Mereo BioPharma Group plc · NASDAQ:MREO
Mereo BioPharma — Investor Presentation (September 2023)
39 slides from Mereo BioPharma's investor presentation, September 2023
Slide 1: Unlocking The Potential Of Novel Targets For Rare Diseases
Unlocking The Potential Of Novel Targets For Rare Diseases September 2023 Mereo BioPharma Group plc NASDAQ: MREO
Slide 2: Disclaimer
Disclaimer This presentation has been prepared by Mereo BioPharma Group plc (the “Company”) solely for your information and for the purpose of providing background information on the Company, its business and the industry in which it operates or any particular aspect thereof. For the purposes of thi
Slide 3: Mereo BioPharma – a rare disease company
Mereo BioPharma – a rare disease company Our Mission To improve the lives of patients with rare diseases Strategic principles guiding us on our journey… Acquire and develop programs in rare Focus on our core competencies and Partner programs where it makes diseases with high prevalence – partner exp
Slide 4: Mereo BioPharma – a mid-late-stage company with validating partnerships
Mereo BioPharma – a mid-late-stage company with validating partnerships • Two rare disease programs in-licensed and ready for pivotal studies within five years o Setrusumab for Osteogenesis Imperfecta (OI) in Phase 3 under the Ultragenyx partnership o Alvelestat for Alpha-1 Antitrypsin Deficiency-As
Slide 5: Late-stage clinical pipeline with core rare disease programs
Late-stage clinical pipeline with core rare disease programs Product Phase 1 Phase 2 Phase 3 Regulatory Successes Candidate Setrusumab ORBIT (5 - <26 yrs old) Orphan drug designation (US and EU), PRIME (EU), Pediatric OI COSMIC ( 2 - <7 years yrs old ) disease designation (PRV) Alvelestat Orphan dru
Slide 6: Rare Disease Day 2023 patient quote
“It’s always a pleasure to come and speak with people who are actually making a difference on the ground and making a difference for people like myself and for others in the community. Because it is what you do that helps us to live the lives that we want and that we deserve.” Thines Ganeshamoorthy,
Slide 7: Setrusumab (UGX143)
—Sw Mereo BioPharma ~~ Setrusumab (UGX143)
Slide 8: Osteogenesis Imperfecta – A rare genetic bone condition with no approved standard of care
Osteogenesis Imperfecta – A rare genetic bone condition with no FDA nor EMA approved standard of care
Slide 9: OI – a rare genetic bone condition with no approved standard of care
OI – a rare genetic bone condition with no approved standard of care Osteogenesis Imperfecta High Unmet Need • Signs and symptoms include frequent bone fractures, skeletal deformities, pain, • A rare genetic bone disease, mostly linked to a respiratory and gastric problems mutation in Type I collage
Slide 10: Setrusumab – mechanism of action is particularly well suited for OI
Setrusumab – mechanism of action is particularly well suited for OI 10
Slide 11: Summary of phase 2b ASTEROID results in adults with OI Types I, III and IV
Summary of phase 2b ASTEROID results in adults with OI Types I, III and IV Statistically significant dose-dependent increases in areal BMD by DXA following 12 months of setrusumab therapy Lumbar Spine Total Hip Femoral Neck 12 Mean (SEM) Change From Baseline at Month 12, % *** 10 6 * 8 *** ** 4 ** 6
Slide 12: Setrusumab improves bone strength in OI Types I,III and IV at 12 months
Setrusumab improves bone strength in OI Types I,III and IV at 12 months • Increase in failure load and stiffness at the radius as measured by finite element analysis (FEA) • Increase in trabecular bone score (TBS) – 3D parameters of trabecular bone architecture, helps predict fracture Failure Load a
Slide 13: Phase 2b ASTEROID study – positive impact on bone strength and reducing fractures
Phase 2b ASTEROID study – positive impact on bone strength and reducing fractures Mean % Δ from baseline 20mg/kg 8mg/kg 2mg/kg 12 months (n=28) (n=22) (n=25) Radius Total vBMD 1.88 0.86 0.04 (p<0.01) Annualized Total Fracture Rate 0.4 months of setrusumab therapy, % 0.35 0.38 Rate of Fracture During
