OTCQB: XCUR. October 2018

Transcription

1 OTCQB: XCUR October 2018

2 Disclaimers SPECIAL NOTE REGARDING FORWARD LOOKING STATEMENTS This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations, business strategy, current and prospective product candidates, results of ongoing clinical trials, planned clinical trials and preclinical activities, product approvals, timing and likelihood of success, plans and objectives of management for future operations, future results of anticipated product candidates, current or planned collaborations, are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in an evolving environment. New risks and uncertainties may emerge from time to time, and it is not possible for management to predict all risks and uncertainties. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. NO OFFER OR SOLICITATION This presentation is not intended to and does not constitute an offer to sell, or the solicitation of an offer to subscribe for or buy, or an invitation to purchase or subscribe for any securities in any jurisdiction pursuant to the proposed transaction or otherwise, nor shall there be any sale, issuance or transfer of securities in any jurisdiction in contravention of applicable law. No offer or sale of securities shall be made except in a private placement in reliance upon the exemption from securities registration afforded by Section 4(a)(2) of the Securities Act of 1933, as amended (the Securities Act ), and Rule 506 of Regulation D promulgated by the SEC under the Securities Act. Subject to certain exceptions to be approved by the relevant regulators or certain facts to be ascertained, the offer of securities will not be made directly or indirectly, in or into any jurisdiction where to do so would constitute a violation of the laws of such jurisdiction, or by use of the mails or by any means or instrumentality (including without limitation, facsimile transmission, telephone and the internet) of interstate or foreign commerce, or any facility of a national securities exchange, of any such jurisdiction. 2

3 Exicure Facts and Figures Based outside Chicago, IL ~30 employees Shares outstanding: ~44.3 million Cash runway into 2020 Cash at June 30, $16.4 million Raised ~$22 million on August 22,

4 Exicure at a Glance Proprietary platform with applications in oncology, inflammatory diseases and genetic disorders Oncology: Advancing through the clinic AST-008 (TLR9 agonist) for immuno-oncology: Phase 1 complete Expected Phase 1b/2 launch in cancer patients Q Expected Phase 1b/2 preliminary results in 2019 Inflammatory disease: Readout in Q XCUR17 for psoriasis; Phase 1 completion Q Preclinical data in oral and liver delivery Genetic Disorders: Expansion in neurology and rare diseases Superior potency compared to nusinersen in spinal muscular atrophy models Improved biodistribution profiles 4

5 Exicure s Proprietary Technology: Spherical Nucleic Acids (SNA) + Synthesis of oligonucleotides Scaffold from benign lipid nanoparticles Generate SNA using Exicure process 5

6 Spherical Nucleic Acid (SNA) Solves Delivery Challenge DNA SNA 6

7 SNA Technology is Uniquely Differentiated SNAs Enter Cells through Ubiquitous Scavenger Receptors High Cell Uptake SNA facilitated cell uptake via scavenger receptors without need for encapsulation or complexation in vitro PNAS, 2013, 110, p7625 Extra-hepatic Delivery Scavenger Receptors SNA architecture enables extra-hepatic delivery and increased half-life of oligos SNA effectively delivered topically into skin in vitro (human) and in vivo (mouse) PNAS, 2012, 109, p11975 Increased Half-life of Oligos Structure protected oligonucleotides from nuclease degradation, extending therapeutic half-life in vitro Science, 2006, 312, p1027 7

8 Better Delivery Leads to Broader Applications DNA/RNA SNA Multiple liver indications 8

9 Development Pipeline Therapeutic Area Therapeutic Candidate/ Target Indication Research Preclinical Development Development Stage Phase 1 Phase 2 Status Immunooncology AST-008 (TLR9 agonist) Solid Tumors Phase 1 complete Phase 1b/2 commences Q4 (1) Dermatology XCUR17 (anti-il17ra) Psoriasis (2) Phase 1 completion Q Neurology SMN2 HTT Spinal Muscular Atrophy Huntington s Disease Superior potency improves survival and safety compared to nusinersen in vivo Target knockdown in vitro Ophthalmology Undisclosed Undisclosed Delivery to retina in vivo Gastroenterology Undisclosed Inflammatory Bowel Disease Target knockdown in tissue Activity in mouse model of IBD Pulmonology Undisclosed Undisclosed Delivery via aerosol Activity in mouse model Partnered Program Dermatology AST-005 (anti-tnfα (3) ) TBD Phase 1b complete (1) In combination with checkpoint inhibitors (2) Mild to moderate (3) In collaboration with Purdue Pharma 9

