Sio Gene Therapies Inc

Sio Gene Therapies — Axovant Gene Therapies — Technical Presentation (October 2020)

30 slides from Sio Gene Therapies's technical presentation, Oct 29, 2020

  1. Slide 1: AXO-Lenti-PD Program Update

    Exhibit 99.2 AXO-LENTI-PD PROGRAM UPDATE Gavin Corcoran, MD – Chief R&D Officer © 2020 Axovant Gene Therapies. All Rights Reserved. 1

  2. Slide 2: Forward-Looking Statements

    Forward-Looking Statements This presentation contains forward-looking statements for the purposes of product candidates will ever receive regulatory approval or be successfully the safe harbor provisions under The Private Securities Litigation Reform commercialized. All forward-looking statements ar

  3. Slide 3: AXO-Lenti-PD Can Address Patient Needs and Transform the Standard of Care

    AXO-LENTI-PD CAN ADDRESS PATIENT NEEDS AND TRANSFORM THE STANDARD OF CARE FOR PARKINSON’S DISEASE Unmet Needs: Efficacy Profile Lack of a disease Loss of levodopa Invasive therapies stabilizing effectiveness are limited in their AXO-LENTI-PD VISION: therapy over time efficacy Establish AXO-Lenti-PD

  4. Slide 4: AXO-Lenti-PD Vision Enabled by Differentiated Product Profile

    AXO-LENTI-PD VISION ENABLED BY DIFFERENTIATED PRODUCT PROFILE FOR PARKINSON’S DISEASE Novel disease-modifying agent Addresses limitations of across stages of Parkinson’s current standard of care disease Improve motor Improve quality function of life  Improves motor without  Potential once-and-done

  5. Slide 5: AXO-Lenti-PD Clinical Development Plan: Current Status

    AXO-LENTI-PD CLINICAL DEVELOPMENT PLAN: CURRENT STATUS AXO-Lenti-PD – Optimized Vector Construct SUNRISE-PD Phase 2 Clinical Study Cohort 3 and EXPLORE-PD Clinical Study Dose Escalation Volume AXO-Lenti-PD Expansion EXPLORE-PD Phase 2 Cohort 3 Clinical Study Cohort 1 Cohort 2 4.2 x 107 TU 6 7 4.2 x

  6. Slide 6: Systematic Data Collection Evaluating Patient Outcomes

    SYSTEMATIC DATA COLLECTION EVALUATING PATIENT OUTCOMES Safety and • Adverse event collection • Focused ongoing surveillance of gene Hauser Diary is completed by the patient Tolerability therapy at home every 30 mins over 3 consecutive days. • OFF • ON without troublesome dyskinesia • Hauser Patient

  7. Slide 7: UPDRS Part III (Motor) Scores Observed in Clinical Trials

    UPDRS PART III (MOTOR) SCORES OBSERVED IN CLINICAL TRIALS • Clinically meaningful differences in UPDRS Part III (motor) scores: • ~5-point change represents a moderate difference, a >10-point change is large treatment effect Placebo Effect in Sham- ~ 1- 5 POINTS Controlled studies ≥ 4 - 8 POINTS Sta

  8. Slide 8: AXO-Lenti-PD Cohort Data Review

    AXO-LENTI-PD COHORT 2 DATA REVIEW Demographics with comparison to ProSavin and Cohort 1 Safety and Adverse Event Profile Key Efficacy Evaluation at 6 months • Efficacy Parameters Summary • Hauser patient diary • UPDRS Part II and III (OFF) • Levodopa Equivalent Daily Dose (LEDD) Summary and Next Ste

  9. Slide 9: AXO-Lenti-PD: Baseline Characteristics Across Cohorts

    AXO-LENTI-PD: BASELINE CHARACTERISTICS ACROSS COHORTS All Cohorts Cohort 1 Cohort 2 ProSavin AXO-Lenti-PD AXO-Lenti-PD Dose: 1.9x107 – 1.0x108 Dose: 4.2x106 Dose: 1.4x107 TU/patient TU/patient TU/patient (N=15) 2,3,4 (N=2) 2 (N=4) 2 Age (years) 57 (4.3) 53 (4.2) 57 (6.1) (range) (48-64) (50-56) (51-

  10. Slide 10: AXO-Lenti-PD Adverse Event Profile

    AXO-LENTI-PD ADVERSE EVENT PROFILE Number of subjects with treatment-emergent adverse events (TEAEs) that occurred in > 2 subjects in each Cohort by MedDRA System Organ Class and Preferred Term Cohort 1 (N=2) Cohort 2 (N=4) Overall (N=6) Any treatment-emergent 2 (100%) 4 (100%) 6 (100%) adverse even

