Mereo BioPharma Group plc · NASDAQ:MREO
Mereo BioPharma — Investor Presentation (September 2021)
53 slides from Mereo BioPharma's investor presentation, September 2021
Slide 1: Unlocking the potential of novel targets for cancer and rare diseases
Unlocking the potential of novel targets for cancer and rare diseases September 2021 Mereo BioPharma Group plc NASDAQ: MREO
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: Our Core Purpose, Mission & Strategy guide us
Our Core Purpose, Mission & Strategy guide us SUMMARY MISSION STRATEGY TRACK RECORD FUNDAMENTALS • Acquire programs in • Acquired/in-licensed 6 Our partners • #1 priority – the patients oncology and rare diseases programs with Phase 1b/2 we seek to serve Improving lives of patients with strong scien
Slide 4: Late Stage Diversified Clinical Pipeline
Late Stage Diversified Clinical Pipeline Core Programs Product Candidate / Indication Phase 1a Phase 1b Phase 2 Phase 3 Next Milestones Etigilimab Solid tumors Phase 1b/2 Alvelestat Phase 2 AATD Alpha-1 antitrypsin deficiency Phase 1b/2 COVID COVID-19 Adult extension study Setrusumab Osteogenesis im
Slide 5: Experienced Management Team and Board
Experienced Management Team and Board Board of Directors Dr. Peter Fellner Chairman Dr. Denise Scots-Knight Executive Director, CEO & Co-Founder Dr. Anders Ekblom Dr. Denise Scots-Knight Christine Fox Charles Sermon Dr. John Lewicki Former CEO, AstraZeneca Chief Executive Officer Chief Financial Off
Slide 6: Etigilimab
TSO Mereo BioPharma ~~ Etigilimab (MPH-343)
Slide 7: TIGIT is a negative regulator of T cell responses
TIGIT is a negative regulator of T cell responses T cell Immunoreceptor with Ig and ITIM domains (TIGIT) Negative regulator of T cell response: • Competes with CD226 for PVR, disrupts CD226 activation, and directly inhibits T cells Expressed on CD4, CD8 and NK cells and is elevated upon activation;
Slide 8: Etigilimab blocks interaction of PVR with TIGIT and inhibits signaling
Etigilimab blocks interaction of PVR with TIGIT and inhibits signaling Etigilimab Blocks PVR Binding In Cell Based Assay Anti-TIGIT inhibits TIGIT phosphorylation in response to PVR ligand Anti-TIGIT blocks PVR-induced suppression of human T-Cell Activation Human TIGIT ECD fused to CD4TM-GFP was tra
Slide 9: Etigilimab – an IgG1 anti-TIGIT monoclonal antibody with ADCC characteristics
Etigilimab – an IgG1 anti-TIGIT monoclonal antibody with inhibitory and ADCC characteristics Control Ab Effector function competent Effector function silent Mereo Biopharma Group plc 7
Slide 10: Phase 1 study design
Phase 1 study design Phase 1A Phase 1B Dose Escalation 20mg/kg Q2W Dose Escalation N=3+3 Tumor types for inclusion Tumor types for inclusion 10mg/kg Q2W 20mg/kg Q2W + nivolumab N=3+3 in dose escalation cohort: N=3+3 in dose escalation cohort: • Histologically confirmed • Histologically confirmed 3mg
Slide 11: Phase 1a best % reduction in target lesion size & duration on study
Phase 1a best % reduction in target lesion size & duration on study Etigilimab monotherapy Waterfall Plot of Best Percentage Change in SLD from Baseline (ITT Population) Duration on Study Patient Dose Cancer Patient Dose Cancer 004-013 10mg/kg adenocarcinoma of the pancreas 001-025 20mg/kg* Endometr
Slide 12: Phase 1b best % reduction in target lesion size & duration on study
Phase 1b best % reduction in target lesion size & duration on study Etigilimab + nivolumab Waterfall Plot of Best Percentage Change in SLD from Baseline (ITT Population) Duration on Study Head and Neck Cancer, 20.0 mg/kg + nivolumab Gastric Cancer, 20.0 mg/kg + nivolumab 100 NSCLC, 3.0 mg/kg + nivol
Slide 13: Phase 1 clinical & biomarker findings
Phase 1 clinical & biomarker findings Seven subjects (30%, n=23) had stable disease as their best response in the single-agent Phase 1a cohort • Majority of patients with tumor types typically non-responsive to anti-PD1 agents One partial response and 1 stable disease evident in initial Phase 1b (co
