Molecular Partners Ag · SIX:MOLN

Molecular Partners — Investor Presentation (July 2018)

51 slides from Molecular Partners's investor presentation, Jul 23, 2018

  1. Slide 1: Making the DARPin Difference Reality for Patients

    Making the ® DARPin Difference Reality for Patients Corporate Presentation of Molecular Partners AG, Switzerland (SIX: MOLN) July 23, 2018 © 2018 Molecular Partners AG – Slide 1

  2. Slide 2: Molecular Partners: Who We Are

    Molecular Partners: Who We Are $ DARPin® Therapies Partnerships Teamwork  Abicipar in Phase 3 (ophtha)  Alliance with Allergan  Swiss biotech (SIX: MOLN)  MP0250 in Phase 2 (onc)  Collaboration with AstraZeneca  120 team members  MP0274 in Phase 1 (onc)  Cash CHF 130mn (Q1 2018)  Discovery

  3. Slide 3: Experienced Management Team & Board of Directors

    Experienced Management Team & Board of Directors Dr. Patrick Amstutz, CEO Bill Burns, Chairman  Co-founder, former CBO & COO  Former CEO of Roche Pharmaceuticals  Member of the Board of Directors  Former board member of Roche, Genentech,  PhD in molecular biology from UZH Chugai Pharmaceuticals

  4. Slide 4: DARPin Proteins: Beyond Target Space of Antibodies

    DARPin® Proteins: Beyond Target Space of Antibodies MONOCLONAL ANTIBODIES DARPin® PROTEINs Binding regions / Binding region / specificities specificity SCALE 15 kDa DARPin® module 150 kDa Multi-DARPin® product candidate • High affinity and specificity • High affinity and specificity • Large size: 15

  5. Slide 5: Modular Approach to Customized Drug Candidates

    Modular Approach to Customized Drug Candidates Building blocks Candidates DARPin® modules Multi-DARPin® product candidate (e.g. MP0250, MP0274) High flexibility permits binding Peptide linkers: Short, long, flexible, rigid with complex geometries DARPin® module conjugated to non-DARPin® element Non-

  6. Slide 6: Rapid Screening and Discovery, Flexible Design, Tailored to Therapeutic Need

    Rapid Screening and Discovery, Flexible Design, Tailored to Therapeutic Need Screening multi-DARPin Space of up DARPin® module Selection to 10,000 functional combinations Identifying novel biological solutions Library of over 1 trillion DARPin® proteins (modules) Combinations of up to 6+ DARPin® mod

  7. Slide 7: Balanced and Robust Portfolio

    Balanced and Robust Portfolio Discovery Preclinical Phase 1 Phase 2 Phase 3 MP0250 in MM Unlimited Source of DARPin® product candidates Oncology MP0250 in EGFR-mut NSCLC* MP0274: HER2+ patients DARPin® Engine: MP0310: 4-1BB-FAP multi-DARPin® I/O Multiple discovery programs Abicipar in wet AMD Ophtha

  8. Slide 8: Turning the DARPin Differentiation into Patient Outcome – Our Target Profiles

    Turning the DARPin® Differentiation into Patient Outcome – Our Target Profiles Preclinical Phase 1 Phase 2 Phase 3 MP0310 MP0274 MP0250 Abicipar NSCLC Wet AMD MM Tumor-restricted activity Molecular handcuff Blocking 2 key escape Long-acting VEGF to avoid dose-limiting inducing cell death in pathways

  9. Slide 9: Ready to Capture Value Beyond Ophthalmology

    Ready to Capture Value Beyond Ophthalmology Oncology Value in our proprietary oncology pipeline Value Ophthalmology Value in ophthalmology with our partner Allergan Time Illustrative only © 2018 Molecular Partners AG – Slide 9

  10. Slide 10: MP0250: A First-in-Class Multi-DARPin Product Candidate

    MP0250: A First-in-Class Multi-DARPin® Product Candidate MP0250  First biologic, blocking VEGF and HGF simultaneously VEGF  VEGF and HGF/c-MET key escape pathways for several SOC treatments DARPin®  Escape described for hematologic malignancies and solid tumors  Blocking these escape pathways ma

