Mereo BioPharma Group plc · NASDAQ:MREO
Mereo BioPharma — Investor Day (May 2021)
112 slides from Mereo BioPharma's investor day presentation, May 13, 2021
Slide 1: Virtual R&D Day
Virtual R&D Day May 13th 2021 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 Virtual R&D Day - Agenda
Mereo Biopharma Virtual R&D Day - Agenda Welcome, introductions and Agenda - Denise Scots-Knight, PhD, CEO Mereo Biopharma Etigilimab : TIGIT as a target/MOA - John Lewicki, PhD, CSO Mereo Biopharma Biomarker strategy - Ann Kapoun, PhD, SVP Translational R&D Mereo Biopharma Etigilimab and the ACTIVA
Slide 4: Today's Speakers
Today’s Speakers Shannon Westin, MD, MPH Kathleen Moore, MD, MS, Priscilla Merriam, MD, Associate Professor of Gynecologic Director, Oklahoma TSET Phase 1 Clinical Director, Sarcoma Center, Oncology and Reproductive Medicine, Program, Associate Professor, Section of Dana-Farber Cancer Institute MD A
Slide 5: Mereo Biopharma: Late Stage Diversified Clinical Pipeline
Mereo Biopharma : Late Stage Diversified Clinical Pipeline Core Programs Product Candidate / Indication Phase 1a Phase 1b Phase 2 Phase 3 Next Milestones Etigilimab Phase 1b/2 Solid tumors Alvelestat Phase 2 AATD Alpha-1 antitrypsin deficiency Phase 1b/2 COVID COVID-19 Adult extension study Setrusum
Slide 6: Etigilimab
—Sw Mereo BioPharma ~~ Etigilimab
Slide 7: TIGIT is a negative regulator of T cell responses
TIGIT is a negative regulator of T cell responses T cell Immunoreceptor with Ig and ITIM domains (TIGIT) Negative regulator of T cell response: • Competes with CD226 for PVR, disrupts CD226 activation, and directly inhibits T cells Expressed on CD4, CD8 and NK cells and is elevated upon activation;
Slide 8: Etigilimab is an IgG1 anti-TIGIT antibody with inhibitory and ADCC characteristics
Etigilimab is an IgG1 anti-TIGIT antibody with inhibitory and ADCC characteristics Control Ab Effector function competent Effector function silent Mereo Biopharma Group plc 7
Slide 9: Mereo's Anti-TIGIT has key differentiating features
Mereo’s Anti-TIGIT has key differentiating features • Anti-TIGIT antibody designed to elicit anti-tumor activity via: - Activation of NK and T-cell subpopulations - Reduction of T-regulatory cells - Increased CD8/Treg ratio • Demonstrated key mechanisms of anti-TIGIT in a dose dependent manner in pr
Slide 10: Phase 1 Clinical Findings Safety and Biomarkers
Phase 1 Clinical Findings • Seven subjects (30%, n=23) had stable disease as their best response in single-agent Phase 1a - Majority of patients are heavily pretreated and have tumor types typically non-responsive to anti-PD1 agents - Clinical benefit observed at doses as low as 3 mg/kg with modest
Slide 11: Mereo's etigilimab has key differentiating features
Mereo’s etigilimab has key differentiating features High affinity Phase 1a and Phase 1b Advanced Biomarker dose escalation and capabilities in place IgG1 antibody safety data available • IgG1 backbone activates • Early clinical signals observed: • Target engagement of etigilimab antibody-dependent c
Slide 12: Biomarker Strategy
—Sw Mereo BioPharma ~~ BIOMARKER STRATEGY
Slide 13: Demonstration of Target Engagement in Phase 1a Patients
Demonstration of Target Engagement in Phase 1a Patients Etigilimab decreases Tregs and increases CD8/Treg ratio Etigilimab decreased the number of Treg Cells in circulation Etigilimab increases CD8/Treg ratio CD8:Treg Flow data shown, increase in CD8/Treg ration also observed by DNA methylation No c
Slide 14: Demonstration of Target Engagement in Phase 1a Patients
Demonstration of Target Engagement in Phase 1a Patients Etigilimab increases activation and proliferation of effector T cells and NK cells Etigilimab increased markers of cell proliferation in T and NK cells 13 Sharma et al, Huang et al
Slide 15: Etigilimab Reduces Cells Destined for Exhausted T-cell lineage in Phase 1a Patients
Etigilimab Reduces Cells Destined for Exhausted T-cell lineage in Phase 1a Patients Etigilimab reduces progenitor CD8 cells thought to be committed to exhausted-like fate • Exhausted and functional memory T cells arise from separate populations of stem-like progenitor committed to distinct fates • T
Slide 16: Biomarker capabilities in place
Biomarker capabilities in place Example TIGIT & PVR Immunohistochemistry • TIGIT biomarker single & multiplex IHC/IF assays developed with image analysis • These assays were used to survey large cohorts of tumor tissues for indication selection • Robust multiplex IHC assays and staining for PVR, TIG
Slide 17: Example Rare Tumors Analysis
Example Rare Tumors Analysis Sarcoma subtypes with high correlation of TIGIT and PD1 expression TCGA data 16
Slide 18: Immune Classification of Sarcoma Subtypes