10 Exicure is Pursuing Multiple Therapeutic Areas Oncology Genetic Disorders Inflammatory Diseases AST-008 clinically benchmarked program Phase 1 complete o Robust activation of natural killer cells and T cells o Confirmed drug mechanisms of action Phase 1b/2 to commence in Q Spinal Muscular Atrophy Superior potency improves survival and safety compared to nusinersen (Spinraza ) in vivo Huntington s Disease Target knockdown in vitro XCUR17 for psoriasis 19 patients enrolled and completed dosing as of Q Phase 1 completion Q AST-005 (anti-tnf) Partnered with Purdue Initial applications in IBD, psoriasis 10

11 Immuno-Oncology

12 Cancer Immunotherapy is a Nobel Prize Winning Idea Immunotherapy is a breakthrough in cancer treatment Checkpoint inhibitors paved the way for immunotherapy 12

13 Combination Therapy will be an Important Driver in Immuno-Oncology Checkpoint therapies fail when patients have an inadequate anti-tumor immune response TLR9 agonists turn cold tumors hot activating anti-tumor T-cells and Natural Killer Cells In combination with checkpoint inhibitors, activating TLR9 has lead to significantly improved responses in both naïve and checkpoint inhibitor refractory patients 13

14 Pre-clinical Data Position AST-008 for Clinical Success Pre-clinical Study Endpoint Outcome Uptake into cells TLR9 activation TLR9 specific activation Cytokine induction profile Route of administration Tumor models Toxicology and immune activation in NHP Higher uptake than non-sna structure Better activation than non-sna structure Immune activation through TLR9 pathway Broad Th1-type cytokine activation Immune activation after subcutaneous, intravenous or intramuscular administration Efficacy in various tumor models (immunogenic memory, abscopal effect, different routes of administration) Safety and immune activation 14

15 Mean Tumor Volume (mm 3 ) Exicure s Clinical Program, AST-008 Shows Efficacy in a Variety of Preclinical Models Comprehensive preclinical data Breast, lung, melanoma, colorectal and lymphoma models Subcutaneous, intra-tumoral, and intravenous delivery Activity as monotherapy and in combination with checkpoint inhibitors Local and abscopal effects Exicure technology may have advantages over other TLR9 agonists based on architecture Enter cells faster, more stable, and higher potency Vehicle anti-pd-1 + mu-ast-008 anti-pd-1 + Linear oligo anti-pd Days 15

16 Phase 1: Positive Results Support Launch of Phase 1b/2 Trial Potent activation of natural killer cells and T cells Important for anti-tumor response Results support strong immune system activation through a TRL9 mechanism No serious adverse events, no dose limiting toxicity Q4 to begin open label, Phase 1b dose-finding lead-in followed by Phase 2; both phases in combination with systemic pembrolizumab Basket study to include solids tumors such as melanoma, Merkel cell carcinoma, cutaneous squamous cell carcinoma, head and neck Preliminary safety and efficacy data expected late 2019 Expand to other oncology indications, other combinations, alternative routes of administration 16

17 Genetic Disorders

18 Why SNAs Matter: Improving Potency Nusinersen-SNA Nusinersen Control SNA Nusinersen, marketed as Spinraza, is used to treat SMA SNA outperformed nusinersen in pre-clinical model Demonstrates potential of SNA platform in SMA and neurology SPINRAZA is a registered trademark of Biogen 18

19 Improving Potency: Spinal Muscular Atrophy Exicure-treated Nusinersen-treated Control Days SNA prolonged survival by four-fold (maximal survival of 115 days vs. 28 days for nusinersen-treated mice) SNA mitigated toxicity of nusinersen 19

20 Opportunities in Genetic Disorders Exicure technology has potential advantages over existing therapies Higher potency and longer persistence could enable less frequent dosing Better uptake profile may enable targeting of peripheral tissue Exicure technology may have application in a variety of neurological disorders Spinal Muscular Atrophy, Duchenne Muscular Dystrophy, Huntington s Disease, Amyotrophic Lateral Sclerosis, others Evaluating opportunities in neurology and genetically defined rare diseases 20

21 Inflammatory Diseases

22 Psoriasis and IL17 Pathway 7.5 million affected in the US; approximately 6 million have mild to moderate disease Mild to moderate psoriasis represents significant unmet medical need Generally not treated with systemic antibody therapy Significant side effects with current topical therapies IL-17/IL-17RA signaling is a critical driver located in epidermal layers Preclinical data confirm that IL-17RA is accessible through local delivery Mice with induced psoriasis Untreated Exicure Treated Unmet need: Specificity of antibodies with the convenience of topical corticosteroids without the side effects of either 22

23 XCUR17: Topically Applied Anti-IL17R Results Expected Q XCUR17 is topically applied antisense oligonucleotide targeting IL-17 receptor Phase 1 commenced April patients enrolled and completed dosing XCUR17 gel applied daily over 26 days Endpoints Safety and tolerability Biomarkers (IL-17RA and pathway markers) Skin histology 23

