Mereo BioPharma Group plc · NASDAQ:MREO
Mereo BioPharma — Investor Presentation (March 2024)
52 slides from Mereo BioPharma's investor presentation, March 2024
Slide 1: Corporate presentation
Corporate presentation March 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 and retain global or regional rights where pos
Slide 5: A mid-late-stage company with validating partnerships
A mid-late-stage company with validating partnerships Achievements and fundamentals Two rare disease programs in-licensed and ready for pivotal studies within five years • Setrusumab for Osteogenesis Imperfecta (OI) in Phase 3 under a partnership with rare disease leader Ultragenyx • Alvelestat for
Slide 6: A mid-late-stage company with validating partnerships
A mid-late-stage company with validating partnerships Corporate development Management team with a proven track record in rare diseases and corporate development • Setrusumab acquired from Novartis and alvelestat in-licensed from AstraZeneca • Setrusumab partnered with Ultragenyx whilst retaining Eu
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 - <26 yrs old) designation in US and OI EU, PRIME (EU), Cosmic (2 - <7 yrs old) Pediatric disease Priority Review Voucher designation Alvelestat Orphan drug designat
Slide 8: Patient community quote from Rare Disease Day event
“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 Osteogenesis Imperfecta • A rare genetic bone disease, mostly • Frequent bone fractures, skeletal linked to a mutation in Type I collagen1,2 deformities, pain, respiratory and gastric • Affects approximately problems 60,000
Slide 11: 80-90% of cases of OI caused by mutations that effect collagen
80-90% of cases of OI caused by mutations that effect collagen or collagen synthesis OI Population Gene Impact • Encodes Type I collagen2 • Different mutations lead to different phenotypes • Mutations leading to: COL1A1, 80-90%1,2 • Reduced synthesis of normal collagen in Type 1 (30-50%)6 COL1A22 •
Slide 12: Phenotypes are not a scale of severity
Phenotypes are not a scale of severity • Bones fracture easily • Initial classification as lethal at or shortly after birth, often • Normal or near-normal stature due to respiratory problems • Loose joints and muscle weakness • Some (historical) Type IIs now survive due to medical • Hearing loss pos
Slide 13: Setrusumab mechanism of action particularly well-suited for OI
Setrusumab mechanism of action particularly well-suited for OI 13
Slide 14: Phase 2b ASTEROID study in adults with OI Types I, III and IV
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 *** 4 ** ** 8 * 6 4 2 * 2 2.
Slide 15: Orbit Phase 2 study and Open Label Extension study design
Orbit Phase 2 study and Open Label Extension study design Phase 2 designed to determine setrusumab dosing strategy based on PK/PD, safety, and available BMD data in subjects with OI Patients Enrolled Stratification 24 patients ages 5 yrs to <26 yrs with OI Types I, Patients with at least 2 fractures
Slide 16: Younger patients in Orbit achieved increases in Lumbar DXA BMD
Younger patients in Orbit achieved increases in Lumbar DXA BMD at 3 months comparable to ASTEROID patients at 12 months • 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 16
Slide 17: Continuous increase in BMD and Z-score through month 6
Continuous increase in BMD and Z-score through month 61 Lumbar Spine BMD Lumbar Spine BMD %Change from Baseline Z-Score Change from Baseline • No significant differences were observed between setrusumab dose groups • Percentage change in BMD at month 6: - 20 mg/kg group=13% - 40 mg/kg group=16% • Ch
Slide 18: Increase in BMD observed in all age groups
Increase in BMD observed in all age groups,1,2 Greatest increase in patients 5-12 years of age Lumbar Spine Lumbar Spine BMD BMD LumbarSpine Lumbar Spine BMD BMD Z-score Z-score Percent Percent Changefrom Change from Baseline Baseline to toMonth Month6262 Change Change rom Baseline from Baseline to
Slide 19: 20/24 patients did not have radiographically confirmed fractures
20/24 patients did not have radiographically confirmed fractures after 6 months treatment with Setrusumab1 Radiographically confirmed fractures Patients without confirmed fractures by Patients with confirmed fractures by 6 months1 6 months1 5 5 Annualized Radiologically Annualized Radiologically A C
