Cypherpunk Technologies Inc. · NASDAQ:CYPH

Cypherpunk Technologies — Leap Therapeutics — Investor Presentation (October 2025)

46 slides from Cypherpunk Technologies's investor presentation, Oct 20, 2025

  1. Slide 1: Leap Therapeutics company presentation

    LEAP THERAPEUTICS company presentation October 20, 2025

  2. Slide 2: Forward looking statements

    Forward looking statements This presentation contains forward-looking statements Because forward-looking statements relate to the future, that involve substantial risks and uncertainties. they are subject to inherent uncertainties, risks All statements, other than statements of historical facts, and

  3. Slide 3: Corporate overview

    Corporate overview Drug Development Strategy Digital Asset • Sirexatamab (DKN-01) Treasury Strategy for patients with • $58.88 million colorectal cancer strategic investment • FL-501 for treatment led by Winklevoss of cachexia-related Capital diseases 3

  4. Slide 4: Pipeline

    Pipeline Indication: Treatment: Preclinical Phase 1 Phase 2 Phase 3 sirexatamab (DKN-01) Colorectal bevacizumab cancer + chemotherapy Anti-DKK1 antibody FL-501 Anti-GDF-15 antibody 4

  5. Slide 5: Sirexatamab (DKN-01)

    SIREXATAMAB (DKN-01) Anti-DKK1 monoclonal antibody

  6. Slide 6: The role of DKK1 in cancer

    The role of DKK1 in cancer Enhances the suppressive activity of MDSCs and M2 macrophages. Cancer cells Reduces NK cell activity and T-cell infiltration. DKK1 Promotes angiogenesis by increasing Cancer cell the number and size of blood vessels. CKAP4 DKK1 is produced and Tumor Angiogenesis PI3K secre

  7. Slide 7: DKK1 production from multiple sources can drive tumor growth

    DKK1 production from multiple sources can drive tumor growth DKK1 DKK1 Bone Blood vessel Tumor DKK1 protein in circulation DKK1 RNA from the tumor is measured by ELISA is measured by RNAscope ELISA Enzyme-Linked Immunosorbent Assay DKK1 high DKK1 low 7

  8. Slide 8: Activity of sirexatamab (DKN-01) to treat cancer

    Activity of sirexatamab (DKN-01) to treat cancer Activates NK cells, reprograms macrophages into the tumor-attacking M1 subtype and promotes Cancer cells T cell infiltration. Reduces MDSCs and tumor sirexatamab suppressive M2 (DKN-01) macrophages in the TME. DKK1 Cancer cell Reduces angiogenesis CKA

  9. Slide 9: Sirexatamab (DKN-01) Colorectal cancer

    SIREXATAMAB (DKN-01) Colorectal cancer

  10. Slide 10: Colorectal cancer background

    Colorectal cancer background • Includes right colon (cecum, ascending and transverse colon) and left colon (descending colon, sigmoid, and rectum) • When symptoms appear, such as rectal bleeding, anemia, or abdominal pain, most patients already have advanced stage disease where cancers are aggressiv

  11. Slide 11: Significant unmet needs in 2L patients

    Significant unmet needs in 2L patients Bevacizumab Bevacizumab Bevacizumab Treatment + Chemo + Chemo + Chemo* Study ML18147 E3200 SLAVE Bevacizumab benchmark Bevacizumab- Bevacizumab- EGFR- studies demonstrate need Population experienced naïve experienced for new options for today’s heterogeneous 40

  12. Slide 12: Circulating DKK1 levels are elevated in CRC and prognostic of worse outcomes

    Circulating DKK1 levels are elevated in CRC and prognostic of worse outcomes Elevated serum levels of DKK1 are associated DKK1 plasma levels are elevated with a worse clinical prognosis for CRC in CRC patients 100 Overall Survival 50 Plog-rank=0.043 Low serum DKK1 (N=28) High serum DKK1 (N=37) 0 0 2

  13. Slide 13: DeFianCe study design

    DeFianCe study design Randomized phase 2 study of FOLFIRI/FOLFOX and bevacizumab +/- sirexatamab (DKN-01) as second-line treatment of advanced colorectal cancer OBJECTIVES Primary: PFS (Investigator assessed) Sirexatamab (DKN-01) + SOC chemotherapy (FOLFIRI or mFOLFOX6) + bevacizumab Secondary: Key