  11. Slide 11: Four Unrelated Serious Adverse Events Reported

    AXO-LENTI-PD: FOUR UNRELATED SERIOUS ADVERSE EVENTS REPORTED Patient SAE Event Onset Event Severity Relatedness to (Reported term) (Study Day) Resolved AXO-Lenti-PD (Study Day) Cohort 1 Psychotic 320 408 Severe Unlikely 1001 depression Worsening of 213 218 Severe Not related Parkinson’s disease Coho

  12. Slide 12: Cohort 6-Month Data Availability

    AXO-LENTI-PD COHORT 1 AND COHORT 2 6-MONTH DATA AVAILABILITY Data Available  Data Unavailable Hauser Diary UPDRS Part II UPDRS Part III Hauser Diary LEDD Change Patient “Good ON” (ADL) (MOTOR) OFF Time (hrs) (mg) Time (hrs) OFF OFF Cohort 1 1001 1003 Cohort 2 2002 2004   2006   2007 • Patient 2

  13. Slide 13: Patient 2002

    PATIENT 2002 51-Year Old Male with Parkinson’s Disease for 7 years UPDRS Part III (OFF) Motor Hauser Diary 100 Baseline Hauser Diary 16 Score* 80 14 Diary ”Good ON” = 13.7 hrs 12 7.54 60 ON time without dyskinesia 10.8 10 12.8 40 ON time with non-troublesome 8 Score Observed 50 dyskinesia 20 28 27*

  14. Slide 14: Patient 2002 – UPDRS Item (Resting Tremor)

    PATIENT 2002 – UPDRS Item 20 (Resting Tremor) The first patient treated in Cohort 2 of SUNRISE-PD, washed OFF L-Dopa for 12 hours 6 MONTHS AFTER BASELINE AXO-LENTI-PD 14

  15. Slide 15: Patient 2002 – UPDRS Item (Gait)

    PATIENT 2002 - UPDRS Item 29 (Gait) The first patient treated in Cohort 2 of SUNRISE-PD, washed OFF L-Dopa for 12 hours BASELINE 6 MONTHS AFTER AXO-LENTI-PD 15

  16. Slide 16: Patient 2004

    PATIENT 2004 60-Year Old Male with Parkinson’s Disease for 13 years Baseline Hauser Diary Hauser Diary 16 Diary ”Good ON” = 10.7 hrs 14 ON time without dyskinesia 12 8.89 8.37 ON time with non-troublesome dyskinesia 10 ON time with troublesome 8 dyskinesia 2.39 6 1.79 0 0.13 Diary OFF = 5.3 hours 4

  17. Slide 17: Patient 2006

    PATIENT 2006 64-Year Old Male with Parkinson’s Disease for 20 years Baseline Hauser Diary Hauser Diary 16 2.48 Diary ”Good ON” = 8 hrs 14 6.32 ON time without dyskinesia 12 ON time with non-troublesome dyskinesia 10 1.75 9.06 ON time with troublesome 8 0 dyskinesia 6 Diary OFF = 7.9 hours 4 7.93 0.4

  18. Slide 18: Patient 2007

    PATIENT 2007 64-Year Old Male with Parkinson’s disease for 13 years UPDRS Part III (Motor) OFF 100 Baseline Hauser Diary Hauser Diary Score* 16 80 Diary ”Good ON” = 8.5 14 6.2 60 12 ON time without dyskinesia 10.1 ON time with non-troublesome 10 40 2.28 dyskinesia 8 Score Observed 53 0 20 34 ON time

  19. Slide 19: Patient 2007 – UPDRS Item (Gait)

    PATIENT 2007 - UPDRS Item 29 (Gait) Gait and Balance Assessment washed OFF L-Dopa for 12 hours BASELINE 6 MONTHS AFTER AXO-LENTI-PD 19

  20. Slide 20: Cohort 1 and 2 Change from Baseline to Month 6

    AXO-LENTI-PD COHORT 1 AND COHORT 2 CHANGE FROM BASELINE TO 6 MONTHS Hauser Diary UPDRS Part II UPDRS Part III Hauser Diary LEDD Change Patient “Good ON” (ADL) (MOTOR) OFF Time (hrs) (mg) Time (hrs) OFF OFF 1001 +2.8 -2.4 -98 -26 -20 1003 -0.5 +2 -150 -13 -14 Cohort 1 Mean +1.2 -0.2 -124 (11%) -19.5

  21. Slide 21: Cohort 1 and 2 Change from Baseline to Month 6

    AXO-LENTI-PD COHORT 1 AND COHORT 2 CHANGE FROM BASELINE TO 6 MONTHS Hauser Diary UPDRS Part II UPDRS Part III Hauser Diary LEDD Change Patient “Good ON” (ADL) (MOTOR) OFF Time (hrs) (mg) Time (hrs) OFF OFF 1001 +2.8 -2.4 -98 -26 -20 1003 -0.5 +2 -150 -13 -14 Cohort 1 Mean +1.2 -0.2 -124 (11%) -19.5

