POTENTIAL IN ONCOLOGY AND RARE DISEASES August 2020 DISCLAIMER - - PowerPoint PPT Presentation

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POTENTIAL IN ONCOLOGY AND RARE DISEASES August 2020 DISCLAIMER - - PowerPoint PPT Presentation

UNLOCKING HEALTHCARE POTENTIAL IN ONCOLOGY AND RARE DISEASES August 2020 DISCLAIMER This presentation has been prepared by Mereo BioPharma Group plc (the Company) solely for your information and for the purp ose of providing background


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SLIDE 1

August 2020

UNLOCKING HEALTHCARE POTENTIAL IN ONCOLOGY AND RARE DISEASES

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SLIDE 2

DISCLAIMER

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Mereo BioPharma Group plc

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 this notice, “presentation” means this document, any oral presentation, any question and answer session and any written or oral material discussed or distributed during any related presentation meeting. This presentation has not been independently verified and no representation or warranty, express or implied, is made or given by or on behalf of the Company or any of its subsidiary undertakings, or any of any such person’s directors, officers, employees, agents, affiliates or advisers, as to, and no reliance should be placed on, the accuracy, completeness or fairness of the information or opinions contained in this presentation and no responsibility or liability is assumed by any such persons for any such information or opinions or for any errors or omissions. All information presented or contained in this presentation is subject to verification, correction, completion and change without notice. In giving this presentation, none of the Company or any of its subsidiary undertakings, or any of any such person’s directors, officers, employees, agents, affiliates or advisers, undertakes any obligation to amend, correct or update this presentation or to provide the recipient with access to any additional information that may arise in connection with it. To the extent available, the data contained in this presentation has come from official or third-party sources. Third party industry publications, studies and surveys generally state that the data contained therein have been obtained from sources believed to be reliable, but that there is no guarantee of the accuracy or completeness of such data. While the Company believes that each of these publications, studies and surveys has been prepared by a reputable source, the Company has not independently verified the data contained therein. In addition, certain of the data contained in this presentation come from the Company’s own internal research and estimates based on the knowledge and experience of the Company’s management in the market in which the Company operates. Further, certain of the data has been provided to the Company by contract research organizations that the Company retains to conduct clinical trials, or by other third parties contracted by the Company. While the Company believes that such internal research and estimates and such other data are reasonable and reliable, they, and, where applicable, their underlying methodology and assumptions, have not been verified by any independent source for accuracy or completeness and are subject to change without notice. Accordingly, undue reliance should not be placed on any of the data contained in this presentation. Forward-Looking Statements This presentation contains “forward-looking statements.” All statements other than statements of historical fact contained in this presentation are forward-looking statements within the meaning of Section 27A of the United States Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the United States Securities Exchange Act of 1934, as amended (the “Exchange Act”). Forward-looking statements usually relate to future events and anticipated revenues, earnings, cash flows or other aspects of our operations or operating results. Forward- looking statements are often identified by the words “believe,” “expect,” “anticipate,” “plan,” “intend,” “foresee,” “should,” “would,” “could,” “may,” “estimate,” “outlook” and similar expressions, including the negative thereof. The absence of these words, however, does not mean that the statements are not forward-looking. These forward-looking statements are based on the Company’s current expectations, beliefs and assumptions concerning future developments and business conditions and their potential effect on the Company. While management believes that these forward-looking statements are reasonable as and when made, there can be no assurance that future developments affecting the Company will be those that it anticipates. Factors that could cause actual results to differ materially from those in the forward-looking statements include risks relating to unanticipated costs, liabilities or delays; failure or delays in research and development programs; the safety and efficacy of the Company’s product candidates and the likelihood of clinical data to be positive and of such product candidates to be approved by the applicable regulatory

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SLIDE 3

Mereo BioPharma Group plc

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 – Etigilimab (anti-TIGIT) and Navicixizumab (licensed to Oncologie for up to $300M in

milestones plus royalties)

