Oryzon Genomics Sa · BME:ORY
Oryzon Genomics Sa — Investor Presentation (March 2026)
43 slides from Oryzon Genomics Sa's investor presentation, March 2026
Slide 1: Pioneering personalized medicine with epigenetics
Pioneering personalized medicine with epigenetics Corporate Presentation 1Q 2026 ORY:SM / ORY.MC
Slide 2: Legal Notice
Legal Notice DISCLAMER This document has been prepared by Oryzon Genomics, S.A. exclusively for informational purposes and to be used during the presentation. As a consequence thereof, this document may not, without the express and prior written consent of Oryzon Genomics, S.A., be disclosed or publ
Slide 3: Oryzon Develops Potent and Selective Epigenetic Drugs
Oryzon Develops Potent and Selective Epigenetic Drugs Epigenetics experts specializing in LSD1 Biology Iadademstat: in Phase II. Potentially best-in-class LSD1i developed in multiple hematology and oncology indications, with well-defined registrational pathways for potential accelerated approval Vaf
Slide 4: Oryzon: a Specialist in Epigenetics Developing New Targeted Therapies in Oncology/Hematology and CNS
Oryzon: a Specialist in Epigenetics Developing New Targeted Therapies in Oncology/Hematology and CNS Developing potent and selective epigenetic drugs with well-defined registrational pathways Iadademstat Vafidemstat • Strong clinical data in unfit 1L AML (100% ORR, • Phase III-ready asset in aggress
Slide 5: Iadademstat
IADADEMSTAT A Phase II LSD1 inhibitor for oncological and hematological diseases Corporate presentation – 1Q 2026 I 5
Slide 6: LSD1 inhibition MoA in AML and Other Malignancies is Well Characterized and Understood
LSD1 inhibition MoA in AML and Other Malignancies is Well Characterized and Understood Mechanism of Action • LSD1 is required for leukemic stem cell survival and blocking leukemic cell differentiation • Iadademstat prevents leukemic stem cell survival and promotes rapid differentiation/death of leuk
Slide 7: Iadademstat: First and Potentially Best-in-Class LSD1 Inhibitor for Hematological Diseases
Iadademstat: First and Potentially Best-in-Class LSD1 Inhibitor for Hematological Diseases The Asset • The most potent (nM) oral LSD1 inhibitor in clinical development • Safety profile well-established: +225 pts treated with iadademstat in multiple Phase I/II trials • Orphan Drug Designation for AML
Slide 8: Iadademstat in Oncology and Hematology: Multiple Opportunities Leveraging CRADA-NCI Agreement
Iadademstat in Oncology and Hematology: Multiple Opportunities Leveraging CRADA-NCI Agreement IIS: investigator-initiated study Corporate presentation – 1Q 2026 I 8 MPN: myeloproliferative neoplasm *Tentative meetings listed
Slide 9: Iadademstat, a pipeline in a single asset
Iadademstat, a pipeline in a single asset Iadademstat Combinations in AML are Highly Encouraging. 100% ORR and 90% pure CR in 1L AML + Venetoclax + Venetoclax and Azacitidine and Azacitidine 1L Unfit AML 1L Unfit AML OHSU-sponsored study FRIDA. 4 iada doses tested in MCW-sponsored NCI-NIH CRADA NCI-
Slide 10: Adding Iadademstat to Standard of Care Provides the Most Comprehensive Leukemia Coverage
Adding Iadademstat to Standard of Care Provides the Most Comprehensive Leukemia Coverage Addresses all three Key Drivers of Leukemia Versus Other Therapeutic Approaches In intermediate- and high-risk patients, iadademstat provides a clear MoA advantage over the emerging gilteritinib triplet by targe
Slide 11: Iadademstat Approval Strategy in 1L AML by stratifying patients