Slide 14: ORBIT Phase 2 study design
ORBIT Phase 2 study design Phase 2 is designed to select a setrusumab dosing strategy based on PK/ PD, safety, and available BMD data in subjects with OI Stratification Patients Enrolled Patients with at least 2 fractures over prior 24 months 24 patients ages 5 to < 26 years with OI Types 1, III, wi
Slide 15: ORBIT – Younger patients had high and early increases in P1NP
ORBIT – Phase 2/3 study Younger patients had high and early increases in P1NP Serum P1NP (bone formation) • Rapid increase in P1NP levels – bone formation biomarker within 1 week • 20mg/kg dose resulted in 80% P1NP AUC than the 40mg/kg dose • Placebo showed no response as expected 15
Slide 16: Younger patients in ORBIT had increases in Lumbar DXA BMD at 3 months
Younger patients in ORBIT had increases in Lumbar DXA BMD at 3 months which compared to 12 months in ASTEROID • BMD Z score change of +0.65 at 3 months for 20mg/kg • 1.0 Z score is equal to 1 standard deviation of the population 16
Slide 17: ORBIT Phase 2/3 study – Phase 2 safety data
ORBIT Phase 2/3 study – Phase 2 safety data • No treatment-related serious adverse events observed • Reported adverse events include infusion-associated events, headache and sinusitis • No reported hypersensitivity reactions • No safety-related differences observed between dosing groups or age group
Slide 18: Ultragenyx – Mereo partnership and long-term plan
Ultragenyx – Mereo partnership and long-term plan Mereo – Ultragenyx partnership Clinical development overview Mereo territories & focus • Ultragenyx leads and funds global • Phase 3 ORBIT* study in ~195 OI • Groundwork for reimbursement of development plan patients 5 -<26 years old patients in setr
Slide 19: Alvelestat (MPH966)
—Sw Mereo BioPharma ~~ Alvelestat (MPH966)
Slide 20: AATD-LD: A rare progressive lung disease with high unmet need
AATD-LD A rare progressive lung disease with high unmet need ALPHA 1 EUROPEAN GROUP MEETING 2023
Slide 21: AATD-LD – A rare progressive lung disease with high unmet need
AATD-LD – A rare progressive lung disease with high unmet need Lack of AAT or misfolded inactive AAT results in risk of progressive lung damage and early onset emphysema. AATD-LD High unmet need Significant market opportunity • Presents age 20 to 50, shortness of breath, • Current treatment limited
Slide 22: Linking biomarkers to pathological pathway
Linking biomarkers to pathological pathway AATD-Lung Disease Pathogenic Pathway Blood NE Aα-Val360 Desmosine CT Density / FEV1 / SGRQ Neutrophil Unopposed NE Alveolar Elastin Lung Tissue Elastase Activity Inflammation Breakdown Loss/Emphysema Increased neutrophil Increase in neutrophil Elastin break
Slide 23: Primary Endpoint: Blood NE Activity – Week 12
Primary Endpoint: Blood NE Activity – Week 12 P value % CFB compared to placebo Week 120 mg 240mg 4 <0.001 <0.001 8 0.012 <0.001 12 0.023 <0.001 • Significant suppression at both doses • > Sustained 90% suppression of blood neutrophil elastase activity at the 240mg dose 23
Slide 24: Primary Endpoint: Disease activity biomarkers % change from baseline at Week 12
Primary Endpoint: Disease activity biomarkers % change from baseline at Week 12 Aα-Val360 Desmosine Statistically significant decrease in desmosine and Aα-Val360 from baseline and vs. placebo with 240mg dose only 24
Slide 25: Association of biomarker responses with St. George's Respiratory Questionnaire
Association of biomarker (Dual Aα-val360 and Desmosine) responses with St. George’s Respiratory Questionnaire Activity Domain in alvelestat Alvelestat Combined Groups Placebo 240mg dose = 12 Responders / 13 Non-responders 120mg dose = 3 Responders / 11 Non-responders Placebo = 3 Responders / 25 Non-
Slide 26: Linking ASTRAEUS change in Desmosine to CT-density decline through RAPID data
Linking ASTRAEUS change in Desmosine to CT-density decline through RAPID data Correlation of change from baseline in desmosine at 2 years and lung density decline (RAPID study) Alvelestat month 3 -0.028 Source: Ma et al. The Effect of Alpha-1 Proteinase Inhibitor on Biomarkers of Elastin Degradation
