unlocking the potential of novel targets for cancer and

N o ve m b e r 2 0 2 1

Unlocking the potential of novel targets for cancer and

rare diseases

M e r e o B i o P h a r m a G r o u p p l c

N A S D A Q : M R E O

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 itoperates 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 duringany 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 subsidiaries, 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 byany 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 givingthis presentation, none of the Company or any of its subsidiaries, 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 toprovide 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 industrypublications, 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 theCompany 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 inthis 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 hasbeen 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 andestimates 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 subjectto change without notice. Accordingly, undue reliance should not be placed on any of the data contained in this presentation.

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1Mereo Biopharma Group plc

Our Core Purpose, Mission & Strategy guide us

• Significant news flow


• Acquire programs in oncology and rare diseases with strong scientific rationale / clinical data

• Focus on core competences –translational R&D, development, CMC, regulatory, rare diseases

• Seek the right partners to unlock the value of our programs

• Commercialize where it makes sense and match with strategic partnerships

Our partners

• Listed on NASDAQ (MREO)

• Cash runway into 2024

through 2021

• #1 priority – the patients we seek to serve

• Identify novel targets with strong scientific rationale and initial clinical data

• Develop & commercialize innovative medicines to treat patients with rare diseases and cancer

• Seek partners to unlock value where more resources required

• Become partner of choice

MISSION STRATEGY TRACK RECORD FUNDAMENTALSSUMMARY

Improving lives of patients with cancer and rare

diseases by unlocking the potential of novel targets

#1 priority – the patients that we

seek to serve

• Acquired/in-licensed 6 programs with Phase 1b/2 data in risk sharing structures

• Delivered three successful Phase 2 studies with a Phase 2 and Phase 1b/2 ongoing

• Global partnership for a core rare disease program with European commercial rights retained outright

• Global out-licensing of one (non-core) program

• Partnering ongoing for two additional non-core programs

Late Stage Diversified Clinical Pipeline

Core Programs

Phase 1b/2 COVID

With partnering opportunities on non-core programs

royalties

3

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

AcumapimodAcute exacerbations of COPD

Separate funding

LeflutrozoleHH Infertility

Partner

NavicixizumabOvarian Cancer

~ $300M milestones +

Product Candidate / Indication Phase 1a Phase 1b Phase 2 Phase 3 Next Milestones

EtigilimabSolid tumors Phase 1b/2

AlvelestatAlpha-1 antitrypsin deficiency

COVID-19

Phase 2 AATD

SetrusumabOsteogenesis imperfecta

Adult extension study

Mereo Biopharma Group plc

Experienced Management Team and Board


Dr. Peter FellnerChairman

Dr. Anders EkblomFormer CEO, AstraZeneca

Sweden AB

Dr. Deepa PakianathanManaging Director, Delphi Ventures

Mike WyzgaFormer CFO, Genzyme

Dr. Brian SchwartzFormer CMO, ArQule

Dr. Jeremy BenderCEO, Day One

Biopharmaceuticals

Dr. Denise Scots-KnightExecutive Director, CEO & Co-Founder

Dr. Pierre JacquetMD and Vice Chairman of

L.E.K. Consulting

Board of Directors

John RichardHead of Corporate Development

Dr. Alastair MackinnonChief Portfolio Management and Development Strategy

Dr. Suba KrishnanSenior Vice President

of Clinical Development

Wills Hughes-WilsonHead of Patient Access & Commercial Planning

Dr. Denise Scots-KnightChief Executive Officer

Charles SermonGeneral Counsel

Christine FoxChief Financial Officer

Dr. John LewickiChief Scientific Officer

Dr. Jackie ParkinTherapeutic Area Head,

Respiratory and Endocrinology

Heidi Petersen SVP Regulatory Affairs

Dr. Ann KapounSVP Translational

Research & Development

Bo Kara Senior Vice President, Head of

Pharmaceutical Development CMC

Etigilimab(MPH-313)

