Mereo BioPharma Group plc · NASDAQ:MREO
Mereo BioPharma — Investor Presentation (August 2024)
47 slides from Mereo BioPharma's investor presentation, August 2024
Slide 1: Corporate presentation
Corporate presentation August 2024
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: Unlocking the potential of novel targets for rare diseases
Unlocking the potential of novel targets for rare diseases Our mission is to improve the lives of people living with rare diseases
Slide 4: Strategic principles guide our journey
Strategic principles guide our journey • Acquire and develop programs in rare diseases with high prevalence – partner of choice for in-licensing • Focus on our core competencies and experience in rare diseases • Develop pipeline of rare disease programs which have already received significant invest
Slide 5: A late-stage rare disease company with a capital efficient model
A late-stage rare disease company with a capital efficient model Achievements and fundamentals Two rare disease programs in-licensed and progressed to pivotal stage: • Setrusumab for Osteogenesis Imperfecta (OI) in Phase 3 under a partnership with rare disease leader Ultragenyx • Alvelestat for Alph
Slide 6: A late-stage company with validating partnerships
A late-stage company with validating partnerships Corporate development Management team with a proven track record in corporate development • Setrusumab acquired from Novartis • Alvelestat in-licensed from AstraZeneca • Setrusumab partnered with Ultragenyx whilst retaining European rights • Navicixi
Slide 7: 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 candidate Setrusumab Orphan drug Orbit (5 -25 yrs old) designation in US and Osteogenesis EU, PRIME (EU), Imperfecta Cosmic (2 - <7 yrs old) Pediatric disease Priority Review Voucher designation Alvelestat*
Slide 8: Patient testimonial, Brittle Bone Society
“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 9: Setrusumab (UGX143)
OIFE Topical Meeting Setrusumab (UGX143) June 2023 Osteogenesis Imperfecta: a rare genetic bone condition with no FDA or EMA approved therapy
Slide 10: A rare genetic bone condition with a high unmet need
A rare genetic bone condition with a high unmet need Osteogenesis Imperfecta Market Opportunity • 80-90% linked to a mutation in Type I • Affects approximately 60,000 individuals3 collagen1,2 (Type I, III and IV) (pediatrics and adults) in the US and • Frequent bone fractures, skeletal Europe deform
Slide 11: Setrusumab – Mechanism of Action
Setrusumab – Mechanism of Action Increased BMD and bone strength, decreased fracture rate 11
Slide 12: Phase 2b ASTEROID study in adults with OI
Phase 2b ASTEROID study 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 12 6 Lumbar Spine Total Hip Femoral Neck Mean (SEM) Change From Baseline at Month 12, % *** * 10 8 *** 4 ** ** * 6 109 patien
Slide 13: Orbit Phase 2 – BMD and Z-score mean increase through month 12
Orbit Phase 2 – BMD and Z-score mean increase through month 121 Improvements consistent across all OI Types studied Lumbar Spine BMD1 Lumbar Spine BMD1 % Change from Baseline Z-Score Change from Baseline 1.25 ± 0.17 22.25 ± 2.71 p<0.0001 p<0.0001 0.85 ± 0.13 14.19 ± 2.15 0.58 ± 0.10 9.16 ± 1.43 Chan
Slide 14: Orbit Phase 2 – increase in BMD observed in all age groups
Orbit Phase 2 – increase in BMD observed in all age groups,1,2 Greatest increase in patients 5-12 years of age Lumbar Spine BMD by Age Group % Change from Baseline to Month 12 Data consistent with ASTEROID Phase 2 data in adults2 Age Groups 1. Data as of June 2024; 2. Lewiecki EM et al. Evaluating S
Slide 15: 67% reduction in annualized fracture rate with setrusumab
Treatment with setrusumab (mean duration of 16 months) resulted in a 67% reduction in annualized fracture rate (AFR) compared to pre-treatment AFR 6 y/o male patient with Type IV OI, increased mobility after 17 months on study 15
Slide 16: Safety evaluation shows setrusumab is well tolerated
Safety evaluation at 14 months shows setrusumab is well tolerated 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 at 6 months*1 Adver
Slide 17: Orbit study – Phase 3 is fully enrolled
Orbit study – Phase 3* is fully enrolled To evaluate the efficacy and safety of setrusumab vs. placebo in children and young adults with OI Enrolled 158 subjects ages 5 to 25 years Patients with at least 1 fracture in prior 12 with OI Types I, III, or IV and a confirmed months or 2 fractures in prio