Iadademstat Approval Strategy in 1L AML by stratifying patients • ALICE-2: Final data readout expected in Q4 2026 (24 pts, for 21 evaluable pts). Registrational ALICE-3: Seamless Phase II–III trial planned in adverse risk patients, with: Accelerated Approval (AA) based on CR-based endpoints, and Ful
Slide 12: LSD1 Inhibition and Iadademstat Show Activity in the Whole Spectrum of Myeloproliferative Diseases
LSD1 Inhibition and Iadademstat Show Activity in the Whole Spectrum of Myeloproliferative Diseases Non-oncological Onco-dysplastic Oncological Oncological diseases diseases diseases diseases ET MDS AML MPN Phase II +data (Bome) +data 100% ORR 90% CRs +data Same expected in IDEAL Iadademstat’s direct
Slide 13: Small Cell Lung Cancer: Iadademstat and anti-PD-L1 Combination Inhibits SCLC Progression
Small Cell Lung Cancer (SCLC): Iadademstat and anti-PD-L1 Combination Inhibits SCLC Progression in Preclinical Model • Iadademstat renders the SCLC cells visible to the immune system • Iadademstat synergizes with ICIs and boosts the host immune system by increasing T cell infiltration and preventing
Slide 14: Ongoing Phase I/II SCLC Trials in Combination with ICI
Ongoing Phase I/II SCLC Trials in Combination with ICI A Phase I Dose Finding and Phase II Randomized Trial of Iadademstat Iadademstat and Radiation Therapy With Atezolizumab in Extensive Combined With Immune Checkpoint Inhibition Maintenance After Initial Stage Small-cell Lung Cancer (ES-SCLC) Pati
Slide 15: Non oncological hematological disorders: SCD and ET
Non oncological hematological disorders: SCD and ET Corporate presentation – 1Q 2026 I 15
Slide 16: Sickle Cell Disease
Sickle Cell Disease Caused by a mutation in B-chain of Hemoglobin (Hb) Around 20-25 million people are living with SCD across the globe Sickle Cell Disease: High Unmet Medical Need Europe Prevalence of Sickle Cell Disease 55,000-60,000 • Severe, lifelong genetic disorder with Country Prevalence Nort
Slide 17: Strong Activity and High Interest from Leading Pharma Companies
Strong Activity and High Interest from Leading Pharma Companies USA average annual direct healthcare costs per adult patient year is > $100,000, Annual US healthcare costs are > $2 B • 2019: Oxbryta received accelerated FDA approval • 2022: Oxbryta achieved $328 million in U.S. sales • Pfizer demons
Slide 18: Iadademstat MoA in Sickle Cell Disease: An FDA-approved MoA
Iadademstat MoA in Sickle Cell Disease: An FDA-approved MoA LSD1 is a component of the protein complexes that repress HBG1/2 transcription. Iadademstat may restore HBG1/2 expression by inhibiting these repressive complexes Strong Preclinical Data • In rodents • In Baboons in single dose • In Baboons
Slide 19: An Open-label Phase Ib in SCD (RESTORE Trial) Approved by EMA
An Open-label Phase Ib in SCD (RESTORE Trial) Approved by EMA First two cohorts enrolled; PoC clinical activity expected in 2026 RESTORE Endpoints Status Sponsor: Oryzon Primary: Recruiting Size N~24-30: Safety and tolerability, RP2D Secondary: By 1H 2026, we expect to • Escalation up to n=18 HbF in
Slide 20: Iadademstat Approval Strategy in Hematology
Iadademstat Approval Strategy in Hematology • RESTORE: Final data readout expected in Q2 2027 (24-30 patients). • Registrational RESTORE-2: Seamless Phase II–III trial planned, with: • 90+45 pts → AA based on HbF-based endpoint, and • Full approval based on VOCs. • Trial initiation expected in 2-3Q
Slide 21: Essential Thrombocythemia (ET): A Fast Follower Strategy
Essential Thrombocythemia (ET): A Fast Follower Strategy Essential Thrombocythemia (ET) Overview • ET is the most common type of myeloproliferative neoplasm (MPN) and increases the risk of serious complications such as stroke, heart attack, and pulmonary embolism. • The disease affects ~200,000 peop