Slide 14: THE ACTIVATE STUDY
TSO Mereo BioPharma ~~ THE ACTIVATE STUDY
Slide 15: ACTIVATE – A Phase 1b/2 Open-label Study
ACTIVATE – A Phase 1b/2 Open-label Study Etigilimab plus nivolumab in advanced/metastatic solid tumors Primary endpoint • Overall Response Rate Rare tumors (e.g., sarcomas) Additional study in rare Secondary subtype of ovarian cancer with • Safety and Tolerability Ovarian MD Anderson/Focus Fund • PK
Slide 16: Study Design: Decision Making
Study Design: Decision Making • Statistical rigor provided by Simon 2-stage design: – Stage 1 futility monitoring for progression to Stage 2 – Clinically meaningful benchmark for Go/No-go beyond Stage 2 • Open label design allows for dynamic decision making • Totality of safety and efficacy data wil
Slide 17: Differentiated Clinical and Biomarker Strategy
Differentiated Clinical and Biomarker Strategy
Slide 18: Key Elements of Etigilimab Phase 1b/2: Differentiated clinical development
Key Elements of Etigilimab Phase 1b/2: Differentiated clinical development Gyn-onc indications ORR with Anti-PD-1 Monotherapy Cervical KN158 14% (KN158) • Focus on Checkpoint-naïve populations Ovarian KN100 • Prioritize TIGIT expressing tumors by: 8.1% ( </=2 prior lines); (i) Low monotherapy checkp
Slide 19: Key Elements of Etigilimab Phase 1b/2 Clinical Biomarker Strategy
Key Elements of Etigilimab Phase 1b/2 Clinical Biomarker Strategy Multi-Pronged Biomarker Approaches Prospective selection, established biomarker Cervical, gastric, SCCHN as per indication on PD-L1 label Prospective selection, emerging biomarker TMB-H/MSS tumors Retrospective evaluation with potenti
Slide 20: Phase 1b/2 Study – Biomarker Strategy
Phase 1b/2 Study – Biomarker Strategy • Baseline tissue required in all patients – PVR and TIGIT will be quantified in all patients retrospectively, prespecified in protocol at 30 patients – Data from these initial patients on study could enable prospective enrollment with CLIA assay(s) – Additional
Slide 21: Summary: Mereo’s etigilimab has key differentiating features
Summary: Mereo’s etigilimab has key differentiating features Phase 1a and 1b safety, High affinity Advanced Biomarker preliminary efficacy and IgG1 antibody biomarker data available capabilities in place • IgG1 backbone activates • Target engagement of • Biomarker methods antibody-dependent etigilim
Slide 22: Alvelestat
TSO Mereo BioPharma ~~ Alvelestat (MPH-966)
Slide 23: Alvelestat mechanism of action
Alvelestat mechanism of action Potent, reversible, oral inhibitor of neutrophil elastase (NE) Compared to natural inhibitors i.e., alpha-1 antitrypsin native protein • Comparable association constant • Not susceptible to oxidative inactivation at sites of inflammation • Active against both soluble a
Slide 24: Signal seeking in Neutrophil-driven diseases – cystic fibrosis and bronchiectasis
Signal seeking in Neutrophil-driven diseases – cystic fibrosis and bronchiectasis – anti-inflammatory and clinical effects CF- Desmosine alvelestat:placebo ratio at week 4* Trial Summary - CF Alvelestat decreases urinary and plasma • Double-blind, placebo controlled > 16 years DESs in CF (n=56); *P<
Slide 25: Alpha-1 Antitrypsin deficiency (AATD) Lung disease impact
Alpha-1 Antitrypsin deficiency (AATD) Lung disease impact Natural protease inhibitor is either absent or levels are insufficient and dysfunctional A rare, serious genetic Unopposed neutrophil elastase → progressive lung damage, early onset emphysema disorder that results in early onset pulmonary Pre
Slide 26: Role of Neutrophil elastase in pathogenesis of AATD Lung Disease
Role of Neutrophil elastase in pathogenesis of AATD Lung Disease Elastase/anti- elastase imbalance Pro-inflammatory cytokines - neutrophil activation and chemotaxis Elastase/anti- elastase imbalance Apoptosis of Epithelial cell Release of pro- inflammatory elastin peptides • Neutrophil elastase (NE)
Slide 27: Example of Desmosine and Correlation with Disease Severity in Cystic Fibrosis
