Cypherpunk Technologies Inc. · NASDAQ:CYPH
Cypherpunk Technologies — Leap Therapeutics — Investor Presentation (July 2018)
35 slides from Cypherpunk Technologies's investor presentation, Jul 23, 2018
Slide 1: Forward-Looking Statements
Forward-Looking This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding our strategy, future operations, future financial position
Slide 2: Leap Therapeutics: Oncology drug development company
Leap Therapeutics Oncology drug development company • Novel targets and compounds – DKN-01 (anti-DKK1) – TRX518 (GITR agonist) • Clinical responses in multiple indications • Strategic relationships established – DKN-01 Collaborations with Merck and Roche – TRX518 Collaboration with Pfizer/EMD Serono
Slide 3: Recent Highlights
Recent Highlights Collaboration with Pfizer/EMD Serono for combination study of TRX518 with BAVENCIO® and cyclophosphamide – Study design based on preclinical data presented by MSKCC at AACR 2018 – Bavencio’s fully Fc functional antibody pairs with TRX518’s structure – Expansion cohorts focused on b
Slide 4: DKK1 and GITR are Compelling Oncology Targets
DKKl and GITR are Compelling Oncology Targets Inhibit Immunosuppression Enhance Immune Activation Proinflammatory Environment MDSC * GITR Stimulation on CDS Cells •-,•• II ...e. Reduce DKK1 \ Reduce Increased NK Ligands on Tumor Cells I GITR .•-Agonist • DKK1 I Decreased Angiogenesis, Metastasis, an
Slide 5: Advancing DKN-01 Clinical Development
Advancing DKN-01 Clinical Development Monotherapy Dose Escalation Study Proof of Concept Combination Studies Multiple Myeloma DKN-01 + Rev/Dex ü Immunotherapy and Biomarker Studies Biliary Tract Cancer DKN-01 + gemcitabine/cisplatinEsophagogastric Cancer DKN-01± paclitaxel Esophagogastric Cancer DKN
Slide 6: Active as a Single-Agent in Heavily Pretreated Esophagogastric Cancer
Active as a Single-Agent in Heavily Pretreated Esophagogastric Cancer Best Overall Response of Evaluable Patients (By Central Imaging Analysis) Partial Response Stable Disease Progressive Disease On Study 1 Year, Response -33.9% Failed prior anti-PD-L1 + IDOi REGARD Ramucirumab + BSC Placebo + BSC P
Slide 7: Combination with Paclitaxel in Esophagogastric Cancer
Combination with Paclitaxel in Esophagogastric Cancer All Patients 100% 80% 60% 40% 20% 0% -20% -40% -60% -80% -100% Data as of March 2018 8 Copyright © 2018 Best Overall Response OKN-01 + Paclitaxel 511-7 26% 34% PR sO PO NPrior TXORR sO (%)
Slide 8: Clinical Activity of DKN-01 + Paclitaxel in Taxane Naive Patients
Clinical Activity of DKN-01 + Paclitaxel in Taxane Naive Patients Tumor Burden Change Over Time (Each Line Represents an Individual Patient) Efficacy Benchmarks Response Rate DCR DKN-01 + Paclitaxel (Taxane Naive) 41% 73% Ramucirumab + Paclitaxel Rainbow Study 28% 80% Paclitaxel Mono Rainbow Study 1
Slide 9: Durable DKN-01 Response in Patient with Beta-Catenin Mutation
Durable DKN-01 Response in Patient with Beta-Catenin Mutation with Esophagogastric Cancer Baseline 40mm 20% 0% -20% -40% -60% Cycle 10 -80% 14mm Off Study -100% 0 2 4 6 810 12 14 16 18 20 22 24 26 28 30 32 Months On Study 10 Copyright © 2018 Target Lesion Change Discontinued Paclitaxel -40% -48% -55
Slide 10: Immunologic Activity of DKK1 Inhibition
Immunologic Activity of DKK1 Inhibition Inhibition of DKK1 targets innate immunity – Reduces Myeloid Derived Suppressor Cells (MDSC) – Enhances NK cell activity – Increases expression of PD-L1 – Induces transcription of T cell chemoattractants Immunologic Activity of DKK1 Inhibition DKN-01 mechanism
Slide 11: DKN-01 + Checkpoint Inhibitor Combination Studies
DKN-01 + Checkpoint Inhibitor Combination Studies DKN-01 in combination DKN-01 ± paclitaxel in combination Dose Escalation Pembro Naive Dose Expansion Pembro Refractory Dose Expansion Study in collaboration with Advanced R/R Esophagogastric Adenocarcinoma (1 prior tx) DKN-01 + atezolizumab 1:1 Rando
Slide 12: Clinical Activity in Dose Escalation with Keytruda