Slide 22: ORYZON developing first-in-class epigenetic drugs in CNS
ORYZON developing first-in-class epigenetic drugs in CNS VAFIDEMSTAT A Phase III-ready LSD1 inhibitor for CNS diseases Corporate presentation – 1Q 2026 I 22
Slide 23: LSD1, an epigenetic key enzyme in CNS
2 3 LSD1, an epigenetic key enzyme in CNS Vafidemstat pharmacology supports use in different mental diseases It plays a critical role in neuro-genesis and the Vafidemstat (aka ORY-2001) and other LSD1i induce expression of genes involved regulation of cortical development in neuronal plasticity, res
Slide 24: Vafidemstat is Safe and Well Tolerated
Vafidemstat is Safe and Well Tolerated A very robust safety package. +425 treated subjects Oral & Brain Penetrant Safe, No DDIs No side effects Oral, once daily Comparable SARs between No weight gain 1.2 mg /day (RP2D) placebo and vafidemstat arms No sedation / somnolence in 6 Phase II trials No sex
Slide 25: Aggression, a Huge Medical Need in CNS Diseases
Aggression, a Huge Medical Need in CNS Diseases AD Up to 52% of Alzheimer’s disease patients show agitation & aggression Agitation and ADHD Up to 50% of Attention Deficit & Hyperactivity patients show agitation & aggression aggression are common in most psychiatric and BPD 73% of Borderline personal
Slide 26: Vafidemstat Current Clinical Development
Vafidemstat Current Clinical Development • Exploring large multifactorial indications (Borderline Personality Disorder, Schizophrenia and Autism) • Exploring also feasibility in some rare genetically-driven neurodevelopmental disorders (Phelan McDermid, Fragile X, Kabuki, etc) Indication Sponsor Pre
Slide 27: Vafidemstat Demonstrated a Relevant Clinical Benefit in Reducing Agitation/Aggression across ASD, ADHD and BPD
Vafidemstat Demonstrated a Relevant Clinical Benefit in Reducing Agitation /Aggression across ASD, ADHD and BPD Patients in PoC Phase IIa Study Eight-week vafidemstat treatment led to a statistically significant reduction in agitation/aggression compared with baseline across all assessments (all par
Slide 28: Borderline Personality Disorder: an Unmet Medical Need & Vast Commercial Opportunity
Borderline Personality Disorder: an Unmet Medical Need & Vast Commercial Opportunity (+$3Bn) 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 sympt
Slide 29: 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 to Inform Subsequent Development Key inclusion criteria Endpoints N=211 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 (C
Slide 30: PORTICO: Vafidemstat Improves Aggression Over Placebo (Secondary Endpoint)
PORTICO: Vafidemstat Improves Aggression Over Placebo (Secondary Endpoint) “STAXI allows us to effectively and efficiently know if someone is getting better over the course of the trial and in ways that are highly relevant to the clinical work with BPD” - Sarah Fineberg, M.D., Ph.D. Primary endpoint
Slide 31: PORTICO: Vafidemstat was Safe and Well Tolerated
PORTICO: Vafidemstat was Safe and Well Tolerated Vafidemstat-treated patients showed a reduced inclination towards self-harm Treatment-Emergent Adverse Placebo Vafidemstat Events by Preferred Term Occurring in > 5% of Subjects (N=104) (N=106) N (%), e N (%), e TEAEs by Preferred Term 68 (65.4%), 214
Slide 32: Vafidemstat: Summary and Next Steps
Vafidemstat: Summary and Next Steps End-of-Phase II Meeting with FDA resulted in positive feedback: • Agitation-Aggression in BPD acknowledged as a possible therapeutic indication • FDA feedback supports initiation of a Phase III trial (PORTICO-2) using STAXI-2 Trait Anger as a primary efficacy endp