  11. Slide 11: MP0250 Blocks Two Tumor Escape Pathways

    MP0250 Blocks Two Tumor Escape Pathways MP0250 Untreated Upregulation of escape Medical Need: agents that block pathways after SOC escape pathways to SOC VEGF VEGF VEGF Tumor HGF HGF HGF pathways (c-MET) (c-MET) (c-MET) HSA SOC MP0250 © 2018 Molecular Partners AG – Slide 11

  12. Slide 12: Combined HGF and VEGF Inhibition Leads to Synergistic Effect in Mouse Model

    Combined HGF and VEGF Inhibition Leads to Synergistic Effect in Mouse Model MP0250 Tumor Growth Inhibition Syngeneic colorectal cancer model* (MC38) 2500 Tumor Volume (mm3) 2000 Vehicle 1500 Anti-HGF 1000 Anti-VEGF 500 Anti-VEGF & Anti-HGF MP0250 0 0 5 10 15 20 Treatment (days) *Syngeneic model: HGF

  13. Slide 13: MP0250 can be Combined with Many Agents Across Different Tumors

    MP0250 can be Combined with Many Agents Across Different Tumors to Increase Their Efficacy MP0250 Gastric cancer PDX model Head & neck cancer PDX model Pancreatic cancer tumor model GXA3027 HNXF1905 KP4 800 1000 2500 V e h ic le V e h ic le V e h ic le M P0250 M P0250 M P0250 Relative Tumor Volume (

  14. Slide 14: MP0250 in Phase 1: Safe, Convenient Dosing

    MP0250 in Phase 1: Safe, Convenient Dosing – Clear Signs of Efficacy even on stand-alone base MP0250 Dosing* Dosing Exposure Safety Safety Efficacy Efficacy Convenient, flexible Favorable exposure Repeated dosing Well tolerated Clear signs of administration resulted in good exposure antitumor even e

  15. Slide 15: Initial Indications Selected for Phase 2: MM and NSCLC

    Initial Indications Selected for Phase 2: MM and NSCLC – multiple indications on radar MP0250 Multiple myeloma Head & neck Biological rationale EGFR-mutated squamous-cell NSCLC HCC Nasopharyngeal Colorectal cancer Anal cancer Feasibility of internal clinical development* Bubble size indicates estima

  16. Slide 16: Resistance in MM: up-regulation of HGF & VEGF

    Resistance in MM: up-regulation of HGF & VEGF HGF score Bone Marrow MM Patients HGF Resistance to SOC VEGF mAbs 3+ 6/8 VEGF HGF HGF&VEGF 2+ 2/8 Newly On partial diagnosed remission Resistant Relapsed 28% 2% 92% 89% p-c-MET p-c-MET 1+ 0/8 40% 3% 7% c-MET c-MET c-MET c-MET Moschetta M, et al. Clin Can

  17. Slide 17: MP0250 Unique Approach in MM – Break Resistance & Restore Sensitivity

    MP0250 Unique Approach in MM – Break Resistance & Restore Sensitivity Resistance to SOC induced by VEGF/HGF upregulation HGF VEGF mAbs VEGF HGF + MP0250 VEGF mAbs MP0250 breaks the resistance to MM drugs HGF © 2018 Molecular Partners AG – Slide 17

  18. Slide 18: MP0250 Combination with Velcade Results in Superior Efficacy in Mouse Model

    MP0250 Combination with Velcade® Results in Superior Efficacy in Mouse Model MP0250 Vehicle Velcade® MP0250 Velcade® + MP0250 Bone morphology Muscle invasion by tumor Xenograft model H929. © 2018 Molecular Partners AG – Slide 18

  19. Slide 19: MP0250 Phase 2 Study in MM

    MP0250 Phase 2 Study in MM MP0250 Part 1: Dose Escalation ® Part 2: Dose Expansion Endpoints: n ≥ 6 Velcade /dexamethasone ORR, PFS MP0250 8 mg/kg q3wk Velcade®/dexamethasone RRMM Velcade®/dexamethasone MP0250 target dose Total: n  40 n ≥ 6 MP0250 12 mg/kg q3wk n ≥ 28  Phase 2 open-label, single-a

  20. Slide 20: MP0250 Phase 2 Study in MM Initial Read-out

    MP0250 Phase 2 Study in MM Initial Read-out: Promising Signs of Efficacy at initial dose (8mg/kg) MP0250 Preliminary results*: Best responses Treatment duration* (5/8 patients with anti-myeloma activity; excludes non-responders) Baseline withdrew Very good partial response Patient 103-001 1 consent

