Cypherpunk Technologies Inc. · NASDAQ:CYPH
Cypherpunk Technologies — Leap Therapeutics — Investor Presentation (September 2021)
42 slides from Cypherpunk Technologies's investor presentation, Sep 21, 2021
Slide 1: Company Overview September 2021
Company Overview September 2021
Slide 2: Forward Looking Statements
Leap Therapeutics | Forward Looking Statements 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 operat
Slide 3: Leap Highlights
Leap Highlights 3 Oncology drug development company focused on DKN-01, an anti-DKK1 antibody STRATEGIC PARTNERSHIP STRONG CLINICAL DATA Endometrial Cancer Esophagogastric Cancer Compelling activity in combination with PD-1 and chemotherapy combinations • Plus tislelizumab/chemo: 68% ORR in 1L patien
Slide 4: The Role of DKK1 in Cancer
The Role of DKK1 in Cancer 4 Promotes activation of Akt by direct signaling through CKAP4 and PI3 kinase Upregulates VEGFR2 to promote angiogenesis Inhibits β-catenin dependent Wnt signaling on Myeloid-derived suppressor cells (MDSCs) to enhance suppressive activity Reduction of Natural Killer (NK)
Slide 5: Activity of DKN-01 to Treat Cancer
Activity of DKN-01 to Treat Cancer 5 Downregulation of Akt signaling decreases cancer cell survival and proliferation Reduces angiogenesis and upregulates key cytokines, IFNy, IL-15 and IL-33 β-dependent Wnt signaling reprograms MDSCs and reduces immunosuppressive activity Production of Granzyme B b
Slide 6: DKN-01 Esophagogastric Cancer Development
DKN-01 Esophagogastric Cancer Development 6
Slide 7: Esophagogastric Cancer is a Global Unmet Medical Need
Esophagogastric Cancer is a Global Unmet Medical Need Esophageal Cancer Gastric Cancer 7 Source: WHO Globocan 2020, American Cancer Society 604,100 New cases 2020 544,076 Deaths 2020 High incidence of esophageal cancer in China Incidence of esophageal cancer in China/Japan/US 19 26 324 US Japan Chin
Slide 8: High Levels of DKK1 Correlate with Shorter Overall Survival
High Levels of DKK1 Correlate with Shorter Overall Survival Across Indications including GEJ/Gastric Cancer Survival Probability Days OS for DKK1 High and Low Samples by Median (TCGA Pan-Cancer Dataset) Low High P < 0.0001 ~2.5 years shorter OS in DKK1-high patients 8 0 1000 2000 3000 4000 0 50 100
Slide 9: High DKK1 Is Associated with Poor Response to First-Line Platinum + Fluoropyrimidine Therapies
High DKK1 Is Associated with Poor Response to First-Line Platinum + Fluoropyrimidine Based Therapies in GEJ/Gastric Cancer Patients 9 Real World Evidence from DKK1-high patients demonstrates faster time to treatment discontinuation
Slide 10: High DKK1 Is Associated with Poor Response to Paclitaxel Therapies
High DKK1 Is Associated with Poor Response to Paclitaxel Therapies in GEJ/Gastric Cancer Patients Real World Evidence from DKK1-high patients demonstrates faster time to treatment discontinuation 10
Slide 11: Study Design in Advanced Gastric/GEJ Adenocarcinoma
Study Design in Patients with Advanced Gastric/GEJ Adenocarcinoma Assess the Safety and Anti-tumor Activity of DKN-01 in Combination with Tislelizumab +/- Chemo 11 Part A All comers, DKK1-high subgroup Part B DKK1-high PD-1 Naïve Get ORR and safety of tislelizumab/chemo combo First-line: DKN-01 + Ti