Slide 33: New and Prestigious US-centric Clinical Advisory Board for CNS
New and Prestigious US-centric Clinical Advisory Board for CNS Alan F. Schatzberg Dr. Emil F. Coccaro Alan F. Schatzberg renowned American psychiatrist. Since 1991, he has been the Dr. Emil F. Coccaro is a psychiatrist in Columbus, Ohio and is affiliated Kenneth T. Norris Jr . Professor of Psychiatr
Slide 34: Vafidemstat: PORTICO-2 Phase III Study Proposed Design
Vafidemstat: PORTICO-2 Phase III Study Proposed Design Aggression: Primary endpoint (STAXI-2 Trait Anger) + Key Secondary endpoint (OAS-M) Endpoints Primary: Double-blind Placebo-controlled Treatment Period Efficacy in Agitation-Agression by STAXI-2 Trait Anger 12 Weeks Key Secondary: Efficacy in Ag
Slide 35: Expanding Aggression Program: New Trials Under Preparation in ASD
Expanding Aggression Program: New Trials Under Preparation in ASD To be conducted initially in Spain financed through the EU-IPCEI grant (13.1 Million Euros) Phelan-McDermid Syndrome (PMS) A rare genetic condition (prevalence estimate 1/30,000 births) primarily caused by a terminal deletion on chrom
Slide 36: Schizophrenia Still an Enormous Unmet Medical Need
Schizophrenia Still an Enormous Unmet Medical Need Despite the approval of Cobenfy (BMS) for positive symptoms, addressing negative or cognitive symptoms, as well as treatment-resistant schizophrenia, remains a significant challenge in managing this disease A prevalent & impairing disease No approve
Slide 37: Vafidemstat in Schizophrenia (SCZ)
Vafidemstat in Schizophrenia (SCZ) Genetic link Preclinical in-vitro No approved drugs Strong market between LSD1 and and animal models yet in negative interest in SCZ data supporting symptoms or Schizophrenia LSD1 inhibition as a Cognitive new MoA in SCZ Impairment symptoms Corporate presentation –
Slide 38: EVOLUTION Phase IIb – a Real-World Trial
EVOLUTION Phase IIb – a Real-World Trial • EVOLUTION is designed as a real-world trial, with inclusion and exclusion criteria crafted to permit comorbidities, provided they are stable and/or under treatment. • Participants must present with predominant negative symptoms (PNS) of schizophrenia. • All
Slide 39: EVOLUTION: A Phase II Study to Measure Negative Symptoms in SCZ
EVOLUTION: A Phase II Study to Measure Negative Symptoms in SCZ Recruitment ongoing in Spain. Trial expansion unfolding in Eastern Europe countries Endpoints Screening Double-blind Placebo-controlled Treatment Period Safety Follow-up Primary: 2 weeks 24 Weeks 4 weeks Improvement in Negative Symptoms
Slide 40: ORY-4001: A selective HDAC6 inhibitor for ALS, CMT and other CNS diseases
ORY-4001 A selective HDAC6 inhibitor for ALS, CMT and other CNS diseases Corporate presentation – 1Q 2026 I 40
Slide 41: ORY-4001 is a highly potent and selective HDAC6 inhibitor
ORY-4001 is a highly potent and selective HDAC6 inhibitor HDAC6 has been suggested as a therapeutic target for Amyotrophic Lateral Sclerosis (ALS), Charcot- Marie-Tooth (CMT), and other CNS diseases Mean Relative Ac.H3 EC50 150 • Highly potent and selective HDAC6 inhibitor with % Relative Ac. Tubul
Slide 42: Oryzon Uniquely Positioned to Pioneer Epigenetic Drugs
Oryzon Uniquely Positioned to Pioneer Epigenetic Drugs Upcoming clinical development milestones Epigenetics experts specializing in LSD1 Biology • Clinical data updates in 1L AML in combo w/ venetoclax/azacitidine: Iadademstat: LSD1i asset developed in multiple • Interim update at EHA-2026 (~75% of
Slide 43: Pioneering personalized medicine in epigenetics
Pioneering personalized medicine in epigenetics Corporate presentation – 1Q 2026 I 43