Mereo BioPharma Group plc · NASDAQ:MREO
Mereo BioPharma — Investor Presentation (October 2020)
41 slides from Mereo BioPharma's investor presentation, October 2020
Slide 1: Unlocking Healthcare Potential in Oncology and Rare Diseases
UNLOCKING HEALTHCARE POTENTIAL IN ONCOLOGY AND RARE DISEASES October 2020
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: Investment Highlights
INVESTMENT HIGHLIGHTS • Clinical stage biopharmaceutical company focused on developing products for oncology and rare diseases • Founded in July 2015, listed on LSE (MPH) in June 2016 and NASDAQ (MREO) in April 2019 through merger with OncoMed • Broad late stage pipeline : • Two oncology programs –
Slide 4: Robust Portfolio of Clinical Stage Products in Oncology and Rare Diseases
ROBUST PORTFOLIO OF CLINICAL STAGE PRODUCTS IN ONCOLOGY AND RARE DISEASES Product Candidate / Indication Phase 1a Phase 1b Phase 2 Phase 3 Milestone Etigilimab Solid tumors • Phase 1b/2 Navicixizumab Ovarian Cancer • Partnered - Ph 2 Alvelestat • Phase 2 AATD Alpha-1 anti-trypsin deficiency • Phase1
Slide 5: Experienced Management
EXPERIENCED MANAGEMENT Industry Leading Management Expertise Executive Select Experience Executive Select Experience Dr. Denise Scots-Knight Dr. John Lewicki Chief Executive Officer Chief Scientific Officer Richard Francis Dr. Alastair MacKinnon Head of Pharmaceutical Chief Medical Officer Developme
Slide 6: Accomplished Board of Directors
ACCOMPLISHED BOARD OF DIRECTORS Dr. Peter Fellner Dr. Jeremy Bender Dr. Denise Scots-Knight Chairman Non-Executive Director Executive Director CEO and Co-Founder Mike Wyzga* Dr. Anders Ekblom Dr. Brian Schwartz Non-Executive Director Non-Executive Director Non-Executive Director Kunal Kashyap Dr. De
Slide 7: Etigilimab
ETIGILIMAB
Slide 8: Etigilimab and TIGIT
ETIGILIMAB AND TIGIT • T CELL IMMUNORECEPTOR WITH IG AND ITIM DOMAINS (TIGIT) • A receptor similar to PD1 in both structure and expression • Anti-TIGIT activity designed to activate the immune system and enable anti-tumor activity • Expressed on CD4, CD8 and NK cells and is elevated upon activation
Slide 9: Mechanism of Action
MECHANISM OF ACTION Fc effector function is essential for anti-tumor activity in mouse models Comparison of Anti-TIGIT mAbs with Differing Effector Function 313R12 = Ig2A 313R13 = Ig2A deglyco mut Preclinical models demonstrate activity as single agent or in combination with anti-PD-1 CT26WT colon l
Slide 10: Phase 1 Study Design
PHASE 1 STUDY DESIGN 20mg/kg Q2W Dose Escalation N=3+3 MTD Expansion Cohort Tumor types for inclusion in Phase 1a dose escalation cohort: 10mg/kg Q2W N=3+3 Tumor types for inclusion in expansion cohort: • Histologically confirmed advanced relapsed or refractory 3mg/kg Q2W • Head and neck cancer soli
Slide 11: Phase 1a Duration on Study
PHASE 1A DURATION ON STUDY 23 Patients enrolled Mereo BioPharma Group plc 10
Slide 12: Phase 1a: Best % Reduction in Target Lesion Size
PHASE 1A: BEST % REDUCTION IN TARGET LESION SIZE Patient Dose Cancer Waterfall Plot of Best Percentage Change in SLD from Baseline (ITT Population) 004-013 10mg/kg adenocarcinoma of the pancreas ITT Population 004-008 3mg/kg CRC MSS adenocarcinoma of the colon 003-024 20mg/kg* HNSCC 003-018 20mg/kg
Slide 13: Early Clinical Data Suggests Etigilimab Compares Favourably to Merck's Anti-TIGIT
EARLY CLINICAL DATA SUGGESTS THAT ETIGILIMAB COMPARES FAVOURABLY TO MERCK’S ANTI-TIGIT MPH-313 MK-7684 Enrolment: N=23 N=34 Adv. Solid tumours; incl. Pts with prior PD1/PDL1 Adv. Solid tumours; incl. cohort of pts who were PD1/PD-1 naive Response: OMP-313M32 Monotherapy MK-7684 Monotherapy Change fr
Slide 14: Phase 1a Safety Data
PHASE 1A SAFETY DATA Related AEs ≥ 5% ≥ Grade 3 Related AEs Immune Related Adverse Events Number Number Adverse event, n (%) Adverse event, n (%) Adverse event, n (%) Number (%) (%) (%) Pruritis 4 (17%) Rash 1 (4%) Skin Disorders 8 (35%) Fatigue 3 (13%) Rash Macular 1 (4%) Pruritis 3 (13%) Nausea 3
Slide 15: Anti-TIGIT Phase 1a Biomarker Summary
