Mechanism differentiation of Action • Iadademstat prevents leukemic stem cell survival and promotes rapid differentiation/death of leukemia cells • Mul
Slide 22: IIS-X002 Program continues to explore iadademstat potential in 1L AML
IIS-X002 Program continues to explore iadademstat potential in 1L AML • Investigator Initiated trial • IND approved Q4 2023 • Expected FPI by Q1 2024: o A Phase Ib Dose Finding of iadademstat combined with venetoclax and azacitidine in AML 1L Unfit patients o N= 21 patients Led by Dr. Curtis Lachowi
Slide 23: FLT3mut+ R/R AML, an interesting market opportunity and a clinical development strategy
FLT3mut+ R/R AML, an interesting market opportunity and a clinical development strategy Combo w • In a competitive market, R/R AML is an underserved population: Majority of AML patients relapse after gilteritinib, 1L treatment and require further treatment best route to • FLT3 is the most common mut
Slide 24: FRIDA: a Phase Ib trial in R/R AML as a foundation for an accelerated development
FRIDA: a Phase Ib trial in R/R AML as a foundation for an accelerated development ESCALATION: EXPANSION FINAL ANALYSIS (up to ~6 pts/ dose level) Up to ~ 14 pts/dose cohort selected endpoints: Adult pts with Relapsed/Refractory FLT3m+ Iadademstat Gilteritinib •Primary: AML PO PO o Safety • Refractor
Slide 25: FRIDA follows FDA's Project Optimus
FRIDA follows FDA’s Project Optimus: requiring identification of the lowest possible effective dose • 12 patients recruited (90% of patients were refractory to the previous treatment ) • 6 patients treated in First Cohort. Starting Dose 100ug. Safe and with strong antileukemic activity • 6 Patients
Slide 26: Neuroendocrine Program: STELLAR and NET trials
Neuroendocrine Program: STELLAR and NET trials
Slide 27: Iadademstat: potentially first and best-in-class LSD1 inhibitor in SCLC and other Neuroendocrine tumors
Iadademstat: potentially first and best-in-class LSD1 inhibitor in SCLC and other Neuroendocrine tumors • LSD1 is required for survival & proliferation of neuroendocrine/SCLC tumor cells • Iadademstat induces Notch, a well characterized tumor suppressor in SCLC and represses ASCL1 Mechanism • Iadade
Slide 28: Iadademstat and anti-PD-L1 combination inhibits SCLC progression
Iadademstat and anti-PD-L1 combination inhibits SCLC progression Nguyen et al 2022 28
Slide 29: NEXT-CTEP-NCI Program
NEXT-CTEP-NCI Program • CRADA agreement • IND ready for submission • FPI expected by Q1 2024: o A Phase 1 Dose Finding and Phase II Randomized Trial of Iadademstat Combined with Immune Checkpoint Inhibition Maintenance After Initial Chemoimmunotherapy in Patients with Extensive-Stage Small Cell Lung
Slide 30: Neuroendocrine Tumors: a Collaborative PoC basket trial in NETs with iadademstat
Neuroendocrine Tumors: a Collaborative PoC basket trial in NETs with iadademstat NET: A Phase II study of iadademstat in combination with paclitaxel in platinum-R/R SCLC and extrapulmonary high grade neuroendocrine carcinomas • High unmet medical need: NETs have dismal outcomes ranging from ORR 5% (
Slide 31: ORY-3001: A refined LSD1 inhibitor for hematological disorders
ORY-3001 A refined LSD1 inhibitor for hematological disorders
Slide 32: Sickle cell disease
Sickle cell disease Sickle cell anemia is an inherited autosomal recessive disorder resulting in qualitative mutation of the hemoglobin structure in red blood cells (RBCs). The mutation of normal hemoglobin A (α2ß2) to hemoglobin S (α2ß26 Val) is caused by the amino acid substitution of valine (GTG)
Slide 33: ORY-3001 inhibition in Sickle Cell Disease
ORY-3001 inhibition in Sickle Cell Disease • 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-me
Slide 34: 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 reticuloc
Slide 35: 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. Approximately, SCD accounts for 305,773 births per year worldwide. Number of Sickle Cell Births Per Year Europe No. of SCD Prevalence of Sickle Ce
Slide 36: ORY-3001 is available for partnering in non-oncological indications
ORY-3001 is available for partnering in non-oncological indications Hematological hematological Non-malignant diseases diseases Sickle Cell disease, Polycythemia vera, etc… Viral Infections Viral infections caused by a variety of viruses Immune-mediated disease: Psoriasis Inhibits CCL2 release in cu
Slide 37: ORY-4001: A selective HDAC6 inhibitor for CMT, ALS and other CNS diseases
ORY-4001 A selective HDAC6 inhibitor for CMT, ALS and other CNS diseases
Slide 38: 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 CNS diseases Mean Relative Ac.H3 EC50 % Relative Ac. Tubulin (%) Relative Ac. Tubulin (%) 150 150 150 150 Relative Ac.H3 (%) Relative Ac.H3 (%) O
Slide 39: CMT: a medical need and a market opportunity
CMT: a medical need and a market opportunity 39
Slide 40: VAFIDEMSTAT: Personalized medicine in CNS
VAFIDEMSTAT Personalized medicine in CNS Pioneering personalized medicine in epigenetics
Slide 41: LSD1i, a precision medicine therapeutic option in CNS to rescue deficits caused by mutations
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 42: 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 43: 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 LSD1i rescues neurogenesis defects in hippocampus of Kmt2d+/bGeo mice • Effects of LSD1i in the phenotype of a KO Kabuki mice* • LSD1i restores methylation balance in the hippocampus • LSD1i rescues
Slide 44: HOPE: a Phase Ib/II trial in Kabuki syndrome patients
HOPE: a Phase Ib/II trial in Kabuki syndrome patients HOPE: An adaptative randomized double blind Phase I/II trial with vafidemstat in KS Type 1 patients • Phase Ib objectives: evaluate safety/tolerability, and determine the RP2D • Phase II objective: evaluate the efficacy of vafidemstat at the RP2D
Slide 45: Value Creation in 2024
ThankORYZON you Value Creation in 2024 A unique dual EPIGENETIC proposition Multiple inflection points in CNS and ONCOLOGY • A validated approach with multiple • Final Read Out in BPD PORTICO 2Q24 shots on goal • EoP2 FDA Meeting to discuss PORTICO • One and only epigenetic company • 2L AML FRIDA an
Slide 46: Pioneering personalized medicine in epigenetics
Pioneering personalized medicine in epigenetics
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