Molecular Partners AG · SIX:MOLN
Molecular Partners — Investor Presentation (May 2021)
48 slides from Molecular Partners's investor presentation, May 18, 2021
Slide 1: Unlock and Expand: Custom Built Biology for Patients
Unlock and Expand: Custom Built Biology for Patients Molecular Partners AG, Switzerland (SIX: MOLN) 1
Slide 2: Disclaimer
Disclaimer This presentation is made pursuant to Section 5(d) of and/or Rule 163B under the Securities Act of 1933, as amended (“test-the-waters”), and is intended solely for investors that are qualified institutional buyers or institutional accredited investors solely for the purposes of familiariz
Slide 3: Pioneering DARPin Therapies to Transform Lives
Pioneering DARPin® Therapies to Transform Lives 3
Slide 4: What are DARPin Proteins
What are DARPin® Proteins MONOCLONAL ANTIBODIES MONO-DARPin PROTEINS Binding region / specificity Binding regions / specificities 15 kDa DARPin module Multi-specific DARPin Product Candidate 150 kDa • High affinity and specificity • High affinity and specificity • Large size: 150 kDa • Small size: 1
Slide 5: Pioneering DARPin Solutions: Right Team, Right Time
Pioneering DARPin® Solutions: Right Team, Right Time • Track-record to deliver a Phase 3 ready candidate in 12 months from idea generation Proven Team • Strong mix of founders and key new hires • Increased cash on balance sheet by $160m in 2020 (Funded into 2023) • Fast & differentiated candidates:
Slide 6: Executive Management and Senior Leadership Team
Executive Management and Senior Leadership Team Ana Cerdeira, VP Partnering & Patrick Amstutz, PhD, CEO 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, General Counsel ▪ Di
Slide 7: Innate Advantages Combined With Proprietary Approaches
Innate Advantages Combined With Proprietary Approaches DARPin® Differentiation: DARPin® Benefit Candidates Turn-key multi-specifics Solving clinically relevant problems Unlock & Expand • MP0310 Localized Activity • MP0317 • Local and temporal control of activity • Next-Gen CD3 Molecular Handcuff • M
Slide 8: Pipeline
Pipeline CANDIDATE / FOCUS PRECLINICAL PHASE 1 PHASE 2 PHASE 3 RIGHTS Ensovibep (MP0420) / COVID-19 MP0423 / COVID-19 AMG 506 (MP0310) / FAP x 4-1BB MP0317 / FAP x CD-40 AML CD3 x CD33 x CD70 x CD123 Abicipar / Neovascular AMD* Abicipar / DME Infectious disease Oncology Ophthalmology *Abicipar has n
Slide 9: Synergistic Partnerships Built on a Versatile Drug Platform
Synergistic Partnerships Built on a Versatile Drug Platform Ophthalmology Oncology Virology Therapeutic Area Deal Product Combination Deal Capability Deal • Partnership for abicipar, two • Partnership with Amgen to • Leverage production, global positive Phase 3 studies combine AMG 506 / MP0310 devel
Slide 10: COVID-19 Program Success Opens Path for Antiviral Portfolio
COVID-19 Program Success Opens Path for Antiviral Portfolio 10
Slide 11: Our COVID-19 Program: Two Outstanding Candidates
Our COVID-19 Program: Two Outstanding Candidates Ensovibep (MP0420)– best-in-class MP0423 – first-in-class • Tri-specific DARPin® antiviral targeting the RBD for • 3 DARPins blocking different domains of the viral spike highest potency & to prevent viral escape • High activity even if RBD mutates he
Slide 12: Cooperative Target Engagement Leads To Super Affinity
Cooperative Target Engagement Leads To Super Affinity DARPin #1; 1 hour off-rate DARPin #2; 1 hour off-rate DARPin #3; 1 hour off-rate Response (RU) Response (RU) Response (RU) Time (s) Time (s) Time (s) Response (RU) Multi-DARPin #1 - #2 - #3; >10 hours off rate sub pM target binding Time (s) 12