Immune Classification of Sarcoma Subtypes Tumors assigned to distinct sarcoma immune classes (SIC) SIC E group - improved survival and high response rate to PD1 blockade with Pembro B cells strongest prognostic factor even in context of high or low CD8 T cells 17 Petitprez et al 2020 Nature
Slide 19: Biomarker Capabilities Established
Biomarker Capabilities Established • Biomarkers key component of indication selection for Phase1a/b basket trial • Demonstrated key mechanisms of anti-TIGIT in preclinical models and in patients treated with etigilimab • Dose dependent biomarker changes observed ➢ Activation of NK and T-cell subpopu
Slide 20: The ACTIVATE Study
—Sw Mereo BioPharma ~~ THE ACTIVATE STUDY
Slide 21: ACTIVATE Phase 1b/2 Study
ACTIVATE Phase 1b/2 Study ACTIVATE: A Phase 1b/2 Open-Label Study of the Efficacy and Safety of Etigilimab (MPH313) Administered in Combination with Nivolumab to Subjects with Locally Advanced or Metastatic Solid Tumors • Overview of study design • Key elements of differentiation strategy • Study st
Slide 22: ACTIVATE Phase 1b/2 Study Design: Etigilimab plus Nivolumab
ACTIVATE Phase 1b/2 Study Design: Etigilimab plus Nivolumab in Advanced/Metastatic solid Tumors Primary endpoint • Overall Response Rate Rare tumors (e.g.sarcomas) Secondary • Safety and Tolerability Ovarian • PK/PD Cervical* • Duration of response Endometrial Exploratory Gastric/GEJ* • Biomarker SC
Slide 23: Study Design: Decision Making
Study Design: Decision Making • Statistical rigor provided by Simon 2-step design: Stage 1 futility monitoring for progression to Stage 2 Clinically meaningful benchmark for Go/No-go beyond Stage 2 • Open label design allows for dynamic decision making • Totality of safety and efficacy data will be
Slide 24: Differentiated Clinical Strategy
Differentiated Clinical Strategy
Slide 25: Key Elements of Etigilimab Phase 1b/2: Differentiated Clinical Development
Key Elements of Etigilimab Phase 1b/2: Differentiated Clinical Development Gyn-onc indications ORR with Anti-PD-1 Monotherapy Cervical KN158 14% (KN158) • Focus on Checkpoint-naïve populations Ovarian KN100 8.1% ( </=2 prior lines); • Prioritize TIGIT expressing tumors by: 9.9% (3-5 prior lines) (i)
Slide 26: Key Elements of Etigilimab Phase 1b/2 Clinical Biomarker Strategy
Key Elements of Etigilimab Phase 1b/2 Clinical Biomarker Strategy Multi-Pronged Biomarker Approaches Prospective selection, established Cervical, gastric, SCCHN as per biomarker indication on label PD-L1 Prospective selection, emerging TMB-H/MSS tumors biomarker Retrospective evaluation by potential
Slide 27: ACTIVATE Study: Status Update
ACTIVATE Study: Status Update
Slide 28: ACTIVATE Study Status
ACTIVATE Study Status Indication 2021 2022 2023 Partner Milestone ACTIVATE - Phase 1b/2 full Etigilimab plus Solid tumors Phase 1b/2 basket study with potential cohort extension enrollment and nivolumab data Phase 2 cohort expansion Initial data Study fully Q4 enrolled •Adult ACTIVATE extension stud
Slide 29: MD Anderson & Cancer Focus Fund Collaboration
MD ANDERSON & CANCER FOCUS FUND COLLABORATION
Slide 30: Etigilimab – Cancer Focus Fund & MD Anderson Collaboration
Etigilimab – Cancer Focus Fund & MD Anderson Collaboration • Cancer Focus Fund, LP • Unique investment fund established in collaboration with The University of Texas MD Anderson Cancer Center. • Provides investment support to advance promising cancer therapies, clinical trial expertise and infrastru
Slide 31: Etigilimab - Cancer Focus Fund & MD Anderson Collaboration
Etigilimab - Cancer Focus Fund & MD Anderson Collaboration • Rationale : • Study runs in parallel to Mereo’s ACTIVATE study that has an ovarian cancer cell arm (which excludes clear cell) • Clear cell represents ~10% of ovarian carcinomas in US/EU • Ovarian cancer generally has poor treatment outcom
Slide 32: Clear Cell Ovarian Cancer
—Sw Mereo BioPharma ~~ CLEAR CELL OVARIAN CANCER
Slide 33: Opportunities for Etigilimab in Ovarian Cancer
Mereo Research and Development Day: Opportunties for Etigilimab in Ovarian Cancer Shannon N. Westin, MD, MPH Associate Professor Director, Early Drug Development and Phase 1 Trials Department of Gynecologic Oncology and Reproductive Medicine 32
Slide 34: Disclosure Information
Disclosure Information • Research Support: AstraZeneca, ArQule, Clovis Oncology, Novartis, Roche/Genentech, Cotinga Pharmaceuticals, GSK/Tesaro, Bayer, Bio- Path, Mereo • Consultant: Agenus, AstraZeneca, Clovis Oncology, Roche/Genentech, Novartis, Circulogene, Pfizer, GSK/Tesaro, Merck, Eisai, Zenta
Slide 35: Ovarian Cancer Basics
Ovarian Cancer Basics • Worldwide: 300,000 • Risk 1/75 34
Slide 36: Where does ovarian cancer originate?
