Mereo BioPharma Group plc · NASDAQ:MREO
Mereo BioPharma — Investor Presentation (October 2023)
44 slides from Mereo BioPharma's investor presentation, October 2023
Slide 1: Unlocking The Potential Of Novel Targets For Rare Diseases
Unlocking The Potential Of Novel Targets For Rare Diseases October 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 people living 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 – partne
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 in US and EU, PRIME (EU), Pediatric OI Cosmic ( 2 - <7 years yrs old ) disease Priority Review Voucher Alvelestat Orp
Slide 6: Rare Disease Day patient testimonial
“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 OIFE TOPICAL MEETING 2023
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
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: Orbit Phase 2 study and Open Label Extension study design
Orbit Phase 2 study and Open Label Extension 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
Slide 13: 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 20 mg/kg • 1.0 Z-score is equal to 1 standard deviation of the population 13
Slide 14: Continuous increase in lumbar spine BMD and z-score through month 6
Continuous increase in lumbar spine BMD and z-score through month 61 • No significant differences were 1 1 observed between setrusumab dose groups • Percentage change in BMD at month 6: - 20 mg/kg group=13% - 40 mg/kg group=16% • Change in BMD Z-score at month 6: - Both dose groups = 0.85 P-values r
Slide 15: Increase in BMD Observed in all Age Groups
Increase in BMD Observed in all Age Groups1,2 Greatest increase observed in patients between 5 and 12 years of age Lumbar Spine BMD Lumbar Spine BMD Z-score Percent Change from Baseline to Month 62 Change from Baseline to Month 61 Mean (SE) Lumbar Spine BMD Z-score 25 19.64 1.6 1.19 Mean (SE) Lumbar
Slide 16: 67% reduction in Annualised Fracture Rate post-treatment with Setrusumab
67% reduction in Annualised Fracture Rate post-treatment with Setrusumab1 1 • Median total confirmed Annualised Fracture Rate post-treatment is 0.0 • 67% reduction in annualized fracture rate, excluding fingers, toes, face, and skull • Mean treatment duration of 9 months (6 - 16 months) in 24 patien
Slide 17: 20/24 patients did not have radiographically confirmed fractures after treatment
20/24 patients did not have radiographically confirmed fractures after treatment with setrusumab1 Radiographically Confirmed Fractures Patients without Confirmed Fractures by 6 months1 Patients with Confirmed Fractures by 6 months1 5 5 Confirmed Fracture Rate* Annualized Radiologically Confirmed Fra
Slide 18: Safety evaluation
Safety evaluation No No unexpected No subject No drug-related treatment-related adverse events or discontinued treatment hypersensitivity SAEs safety concerns for any adverse event reactions Most common adverse events (AEs) reported*1 Adverse Event Phase 2 Patients (N=24) Infusion-related event (not
Slide 19: Patient with increased mobility after 17 months on study
Patient with increased mobility after 17 months on study 6 year old male with Type IV OI In addition – other high impact events did not result in fractures High-impact motor vehicle accident Patient fell down a flight of stairs with a backpack at at Month 5.5 of treatment resulted in no fractures Mo
Slide 20: Orbit Study – Phase 3
Orbit Study – Phase 3* Designed to evaluate the efficacy and safety of setrusumab vs. placebo in children and young adults with OI Approximately 195 subject ages 5 to < 26 years with Patients with at least 2 fractures over prior 24 months OI Types 1, III, or IV and a confirmed COL1A1 or will be enro
Slide 21: Cosmic Study – Phase 3
Cosmic Study – Phase 3* Designed to evaluate the efficacy and safety of setrusumab vs. bisphosphonates in young children with OI Approximately 66 subject ages 2 to < 7years with OI Patients with at least 2 fractures over prior 24 months Types 1, III, or IV and a confirmed COL1A1 or COL1A2 will be en
Slide 22: Ultragenyx – Mereo partnership and long-term plan
Ultragenyx – Mereo partnership and long-term plan Mereo – Ultragenyx partnership Mereo territories & focus Significant market opportunity • Ultragenyx leads and funds global • Groundwork for reimbursement of • OI affects approximately 60,000 development plan setrusumab in Europe and UK pediatrics an
Slide 23: Alvelestat (MPH966)
—Sw Mereo BioPharma ~~ Alvelestat (MPH966)
Slide 24: Alpha-1 Antitrypsin Deficiency-associated Lung Disease – high unmet need
Alpha-1 Antitrypsin Deficiency-associated Lung Disease – A rare progressive lung disease with high unmet need Alpha-1 Support Group UK, Information Day 2023