TIGIT is a negative regulator of T cell responses

6

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; co-expressed with PD1 on T memory stem cells

Highly expressed on regulatory T cells (Tregs), exhausted T-cells

Human tumors co-express high levels of TIGIT and PD1

Co-blockade of anti-TIGIT and anti-PD1 elicits anti-tumoractivity preclinically and clinically (Johnson et al. 2014, Cancer Cell; Rodriguez-Abreu et al. 2020, ASCO)


Etigilimab blocks interaction of PVR with TIGIT and inhibits signaling


Anti-TIGIT inhibits TIGIT phosphorylation in response to PVR ligandEtigilimab Blocks PVR Binding In Cell Based Assay

Anti-TIGIT blocks PVR-induced suppression of human T-Cell Activation

Park et al., AACR 2017

Human TIGIT ECD fused to CD4TM-GFP was transiently expressed in 293T cells and incubated with

indicated amount of anti-TIGIT antibody followed by addition of human PVR-rabbit Fc fusion protein.

Anti-TIGIT antibody dose-dependent suppression reflects specific blockade of PVR binding to

TIGIT. Data above shows etigilimab and competitor Ab currently in the clinic is equivalent with

respect to blocking PVR binding.

7

Effector function silentEffector function competentControl Ab

Etigilimab – an IgG1 anti-TIGIT monoclonal antibody with inhibitory and ADCC

characteristics


Phase 1 study design

N=3+3

N=3+3

Mereo Biopharma Group plc 8

0.3mg/kg* Q2W

N=3+3

3mg/kg Q2W + nivolumab1mg/kg Q2W

N=3+3

10mg/kg Q2W + nivolumab3mg/kg Q2W

N=3+3

20mg/kg Q2W + nivolumab

N=3+3

10mg/kg Q2W

N=3+3

Tumor types for inclusion in dose escalation cohort:

• Histologically confirmed advanced relapsed or refractory solid tumors

• Refractory to or progressed after prior anti-PD1/L1 treatment

• All patients heavily pretreated

Tumor types for inclusion in dose escalation cohort:

• Histologically confirmed advanced relapsed or refractory solid tumors

• All patients heavily pretreated

Dose Escalation20mg/kg Q2W

N=3+3Dose Escalation

Phase 1BPhase 1A

Phase 1a best % reduction in target lesion size & duration on studyEtigilimab monotherapy

Waterfall Plot of Best Percentage Change in SLD from Baseline (ITT Population) Duration on Study

23 patients enrolled


Reduction or no Growth

Patient Dose Cancer Patient Dose Cancer

004-013 10mg/kg adenocarcinoma of the pancreas 001-025 20mg/kg* Endometrial

004-008 3mg/kg CRC MSS adenocarcinoma of the colon 002-004 1mg/kg endometrial adenocarcinoma of uterus

003-024 20mg/kg* HNSCC 001-002 0.3/kg CRC MSS adenocarcinoma

003-018 20mg/kg triple negative breast cancer 003-016 20mg/kg CRC MSI

002-015 20mg/kg pancreatic adenocarcinoma 001-001 0.3mg/kg CRC MSS

005-006 1mg/kg CRC MSS 005-005 1mg/kg salivary duct

005-026 20mg/kg* Lung 001-011 10mg/kg endometrial

002-012 10mg/kg CRC MSS colorectal adenocarcinoma 005-023 20mg/kg* parotid

004-021 20mg/kg metastatic endometrial / papillary serous 005-010 3mg/kg Fallopian

005-017 20mg/kg endometrial

Head and Neck Cancer, 20.0 mg/kg + nivolumab

Gastric Cancer, 20.0 mg/kg + nivolumab

NSCLC, 3.0 mg/kg + nivolumab

RENAL CELL CARCINOMA, 10.0 mg/kg + nivolumab

Gastric Cancer, 3.0 mg/kg + nivolumab

METASTATIC OVARIAN CANCER, 3.0 mg/kg + nivolumab

COLORECTAL CANCER, 3.0 mg/kg + nivolumab

Subject ID

Phase 1b best % reduction in target lesion size & duration on studyEtigilimab + nivolumab