Clinical Activity in Dose Escalation with Keytruda Two partial responses in patients with immune resistant phenotype • Dose expansion cohorts actively enrolling Clinical Activity in Dose Escalation with Keytruda DKN-01 Dose Prior a-PD-1 or a-PD-L1 Medical History MSI TMB PD-L1 Best Overall Response
Slide 13: Durability and Depth of Response
Durability and Depth of Response Target Lesion Change O!er Time D%'e E'ca"a(!%$ Pa(!e$(' 300 #g DKN-01 + Pe#b&%"!+)#ab Benchmark Stdies 100% 80% ORR 11.1% 12.5% 11.6% 10% 60% 40% 20% PFs 1.5 # 4.1 # 2.0 # 2.0 # % -20% PD-L1-ORR 6.4% 6% -40% -60% -80% PD-L1-sD 14.7% 12% -100% 0 50 100 Da*' s!$ce F!&'
Slide 14: Partial Responses in Patients with Immune Resistant Phenotype
Partial Responses in Patients with Immune Resistant Phenotype • Ongo ng conf rmed part a response (-82%), pat ent n Cyc e 10 December 2017 March 2018 Target Lesion: Hepatic Lobe Target Lesion: Renal/ Perirenal Mass 15 Copyright © 2018
Slide 15: Partial Responses in Patients with Immune Resistant Phenotype
Partial Responses in Patients with Immune Resistant Phenotype • Ongoing partial response (-42%) with declining CA 19-9; patient in Cycle 10 Baseline: 01DEC2017 Follow Up 3: 20APR2018 1002 0729 0735 0731 0813 0934 0750 0810 0738 0905 0809 0743 844.0. ...1071.4. ... 959.3.... 970.0....721.5.... 678.3.
Slide 16: DKN-01 in Advanced Biliary Tract Cancer
DKN-01 in Advanced Biliary Tract Cancer ORR 31.8%, DCR 95.5% PFS 9.4 months DKN-01 + gemcitabine/cisplatin in treatment-naïve advanced BTC Historical gemcitabine/cisplatin studies: • Overall response rates: 19.5 to 25.5% • Disease control rate: 68.3 to 81.4% • PFS: 5.8 to 8 months Data presented at
Slide 17: Selecting Patients for DKN-01 Treatment
Selecting Patients for DKN-01 Treatment • Beta-catenin turns on production of DKK1 • DKK1 is overexpressed in cancers with beta catenin activating mutations • Patients with mutations in betacatenin and/or elevated levels of DKK1 have poor prognosis • Patients with beta catenin mutations potentially
Slide 18: Key Wnt Biomarker Populations
Key Wnt Biomarker Populations Esophagogastric Cancer Hepatobiliary Cancer Uterine and Ovarian Cancer US Incidence Esophagus: 17,000 Stomach: 28,000 Liver: 40,000 Biliary: 6,000 Endometrial: 61,000 Ovarian: 22,000 β-catenin Mutational Frequency Gastric 6-9% of patients Hepatocellular Carcinoma 27-36%
Slide 19: Study in Gynecologic Cancers with Wnt Biomarkers
Study in Gynecologic Cancers with Wnt Biomarkers DKN-01 as a monotherapy and in combination with paclitaxel Study enriched for activating β-catenin mutations and/or Wnt signaling alterations (50% of patients) Groups Planned n Epithelial Endometrial Monotherapy 21 DKN-01 + Paclitaxel 31 Epithelial Ov
Slide 20: Hepatocellular Carcinoma Study with DKN-01 and Sorafenib
Study of patients with treatment-naive advanced hepatocellular carcinoma with DKN-01 monotherapy and in combination with sorafenib Hepatocellular Carcinoma Study Design DKN-01 Monotherapy DKN-01 + Sorafenib • Investigator sponsored study at 5+ sites, based at the University Medical Center of the Joh
Slide 21: DKK1 in Prostate Cancer
DKK1 in Prostate Cancer Strong rationale for combination with AR therapies in non-neuroendocrine subtypes due to increased expression of DKK1 and reduction of inflammatory immune infiltrate DKK1 Expression is Regulated by AR in CRPC Tumor Biopsies CIBERSORT Analysis Shows DKK1 Expression Associated
Slide 22: TRX518: Engineered to Maximize GITR Activation
TRX518: Engineered to Maximize GITR Activation of Immune Response to Tumors • • TRX518 is a differentiated humani"ed non-depleting IgG1 GITR agonist mAb GITR agonist ithout FeR binding signals to and does not deplete GITR e!pressing T eells 23 Copyright © 2018
Slide 23: TRX518 Clinical Development Studies
Single-Dose Monotherapy Dose Escalation Study Dose and Schedule Ranging Repeat-Dose Monotherapy Studies Loading Dose + Q3W Dosing Advanced Solid Tumors ü Immunotherapy and Chemotherapy Studies Biweekly Dosing Advanced Solid Tumors TRX518 + Gemcitabine TRX518 + Nivolumab TRX518 + Pembrolizumab TRX518
