Exicure, Inc. · NASDAQ:XCUR
Exicure — Technical Presentation (September 2020)
91 slides from Exicure's technical presentation, Sep 16, 2020
Slide 1: Cavrotolimod (AST-008) Intratumoral Immunotherapy KOL Day
Sept Exhibit 99.2 16 2020 Cavrotolimod (AST-008) Intratumoral Immunotherapy KOL Day 16 Sept 2020
Slide 2: Cautionary Note Regarding Forward Looking Statements
Cautionary Note Regarding Forward Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "anticipate," "expect," "plan," "may," "will," and similar expressions (as well as other words or expre
Slide 3: Today's Speakers
Today’s Speakers David Giljohann, PhD Doug Feltner, MD Matthias Schroff, PhD Steven O’Day, MD Exicure Exicure Exicure Executive Director CEO CMO COO John Wayne Cancer Institute and Cancer Clinic Shailender Bhatia, MD Emil deGoma, MD Weston Daniel, PhD Associate Professor Exicure Exicure University o
Slide 4: Program Agenda
Program Agenda Cavrotolimod (AST-008): Exicure Vision and Spherical Nucleic Closing Remarks Q&A Session Strategy Acid TLR9 Agonist Immunotherapy for Oncology David Giljohann, PhD All David Giljohann, PhD All 4
Slide 5: Vision and Strategy
Vision and Strategy David Giljohann PhD; CEO
Slide 6: The Exicure Difference
The Exicure Difference PLATFORM THERAPEUTICS VALUE Better Uptake, Greater Stability Growing Development Pipeline XCUR (NASDAQ) RARE DISEASE FORMS MARKET CAP CASH 3-D architecture drives NEURO IMMUNO- better uptake Friedreich’s Ataxia ONCOLOGY $200M $99M (IND-enabling CAVRO 8/1/20 3/31/20 and greater
Slide 7: SNAs Differentiated from Conventional Linear Oligos
SNAs Differentiated from Conventional Linear Oligos The Benefits Differentiated Uptake 1 HIGH CELL UPTAKE SNA Others Without encapsulation or SNAs Linear Oligos chemical modifications 2 Binding ENHANCED STABILITY VS Extended therapeutic half-life Cell surface in cells Scavenger receptor 3 EXTRA-HEPA
Slide 8: Our Broad SNA Therapeutic Opportunity
Our Broad NEUROLOGY IMMUNO- Near-Term Therapeutic ONCOLOGY SNA Therapeutic Opportunity Focus Technology DERMATOLOGY SNA technology allows nucleic acids to be OPHTHALMOLOGY delivered to local sites throughout the body, GI TRACT expanding the potential application of nucleic LUNG acid therapeutics LIV
Slide 9: Focused Development Pipeline
Focused Development Pipeline PRECLINICAL DEV PHASE 1 PHASE 2 IMMUNO-ONCOLOGY MERKEL CELL CARCINOMA1 CAVROTOLIMOD (TLR9 AGONIST) CUTANEOUS SQUAMOUS CELL CARCINOMA1 NEUROLOGY XCUR-FXN FRIEDREICH’S ATAXIA XCUR-NEURO-02 UNDISCLOSED DERMATOLOGY XCUR17 (ANTI-IL17RA) INFLAMMATORY DISORDERS currently unpart
Slide 10: Cavrotolimod Targeting Merkel Cell and Cutaneous Squamous Cell Carcinoma
NEUROLOGY IMMUNO- ONCOLOGY Cavrotolimod SNA Technology DERMATOLOGY Targeting Merkel cell carcinoma and cutaneous OPHTHALMOLOGY squamous cell carcinoma GI TRACT LUNG LIVER 10
Slide 11: Cavrotolimod (AST-008)
Cavrotolimod (AST-008) Douglas Feltner MD; CMO
Slide 12: Summary of Cavrotolimod and Dose Escalation Results
Summary of Cavrotolimod and Dose Escalation Results • Cavrotolimod (AST-008) is a TLR9 agonist that leverages Exicure’s SNA platform • Cavrotolimod has shown a positive efficacy profile in the Phase 1b dose escalation study evaluating intratumoral (IT) cavrotolimod + IV pembrolizumab in patients wit
Slide 13: Advancing Cavrotolimod in Nonmelanoma Skin Cancers with Significant Unmet Need
