Mereo BioPharma Group plc · NASDAQ:MREO
Mereo BioPharma — Technical Presentation (March 2022)
20 slides from Mereo BioPharma's technical presentation, Mar 14, 2022
Slide 1: Alvelestat (MPH966) R&D Day
Mereo BioPharma Group plc NASDAQ: MREO March 14 2022 Alvelestat (MPH966) R&D Day Exhibit 99.1
Slide 2: Disclaimer
Disclaimer This presentation has been prepared by Mereo BioPharma Group plc (the “Company”) solely for your information and for the purpose of providing background information on the Company, its business and the industry in which it operates or any particular aspect thereof. For the purposes of thi
Slide 3: Summary
Summary The ASTRAEUS 12-week trial is on track to deliver top-line Phase 2 data for alvelestat in AATD patients with lung emphysema in early Q2 2022* Primary endpoints evolved to three key biomarkers on the pathogenic pathway of the lung disease including detection of neutrophil elastase levels in p
Slide 4: Upcoming Key Milestones & Opportunities
Upcoming Key Milestones & Opportunities Upcoming Milestone For Core Programs Product Candidate Indication 2022 2023 2024 Partner Next Milestone Etigilimab Solid tumors Phase 1b/2 full enrolment and data Phase 2 cohort expansion Alvelestat AATD AATD Phase 2 top-line data BOS Phase 2 initiation BOS Se
Slide 5: ASTRAEUS Phase 2 Study in AATD-Associated Emphysema
ASTRAEUS Phase 2 Study in AATD-Associated Emphysema Randomisation Alvelestat Placebo bid ~ 36 Alvelestat Dose 1 120 mg bid ~ 22 Dose escalation design 12-week dosing period, 4 weeks FU Alvelestat Dose 2 ~ 41 Trial Population Age ≥18 and ≤80 years Pi*ZZ, Pi*Z Null, Pi*Null genotype/phenotype, other r
Slide 6: ASTRAEUS Phase 2 Initial Endpoints
ASTRAEUS Phase 2 Initial Endpoints Primary Endpoints Within individual % change from baseline in plasma desmosine/isodesmosine at end of treatment compared to placebo to week 12 Secondary and Exploratory Endpoints Blood Neutrophil Elastase activity Blood Aα-Val360 levels Safety and tolerability Lung
Slide 7: ASTRAEUS Demographics And Baseline AATD Characteristics
ASTRAEUS Demographics And Baseline AATD Characteristics ASTRAEUS RAPID* All, (N=99) A1PI(n=93) Placebo (n=87) Age years Mean ±SD (Range) 57.3 ±10.1 (26-75) 53.8±6.9 52.4±7.8 Sex Male (%) Female (%) 39(40%) 60(60%) 48(52%) 45(48%) 50(57%) 37(43%) Race White (%) 95(96%) 93(100%) 87(100%) FEV1 % predic
Slide 8: Plasma Desmosine as a Biomarker of Proposed Pathogenic Mechanism (Elastosis)
Plasma Desmosine as a Biomarker of Proposed Pathogenic Mechanism (Elastosis) Marker of Effect on Target Tissue Measure of elastolytic rate (desmosine/isodesmonsine = "desmosine“) Consistently increased in AATD-associated lung disease (emphysema) Addresses question of whether NE inhibition alone modi
Slide 9: Elevated Blinded Baseline Desmosine Levels In ASTRAEUS Consistent With Other Studies
Elevated Blinded Baseline Desmosine Levels In ASTRAEUS Consistent With Other Studies Data, including therapeutic response, available in AATD Correlate with clinical measures of disease severity (FEV1), respiratory function (diffusion factor) and structure (lung density) in AATD population Elevated i
Slide 10: Monitoring Neutrophil Elastase (NE) Levels In Patients With AATD
Monitoring Neutrophil Elastase (NE) Levels In Patients With AATD “Functional PK” assays used in AAT augmentation measure NE inhibiting capacity of serum to quantitate level of “biologically active” AAT Does not measure NE activity within a patient and cannot be used as a measure of ongoing in vivo s
Slide 11: Measurement Of Target Engagement - Activity-based NE Immunoassay
Measurement Of Target Engagement - Activity-based NE Immunoassay For In-vivo Blood Monitoring Of NE Suppression The ProteaseTag® activity-based immunoassay specifically measures active neutrophil elastase levels Improved sensitivity, enables detection in blood supports potential detection of therape
Slide 12: Simultaneous incubation
Simultaneous incubation = Oo Oo © oO So o 2 G 2 3 < £ @ D < G = rs) x 10 AAT (uM)
Slide 13: Preincubation
Preincubation i= Oo - Oo Oo o o © o st N ogel@A-PV Ul aBueyo % oO
Slide 14: Alvelestat/elastase
Alvelestat/elastase *AZD9668: alvelestat *
Slide 15: Plasma Aα-Val360 Blinded Baseline Levels Raised In ASTRAEUS AATD Population
Plasma Aα-Val360 Blinded Baseline Levels Raised In ASTRAEUS AATD Population Mereo Biopharma Group plc Blinded baseline level ASTRAEUS mean 15.05nM (SD 4.81) Similar to levels in AATD Registry study in PiZZ (Carter et al 2013) Positive correlation between desmosine and Aα-Val360 levels at baseline in
Slide 16: No Safety Signals Identified To-date In AATD Patients
No Safety Signals Identified To-date In AATD Patients (Data Blinded To Mereo) Independent Data Monitoring Committee reviews unblinded safety data ~ quarterly. There have been no safety signals detected on adverse event or lab monitoring, including in infectious events, liver, hematology or ECG revie
Slide 17: Linking Biomarkers To Pathological Pathway
Linking Biomarkers To Pathological Pathway AATD-Lung Disease Pathogenic Pathway Neutrophil Elastase Activity Unopposed NE Alveolar Elastin Breakdown Lung Tissue Loss/Emphysema Increased neutrophil elastase activity Increase in neutrophil elastase-driven target (fibrinogen) breakdown Elastin breakdow
Slide 18: ASTRAEUS Phase 2 Revised Endpoints
ASTRAEUS Phase 2 Revised Endpoints Primary Endpoints Within individual % change from baseline up to end of treatment within treatment arm and in comparison, to placebo up to week 12 in: Plasma desmosine/isodesmosine levels Blood Neutrophil Elastase activity Blood Aα-Val360 levels Secondary and Explo
Slide 19: ATALANTa: Alvelestat For Treatment Of Alpha-1 Antitrypsin Deficiency
Alvelestat (MPH966) For The Treatment of ALpha-1 ANTitrypsin Deficiency “ATALANTa” (Investigator-initiated – Principal Investigator Prof Mark Dransfield, UAB) Randomisation Alvelestat Placebo bid N=33 Alvelestat 120 mg bid N=33 N = 66 1:1 active to placebo 12 week dosing period Trial Population Age
Slide 20: ATALANTa - Consistent Supportive Safety Profile Of Alvelestat In Patients With AATD
ATALANTa - Consistent Supportive Safety Profile Of Alvelestat In Patients With AATD 10 active sites in USA 37 patients randomized No SAEs reported in the study to date No clinically important abnormalities in hematology and clinical chemistry reported to date 6 monthly DSMB meeting (last Dec 2 2021)
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