  • Two rare disease programs – Alvelestat and Setrusumab
  • Additional two large Phase 2’s successfully completed for specialty disease products
  • Partnering discussions well underway on Setrusumab and specialty products
  • Management team with extensive experience in clinical development, manufacturing, corporate development,

patient access and commercial planning and corporate finance

2

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SLIDE 4

Mereo BioPharma Group plc

ROBUST PORTFOLIO OF CLINICAL STAGE PRODUCTS IN ONCOLOGY AND RARE DISEASES

Product Candidate / Indication Phase 1a Phase 1b Phase 2 Phase 3 Financing Milestone

Etigilimab

Solid tumors

  • Phase 1b complete

Navicixizumab1

Ovarian Cancer

  • Partnered - Ph 2

Alvelestat

Alpha-1 anti-trypsin deficiency Covid19

  • Phase 2 AATD
  • Phase1/2 COVID

Setrusumab

Osteogenesis imperfecta

  • Extension study
  • Partner - Ph 3

3 Product Candidate / Indication Phase 1 Phase 2 Phase 3 Financing Milestone

Acumapimod Acute

exacerbations of COPD

  • Separate funding

Leflutrozole HH Infertility

  • Partner

Alpha-1 Antitrypsin Deficiency (AATD)

With additional partnering opportunities on specialty programs

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SLIDE 5

Mereo BioPharma Group plc

  • Dr. Peter Fellner

Chairman

EXPERIENCED MANAGEMENT & BOARD

  • Dr. Denise Scots-Knight

Chief Executive Officer

Charles Sermon

General Counsel

  • Dr. Alastair MacKinnon

Chief Medical Officer

Executive Select Experience

  • Dr. Denise Scots-Knight

Executive Director CEO and Co-Founder

  • Dr. Anders Ekblom

Non-Executive Director Peter Bains Non-Executive Director Kunal Kashyap Non-Executive Director Paul Blackburn Non-Executive Director

  • Dr. Deepa R. Pakianathan

Non-Executive Director Michael Wyzga * Non-Executive Director

Ind Industry ry Lea Leading Management Ex Expertise se Acc ccomplished Boar Board of

  • f Di

Directors

4 *Interim CFO John Richard

Head of Corporate Development

Wills Hughes-Wilson

Head of Patient Access & Commercial Planning

John Lewicki

Chief Scientific Officer

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SLIDE 6

ETIGILIMAB

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SLIDE 7

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

  • TIGIT expression is pronounced on regulatory T cells

(Tregs)

  • TIGIT mediates an inhibitory signal that is thought to

prevent T-cells from attacking tumor cells

  • ETIGILIMAB IS A NOVEL IGG1 ANTI-TIGIT ANTIBODY THAT

HAS INHIBITORY AS WELL AS ADCC CHARACTERISTICS

6

Mereo BioPharma Group plc

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SLIDE 8

313R12 = Ig2A 313R13 = Ig2A deglyco mut

Comparison of Anti-TIGIT mAbs with Differing Effector Function

MECHANISM OF ACTION Fc effector function is essential for anti-tumor activity in mouse models

CT26WT colon line

Preclinical models demonstrate activity as single agent or in combination with anti-PD-1

7

Mereo BioPharma Group plc

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SLIDE 9

Mereo BioPharma Group plc

PHASE 1 STUDY DESIGN

8

Tumor types for inclusion in expansion cohort:

  • Head and neck cancer
  • Esophageal cancer
  • Gastric cancer
  • Cervical cancer
  • Triple-negative breast cancer
  • Anal cancer
  • Hepatocellular cancer
  • Known MSI high solid tumors

(including MSI CRC and others)

  • NSCLC

Mandatory pre- and post-treatment biopsies

MTD

10mg/kg Q2W N=3+3 3mg/kg Q2W N=3+3 1mg/kg Q2W N=3+3 0.3mg/kg* Q2W N=3+3 20mg/kg Q2W N=3+3 Expansion Cohort Tumor types for inclusion in dose escalation cohort:

  • Histologically confirmed

advanced relapsed or refractory solid tumors

  • Preference to enroll subjects

with the tumor types specified for the dose expansion cohort.