Advancing Cavrotolimod in Nonmelanoma Skin Cancers with Significant Unmet Need INDICATIONS PHASE 1 PHASE 2 Merkel Cell Carcinoma Refractory to Anti-PD-(L)-1 Cavrotolimod + Pembrolizumab Cutaneous Squamous Cell Carcinoma Refractory to Anti-PD-1 Cavrotolimod + Cemiplimab 13
Slide 14: Shailender Bhatia, MD
Shailender Bhatia, MD Dr. Bhatia is Associate Professor of Medical Oncology at the University of Washington and Fred Hutchinson Cancer Research Center. Focused on immunotherapy clinical trials that aim at improving outcomes in skin cancer Especially interested in intratumoral and other novel therape
Slide 15: Steve O'Day, MD
Steve O’Day, MD Dr. O’Day is the Executive Director of John Wayne Cancer Institute and Cancer Clinic at Providence Saint John’s Health Center, Regional Director of Research and Professor of Medical Oncology. Recognized as one of the preeminent melanoma specialists in the world Leader in the developm
Slide 16: Disclosures
Disclosures Steve O’Day, MD • Advisory Board – Exicure, Biothera, BMS, BioNTech, Immunsys, Merck • Consultant – Agenus, Immunsys • Grants/Research Support – Agenus, Amgen, Biothera, BMS, Exicure, Genocea, Incyte, Merck, Ultimovacs, Viralytics • Speaker’s Bureau – BMS Shailender Bhatia, MD • Advisory
Slide 17: Cancer Immunotherapy and TLR9 Agonism
Cancer Immunotherapy and TLR9 Agonism Shailender Bhatia MD
Slide 18: Immune Checkpoint Blockade Established the Role of Immunotherapy for Cancer
Immune Checkpoint Blockade, a Transformational Therapeutic Advance, Established The Role Of Immunotherapy For Cancer Anti-PD-1 Mechanism FDA Approved Indications › Cervical Cancer › Colorectal Cancer Merkel Cell › Cutaneous Squamous Cell Carcinoma Carcinoma › Endometrial Carcinoma › Esophageal Cance
Slide 19: Cancer Immunity Cycle as an Immunotherapy Pharmacodynamic Model
Cancer Immunity Cycle as an Immunotherapy Pharmacodynamic Model 4 Step Release of cancer cell antigens 1 3 Step Cancer antigen presentation 2 Step Priming and activation 5 3 Step Trafficking of T cells to tumors 4 Step Infiltration of T cells into tumors 2 5 6 Step 6 Recognition of cancer cells by T
Slide 20: Anti-PD-1 Pharmacodynamics Help Propagate Two Steps of the Cycle
Anti-PD-1 Antibody Pharmacodynamics Help Propagate Two, not All, Steps of the Cancer Immunity Cycle Step Release of cancer cell antigens 1 3 Step 2 Cancer antigen presentation Step Priming and activation 3 Disinhibited by anti-PD-1 / anti-PD-L1 Step 4 Trafficking of T cells to tumors Step 5 Infiltra
Slide 21: Hypothesis: A TLR-Targeting SNA Will Promote Remaining Steps
Hypothesis: A TLR-Targeting SNA will Help Promote the Remaining Steps of the Cancer Immunity Cycle and Produce Anti-tumor Responses in Anti-PD-1 Resistant Tumors 4 Step Release of cancer cell antigens 1 Driven by activated NK and T cells 3 Step Cancer antigen presentation 2 Driven by TLR agonism Ste
Slide 22: TLR9 and SNAs
TLR9 and SNAs Weston Daniel PhD; VP Translational Research
Slide 23: SNAs are Ideal for TLR9 Activation
SNAs are Ideal for TLR9 Activation SNA Scavenger Receptors Toll like receptor 9 (TLR9) agonism can produce the desired pharmacodynamics TLR9 is found in the endosome of cells - SNAs are colocalized in the endosome Endosome after internalization into cells TLR9s The SNAs are coated externally with ol
Slide 24: Cavrotolimod (AST-008) is Exicure's TLR9 Agonist
Cavrotolimod (AST-008) is Exicure’s TLR9 Agonist TLR9 agonist oligonucleotides – potent activators Cavrotolimod of immunity • Cytokines/chemokine signaling (IP-10, IL-12) for immune cell trafficking • T cell activation • NK cell activation Benign lipid nanoparticle • Scaffold for SNA structure Oligo