  21. Slide 21: Unique Potential of MP0250 in MM

    Unique Potential of MP0250 in MM MP0250  Multiple myeloma: 2nd most common blood cancer  Global market value ~USD 9.8bn, expected to reach > USD 12bn by 2021 1 75% 25% IMiD or PI + mAb Transplant 1st/2nd-line n >100,0001 PI or IMiD + mAb HGF/ No later-line treatments c-MET target these key escape

  22. Slide 22: HGF & VEGF Rationale in NSCLC is Supported by Preclinical & Clinical Data

    HGF & VEGF Rationale in NSCLC is Supported by Preclinical & Clinical Data MP0250 Preclinical Rationale Clinical Rationale MP0250 in Lung Cancer Model HGF Rationale 3000 Activation of MET pathway appears to be significantly involved in acquired resistance to TKI  HGF/c-MET pathway is most frequently

  23. Slide 23: Unique Potential of MP0250 in EGFR mut NSCLC

    Unique Potential of MP0250 in EGFR mut NSCLC MP0250 Current Treatment Option 1 Treatment Line Current Treatment Option 2 Iressa® or Tarceva® 1st-line Tagrisso® n  35’0001 HGF/c-MET Tagrisso® 2nd-line MP0250 + Tagrisso® n  20’0001 Our Phase 2 Study HGF/c-MET MP0250 + Tagrisso® 3rd/4th-line n  15’0

  24. Slide 24: MP0250 Phase 2 Study in NSCLC

    MP0250 Phase 2 Study in NSCLC MP0250 Part 1: Dose Escalation Part 2: Dose Expansion Endpoints: n ≥ 6 Tagrisso® n ≥ 28 ORR, PFS EGFR mut MP0250 8 mg/kg q3wk Tagrisso® NSCLC after Tagrisso Tagrisso® MP0250 target dose n ≥ 6 MP0250 12 mg/kg q3wk  Status: FDA approval Sep 2017 – 1st oncology DARPin® dr

  25. Slide 25: MP0274: Killing HER2+ Cells with New MoA

    MP0274: Killing HER2+ Cells with New MoA MP0274 HSA  Medical need: eventually advanced cancer patients progress on DARPin® standard antibody-based HER2+ treatments HER2 DARPin® A  MP0274 is an allosteric inhibitor of HER2 blocking HER2- and HER3- mediated signaling and inducing apoptosis  New mod

  26. Slide 26: MP0274 Forces Her2 in Conformational Deadlock Leading to Cell Death

    MP0274 Forces Her2 in Conformational Deadlock Leading to Cell Death MP0274 MP0274 Her2 EC-Domain Trastuzumab & Pertuzumab Bi-paratopic DARPin® Perjeta Herceptin Her2 has several «active sites» Herceptin and Perjeta block MP0274 handcuffs Her2 into fully with conformational flexibility two distinct H

  27. Slide 27: Direct Induction of Tumor Cell Death with MP0274

    Direct Induction of Tumor Cell Death with MP0274 MP0274 MP0274 «Open» «Locked» Effector-cell independent Apoptosis tumor cell death HER2 HER3 HER1 Natural Killer Cell HER2 signals tumor cell survival Effector-cell mediated & proliferation ADCC tumor cell death Herceptin® & Perjeta® ADCC, antibody-de

  28. Slide 28: MP0274 is a Highly Potent Tumor Cell Killer

    MP0274 is a Highly Potent Tumor Cell Killer MP0274 Tumor Cell Apoptosis Tumor Cell Killing BT474 BT474 100 100 100 MP0274 MP0274 Ado-trastuzumab 80 80 80 emtansine (Kadcyla®) 60 % Killing 60 60 40 40 40 Trastuzumab/ 20 Pertuzumab 20 20 (Herceptin®/ Perjeta®) 0 00 0 0 100 101 102 103 100 10 0 11 110

  29. Slide 29: MP0274 Efficacy in PDX Mouse Models

    MP0274 Efficacy in PDX Mouse Models MP0274 Vehicle Trastuzumab Trastuzumab + Pertuzumab MP0274 Breast cancer PDX model Gastric cancer PDX model Colorectal cancer PDX model Maca4898 (Her2 IHC2+) GXA3039 (Her2 IHC3/2+) CXF1991 (Her2 IHC3+) 2000 800 1500 Relative Tumor Volume (%) 1600 Tumor Volume (mm3

