Slide 1: Gene Therapy for the Treatment of Radiation-Induced Xerostomia: AAV2-hAQP1 Program Update
Gene Therapy for the Treatment of Radiation-Induced Xerostomia: AAV2-hAQP1 Program Update June 27, 2023 CONFIDENTIAL
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this presentation that do not relate to matters of historical fact should be considered forward-looking statements,
Slide 3: Agenda
Agenda 1. Introduction Zandy Forbes, PhD President & CEO MeiraGTx 2. Radiation-Induced Xerostomia: Disease Background and Unmet Medical Need Robert K. Zeldin, MD Chief Medical Officer MeiraGTx 3. AQUAx Phase 1 Study Data Zandy Forbes, PhD President & CEO MeiraGTx 4. AQUAx 2: Phase 2 Study Robert K.
Slide 4: Salivary Gland Gene Therapy for Radiation-Induced Xerostomia
Salivary Gland Gene Therapy for Radiation-Induced Xerostomia Robert K. Zeldin, MD
Slide 5: Radiation-Induced Hyposalivation and Xerostomia (RIX)
Radiation-Induced Hyposalivation and Xerostomia (RIX) Serious, debilitating complications as a result of reduced saliva production ❖ RIX is one of the most frequent complications of radiation treatment for head and neck cancer ❖ 85% of radiation-treated patients experience reduced saliva production,
Slide 6: No Effective Treatment Options for Grade 2/3 RIX
No Effective Treatment Options for Grade 2/3 RIX Currently therapies only treat symptoms, with limited efficacy and poor tolerability, leaving a significant unmet need in grade 2/3 RIX ❖ Providers generally recommend lifestyle interventions first (e.g., extra water consumption) followed by topical a
Slide 7: Large Commercial Opportunity
Large Commercial Opportunity Large indication for a gene therapy: both prevalence and incidence ❖ >170,000 1,2,3 long term (2 years post successful treatment) grade 2/3 RIX patients currently in the US alone ❖ 54,000 new cases of head and neck cancer per year in the US with >15,000 new long-term gra
Slide 8: AAV2-hAQP1 Mechanism of Action and Delivery
AAV2-hAQP1 Mechanism of Action and Delivery Mechanism of Action: Viral Vector Configuration: CAPSID ITR CMV hAQP1 polyA ITR AAV2 • Water-impermeable duct cells generate an AAV2 Capsid - AAV2: osmotic gradient (lumen > interstitium) • Transduces human primary salivary gland tissue more effectively th
Slide 9: AQUAx Phase 1 Study Data
AQUAx Phase 1 Study Data Zandy Forbes, PhD
Slide 10: AQUAx Phase 1 Study Design
AQUAx Phase 1 Study Design Study Design • Open label, multi-center, dose escalation study at 4 sites in USA and Canada Cohort Dose • One-time administration of AAV2-hAQP1 to one (unilateral) or both (bilateral) 1 1 × 1011 vg/gland (single gland) parotid glands 2 3 × 1011 vg/gland (single gland) • Fo
Slide 11: Summary: MGT016 AQUAx Phase 1 Study
Summary: MGT016 AQUAx Phase 1 Study Study Status: COMPLETED • Four unilateral treated cohorts (n=12) • Four bilateral treated cohorts (n=12) • Study completed, database locked • Subjects continue to be followed for up to 5 years in the long term follow up study Data Presented Today: • Data from all
Slide 12: What are Salivary Hypofunction and Xerostomia?
What are Salivary Hypofunction and Xerostomia? ❖ Hyposalivation: Objective measure of saliva production – assessed by collecting whole saliva ❖ Xerostomia: Subjective feeling of dry mouth – assessed using patient reported outcome measures (PROs) ❖ Relationship between Xerostomia and Saliva Productio
Slide 13: Global Rate of Change Questionnaire (GRCQ)
Global Rate of Change Questionnaire (GRCQ) ❖ Patients are asked if there is a change in their symptom of Dry Mouth ❖ They may reply, “Better”, “Worse”, or “About the Same” ❖ If patients reply “Better” or “Worse”, they are asked to quantify the change on a 7-point scale with the maximum score of 7 an
Slide 14: GRCQ: Strong, Durable Improvements 12 Months After Unilateral Treatment
GRCQ: Strong, Durable Improvements in Severity of Xerostomia was Demonstrated 12 Months After Unilateral Treatment Dry Mouth Symptoms? GRCQ Score for Unilateral Treatment (n=12) GRCQ Better (+), Worse (X), All participants to 12 months or more UNILATERAL or Same (=), How Much Better/Worse? Day Day D
Slide 15: GRCQ: Strong Improvements At 12 Months Following Bilateral Treatment
GRCQ: Strong Improvements in Severity of Xerostomia At 12 Months Following Bilateral Treatment Dry Mouth Symptoms? GRCQ Better (+), Worse (X), GRCQ Score for Bilateral Treatment (n=12) BILATERAL or Same (=), How Much Better/Worse? All participants to 12 months Cohort Participant Day 90 Day 180 Month
Slide 16: GRCQ: Overall Improvement Greater in Bilateral than Unilateral