  14. Slide 14: Intent-to-treat population

    INTENT-TO-TREAT POPULATION

  15. Slide 15: Sirexatamab increased median PFS by ~1 month

    Sirexatamab increased median PFS by ~1 month Intent-to-Treat (ITT) population – Investigator Assessment • PFS demonstrates ~1 month advantage • Median: 9.2 vs. 8.3 months • HR 0.84 • p = 0.1712 (pre-defined SAP primary endpoint p = 0.10) Event-free rate favors sirexatamab arm beginning at month 9 (5

  16. Slide 16: Sirexatamab improved ORR by 8% (35% vs. 27%)

    Sirexatamab improved ORR by 8% (35% vs. 27%) Intent-to-Treat (ITT) population – Investigator Assessment Sirexatamab Control Experimental N=94 N=94 Response n (%) n (%) CR 0 (0) 2 (2) PR 33 (35) 23 (25) ORR 35.1% 26.6% 95% CI (25.5, 45.6) (18.0, 36.7) p value p=0.1009 SD 48 (51) 54 (57) DCR 86.2% 84.

  17. Slide 17: Sirexatamab improved ORR by 13% (33% vs. 20%) assessed by BICR

    Sirexatamab improved ORR by 13% (33% vs. 20%) assessed by BICR Intent-to-Treat (ITT) population - BICR Sirexatamab Control Experimental Response N=94 N=94 n (%) n (%) CR 1 (1) 2 (2) PR 30 (32) 17 (18) ORR 33.0% 20.2% 95% CI (23.6, 43.4) (12.6, 29.8) p value p=0.0203 SD 47 (50) 52 (55) Non-CR / 2 (2)

  18. Slide 18: Overall Survival

    Overall Survival Intent-to-Treat (ITT) population • OS not mature due to limited number of events • 25 deaths Control Arm vs. 21 deaths Experimental Arm 18

  19. Slide 19: DKK1 biomarker – upper quartile (top 25%)

    DKK1 BIOMARKER – UPPER QUARTILE (TOP 25%)

  20. Slide 20: 3.5 months longer Progression-free Survival with sirexatamab

    3.5 months longer Progression-free Survival with sirexatamab DKK1-high subgroup – Upper Quartile • Statistically significant improvement in PFS • Median: 9.36 vs. 5.88 months • HR 0.46 • p = 0.0168 • Enhanced, statistically significant 5 month improvement in PFS by BICR • Median: 9.0 vs. 3.9 months

  21. Slide 21: 28% higher response rate (44% vs 16%) with sirexatamab

    28% higher response rate (44% vs 16%) with sirexatamab DKK1-high subgroup – Upper Quartile Sirexatamab Control Experimental N=25 N=19 Response n (%) n (%) CR 0 (0) 0 (0) PR 11 (44) 3 (16) ORR 44.0% 15.8% 95% CI (24.4, 65.1) (3.4, 39.6) p value p=0.0149 SD 12 (48) 12 (63) DCR 92.0% 78.9% PD 2 (8) 3 (

  22. Slide 22: 28% higher response rate (44% vs 16%) with sirexatamab

    28% higher response rate (44% vs 16%) with sirexatamab DKK1-high subgroup – Upper Quartile Sirexatamab Control Experimental N=25 N=19 Response n (%) n (%) CR 0 (0) 0 (0) PR 11 (44) 3 (16) ORR 44.0% 15.8% 95% CI (24.4, 65.1) (3.4, 39.6) p value p=0.0149 SD 12 (48) 12 (63) DCR 92.0% 78.9% PD 2 (8) 3 (

  23. Slide 23: Sirexatamab significantly improved Overall Survival

    Sirexatamab significantly improved Overall Survival DKK1-high subgroup – Upper Quartile • Statistically significant improvement in OS • 12 deaths Control Arm vs. 5 deaths Experimental Arm • Median: Not Yet Reached vs. 9.49 months • HR 0.17 • p < 0.001 23