Slide 12: DKK1 Expression Determined Using RNAscope and Digital Pathology
DKK1 Expression Determined Using RNAscope and Digital Pathology 12 DKK1-high Patient (H-score = 108) DKK1-low Patient (H-score = 4) Tumor specimens were stained for DKK1 expression and quantified using a digital image analysis algorithm.1 • An H-score was calculated by determining the percentage of
Slide 13: Best Overall Response by DKK1 Expression 1L GEJ/GC
Best Overall Response by DKK1 Expression 1L GEJ/GC – DKN-01 Plus Tislelizumab Plus Chemotherapy 13 -100 -50 0 50 100 Best % Change in Sum of Diameters SD SD SD SD SD SD PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR DKK1 RNAscope H-score Status: High (≥35) Low (<35) Unknown Tumor type: GEJ adenocarcin
Slide 14: Durable Response by DKK1 Expression 1L GEJ/GC
Durable Response by DKK1 Expression 1L GEJ/GC – DKN-01 Plus Tislelizumab Plus Chemotherapy 14
Slide 15: All Evaluable DKK1-high Patients had Partial Response
All Evaluable DKK1-high Patients had Partial Response 1L GEJ/GC – DKN-01 Plus Tislelizumab Plus Chemotherapy • 90.0% of DKK1-high patients had PR; 7 of 9 responders still on therapy • 55.6% of DKK1-low patients had PR; 4 of 5 responders still on therapy 15 Best Overall Response, n (%) Partial Respon
Slide 16: Best Overall Response by PD-L1 and DKK1 Expression
Best Overall Response by PD-L1 and DKK1 Expression 1L GEJ/GC – DKN-01 Plus Tislelizumab Plus Chemotherapy 16 -100 -50 0 50 100 Best % Change in Sum of Diameters Subjects SD SD SD SD SD SD PR PR PR PR PR PR PR PR PR PR PR PR PR PR PR + + + + + + + + + ? ? ? – – – – – – – – – CPS Status: ≥5 <5 Unknown
Slide 17: Durable Response Independent of PD-L1 Expression
Durable Response Independent of PD-L1 Expression 1L GEJ/GC – DKN-01 Plus Tislelizumab Plus Chemotherapy 17
Slide 18: DKK1 High Patients Respond Regardless of PD-L1 Status
DKK1 High Patients Respond Regardless of PD-L1 Status 1L GEJ/GC – DKN-01 Plus Tislelizumab Plus Chemotherapy • 79% ORR in patients with PD-L1-low expression (CPS < 5) ‒ 100% ORR in DKK1-high, PD-L1 low patients • 67% ORR in patients with PD-L1 high expression (CPS ≥ 5) ‒ 75% ORR in DKK1-high, PD-L1
Slide 19: DKK1 and PD-L1 Expression are not Correlated
DKK1 and PD-L1 Expression are not Correlated 1L GEJ/GC – DKN-01 Plus Tislelizumab Plus Chemotherapy 19 vCPS: Visually-Estimated Combined Positive Score; PD-L1: Programmed Death-Ligand 1
Slide 20: Adverse Events Summary 1L GEJ/GC
Adverse Events Summary 1L GEJ/GC – DKN-01 Plus Tislelizumab Plus Chemotherapy 20 Part A Patients N=25 Preferred Terms No. Patients % Deaths within 30 days of last dose 3 12% Any adverse event 25 100% Grade ≥ 3 events 13 52% DKN-01-related 5 20% Serious adverse events 7 28% DKN-01-related 2 8% Events
Slide 21: PD-1 Antibodies + Chemo in First-Line HER2- GEJ/Gastric Cancer
PD-1 Antibodies + Chemo in First-Line HER2- GEJ/Gastric Cancer Patients 21 nivolumab tislelizumab pembrolizumab Checkmate-649 (All) Checkmate-649 (CPS > 5) (All) Keynote-062 (CPS > 1) N 789 473 15 251 ORR (%) (95% CI) 47 (43, 50) 50 (46, 55) 46.7 (21.3, 73.4) 48.6 (42.4, 54.9) DOR months (95% CI) 8.