Slide 25: Cavrotolimod and Anti-PD-1 Robustly Activate All Steps of the Cycle
Cavrotolimod and Anti-PD-1 Robustly Activate All Steps of the Cancer Immunity Cycle 4 Step Release of cancer cell antigens 1 ✓ 3 Step Cancer antigen presentation 2 ✓ Step Priming and activation 5 3 ✓ Step Trafficking of T cells to tumors 4 ✓ Step Infiltration of T cells into tumors 2 5 ✓ 6 Step 6 Re
Slide 26: Nonclinical Studies
Nonclinical Studies Matthias Schroff PhD; COO
Slide 27: Cavrotolimod Demonstrates Higher Cell Uptake than Linear Structures
Cavrotolimod Demonstrates Higher Cell Uptake than Linear Structures 100 Cavrotolimod Linear TLR9 agonist SNAs 50 VS Loaded PBMC (%) Others 0 0.1 1 10 100 Linear Oligos Oligonucleotide (μM) PBMC = peripheral blood mononuclear cells 27
Slide 28: Cavrotolimod Demonstrates Better TLR9 Activation than Linear Structures
Cavrotolimod Demonstrates Better TLR9 Activation than Linear Structures 4 Cavrotolimod Linear TLR9 agonist GpC control SNA 3 SNAs VS 2 B Activation (fold PBS) (fold B Activation κ After 4 hr IncubationAfter 4 Others - NF 1 0.1 1.0 10 Linear Oligos Oligonucleotide (μM) 28
Slide 29: Murine Cavrotolimod Produces a Superior Anti-tumor Response
Murine Cavrotolimod Produces a Superior Anti-tumor Response Versus Linear Oligonucleotides Cavrotolimod Superior to Linear Naïve Mice Naïve Mice Naïve Mice Vehicle EMT6 4T1 ) Anti-PD-1 CT26 3 2000 Anti-PD-1+Linear Oligo Cavro-Treated Mice Cavro-Treated Mice Anti-PD-1+Cavro EMT6 4T1 CT26 1500 1000 50
Slide 30: Murine Cavrotolimod Produces a Tumor-specific Memory Response
Murine Cavrotolimod Produces a Tumor-specific Memory Response Cavrotolimod Cavrotolimod-Treated Mice Superior Develop Long Term Immunity to to Linear EMT6 Tumors Naïve Mice Naïve Mice Naïve Mice Vehicle EMT6 4T1 ) Anti-PD-1 CT26 3 2000 Anti-PD-1+Linear Oligo Cavro-Treated Mice Cavro-Treated Mice Ant
Slide 31: Superior Anti-tumor Response and Tumor-specific Memory Response
Murine Cavrotolimod Produces Both a Superior Anti-tumor Response Versus Linear Oligonucleotides and a Tumor-specific Memory Response Cavrotolimod Cavrotolimod-Treated Mice Immunity is Tumor- Superior Develop Long Term Immunity to Specific to Linear EMT6 Tumors Naïve Mice Naïve Mice Naïve Mice Vehicl
Slide 32: Dose Escalation Data
Dose Escalation Data Steve O’Day MD
Slide 33: Phase 1b Dose Escalation Summary
Phase 1b Dose Escalation Summary Clinically meaningful overall Durable response Systemic effects response rate Proof of concept in largely Pharmacodynamic profile Good safety profile and well refractory population corroborating efficacy tolerated 33
Slide 34: Phase 1b Dose Escalation Summary: Response Rate
Phase 1b Dose Escalation Summary Clinically meaningful overall response rate ORR 21% (all doses) ORR 33% (highest and Phase 2 dose) 34
Slide 35: Phase 1b Dose Escalation Summary: Durable Response
Phase 1b Dose Escalation Summary Clinically meaningful overall Durable response response rate ORR 21% (all doses) 16 months to date and ongoing in all 4 responders ORR 33% (highest and Phase 2 dose) 6+ months in all 4 responders 35
Slide 36: Phase 1b Dose Escalation Summary: Systemic Effects
Phase 1b Dose Escalation Summary Clinically meaningful overall Durable response Systemic effects response rate ORR 21% (all doses) 16 months to date and ongoing in Regression in distant and regional all 4 responders lesions ORR 33% (highest and Phase 2 dose) 6+ months in all 4 responders 36