Example of Desmosine and Correlation with Disease Severity in Disease with Elastase/anti-elastase imbalance in Cystic Fibrosis Increased levels desmosine similar to AATD Ma S, Geraghty P, Dabo A, et al. Cystic fibrosis disease severity correlates with plasma levels of desmosine and isodesmosine, bio
Slide 28: Astraeus Phase 2 study design in Alpha-1 Antitrypsin Deficiency
Astraeus Phase 2 study design (NCT03636347) in Alpha-1 Antitrypsin Deficiency A 12-week Study Treating Participants Who Have alpha1-antitrypsin-related COPD with Alvelestat (MPH966) or Placebo. (ASTRAEUS) Primary Endpoint • Within-individual % change in N = 165 12 week dosing period plasma desmosine
Slide 29: Alvelestat for AATD “ATALANTa” investigator-initiated study
Alvelestat (MPH966) for the Treatment of ALpha-1 ANTitrypsin Deficiency “ATALANTa”(Investigator-initiated – Mark Dransfield, UAB N = 66 12 week dosing period Primary Endpoint 1:1 active to placebo Alvelestat Placebo bid N=33 • Within-individual % change in plasma desmosine/isodesmosine Randomization
Slide 30: COVID-19 Phase 1b/2 Investigator-initiated study “COSTA”
COVID-19 Phase 1b/2 Investigator-initiated study “COSTA” (Prof. Mike Wells, UAB Primary Endpoint • Safety and tolerability (Day 60) 10 day dosing period N = 15 2:1 active to placebo Secondary Endpoints Alvelestat bid Pharmacodynamic Biomarkers of: • NETosis Randomization Follow-up to Day 90 • Inflam
Slide 31: Bronchiolitis Obliterans Syndrome (BOS)
Bronchiolitis Obliterans Syndrome (BOS) Occurs in lung transplant and allogeneic stem cell recipients • Immune-mediated proliferation of fibrotic tissue progressively obliterates small airways • Airway neutrophilia and NE play key role in driving disease process • ‘Allo-immune’ syndrome identical in
Slide 32: Summary: Alvelestat key differentiating features
Summary : Alvelestat key differentiating features Profile for long-term treatment of AATD lung disease and NETosis-driven diseases Rapid onset of Combination of Highly specific neutrophil elastase action < 4 hours twice daily dosing to > 90% enzyme High neutrophil and high neutrophil inhibition – el
Slide 33: Setrusumab
TSO Mereo BioPharma ~~ Setrusumab (BPS-804)
Slide 34: Anti-Sclerostin as a target for OI
Anti-Sclerostin as a target for OI Mereo Biopharma Group plc 32
Slide 35: Osteogenesis imperfecta (OI)
Osteogenesis imperfecta (OI) • Rare genetic bone disease, key symptoms include: • Frequent bone fractures, skeletal deformities, pain and respiratory insufficiency • 85-90% linked to a mutation in Type I collagen1,2 • Tangible symptomatology leads to early diagnosis: • Approx 60,000 patients in deve
Slide 36: Partnership with Ultragenyx Pharmaceutical
Partnership with Ultragenyx Pharmaceutical MREO :Development and Terms Development Plan commercialization Rights • MREO grants RARE license to • RARE to lead future global • Completes ongoing adult develop and commercialize development in both pediatric extension of Phase 2b study setrusumab in US a
Slide 37: Summary of Phase 2b data
Summary of Phase 2b data Hierarchical primary end- Secondary end-points Study not powered to Phase 2b – 110 adult point based on HRPQCT based on areal bone show a difference in OI patients comparing mineral density measured fracture rates but a 3 doses of setrusumab • Trabecular vBMD at the radius b
Slide 38: Upcoming Milestones
TSO Mereo BioPharma ~~ Upcoming Milestones
Slide 39: Upcoming Key Milestones & Opportunities
Upcoming Key Milestones & Opportunities Product Candidate Indication 2021 2022 2023 Partner Milestone Phase 1b/2 full enrolment Phase 1b/2 basket study with potential cohort expansion Etigilimab Solid tumors and data Phase 2 cohort expansion AATD Core Programs Ph. 2 PoC AATD: Phase 2 data readout AA
Slide 40: Financial highlights
Financial highlights Cap Table ADSs1 Cash runway into 2024 (February 28, 2021) (in thousands) Shareholders > 5% holding 51,440 Cash resources of Shareholders < 5% holding 56,703 $31.9 million (£23.5m) Share capital - Issued and outstanding 108,144 as of December 31, 2020 $50 million upfront for Pote
