Slide 1: HER-096: Advancing Toward the First Disease-Modifying Treatment for Parkinson's Disease
HER-096: Advancing Toward the First Disease-Modifying Treatment for Parkinson’s Disease Antti Vuolanto, D.Sc. antti.vuolanto@herantis.com 1
Slide 2: Forward-looking statements
Forward-looking statements © 2014-2026 HERANTIS PHARMA Plc. All rights reserved. 2
Slide 3: Herantis Pharma
Herantis Pharma Nasdaq First North Growth Market Finland - HRTIS Clinical-stage public company developing disease-modifying therapies for Parkinson’s disease (PD) Lead asset HER-096 • Phase 2 efficacy trial initiation-ready • Novel mechanism (CDNF mimicking) designed to protect and restore dopaminer
Slide 4: Parkinson's Disease: High Unmet Need Driving Market Growth
Parkinson’s Disease: High Unmet Need Driving Market Growth Unmet clinical need Market is growing rapidly Current therapies only treat the symptoms, not the disease itself 10 è 25 million patients Estimated increase until 2050 Many patients have no symptomatic $ >250 billion benefit or may have signi
Slide 5: HER-096: De-Risked and Ready for Phase 2
HER-096: De-Risked and Ready for Phase 2 Key achievements Differentiated asset Reduced development Completed two Phase 1 studies including PD Designed to modify disease progression patients MoA confirmation (biomarkers) First-in-class CDNF-based mechanism Biomarker and brain penetration data support
Slide 6: Phase 2a: To Demonstrate Symptomatic Improvement in Early-Stage Parkinson's Patients
Phase 2a: To Demonstrate Symptomatic Improvement in Early-Stage Parkinson’s Patients § Randomized, placebo-controlled, double-blind multicenter trial • 6-month placebo-controlled period followed by 6-month open-label HER-096 treatment for all participants • 100 patients with early-stage idiopathic P
Slide 7: HER-096: Strong Position Within PD Disease-Modifying Landscape
HER-096: Strong Position Within PD Disease-Modifying Landscape Phase 3 a-synuclein § Parkinson’s disease-modifying treatment • Despite significant investment, broader clinical validation of pipeline remains limited despite substantial α-synuclein-targeted disease modification remains ongoing • Prasi
Slide 8: Strong External Validation and Financial Support for HER-096
Strong External Validation and Financial Support for HER-096 €3.6M research financing Phase 1b clinical trial and biomarker development (completed) € 2.5 million grant for biomarker development (completed) € 8 million grant for the Phase 2 trial conduct € 15 million equity investment commitment from
Slide 9: Over 50% of Funding for Phase 2 Execution Secured
Over 50% of Funding for Phase 2 Execution Secured The total need of funding is EUR 30-35 M currently in discussions with: • Pharma • Investors EUR 13-18M • Disease-focused organizations such as Remaining Parkinson’s UK and MJ Fox funding requirement EIC Fund: term sheet signed 2023, they can invest
Slide 10: Unique Mechanism of Action and Robust Preclinical Data
Unique Mechanism of Action and Robust Preclinical Data © 2014-2026 HERANTIS PHARMA Plc. All rights reserved. 10
Slide 11: HER-096 Mimics CDNF's Neuroprotective Activity via Interaction with GRP78
HER-096 Mimics CDNF’s Neuroprotective Activity via Interaction with GRP78 GRP78 Serves as the Master Regulator of the Unfolded Protein Response (UPR) Pathway Unfolded Protein Response (UPR) Pathway Signaling and CDNF HER-096 is designed based on the CDNF / GRP78 binding interface Pathological ER str
Slide 12: Parkinson's disease: A Vicious Cycle Drives the Disease Pathology
Parkinson’s disease: A Vicious Cycle Drives the Disease Pathology Accumulation of Toxic α-Synuclein Aggregates, Chronic ER Stress and Neuroinflammation Parkinson’s disease is driven by proteostasis failure, where impaired protein quality control leads to toxic α-synuclein aggregation that progressiv
Slide 13: Disease modification – Effect on α-synuclein and Neuroinflammation
Disease modification – Effect on ⍺-synuclein and Neuroinflammation In vivo Preclinical Studies (Parkinson’s mouse model) a-SYNUCLEIN AGGREGATES Improvement Mice were administered IP a human-equivalent dose of 200 mg HER-096 3 times per week for 4 weeks. Control = normal aged mouse without drug (vehi
Slide 14: Disease Modification – Effect on Dopamine System
Disease Modification – Effect on Dopamine System In vivo Preclinical Studies (Parkinson’s mouse model) PROTECTION OF DOPAMINE NEURONS DOPAMINE LEVEL IN STRIATUM IMPROVEMENT OF MOTOR SYMPTOMS Improvement Improvement Improvement Mice were administered IP a human-equivalent dose of 200 mg HER-096 3 tim
Slide 15: HER-096 demonstrate robust neuroprotection
HER-096 demonstrate robust neuroprotection PD mouse administered with HER-096 has superior beam walking speed to both untreated PD mouse and normal aged mouse VIDEO SCREENSHOT CLICK THE BELOW LINK TO SEE THE VIDEO: https://youtu.be/L 3WmkhP2Opw © 2014-2026 HERANTIS PHARMA Plc. All rights reserved. 1
Slide 16: Preclinical Studies: HER-096 Modulation of UPR Showed Broad Effects on Neuronal Functionality
Preclinical Studies: HER-096 Modulation of UPR Showed Broad Effects on Neuronal Functionality Restorative Effects on Neuronal Proteostasis and Mitochondrial Function Preclinical studies have shown that in addition to the proteostasis effects, HER-096 has effects that support + g re s gg ER n io s at