Slide 37: Phase 1b Summary: Refractory Population
Phase 1b Dose Escalation Summary Clinically meaningful overall Durable response Systemic effects response rate ORR 21% (all doses) 16 months to date and ongoing in Regression in distant and regional all 4 responders lesions ORR 33% (highest and Phase 2 dose) 6+ months in all 4 responders Proof of co
Slide 38: Phase 1b Summary: Pharmacodynamic Profile
Phase 1b Dose Escalation Summary Clinically meaningful overall Durable response Systemic effects response rate ORR 21% (all doses) 16 months to date and ongoing in Regression in distant and regional all 4 responders lesions ORR 33% (highest and Phase 2 dose) 6+ months in all 4 responders Proof of co
Slide 39: Phase 1b Summary: Safety Profile
Phase 1b Dose Escalation Summary Clinically meaningful overall Durable response Systemic effects response rate ORR 21% (all doses) 16 months to date and ongoing in Regression in distant and regional all 4 responders lesions ORR 33% (highest and Phase 2 dose) 6+ months in all 4 responders Proof of co
Slide 40: Seamless Phase 1b/2 Dose Escalation and Dose Expansion Study
Seamless Phase 1b/2 Dose Escalation and Dose Expansion Study STUDY ELEMENTS PHASE 1b DOSE ESCALATION Open-label, multicenter Phase 1b/2 combined dose-escalation/dose-expansion study Intratumoral (IT) cavrotolimod plus pembrolizumab across all solid tumors in the Phase 1b dose escalation portion Two
Slide 41: Study Dosing Schedule and Assessments
Study Dosing Schedule and Assessments DOSING CYCLE 1 CYCLE 2 CYCLE 3 CYCLE 4+ W1 W2 W3 W4 W5 W6 W7 W8 W9 W10 W11 Cavrotolimod IT Pembrolizumab IV Assessments CT/MRI scans (RECIST v1.1) Peripheral pharmacodynamic assessments: • Cytokines/chemokines Tumor photography • Immune cell profiling Tumor biop
Slide 42: Dose Escalation Mostly Enrolled Patients with Cutaneous Tumors
Dose Escalation Mostly Enrolled Patients with Cutaneous Tumors that had Previously Progressed on Anti-PD-1 Antibodies Baseline characteristics (N=20) n (%) Melanoma 10 (50%) Merkel cell carcinoma 5 (25%) Cancer type Cutaneous squamous cell carcinoma 2 (10%) Head & neck squamous cell carcinoma 2 (10%
Slide 43: Clinically Meaningful Confirmed Overall Response Rate
Clinically Meaningful Confirmed Overall Response Rate Observed in Phase 1b Patients 21% ORR 33% ORR All Dose Levels 32 mg Dose Level 4 PR of 19 evaluable patients 2 PR of 6 patients 43
Slide 44: Durable Confirmed Responses Observed After Treatment
Durable Confirmed Responses Observed After Treatment All Four Responses Ongoing, All at Least 6 Months in Duration; One Patient With 16 Month Response End of combination treatment 10 Merkel2- Follow-up after end of combination treatment 2 mg0… 10 Merkel1- 4 mg0… 10 Melanoma4- 32 mg0… End of cavrotol
Slide 45: Confirmed Responses Observed in Anti-PD-1 Refractory Tumors
Confirmed Responses Observed in Anti-PD-1 Refractory Tumors Three of Four Responders Were Progressing on Anti-PD-1 at Enrollment Prior Anti-PD-1 Time Between Last Tumor Last Response Dose of PD-1 and First Cavro Dose End of combination treatment MCC Relapsed off anti-PD-1 69 weeks Follow-up after en
Slide 46: Response in Refractory Melanoma Patient: Prior to Cavro
Response in Refractory Melanoma Patient with Progression on Anti-PD-1 at Enrollment PRIOR TO CAVRO, PROGRESSION ON PEMBROLIZUMAB Before pembrolizumab After 3 cycles of pembrolizumab 76-year-old man with melanoma 46
