Merck KGaA · XETR:MRK
Merck KGaA — Technical Presentation (November 2022)
50 slides from Merck KGaA's technical presentation, Nov 21, 2022
Slide 1: R&D Update call 2022
R&D Update call 2022 More medicines, to more patients, faster Danny Bar-Zohar Global Head of Research & Development and Chief Medical Officer Andrew Paterson Chief Marketing Officer Klaus Urbahns Global Head of Discovery and Development Technologies Victoria Zazulina Global Head of Development Unit
Slide 2: Disclaimer
Disclaimer Cautionary Note Regarding Forward-Looking Statements and financial indicators This communication may include “forward-looking statements.” Statements that include words such as “anticipate,” “expect,” “should,” “would,” “intend,” “plan,” “project,” “seek,” “believe,” “will,” and other wor
Slide 3: Participants in today's call
Participants in today’s call R&D and Commercial Danny Bar-Zohar Andrew Paterson Klaus Urbahns Victoria Zazulina Jan Klatt Head of Research and Chief Marketing Global Head of Discovery Global Head of Global Head of Development and Chief Officer and Development Development Development Medical Officer
Slide 4: Today's Call Agenda
Today‘s Call Agenda 1 R&D Roadmap 2 Enabling technologies – Antibody Drug Conjugates 3 Oncology - Clinical pipeline 4 Neurology & Immunology – Clinical pipeline 5 Q&A Session 4 Healthcare R&D Update Call | November 21, 2022
Slide 5: R&D roadmap
1 R&D roadmap
Slide 6: Healthcare growth driven by innovation, building on a solid established portfolio
Healthcare Growth driven by innovation, building on a solid established portfolio New products Global specialty innovator Mid single-digit ▪ Committed to drive Wave 1 CAGR launches Bavencio®, Mavenclad® and Tepmetko® ▪ Wave 2 expands with evobrutinib contribute to (BTKi) with BiC potential in RMS an
Slide 7: R&D Roadmap: Performance ambition
R&D Roadmap Performance ambition Getting more medicines to more patients, faster 2x 1 in 1.5 Doubling Merck’s One launch historic productivity every 1.5 years* *rolling average 7 Healthcare R&D Update Call | November 21, 2022
Slide 8: Three strategies to double R&D productivity
R&D Roadmap Three strategies to double R&D productivity focused Building on existing strengths & capabilities leadership in biology, technology and therapeutic areas Increase contribution from external innovation external to over 50% in our core areas of expertise, innovation bolstering our capabili
Slide 9: Building on R&D focused leadership
focused R&D Roadmap leadership Building on R&D focused leadership Focus areas of internal innovation Underlying Therapeutic Technologies biology areas ▪ DDR ▪ Neuroinflammation ▪ Track record in NCEs, NBEs ▪ Apoptosis ▪ Multiple Sclerosis ▪ Antibody drug conjugates ▪ Innate immunity ▪ SCCHN ▪ Protei
Slide 10: Further amplifying our external innovation efforts
External R&D Roadmap innovation Further amplifying our external innovation efforts Key deals in the last 24 months Company Asset/capacity Strategic match Debiopharm Xevinapant Expertise in SCCHN, asset post PoC Nerviano NMS-293 Selective PARPi complementing DDR strategy Medical Sciences Cladribine S
Slide 11: Trial design simplicity and agility in execution driving efficiency
R&D Roadmap agility Trial design simplicity and agility in execution driving efficiency Decomplexified studies and leaner protocols Design Securing high efficiency Working closely with of R&D engine clinical sites to be • Increased output able to react quickly - more clinical studies Execution Lever
Slide 12: Enabling technologies – Antibody Drug Conjugates
2 Enabling technologies – Antibody Drug Conjugates
Slide 13: Expanding expertise in ADCs and Targeted Protein Degraders
Enabling Technologies Expanding expertise in ADCs and Targeted Protein Degraders Established Focused Leadership: Antibodies Protein Kinase Inhibitors Expanding our toolbox: Antibody Targeted Drug Conjugates Protein Degraders Aspiring for technology leadership in selected areas. Acronyms: ADC=Antibod
Slide 14: Merck's ADC technology addresses the limitations of first-gen ADCs