Slide 22: Better and More Durable Responses for DKK1-high Patients
Better and More Durable Responses for DKK1-high Patients Anti-PD-1/PD-L1 Naïve 2L+ GEJ/GC – DKN-01 Plus Pembrolizumab 22 Maximum Percent Decrease PR & DKK1-high SD & DKK1-low SD & DKK1-high PD & DKK1-low PD & DKK1-high Primary Location Total (n) RE* (n) PR (n) SD (n) PD (n) NE (n) RE* ORR (n, %) DCR
Slide 23: Longer PFS for DKK1-high Patients
Longer PFS for DKK1-high Patients Anti-PD-1/PD-L1 Naïve 2L+ GEJ/GC – DKN-01 Plus Pembrolizumab 23 Median (95% CI) DKK1-high 22.1 (5.0, 35.9) DKK1-low 5.9 (5.3, 6.9) Median PFS longer in DKK1-high (22.1 weeks) vs. DKK1-low (5.9 weeks) patients Progression - Free Survival Probability 1.0 0.9 0.8 0.7 0
Slide 24: Longer OS for DKK1-high Patients
Longer OS for DKK1-high Patients Anti-PD-1/PD-L1 Naïve 2L+ GEJ/GC – DKN-01 Plus Pembrolizumab 24 Median OS longer in DKK1-high (31.6 weeks) vs. DKK1-low (17.4 weeks) patients Median (95% CI) DKK1-high 31.6 (11.0, 63.0) DKK1-low 17.4 (8.6, 23.1) Overall Survival Probability 1.0 0.9 0.8 0.7 0.6 0.5 0.
Slide 25: PD-L1 CPS Scores Not Associated with PFS
PD-L1 CPS Scores Not Associated with PFS Anti-PD-1/PD-L1 Naïve 2L+ GEJ/GC – DKN-01 Plus Pembrolizumab Median (95% CI) CPS Negative 11.7 (2.0, 22.1) CPS Positive – low 6.1 (5.0, 12.1) CPS Positive – high 6.9 (5.1, 31.6) 13 9 4 2 2 2 2 1 0 0 Progression - Free Survival Probability 1.0 0.9 0.8 0.7 0.6
Slide 26: PD-L1 CPS Scores Not Associated with OS
PD-L1 CPS Scores Not Associated with OS Anti-PD-1/PD-L1 Naïve 2L+ GEJ/GC – DKN-01 Plus Pembrolizumab Median (95% CI) CPS Negative 17.4 (2.0, 43.7) CPS Positive – low 21.8 (5.6, 60.9) CPS Positive – high 18.3 (8.7, NA) 13 11 8 7 4 4 3 2 2 0 Overall Survival Probability 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3
Slide 27: Clinical Activity of DKN-01 Plus Paclitaxel
Clinical Activity of DKN-01 Plus Paclitaxel Evaluable Esophagogastric Patients by Tumor Location Therapy Patients Treated Prior Therapies Overall Response Rate Stable Disease Rate Disease Control Rate DKN-01 + paclitaxel 52 1-7 25% 35% 60% + = PD, - = PR, no symbol = SD + + + + + + + + + + + + + + +
Slide 28: DKN-01 Plus Paclitaxel Exceeds Benchmarks in Second-Line Esophagogastric Cancer
DKN-01 Plus Paclitaxel Exceeds Benchmarks in Second-Line Esophagogastric Cancer 2nd Line Study n ORR (%) DCR (%) PFS (months) OS (months) DKN-01 + pac 15 46.7% 73.3% 4.5 14.1 Ram + pac RAINBOW 330 28% 80% 4.4 9.6 Pac RAINBOW 335 16% 64% 2.9 7.4 Chemo KN-181 314 6.7% - 3.4 7.1 100% 75% 50% 25% 0% -25
Slide 29: DKN-01 Single-Agent Activity in Heavily Pretreated Esophagogastric Cancer Patients
Baseline 4-month scan On Study 1 Year, Reduction -33.9% Failed Prior anti-PD-L1 + IDOi Best Overall Response of 20 Evaluable Patients* Partial Response 2 Stable Disease 6 Progressive Disease 12 DKN-01 Single-Agent Activity in Heavily Pretreated Esophagogastric Cancer Patients 29 *By Blinded Independ
Slide 30: DKN-01 Highlights in Gastric Cancer
DKN-01 Highlights in Gastric Cancer • DKN-01 in combination with tislelizumab and chemotherapy has demonstrated compelling overall response rates as a first line treatment for advanced gastric/GEJ cancer ‒ 68.2% ORR; 90% ORR in DKK1-high patients vs 56% ORR in DKK1-low patients • Response is correla
Slide 31: DKN-01 Endometrial Cancer Development