Where does ovarian cancer originate? Germ Cell Stromal cells Surface Epithelium 35 Naora et al., 2005
Slide 37: Epithelial Ovarian Cancer: Histologies
Epithelial Ovarian Cancer: Histologies 90% of ovarian cancers are malignant epithelial tumors Low-grade serous Other Clear Cell Endometrioid High-grade Mucinous serous Prat and FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet. 2014 36
Slide 38: 2020 Treatment Paradigm: Frontline Therapy for Ovarian Cancer
2020 Treatment Paradigm: Frontline Therapy for Ovarian Cancer GOG218; ICON7 Active SOLO-1; PRIMA; PAOLA; VELIA surveillance D D IV paclitaxel and PARPi e i C C carboplatin a a H H g E E t IV paclitaxel and Bevacizumab h Symptoms n M M carboplatin and o Cure O O bevacizumab s Bevacizumab i IV paclita
Slide 39: Presence of TILs is associated with better clinical outcomes in OC
Presence of TILs is associated with better clinical outcomes in OC OC is immunogenic TILs* are associated with longer OS • TILs found at diagnosis 100 p<0.001 in ~55% of patients Overall survival (%) 75 • Spontaneous anti-tumour 50 Intratumoral T cells response reported in 25 some patients in clinic
Slide 40: The correlation between TILs and survival is supported by multiple clinical studies in OC
The correlation between TILs and survival is supported by multiple clinical studies in OC Independent of tumour grade, stage or histologic subtype1 HR HR Study or Subgroup Log [HR] SE Weight (%) [95% Cl] [95% Cl] Zhang (2003) 0.61 0.18 12.5 1.84 [1.29–2.62] Sato (2005) 1.11 0.307 8.8 3.03 [1.66–5.54
Slide 41: Mutational Load Matters
Mutational Load Matters 500 300 200 100 Somatic mutation burden 50 (mut/Mb) 10 5 1 • Red line indicates the threshold for samples with a high mutational burden (13.8 mutations/Mb) • Mb, megabase; OC, ovarian cancer 40 Zehir et al. Nat Med 2017
Slide 42: Rationale for targeting PD-L1 in OC
Rationale for targeting PD-L1 in OC Tumour mutations OC is associated with >50% of OC tumours increase tumour-specific mutational burden show TILs at diagnosis antigens Increased expression Anti-PDL1 or anti-PD1 of immune checkpoint Improved OC Immunosuppressive outcomes? modulators tumour (PD-L1 an
Slide 43: Anti-PDL1/PD1 have minimal activity as a single agent in OC
Anti-PDL1/PD1 have minimal activity as a single agent in OC Therapeutic agent Phase and trial name N Setting ORR, n/N (%) Ia Atezolizumab 12 PR ROC 2/8 (25) (PCD4989g)1 Ib Avelumab 75 ROC 8/75 (11) (JAVELIN solid tumour)2 II Nivolumab 20 PR ROC 3/20 (15) (UMIN000005714)3 Ib Pembrolizumab 26 ROC 3/26
Slide 44: Immunotherapy Combinations
Immunotherapy Combinations • Differential expression of checkpoints on immune cells • Differential downstream signaling that follows receptor activation • Opportunity for combination with checkpoint agonists Chen and Flies Nature Rev Immunology 2013, Rotte Annals Oncol 2018
Slide 45: Nivolumab and Ipilimumab in recurrent ovarian cancer
Nivolumab and Ipilumimab in recurrent ovarian cancer NRG GY003: Randomized phase II of nivolumab with or without ipilumimab for recurrent ovarian cancer (NCT 02498600 ) Response Rate R A Arm A Nivolumab 3mg/kg • Arm A: 12.2% (6/49) N D Q2wk • Arm B: 31.4% (16/51) O M Progression Free Survival I Z •
Slide 46: Preclinical evidence supports a role for TIGIT inhibition