  • Optional pre-and post-tumor

biopsies

Dose Escalation

10mg/kg Q2W + nivolumab N=3+3 3mg/kg Q2W + nivolumab N=3+3 20mg/kg Q2W + nivolumab N=3+3

Phase 1a Phase 1b

Tumor types for inclusion in dose escalation cohort:

  • Histologically confirmed advanced

relapsed or refractory solid tumors

  • Refractory to or progressed after

anti-PD1/L1

  • Pre and post-tumor biopsies for

cohorts 2/3

Dose Escalation

Mereo BioPharma Group plc

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SLIDE 10

PHASE 1A DURATION ON STUDY

9

23 Patients enrolled

Mereo BioPharma Group plc

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SLIDE 11

PHASE 1A: BEST % REDUCTION IN TARGET LESION SIZE

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Note: SLD= Sum of Longest Diameter. Note: Charted values (one bar per patient) represent the maximum reduction from the baseline total tumor length during the study. Negative values indicate a reduction from baseline total tumor length whereas positive numbers represent an increase. \\syncorp.local\dfs\data\sas\OMED\OMED-01733\stats\production\programs\f-waterf.sas 2019-09-18 11:03 FINAL Data Base Lock: 16SEP2019 Waterfall Plot of Best Percentage Change in SLD from Baseline (ITT Population) ITT Population

Patient Dose Cancer 004-013 10mg/kg adenocarcinoma of the pancreas 004-008 3mg/kg CRC MSS adenocarcinoma of the colon 003-024 20mg/kg* HNSCC 003-018 20mg/kg triple negative breast cancer 002-015 20mg/kg pancreatic adenocarcinoma 005-006 1mg/kg CRC MSS 005-026 20mg/kg* Lung 002-012 10mg/kg CRC MSS colorectal adenocarcinoma 004-021 20mg/kg metastatic endometrial / papillary serous 001-025 20mg/kg* Endometrial 002-004 1mg/kg endometrial adenocarcinoma of the uterus 001-002 0.3mg/kg CRC MSS adenocarcinoma 003-016 20mg/kg CRC MSI 001-001 0.3mg/kg CRC MSS 005-005 1mg/kg salivary duct 001-011 10mg/kg endometrial 005-023 20mg/kg* parotid 005-010 3mg/kg Fallopian 005-017 20mg/kg endometrial

*Expansion cohort Mereo BioPharma Group plc

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SLIDE 12

OMP-313M32 Monotherapy Change from Baseline, % MK-7684 Monotherapy

EARLY CLINICAL DATA SUGGESTS THAT ETIGILIMAB COMPARES FAVOURABLY TO MERCK’S ANTI-TIGIT

Enrolment: Safety: Response:

Very similar safety profile, No DLTs observed with either antibody

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

ORR 0% DCR 30% ORR 3% DCR 35% Partial Response: Partial Response: 1 (3%) Stable Disease: 7 (30%) Stable Disease: 11 (32%) Progressive Disease: 13 (57%) Progressive Disease: 13 (38%) n/a: 3 (13%) n/a: 9 (26%)

MK-7684 OMP-313M32

11

Mereo BioPharma Group plc

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SLIDE 13

12

Adverse event, n (%) Number (%) Pruritis 4 (17%) Fatigue 3 (13%) Nausea 3 (13%) Rash 3 (13%) Rash maculopapular 3 (13%) Chills 2 (9%) Cough 2 (9%) Rash macular 2 (9%) Related AEs ≥ 5% Adverse event, n (%) Number (%) Rash 1 (4%) Rash Macular 1 (4%) Rash Maculopapular 1 (4%) Autoimmune Hepatitis 1 (4%) ALT Increased 1 (4%) AST Increased 1 (4%) Hypophosphatemia 1 (4%) Adverse event, n (%) Number (%) Skin Disorders 8 (35%) Pruritis 3 (13%) Rash 3 (1)3% Rash Maculopapular 3 (13)% Rash macular 1 (4%) Rash pruritic 1 (4)% Skin disorder 1 (4%) Chills 2 (9)% Pyrexia 1 (4%) Arthralgia 1 (4%) Myalgia 1 (4%) Immune Related Adverse Events ≥ Grade 3 Related AEs

PHASE 1A SAFETY DATA

N=23 as of data cut off Sept 2019

Generally safe and well tolerated

Mereo BioPharma Group plc

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SLIDE 14

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 signals more significantly in patients

with immune related AEs

  • Anti-TIGIT reduces TIGIT staining on cell surface by flow cytometry
  • Anti-TIGIT decreases TIGIT gene expression
  • Regulation of Treg associated genes by Anti-TIGIT