Slide 27: SGRQ Activity Domain detects symptoms most disruptive for patients with AATD
SGRQ Activity Domain detects symptoms most disruptive for patients with AATD: ASTRAEUS findings consistent with published literature ASTRAEUS Baseline SGRQ Scores Published Studies with AATD 27
Slide 28: AlphaNet Study– HRQoL in patients with AATD – greater impact on physical activities
AlphaNet Study– HRQoL in patients with AATD – greater impact on physical activities • Cross-sectional study of 4,694 participants in AlphaNET – Health Management Organization for patients with AATD • Majority of patients were of the ZZ/ZNull/Nuull genotypes – severe AATD • SGRQ measured the impact o
Slide 29: End-of-Phase 2 meetings and next steps
End-of-Phase 2 meetings and next steps • Global Phase 3 – 12-18 months in ~200 patients with two different independent Primary Endpoints for full approval - FDA – SGRQ*: Mereo will focus on the activity domain ˃ Next step Feedback from Division of Clinical Outcome Assessment (DCOA) and FDA division
Slide 30: Etigilimab (MPH313)
—Sw Mereo BioPharma ~~ Etigilimab (MPH313)
Slide 31: Etigilimab – an Anti-TIGIT antibody in development in combination with anti-PD1
Etigilimab – an Anti-TIGIT antibody in development in combination with anti-PD1 - T Cell Immunoreceptor with IG and ITIM domains (TIGIT) - Anti-TIGIT designed to activate the immune system and enable anti-tumor activity - Expressed on CD4, CD8 and NK cells and expression is pronounced on regulatory
Slide 32: ACTIVATE Trial – Preliminary efficacy data
ACTIVATE Trial – Preliminary efficacy data Response summary, as of a data cut-off date of 4/20/2022 (efficacy analysis set; n=38)* Objective Cohort responses by RECIST A C E F (Rare) F (Rare) F (Rare) H Total Endometrial Cervical TMB-H/MSS Uveal Sarcoma GCT Ovarian Cancer Cancer (HGSOC) (CPI-naïve)
Slide 33: ACTIVATE – Swimmer plot of duration on treatment
ACTIVATE – Swimmer plot of duration on treatment* Duration represents time from start to end of treatment/cut off date (*4/20/2022) if on treatment; efficacy analysis set n=38 indicates on treatment at cut off date 33
Slide 34: Etigilimab shows robust target engagement in patients
Etigilimab shows robust target engagement in patients and exploratory biomarker correlation with clinical response Baseline tumor expression: correlation with reductions in Etigilimab shows robust target engagement target lesions CD226/CD8 Co-expression % Change From Baseline PVR Sarikonda et al, ES
Slide 35: EON Phase 1b/2 study design: etigilimab plus nivolumab in Clear Cell Ovarian Carcinoma
EON Phase 1b/2 study design: etigilimab plus nivolumab in Clear Cell Ovarian Carcinoma Two Stage Phase 1/2 Design with stopping boundaries for efficacy and toxicity Mereo Biopharma Group plc 35
Slide 36: Partnerships overview
Partnerships overview Current partnerships • Ultragenyx leads global development of setrusumab, Mereo retains rights in Europe and the UK • Received $50 million upfront, up to $254 million in additional milestones plus royalties • $9 million milestone following first patient dosed in ORBIT Phase 3 s
Slide 37: Upcoming key milestones
Upcoming key milestones Upcoming key milestones for core programs Product 2022 2023 2024 Next milestone candidate H1 H2 H1 H2 H1 H2 Phase 3 ORBIT (5-<26 yrs old) Phase 3 data Setrusumab Phase 2 ORBIT Open label Phase 2 update mid-October OI Phase 3 COSMIC study ( 2-<7 yrs old ) Phase 3 data AATD-LD
Slide 38: Financial highlights
Financial highlights Cap Table ADSs1 (August 31, 2023) (in thousands) Shareholders > 2% holding 61,638 Cash runway into 2026 Shareholders < 2% holding 78,539 $53.1 million as of Share capital – Issued and outstanding 140,177 June 30, 2023 Potential Future Dilution: $9M milestone payment and Warrants
Slide 39: Mereo BioPharma Group plc
Mereo BioPharma Group plc One Cavendish Place London W1G 0QF United Kingdom +44 (0)333 0237 300
Mereo BioPharma Group — Investor Presentation (September 2023) on 6ix