Slide 47: Response in Refractory Melanoma Patient: Response to Cavrotolimod
Response in Refractory Melanoma Patient with Progression on Anti-PD-1 at Enrollment RESPONSE TO CAVROTOLIMOD + PRIOR TO CAVRO, PROGRESSION ON PEMBROLIZUMAB PEMBROLIZUMAB AT 12 WEEKS Before pembrolizumab After 3 cycles of pembrolizumab PR ongoing through 36 weeks 76-year-old man with melanoma 47
Slide 48: Response in Refractory Melanoma Patient: Lesions at Baseline
Response in Refractory Melanoma Patient with Progression on Anti-PD-1 at Enrollment RESPONSE TO CAVROTOLIMOD + LESIONS AT BASELINE PEMBROLIZUMAB AT 12 WEEKS Effects on both lesions Non-injected Injected 76-year-old man with melanoma 48
Slide 49: Robust Pharmacodynamic Response in Refractory Melanoma Patient
Robust Pharmacodynamic Response in Refractory Melanoma Patient with Progression on Anti-PD-1 at Enrollment Peripheral Chemokine and Cell Activation IP-10 NK Cells Cytotoxic T Cells (pg/mL) (% Activated) (% Activated) 2399 86 63 26 25 132 Predose Postdose Predose Postdose Predose Postdose 49 Postdose
Slide 50: Complete Response in Anti-PD-1 Relapsed Merkel Cell Patient
Complete Response of Injected and Noninjected Tumors in Anti- PD-1 Relapsed Merkel Cell Patient Week 3 86-year-old woman with Merkel cell carcinoma Complete response on pembrolizumab; relapsed after discontinuation On cavrotolimod + pembrolizumab, overall partial response/complete target response ob
Slide 51: Complete Response in Anti-PD-1 Relapsed Merkel Cell Patient
Complete Response of Injected and Noninjected Tumors in Anti- PD-1 Relapsed Merkel Cell Patient Week 3 Week 12 86-year-old woman with Cavrotolimod + Merkel cell carcinoma pembrolizumab Complete response on pembrolizumab; relapsed after discontinuation On cavrotolimod + pembrolizumab, overall partial
Slide 52: Systemic Immune Activation in Relapsed Merkel Cell Patient
Systemic Immune Activation Observed after Cavrotolimod Dosing in Relapsed Merkel Cell Patient Peripheral Chemokine and Cell Activation IP-10 NK Cells Cytotoxic T Cells (pg/mL) (% Activated) (% Activated) 547 57 51 17 11 46 Predose Postdose Predose Postdose Predose Postdose 52 Postdose: 24 hours post
Slide 53: Decreased Target Tumor Diameter Observed in 37% of Patients
Decreased Target Tumor Diameter Observed in 37% of Patients Target Tumor Response: Sum of Injected and Noninjected Lesions 100% 0% Mel CSCC MCC Mel Mel Mel MCC MCC HSNCC Mel Mel Mel MCC MCC LMS Mel Mel Change in from Change Baseline Target Lesion Diameters (%) Lesion Diameters Target -100% Figure ex
Slide 54: Regression Observed in Injected and Noninjected Tumors
Regression Observed in Both Cavrotolimod-Injected and Noninjected Tumors Target Tumor Response: Sum of Injected Lesions vs Sum of Noninjected Lesions 100% Mel Mel 0% n/a Mel CSCC MCC Mel MCC MCC HSNCC Mel Mel Mel MCC MCC LMS Mel Mel n/a Change from Baseline from Change in Target Lesion Diameters (%)
Slide 55: Tumor Regression Observed in Distant, Noninjected Lesions
Tumor Regression Observed in Distant, Noninjected Lesions Injected Noninjected CSCC -33% R face -33% L neck -20% R lung 55
Slide 56: Tumor Regression Observed in Distant, Noninjected Lesions
Tumor Regression Observed in Distant, Noninjected Lesions Injected Noninjected CSCC MCC Melanoma MCC -33% R face -33% -29% L neck R axillary LN -47% L abdomen -20% R lung -100% -50% L leg -30% L axillary LN R axillary LN -29% L abdomen -100% L leg Overall response PD (new lesion) PR PD (new lesion)
Slide 57: Cavrotolimod Safe and Generally Well Tolerated