13

Mereo BioPharma Group plc

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SLIDE 15

PHASE 1B: BEST % REDUCTION IN TARGET LESION SIZE

14

003-110 001-108 005-101 004-107 003-104 005-102 003-103

Subject ID

  • 100
  • 80
  • 60
  • 40
  • 20

20 40 60 80 100 120

%Change from Baseline

COLORECTAL CANCER, 3.0 mg/kg + nivolumab METASTATIC OVARIAN CANCER, 3.0 mg/kg + nivolumab Gastric Cancer, 3.0 mg/kg + nivolumab RENAL CELL CARCINOMA, 10.0 mg/kg + nivolumab NSCLC, 3.0 mg/kg + nivolumab Gastric Cancer, 20.0 mg/kg + nivolumab Head and Neck Cancer, 20.0 mg/kg + nivolumab

Patient Dose Cancer 003-110 20mg/kg Head and Neck cancer, tonsils to lung 001-108 20mg/kg Gastric Cancer MSS adenocarcinoma 005-101 3mg/kg NSCL adenocarcinoma 004-107 10mg/kg Renal Cell carcinoma MSS adenocarcinoma 003-104 3mg/kg Gastric cancer MSS adenocarcinoma 005-102 3mg/kg Ovarian serious metastatic 003-103 3mg/kg Colon CRC MSI adenocarcinoma Mereo BioPharma Group plc

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SLIDE 16

PHASE 1B DURATION ON STUDY

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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 003-106 10mg/kg Gastric cancer invasive adenocarcinoma 002-109 20mg/kg Hepatocellular carcinoma 001-108 20mg/kg Gastric Cancer MSS adenocarcinoma 003-110 20mg/kg Head and Neck cancer, tonsils to lung Mereo BioPharma Group plc

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SLIDE 17

SELECTION OF TUMOR TYPES FOR THE PROPOSED PHASE 1B

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  • 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 tumor types
  • ROBUST BIOMARKER TOOLS ESTABLISHED FOR FURTHER STRATIFICATION
  • IHC for PVR, TIGIT, FOXP3, TILs, PDL1
  • Tumor mutation burden (TMB)
  • Key gene expression IO signatures (Treg, T cell exhaustion, Ifg, TIGIT)

Mereo BioPharma Group plc

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SLIDE 18

SUMMARY

17

  • 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 well safe and well tolerated with no DLT’s being observed
  • Adverse events consistent with immune system activation
  • No evidence of anti-drug antibodies
  • Strategy in place for selection of tumor types for Phase 1b study

NEXT STEPS - Mereo has an open IND and sufficient drug product for the next Phase 1b study – plan to run a 75-100 patient Phase 1b basket study in combination with a PD-1 in selected tumor types - study initiation expected Q4 2020

Mereo BioPharma Group plc

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SLIDE 19

ALVELESTAT (MPH-966)

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SLIDE 20

Mereo BioPharma Group plc

North America ~50,000 Europe ~60,000 Estimated prevalence of target patients (PiZZ and Nulls) Current treatment weekly IV alpha-1 antitrypsin protein Alvelestat in 1,000 patients in range of studies

Genetic mutation produces deficiency through abnormal folding of the protein or zero production of the protein Mutations in SERPINA1 gene chromosome 14 Only homozygotes (ZZ’s) and Nulls have severe disease

ALPHA-1 ANTITRYPSIN DEFICIENCY (AATD)

19

A rare, serious genetic disorder that results in early onset pulmonary disease

Symptoms:

  • Age 20-50 – shortness of breath, wheeze and decreased

lung function

  • PiZZ and Null adults develop early onset emphysema
  • Some mutations can cause cirrhosis in children
  • Progression, lung transplantation, reduced life expectancy

Francisco et al (2012) Rare alpha-1-antitrypsin variants: are they really so rare? Therapeutic Advances in Respiratory Disease January 30 Luisetti et al (2004) α1-Antitrypsin deficiency · 1: Epidemiology of α1-antitrypsin deficiency Thorax 59:164-169

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SLIDE 21

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

  • utcome data
  • Cost $150k pa
  • ~9,000 patients treated
  • Surgery – lung volume reduction surgery
  • r transplant