24 Topically Applied Anti-TNF AST-005 Anti-TNF SNA in IBD Designed to provide specificity and efficacy of antibodies with safety profile of topical therapeutics Applications in inflammatory disorders including psoriasis, IBD, Behçet's disease, rheumatoid arthritis Healthy Mice Untreated Exicure-treated Phase 1b trial in psoriasis patients complete 18 months from nomination through patient read-through and $3.7 MM in total cost Partnered with Purdue Pharma, $10 MM upfront Purdue retains rights Oral gavage results in distribution throughout GI tissue Statistically significant improvement in clinical score in TNBS model 24

25 Preclinical Data

26 PBS Better Delivery: SNA Technology Improves Functional Delivery in Liver Time Course of Activity Dose-dependence Naked Anti-Let-7 Cholesterolconjugated Anti-Let-7 Anti-Let-7 SNA Naked Anti-Let-7 Cholesterolconjugated Anti-Let-7 Anti-Let- 7 SNA Functional delivery is up to >10-folder higher after subcutaneous administration 26

27 Better Delivery: Distribution Throughout the GI Tract SNA constructs are administered via oral gavage in mice Cryofluorescence tomography imaging of SNA distribution in GI tissues 27

28 Better Delivery: Longer Persistence in CNS SPINRAZA is a registered trademark of Biogen Exicure s technology shows higher persistence in CNS and lower clearance through kidney compared to nusinersen 28

29 Better Delivery Leads to Broader Applications SNAs activate immune cells in humans Potential as combination with checkpoint inhibitors, and/or other agents such as OX40 agonists SNAs knock down genes when topically applied to human skin Topical mrna regulation/modification potentially applicable to over 200 dermatological conditions Demonstrated superior exon inclusion in patient cells when compared to nusinersen (Spinraza ) Superior potency improves survival and safety compared to nusinersen in vivo Potential for SNAs formulated as eye drops Demonstrated distribution to cornea and retina in vivo after topical application Induced target knock down and distribution in GI tissue after oral administration Demonstrated therapeutic activity in preclinical IBD models Potential for nebulized formulation of SNA Nebulized compound active in vitro and in vivo Up to 10-fold higher functional delivery after subcutaneous administration SPINRAZA is a registered trademark of Biogen 29

30 Intellectual Property Portfolio Exclusive, worldwide license to make, modify and use SNAs for therapeutic applications IP portfolio includes over 60 issued or allowed patents and 120 pending applications across multiple nucleic acid modalities Multiple layers of protection exist extending platform coverage beyond 2030 Composition of Matter Example Claim Classes Methods of modulating nanoparticle uptake via oligonucleotide surface density SNAs comprising cross-linked oligonucleotides sirna modified nanoparticles Mechanism of Action Method of Use Drug Specific Antisense inhibition by oligonucleotides bound to inorganic nanoparticles Immuno-modulatory SNAs Administration of oligonucleotide functionalized nanoparticles to skin TNF antisense sequences and chemistries 30

31 Platform Encompasses All Mechanisms sirna Antisense Splice Correction TLR9 Activation Clinical Data Market Cap 1 ($) 177M 1.4B 941M 779M 735M 237M 1.7B 6.9B 8.9B 1. Market cap data from Yahoo Finance as of EOD October 1,

32 Management, Board, Advisors Management David Giljohann, PhD Chief Executive Officer David Snyder, MBA Chief Financial Officer Ekambar Kandimalla, PhD Chief Scientific Officer Matthias Schroff, PhD Chief Operating Officer Jocelyn Trokenheim VP, Head of Business Development Board of Directors Consultant/ Advisors Chad Mirkin, PhD Founder Helen Kim, MBA C. Shad Thaxton, MD, PhD Founder David Walt, PhD Jay Venkatesan, MD, MBA Michael Hodges, MBBS former CMO, Santaris Alice Bexon, MD former VP, Clin. Dev., Idera Pharmaceuticals Steve Rosen, MD CSO, City of Hope Hospital Amy Paller, MD Chair, Dept. of Dermatology, Northwestern University Lee Zane, MD former CMO, Anacor 32

33 Company Highlights Spherical Nucleic Acids: a disruptive platform technology expanding the promise of nucleic acid therapeutics Applications in cancer, inflammatory diseases and genetic disorders Key 2018 milestones Announced pre-clinical SMA data June 2018 AST-008 (TLR9 agonist) for immuno-oncology; Phase 1 completed o Expected Phase 1b/2 launch Q XCUR17 for psoriasis; Phase 1 completion Q Leveraging platform through partnering opportunities across therapeutic areas Expanding application into eye, GI tract, lung 33

34 Contacts David Giljohann, PhD, CEO David Snyder, CFO 34

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