Slide 25: 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 t
Slide 26: 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 27: 12 week studies of alvelestat in AATD-Lung Disease
12 week studies of alvelestat in AATD-Lung Disease ASTRAEUS – Enrolled PI*ZZ patients not on augmentation Placebo bid N=36 Randomization Alvelestat 120 mg bid N=22 N=99 Alvelestat 240 mg bid N=41 Clin Trials Identifier: NCT03636347 ATALANTa Investigator-led study – Mark Dransfield, University of Ala
Slide 28: Disease activity biomarkers % change from baseline at Week 12
Disease activity biomarkers % change from baseline at Week 12 ASTRAEUS ATALANTa • Consistent with ASTRAEUS data at the 120 mg dose • No significant change from baseline in desmosine • Significant change from baseline in Aα-Val 360 (p=0.03), no other significant changes Aα-Val360 Desmosine Statistica
Slide 29: Blood NE Activity – Week 12
Blood NE Activity – Week 12 ASTRAEUS – P values % CFB at week 12 120 mg 240 mg Vs. baseline 0.026 <0.001 Vs. placebo 0.023 <0.001 ATALANTa – P values CFB at week 12 120 mg Subgroup* Vs. baseline 0.0005 0.058 • Significant suppression at both doses Vs. placebo 0.0059 NS • Suppression demonstrated on
Slide 30: ATALANTa – Patient Reported Outcomes
ATALANTa – An Investigator-led study – Patient Reported Outcomes • Improvement in SGRQ-Activity domain was observed • Pre-defined sub-group analysis in patients not on augmentation met statistical significance (p=0.0106 versus placebo) • No effect observed in patients on augmentation • Link of a cli
Slide 31: ATALANTa – Safety data consistent with ASTRAEUS
ATALANTa – Safety data consistent with ASTRAEUS including on top of augmentation Alvelestat Placebo N= 32 N= 31 #events (#subjects) #events (#subjects) AE 70 (25) 65 (23) Deaths 0 0 SAES 0 0 TEAE 70 (25) 64 (23) AESI 6 (5) 12 ( 11) Related TEAE 24 (15) 23 (10) Serious Related TEAE 0 0 Withdrawal due
Slide 32: Linking ASTRAEUS change in Desmosine to CT-density decline
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 33: 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 33
Slide 34: Summary and next steps
Summary and next steps • ASTRAEUS and ATALANTa Phase 2 studies consistent in activity of alvelestat on biomarkers of AATD-LD and safety • ATALANTa demonstrates suppression of neutrophil elastase and safety on top of augmentation at the 120 mg dose and confirms potential impact of alvelestat on the S
Slide 35: Etigilimab (MPH313)
—Sw Mereo BioPharma ~~ Etigilimab (MPH313)
Slide 36: 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 37: ACTIVATE – Efficacy data: Select cohorts
ACTIVATE – Efficacy data: Select cohorts* Disease Control Rate (CR+PR+SD) = 21 of 40 (52.5%) All responses confirmed *Efficacy analysis set: Best Observed Response (BOR) by investigator-assessed response per RECIST 1.1/clinical ^Cervical cancer patient (E025) enrolled in TMB-H cohort with PD-L1 CPS>
Slide 38: ACTIVATE – Select cohorts
ACTIVATE – Select cohorts Median time on treatment for EC-N, cervical, GCT, “ Sarcoma subjects only include those with De-differentiated liposarcoma de-differentiated liposarcoma, uveal patients ^Cervical cancer patient (E025) enrolled in TMB-H cohort with PDL-1 CPS>1% ^^Endometrial cancer – CPI naï
Slide 39: 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 40: EON Investigator led Study in Clear Cell Ovarian Carcinoma
EON Investigator led Study at MD Anderson Phase 1b/2 in Clear Cell Ovarian Carcinoma Two Stage Phase 1/2 Design with stopping boundaries for efficacy and toxicity Based on responses from initial 10 patients, study is being expanded to 20 patients 40
Slide 41: Other programs – Partnerships overview
Other programs – Partnerships overview Current partnerships • Navicixizumab global rights out-licensed to OncXerna for further development • Payments of up to $300 million in milestones plus royalties • OncXerna initiated a Phase 2 basket study in a range of solid tumors in 2H 2022 Partnering opport
Slide 42: 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 Phase 2 OL – update OI Phase 3 Cosmic study (2-<7 yrs old) Phase 3 data Phase 2 ASTRAEUS EOP2 Ongoin
Slide 43: Financial highlights
Financial highlights Cap Table ADSs1 (September 30, 2023) (in thousands) Shareholders > 2% holding 61,638 Shareholders < 2% holding 78,539 Cash runway into 2026 Share capital – Issued and outstanding 140,177 $62.4 million as of September 30, 2023 Potential Future Dilution: Warrants2 1,360 Convertibl
Slide 44: 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 (October 2023) on 6ix