Slide 41: Investment highlights
Investment highlights Developing therapeutics for oncology and rare diseases based on novel targets with strong biological rationale • Etigilimab is an anti-TIGIT antibody which actively engages FcyR in an ongoing Phase 1b/2 oncology basket study • Alvelestat is an oral neutrophil elastase inhibitor
Slide 42: Appendix
TSO Mereo BioPharma ~~ Appendix
Slide 43: Intellectual property portfolio
Intellectual property portfolio 2021 2023 2025 2027 2029 2031 2033 2035 2037 2039 2041 1SPC Antibody and use – granted/pending in all major territories 1,2PTE Etigilimab Medical use – pending in all major territories 1Data & Marketing Exclusivity - EUROPE 1Biologics Data & Marketing Exclusivity - US
Slide 44: Etigilimab – Cohort Indications: PD-1 Inhibitors Historical Data
Etigilimab – Cohort Indications : PD-1 Inhibitors Historical Data Tumor Type PD-1 Inhibitors Historical data ORR Sarcoma Pembro or Nivo 18% Rare tumor 1 Pembro or Nivo ORR 5 – 16% Pembro or Nivo + Ipilimumab Rare tumor 2 Pembro ORR <5% Rare tumor 3 (metastatic) Pembro ORR 11% Ovarian (all comers) Pe
Slide 45: Etigilimab – Cancer Focus Fund & MD Anderson Collaboration
Etigilimab – Cancer Focus Fund & MD Anderson Collaboration • Cancer Focus Fund, LP • Unique investment fund established in collaboration with The University of Texas MD Anderson Cancer Center. • Provides investment support to advance promising cancer therapies, clinical trial expertise and infrastru
Slide 46: Etigilimab - Cancer Focus Fund & MD Anderson Collaboration
Etigilimab - Cancer Focus Fund & MD Anderson Collaboration • Rationale: • The EON Study runs in parallel to Mereo’s ACTIVATE study that has an ovarian cancer cell arm (which excludes clear cell) • Clear cell represents ~10% of ovarian carcinomas in US/EU • Ovarian cancer generally has poor treatment
Slide 47: Biomarkers established for tumor analysis and potential patient selection
Biomarkers established for tumor analysis and potential patient selection Robust multiplex IHC assays and staining for PVR, TIGIT and ~15 immune-related tumor parameters Mereo Biopharma Group plc 45
Slide 48: Alpha-1 antitrypsin deficiency (AATD) – current standard of care
Alpha-1 antitrypsin deficiency (AATD) – current standard of care Clinical Management A rare, serious genetic disorder that results in ‘COPD’ maintenance treatment, personal lifestyle early onset pulmonary management, e.g., avoidance of smoking and disease pollution Intravenous plasma-derived augment
Slide 49: Signal seeking in Neutrophil-driven diseases (2) bronchiectasis
Signal seeking in Neutrophil-driven diseases (2) bronchiectasis – anti inflammatory and clinical effect Spirometry at week 4 Lung Function Improvement over Trial Summary P Value Parameter placebo LSM(SEM) • Double-blind, placebo controlled FEV1 100 mls (34.0) 0.006 SVC 130 mls (74.0) 0.079 • 18-80 y
Slide 50: Role of Neutrophil elastase in pathogenesis of AATD Lung Disease
Role of Neutrophil elastase in pathogenesis of AATD Lung Disease Elastase/anti- elastase imbalance Elastase/anti- elastase imbalance Pro-inflammatory cytokines - neutrophil activation and chemotaxis Apoptosis of epithelial cell Release of pro- inflammatory elastin peptides Mereo Biopharma Group plc
Slide 51: Alvelestat MOA in NETosis-driven disease (COVID-19)
Alvelestat MOA in NETosis-driven disease (COVID-19) Chromatin studded with NETs activate elastase extruded cytokine storm Dysregulated inflammatory response Alpha-1 antitrypsin physiological elastase inhibitor is overwhelmed Mereo Biopharma Group plc 50
Slide 52: Thank You
Thank You Mereo BioPharma Group plc NASDAQ: MREO
Slide 53: Mereo BioPharma Group plc
Mereo BioPharma Group plc One Cavendish Place London, W1G 0QF UK +44 (0)333 0237 300 Mereo Biopharma Group plc
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