Slide 13: High Potency Inhibition Translates To In Vivo Properties
High Potency Inhibition Translates To In Vivo Prophylactic And Therapeutic Properties In vitro activity: Pseudotype In vivo activity: Kaplan Meier Plot - Neutralization Assay Hamster Model (6 animals/group) Pseudotype Neutralization Assay 100 1 Probability of MP0420, MP0423 Infection [%] Survival 50
Slide 14: Ensovibep Blocks the Virus and Prevents Infection in the Lung
Genome Copi Genome Copi 10 4 10 4 10 3 10 3 10 2 10 2 Ensovibep Blocks the Virus and Prevents Infection in the Lung 10 1 10 0 10 1 10 0 qPCR - lung Day 3 qPCR - lung Day 5 Red symbols: animals taken out of the study (at day 2 and 3) due to Viral 10 titer in the lung 8 Viral infectivity in the lung s
Slide 15: New SARS-CoV-2 Variant Analysis – Ensovibep May 2021
New SARS-CoV-2 Variant Analysis – Ensovibep May 2021 Neutralization Potency Variants Combined mutations IC50 [ng/mL] wild type (Wuhan) 1.0 B.1.1.7 / 69-70 del, del145, E484K, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H 3.2 United Kingdom 69-70 del, del145, S494P, N501Y, A570D, D614G, P681H, T71
Slide 16: Novartis Deal Terms
Novartis Deal Terms • CHF 210m in upfront and near term potential milestones • CHF 60m upfront • CHF 20m as a cash payment • CHF 40m in MOLN shares • CHF 150m milestone payment upon option exercise to license • 22% royalty on sales in commercial countries • Molecular Partners has agreed to forgo roy
Slide 17: Draft Development plan for MP0420
Draft Development plan for MP0420 2020 2021 2022 Possible EUA* Potential BLA Submission Phase 2-3 part A (N 400-500) / Phase 2-3 Part B (N >1700) Ph.1 studies 75 mg EMPATHY trial (healthy volunteers) 225 mg ambulatory patients with mild to 600 mg moderate symptomatic COVID-19 Subcutaneous bridging s
Slide 18: Ensovibep (MP0420) Phase 1
Ensovibep (MP0420) Phase 1 • Study initiated November 2020, all three cohorts fully enrolled • Double-blind, placebo controlled trial exploring safety and pharmacokinetics • IV administration • Up to 24 subjects total, stratified 3:1 (active: placebo) • Ages 18-65 • Dose range covers clinical doses
Slide 19: Ensovibep Upcoming Milestones
Ensovibep Upcoming Milestones • Final data from phase 1 • Initiate EMPATHY (Novartis / MP) • Part A results (N=400-500) • Part B initiate (N≥1,700) • Open label 2a initiation • Potential EUA in 2021 • 2a results mid 2021 • Potential S.C. bridging trials (Novartis / • Additional variant data MP) • In
Slide 20: DARPin Opportunities in Virology
DARPin® Opportunities in Virology Respiratory • RSV, influenza and others Viruses • Benefits as per COVID DARPin® • Multi-valency for superior potency • Corona, influenza Pandemic readiness • Early intervention • Multi-specificity for mutation to prevent spread resistance COVID • Speed of candidate
Slide 21: Clinical Programs: Expanded
Clinical Programs: Expanded 21
Slide 22: Unlock and Expand: Therapeutic Modalities
Unlock and Expand: Therapeutic Modalities Targeting peptide MHC complexes Next-generation T-cell engagers Unlock therapeutic platforms Tumor-localized immune cell activation Expand application space 22
Slide 23: Recent data at AACR Highlight Platform Potential
Recent data at AACR Highlight Platform Potential MP0317 (targeting CD40 and FAP) • MP0317, a FAPxCD40 targeting multi-specific DARPin® therapeutic, drives immune activation and leads to macrophage repolarization in vitro and ex vivo T-cell engager programs • Novel multi-specific DARPin® T-cell engag