Preclinical evidence supports a role for TIGIT inhibition Anti‐TIGIT treatment significantly improved the survival rates Anti-TIGIT Promotes Activation of CD8+ and CD4+ T Cells and of ovarian cancer mice induced by ID8 cells1 NK Cells in the Tumor Microenvironment CD155 and PD-L1 exhibit contrasting
Slide 47: Early clinical evidence demonstrates potential for use in ovarian cancer
Early clinical evidence demonstrates potential for use in ovarian cancer Phase 1a: Best % Reduction in Phase 1b: Best % Reduction in Target Lesion Size Target Lesion Size 120 Head and Neck Cancer, 20.0 m g/kg + nivolum ab Gastric Cancer, 20.0 m g/kg + nivolum ab 100 NSCLC, 3.0 m g/kg + nivolum ab RE
Slide 48: Plan for High Grade Serous
Plan for High Grade Serous Addition of arm to ongoing “A Phase 1b/2 Open-Label Study of the Efficacy and Safety of Etigilimab (MPH313) Administered in Combination with Nivolumab to Subjects with Locally Advanced or Metastatic Solid Tumors” 47
Slide 49: Novel opportunity: Clear Cell Ovarian Cancer
Novel opportunity: Clear Cell Ovarian Cancer • Younger age • 10% of all EOC • 67% Stage 1 • Chemoresistance • Molecular aberrations • PIK3CA mutations • ARID1A mutations • High mutation load 500 300 200 100 mutation burden 50 (mut/Mb) 48
Slide 50: Interesting signal in clear cell ovarian cancer
Interesting signal in clear cell ovarian cancer Therapeutic Phase and trial ORR, n/N agent name N Setting (%) Ia Atezolizumab 12 PR ROC 2/8 (25) (PCD4989g)1 Ib Avelumab (JAVELIN solid 75 ROC 8/75 (11) 2/2 CC pts tumour)2 II Nivolumab (UMIN0000057 20 PR ROC 3/20 (15) 1/2 CC pts 14)3 Ib Pembrolizum (K
Slide 51: Potential for combination success in clear cell ovarian cancer
Potential for combination success in clear cell ovarian cancer Association with clear cell histology and benefit from experimental arm/combination therapy 50
Slide 52: Plan for Clear Cell
Plan for Clear Cell EON: A Single-arm Phase II study of Etigilimab (OMP- 313M32) in Combination with Checkpoint Inhibition (Nivolumab) in Patients with Platinum-resistant, Recurrent Epithelial Ovarian Cancer 51
Slide 53: Two Stage Phase 1/2 BOP2 Design
Two Stage Phase 1/2 BOP2 Design • Stopping boundaries for efficacy and toxicity • Continuous monitoring of toxicity 52
Slide 54: Objectives
Objectives Primary - To estimate the objective response rate of the combination of etigilimab and PD-1/PD-L1 inhibitor in patients with clear cell ovarian cancer. - To evaluate the toxicity of the combination of etigilimab and PD-1/PD-L1 inhibitor in patients with clear cell ovarian cancer. 53
Slide 55: Objectives
Objectives Secondary - To determine PFS of the combination of etigilimab and PD-1/PD-L1 inhibitor in patients with platinum resistant clear cell ovarian cancer - To estimate the disease control rate of the combination of etigilimab and PD- 1/PD-L1 inhibitor in patients with platinum resistant clear
Slide 56: Key Inclusion Criteria
Key Inclusion Criteria - Patients with platinum refractory* and platinum resistant** high grade clear cell ovarian, fallopian tube or peritoneal carcinoma * Platinum refractory: progression during platinum-containing therapy or within 4 weeks of last dose ** Platinum resistant: relapse-free interval
Slide 57: Conclusions