Slide 24: Stable Disease Achieved in Over 50% of Patients on TRX518
Stable Disease Achieved in Over 50% of Patients on TRX518 Multidose Monotherapy All Patients (N=43) Best Overall Response Stable Disease (SD) 24 (55.8%) Progressive Disease (PD) 11 (25.6%) Not Evaluable 8 (18.6%) Duration on Study (days) Data as of June 2018 Patient
Slide 25: TRX518 Monotherapy Patient with Long-Term Stable Disease
TRX518 Monotherapy Patient with Long-Term Stable Disease Hepatocellular carcinoma patient • Currently in Cycle 21 with 15% reduction in liver lesion • Failed prior CTLA4/PD-L1 therapy • Paired tumor biopsy analysis – Reduction in Treg cells – Increase in CD8/Treg ratio
Slide 26: TRX518 Combination Study
TRX518 Combination Study Combination with Gemcitabine Dose Escalation Dose Confirmation Advanced solid tumors where gemcitabine indicated Combination with PD-1 or PD-L1 Immunotherapy Dose Escalation Dose Expansion Dose Expansion Dose Escalation Advanced solid tumors with labeled indications either a
Slide 27: TRX518 Combination Study Clinical Update
TRX518 Combination Study Clinical Update • Keytruda Combination: enrolling in higher dose escalation group – First 2 patients treated at higher dose demonstrated clinical benefit at first scan • Partial Response (-36%) in patient with esophageal squamous cell carcinoma oPD-L1 positive, MSS, TMB inte
Slide 28: CTX has Synergistic Activity with GITR agonist
CTX has Synergistic Activity with GITR agonist and modulates T cell ratios Presented at AACR 2018 by Betof Warner, Hirschhorn, Wolchok, Merghoub (MSKCC)
Slide 29: GITR Agonist Synergizes with anti-PD-1 Therapy
GITR Agonist Synergizes with anti-PD-1 Therapy 816 Melanoma Mouse Model 100 /20 ** *** )GITR+)PD-1 Da( 7 50 6/20 )GITR Da( 4 )PD-1 Da( 7 )GITR Da( 7 0 0 25 50 75 100 125 Days post 816 injection Da&a f$"! Za##a%"d , W" ch"k, Me$gh"'b (MSKCC) 31 Copyright © 2018 Tumor-free (%) Tumor-Free Survival 11
Slide 30: Mechanistic Rationale for Triple Therapy
Mechanistic Rationale for Triple Therapy PD1/PD-L1 therapy blocks CD8 exhaustion complementing GITR Therapy GITR, as a costimulatory receptor, works best when antigen primed quiescent T cells are re-stimulated with appropriately processed antigen on APC bearing GITRL CTX promotes immunogenic cell de
Slide 31: TRX518 Chemoimmunotherapy Combination Study
TRX518 Chemoimmunotherapy Combination Study 33 TRX518 Chemoimmunotherapy Combination Study Study in collaboration with Dose Escalation Phase lb: Double and Triplet Therapy Stages Dose Escalation Stage 1: Doublet Therapy Group 1 CTX 01 (600 or 750 mg/m2} + TRX518 02 + 016 ----to Q28 days in advanced
Slide 32: Leadership
Leadership Management Team Chris Mirabelli, PhD CEO Company Experience Gus Lawlor COO Doug Onsi CFO Walter Newman, PhD Research Mark O’Mahony CMC & Quality Approved Drugs Cyndi Sirard, MD Clinical § Christopher Mirabelli, Chairman of the Board, CEO of Leap § James Cavanaugh, Managing Director at Hea
Slide 33: Historical Financials
Historical Financials (in thousands) (Unaudited) Current assets: Research and development incentive receivable 998 Research and development incentive receivable, net of current portion 632 Accrued expenses 1,715 Warrant liability 16,713 Commitments and contingencies Cash Ba ance at June 30, 2018: $3
Slide 34: Clinical Program Milestones
36 Esophagogastric & Biliary Cancer (TECENTRIQ® ± paclitaxel) Proof of Concept TRX518 Biliary Tract Cancer (gemcitabine + cisplatin) Solid Tumor Malignancies (mono) DKN-01 Biomarker Populations Immunotherapy Hepatocellular Carcinoma (mono + sorafenib) Gynecologic Cancer (mono + paclitaxel) Gastric C
Slide 35: Clinical Program Milestones
Clinical Program Milestones Immuno- Esophagogastric Cancer (com jion with KEYTRUDA®) Data presented AACR 2018, Expansion 2H-18 EICETIIN — esophagogastric & Biliary Cancer (TECENTRIO® + pocore) (LER ER SEO Gynecologio Cancer (mono + pacar!) Interim data 24-18 (Net) MLO Gastric Cancer (monotherapy + p
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