  22. Slide 22: AXO-Lenti-PD: Improvement in Hauser Patient Diaries

    AXO-LENTI-PD: IMPROVEMENT IN HAUSER PATIENT DIARIES Cohort 1: (N=2) Cohort 2: (N=4) Minimal change in Increase of 2.2 hours in 14 “Good ON Time” 14 “Good ON Time” 10 10 6 12.6 12.4 6 12.4 10.2 2 “Good” 2 “Good” 1.5 3.0     -2 hours Normalized -2 -3.5 1.8 Normalized hours Normalized -5.8 “Bad” “B

  23. Slide 23: AXO-Lenti-PD: Change in Levodopa Equivalent Daily Dose (LEDD)

    AXO-LENTI-PD: CHANGE IN LEVODOPA EQUIVALENT DAILY DOSE (LEDD) 0 Cohort 1: (N=2) 1 LEDD Baseline: 1116.5 mg -50 Average Reduction: 6 Months : -124 mg (11 %) -100 -124 (11%) -150 Cohort 2: (N=4) 2 LEDD Baseline: 1696.6 mg Average Improvement: -200 6 Months : -271 mg (13 %) Change Change from Baseline

  24. Slide 24: AXO-Lenti-PD: Change in UPDRS Part II (ADL) OFF Score at 6 Months

    AXO-LENTI-PD: CHANGE IN UPDRS PART II (ADL) OFF SCORE AT 6 MONTHS ProSavin AXO-Lenti-PD 20 18 16 14 12 10 8 6 Improvement Improvement (points) 8.7 19.5 4 (64.7%) 13.5 2 3.7 (71.3%) 0 1.2 Cohort 1 (n=3) Cohort 2 (n=6) Cohort 3 (n=6) Cohort 1 (N=2) Cohort 2: (N=2) Target Dose: Target Dose: Target Dose

  25. Slide 25: AXO-Lenti-PD: Change in UPDRS Part III (Motor) OFF Score at 6 Months

    AXO-LENTI-PD: CHANGE IN UPDRS PART III (MOTOR) OFF SCORE AT 6 MONTHS UPDRS PART III (MOTOR) OFF SCORE IMPROVEMENT IN HUMANS (CROSS-STUDY COMPARISON)1 25 20 15 10 21 17 15 13 5 8 Improvement at Months 6 at Improvement 0 Average UPDRS Part III UPDRS(Motor) Score Part Average ProSavin ProSavin ProSavin

  26. Slide 26: AXO-Lenti-PD: Potentially Turning Back the Clock for Parkinson's Patients

    AXO-LENTI-PD: POTENTIALLY TURNING BACK THE CLOCK FOR PATIENTS WITH PARKINSON’S DISEASE CHANGE FROM BASELINE ON UPDRS PART III (MOTOR) “OFF” SCORE 25 20 15 10 Worsening 5 0 -5 -10 -15 Improvement -20 -25 BaselineMonth 6 Month 12 Month 24 Month 36 Month 48 Month 60 ProSavin Low-dose ProSavin Medium-do

  27. Slide 27: Totality of AXO-Lenti-PD Data Suggests Consistent Patient Benefit

    TOTALITY OF AXO-LENTI-PD DATA ACROSS COHORTS SUGGESTS CONSISTENT PATIENT BENEFIT Consistent patient benefit across multiple objective measures Safety and • Generally well-tolerated with no serious adverse events related to therapy tolerability Improved • 17-21-point mean improvement in the UPDRS Par

  28. Slide 28: AXO-Lenti-PD Clinical Development Plan: Next Steps

    AXO-LENTI-PD CLINICAL DEVELOPMENT PLAN: NEXT STEPS Cohort 3 and EXPLORE-PD Clinical Study Volume Expansion AXO-Lenti-PD Cohort 3 EXPLORE-PD Phase 2 4.2 x 107 TU Clinical Study 1800 µL total infusion volume Randomized, double- blinded clinical trial with Evaluates safety, highest safe dose vs. tolera

  29. Slide 29: Critical Success Factors for EXPLORE-PD Study

    CRITICAL SUCCESS FACTORS FOR EXPLORE-PD STUDY Acquiring the best data set to make important decisions will depend on the following factors: 1 Execute a patient-focused study • Ensure that all the evaluations can be completed in the sequence set out in the protocol  Conducted a patient advisory boar

  30. Slide 30: Summary

    SUMMARY • AXO-Lenti-PD has the potential to provide clinically meaningful benefits to patients with advanced PD continuing to progress on medical therapy. • Cohort 2 shows: • Very favorable safety profile that is similar to cohort 1 and Prosavin. • Positive assessments focused on the change in motor

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