Conclusions • There are critical opportunities to improve outcomes in ovarian cancer • Improving activity of checkpoint inhibition in high grade serous • Potential registration pathway for clear cell subtype • Transition to upfront therapy if activity in the recurrent setting • Translational studies
Slide 58: Thank you
Thank you @ShannonWestin [email protected] 57
Slide 59: Cervical Cancer
—Sw Mereo BioPharma ~~ CERVICAL CANCER
Slide 60: Management of Advanced Cervical Cancer
MANAGEMENT OF ADVANCED CERVICAL CANCER Kathleen N. Moore, MD Associate Director, Clinical Research Director, TSET Phase I Drug Development Unit Stephenson Cancer Center at the University of Oklahoma Director, Gynecologic Fellowship Division of Gynecologic Oncology 59
Slide 61: Cervical Cancer in an International Health Concern
Cervical Cancer in an International Health Concern Jung HS et al. J Clin Med. 2015. 4(5): 1126 60
Slide 62: An Estimated 13,800 Cases of Invasive Cervical Cancer in the US in 2020
An Estimated 13,800 Cases of Invasive Cervical Cancer in the US in 2020 ✓ Death rate in 2016 (2.2 per 100,000) was less than half that in 1975 (5.6 4290Deaths per 100,000) ✓ From 2007 to 2016, the death rate decreased by about 1% per year in women > 50 years of age and older, but was stable in < 50
Slide 63: Cervical Cancer: Summary of Treatment
Cervical Cancer: Summary of Treatment Initial Diagnosis Colposcopy / Biopsy Cervical Locally Advanced Dysplasia Early disease 46%2 Disease 36%2 Metastatic Disease 15%2 CIN 2 / CIN 3 FIGO IA1 FIGO IA2 FIGO IB2 + IIA FIGO IB3 /IIB /IIIB FIGO IVA FIGO IVB Cone Biopsy Platinum-based Cryotherapy Surgery
Slide 64: Mutational Burden Compared With Other Tumors
63 Alexandrov LB, et al. Nature. 2013;500(7463):415-421. Mutational Burden Compared With Other Tumors Melanoma Lung squamous Lung adenocarcinoma Bladder Lung small cell Esophagus Colorectum Cervix Head and neck Stomach Uterus Liver Kidney clear cell Kidney papillary Ovary Prostate Myeloma Lymphoma B
Slide 65: Evolution of 1L metastatic Cervical Cancer Treatment
Evolution of 1L metastatic Cervical Cancer Treatment Design N ORR (%) PFS P-value OS P-value Reference (months) (months) Bev + PC or TP 227 48 8.2 17.0 GOG 240 Study 0.0002 0.0004 vs. PC or TP 225 36 5.9 13.3 Tewari et al., NEJM.2014 PC vs. 121 -- 6.9 18.3 JCOG 0505 Study 0.053 0.032 Carbo/Pacli 123
Slide 66: GOG 240
GOG GO GOG 240 Paclitaxel 135 or 175 mg/m2 IV I Cisplatin 50 mg/m2 IV R Chemo alone Carcinoma of the cervix Paclitaxel 135 or 175 mg/m2 IV • Primary stage IVB A • Recurrent/persistent N II Cisplatin 50 mg/m2 IV • Measureable disease D O Bevacizumab 15 mg/kg IV • GOG PS 0-1 q 21 d Rx to PD, • No prio
Slide 67: GOG 240: Mature OS
140 Online Supplement Figure 2. Kaplan-Meier curves depicting the intent-to-treat final protocol-specified 141 survival among patients not previously treated with pelvic radiation with and without bevacizumab. 142 GOG 240 : Mature OS 143 144 145 146 ITT 147 Not Previously Irradiated 148 149 150 151
Slide 68: GOG 240 Mature Post-Progression OS
GOG 240 Mature Post-Progression OS Varies between 6.2 months to 8.7 months ITT All 4 Arms HR 0.83 (95% CI 0.60-1.15); P = .13 HR 0.84 (95% CI 0.60-1.17); P = .14 HR 0.83 (95% CI 0.66-1.05); P = .06 67 Tewari KS, et al. Lancet. 2017;390(10103):1654-1663.