Enabling Technologies: ADCs Merck's ADC technology addresses the limitations of first-gen ADCs First generation ADCs Merck’s ADC Platform Unfavorable target expression Mono & bispecific internalizing Antibody Suboptimal half-life and binders internalization Designed physiochemical properties
Slide 15: Merck HC's ADCs based on most advanced linker/payload technologies
Antibody drug conjugates (ADC’s) Merck HC’s ADCs are based on the most advanced linker/payload technologies Val-Cit or Val-Ala Cathepsins Disulfides (Adcetris, Polivy, Padcev) ß-Glucuronide Reductive cleavage (Elahere) Maleimido-caproates “GGFG” Lysosomal processing Cathepsins Hydrazones Linkers Aci
Slide 16: Design Features of M9140 (anti CEACAM-5 ADC)
Enabling Technologies: ADCs Example: Design Features of M9140 (anti CEACAM-5 ADC) Highly specific CEACAM-5 antibody, with excellent DMPK, long half-life and robust in vitro stability High polarity of glucuronide linker improves ADC stability and reduces aggregation Stable glucuronidase-based l
Slide 17: Merck's ADC technologies translate into superior pre-clinical profiles
Example: Anti CEACAM5 ADC: M9140 Merck’s ADC technologies translate into superior pre-clinical profiles In vitro effect on MDA-MB-231 In vivo effect in CRC PDX model Safety studies in non-human primates and SK-CO-1 cells 6000 #of cells 1500 Tumor volume [mm] Comparator M9140 0 No pre-clinical eviden
Slide 18: Oncology - Clinical pipeline
3 Oncology - Clinical pipeline
Slide 19: Building on understanding of cancer biology and hallmarks
Oncology Building on understanding of cancer biology and unique cancer hallmarks1 Cancer is a disease of the Merck’s expertise in cancer biology Killing cancer cells genome, caused by changes to Focus on key hallmarks of cancer2 through disruption of DNA genes which control cell growth and prolifera
Slide 20: Three therapeutic approaches offer combination opportunities
Oncology Three therapeutic approaches offer combination opportunities to maximize tumor cell killing Induce cancer cell death Block DNA damage repair Restore cancer cell sensitivity targeted delivery of cytotoxic tipping balance from cancer cell survival to apoptosis chemotherapy towards death induc
Slide 21: Oncology - Cancer DNA
Oncology - Cancer DNA Exploiting major vulnerability of tumor cells and striking them right at the core Validated therapeutic approaches, with strong innovation potential: CEACAM5 ATRi Chemo/radio ADC DDRi sensitizers ADC Ability to drive new standard of care: ATMi ▪ In all-comer indications Other e
Slide 22: Xevinapant: Leveraging our long-lasting expertise in SCCHN
Oncology - Xevinapant Leveraging our long-lasting expertise in SCCHN Treatment paradigm of LA SCCHN Disease Treated stage III & IVA/B SCCHN patients (total ~110K patients)1 >50% Segment Unresected Resected with recurrence and/or distant High risk metastasis within 2 years of RT- Int Low Cis-eligible
Slide 23: Phase II: Xevinapant nearly doubled cure rate in LA SCCHN
Oncology - Xevinapant Phase II: Addition of xevinapant to chemoradiotherapy nearly doubled cure rate in patients with LA SCCHN OS (5-year analysis)1 100 1 year 2 years 3 years 4 years 5 years 91% 80 73% OS, (KM-estimate; %) 66% 79% The risk of death was more than 60 halved and median OS was prolonge
Slide 24: Phase II: Consistent improvement across all efficacy endpoints
Oncology - Xevinapant Phase II: Consistent improvement across all efficacy endpoints with no compromise in delivery of backbone chemoradiotherapy (CRT) PhII: Double-blind, multi-centre, Selected efficacy endpoints Combination tolerability profile randomized trial1 Efficacy Xevi + Pbo+ Category of AE
Slide 25: Phase III program on track to deliver on blockbuster potential
Oncology - Xevinapant Phase III program on track to deliver on a blockbuster potential TrilynX™ 2021 2022 2023 2024 2025 ≥ 2026 Confirming PhII results in unresected LA SCCHN Unresected Xevinapant1 + CRT LA SCCHN Suitable for R 1:1 definitive CRT (NCT04459715) IA PA (N=700) Placebo + CRT • 250+ site