20

Mereo BioPharma Group plc

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SLIDE 22

Mereo BioPharma Group plc

HYPOTHESIS: RESTORING THE BALANCE IN ALPHA-1 ANTITRYPSIN DEFICIENCY RELATED LUNG DISEASE WITH NEUTROPHIL ELASTASE INHIBITOR – ALVELESTAT

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Elastase Anti-Elastase Alpha-1 antitrypsin Alvelestat is an Oral Neutrophil Elastase Inhibitor

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SLIDE 23

ALVELESTAT– RELEVANT CLINICAL STUDIES TO-DATE

Phase 2 - Cystic Fibrosis

  • Total of 56 patients in one study
  • 27 patients treated for 4 weeks with

60mg BD

  • Clear reduction (16%) of plasma

desmosine and blood and sputum inflammatory markers

  • Statistically significant reduction of

free desmosine in urine corrected for creatinine (p=0.002) Phase 2 - Bronchiectasis

  • Total of 38 patients in one study
  • 22 patients treated for 4 weeks with

60mg BD

  • Statistically significant improvement

in lung function – FEV1 of 100ml (p=0.006) and SVC improved

  • Improvement in blood and sputum

inflammatory markers – reduction of plasma desmosine

  • Improvement in St Georges

Respiratory Questionnaire

22

  • In addition total of 970 patients across four COPD studies

Mereo BioPharma Group plc

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SLIDE 24

Mereo BioPharma Group plc

ALVELESTAT ONGOING PHASE 2 STUDY

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1. A biomarker in KAMADA’s RAPID study. Ref: Ma S, Lin YY, Cantor JO, et al. The effect of alpha-1 proteinase inhibitor on biomarkers of elastin degradation in alpha-1 antitrypsin deficiency: An analysis of the RAPID/RAPID Extension trials. Chronic Obstr Pulm Dis. 2017; 4(1): 34-44. Mereo BioPharma Group plc

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 Proposed Patient Population

  • CT scan – emphysema
  • Confirmed genotype (PiZZ or Null)
  • FEV1 >25%
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SLIDE 25

ALVELESTAT, NEUTROPHIL EXTRACELLULAR TRAPS (NETS) AND COVID-19

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  • 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 activated neutrophils and coated with tissue damaging enzymes- recently

demonstrated to be central to the disease:

  • Uncontrolled, NETs are cytotoxic to endothelial and epithelial cells promoting cytokine release and thromboses
  • NETs correlate with COVID-19 disease severity biomarkers and clinical outcomes (hospitalized patients) - present in

post-mortem examination of COVID lungs

  • Loss of Control of NETs in COVID-19:
  • NETs are dependent on Neutrophil Elastase (NE) for both formation AND maintenance of NET activity:
  • Levels of the physiological NE inhibitor (Alpha-1 antitrypsin) are overwhelmed in COVID-19
  • Potential role of alvelestat in disease modulation:
  • Efficacy in pre-clinical models, protecting the lung from NET-induced ALI
  • Oral therapy, achieving the systemic exposure needed plus known ability to penetrate sputum (for local NETosis)

Mereo BioPharma Group plc

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SLIDE 26

A PHASE IB/II PLACEBO-CONTROLLED, RANDOMIZED, BLINDED STUDY IN ADULTS WITH COVID-19 RESPIRATORY DISEASE

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  • 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 objective:
  • Safety of alvelestat administered twice daily for 10 days
  • Key Secondary Objectives:
  • Biomarkers of NETs, inflammation and coagulopathy
  • Proportion of subjects alive and free of respiratory failure
  • The effect of alvelestat on disease severity (WHO scale)
  • Outcomes to Day 90 for mortality
  • Study Design

WHO 9-point ordinal scale:

  • 0. Uninfected, no clinical or virological evidence of infection

1. Ambulatory, no limitation of activities 2. Ambulatory, limitation of activities 3. Hospitalised – mild disease, no oxygen therapy 4. Hospitalised – mild disease, oxygen by mask or nasal prongs 5. Hospitalised – severe disease, noninvasive ventilation or high flow oxygen 6. Hospitalised – severe disease, intubation and mechanical ventilation 7. Hospitalised – severe disease, ventilation and additional organ support – vasopressors, renal replacement therapy (RRT), extracorporeal membrane oxygenation (ECMO) 8. Death