Slide 17: Phase 1 Program is Completed With Very Encouraging Data
Phase 1 Program is Completed With Very Encouraging Data © 2014-2026 HERANTIS PHARMA Plc. All rights reserved. 18
Slide 18: HER-096 Phase 1 Program is Completed
HER-096 Phase 1 Program is Completed PHASE 1A STUDY PHASE 1B STUDY Single Ascending Dose HER-096 (10 – 300 mg) Single Dose HER-096 Multiple Doses (200 or 300 mg) Safety and PK, including CSF T½ in elderly HV CSF T½ in elderly HV Safety, PK & biomarkers in PD patients N = 60 N=8 N = 24 N = 48 young h
Slide 19: Phase 1 Summary: Safety and Brain Penetration in Humans
Phase 1 summary: Safety and Brain Penetration in Humans Clean safety profile HER-096 in the CSF of Parkinson’s patients • Favorable safety profile observed across all tested 250 dose levels, including highest planned clinical 200 exposure HER-096 (ng/ml) • Low incidence of systemic adverse events 15
Slide 20: Biomarker Profiling with over 2.5 Million Data Points Generated
Biomarker Profiling with over 2.5 Million Data Points Generated Exploratory Fluid Biomarker Analyses in the Phase 1b Clinical Study Screening First dosing HER-096 dosing Last dosing End of follow-up 0, 8 and 24 h 0, 6/8 and 24 h • 24 patients with Parkinson’s • Received either placebo, 200 mg Short-
Slide 21: Example of Biomarker data: Plasma Proteomics – Systemic Biological Response to HER-096
Example of Biomarker data: Plasma Proteomics – Systemic Biological Response to HER-096 Aptamer-based Proteomics Used for Longitudinal Monitoring of 11 000 Plasma Proteins Column: one protein Row: one subject Placebo 200 mg HER-096 300 mg HER-096 Low High Changes from mean expression in individual su
Slide 22: HER-096 Broadly Modulates Proteostasis-Regulating Proteins in Plasma
HER-096 Broadly Modulates Proteostasis-Regulating Proteins in Plasma Aptamer-based Proteomics: Overrepresentation Analysis of HER-096 Effect vs Placebo Over 28 days Overrepresentation Analysis (ORA): All HER-096 vs Placebo Number of Gene Ontology Category Adjusted p-value terms Data interpretation:
Slide 23: Clear Biomarker Responses to HER-096 Dosing in Humans
Clear Biomarker Responses to HER-096 Dosing in Humans Multiple Data Layers Show Concordant Shifts in Biology Aligned with Mechanism of Action Cells / Sample type System Pathways affected Interpretation Source Proteostasis and Proteostasis and redox Proteostasis modulation and CSF Neurons oxidative s
Slide 24: HER-096 dosing: Clinical Biomarker Changes Aligned with Restoration of UPR Function
HER-096 dosing: Clinical Biomarker Changes Aligned with Restoration of UPR Function Consistent biomarker changes support normalization of UPR signaling in line with established biology Parkinson’s disease: HER-096 treatment: chronically activated Unfolded Protein Response (UPR) normalized UPR operat
Slide 25: Phase 1b Biomarker Data: De-Risking the Path to Clinical Efficacy
Phase 1b Biomarker Data: De-Risking the Path to Clinical Efficacy § Proof of biology: clear evidence of biological response to HER-096 in Parkinson’s patients § A key development milestone demonstrating preclinical-to-clinical translatability § A key catalyst for strategic partnering and investment
Slide 26: HER-096: Advancing Towards Phase 2 Proof-of-Concept
HER-096: Advancing Towards Phase 2 Proof-of-Concept © 2014-2026 HERANTIS PHARMA Plc. All rights reserved. 27
Slide 27: Phase 2a Study Design: Signal-Finding Design Driven by Digital Biomarkers
Phase 2a Study Design A Signal-Finding Phase 2a Study Design Driven by Digital Biomarkers § Sample size: 100 patients • De novo Parkinson’s disease: early stage, no symptomatic medication • Two subcutaneous injections per week of a single dose level of HER-096 or placebo • A randomized, placebo-cont
Slide 28: Phase 2a Study Design
Phase 2a Study Design A Double-Blind, Placebo-Controlled, Randomized, Efficacy and Safety Study Followed by an Open-Label Extension Double-Blind, Placebo-Controlled Open-Label Extension Placebo Screening Baseline HER-096 Follow-up HER-096 6 months with twice 2 weeks weekly s.c. dosing Within 6 weeks
Slide 29: Linking Biological Activity to Clinical Outcomes
Linking Biological Activity to Clinical Outcomes PHASE 1B BIOMARKER DATA TRANSLATIONAL PRECLINICAL EVIDENCE PHASE 2A ENDPOINT STRATEGY Evidence of Target & Gradually Developing Digital Motor Score as Biological Engagement Functional Effects in PD Models Primary Endpoint • Concordant biomarker change
Slide 30: Participating Countries and Clinical Sites
Participating Countries and Clinical Sites EU Horizon Grant HERMOD Project Funding Directly Three Clinical Sites § Currently confirmed participating clinical sites – EU Grant • Sweden: Karolinska University Hospital (Stockholm) and Lund University Hospital • Luxembourg: Central Hospital of Luxembour
Slide 31: HER-096 is a potentially game-changing therapy for Parkinson's disease
HER-096 is a potentially game-changing therapy that could become the first disease-modifying treatment for Parkinson’s disease Huge market opportunity: the PD therapeutic market is expected to grow to up to $13bn by 2034, while no disease-modifying therapies currently available and few are in develo