  30. Slide 30: MP0274: Phase 1 Study in HER2+ Cancer Patients

    MP0274: Phase 1 Study in HER2+ Cancer Patients MP0274  Phase 1, first-in-human, single-arm, multicenter, open-label, repeated-dose, dose escalation study – assess safety, tolerability and pharmacokinetics of MP0274 in patients with advanced HER2-positive solid tumors – with expansion cohort at reco

  31. Slide 31: Improving the Therapeutic Index of IO Agents

    Improving the Therapeutic Index of IO Agents ACTIVATE KILL Costimulatory Targets T-Cell Engagers Immune- cell Toxicity BLOCK Efficacy Checkpoint Targets Tumor Tumor localized IO agents may achieve both, Cells reduce systemic toxicity and improve efficacy © 2018 Molecular Partners AG – Slide 31

  32. Slide 32: How do we achieve the improved therapeutic index?

    How do we achieve the improved therapeutic index? IN CIRCULATION (SYSTEMIC) IN THE TUMOR Clustering: IN CIRCULATION (SYSTEMIC) activation of T-cells everywhere in body IN THE TUMOR Activated Cell Activated Tumor T-cell T-cell Cell No Clustering = no effect Tumor Clustering: T-cell activation Stroma

  33. Slide 33: All Successful DARPin Stimulators to Date

    All Successful DARPin® Stimulators to Date Without Clustering  1 0 77 11×10 OX-40 5 0 ,0 0 0 4-1BB1 2000 CD40 Luminescence Signal  1 0 66 88×10 4 0 ,0 0 0 1500  1 0 66 66×10 3 0 ,0 0 0 1000  1 0 66 44×10 2 0 ,0 0 0 OFF 500  1 0 66 22×10 1 0 ,0 0 0 0 0 0 -3 -2 -1 0 1 2 0 1 0 -2 1 0 -1 1 0 0 1 0

  34. Slide 34: DARPin I/O Platform with Multiple Opportunities

    DARPin® I/O Platform with Multiple Opportunities: MP0310 as the first DARPin® product candidate Stimulator Switch OX-40 4-1BB a CD40 c A B Localizer FAP MP0310 C D Many DARPin® candidates are under investigation for both solid and liquid tumors (including combinations) © 2018 Molecular Partners AG –

  35. Slide 35: MP0310: Activating T-cells (only) in the Tumor

    MP0310: Activating T-cells (only) in the Tumor MP0310  FAP: 4-1BB Tumor-restricted expression of FAP used to direct T-cell activation HSA DARPin®  Tumor-selective activation of T cells FAP  No systemic side effects expected DARPin®  Potential to combine with other IO SOCs (anti-PD-1, anti-CTLA4)

  36. Slide 36: Overview of MP0310 Data

    Overview of MP0310 Data MP0310 No systemic toxicity Ideally suited for combinations Vehicle 2000 40000 *** 10 Body weight loss >10% TAA-CD3-AB *** M e a n tu m o r v o lu m e [m m ] 3 8 TAA-CD3-AB V e h ic l e H u m a n C D 8 T c e lls 1500 + MP0310 30000 p e r 0 .2 g t u m o r CD8 T-Cells Animals (

  37. Slide 37: Retinal Diseases: Unmet Medical Needs Remain

    Retinal Diseases: Unmet Medical Needs Remain  Wet AMD and DME are leading causes of blindness in Western world  Large and rapidly growing group driven by aging population  Current standard of care is Lucentis® or Eylea® – Both require monthly or bi-monthly intravitreal injections  Significant un

  38. Slide 38: Abicipar: Most Advanced DARPin Therapy

    Abicipar: Most Advanced DARPin® Therapy, to become first and only true long-acting anti-VEGF Abicipar  Long-acting PEGylated mono-DARPin® protein blocking VEGF  Potentially transformative therapy with less frequent ocular injections compared with standard of care anti-VEGF DARPin®  Phase 2 data a

  39. Slide 39: Phase 3 CEDAR & SEQUOIA Study Design

    Phase 3 CEDAR & SEQUOIA Study Design Abicipar Source: Allergan presentation, 19 July 2018 © 2018 Molecular Partners AG – Slide 39