GRCQ: Overall Improvement Greater in Bilateral compared to Unilateral treatment group; Unprecedented 4-point Improvement at 12 Months GRCQ improvements for Bilateral and Unilateral and Treated Cohorts 4.5 - Bilateral ❖ In the overall cohorts, the average improvement score in GRCQ - Unilateral was gr
Slide 17: Xerostomia Questionnaire (XQ)
Xerostomia Questionnaire (XQ) • A Patient Reported Outcome measure • 8 symptom-specific questions wherein the patient rates each symptom from 0 (not present) to 10 (worst possible) • Responses are summed (0-80), providing an overall measure of disease burden • An improvement (decrease) of 8 points (
Slide 18: XQ: Very Strong Improvements Compared to Baseline in Both Cohorts
Xerostomia Questionnaire (XQ): Very Strong Improvements (Decrease in Score) Compared to Baseline Observed in Both Unilateral and Bilateral Cohorts Change From Baseline Change From Baseline Unilateral Bilateral ❖ Unilateral: 7/12 had score improvements Day Day Day Month Year Year Day Day Month (decre
Slide 19: XQ: Substantial Clinically Meaningful Improvements From Baseline
XQ: Substantial Clinically Meaningful Improvements From Baseline in XQ in both Unilateral and Bilateral treated Cohorts 1.4 - Bilateral ❖ Unilateral: 13-point improvement from baseline 0 - Unilateral at 12 months - Updated data point -4.5 -4.8 ❖ Bilateral: 21-point improvement from baseline at 12 mo
Slide 20: Bilateral Cohorts: Meaningful Improvement in Unstimulated Whole Saliva Production
Bilateral Cohorts: Meaningful Improvement in Unstimulated Whole Saliva Production Achieved Reaching Normal Levels Following AAV2-hAQP1 Treatment Whole Salivary Flow Rate (mL/min) Average % Change from Baseline Flow Rate 120% 0.40 0.4 112% 0.35 0.31 80% 79% (n=11) 0.33 83% 69% 70% % Change from Basel
Slide 21: Unilateral Treated Subjects Also Showed Improvement in Whole Saliva Measures
Unilateral Treated Subjects Also Showed Improvement in Absolute Whole Saliva Measures (Stimulated) Absolute Salivary Flow Rate (mL/min) Average % Change from Baseline Flow Rate 40% 0.85 0.88 34% 0.82 20% 0.78 % Change from Baseline 0.74 17% 20% 0.75 15% Flow Rate mL/min 0.68 7% 0.70 0% 0% 0.65 -1% 0
Slide 22: Improvements in Both Xerostomia Severity Scores and Saliva Production
Improvements in Both Xerostomia Severity Scores and Saliva Production Demonstrated Following AAV2-hAQP1 Treatment SUMMARY ❖ Meaningful improvements in xerostomia symptoms were reported across both unilateral and bilateral treated cohorts ❖ As assessed by the GRCQ in unilateral and bilateral treated
Slide 23: Study MGT001: AAV2-hAQP1 Persists in Parotid Gland for at Least 24 Months
Study MGT001: AAV2-hAQP1 Persists in Parotid Gland for at Least 24 Months After Treatment Dose Dose Participant Cohort per Visit of Biopsy Copy #/ng DNA Copy #/Cell Concentration gland AAV001 1 1E10 1.43E10 18 Months 160 0.96 AAV005 1 1E10 5.00E9 24 Months 122 0.73 AAV002 2 3E10 1.76E11 18 Months 23
Slide 24: Study MGT001: AAV2-hAQP1 Persists in Parotid Gland for at Least 24 Months
Study MGT001: AAV2-hAQP1 Persists in Parotid Gland for at Least 24 Months After Treatment • The image in this slide comes from a core needle biopsy from DAPI AQP5 CTK AQP1 participant AAV019 in the NIH Phase 1 study acini, non acini, transduced transduced • AQP1 protein expression is observed in par
Slide 25: Wholly-Owned, In-House, End-to-End cGMP Manufacturing
Wholly-Owned, In-House, End-to-End cGMP Manufacturing Most comprehensive viral vector manufacturing infrastructure in the industry, supported by robust know-how and patent estate • In-house, commercial scale cGMP viral vector manufacturing – 2 facilities, London and Shannon, support commercial produ
Slide 26: AQUAx 2: Phase 2 Study Design and Efficacy Endpoints
AQUAx 2: Phase 2 Study Design and Efficacy Endpoints Phase 2 randomized, double-blind, placebo-controlled study is now open Study Design ➢ Randomized, double-blind, placebo-controlled ➢ 120 participants: Two active doses of AAV2-hAQP1 vs Placebo 1:1:1 ➢ Active Doses: 0.4E12 and 1.2E12 (n=40 for each
Slide 27: AAV-hAQP1 is a Potentially Transformative Treatment for Grade 2/3 Radiation-Induced Xerostomia
AAV-hAQP1 is a Potentially Transformative Treatment for Grade 2/3 Radiation-Induced Xerostomia • AAV2-hAQP1 has potential to become a standard of care for long term grade 2/3 radiation induced xerostomia patients based on its disease-modifying mechanism of action and meaningful improvements in both
Slide 28: Audience Q&A
Audience Q&A CONFIDENTIAL