Duration on Study


%C

hange

from

Base

line

*

*HCC

100

80

60

40

20

0

-20

-40

-60

-80

-100

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

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 Reduction

003-103 3mg/kg Colon CRC MSI adenocarcinoma

Waterfall Plot of Best Percentage Change in SLD from Baseline (ITT Population)

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 (combination with nivolumab)

cohorts (n=8 evaluable, n=7 with tumor assessments)

No DLTs were observed; etigilimab generally well-tolerated

Etigilimab elicited adverse events consistent with immune system activation

The pharmacokinetic profile of etigilimab is favorable and no evidence of anti-drug antibodies observed

Target engagement of etigilimab demonstrated in Phase 1a patients in blood• Activated immune cells measured by increases in Ki67+TIGIT+CD4 as well as NK cells and increased in intracellular cytokines

• Reduced Tregs in circulation, with a corresponding increase in the CD8/Treg ratio


THE ACTIVATE STUDY

ACTIVATE – A Phase 1b/2 Open-label Study

Etigilimab plus nivolumab in advanced/metastatic solid tumors

14

Primary endpoint • Overall Response Rate

Secondary• Safety and Tolerability• PK/PD• Duration of response

Exploratory• Biomarker• PFS • OS

Simon two-stage design allowing for dynamic decision making and flexible designN= ~ 125 subjects

Rare tumors (e.g., sarcomas)

*PDL1+ required for enrollmentFlat dosing Q2W

Ovarian

Cervical*

Endometrial

Gastric/GEJ*

SCCHN*

TMB-High/MSS

Additional study in rare subtype of ovarian cancer with MD Anderson/Focus Fund collaboration:

EON Study: A Single-arm Phase II study of Etigilimab plus Nivolumab in Clear Cell Ovarian Cancer


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 will be considered• Each cohort to be managed uniquely

15


Differentiated Clinical and

Biomarker Strategy


Key Elements of Etigilimab Phase 1b/2: Differentiated clinical development

• Focus on Checkpoint-naïve populations

• Prioritize TIGIT expressing tumors by:

(i) Low monotherapy checkpoint inhibitor activity

(ii) Rare cancers

(iii) High unmet need

Gyn-onc indications ORR with Anti-PD-1 Monotherapy

Cervical KN15814% (KN158)

Ovarian KN1008.1% ( </=2 prior lines);9.9% (3-5 prior lines)

Rare Cancers ORR with Anti-PD-1 Monotherapy

Sarcoma (Select histological subtypes)

0-20% (Sarc028)

Others 0-5%

18

Key Elements of Etigilimab Phase 1b/2 Clinical Biomarker Strategy

Multi-Pronged Biomarker Approaches

Prospective selection, established biomarkerPD-L1

Cervical, gastric, SCCHN as per indication on label

Prospective selection, emerging biomarker TMB-H/MSS tumors

Retrospective evaluation with potential novel biomarker(s)PVR/TIGIT expression

All enrolled subjects


Phase 1b/2 Study – Biomarker Strategy


19

Robust multiplex IHC assays and staining for PVR, TIGIT

and ~ immune-related tumor parameters

• 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 exploratory biomarkers e.g. CD226, PVRL2 will be measured

• Blood and tissue-based quantification will be employed for tumor mutation burden cohort to enable patient selection

– Guardant blood, Foundation Medicine and MSKCC tumor test

– Abbreviated IDE diagnostic process may enable fast approval

Summary: Mereo’s etigilimab has key differentiating features

capabilities in place


• Target engagement of etigilimab demonstrated in Phase 1a patients

• Potential early clinical signals observed in non-IO responsive tumor types

• 30% SD in Phase 1a;1PR in Phase1b(Majority heavily pre-treated, all post-CPI in Phase 1b)

• IgG1 backbone activates antibody-dependentcellular cytotoxicity (ADCC).