  40. Slide 40: Primary Endpoint: Abicipar Q8 and Q12 Non-Inferior to Ranibizumab Q4

    Primary Endpoint: STABLE VISION Abicipar Q8 and Q12 Non-Inferior to Ranibizumab Q4 With Fewer Injections Source: Allergan presentation, 19 July 2018 © 2018 Molecular Partners AG – Slide 40

  41. Slide 41: Abicipar Dosed Every 8 and Every 12 Weeks Demonstrated Non-Inferiority

    Abicipar Dosed Every 8 and Every 12 Weeks Demonstrated Non-Inferiority to Ranibizumab Dosed Every 4 Weeks Source: Allergan presentation, 19 July 2018 © 2018 Molecular Partners AG – Slide 41

  42. Slide 42: Economic Potential of Abicipar Collaboration

    Economic Potential of Abicipar Collaboration  Total of USD 360m in potential future milestones – USD 210m development milestones pre launch – Additional USD 150m sales-based milestones  Tiered royalties: Low double-digit to mid-teens  Attractive >USD 8 billion market, reducing the injection frequ

  43. Slide 43: Multiple Value Inflection Points Ahead

    Multiple Value Inflection Points Ahead 2018 2019 2020 wAMD: 1-y Ph 3 wAMD: Filing to FDA Abicipar efficacy planned for H1 2019 MM: initial efficacy MM: efficacy MP0250 NSCLC: efficacy NSCLC: initial safety NSCLC: initial efficacy MP0274 Initial safety Initial efficacy MP0310 Preclinical data FIH Fun

  44. Slide 44: Investment Case and Key Messages

    Investment Case and Key Messages  Successful transition from DARPin® platform into clinical product company  Key value inflection points ahead: –MP0250 (2x Phase 2) and MP0274 (Phase 1) in oncology –Abicipar FDA filing in ophthalmology  MP0310 selected as 1st development candidate from our I/O DA

  45. Slide 45: Appendix

    Appendix © 2018 Molecular Partners AG – Slide 45

  46. Slide 46: Phase 2 Data Suggest Quarterly Dosing for Wet AMD

    Phase 2 Data Suggest Quarterly Dosing for Wet AMD Abicipar Change of Best-Corrected Visual Acuity (BCVA)* Safety Data 12 Abicipar 2.0 mg 10 Vision Gain (letters) Safety (n/N) Abicipar 1.0 mg BCVA (letters ± SE) Wk 16 Wk 20 AEs† Lucentis® 0.5 mg 8 8.2 9.0 2/23 6.3 7.1 3/25 6 5.3 4.7 0/16 4 2 0 0 1 4

  47. Slide 47: Financial Summary FY 17

    Financial Summary FY 17 Financial Guidance for (CHF million; as per IFRS) FY 2017 FY 2016 change Full-Year 20184  Total expenses of ca. CHF 50-60 Revenues 20.0 23.0 (3.0) million, of which ca. CHF 5 million non-cash effective costs Total expenses1 (45.8) (42.5) (3.3)  Capital expenditures of Opera

  48. Slide 48: Shareholder Structure

    Shareholder Structure Shareholder structure as of Dec 31, 2017 Highlights  VC holdings reduced to 23% (from 42% end of 2016) 23%  Listed on SIX Swiss Exchange (SIX: MOLN) 59%  Included in key indices: SPI, SPI Extra, SXI Life Sciences and SXI Bio+Medtech 18%  21,044,062 shares outstanding as of

  49. Slide 49: IR Agenda

    IR Agenda Date Event August 30, 2018 Publication of Half-year Results 2018 November 01, 2018 Q3 2018 Management Statement © 2018 Molecular Partners AG – Slide 49

  50. Slide 50: Disclaimer

    Disclaimer This presentation is not an offer to sell or a solicitation of offers to purchase or subscribe for shares of Molecular Partners AG, nor shall it or any part of it nor the fact of its distribution form the basis of, or be relied on in connection with, any contract or investment decision. T

  51. Slide 51: Molecular Partners AG

    Molecular Partners AG Wagistrasse 14 8952 Zürich-Schlieren Switzerland www.molecularpartners.com T +41 44 755 77 00 © 2018 Molecular Partners AG – Slide 51

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