Cavrotolimod Safe and Generally Well Tolerated Injection Site Reactions and Flu-like Symptoms as Expected from Local and Systemic Immune Activation • Majority (98%) of treatment-related adverse events (AEs) were Grade (G) 1 or 2 • Injection site reactions and flu-like symptoms were the most commonly
Slide 58: Pharmacodynamic Data
Pharmacodynamic Data Weston Daniel, PhD; VP Translational Research
Slide 59: Comprehensive Pharmacodynamic Profile Consistent with Antitumor Immune Activation
Comprehensive Pharmacodynamic Profile Consistent with Antitumor Immune Activation INCREASED CYTOKINES AND CHEMOKINES ACTIVATED CIRCULATING IMMUNE EFFECTOR CELLS >20x IP-10/CXCL10 35% → 91% 21% → 62% >1.5x IL-12p40 Activated NK cells Activated Cytotoxic T cells (% that are activated) (% that are acti
Slide 60: Comprehensive Pharmacodynamic Profile Consistent with Antitumor Immune Activation
Comprehensive Pharmacodynamic Profile Consistent with Antitumor Immune Activation INCREASED CYTOKINES AND CHEMOKINES ACTIVATED CIRCULATING IMMUNE EFFECTOR CELLS >20x IP-10/CXCL10 35% → 91% 21% → 62% >1.5x IL-12p40 Activated NK cells Activated Cytotoxic T cells (% that are activated) (% that are acti
Slide 61: Comprehensive Pharmacodynamic Profile Consistent with Antitumor Immune Activation
Comprehensive Pharmacodynamic Profile Consistent with Antitumor Immune Activation INCREASED CYTOKINES AND CHEMOKINES ACTIVATED CIRCULATING IMMUNE EFFECTOR CELLS >20x IP-10/CXCL10 35% → 91% 21% → 62% >1.5x IL-12p40 Activated NK cells Activated Cytotoxic T cells (% that are activated) (% that are acti
Slide 62: Cavrotolimod Promotes the Remaining Steps of the Cancer Immunity Cycle
Cavrotolimod Promotes the Remaining Steps of the Cancer Immunity Cycle and Contributes to Anti-tumor Responses in Anti-PD-1 Resistant Tumors 4 Step Release of cancer cell antigens 1 Driven by activated NK and T cells 3 Step Cancer antigen presentation 2 Driven by TLR agonism Step Priming and activat
Slide 63: Phase 1b Dose Escalation Summary
Phase 1b Dose Escalation Summary Clinically meaningful overall Durable response Systemic effects response rate ORR 21% (all doses) 16 months to date and ongoing in Regression in distant and regional all 4 responders lesions ORR 33% (highest and Phase 2 dose) 6+ months in all 4 responders Proof of co
Slide 64: Merkel Cell Carcinoma and Cutaneous Squamous Cell Carcinoma
Merkel Cell Carcinoma and Cutaneous Squamous Cell Carcinoma Shailender Bhatia MD
Slide 65: Skin, the Largest Organ, is Also the Most Vulnerable to Cancer
Skin, the Largest Organ, is Also the Most Vulnerable to Cancer Development Non-melanoma Skin Cancers Skin Cancer Incidence (US) Skin Cancer Deaths (US) (NMSCs) Mel: 60,000 BCC: 1,250 • 5.4 million diagnosed in 2012 CSCC: 700,000 • 3.3 million treated MCC: 600 CSCC: 1,250 – 80% BCCs MCC: 3,000 – 20%
Slide 66: Alarming Increase in Incidence of Aggressive Skin Cancers
Alarming Increase in Incidence of Aggressive Skin Cancers 2500 New MCC Cases in 2013; Incidence Rate by Age Estimated ~3300 by the Year 2025 Paulson K, et al. J Am Acad Dermatol. 2017. MCC: Merkel cell carcinoma 66
Slide 67: Merkel Cell Carcinoma: An Aggressive Cancer With Poor Outcomes
Merkel Cell Carcinoma (MCC): An Aggressive Cancer With Poor Outcomes Rapid Progression of MCC After ~1 year • Disease-mortality rate ~45% (3-fold higher than melanoma) • Historical 5-year overall survival for stage IV MCC < 20% Lemos BD, et al. J Am Acad Dermatol. 2010. 67
