Herantis Pharma Plc · OMXHEX:HRTIS

Herantis Pharma — Technical Presentation (September 2020)

42 slides from Herantis Pharma's technical presentation, Sep 15, 2020

  1. Slide 1: CDNF Phase I 12-month topline results: Safety, UPDRS and DAT PET data

    CDNF Phase I 12-month topline results: Safety, UPDRS and DAT PET data 15 September 2020 www.herantis.com © 2014-2020 HERANTIS PHARMA Plc. All rights reserved.

  2. Slide 2: Disclaimer

    Disclaimer • This presentation does not intend to provide a thorough and detailed view of Herantis Pharma Plc (‘Company’). The information provided in this presentation shall not be considered sufficient for making any investment decisions related to the Company. Anyone considering an investment in

  3. Slide 3: Agenda

    Agenda 01 CDNF: • The Disease • The Treatment • The Study • The Data 02 Conclusions & Next Steps 03 Q&A 3 www.herantis.com © 2014-2020 HERANTIS PHARMA Plc. All rights reserved.

  4. Slide 4: The Disease

    The Disease 4 www.herantis.com © 2014-2020 HERANTIS PHARMA Plc. All rights reserved.

  5. Slide 5: Parkinsons Disease (PD) An Incurable Debilitating Illness

    Parkinsons Disease (PD) An Incurable Debilitating Illness • An incurable brain disease caused by degeneration of dopaminergic neurons in midbrain • Massive medical need with 7-10 million patients worldwide, societal costs $25bn US • Standard of care Levodopa … since the 1960’s • Main symptoms → Trem

  6. Slide 6: The Treatment

    The Treatment 6 www.herantis.com © 2014-2020 HERANTIS PHARMA Plc. All rights reserved.

  7. Slide 7: CDNF For Parkinson's Disease (PD)

    CDNF For Parkinson’s Disease (PD) • CDNF is a natural protein whose role is to protect neurons • Promotes functional recovery of dopaminergic terminals in putamen and the cell bodies in the substantia nigra – the dopamine rich areas of the brain (the nigrostriatal pathway) • Potential to modify the

  8. Slide 8: CDNF Administered Directly Into The Brain

    CDNF Administered Directly Into The Brain • Blood-brain barrier is a common challenge for drug delivery in brain ○ CDNF is dosed directly into the putamen area of the brain with a sophisticated medical device (provided by Renishaw Neuro Solutions (www.renishaw.com) Putamen • Changes in the functiona

  9. Slide 9: CDNF's Multimodal Mechanisms Of Action

    CDNF’s Multimodal Mechanisms Of Action 1• Promotes neuronal functionality through reduced endoplasmic reticulum stress 2• Reduces alpha-synuclein aggregation and toxicity 3• Promotes neuronal survival through 3 2 Protein Kinase B (Akt) 1 4• Suppresses production and secretion of proinflammatory cyto

  10. Slide 10: Significant Effect On Neuronal Regeneration In Animals

    Significant Effect On Neuronal Regeneration In Animals (1) MPTP lesion model of Parkinson’s in primates(2) CDNF treatment results in significant neurorestoration Without treatment 80% loss of dopaminergic CDNF treatment doubled the number of neurons dopaminergic neurons ”Lazarus neurons”(3) • Model:

  11. Slide 11: The Study

    The Study 11 www.herantis.com © 2014-2020 HERANTIS PHARMA Plc. All rights reserved.

  12. Slide 12: Clinical Study Design: Three Groups, Three Parts

    Clinical Study Design: Three Groups, Three Parts Re-randomization (placebo crossover patients) Extension study/ Extension study/6-month baseline 12-month endpoint Baseline End of Main study End of Extension study Follow-up study (0 months) (6 months) (12 months) (25 months) MAIN STUDY EXTENSION STUD

  13. Slide 13: Endpoints (Drug-related)

    Endpoints (Drug-related) • Primary endpoint ○ Safety (drug and device) • Secondary endpoints ○ UPDRS Part III motor scores - severity of motor symptoms ○ TUG test - mobility ○ UPDRS Part I-IV total scores ON & OFF state - severity non-motor & motor symptoms ○ Home diary score - functional status ○ P

  14. Slide 14: The Data - Demographics

    The Data - Demographics - 14 www.herantis.com © 2014-2020 HERANTIS PHARMA Plc. All rights reserved.

  15. Slide 15: Demographic and PD Characteristic Data At Screening

    Demographic and PD Characteristic Data At Screening Placebo CDNF (low-mid-mid) CDNF (low-mid-high) Characteristic n=6 n=6 n=5 Age (years) 63.8 ± 6.4 63.2 ± 8.9 57.8 ± 6.7 Male sex, n (%) 5 (83.3%) 3 (50%) 4 (80%) White race, n (%) 6 (100%) 6 (100%) 5 (100%) Hoehn & Yahr (OFF), n (%) Stage 2 4 (66.7%

  16. Slide 16: Safety Study Only, Not Efficacy – Here's Why

    Safety Study Only, Not Efficacy – Here’s Why Dopamine transporter (DAT) staining • By 5 years post-diagnosis, the putamen is nearly completely devoid of DAT-positive dopaminergic neuron terminals • The target of CDNF, the stressed and degenerating dopamine neurons and their terminals, are nearly com

  17. Slide 17: The Data - Safety

    The Data - Safety - 17 www.herantis.com © 2014-2020 HERANTIS PHARMA Plc. All rights reserved.