• Preclinical data suggest advantages of thisbackbone over competitor ADCC-null anti-TIGIT mAbs

ACTIVATE Trial

Differentiated Phase 1b/2Trial Design

Advanced BiomarkerPhase 1a and 1b safety, preliminary efficacy and biomarker data available

High affinity

IgG1 antibody

• Biomarker methods established to evaluate and enable future patient stratification and selection, including TIGIT and PVR expression

20

Alvelestat(MPH-966)

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 and cell-bound NE

Well-characterised exposure-response profile – significant lung penetration

Safety established in >1000 subjects

Activity in pre-clinical models of NE and NETosis pathology

Studies underway include:

• AATD and BOS (NE)

• COVID-19 (NETosis)

Potential mechanistic indication expansion

Mereo Biopharma Group plc22

Signal seeking in Neutrophil-driven diseases – cystic fibrosis and bronchiectasis –anti-inflammatory and clinical effects

Trial Summary - CF

• Double-blind, placebo controlled > 16 years

• Clinical diagnosis of CF

• FEV1 > 40% predicted

• 60 mg alvelestat or placebo BD for 4 weeks

• Randomized = 56 (27 alvelestat, 29 placebo)


Alvelestat decreases

urinary and plasma

DESs in CF (n=56);

*P<0.05

MPH966:placebo

CF- Desmosine alvelestat:placebo ratio at week 4*

CF Week 4 : Sputum : IL-6 (sputum) alvelestat:placebo = 0.59 p=0.006

• Double-blind, placebo controlled 18-80 years old

• Non-CF bronchiectasis, stable for 6 weeks

• 60 mg alvelestat or placebo BD for 4 weeks

• Randomized = 38 (22 alvelestat, 16 placebo)

Trial Summary - Bronchiectasis

P ValueParameter placebo LSM(SEM)

Bronchiectasis Study - Spirometry at week 4**

Lung Function Improvement over

FEV1 100 mls (34.0) 0.006

SVC 130 mls (74.0) 0.079

**Stockley et al. Respiratory Medicine (2013) 107, 524- 533

BE Week 4 : Sputum : alvelestat:placebo:• IL-6 = 0.72 p=0.058• RANTES = 0.63 p =0.018

*Elborne et al. Eur Respir J (2012) 40, 969–976

A rare, serious geneticdisorder that results inearly onsetdisease

pulmonary

Therapeutic Advances in Respiratory Disease January 30 23Mereo Biopharma Group plc*Luisetti et al (2004) α1-Antitrypsin deficiency · 1: Epidemiology of α1-antitrypsindeficiency Thorax 59:164-169

Natural protease inhibitor is either absent or levels are insufficient and dysfunctional

Unopposed neutrophil elastase → progressive lung damage, early onset emphysema

Presents age 20 to 50 - symptoms include shortness of breath, cough and reduced exercise tolerance, can progress to chronic oxygen therapy, lung transplant and death

Prevalance – target population estimated to be 50,000 inNorth America and 60,000 in Europe and the UK*

Clinical management is COPD maintenance treatment and lifestyle management

*Francisco et al (2012) Rare alpha-1-antitrypsin variants: are they really so rare?

Intravenous plasma-derived augmentation therapy: weekly, approved in N. America and EU, clinical efficacy not uniformly recognized by physicians or payors:

• Limited penetration into lung

• Inability to ‘titrate’ up to cover periods of acute lung inflammation, elastase activity and lung damage• Growing evidence that higher doses are needed for clinical efficacy with cost and convenience implications

Alpha-1 Antitrypsin deficiency (AATD) Lung disease impact

Role of Neutrophil elastase in pathogenesis of AATD Lung Disease


Release of pro-inflammatory

elastin peptides

Apoptosis ofEpithelial cell

Pro-inflammatory cytokines -

neutrophil activation and chemotaxis

Elastase/anti-elastase

imbalance

Elastase/anti-elastase imbalance

• Neutrophil elastase (NE) key enzyme driving lung elastin breakdown (30% tissue) alveolar damage and loss of lung density

• Desmosine is direct elastin breakdown product associated with disease severity in disorders with imbalance between NE and its physiological inhibitor (alpha-1 antitrypsin), CF, bronchiectasis and AATD.