Slide 68: Cutaneous Squamous Cell Carcinoma: An Aggressive Cancer With Poor Outcomes
Cutaneous Squamous Cell Carcinoma (CSCC): Like MCC, an Aggressive Cancer With Poor Outcomes Metastatic CSCC Overall Survival for Metastatic CSCC • Historical 5-year overall survival rate of 26% for stage 4 disease • Historical median overall survival was 2.2 years Gutzmer R, et al. Dtsch Arztebl Int
Slide 69: NMSCs Have a Strong Rationale for Immunotherapy
NMSCs Have a Strong Rationale for Immunotherapy BCC also has a very high TMB (median ~45/MB) Yarchoan, et al. NEJM. 2017. Harms, et al. CA Res. 2015. Walter A, et al. CCR. 2010. Paulson, et al. Unpublished. BCC: basal cell carcinoma; CSCC: cutaneous squamous cell carcinoma; MB: megabase; MCC: Merkel
Slide 70: High Response Rates with Anti-PD-1 Therapy But Unmet Need Remains
High Response Rates with Anti-PD-1 Therapy in NMSCs Like MCC But Distinct Populations with Unmet Need Have Emerged Intrinsic Resistance First Line Pembrolizumab in MCC Non-responders to PD-1 blockade Acquired Resistance Progressors after initial response Nghiem P, Bhatia S et al. 2016 NEJM 70
Slide 71: Nonmelanoma Skin Cancers Are Optimal Tumors for Intratumoral Immunotherapies
Nonmelanoma Skin Cancers Are Optimal Tumors for Development of Intratumoral Immunotherapies Like Cavrotolimod Rare but Strategic Confluence of favorable factors 71
Slide 72: Nonmelanoma Skin Cancers Are Optimal Tumors: Responsive to Immunotherapy
Nonmelanoma Skin Cancers Are Optimal Tumors for Development of Intratumoral Immunotherapies Like Cavrotolimod Rare but Strategic Confluence of favorable factors Responsive to Immunotherapy Among cancers with the highest tumor mutational burdens (TMB) Large diversity of neoantigens available as immun
Slide 73: Nonmelanoma Skin Cancers Are Optimal Tumors: Unmet Medical Need
Nonmelanoma Skin Cancers Are Optimal Tumors for Development of Intratumoral Immunotherapies Like Cavrotolimod Rare but Strategic Unmet Medical Need High morbidity and mortality of Confluence of favorable factors advanced MCC and CSCC; even greater than melanoma Responses to anti-PD-(L)1 appear less
Slide 74: Nonmelanoma Skin Cancers Are Optimal Tumors: Practical, Personalized Dosing
Nonmelanoma Skin Cancers Are Optimal Tumors for Development of Intratumoral Immunotherapies Like Cavrotolimod Practical, Personalized Rare but Strategic Unmet Medical Need Dosing High morbidity and mortality of Superficial lesions amenable to advanced MCC and CSCC; even Confluence of favorable facto
Slide 75: Phase 2 Dose-Expansion Stage
Phase 2 Dose-Expansion Stage Emil deGoma MD; VP Clinical Development
Slide 76: Rationale for Prioritization of MCC and CSCC in Phase 2
Rationale for Prioritization of Advanced MCC and CSCC Refractory to Anti-PD-(L)1 Therapy in Phase 2 Dose-Expansion Stage UNMET MEDICAL NEED RESPONSIVE TO IMMUNOTHERAPY EFFICIENT DEVELOPMENT • High morbidity and mortality of • Robust mechanistic rationale • Rare refractory skin tumors, advanced MCC a
Slide 77: Phase 2 Dose-Expansion Stage in Anti-PD-(L)1 Refractory Patients
Phase 2 Dose-Expansion Stage in Anti-PD-(L)1 Refractory Patients Merkel cell carcinoma Documented progression on anti-PD-(L)1 therapy Cavrotolimod 32 mg IT + pembrolizumab IV N=29 Cutaneous squamous cell carcinoma Documented progression on anti-PD-1 therapy Cavrotolimod 32 mg IT + cemiplimab IV N=29
Slide 78: Phase 2 Dosing Schedule and Assessments
