Molecular Partners Ag · SIX:MOLN
Molecular Partners — Investor Presentation (June 2020)
34 slides from Molecular Partners's investor presentation, Jun 18, 2020
Slide 1: Molecular Partners: Pioneering a new class of drugs
Molecular Partners: Pioneering a new class of drugs with a broad portfolio and global partnerships Molecular Partners AG, Switzerland (SIX: MOLN) June 2020 1
Slide 2: 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
Slide 3: Pioneering DARPin therapies to transform the lives of patients
Molecular Partners: Pioneering DARPin® therapies to transform the lives of patients with cancer and other diseases A global team united around a common purpose of bringing a new class of drugs to life • Benefit from unique expertise of founding DARPin inventors Broad pipeline of custom-built protein
Slide 4: Executive Management and Senior Leadership Team
Executive Management and Senior Leadership Team Ana Cerdeira, VP Strategic Planning Dr. Patrick Amstutz, CEO and Portfolio Strategy Co-founder, former CBO & COO Former VP Emerging Markets Portfolio Member of the Board of Directors Mgmt. at Takeda PhD in biochemistry from UZH Julien Gander, G
Slide 5: Custom-built DARPin Proteins: Novel Therapeutic Modality
Custom-built DARPin Proteins: Novel Therapeutic Modality DARPin® module selection Ideal drug-like properties Natural multi-specific binding protein of human origin DARPin® Library with High potency and specificity 1012 modules High stability and solubility Systemic half-life of 14 days (HSA-
Slide 6: DARPin Features and Benefits
DARPin Features and Benefits Multi-DARPins: Incredible versatility by design Rigid-body target binding Unlock super-potent MoAs: Localized activation and pro-drugs Super-potency: Cooperative binding for complete inhibition DARPin® domain Rigid-body target binding Expand target space: Specific bindin
Slide 7: A Balanced and Robust Portfolio
A Balanced and Robust Portfolio Product Indication/ Research/ Commercial Phase 1 Phase 2 Phase 3 Candidates Target Pre-clinical Rights Ophthalmology abicipar DME Neovascular AMD Additional Various in DARPin® candidates Ophthalmology MP0250 Multiple Myeloma, PI combo Validated Targets MP0274 HER2+ tu
Slide 8: Abicipar: Potential to be the First Fixed 12-Week anti-VEGF
Abicipar: Potential to be the First Fixed 12-Week anti-VEGF Potential best in class anti-VEGF offering sustained vision and reduction in treatment burden Two positive clinical trials (CEDAR & SEQUOIA) show improved and maintained visual acuity at both 1-year and 2-year timepoints with quarterly
Slide 9: Remaining Medical Need & market potential in nAMD
Remaining Medical Need & market potential in nAMD What Retina Specialists are looking for when treating nAMD patients: Long-acting / sustained delivery Global Wet AMD Market Size SOC: Eylea® and Lucentis®: bi-monthly or 56% monthly injections $11bn annual sales for approved anti- Reduced Treatme
Slide 10: Phase 3 Efficacy Results (SEQUOIA study, 1yr data)
Phase 3 Efficacy Results (SEQUOIA study, 1yr data) Secondary Endpoint: Change in BCVA From Baseline Abicipar Q8 and Q12 in SEQUOIA Non-Inferior to Ranibizumab Primary Endpoint: STABLE VISION Abicipar Q8 and Q12 Non-Inferior to Ranibizumab Q4 Secondary Endpoint: Change in CRT similar across in all
Slide 11: Phase III CEDAR & SEQUOIA
Phase III CEDAR & Secondary Endpoint: Mean Change in CRT SEQUOIA From Baseline at Weeks 52 and 104 0 . = Week 52 | Week 104 £ 143, -148, -145 “447, -146, -142 > 754 | SE | g s © 2-150 4 So 88 me 225 J in (6) -300 i 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 100104 Week t
Slide 12: Intraocular Inflammation by Maximum Severity in MAPLE
Intraocular Inflammation by Maximum Severity in MAPLE (123pts) Severity was reported according to investigator assessment 12