• In a large AAT replacement study (‘RAPID’*) reductions in desmosine associated with clinical endpoints FEV1 and DLCO, and lung density decline

• Clinical outcomes for registrational trial (potentially lung density by CT scan) may require 2 year end-point

*Ma et al *Chronic Obstr Pulm Dis. 2017; 4(1): 34-44

Example of Desmosine and Correlation with Disease Severity in Disease with Elastase/anti-elastase imbalance in Cystic Fibrosis

Ma S, Geraghty P, Dabo A, et al. Cystic fibrosis disease severity correlates with plasma levels of desmosine and isodesmosine, biomarkers of elastin degradation. ERJ Open Res 2019

Increased levels desmosine similar to AATD


Astraeus Phase 2 study design (NCT03636347) in Alpha-1 Antitrypsin Deficiency

A 12-week Study Treating Participants Who Have alpha1-antitrypsin-relatedCOPD with Alvelestat (MPH966) or Placebo. (ASTRAEUS) Primary Endpoint

• Within-individual % change inplasma desmosine/isodesmosine

Secondary Endpoints•

•

Safety and tolerability

Other blood biomarkers of neutrophil elastase activity

St. George's Respiratory

Questionnaire

Forced expiratory volume in 1 second (FEV1)

•

•

Trial Population• Emphysema, FEV1 ≥20% predicted

• Not receiving augmentation therapy•

•

•

Age ≥18 and ≤80 years

Pi*ZZ, Pi*Z Null, or Pi*Null genotype/phenotype#

Anti-alpha1 antitrypsin <11uM


review of safety data from Dose 1

N = 165 12 week dosing period

1:1 active to placebo Alvelestat Placebo bid N=55

Randomization

Alvelestat Dose 1 bid N=55

• Initially randomisation to placebo or Dose 1

• Randomisationto Dose 2 initiated after DMC Alvelestat Dose 2 bid N=55

# or other rare mutations associated with severe deficiency

Alvelestat (MPH966) for the Treatment of ALpha-1 ANTitrypsin Deficiency

“ATALANTa”(Investigator-initiated – Mark Dransfield, UAB

Primary Endpoint• Within-individual % change in

plasma desmosine/isodesmosine(week 12)

Safety and tolerability•

Trial Population• Not currently receiving augmentation OR on

stable augmentation for at least 12 weeksprior to screening

•

•

•

Age ≥18 and ≤80 yearsFEV1 ≥25% predicted

Pi*ZZ, Pi*SZ, Pi*Z Null, or Pi*Null genotype/phenotype or other rare mutations associated with severe deficiency

Funded by NCATS


N = 66 12 week dosing period

1:1 active to placebo Alvelestat Placebo bid N=33

Randomization

Alvelestat Dose 1 bid N=33

COVID-19 Phase 1b/2 Investigator-initiated study “COSTA” (Prof. Mike Wells, UAB

Primary Endpoint• Safety and tolerability (Day 60)

N = 15Secondary EndpointsPharmacodynamic Biomarkers of:

•

•

•

NETosis

Inflammation

Elastase

Clinical outcomes

Day 90 MortalityTrial Population•

•

•

> 18 years, hospitalized

Moderate/Severe SARS-CoV-2 infection (WHO grade 3-5)

Not on invasive ventilation


10 day dosing period

2:1 active to placeboAlvelestat bid

Randomization Follow-up to Day 90

Placebo bid

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 both conditions from clinical, pathological and immune perspective

High unmet need:

BOS is the leading cause of graft loss and death following lung transplant:

• Develops in 50% recipients by 5 years, median survival ~3-4 years

• Accounts for lack of improvement in long term lung transplant outcomes in last 20 years