Slide 26: Unique portfolio of DDR inhibitors testing three distinct hypotheses
Oncology - DNA Damage Response (DDR) Unique portfolio of DDR inhibitors testing three distinct hypotheses to enhance tumor cell killing Selectively kill tumors with DDR mutations Peposertib (Synthetic Lethality) NMS-293 Amplify DNA damage-inducing chemotherapy and radiotherapy M1774 M4076 Activating
Slide 27: M1774 strongly synergizes with multiple drug classes
Oncology - DNA Damage Response (DDR) M1774 strongly synergizes with multiple drug classes1 COMBINATION screen in vitro: (platinum, Topo-I inhibitors, PARPi, and other DDRi) ATMi In vivo efficacy studies confirm the combination potential suggested from in vitro studies Chemotherapy combination ATMi c
Slide 28: M1774 Phase I study: potency, exposure and safety
Oncology - DNA Damage Response (DDR) M1774 Phase I study: integration of potency, exposure and safety supports strong combination potential DDriver Solid Tumors 301 Pharmacologically robust ATRi Compares favorably on early safety data (PhI) NCT04170153 that achieves strong target M1774 Elimusertib1
Slide 29: Exploring combination potential of M1774 in DDRiver program
Oncology - DNA Damage Response (DDR) Exploring combination potential of M1774 in a broad DDRiver development program DDriver Solid Tumors 301 NCT04170153 Nov 2022 2023 2023+ Part A1 dose escalation: MTD, RDE, PK and PD of M1774 Part A2: food effect Part A3: M1774 in patients with key loss-of-functio
Slide 30: M9140: designed to fight CRC and other GI cancers
Oncology - Antibody-Drug Conjugates M9140: specifically designed to fight CRC and other GI cancers, with optionality in additional tumors Scientific Rationale Differentiation Phase I study ongoing NCT05464030 CEACAM5 expression M9140 vs DM4 ADC 2023 2024 CEACAM5 Tubulin PL–based ADC Dose escalation
Slide 31: Merck Oncology – building focused leadership while balancing risks
Oncology Merck Oncology – building focused leadership in core areas while balancing risks Right Science Right Balance • Exploits major vulnerability of cancers • Clinically validated approaches (ADC, PARPi), but still with lots of innovation • Multiple pipeline and SOC synergies CEACAM5 ATRi potenti
Slide 32: Neurology & Immunology – Clinical pipeline
4 Neurology & Immunology – Clinical pipeline
Slide 33: N&I Strategy: Gradual expansion on a solid foundation
N&I - Strategy Gradual expansion on a solid foundation MAXIMIZE MS EXPAND IN DIVERSIFY WITH PORTFOLIO NEUROLOGY IMMUNOLOGY Area of focused Focus on rare neurological Accelerate discovery & leadership diseases where development on targets inflammation is the with proven biology via novel World-class
Slide 34: Evobrutinib: Silent progression in MS is a critical unmet need
N&I - Evobrutinib Silent progression - disability accumulation despire DMT in the absence of focal MRI lesions and relapses is a persistent critical unmet need in MS CIS RELAPSING PHASE PROGRESSIVE PHASE Total Disability Accrual If Disability Accrual Untreated Total Disability Accrual on DMT Disabil
Slide 35: Evobrutinib: Dual Mode of Action for dual efficacy potential
N&I - Evobrutinib Dual Mode of Action for dual efficacy potential Dual MOA Dual efficacy BTK inhibition Reduction in progression modulates1-5 B cells and associated with relapses microglia in the CNS AND AND independent of B cells & monocytes in relapses (i.e. silent the periphery* progression) Clin
Slide 36: Compelling clinical data in Phase II and ongoing extension
N&I - Evobrutinib Compelling clinical data in Phase II and the ongoing extension Very low and sustained ARR Long-term Clinical Stability (EDSS) * * Acronyms: ARR=annualized relapse rate; BID=twice daily; BTKi=Bruton’s tyrosine kinase inhibitor; CI=confidence interval; CNS=central nervous system; DBP
Slide 37: Slowly Expanding Lesions associated with disability progression in RMS
N&I - Evobrutinib Slowly Expanding Lesions (SELs) are associated with long-term disability progression in patients with RMS Slowly Expanding Lesions are: • Chronically active, demyelinated MS lesions • Driven by sustained microglial activity resulting in progressive accumulation of irreversible neur