Slide 24: Localized Immune Activators AMG 506 (MP0310) & MP0317
Localized Immune Activators AMG 506 (MP0310) & MP0317 24
Slide 25: Local Activation of Immune cells: FAP as a General Switch
Local Activation of Immune cells: Fibroblast Activation Protein (FAP) as a General Switch BODY TUMOR • In normal tissues, receptor is • High FAP concentration near broadly distributed tumor clusters receptors • Immune cell remains inactive • Immune cell is activated 4-1BB or CD40 FAP VS Tumor stroma
Slide 26: AMG 506/MP0310: Localized Activation of 4-1BB
AMG 506/MP0310: Localized Activation of 4-1BB HSA FAP 4-1BB 4-1BB HSA DARPin® DARPin® DARPin® DARPin® DARPin® Half-life extender Localizer Immune activator Immune activator Half-life extender ➢ Good safety profile without major systemic toxicity ➢ No liver toxicity or systemic activation of immune c
Slide 27: Combination of AMG 506/MP0310 and TAA x CD3 Bi-Specific
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 27
Slide 28: AMG 506 / MP0310 Accumulates in Tumor Tissue in Dose Dependent Manner
AMG 506 / MP0310 Accumulates in Tumor Tissue in Dose Dependent Manner MP0310 low dose colocalizes with FAP MP0310 high dose saturates FAP MP0310 < FAP MP0310 > FAP FAP+ Stroma rich area Endometrial carcinoma (Liver metastasis), C1D15 NSCLC (lung), C1D15 28
Slide 29: PD Activity in Paired Biopsies Supports MoA on 4-1BB Activation
PD Activity in Paired Biopsies Supports AMG 506 / MP0310 MoA on 4-1BB Activation BLOOD TUMOR CD8 T IFN Cytotoxicity NK Cells T Cells TH1 Cells Cells Gamma CD8+ T-cells: CD25+ 6 Signature score (log2) 100 5 % of CD8+ T-cells 80 60 40 4 20 3 0 C1D1 C1D8 C2D1 C2D8 2 Treatment on C1D1 & C2D1 Note: C1D1
Slide 30: MP0317: Localized Activation of CD40
MP0317: Localized Activation of CD40 ➢ Highly promising target with potential to significantly impact clinical outcomes for patients ➢ Complex biology to manage and administer safely and efficaciously ➢ FAP localization translating well, and will provide insights into dosing strategies ➢ First patie
Slide 31: MP0317: FAP-dependent Activation of Specific Immune Cells
MP0317: FAP-dependent Activation of Specific Immune Cells A B C Dendritic cells: Macrophages: B cells: CD86 ✓ IL-12 ✓ TNFα ✓ IL-12 ✓ CD69 ✓ CD83 ✓ CD80 ✓ IL-6 ✓ CCL17 ✓ CD86 ✓ x10 MP0317 in presence of FAP MP0317 in presence of FAP MP0317 in presence of FAP 3 MP0317 in absence of FAP MP0317 in absen
Slide 32: 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 Neg. CTRL* Tumor growth (mm3) mFAP x mCD40 mCD40 Ab Time after tumor inoculation (days) 32
Slide 33: New Therapeutic Platforms: Unlocked
New Therapeutic Platforms: Unlocked 33
Slide 34: Unlock and Expand: Therapeutic Modalities
Unlock and Expand: Therapeutic Modalities Targeting peptide MHC complexes Next-generation T-cell engagers Unlock therapeutic platforms Tumor-localized immune cell activation Expand application space 34
Slide 35: Current Limitations of CD3 Approaches
Current Limitations of CD3 Approaches Safety Efficacy Hyperimmune-stimulation Tumor escape Neurotoxicity Target engagement Cytokine release syndrome (CRS) 35
Slide 36: Our Solutions - Next Generation T-cell Engagers
Our Solutions - Next Generation T-cell Engagers Local & Slow conditional activation activation over time Tumor Concentration anti-CD3 cell Conventional Multi-specific T-cell engagers TCE dosage Controlled release anti- T-cell CD3 Time Tumor cell Improve safety to allow optimal dosing and Deepen Effi
Slide 37: Multi-DARPin Versatility Allows Screening for Function Sweet Spot