ANTI-TIGIT PHASE 1A BIOMARKER SUMMARY DATA FROM PHASE1A DOSE ESCALATION PATIENTS • ANTI-TIGIT SHOWED TARGET ENGAGEMENT IN PHASE 1A PATIENTS - Anti-TIGIT reduces Tregs, more pronounced at >10mg/kg, and increases the CD8/Treg ratio - Anti-TIGIT increases immune cell proliferation and activation signal
Slide 16: Phase 1b: Best % Reduction in Target Lesion Size
PHASE 1B: BEST % REDUCTION IN TARGET LESION SIZE 120 Patient Dose Cancer Head and Neck Cancer, 20.0 mg/kg + nivolumab Gastric Cancer, 20.0 mg/kg + nivolumab 003-110 20mg/kg Head and Neck cancer, tonsils to lung 100 NSCLC, 3.0 mg/kg + nivolumab 001-108 20mg/kg Gastric Cancer MSS adenocarcinoma RENAL
Slide 17: Phase 1b Duration on Study
PHASE 1B DURATION ON STUDY Patient Dose Cancer 005-102 3mg/kg Ovarian serious metastatic 003-104 3mg/kg Gastric MSS adenocarcinoma 003-103 3mg/kg Colon CRC MSI adenocarcinoma 005-101 3mg/kg NSCLC adenocarcinoma 004-107 10mg/kg Renal Cell MSS carcinoma 003-105 10mg/kg Lung Cancer squamous cell 003-10
Slide 18: Selection of Tumor Types for the Proposed Phase 1b/2
SELECTION OF TUMOR TYPES FOR THE PROPOSED PHASE 1B/2 • TUMOR TYPES WITH HIGH PVR-TIGIT AND LOWER RESPONSE RATES TO ANTI-PD1/PDL TREATMENTS • CANDIDATE TUMOR TYPES BASED ON OUR CLINICAL OBSERVATIONS AND A SURVEY OF ~350 TUMORS - Bladder, Head and Neck, Gastric, Endometrial, Colon, Ovarian and rare tu
Slide 19: Summary
SUMMARY • Etigilimab is a novel IgG1 anti-TIGIT antibody with inhibitory as well as ADCC characteristics • Phase 1a successfully completed with several subjects having prolonged stable disease as their best response and favorable results compared with Merck Phase 1a data • Etigilimab was generally w
Slide 20: Alvelestat (MPH-966)
PPP —Sw Mereo BioPharma ~~
Slide 21: Alpha-1 Antitrypsin Deficiency (AATD)
ALPHA-1 ANTITRYPSIN DEFICIENCY (AATD) A rare, serious genetic disorder that results in early onset pulmonary disease Estimated prevalence of target patients Genetic mutation (PiZZ and Nulls) produces deficiency through abnormal folding of the protein or Mutations in SERPINA1 gene chromosome 14 North
Slide 22: Alpha-1 Antitrypsin Deficiency Current Treatment
ALPHA 1 ANTITRYPSIN DEFICIENCY CURRENT TREATMENT • Routine COPD medications • Augmentation therapy: - Plasma derived alpha 1 anti trypsin - Weekly one hour IV infusion - Approval based on restoration of A1AT to a threshold level NOT clinical outcome data - Cost $150k pa - ~9,000 patients treated • S
Slide 23: Hypothesis: Restoring the Balance in AATD Related Lung Disease
HYPOTHESIS: RESTORING THE BALANCE IN ALPHA-1 ANTITRYPSIN DEFICIENCY RELATED LUNG DISEASE WITH NEUTROPHIL ELASTASE INHIBITOR – ALVELESTAT Anti-Elastase Alpha-1 antitrypsin Alvelestat is an Oral Elastase Neutrophil Elastase Inhibitor Mereo BioPharma Group plc 22
Slide 24: Alvelestat: Relevant Clinical Studies To-Date
ALVELESTAT– RELEVANT CLINICAL STUDIES TO-DATE Phase 2 - Cystic Fibrosis Phase 2 - Bronchiectasis • Total of 56 patients in one study • Total of 38 patients in one study • 27 patients treated for 4 weeks with • 22 patients treated for 4 weeks with 60mg BD 60mg BD • Clear reduction (16%) of plasma • S
Slide 25: Alvelestat Ongoing Phase 2 Study
ALVELESTAT ONGOING PHASE 2 STUDY Study Design Three-arm study with two different dosing arms versus placebo Enrollment Status N=165 patients Treatment Duration 12 weeks Primary Endpoint Desmosine – biomarker shown to have correlation with lung density by CT scan1 • CT scan – emphysema Proposed Patie
Slide 26: Alvelestat, Neutrophil Extracellular Traps (NETs) and COVID-19
ALVELESTAT, NEUTROPHIL EXTRACELLULAR TRAPS (NETS) AND COVID-19 • COVID-19 is a dysregulated hyper-inflammatory response to SARS-CoV-2, with tissue damage through cytokine storm, coagulopathy - progresses to Acute Lung Injury (ALI) • NETs in pathogenesis: • NETs - chromatin threads exuded from activa
Slide 27: Phase 1b/2 Study in Adults with COVID-19 Respiratory Disease
A PHASE IB/II PLACEBO-CONTROLLED, RANDOMIZED, BLINDED STUDY IN ADULTS WITH COVID-19 RESPIRATORY DISEASE • Investigator initiated study (Mike Wells, UAB) under Mereo IND – single site • Target population: Hospitalized adult patients with moderate/severe SARS-CoV-2 infection (WHO grade 3-5) • Primary