Slide 69: Regimen for 2L+ Metastatic Cervical Cancer
Regimen for 2L+ Metastatic Cervical Cancer Design N ORR (%) PFS (months) OS (months) Topotecan 45 12.5 2.1 6.6 Vinorelbine 44 13.7 NS NS Pemetrexed 29 15 3.1 7.4 Pemetrexed 43 13.9 2.3 8.05 Docetaxel 27 8.7 3.8 7.0 Gemcitabine 22 4.5 2.1 6.5 Bevacizumab 46 10.9 3.4 7.29 Pembrolizumab 77 14.3 -- -- 1
Slide 70: The Cancer Immunity Cycle
The Cancer Immunity Cycle Engineering Anti-tumor Immunity to Treat Cancer with Cell based Therapies Chen DS, Mellman I. Oncology meets immunology: the cancer- immunity cycle. Immunity. 2013 Jul 25;39(1):1-10 69
Slide 71: The Cancer Immunity Cycle
The Cancer Immunity Cycle Engineering Anti-tumor Immunity to Treat Cancer with Cell based Therapies Chen DS, Mellman I. Immune Check Oncology meets immunology: the cancer- Point immunity cycle. Immunity. 2013 Jul Inhibition 25;39(1):1-10 PD-1, PDL-1 Blockade TIGIT is emerging 70
Slide 72: The Cancer Immunity Cycle
The Cancer Immunity Cycle Engineering Anti-tumor Immunity to Treat Cancer with Cell based Therapies Adoptive Cell Therapy TIL, CAR, TCR Chen DS, Mellman I. Immune Check Oncology meets immunology: the cancer- Point immunity cycle. Immunity. 2013 Jul Inhibition 25;39(1):1-10 PD-1, PDL-1 Blockade 71
Slide 73: KEYNOTE-158: Phase II basket study, cervical cancer cohort
KEYNOTE-158 (NCT02628067): Phase II basket study, single-agent pembrolizumab, cervical cancer cohort • Advanced cervical squamous cell carcinoma Primary endpoint: IRC-assessed ORR (RECIST v1.1) with progression on/intolerance to ≥1 prior line of standard therapy Secondary endpoints: DoR, IRC-assesse
Slide 74: Keynote-158: SGO 2021 Update
Keynote-158: SGO 2021 Update ORR 17.1% (PDL1+ patients; n=82) Median DOR not reached (all patients; N=98) 100% 13.5% 90% 80% 70% 60% 53.7% PD 53.7% 50% 40% 30% 15.9% 20% 10% 11.0% ORR 6.1% 17.1% 0% Complete Response Partial Response Stable Disease Progressive Disease Not evaluated DOR, duration of r
Slide 75: Keynote-158: SGO 2021 Update (cont)
Keynote-158: SGO 2021 Update (cont) Best Percentage Change from Baseline in Target Lesion Size (RECIST v1.1, Central Review) Includes patients with ≥1 evaluable pose-baseline tumor assessment (n=86). Data cutoff date: June 27, 2019. 1. Chung, HC, et al, Presented at SGO 2021. 74
Slide 76: Keynote-158: SGO 2021 Update (cont)
Keynote-158: SGO 2021 Update (cont) Time to and Duration of Response (RECIST v1.1, Central Review) CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease. Includes patients with best overall response of complete or partial response (n=14). The length of the bars rep
Slide 77: Keynote-158: SGO 2021 Update (cont)
Keynote-158: SGO 2021 Update (cont) Kaplan-Meier Estimate of PFS (RECIST v1.1, Central Review) PFS, progression-free survival. Data cutoff date: June 27, 2019. 76 1. Chung, HC, et al, Presented at SGO 2021.
Slide 78: Keynote-158: SGO 2021 Update (cont)
Keynote-158: SGO 2021 Update (cont) Kaplan-Meier Estimate of OS OS, overall survival. Data cutoff date: June 27, 2019. 1. Chung, HC, et al, Presented at SGO 2021. 77
Slide 79: Randomized Phase III Trial of Cemiplimab in Cervical Cancer: EMPOWER-CERVICAL 1
Randomized Phase III Trial of Cemiplimab Versus Investigator’s Choice of Chemotherapy in Cervical Cancer: “EMPOWER- CERVICAL 1” (GOG 3016) Metastatic cervical cancer resistant to platinum-based chemotherapy, ≥ Second-Line (N = 436) Investigators’ ECOG PS 0 or 1 choice Cemiplimab Primary Endpoint is
Slide 80: Libtayo (cemiplimab): Top-Line Results from EMPOWER Cervical-01
Libtayo (cemiplimab): Top-Line Results from the Phase 3 EMPOWER Cervical-01 Study Cemiplimab Chemotherapy Study design Total population (N) 304 304 • Largest P3 randomized controlled 12 months 8.5 months trial in advanced CC mOS • Recurrent or metastatic cervical HR: 0.69 (95% CI: 0.56-0.84); P<0.00
Slide 81: Checkpoint Inhibitors in Cervical Cancer
Checkpoint Inhibitors in Cervical Cancer KEYNOTE-1583 Lheureux et al.1 KEYNOTE-0282 (Cohort E)b Checkmate 3584 Phase(s) 2 1b 2 1/2 Population Metastatic or recurrent cervical PD-L1+ advanced cervical Advanced cervical cancer with HPV-associated tumors, cancer with progression after squamous cell can