Slide 38: Biomarker data supports impact on silent progression
N&I - Evobrutinib Biomarker data further supports impact on silent progression in Phase II Reduction in established biomarkers of Reduction in SEL volume neuronal damage (NfL) Acronyms: BTKi=Bruton’s tyrosine kinase inhibitor; CNS=Central Nervous System; SEL=Slowly Expanding Lesions; NfL=Neurofilame
Slide 39: Comprehensive assessment of disability in Phase III program
N&I - Evobrutinib Broad and comprehensive assessment of disability in the Phase III program Composite measures: CDP, NEP, NEPAD, RAW, PIRA, PIRMA Disability improvement: CDI Manual dexterity: 9 Hole Peg Test Additional studies to start: Walking ability: T25FW PET (Imaging) study Biomarke
Slide 40: Evobrutinib on track for Q4 2023 readout
N&I - Evobrutinib Evobrutinib – potential for Best-in-Class and on track for Q4 2023 readout Rapid Response to Emerging Operational Challenges ▪ Protocol switched to an event-driven design ▪ Extension of study period to 3 years Readout ▪ Re-opened sites outside of UKR/RUS crisis region in Q4 2023 St
Slide 41: Enpatoran: TLR7/8 inhibition in autoimmune diseases
N&I - Enpatoran TLR7/8 inhibition: Potential to transform treatment of autoimmune diseases Rationale ▪ TLR7 and TLR8 detect ssRNA, triggering activation of both innate and adaptive immune cells1,2 ▪ Aberrant TLR7/8 activation is linked to multiple autoimmune and inflammatory diseases3 ▪ Monogenic ga
Slide 42: Unique adaptive design of WILLOW study in SLE & CLE
N&I - Enpatoran Unique adaptive design of WILLOW study in SLE & CLE 2021 2022 2023 2024 2025 WILLOW 2027 2026 Design Features 2028 ▪ Cohort B part 2 – dose adaptation, PhIb: CLE & SLE safety informed by Phase Ib and Phase II doses up to 150mg BiD Cohort A at the interim analysis PhII Cohort A (SLE/C
Slide 43: Enpatoran: Expansion into myositis
N&I - Enpatoran Expansion into myositis, First-in-Class Potential Development Rationale Neptunia Study ▪ G7 prevalence of 100 – 120K ▪ Debilitating autoimmune disease, characterized by muscle weakness, fatigue and disability ▪ Patients show lupus-like patterns of immune activation and TLR7/8 express
Slide 44: Cladribine – going beyond multiple sclerosis
N&I - Cladribine Cladribine – going beyond multiple sclerosis s.c. Cladribine Open Label Study in MG Development Rationale ▪ Myasthenia gravis is a neuromuscular disease with high unmet need ▪ There is potential for a highly differentiated therapy that can deliver high efficacy and convenience with
Slide 45: Key Takeaways & Q&A Session
5 Key Takeaways & Q&A Session
Slide 46: Upcoming milestones
R&D Update call 2022 Upcoming milestones Significant readouts Study initiations 2023 2023 Evobrutinib PhIII program Enpatoran PhII DM/PM Enpatoran PhII CLE/SLE - futility analysis Evobrutinib PET Study PhIIIb Xevinapant (cis-eligible) PhIII - IA M1774 + ICI PhII Tepotinib NSCLC EGFRm/M
Slide 47: Key take-away points
R&D Update call 2022 Key take-away points More medicines to more patients, Strong progress in clinical 1 3 faster development • Building on leadership in H&N: xevinapant ✓ 5ys OS data indicating nearly doubling of cure rates ✓ TrylinX Interim Analysis (IA) in 2023 • Maximizing presence in MS: evobru
Slide 48: Investor Relations contacts
CONSTANTIN FEST SVENJA DJAVAHERI PETRA HOLTZ Head of Investor Relations Assistant Investor Relations Assistant Investor Relations +49 6151 72-5271 +49 6151 72-3744 +49 6151 72-3321 constantin.fest@merckgroup.com svenja.djavaheri@merckgroup.com petra.holtz@merckgroup.com ADRIAN GORSKI GUNNAR ROMER FL
Slide 49: Appendix: Healthcare pipeline
+ Appendix Healthcare pipeline
Slide 50: Merck pipeline
Merck pipeline November 21, 2022 Healthcare pipeline Phase I Phase II Phase III Registration Marketed7 evobrutinib (BTK inhibitor) Relapsing multiple sclerosis enpatoran (TLR7/8 antagonist) Cutaneous lupus erythematosus enpatoran (TLR7/8 antagonist) Systemic lupus erythematosus xevinapant (IAP inhib