30

Kulkarni et al. Bronchiolitis obliterans syndrome–free survival after lung transplantation. J Heart Lung Transplant (2019), 38, 1: 5-16


Summary : Alvelestat key differentiating features

Profile for long-term treatment of AATD lung disease and NETosis-driven diseases

action < 4 hours

inhibition

for side effects

enzyme coverage


Rapid onset of

to > 90% enzyme

Highly specific neutrophil elastase

inhibition –reduces potential

Combination of twice daily dosing

and high neutrophil elastase inhibition

allows for 24/7

High neutrophil elastase inhibition

> 90% at doses trialed

Oral, twice daily dosing

Setrusumab(BPS-804)

Anti-Sclerostin as a target for OI


Osteogenesis imperfecta (OI)

1. Based on Osteogenesis Imperfecta Foundation estimates; 2. Based on Orphanet estimates


• 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 developed countries

• Children have highest unmet need – disease management pathways in key centres

• Adult opportunity is significant – progressive condition, patients remain symptomatic

but often burden is overlooked and patient management less organized than children

• Well-established patient groups – OIFE and OIF >50 years old

• Despite the above – no FDA or EMA approved therapies

• Setrusumab (BPS-804) is an antibody targeting sclerostin

• Orphan designation EU and US, PRIME (Priority Medicine) designation by EMA

and Pediatric Rare Disease designation by FDA

Partnership with Ultragenyx Pharmaceutical

commercialization Rights


• RARE to lead future global development in both pediatric and adult patients until approval

• Initial prioritization of pediatric patients with OI

• Development plans being finalized – in discussions withregulators

• Pediatric Phase 2/3 first to determine optimum dose, then adapt to Phase 3 fracture study

• Pediatric Phase 2b/3 study expected to start in 2021

• Separate study planned for adults

• MREO grants RARE license to develop and commercialize setrusumab in US and ROW excluding EU and UK

• Upfront payment of $50M

• Funding of global development program until approval

• Up to $254M for clinical, regulatory and commercial milestones

• RARE pays MREO tiered double digit % royalties on net sales outside EU

• MREO pays RARE fixed double digit % royalty on net sales in EU

Attractive partnership with established player in

rare diseases

Aligns with MREO’sstrategic objectives

MREO :Development andDevelopment PlanTerms

• Completes ongoing adult extension of Phase 2b study investigating the “off-effect post 12 months treatment with setrusumab

• Joint Committees and attends regulatory meetings

• Option to commercialize in EU, EEA and UK

• Responsible for post-marketing commitments in the EU, EEA and UK

• Under a 2015 agreement, pays Novartis a percentage of proceeds subject to certain retaining substantial majority deductions (but with MREO)

Summary of Phase 2b data

OI patients comparing

once monthly for 12

in adults

increase in areal BMD


Phase 2b – 110 adult

3 doses of setrusumab

months

Largest clinical study

demonstrating highest

changes including in more severe OI patient population Type III/IV

Study not powered to show a difference in fracture rates but a trend of reduction in fractures and fracturingpatients observed in the high dose cohort –15% of high dose patients fracturing

versus 25-35%

Secondary end-points based on areal bone

mineral density measured by DXA

• Dose dependent statistically significant changes in areal BMD at 6 and 12 months at all doses and in all OI phenotypes (+4.5% p<0,001 at 6 months and +8.8% p,0.001 at 12 months at the high dose

• Dose dependent increase in areal BMD at all the anatomical sites tested (femoral neck and total hip) 3.2% p=0.022 and 2.3% p=0.009 at high dose

Hierarchical primary end-point based on HRPQCT

• Trabecular vBMD at the radius

improved at high dose but not

statistically significant

• Total vBMD statistically

significant increases at high

and medium doses (+4.1%

p=0.004)

• Bone strength (Failure Load

and Bone Stiffness) dose-

dependent increases –

statistical significance at the

high dose (+2% p=0.037) and

(+2.2%, p=0.022)