Multi-DARPin® Versatility Allows Screening for Function Sweet Spot # molecules Multi-domain DARPin® space Library to generate binders 1012 against TAA1 / TAA2 / TAA3… Identified functional and well behaved 10s DARPin® modules (for each target) Sweet X X spot Recombination of DARPin® modules: CD3 TAA
Slide 38: AML: Deadly Disease for About Half of the Patients
AML: Deadly Disease for About Half of the Patients 19,940 patients 11,180 patients diagnosed died US 2020 Patient are either unmet need cured or die within to cure more 1-2 years patients or (rapid, aggressive substantially delay relapses) the relapses MRD+ is driver of relapse (only partial eradica
Slide 39: The DARPin Solution: avidity driven multi-specific T-cell engager
The DARPin® Solution: an avidity driven multi-specific DARPin® T-cell engager Multi targets High avidity engagement CD70 CD123 CD33 CD3 Single targets Low affinity engagement Response T-cell 100% T-cell Efficient attack Therapeutic of heterogenous Minimal effect on TAA window healthy cells cancer ce
Slide 40: DARPin solution
DARPin® solution Multi-specific T-cell engager with improved benefit/risk in AML Efficacy Safety • Higher dose levels for efficient killing of cancer cells • Reduce off-tumor effects • Multiple attack: Specific killing of several malignant • Reduce hyper-immune stimulation cell types (e.g. cytokine
Slide 41: Summary and Outlook
Summary and Outlook Targeting peptide MHC complexes Next-generation T-cell engagers Unlock Virology therapeutic platforms Tumor-localized immune cell activation Expand application space 41
Slide 42: Summary and Outlook
Summary and Outlook Solid pMHC DARPin® platform Targeting peptide established: progressing candidates MHC complexes internally and in partnerships Progressing multi-specific T-cell Engager Next-generation candidates and expanding first product T-cell engagers candidates with "controlled activation"
Slide 43: Pipeline
Pipeline CANDIDATE / FOCUS PRECLINICAL PHASE 1 PHASE 2 PHASE 3 RIGHTS Ensovibep (MP0420) / COVID-19 MP0423 / COVID-19 AMG 506 (MP0310) / FAP x 4-1BB MP0317 / FAP x CD-40 AML CD3 x CD33 x CD70 x CD123 Abicipar / Neovascular AMD* Abicipar / DME Infectious disease Oncology Ophthalmology *Abicipar has n
Slide 44: Upcoming Potential Catalysts Across The Portfolio in 2021
Upcoming Potential Catalysts Across The Portfolio in 2021 Antiviral portfolio Ensovibep ▪ POC with potential Emergency Use Authorization in 2021 (MP0420) ▪ BLA submission possible in 2022 MP0423 ▪ MP0423 FIH Novel antivirals ▪ Develop novel DARPins for viral targets with first new target expected to
Slide 45: Upcoming Catalysts Across The Portfolio
Upcoming Catalysts Across The Portfolio Antiviral portfolio Ensovibep ▪ POC with Emergency Use Authorization in 2021 (MP0420) POC for ▪ BLA submission possible in 2022 MP0423 ensovibep ▪ MP0423 FIH Novel antivirals ▪ Develop novel DARPins for viral targets with first new target announced 2021 Immuno
Slide 46: Financials
Financials 46
Slide 47: Financial Overview & Milestones
Financial Overview & Milestones: • Q1 Cash 2021: CHF 145.6 (~$155m), no debt • Successful capital raise of CHF 75m, completed in early July 2020 • Additional funding from Novartis transaction (CHF 60, received in October-November 2020) • Funded into 2023, without consideration of potential future mi
Slide 48: Molecular Partners AG
Molecular Partners AG Wagistrasse 14 8952 Zürich-Schlieren Switzerland www.molecularpartners.com T +41 44 755 77 00 48
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