Slide 18: Cosmic study – Phase 3 is fully enrolled
Cosmic study – Phase 3* is fully enrolled To evaluate the efficacy and safety of setrusumab vs. bisphosphonates in young children with OI Enrolled 69 subjects ages 2 to < 7 years Patients with at least 1 fracture in prior 12 with OI Types I, III, or IV and a confirmed months or 2 fractures in prior
Slide 19: The Ultragenyx partnership, a highly effective collaboration
The Ultragenyx partnership, a highly effective collaboration Key terms • Signed in December 2020 • Ultragenyx leads and funds the global development plan, including CMC • Mereo retains European rights (including UK) and Ultragenyx has the USA and Rest of the World rights • Mereo received $50M upfron
Slide 20: Critical steps toward commercialization
Critical steps toward commercialization Navigating the EU regulatory and access pathways to unlock value across the region Sequential process to de-risk the program and build the data sets that HTA committees and payors will require. Regulatory/ Engaged early (since 2019) and regularly with stakehol
Slide 21: Alvelestat (MPH966)
Alpha 1 Support Group UK Alvelestat (MPH966) Information Day September 2023 Alpha-1 Antitrypsin Deficiency-associated Lung Disease: a rare progressive lung disease with high unmet need
Slide 22: 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 results in risk of progressive lung damage and early onset emphysema Current treatments create Significant market Disease overview high unmet need opportunity • Presents age 20 to 50, • Currently COPD treated and • US AAT augm
Slide 23: Alvelestat – clinical trials in ~2,000 subjects
Alvelestat – 16 clinical trials in ~2,000 subjects • Phase 1 (6 studies) Phase 2 Bronchiectasis (Stockley et al 2013) o Safety, PK and pharmacodynamics support safety and • 60 mg alvelestat or placebo BD for 4 weeks dose-decisions • 38 randomized, 16 alvelestat, 22 placebo • Phase 2 (9 completed, 1
Slide 24: AATD – Progressive lung disease driven by Neutrophil Elastase
AATD – Progressive lung disease driven by Neutrophil Elastase HEALTHY AAT DEFICIENCY Alvelestat an Oral Neutrophil Elastase (NE) Inhibitor Lungs • Targets the cause of lung damage • Potential to treat early stages of lung disease to delay progression AAT protects lung Unopposed NE leads from Neutrop
Slide 25: Two Phase 2 studies in AATD-Lung Disease completed
Two Phase 2 studies in AATD-Lung Disease completed across different populations Placebo bid ASTRAEUS No subjects on augmentation NCT03636347 Patients with established disease Alvelestat 120 mg bid 12 weeks Baseline scores (median): N=99 FEV1 - 59% Alvelestat 240 mg bid *SGRQ total score – 32.2 Enrol
Slide 26: Alvelestat suppression of Blood Neutrophil Elastase Activity
Alvelestat suppression of Blood Neutrophil Elastase Activity Rapid and consistent suppression with dose response • 120 mg reduction at week 12 ASTRAEUS p<0.05 (vs placebo) • 240 mg reduction at week 12 ASTRAEUS <0.001 (vs placebo) • 240 mg met target > 90% NE suppression in blood 26
Slide 27: Biomarkers and PK modelling confirm 240 mg dose
Biomarkers and PK modelling confirm 240 mg dose for progression ASTRAEUS (Primary Endpoints) ASTRAEUS • 240 mg – progressive reduction in Aα-Val360 Desmosine biomarkers of NE-driven protein breakdown (A-val360 ) and elastin turnover (desmosine) • 120 mg – no effect on desmosine ATALANTa • Consisten
Slide 28: Safety data from two AATD Phase 2 studies
Safety data from two AATD Phase 2 studies, builds on extensive safety database Alvelestat 240 mg Alvelestat 120 mg Placebo N=40 (%) N=54 (%) N=67 (%) SAE 3 (7.5) 1 (1.9) 0 (0) Adverse Events of 11 (27.5) 10 (18.5) 18 (26.9) Special Interest Infections requiring antimicrobial 10 (25.0) 10 (18.5) 18 (
Slide 29: Outcome of End-of-Phase 2 and Type C meetings
Outcome of End-of-Phase 2 and Type C meetings Phase 3 design • End-of-Phase 2 meeting with FDA and scientific advice (EMA) to discuss endpoints for Phase 3 registrational trial • Subsequent Type C meeting held with the FDA and DCOA* • Additional communications following Type C meeting • SGRQ Total (
Slide 30: Association of alvelestat treatment with improvement in SGRQ
Association of alvelestat treatment with improvement in Respiratory Health Status (SGRQ) • St. George's Respiratory Questionnaire – Patient reported outcome in COPD recognized by FDA o Total score = Activity, Symptoms and Impacts domains o Activity domain most impacted in patients with AATD • Potent