Upcoming Milestones

Upcoming Key Milestones & Opportunities

38

Product Candidate Indication 2021 2022 2023 Partner Milestone

Co

re P

rogr

ams

Etigilimab Solid tumorsPhase 1b/2 full enrolment and data Phase 2 cohort expansion

Alvelestat

AATDAATD: Phase 2 data readout AATD: Investigator lead study

COVID-19: Phase 1b/2 data

BOS: Phase 1b

COVID-19

BOS

SetrusumabOsteogenesis imperfecta

Initiation of pediatric pivotal study. Adult registration strategy

No

n-C

ore

Pro

gram

s NavicixizumabOvarian cancer

Initiation of registrational trial

Leflutrozole HH infertility Partnering Discussions

Ongoing

Partnering

AcumapimodAcute exacerbations of COPD

Partnering

Phase 1b

Pediatric Phase 2b/3 fracture study

Phase 1b/2 basket study with potential cohort expansion

Outlicensed

Phase 2b study complete

Phase 2 study completeKey data or milestone event

Ph. 1b/2 study

Ph. 2 PoC

Financial highlights

1 One ADS represents five ordinary shares2 Assumes a market price of $4.00 per ADS and cashless exercise. The maximum number of

warrants outstanding is 29.8m.3 Excludes 2.9m ADSs payable either in ADSs or cash at election of the note holder4 Excludes 1.9m ADSs for employee share awards with an exercise price in excess $8.00


Cash runway into 2024

Cash resources of $152 million (£110m) as of

June 30, 2021, including:

• $50 million upfront for Setrusumab agreement received in January 2021

• $115 million gross proceeds from financing in February 2021

:

Cap Table(June 30, 2021)

ADSs1

(in thousands)

Shareholders > 5% holding 40,799

Shareholders < 5% holding 67,612

Share capital - Issued and outstanding 108,411

Potential Future Dilution:

Warrants2 11,961

Convertible loan notes3 25,597

Employee share schemes4 4,422

Investment highlights

• Acumapimod for AECOPD• Leflutrozole for infertility• Navicixizumab partnered with OncXerna ($300M + royalties)


Multiple near-term clinical and pipeline milestones

Highly experienced management team with significant expertise in drug development and oncology and rare diseases

Cash runway into 2024

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 ongoing Phase 2 studies for AATD and COVID-19• Setrusumab is an anti-sclerostin antibody proven to build bone in Osteogenesis imperfecta patients in a Phase 2b study in adults -

partnered with Ultragenyx

Additional programs for partnering or partnering income

Appendix

2021 2023 2025 2027 2029 2031 2033 2035 2037 2039 2041

1

Intellectual property portfolio

1Data & Marketing Exclusivity - EUROPE

Granted in all major territories

Tosylate salt – granted in all major territories


Medical use – pending in all major territories

3SPC/2,3PTE

Medical use – granted EP and US / pending in all other major territories


1Orphan Exclusivity - US

1.2.3.

Subject to final marketing approval datesPreliminary view of patent term extension (PTE) – TBCSPC/PTE base patent to be determined

41

Setr

usu

mab

Alv

ele

stat

Etig

ilim

ab

1SPC

1,2PTEAntibody and use – granted/pending in all major territories

Medical use – pending in all major territories

1Biologics Data & Marketing Exclusivity - US

Molecule and use

Antibody and use – granted an all major territories

Orphan Exclusivity - EUROPE

1Biologics Data & Marketing Exclusivity - US

1Paediatric extension of orphan exclusivity

1,2,3PTE (US)

1,3 SPC (EP)

SPC/2PTE

1,2NCE Exclusivity - US


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 NivoPembro or Nivo + Ipilimumab

ORR 5 – 16%

Rare tumor 2 Pembro ORR <5%

Rare tumor 3 (metastatic) Pembro ORR 11%

Ovarian (all comers) Pembro ORR 11.6% (high PD-1 expression)No diff Pt sensitivity