Slide 13: MP0250: First Multi-DARPin Product Candidate with potential in MM
MP0250: First Multi-DARPin® Product Candidate with potential in MM HGF/cMET VEGF/VEGFR2 Upregulation of Highly specific First in class approach in targeting tumor micro-environment that c-MET signalling inhibition via anti- associated with selectively targets both the VEGF/VEGFRR2 and HGF/cMET VEG
Slide 14: MP0250: Deep and Durable Responses
MP0250: Deep and Durable Responses • Heavily pretreated patients, representative of typical RRMM population; median of 4 prior lines • Responses in patients who had never responded • 4/6 patients coming directly from Dara had clinical benefit (incl. 4/5 Dara-refractory patients) as presented at ASH
Slide 15: MP0274: Killing HER2+ Cells by New MoA
MP0274: Killing HER2+ Cells by New MoA Despite good antibody-based HER2+ treatments, eventually patients progress HSA HER2 HER2 HSA Novel mode of action: MP0274 is an allosteric inhibitor blocking HER2- DARPin® DARPin A DARPin® B ® DARPin® and HER3-signaling and inducing apoptosis Dose escalat
Slide 16: Applying our Therapeutic DARPin Designs
Applying our Therapeutic DARPin® Designs Tumor-localized immune Next-generation T-cell engagers cell activation CD3 Prodrug SWITCH 4-1BB or CD40 (too) potent MoAs FAP Tumor tumor stroma activated immune cell cells Un-lock pMHC Targeting peptide resting immune-cell MHC complexes Expand target space 1
Slide 17: Fibroblast Activation Protein (FAP) as a general switch
Local Activation of Immune cells: Fibroblast Activation Protein (FAP) as a general switch AMG506 (FAPx4-1BB) FAP expression adequate for immune activation in multiple solid tumors T NK Resting Cell Cell immune cell MP0317 (FAPxCD40) Dendritic Macrophage B Cell Cell No activation by mono-binding of
Slide 18: MP0310/AMG 506: Localized Activation of 4-1BB
MP0310/ AMG 506: Localized Activation of 4-1BB Immune Half-life modulator Localizer extender + + 4-1BB is a potent co-stimulatory molecule on T cells, but 4-1BB FAP HSA development has been slowed due to systemic toxicity concerns Novel mode of action: localized activation of 4-1BB in a FAP depe
Slide 19: AMG 506/MP0310 with TAA x CD3 Increases Intratumoral CD8+ T Cells
Combination of AMG 506/MP0310 and TAA x CD3 Bi-Specific Results in Significant Increase of Intratumoral CD8+ T Cells FAP-Mediated Tumor Intratumoral CD8 T cells Accumulation of AMG 506 HT-29-T-implanted NSG mice TAA x CD3 Tumor + AMG 506 TAA x CD3 + mFAP x 4-1BB no-FAP x 4-1BB mFAP x 4-1BB 19
Slide 20: Cornerstones of Amgen Collaboration for MP0310/AMG 506
Cornerstones of Amgen Collaboration for MP0310/AMG 506 AMG 506 Co-development – MP tests mono dose escalation – Amgen tests combinations Single-Agent Minimally Dose Dose active Mono Deal terms: Escalation dose therapy – $50m upfront payment Leads to – $497m in potential MS Combo Dose Safety, PK/
Slide 21: MP0317: Localized Activation of CD40
MP0317: Localized Activation of CD40 Immune Half-life modulator Localizer extender + + CD40 serves pivotal role in the immune response via interactions CD40 FAP HSA between T cells and antigen-presenting cells Novel mode of action: Localized activation of CD40 in a FAP dependent manner, potentia
Slide 22: MP0317: FAP-dependent activation of specific immune cells
MP0317: FAP-dependent activation of specific immune cells A Dendritic cells: B Macrophages: C B cells: CD86 IL-12 TNFα IL-12 CD69 CD83 CD80 IL-6 CCL17 CD86 x10 MP0317 in presence of FAP In presence of FAP MP0317 in presence of FAP 3 MP0317 in absence of FAP In absence of FAP MP03
Slide 23: MP0317 shows full activity with no detectable side-effects