DKN-01 Endometrial Cancer Development 31
Slide 32: Endometrial Cancer
Endometrial Cancer • Most common gynecological cancer in the western world • ~66,500 annual cases in the United States and the incidence is increasing • Fourth most common cancer in women in the United States • Clinical risk factors include estrogen- only hormone replacement, obesity, chronic anovul
Slide 33: High DKK1 Associated with Poor Response to anti-VEGF and anti-PD-(L)1 in Endometrial Cancer
PD-(L)1 treatment Anti-VEGF treatment High DKK1 Is Associated with Poor Response to anti-VEGF and anti-PD-(L)1 in Endometrioid Endometrial Cancer Patients 33
Slide 34: DKN-01 Phase Study Design
DKN-01 Phase 2 Study Design DKN-01 300 mg Monotherapy N=52 DKN-01 300 mg + Paclitaxel 80 mg N=59 Eligible Patients • Recurrent EEC • Recurrent platinum- resistant/refractory EOC • Recurrent MMMT • ≥ 1 prior therapy • Measurable disease • 50% in each group with Wnt signaling alteration Data as of 28
Slide 35: DKN-01 Well Tolerated as Monotherapy and with Paclitaxel
DKN-01 Was Well Tolerated as Monotherapy and in Combination with Paclitaxel • Related SAEs: ‒ DKN-01 monotherapy: 5.8% ‒ DKN-01 + paclitaxel combination: 6.8% • No TEAEs which led to death Most Common DKN-01 Related TEAEs Monotherapy: • Nausea (28.8%) • Fatigue (26.7%) • Constipation (11.5%) Combina
Slide 36: DKN-01 Monotherapy - Overall Response by DKK1 Tumoral Expression
DKN-01 Monotherapy - Overall Response by DKK1 Tumoral Expression 36 *H score ≥ 18, upper tertile of overall study population Status N ORR DCR CR PR SD PD NE EEC monotherapy DKK1-high (≥18)* 8 25% 63% 1 1 3 3 0 DKK1-low (<18) 15 0% 7% 0 0 1 11 3 Unknown 6 0% 83% 0 0 5 1 0 DKK1-high tumors have better
Slide 37: DKN-01 Monotherapy - Durable Clinical Benefit in DKK1-high Tumors
DKN-01 Monotherapy - Durable Clinical Benefit in DKK1-high Tumors DKK1-high patients have more durable clinical benefit 37
Slide 38: DKN-01 Monotherapy - Improved PFS with High Tumoral DKK1 Expression
DKN-01 Monotherapy - Improved PFS with High Tumoral DKK1 Expression DKK1-high patients have longer PFS (4.3 vs. 1.8 months [HR 0.26; 95 CI: 0.09, 0.75]) 38
Slide 39: Corporate Strategy
Corporate Strategy 39
Slide 40: Leap-BeiGene Strategic Partnership
Leap-BeiGene Strategic Partnership Royalties High-single digit to mid-teen double digits 40 Option and License Agreement Option Fee $3M Equity Investment $5M > $10M Option exercise fee Based on data from DKN-01 plus tislelizumab combination studies in gastric cancer Asia (excluding Japan), Australia
Slide 41: Management Team
Management Team 41 Mark O’Mahony Chief Manufacturing Officer Douglas Onsi President & Chief Executive Officer Walter Newman, PhD Senior Research Fellow Gus Lawlor Chief Operating Officer Cyndi Sirard, MD Chief Medical Officer Christopher Mirabelli, PhD Chairman of the Board Jason Baum, PhD Vice Pres
Slide 42: Leap 2021-2022 Objectives and Milestones
Investigator-Sponsored Study Q1 Q2 Q3 Q4 Q1 Q2 Leap 2021-2022 Objectives and Milestones 42 DKN-01 + tislelizumab gastric DKN-01 ± paclitaxel endometrial 2021 2L Initial Data LPI 1L First-line patients combination with chemotherapy Second-line patients DKK1-high DKN-01 ± docetaxel prostate 2022 Final
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