Mereo BioPharma Group plc · NASDAQ:MREO
Mereo BioPharma — Investor Presentation (May 2021)
45 slides from Mereo BioPharma's investor presentation, May 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 May 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, Strategy & Vision guide us
Our Core Purpose, Strategy & Vision guide us SUMMARY MISSION STRATEGY TRACK RECORD FUNDAMENTALS • #1 priority – the patients Improving lives of • Acquire programs for • Acquired/in-licensed 6 Our partners we seek to serve patients with oncology oncology and rare diseases programs with Phase 1b/2 and
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 Phase 1b/2 Solid tumors 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 Sweden AB Chief Executive Officer Chief Fin
Slide 6: Etigilimab
—Sw Mereo BioPharma ~~ Etigilimab
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 in cis Expressed on CD4, CD8 and NK cells and is elevated upon activ
Slide 8: Etigilimab - an IgG1 anti-TIGIT monoclonal antibody with inhibitory and ADCC characteristics
Etigilimab - an IgG1 anti-TIGIT monoclonal antibody with inhibitory and ADCC characteristics Control Ab Effector function competent Effector function silent 7 Mereo Biopharma Group plc
Slide 9: 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 10mg/kg Q2W Tumor types for inclusion 20mg/kg Q2W + nivolumab in dose escalation cohort: N=3+3 in dose escalation cohort: N=3+3 • Histologically confirmed • Histologically confirmed 3mg
Slide 10: 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 11: Phase 1b best % reduction in target lesion size & duration on study
Phase 1b best % reduction in target lesion size & duration on study Etigilimab + nivolumab W12a0terfall 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 + ni
Slide 12: 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 13: Overall Phase 1b/2 basket study design
Overall Phase 1b/2 basket study design Rare Tumors Primary endpoint • Overall Response Rate Cervical carcinoma* Secondary • Safety and Tolerability Endometrial carcinoma • PK/PD • Duration of response Gastric/GE carcinoma* Phase 1b/2 study Exploratory planned recently • Biomarker • PFS initiated • O
Slide 14: Etigilimab Phase 1b/2 Initial Focus Checkpoint-Naïve Indications
Etigilimab Phase 1b/2 Initial Focus Checkpoint-Naïve Indications (CPI-Naïve) Rare Tumors total n =45 incl sarcoma (15) & 2 other rare tumors (30) 2021 Focus on: Gynonc – 2L cervical carcinoma (CPI-naïve)* n=10 1. Rare Cancers Phase 1b/2 2. Checkpoint- Gynonc 3L Endometrial carcinoma (CPI- naïve)* n=
Slide 15: 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 16: 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 15
Slide 17: 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 18: Summary: Mereo's etigilimab has key differentiating features
Summary: Mereo’s etigilimab has key differentiating features High affinity Phase 1a and Phase 1b Advanced Biomarker dose escalation and IgG1 antibody safety data available capabilities in place • IgG1 backbone activates • Active IND and drug product • Target engagement of etigilimab antibody-depende
Slide 19: Alvelestat (MPH-966)
—Sw Mereo BioPharma ~~ Alvelestat (MPH-966)
Slide 20: 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 21: Signal seeking in Neutrophil-driven diseases (1): cystic fibrosis
Signal seeking in Neutrophil-driven diseases (1) cystic fibrosis – anti-inflammatory and clinical effect Desmosine alvelestat:placebo ratio at week 4 Alvelestat decreases Trial Summary urinary and plasma DESs in CF (n=56); *P<0.05 • Double-blind, placebo controlled • > 16 years • Clinical diagnosis
Slide 22: 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 23: Alpha-1 antitrypsin deficiency (AATD) – disease impact
Alpha-1 antitrypsin deficiency (AATD) – disease impact AATD-Lung Disease A rare, serious genetic disorder that results in Natural protease inhibitor is either absent or levels are early onset pulmonary insufficient and dysfunctional disease Unopposed neutrophil elastase → progressive and severe lung
Slide 24: 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 25: 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 26: Desmosine as a Primary Endpoint for Phase 2 in AATD
Desmosine as a Primary Endpoint for Phase 2 in AATD ~ 30% lung tissue is elastin Neutrophil elastase (NE) key enzyme driving lung elastin breakdown alveolar damage and loss of lung tissue/density Desmosine is direct elastin breakdown product Desmosine associated with disease severity in disorders wi
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 Cystic Fibrosis Increased levels desmosine similar to AATD Ma S, Geraghty P, Dabo A, et al. Cystic fibrosis disease severity correlates withplasma levels of desmosine and isodesmosine, biomark
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: ATALANTa: Investigator-initiated study of alvelestat in AATD
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 Randomisati
Slide 30: 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 29
Slide 31: 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) • Mortality (Day 90) 10 day dosing period N = 15 2:1 active to placebo Secondary Endpoints Alvelestat bid Pharmacodynamic Biomarkers of: • NETosis Randomisation Follow
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 (BPS-804)
—Sw 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 33
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: • More than 55,000 patients in U
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 the Phase 2b study setrusumab in US
Slide 37: Summary of phase 2b data
Summary of phase 2b data Hierarchical primary Secondary end-points Study not powered to Phase 2b – 110 adult end-point based on based on areal bone show a difference in OI patients comparing HRPQCT mineral density fracture rates but a • Trabecular vBMD at the measured by DXA 3 doses of setrusumab tr
Slide 38: Upcoming Milestones
—Sw Mereo BioPharma ~~ Upcoming Milestones
Slide 39: Mereo upcoming key milestones & opportunities
Mereo upcoming key milestones & opportunities Product Indication 2021 2022 2023 Partner Milestone Candidate Phase 1b/2 full Etigilimab Solid tumors Phase 1b/2 basket study with potential cohort expansion enrollment and data Phase 2 cohort expansion Phase 2 PoC study ASTRAEUS Phase 2 data readout Cor
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 in
Slide 42: Appendix
—Sw Mereo BioPharma ~~ Appendix
Slide 43: Intellectual Property Portfolio
INTELLECTUAL PROPERTY PORTFOLIO 2019 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
Slide 44: Thank You
Thank You Mereo BioPharma Group plc NASDAQ: MREO
Slide 45: Mereo BioPharma Group plc
Mereo BioPharma Group plc One Cavendish Place London, W1G 0QF UK +44 (0)333 0237 300 Mereo Biopharma Group plc 42
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