Phase 2 Dosing Schedule and Assessments DOSING CYCLE 1 CYCLE 2 CYCLE 3 CYCLE 4+ W1 W2 W3 W4 W5 W6 W7 W8 W9 W10 W11 Cavrotolimod 32 mg IT Pembrolizumab IV (MCC) or Cemiplimab IV (CSCC) Assessments CT/MRI scans (RECIST v1.1) Peripheral pharmacodynamics: Cytokines/chemokines; Tumor photography Immune c
Slide 79: Support from Leading Investigators and Top-Tier Sites
Support from Leading Investigators and Top-Tier Sites Dana-Farber Cancer Institute Northwestern University University of Seattle Cancer Care Alliance University of Iowa Pittsburgh (University of Washington) University of Cincinnati Memorial Sloan Kettering Mount Sinai University of California San Fr
Slide 80: Timelines for Phase 2 Stage
Timelines for Phase 2 Stage INDICATIONS 2020 2021 2022 Merkel Cell Carcinoma Refractory to Anti-PD-(L)1 Cavrotolimod IT + pembrolizumab IV Phase 2 ORR readout N=29 Interim ORR readout Cutaneous Squamous Cell Carcinoma Refractory to Anti-PD-1 Cavrotolimod IT + cemiplimab IV Phase 2 ORR readout N=29 I
Slide 81: Vision for Expansion
Vision for Expansion Douglas Feltner MD; CMO
Slide 82: Leveraging Experience to Address Additional Skin Cancers
Leveraging Experience to Address Additional Skin Cancers Cutaneous Squamous Merkel Cell Carcinoma Cell Carcinoma Skin Cancers Amenable to intratumoral injection Highly immunogenic Basal Cell Carcinoma Overlapping provider population Melanoma • Addressable population • Further assess as data of 7,500
Slide 83: Adjacent Skin Cancers as Most Proximal Potential Next Steps
Adjacent Skin Cancers as Most Proximal Potential Next Steps Locally Advanced/Metastatic Melanoma • Responses (2/4) observed in PD-1 resistant patients with cavrotolimod in Phase 1b at 32 mg • Further assess ORR in Phase 2 cohort • Encouraging data from other TLR9 agonists Locally Advanced/Metastatic
Slide 84: Indication Expansion Opportunities
Indication Expansion Opportunities Market Opportunity (2026, estimated) Indication Primary or Secondary Incident Cavro Target Resistance to anti-PD-1 Patient Population Melanoma 70-80% ~10,000 Basal Cell Carcinoma 70-80% ~7,500 Head and Neck Squamous Cell Carcinoma 75-85% ~13,000 Non-Small Cell Lung
Slide 85: Cavrotolimod Positioning
Cavrotolimod Positioning Douglas Feltner MD; CMO
Slide 86: Cavrotolimod Clinical Profile Highly Competitive vs Other TLR9 Agonists
Cavrotolimod Clinical Profile Highly Competitive vs Other TLR9 Agonists Sponsor Efficacy Combination ORR Durability Safety All solid tumors: Median: not reached Unrelated SAEs: 5% Exicure Pembrolizumab 21% (all doses) ≥6 months: 100% Related SAE: 0 33% (highest dose) (4 of 4) Median: 20 months Check
Slide 87: Cavrotolimod Summary
Cavrotolimod Summary Douglas Feltner MD; CMO
Slide 88: Summary of Cavrotolimod and Dose Escalation Results
Summary of Cavrotolimod and Dose Escalation Results • Cavrotolimod (AST-008) is a TLR9 agonist that leverages Exicure’s SNA platform • Cavrotolimod has shown a positive efficacy profile in the Phase 1b dose escalation study evaluating intratumoral (IT) cavrotolimod + IV pembrolizumab in patients wit
Slide 89: Summary of Cavrotolimod and Dose Escalation Results Continued
Summary of Cavrotolimod and Dose Escalation Results Continued • Highest Phase 1B dose (32 mg) chosen for Phase 2, as recommended by Data Review Committee • The cavrotolimod clinical profile is highly competitive compared with other TLR9 agonists in development • First-to-market opportunity in two ra
Slide 90: Closing Remarks
Closing Remarks David Giljohann PhD, CEO
Slide 91: Exicure
exicure