Slide 31: Earlier stage lung disease patients show greater SGRQ response
Earlier stage lung disease patients show greater SGRQ response ATALANTa study (non-augmentation • ATALANTa study – Non-augmentation subgroup (median subgroup) – Change in SGRQ Total Score FEV1 89.3%). Between group changes at week 12: • SGRQ Total = 4.7-point improvement (p=0.10) • SGRQ Activity = 1
Slide 32: Mereo's approach to Phase 3
Historical augmentation studies Mereo’s approach to Phase 3 Limited to FEV1 <70% or <80% No upper FEV1 limit (Average FEV1 in RAPID, EXACTLE ~50%) • FEV1 – weighting towards patients >75% • Patients earlier in their disease not eligible • More patients eligible, including those not eligible • Interv
Slide 33: Translating desmosine changes to CT efficacy endpoint
Translating desmosine changes (elastin) to CT efficacy endpoint Significant correlation of desmosine reduction and rate of lung tissue loss by CT Augmentation Alvelestat (240 mg, ASTRAEUS) density in AATD1 therapy1 Desmosine Month 3 -0.013 ng/ml -0.028 ng/ml† (absolute reduction from baseline, Study
Slide 34: Development strategy for Phase 3 registrational trial
Development strategy for Phase 3 registrational trial Earlier stage severe PI*ZZ patients observed to have greater response in SGRQ Total and Activity scores Clinical data Literature indicates that earlier stage patients with higher FEV1 may be more likely to show spirometry benefit Study population
Slide 35: Other programs, milestones and financials
Other programs, milestones and financials
Slide 36: Key milestones for core programs
Key milestones for core programs Product 2023 2024 2025 Next milestone candidate H1 H2 H1 H2 H1 H2 Setrusumab Phase 2 Orbit (5 - <26 yrs old) Additional Phase 2 Orbit data OI Phase 3 Orbit (5 - 25 yrs old) Phase 3 Interim analysis Phase 3 Cosmic (2 - <7 yrs old) Phase 3 Interim analysis Alvelestat P
Slide 37: Other programs
Other programs Other current partnerships Navicixizumab – global rights out-licensed to Feng Biosciences for further development in ovarian cancer • Payments of up to $300 million in milestones plus royalties Leflutrozole – global rights out-licensed to ReproNovo for further development • ReproNovo
Slide 38: Financial highlights
Financial highlights Cap Table ADSs (June 2024) (in thousands) Shareholders > 2% holding 79,675 Shareholders < 2% holding 74,089 Cash runway into 2027 Share capital – Issued and outstanding $87.4 million as of as of June 30, 20241 153,764 June 30, 2024 Potential Future Dilution: Warrants2 1,401 Conv
Slide 39: Thank you
Thank you With a special thank you to members of our community, who generously agreed to be featured in this presentation.
Slide 40: Appendix
APPENDIX Mereo BioPharma
Slide 41: Etigilimab (MPH313)
Etigilimab (MPH313) Anti-TIGIT antibody in development in combination with anti-PD1
Slide 42: Etigilimab: an Anti-TIGIT antibody 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 T
Slide 43: 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 progression; data cut-off 3/29/2023. ^ Includes 1 TMB-H cervical pt E025 w
Slide 44: ACTIVATE efficacy data: select cohorts (continued)
ACTIVATE efficacy data: select cohorts (continued) ^Cervical cancer patient (E025) enrolled in TMB-H cohort with PD-L1 CPS>1% ^^ Endometrial cancer – CPI-naïve patient (G101) enrolled in post-CPI cohort ^^ Sarcoma subjects only include those with de-differentiated liposarcoma + best overall response
Slide 45: ACTIVATE efficacy data: select cohorts (continued)
ACTIVATE efficacy data: select cohorts (continued) Median time on treatment for EC-N, cervical, GCT, de-differentiated liposarcoma, uveal patients “ Sarcoma subjects only include those with De-differentiated liposarcoma • CR (3 pts) = 11.5 months ^Cervical cancer patient (E025) enrolled in TMB-H coh
Slide 46: EON investigator-led study at MD Anderson in Clear Cell Ovarian Carcinoma
EON* investigator-led study at MD Anderson Phase 1b/2 in Clear Cell Ovarian Carcinoma Etigilimab + On-combination treatment tumor Pre-treatment tumor expression express and immuno-profiling Recurrent platinum resistant Nivolumab clear cell ovarian carcinoma and immuno-profiling Two-stage design: Unt
Slide 47: Mereo BioPharma Group plc
Mereo BioPharma Group plc 4th Floor, One Cavendish Place London W1G 0QF United Kingdom +44(0)333 023 7300
Mereo BioPharma Group — Investor Presentation (August 2024) on 6ix