Slide 20: Annualized Fracture Rate post-treatment with Setrusumab
Annualized Fracture Rate post-treatment with Setrusumab1 • Median total confirmed Annualized 1 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 patients median(AFR pos
Slide 21: Safety evaluation shows setrusumab is well tolerated
Safety evaluation 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*1 Adverse Event Phase 2 Patients
Slide 22: Patient with increased mobility after 17 months on study
Patient with increased mobility after 17 months on study In addition…other high impact events Six-year-old male with Type IV OI did not result in fracture Other high impact events: • High-impact motor vehicle accident at Month 5.5 of treatment resulted in no fractures • Patient fell down a flight of
Slide 23: 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 150 subjects ages 5 to < 26 Patients with at least 2 fractures over prior years with OI Types I, III, or IV and a 24 months will be enrolled and confirmed
Slide 24: 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 60 subjects ages 2 to < 7 Patients with at least 2 fractures over prior years with OI Types I, III, or IV and a 24 months will be enrolled and confirmed COL1
Slide 25: Mereo – Ultragenyx partnership
Mereo – Ultragenyx partnership Key terms • Signed in December 2020 • Ultragenyx leads and funds the global development plan, including CMC • Mereo retains European rights (including UK) and Ultragenyx the USA and Rest of the World rights • Mereo received $50M upfront with potential additional $245M
Slide 26: Mereo – Ultragenyx partnership and long-term plan
Mereo – Ultragenyx partnership and long-term plan Mereo territories and focus Significant market opportunity • Groundwork for reimbursement of setrusumab • OI affects approximately 60,000 pediatrics and in Europe and UK adults in the US and Europe • Intensive engagement with highly networked • Mereo
Slide 27: 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 28: 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 Significant market AATD-LD High unmet need opportunity • Presents age 20 to 50, • Currently COPD treated and • US AAT augmentation shortness of breath, cough
Slide 29: Alvelestat – a potent, oral inhibitor of Neutrophil Elastase
Alvelestat – a potent, oral inhibitor of Neutrophil Elastase Healthy Alveolus • Alpha-1 antitrypsin (AAT) produced in the liver, released to blood and lungs • AAT protects from Neutrophil Elastase (NE) – a protease that drives tissue destruction in lung AAT Deficiency • Lack of AAT – unopposed NE an
Slide 30: Two Phase 2 studies of alvelestat in AATD-Lung Disease completed
Two Phase 2 studies of alvelestat in AATD-Lung Disease completed ASTRAEUS – Enrolled PI*ZZ patients not on augmentation, 12 weeks Placebo bid N=36 Randomization Alvelestat 120 mg bid N=22 N=99 Alvelestat 240 mg bid N=41 Clinical Trials Identifier: NCT03636347 ATALANTa Investigator-led study – Mark D
Slide 31: Comparison of ATALANTa and ASTRAEUS patient populations
Comparison of ATALANTa and ASTRAEUS patient populations ATALANTa was a US study, ASTRAEUS enrolled predominantly in EU • Augmentation available in the US unlike in many EU countries and the UK • Augmentation population in ATALANTa is similar to the population enrolled in ASTRAEUS • Non-Augmentation
Slide 32: ASTRAEUS Phase 2 study – Dose-related effects on Neutrophil Elastase
ASTRAEUS Phase 2 study – Dose-related effects on Neutrophil Elastase activity and Disease Activity Biomarkers by 12 weeks (Per Protocol Set) Neutrophil Elastase Aα-Val360 Desmosine • 240 mg, but not 120 mg dose, met target > 90% NE suppression in blood • PK predicts 240 mg achieves target drug level
Slide 33: CT-density: Linking ASTRAEUS data to the RAPID study
CT-density: Linking ASTRAEUS data to the RAPID study Reduction in the biomarker desmosine for Significant correlation of change in desmosine 240 mg alvelestat at 12 weeks at 2 years and lung density decline by CT* comparable to Augmentation therapy at 12 months Augmentation Alvelestat (240mg, therap
Slide 34: Biomarker data from ATALANTa confirm dose selection for Phase 3
Biomarker data from ATALANTa confirm dose selection for Phase 3 (Full Analysis Set) ATALANTa Phase 2 Study • Addition inhibition of NE activity observed in patients on augmentation therapy • With 120 mg dose a significant change (reduction) from baseline in Aα-Val360 (p=0.03) observed o Improved com