Slide 82: Evolving r/mCC Treatment Landscape
Evolving r/mCC Treatment Landscape Current Standard of Care Current selected studies with novel agents* 1L systemic therapies • Paclitaxel + cisplatin / Adding anti-PD-(L)1 to current standard of care carboplatin with or without • KEYNOTE-826 (NCT03635567) Ph 3: Pembrolizumab vs placebo in combinati
Slide 83: KEYNOTE-826
KEYNOTE-826 • Untreated persistent, recurrent, or metastatic cervical Every 3 week pembrolizumab 200 mg PLUS • Measurable disease per investigator choice of chemotherapy* RECIST 1.1 R • Available archival tumor tissue Every 3 week placebo PLUS • Performance status of 0 to1 1:1 investigator choice of
Slide 84: BEATcc: Study Design
BEATcc: Study Design • Primary stage IVB, persistent or Control Arm recurrent carcinoma of the cervix Cisplatin + paclitaxel + bevacizumab • Measurable disease by RECIST (GOG#240) until disease progression, v1.1 unacceptable toxicity, death or withdrawal R: of consent • ECOG-PS: 0-1 1:1 • No previou
Slide 85: Autologous TILs (LN-145) 2L+ FDA Breakthrough Designation
Autologous TILs (LN-145) 2L+ FDA Breakthrough Designation ORR = 44.4% ➢ CR = 11.1% NCT03108495; Jazaeri AA et al. J Clin Onc. 2019;37(15)2538. 84
Slide 86: Prevalence of TIGIT in TCGA Tumors
Prevalence of TIGIT in TCGA Tumors The quartile RSEM value of TIGIT gene is ~100 85 CONFIDENTIAL Mereo Biopharma, unpublished
Slide 87: High PVR expression associated with poor clinical outcome
High PVR expression associated with poor clinical outcome Survival probability Time TCGA Blue=low PVR Purple=high PVR 86 Mereo Biopharma, unpublished
Slide 88: ACTIVATE Phase 1b/2 Study Design: Etigilimab plus Nivolumab
ACTIVATE Phase 1b/2 Study Design: Etigilimab plus Nivolumab in Advanced/Metastatic solid Tumors Primary endpoint • Overall Response Rate Secondary Rare tumors (e.g.sarcomas) • Safety and Tolerability Ovarian • PK/PD • Duration of response Cervical* Endometrial Exploratory • Biomarker Gastric/GEJ* •
Slide 89: Key Phase 2/3 Trials in Cervical Cancer
Key Phase 2/3 Trials in Cervical Cancer 88
Slide 90: Summary and Conclusions
Summary and Conclusions • Weekly cisplatin plus radiotherapy (CCRT) global standard in locally advanced primary disease • Platinum + paclitaxel +/- bevacizumab for metastatic disease • Immunotherapy is the new frontier! • Checkpoint inhibitors (PD-1, PDL-1, TIGIT) • Accelerated approval of pembroliz
Slide 91: Sarcoma
—Sw Mereo BioPharma ~~ SARCOMA
Slide 92: Immunotherapy in Sarcoma
Immunotherapy in Sarcoma Priscilla Merriam, MD Clinical Director Sarcoma Center Dana-Farber Cancer Institute Boston, MA May 13, 2021 Priscilla Merriam, MD 91
Slide 93: Disclosures
Disclosures None v= Dana-Farber Cancer institute
Slide 94: Sarcoma Overview
Sarcoma Overview • <1% of cancers in adults • Cancer that arises from mesenchymal cells (connective tissue precursors) • More than 50 kinds of sarcomas of soft tissue and bone (80% STS) • 50% of large high-grade sarcomas develop metastasis Liposarcoma 20% • Median overall survival < 2 yrs for metast
Slide 95: Sarcoma: Current Standard of Care
Sarcoma: Current Standard of Care Chemotherapy Overall Response Rate Progression Free (CR+PR) Survival (months) Doxorubicin 18% 6.8 Ifosfamide 21% 2.2 Gemcitabine + 20% 5.4 Docetaxel Trabectedin 10% 4.2 Pazopanib 6% 4.6 Eribulin 4% 2.6 Tap et al. ASCO Annual Meeting 2019 Antman et al. J Clin Oncol 1
Slide 96: Sarcoma: Many subtypes, variable immunogenicity
Sarcoma: Many subtypes, variable immunogenicity • Tumor mutational burden in translocation associated sarcomas lower than non-translocation associated sarcoma • Variability in tumor infiltrating lymphocytes by histology • PD-1 and PD-L1 expression low overall 10% and 22% respectively • There may be
Slide 97: Sarcoma Immunology: Sarcoma Immune Classes
Sarcoma Immunology: Sarcoma Immune Classes • Tumor mutations burden low overall • Immune classification based on tumor environment (B cells) may better represent immune status • Immune class status may be associated with overall survival Petitprez et al. Nature 2020 96