MP0317 shows full activity with no detectable side-effects FAPHIGH TUMOR: MC38-FAP Colorectal cancer Vehicle Tumor growth (mm3) Neg. CTRL* mFAP x mCD40 mCD40 Ab Time after tumor inoculation (days) *Neg. CTRL, DARPin® molecule binding CD40 and HSA, but not FAP 23
Slide 24: Peptide MHC: Approach for Inaccessible Highly Selective Targets
Peptide MHC: Approach for “Inaccessible” Highly Selective Targets Tumor Surface Antigens Effector: DARPin® CD3 binder DARPin® - pMHC binder MHC Intra-cellular targets (presented on MHC) peptide Peptide MHC complex Soluble T Cell Receptors and Antibodies are not capable of broadly targeting pMHC effe
Slide 25: DARPins are uniquely designed to target Peptide MHC
DARPins are uniquely designed to target Peptide MHC Antibody (Ig-) Domain: binding via flexible loops CDR1 CDR2 CDR3 VL VH Randomized residues in loops DARPin® Domain: binding via rigid surface N-Cap 2-3 Repeats C-Cap Randomized residues on rigid surface 25
Slide 26: pMHC: Rapid Selection of Diverse DARPin pMHC Binders
pMHC: Rapid and Straightforward Selection of Diverse DARPin® pMHC Binders with High Selectivity Selectivity Activity & Selectivity (binding pattern by Alanine scanning) (T cell activation assay) DARPin® candidate pMHC-A x CD3 Ag+ cell line Ag- cell line PBMCs only anti-pMHC anti-CD3 pMHC-B x CD3 Ag+
Slide 27: DARPin Antiviral: Multi-epitope targeting for potent neutralization
DARPin® Antiviral: Multi-epitope targeting for potent neutralization and prevention of viral resistance Best-in-Class for therapy and broad scale prevention Highest potency for anti-viral effect in therapeutic setting – Rapid and strong knockdown of virus Multi-epitope targeting to prevent esc
Slide 28: Pseudotype virus neutralization
Hundreds of active Mono-DARPins selected Random assembly of Tri-DARPins for cooperative blocking Mono-DARPin®s Tri-DARPin®s Pseudotype virus neutralization Random assembly of tri-DARPins Binding on SPR • Single-digit nM potency • pM potency • broad epitope coverage • Information for rational design
Slide 29: Rational Design for Cooperative Binding: sub-pM binding
Rational Design for Cooperative Binding: sub-pM binding DARPin A – 1 hour off-rate DARPin B – 1 hour off-rate DARPin C – 1 hour off-rate DARPin A-B-C – 10 hour off-rate Sub-picomolar spike protein binding 29
Slide 30: Titration on Infectious SARS-CoV-2: low pM potency
Titration on Infectious SARS-CoV-2: low pM potency Protection of susceptible Vero E06 cells Protection of susceptible Vero E06 cells with positive patient serum at 1:500 with 4 different Tri-DARPin Candidates dilution Cytopathic Effect (CPE) Staining with Crystal Violet 30
Slide 31: Rapid action with DARPin molecules for COVID-19
Rapid action with DARPin molecules for COVID-19 Q1 / 2020 Q2 / 2020 Q3 / 2020 Q4 / 2020 Planning CMC FIH Selections Scale-up In vitro GMP Analysis of competitive Landscape and DARPin In vivo CTA Differentiation potential Research to generate differentiated Intensive dialogue with regulatory experts
Slide 32: Financial Overview & Milestones
Financial Overview & Milestones: Cash March 31, 2020: CHF 80.7m, No debt – Expense Guidance for FY2020: CHF 60-70m – Funded into H2 2021, without consideration of future milestones. Since our founding, collected in excess of $250m in capital from R&D Partners: – Allergan & Amgen ongoing – Prior
Slide 33: Expected 2020 Catalysts
Expected 2020 Catalysts 2020 Abicipar Approval and launch in nAMD (US and EU) Initiation of Abicipar Phase 3 in DME patients MP0250 Additional P2 data from PI-combo trial Continued development of MP0250 in partnership MP0274 Establish dose and define path forward AMG 506/ Identify AMG 50
Slide 34: Molecular Partners AG
Molecular Partners AG Wagistrasse 14 8952 Zürich-Schlieren Switzerland www.molecularpartners.com T +41 44 755 77 00 34
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