  18. Slide 18: Treatment Emergent Adverse Events Transient And Mild

    Treatment Emergent Adverse Events* Transient And Mild 0 – 6 month Main Study 6 - 12 month Extension Study NERVOUS SYSTEM DISORDERS GENERAL DISORDERS AND 9% ADMINISTRATION SITE CONDITIONS 9% PSYCHIATRIC DISORDERS 7% 28 % 30 % INJURY, POISONING AND 13 % 5% PROCEDURAL COMPLICATIONS INFECTIONS AND INFES

  19. Slide 19: Treatment Related Serious Adverse Events Resolved

    Treatment Related Serious Adverse Events Resolved • Brain abscess occured in Main study during the first 6-month period Infectious events: • Port skin necrosis in Main study during the first 6-month period Risk mitigation improvements made to surgical procedure, infusion procedure, device maintenanc

  20. Slide 20: Primary Endpoint Of The Study Was Met

    Primary Endpoint Of The Study Was Met Majority of the reported drug-related TEAEs were mild and have recovered Similar safety profile in Main (0 – 6 months) and Extension (6 – 12 months) study Similar safety profile between dose-groups SAE’s related to device, improvements made to use and preparatio

  21. Slide 21: The Data - Efficacy

    The Data - Efficacy – 21 www.herantis.com © 2014-2020 HERANTIS PHARMA Plc. All rights reserved.

  22. Slide 22: UPDRS Part III and Home Diary Explained

    UPDRS Part III and Home Diary Explained • UPDRS Total (Parts I-IV): ○ Rating tool used to gauge the course of movement hindrances of PD patients ○ Five segments including mentation, behaviour, mood, ADL, motor sections ○ Grades assigned to each extremity: → possible maximum of 199 points worst total

  23. Slide 23: Some Impressive Individual Cases

    Some Impressive Individual Cases Placebo Mid-dose CDNF 30 60 % Change Placebo Mid-dose CDNF % Change in UPDRS-III 30 60 (off, from baseline) Improvement 40 % Changefrom % Change in UPDRS-III (off, from baseline) Improvement 40 UPDRS part III (off) (DAT 20 2020 UPDRS part III (off) (DATBP 20 Expected

  24. Slide 24: UPDRS Part III (off) Absolute Scores: Expected

    UPDRS Part III (off) Absolute Scores What We Would Expect in Parkinsons Patients Re-randomization of placebo patients Baseline to active treatment groups 50 UPDRS part III (off) 40 Expected annual decline 30 Improvement 20 PD patients typically worsen by 2 to 2.5 points per year 10 0 3 6 9 12 Months

  25. Slide 25: UPDRS Part III (off) Absolute Scores: Observed

    UPDRS Part III (off) Absolute Scores What We Actually Observed in Study Patients Re-randomization of placebo patients Baseline to active treatment groups 50 Placebo (n=6) UPDRS part III (off) Mid-dose CDNF (n=6) 40 High-dose CDNF (n=5) Expected annual decline 30 Improvement All CDNF-treated patients

  26. Slide 26: UPDRS Part III (off) Absolute Scores: Observed

    UPDRS Part III (off) Absolute Scores What We Actually Observed in Study Patients Re-randomization of placebo patients Baseline to active treatment groups 50 Placebo (n=6) UPDRS part III (off) Mid-dose CDNF (n=6) 40 High-dose CDNF (n=5) Placebo > mid-dose CDNF (n=3) 30 Improvement Placebo > high-dose

  27. Slide 27: UPDRS-III (off) First 6-Month Treatment vs Placebo: Expected

    UPDRS-III (off) First 6-Month Treatment vs Placebo What We Would Expect in Parkinsons Patients Respective baseline Respective 6-month UPDRS-III 40 % Change from baseline (UPDRS-III, OFF) Placebo (n=5) 30 Mid-dose CDNF (n=6) High-dose CDNF (n=5) Placebo > mid-dose CDNF (n=3) 20 Expected annual declin

  28. Slide 28: UPDRS-III (off) First 6-Month Treatment vs Placebo: Observed

    UPDRS-III (off) First 6-Month Treatment vs Placebo What We Actually Observed in Study Patients Respective baseline Respective 6-month UPDRS-III 40 % Change from baseline (UPDRS-III, OFF) Placebo (n=5) 30 Mid-dose CDNF (n=6) High-dose CDNF (n=5) Placebo > mid-dose CDNF (n=3) 20 Expected annual declin

  29. Slide 29: The Data At 12 Months - Exploratory Endpoints: Dopamine Transporter PET

    The Data At 12 Months - Exploratory Endpoints – Dopamine Transporter PET 29 www.herantis.com © 2014-2020 HERANTIS PHARMA Plc. All rights reserved.