Mereo BioPharma Group plc

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SLIDE 27

SUMMARY AND NEXT STEPS

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  • 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 differentiated from the current augmentation therapy for AATD
  • Alvelestat has potential in COVID infections where NETosis is know to play a significant role

NEXT STEPS - Mereo intends to complete the ongoing Phase 2 in AATD and to then engage with the FDA/EMA to discuss the pathway to approval. Mereo intends to work with the University of Alabama to complete the 15 patient Phase 1b/2 in COVID infected patients prior to considering other sources of financing

Mereo BioPharma Group plc

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SLIDE 28

SETRUSUMAB (BPS-804)

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SLIDE 29

Mereo BioPharma Group plc

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-804) is a monoclonal antibody targeting sclerostin
  • Setrusumab received PRIME (PRIority MEdicine) designation by the European

Medicines Agency (EMA) and Orphan Drug status in EU and US

  • Crysvita approved in EU and US for hypophosphatemia is the closest

pricing analogue - $160,000 pa children and $200,000 for adults

̴ 6.2

OI cases per 100,000 population in the US 1

̴ 10

OI cases per 100,000 population in the EU 2

Prevalence:

85% - 90%

linked to a gene mutation that produces abnormal type 1 collagen 1, 2

72% - 77%

  • f total OI population 3

OI types I, III and IV occur in

  • 1. Based on Osteogenesis Imperfecta Foundation estimates; 2. Based on Orphanet estimates; 3. Shapiro J (2014) Osteogenesis Imperfecta: A Translational Approach to Brittle Bone Disease. Academic Press. Chapter 2: p15-22

28

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SLIDE 30

Mereo BioPharma Group plc

SETRUSUMAB’S MECHANISM OF ACTION IS PARTICULARLY WELL-SUITED FOR OI

Osteocyte sclerostin

Osteoblast cytoplasm

LRP 5/6

Wnt

Frizzled

Dishevelled

β-catenin ↑

Axin

AP C Glycogen Synthase Kinase 3β

Nucleus

T-cell factor

Lymphoid enhancer- binding factor-1

↑ Gene

expression Bone formation

Osteoblast differentiation

  • +

Wnt

P β-catenin Setrusumab

↑ Osteoprotegerin

↓RANKL

↓ ↓ Osteoclast

differentiation and activity

29

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SLIDE 31

PHASE 2B ASTEROID STUDY DESIGN

PATIENT DEMOGRAPHICS WELL MATCHED ACROSS ALL ARMS

Treatment Period = 12 months 28 day screening High dose open label High dose blinded (31pts) Medium dose blinded (29pts) Low dose blinded (30pts) Placebo Patients on placebo given high dose open label and new participants randomized 1:1:1:1 Follow-Up Period = 12 months Option to receive zoledronic acid at M12 and M18 – discretion of physician DXA and HR-PQCT scans at 18 and 24 months

30

Mereo BioPharma Group plc

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SLIDE 32

HIERARCHICAL PRIMARY END POINT BASED ON HRPQCT

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  • 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 end point – Bone Strength (Failure Load and Bone Stiffness) dose dependent increases, both statistically

significant in the high dose cohort

  • Bone Strength measured by Finite Element Analysis (FEA) - based on the totality of the bone compartments (trabecular and cortical bone)

and was the second primary endpoint of the study on a hierarchical basis

Mereo BioPharma Group plc

Dose Cohort Mean % Change in Failure Load at 12 months P value at 12 months High (n=27) +2.0% p<0.037 Med (n=20) +1.1% NS Low (n=22)

  • 0.06%

NS

Increase in stiffness at the radius determined by FEA and by dose cohort (all OI subtypes)

Dose Cohort Mean % Change in Stiffness at 12 months P value at 12 months High (n=27) +2.2% P<0.022 Med (n=20) +1.0% NS Low (n=22) +0.1% NS

Increase in Failure Load at the radius determined by FEA and by dose cohort (all OI subtypes) Increase in TrvBMD and TvBMD (all OI subtypes)