PD-1 Inhibitors Approved

Cervical Pembro 2L +R/M with CPS>/= 1 ORR 14% Post SOC, TMB-H ORR = 16%

Endometrial Pembro 2L + MSI-H or dMMR

Pembro + Lenvatinib MSS</= 2 prior lines of systemic therapy

ORR 57% ORR 11% (TMB unselected)

ORR 38%


Etigilimab – Cancer Focus Fund & MD Anderson Collaboration

44

• 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

infrastructure of MD Anderson• Collaboration represents the first investment from the Cancer Focus Fund

• Funding provided for:• Investigator sponsored clinical study in Phase 1/2 for etigilimab in combination with nivolumab in

clear cell ovarian cancer • Support for CMC and pharmacovigilance expenses

• Terms • $1.5 million in equity• Milestones for licensing (capped) and FDA/EMA approval that includes ovarian clear cell carcinoma


Etigilimab - Cancer Focus Fund & MD Anderson Collaboration

45

• 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 outcomes but data on clear cell subtype with anti-PD1 therapy

promising albeit limited data set• Dr Shannon Westin, Lead PI is a KOL in ovarian cancer: MD Anderson is one of the primary referral centers for

clear cell ovarian patients• MD Anderson also key study site for ACTIVATE study enrolling the HGSOC ovarian population


Biomarkers established for tumor analysis and potential patient selection

Robust multiplex IHC assays and staining for

PVR, TIGIT and ~15 immune-related tumor

parameters


Alpha-1 antitrypsin deficiency (AATD) – current standard of care

A rare, serious geneticdisorder that results inearly onsetdisease

pulmonary


Clinical Management

‘COPD’ maintenance treatment, personal lifestyle

management, e.g., avoidance of smoking and

pollution

Intravenous plasma-derived augmentation

therapy: weekly, approved in N. America and EU,

but clinical efficacy not uniformly recognized by

physicians or payors:

• Limited penetration into lung

• Inability to ‘titrate’ up to cover periods of acute lung inflammation,

elastase activity and lung damage

• Growing evidence that higher doses are needed for clinical

efficacy with cost and convenience implications

Signal seeking in Neutrophil-driven diseases (2)bronchiectasis – anti inflammatory and clinical effect

Trial Summary

•

•

•

•

•

Double-blind, placebo controlled

18-80 years old

Non-CF bronchiectasis, stable for 6 weeks

60 mg alvelestat or placebo BD for 4 weeks

Randomized = 38 (22 alvelestat, 16 placebo)

Mereo Biopharma Group plc *Stockley et al. Respiratory Medicine (2013) 107, 524- 533 47

Phase 2 study of a neutrophil elastase inhibitor (MPH966) in patients with bronchiectasis. *

Pro-Inflammatory Cytokines at week 4

Cytokine Ratioalvelestat:placebo P Value

IL-6 (sputum) 0.72 0.058

RANTES (sputum) 0.63 0.018

IL-8 (blood) 0.74 0.085

P ValueParameter placebo LSM(SEM)

Spirometry at week 4

Lung Function Improvement over

FEV1 100 mls (34.0) 0.006

SVC 130 mls (74.0) 0.079

Role of Neutrophil elastase in pathogenesis of AATD Lung Disease

cell


Release of pro-inflammatory

elastin peptides

Apoptosis ofepithelial

Pro-inflammatory cytokines -

neutrophil activation and chemotaxis

Elastase/anti-elastase

imbalance

Elastase/anti-elastase imbalance

Alvelestat MOA in NETosis-driven disease (COVID-19)


Alpha-1 antitrypsin physiological elastase inhibitor is overwhelmed

Dysregulated inflammatory

response

NETs activate cytokine storm

Chromatin studded with

elastase extruded

Thank You

M e re o B i o P h a r m a G ro u p p l c

N A S DA Q : M R EO

Mereo BioPharma Group

One Cavendish Place London, W1G 0QF

UK

plc

+44 (0)333 0237 300


unlocking the potential of novel targets for cancer and

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