POTENTIAL IN ONCOLOGY AND RARE DISEASES August 2020 DISCLAIMER - - PowerPoint PPT Presentation
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
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
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
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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
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
ETIGILIMAB
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
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Mereo BioPharma Group plc
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
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Mereo BioPharma Group plc
PHASE 1 STUDY DESIGN
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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
PHASE 1A DURATION ON STUDY
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23 Patients enrolled
Mereo BioPharma Group plc
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
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
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Mereo BioPharma Group plc
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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
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
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Mereo BioPharma Group plc
PHASE 1B: BEST % REDUCTION IN TARGET LESION SIZE
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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
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
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
SUMMARY
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- 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
ALVELESTAT (MPH-966)
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)
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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
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
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Mereo BioPharma Group plc
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
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
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- In addition total of 970 patients across four COPD studies
Mereo BioPharma Group plc
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%
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
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
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
SETRUSUMAB (BPS-804)
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
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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
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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
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Mereo BioPharma Group plc
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
Mereo BioPharma Group plc
AREAL BONE MINERAL DENSITY AS MEASURED BY DXA PER PROTOCOL
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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
Mereo BioPharma Group plc
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- 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
SUMMARY AND NEXT STEPS
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- 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
UPCOMING MILESTONES AND FINANCIAL OVERVIEW
Mereo BioPharma Group plc
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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
Mereo BioPharma Group plc NASDAQ: MREO, AIM: MPH
THANK YOU
CONFIDENTIAL
NETosis References
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