Dose Cohort Mean % Change in TrvBMD at 12 months Mean % change in TvBMD at 12 months High (n=27) +0.7% (NS) +4.1% p=0.004 Med (n=20)

  • 0.8% (NS)

+4.8% p=0.03 Low (n=22)

  • 0.6% (NS)
  • 0.2% NS
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SLIDE 33

Mereo BioPharma Group plc

AREAL BONE MINERAL DENSITY AS MEASURED BY DXA PER PROTOCOL

32

Dose Cohort Mean % Change in Areal BMD 6 months Mean % Change in Areal BMD 12 months High (n=23) +4.4% (p<0.001) +8.8% (p<0.001) Medium (n=17) +3.61% (p<0.001) +6.8% (p<0.001) Low (n=21) +1.52% (p=0.057) +2.6% (p=0.057)

Increase in areal BMD at the lumbar spine as measured by DXA by dose cohort all OI subtypes

OI Type Mean % Change in Areal BMD 6 months Mean % Change in Areal BMD 12 months Type I (n=17) +4.1% +8.8% Type III & IV (n=6) +5.4% +9.8%

Increase in areal BMD at the vertebrae as measured by DXA by OI subtype at the high dose

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SLIDE 34

Mereo BioPharma Group plc

33

  • 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 efficacious than teriparatide in all OI types but especially in OI Types III and

IV were teriparatide = 2.8% at the lumbar spine setrusumab = 9.8%

INCREASE IN AREAL BONE MINERAL DENSITY AT ALL ANATOMICAL SITES AND FRACTURE DATA

Dose Cohort Percentage of patients fracturing Occurrence rate High (n=27) 15% 0.16 Medium (n=20) 35% 0.49 Low (n=22) 23% 0.39

Percentage of patients with at least one fracture and occurrence rate per patient year

  • ASTEROID study not powered to show a difference in fracture rates but trend of reduction in fractures observed

in the high dose cohort.

Fractures both X-ray confirmed as well as those confirmed by a local radiologist dependent on the nature of the fracture

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SLIDE 35

SUMMARY AND NEXT STEPS

34

  • Setrusumab demonstrated a dose dependent statically 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 with OI
  • Outline of a Phase 3 registrational trial discussed with FDA and EMA
  • 165 children (2-18 yrs) comparing setrusumab with bisphosphonate
  • primary end point of fracture and BMD as a secondary end point
  • Patient population with highest unmet medical need and higher fracture rates than adults

NEXT STEPS – Mereo intends to complete a partnership(S) for setrusumab prior to initiation of the registrational trial – this could include retaining regional rights

Mereo BioPharma Group plc

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SLIDE 36

UPCOMING MILESTONES AND FINANCIAL OVERVIEW

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SLIDE 37

Mereo BioPharma Group plc

36

2020 2021 2022 Etigilimab Alvelestat Setrusumab Partnering

Acumapimod Leflutrozole

MEREO UPCOMING KEY MILESTONES AND OPPORTUNITIES

Paediatric Pivotal 12 month fracture study Partnering Phase 2 POC Study Adult 12m extension study ✓ Navi Out-licensed to Oncologie Partnering Phase 1b study Phase 1b/2 COVID

Key data or milestone event

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SLIDE 38

Mereo BioPharma Group plc NASDAQ: MREO, AIM: MPH

THANK YOU

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SLIDE 39

CONFIDENTIAL

NETosis References

38

  • 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 bring you necroinflammation [sic]. Cell Death Differ, 26(1), 25-40

  • Li, H., Zhou, X., Tan, H. et al. (2018). Neutrophil extracellular traps

contribute to the pathogenesis of acid-aspiration-induced ALI/ARDS. Oncotarget 9(2), 1772-1784

  • McElvaney, O.J, McEvoy, N., McElvaney O.F. et al. (2020). Characterization
  • f the Inflammatory Response to Severe COVID-19 Illness. AJRCCM

Published June 25

  • Papayannopoulos, V., Metzler, K.D., Hakkim, A. et al. (2010). Neutrophil

elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol, 191(3), 677-691

Barnes et al

Mereo BioPharma Group plc

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SLIDE 40

Mereo BioPharma Group plc One Cavendish Place London, W1G 0QF UK +44 (0)333 0237 300