Slide 98: Multicenter phase II study of pembrolizumab in sarcomas (SARC028)
Multicenter phase II study of pembrolizumab in advanced soft tissue and bone sarcomas (SARC028) Soft Tissue Sarcoma (n=40) Number Leiomyosarcoma 10 • Pembrolizumab 200 mg IV every 3 weeks Undifferentiated pleomorphic 10 sarcoma (UPS) • Primary objective: ORR Liposarcoma 10 • Over 50% in both cohorts
Slide 99: Multicenter phase II study of pembrolizumab in sarcomas (SARC028)
Multicenter phase II study of pembrolizumab in advanced soft tissue and bone sarcomas (SARC028) • UPS ORR 40% Cohort CR PR ORR • Liposarcoma with ORR Leiomyosarcoma (n=10) 0 0 0% (0/10) 20% and SD UPS (n=10) 1 3 40% (4/10) Liposarcoma (n=10) 0 2 20% (2/10) Synovial sarcoma (n=10) 0 1 10% (1/10) Chon
Slide 100: Multicenter phase II study of pembrolizumab in sarcomas (SARC028)
Multicenter phase II study of pembrolizumab in advanced soft tissue and bone sarcomas (SARC028) Median PFS in soft tissue (STS) cohort: 18 wks (~4 mo) Tawbi et al. Lancet Oncol 2017 Burgess et al. ASCO Annual Meeting 2017 99
Slide 101: Pembrolizumab in UPS and Liposarcoma: SARC028 Expansion Cohorts
Pembrolizumab in Undifferentiated Pleomorphic Sarcoma (UPS) and Dedifferentiated/Pleomorphic Liposarcoma (LPS): SARC028 Expansion Cohorts • Enrolled 30 additional pts to UPS cohort and 30 to LPS cohorts • Primary objective: ORR in UPS and LPS Burgess et al. ASCO Annual Meeting 2019 (Abstract 11015)
Slide 102: Final Results of SARC028 Expansion Cohorts: UPS
Final Results of SARC028 Expansion Cohorts: UPS • 23% ORR (9/40) Burgess et al. ASCO Annual Meeting 2019 101
Slide 103: Final Results of SARC028 Expansion Cohorts: Liposarcoma
Final Results of SARC028 Expansion Cohorts: Liposarcoma • 10% ORR (4/40) • Not meet endpoint • Histology matters Burgess et al. ASCO Annual Meeting 2019 102
Slide 104: Sarcoma Immunology: Sarcoma Immune Classes
Sarcoma Immunology: Sarcoma Immune Classes • Evaluated 47 pre- treatment biopsies from patients in SARC028 and expansion cohort • Responses in SARC028 clustered mainly in SIC E (immune high class) responses to PD-1 inhibition in SIC class E • No responses seen in SIC A or B Petitprez et al. Nature 2
Slide 105: Nivolumab with or without ipilimumab for metastatic sarcoma (Alliance A091401)
Nivolumab with or without ipilimumab for metastatic sarcoma (Alliance A091401) Histology Nivolumab Nivolumab + Ipilimumab n=43 (%) n=42 (%) Angiosarcoma 0 3 (7) • Diversity in histologies Bone * 5 (12) 4 (10) • Randomized to nivolumab 3 mg/kg Leiomyosarcoma 15 (35) 14 (33) q2w or nivolumab 3 mg/kg +
Slide 106: Nivolumab Monotherapy
Nivolumab with or without ipilimumab for metastatic sarcoma (Alliance A091401): Monotherapy Nivolumab Monotherapy • 38 evaluable pts • Confirmed PR in alveolar soft part sarcoma (1) and non- uterine leiomyosarcoma (1) • 1 with sarcoma NOS had an unconfirmed PR • mPFS 1.7 months and mOS 10.7 months •
Slide 107: Nivolumab + Ipilimumab
Nivolumab with or without ipilimumab for metastatic sarcoma (Alliance A091401): Nivolumab + ipilimumab Nivolumab + Ipilimumab • 6/38 evaluable confirmed PR or CR (ORR 16%) ➢ CR in uterine leiomyosarcoma (1), myxofibrosarcoma (1) ➢ PR non-uterine leiomyosarcoma (1), UPS (2), angiosarcoma (1) • mPFS 4
Slide 108: Alliance A091401: Expansion Cohorts
Nivolumab with or without ipilimumab for metastatic sarcoma (Alliance A091401): Expansion Cohorts • Expansion cohorts included UPS DDLPS dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma subtypes • Pretreated patients, randomized to nivolumab or nivolumab + ipilimumab • Primary e
Slide 109: Conclusions
Conclusions • Standard of care chemotherapy options are lacking with low response rates, transient benefits, and undesirable side effects • Rates of expression of PD-1 and PD-L1 low, other potential targets may have higher expression in sarcomas • Single-agent PD-1 and PD-L1 inhibitors with some enc
Slide 110: Q&A
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Slide 111: Thank You
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Slide 112: Mereo BioPharma Group plc
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