Slide 35: St George's Respiratory Questionnaire (SGRQ)
St George's Respiratory Questionnaire (SGRQ) • Validated patient reported outcome in COPD recognized by ATALANTa study (non-augmentation FDA comprising Total Score made up from Activity, subgroup) – Change in SGRQ Total Score Symptoms and Impacts domain scores • ATALANTa study – greater effect in no
Slide 36: Earlier stage patients – greater SGRQ change and potentially FEV1
Earlier stage patients – greater SGRQ change and potentially FEV1 ASTRAEUS Study Fraughen et al, Nov 2023* In addition to effects observed in earlier stage patients Multinational registry retrospective analysis (N=615, in the ATALANTa study, post hoc analysis of baseline N=365 never received AAT). F
Slide 37: Consistent safety data in AATD-LD in ASTRAEUS and ATALANTa
Consistent safety data in AATD-LD in ASTRAEUS and ATALANTa ATALANTa ASTRAEUS Alvelestat 120mg Placebo Alvelestat 120mg Alvelestat 240mg Placebo N=32 N=31 N=22 N=40 N=36 subjects (%) subjects (%) subjects (%) subjects (%) subjects (%) SAE 0 0 1 (4.5) 3 (7.5) 0 Adverse Events of 5 (15.6) 11 (35.5) 5 (
Slide 38: Phase 3 endpoints
Phase 3 endpoints Phase 2 data to support Agency Phase 3 endpoints Phase 3 plan • Change in desmosine observed at European 240 mg dose in ASTRAEUS study Change in CT density Medicines Agency P<0.1 could be acceptable • Significant correlation of desmosine change to CT density change in (EMA) longtit
Slide 39: Development strategy for Phase 3 pivotal clinical trial
Development strategy for Phase 3 pivotal clinical trial Earlier stage severe PI*ZZ patients appear to have Phase 3 design greater response in SGRQ Total and Activity Clinical data Literature shows that earlier stage patients with higher FEV1 may be more likely to show spirometry • SGRQ Total Score a
Slide 40: Etigilimab (MPH313)
Etigilimab (MPH313) Anti-TIGIT antibody in development in combination with anti-PD1
Slide 41: Etigilimab: an Anti-TIGIT antibody in development 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 42: 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 43: 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 44: 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 45: Etigilimab shows robust target engagement in patients
Etigilimab shows robust target engagement in patients and exploratory biomarker correlation with clinical response Etigilimab shows robust target Baseline tumor expression: correlation engagement with reductions in target lesions % Change From Baseline CD226/CD8 Co-expression PVR Sarikonda et al, ES
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 On-combinatioion treatment tumor Etigilimab + Pre-treatment tumor expression express and immuno-profiling Recurrent platinum resistant Nivolumab clear cell ovarian carcinoma and immuno-profiling Two-stage design: U
Slide 47: Other programs, milestones and financials
Other programs, milestones and financials
Slide 48: Upcoming key milestones for core programs
Upcoming key milestones for core programs Product 2023 2024 Next milestone candidate H1 H2 H1 H2 Setrusumab Phase 2 Orbit (5 - <26 yrs old) Phase 2 OL data 2024 OI Phase 3 Orbit (5 - <26 yrs old) Phase 3 LPI ~ end Q1 2024 Phase 3 Cosmic (2 - <7 yrs old) Phase 3 LPI 2H 2024 Alvelestat Potential partn
Slide 49: Other programs: current partnerships
Other programs: current partnerships Other current partnerships Navicixizumab – global rights out-licensed to Feng Biosciences for further development • Payments of up to $300 million in milestones plus royalties Leflutrozole – global rights out-licensed to ReproNovo for further development • ReproN
Slide 50: Financial highlights
Financial highlights Cap Table ADSs1 (February 2024) (in thousands) Shareholders > 2% holding 77,469 Shareholders < 2% holding 62,788 Cash runway into 2026 Share capital – Issued and outstanding 140,257 $57.4 million as of December 31, 2023 Potential Future Dilution: Warrants2 1,360 Convertible loan
Slide 51: Thank you
Thank you With a special thank you to members of our community, who generously agreed to be featured in this presentation.
Slide 52: Mereo BioPharma Group plc
Mereo BioPharma Group plc 4th Floor, One Cavendish Place London W1G 0QF United Kingdom +44(0)333 023 7300
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