Slide 28: Summary and Next Steps
SUMMARY AND NEXT STEPS • Alvelestat has been broadly studied to-date in over 1,000 patients • Two studies relevant to AATD – cystic fibrosis and bronchiectasis • Generally safe and well tolerated in previous studies with the main related AE being headache • As an oral therapy Alvelestat is highly di
Slide 29: Setrusumab (BPS-804)
PPP —Sw Mereo BioPharma ~~
Slide 30: No FDA or EU-Approved Therapies for Osteogenesis Imperfecta
THERE ARE CURRENTLY NO FDA OR EU-APPROVED THERAPIES FOR THE TREATMENT OF OSTEOGENESIS IMPERFECTA (OI) • OI is rare genetic bone disease characterized by frequent bone fractures resulting in skeletal deformities, pain, respiratory insufficiency, early hearing loss and brittle teeth • Setrusumab (BPS-
Slide 31: Setrusumab's Mechanism of Action Is Well-Suited for OI
SETRUSUMAB’S MECHANISM OF ACTION IS PARTICULARLY WELL-SUITED FOR OI Setrusumab Osteocyte Wnt sclerostin - Wnt LRP 5/6 Frizzled Osteoblast cytoplasm + Dishevelled Bone formation ↑ P - Nucleus Osteoblast AP Lymphoid Axin Glycogen C enhancer- differentiation Synthase binding factor-1 ↑ Osteoprotegerin
Slide 32: Phase 2b ASTEROID Study Design
PHASE 2B ASTEROID STUDY DESIGN PATIENT DEMOGRAPHICS WELL MATCHED ACROSS ALL ARMS Treatment Period = 12 months Follow-Up Period = 12 months High dose blinded (31pts) Option to receive zoledronic acid at M12 and M18 – discretion of physician Medium dose blinded (29pts) 28 day screening DXA and HR-PQCT
Slide 33: Hierarchical Primary End Point Based on HRpQCT
HIERARCHICAL PRIMARY END POINT BASED ON HRPQCT • First primary end point – Trabecular vBMD (TrvBMD) at the radius – high dose improved but not statistically significant – confounded by baseline values. Total vBMD (TvBMD) improved statistically significantly in high and medium doses • Second primary
Slide 34: Areal Bone Mineral Density as Measured by DXA
AREAL BONE MINERAL DENSITY AS MEASURED BY DXA PER PROTOCOL Increase in areal BMD at the lumbar spine as measured by DXA by dose cohort all OI subtypes Mean % Change in Areal BMD Mean % Change in Areal BMD Dose Cohort 6 months 12 months High (n=23) +4.4% (p<0.001) +8.8% (p<0.001) Medium (n=17) +3.61%
Slide 35: Increase in Areal BMD at All Anatomical Sites and Fracture Data
INCREASE IN AREAL BONE MINERAL DENSITY AT ALL ANATOMICAL SITES AND FRACTURE DATA • Increase in areal BMD at the femoral neck and total hip by DXA – dose dependent increase observed with 3.2% (p=0.022) at the neck and 2.3% (p=0.009) at hip at the high dose • High dose setrusumab clearly more efficaci
Slide 36: Summary and Next Steps
SUMMARY AND NEXT STEPS • Setrusumab demonstrated a dose-dependent statistically significant increase in bone mineral density at the high and medium doses with a statistically significant increase in bone strength at the high dose • Setrusumab was safe and well tolerated in the Phase 2b in adults wit
Slide 37: Upcoming Milestones and Financial Overview
UPCOMING MILESTONES AND FINANCIAL OVERVIEW
Slide 38: Mereo Upcoming Key Milestones and Opportunities
MEREO UPCOMING KEY MILESTONES AND OPPORTUNITIES 2020 2021 2022 Etigilimab Phase 1b study Phase 2 POC Study Alvelestat Phase 1b/2 COVID Adult 12m extension study Setrusumab Partnering Paediatric Pivotal 12 month fracture study Partnering Partnering Acumapimod Leflutrozole ✓ Navi Out-licensed to OncXe
Slide 39: Thank You
THANK YOU Mereo BioPharma Group plc NASDAQ: MREO, AIM: MPH
Slide 40: NETosis References
NETosis References • Barnes, B.J., Adrover, J.M., Baxter-Stoltzfus, A. et al. (2020). Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med, 217(6). • Kim, E.H., Wong, S-W., & Martinez, J. (2018). Programmed Necrosis and Disease:We interrupt your regular programming to b
Slide 41: Mereo BioPharma Group plc, One Cavendish Place, London
Mereo BioPharma Group plc One Cavendish Place London, W1G 0QF UK +44 (0)333 0237 300
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