  30. Slide 30: Exploratory Endpoint Dopamine Transporter DAT Explained

    Exploratory Endpoint Dopamine Transporter DAT Explained Example of decreased signal: patient on placebo • Marker of integrity and density of dopamine neurons and terminals • Visualization of loss of striatal dopaminergic nerve endings correlates with motor symptoms and disease stage • Annual rate of

  31. Slide 31: Some Impressive Individual PET Cases

    Some Impressive Individual PET Cases Mid-dose CDNF 60 100 % Change from baseline % Change in UPDRS-III 80 (off, from baseline) Improvement UPDRS part III (off) (DAT BPND) 40 60 Expected decline in UPDRS 40 DAT PET Improvement 20 20 Expected decline in DAT PET 0 A mid-dose patient showed >50% gain in

  32. Slide 32: Some Impressive Individual PET Cases

    Some Impressive Individual PET Cases Placebo Mid-dose CDNF 30 60 % Change from baseline % Change in UPDRS-III (off, from baseline) Improvement 40 UPDRS part III (off) (DAT BPND) 20 20 Expected decline in UPDRS DAT PET Improvement 0 10 Expected decline in DAT PET -20 A patient who had crossed over fr

  33. Slide 33: DAT PET Responses Over Months: Expected

    DAT PET Responses Over 12 Months What We Would Expect in Parkinsons Patients Baseline Re-randomization of placebo patients to active treatment groups 30 % Change from baseline 20 Improvement (DAT BPND) 10 0 -10 Expected annual decline -20 PD patients’ average annual decrease is 6-13% -30 0 6 12 Mont

  34. Slide 34: DAT PET Responses Over Months: Observed

    DAT PET Responses Over 12 Months What We Actually Observed in Study Patients Baseline Re-randomization of placebo patients to active treatment groups 30 % Change from baseline 20 Improvement Placebo (n=6) (DAT BPND) 10 Mid-dose CDNF (n=6) 0 High-dose CDNF (n=5) -10 Placebo > mid-dose CDNF Expected a

  35. Slide 35: DAT PET Response First 6-Month Treatment vs Placebo: Expected

    DAT PET Response First 6-Month Treatment vs Placebo What We Would Expect in Parkinsons Patients Respective baseline Respective 6-month PET timepoint 30 % Change from baseline 20 Placebo (n=5) (DAT BPND) 10 0 -10 Expected annual decline -20 -30 0 6 Note! For the two Placebo > High-dose CDNF patients,

  36. Slide 36: DAT PET Response First 6-Month Treatment vs Placebo: Observed

    DAT PET Response First 6-Month Treatment vs Placebo What We Actually Observed in Study Patients Respective baseline Respective 6-month PET timepoint 30 % Change from baseline 20 Placebo (n=5) (DAT BPND) 10 Mid-dose CDNF (n=5) 0 High-dose CDNF (n=5) Placebo > mid-dose CDNF (n=3) -10 Expected annual d

  37. Slide 37: Good CDNF Infusate Coverage Achieved In The Putamen

    Good CDNF Infusate Coverage Achieved In The Putamen • Quantitative MRI analysis of contrast agent distribution showed 60-75% coverage of the putamen volume • Gadolinium contrast agent test infusions were carried only for the two first patients. The lines shown within the putamen indicate the infusat

  38. Slide 38: Conclusions & Next Steps

    Conclusions & Next Steps 38 www.herantis.com © 2014-2020 HERANTIS PHARMA Plc. All rights reserved.

  39. Slide 39: Key Conclusions

    Key Conclusions • From safety perspective • CDNF drug safety established • Study procedures improved for future studies • From efficacy perspective • Not possible to gauge efficacy in this group of patients – a lot of ‘noise’ due to: • Disease severity (CDNF dopamine target already lost hence nothin

  40. Slide 40: Moving Forward

    Moving Forward • Shape program moving forward to maximise chances of success and partnerability • Finalise outstanding data on alpha-synuclein, proteomics, CSF • Key areas of focus ○ Earlier disease patients where dopaminergic neurons are still present ○ Adequately powered study with sufficient pati

  41. Slide 41: CDNF Results Compelling Platform For Next Gen xCDNF

    CDNF Results Compelling Platform For Next Gen xCDNF • Common challenge in CNS diseases is drug delivery to the brain (as noted in this study) • CDNF currently administered via surgically implanted device • xCDNF, i.e. smaller selected fragments of CDNF • retain the biological activity of CDNF • pene

  42. Slide 42: Thank You

    Thank You 42 www.herantis.com © 2014-2020 HERANTIS PHARMA Plc. All rights reserved.

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