  24. Slide 24: DKK1 biomarker – upper median (top 50%)

    DKK1 BIOMARKER – UPPER MEDIAN (TOP 50%)

  25. Slide 25: ~2 months longer PFS with sirexatamab

    ~2 months longer PFS with sirexatamab DKK1-high subgroup – Upper Median • Statistically significant improvement in PFS • Median: 9.03 vs. 7.06 months • HR 0.61 • p = 0.0255 • Consistent 2 month improvement in PFS by BICR • Median: 9.5 vs. 7.2 months • HR 0.64 • p = 0.0763 25

  26. Slide 26: 14% higher response rate (38% vs 24%) with sirexatamab

    14% higher response rate (38% vs 24%) with sirexatamab DKK1-high subgroup – Upper Median Sirexatamab Control Experimental N=50 N=38 Response n (%) n (%) CR 0 (0) 0 (0) PR 19 (38) 9 (24) 38.0% 23.7% ORR (24.7, 52.8) (11.4, 40.2) P value p=0.0706 SD 26 (52) 23 (61) DCR 90.0% 84.2% PD 4 (8) 4 (11) No a

  27. Slide 27: Sirexatamab significantly improved Overall Survival

    Sirexatamab significantly improved Overall Survival DKK1-high subgroup – Upper Median • Statistically significant improvement in OS • 15 deaths Control Arm vs. 11 deaths Experimental Arm • Median: Not Yet Reached vs. 14.39 months • HR 0.42 • p = 0.0118 27

  28. Slide 28: No prior anti-VEGF population

    NO PRIOR ANTI-VEGF POPULATION

  29. Slide 29: ~2.6 months longer Progression-free Survival with sirexatamab

    ~2.6 months longer Progression-free Survival with sirexatamab No prior anti-VEGF subgroup • Statistically significant improvement in PFS • Median: 10.94 vs. 8.34 months • HR 0.62 • p = 0.0387 • Enhanced, statistically significant ~4.6 month improvement in PFS by BICR • Median: 14.7 vs. 9.3 months •

  30. Slide 30: Sirexatamab improved ORR by 22% (55% vs. 33%)

    Sirexatamab improved ORR by 22% (55% vs. 33%) No prior anti-VEGF subgroup Sirexatamab Control Experimental N=49 N=46 Response n (%) n (%) CR 0 (0) 2 (4) PR 27 (55) 13 (28) ORR 55.1% 32.6% 95% CI (40.2, 69.3) (19.5, 48.0) p value p=0.0116 SD 19 (39) 24 (52) DCR 93.9% 84.8% PD 0 (0) 4 (9) No assessmen

  31. Slide 31: Overall Survival

    Overall Survival No prior anti-VEGF subgroup • Early advantage in OS with limited number of events • 13 deaths Control Arm vs. 7 deaths Experimental Arm • Median: Not Yet Reached vs. Not Yet Reached • HR 0.41 • p = 0.0248 31

  32. Slide 32: Liver metastasis population

    LIVER METASTASIS POPULATION

  33. Slide 33: High circulating DKK1 is associated with liver metastasis and poor prognosis in CRC

    High circulating DKK1 is associated with liver metastasis and poor prognosis in CRC CRC liver metastases patients with high and low serum DKK1 Sui et al; 2019, BMC Cancer DeFianCe Part B Patients DKK1-High Full ITT ≥25% ≥50% ≥75% Cutoff % of patients 72% (136/188) 71% (94/132) 76% (67/88) 82% (36/44

  34. Slide 34: ~2 months longer Progression-free Survival with sirexatamab

    ~2 months longer Progression-free Survival with sirexatamab Liver Mets subgroup • ~2 month and 34% risk reduction favoring the Experimental Arm • Median: 9.20 vs. 7.23 months • HR 0.66 • p = 0.0217 • Enhanced advantage for Experimental Arm in biomarker high patients • DKK1 Upper Median PFS: • HR 0.4

  35. Slide 35: 9% higher response rate with sirexatamab

    9% higher response rate with sirexatamab Liver Mets subgroup Sirexatamab Control Experimental N=72 N=67 Response n (%) n (%) CR 0 (0) 1 (1) PR 27 (38) 18 (27) ORR 37.5% 28.4% 95% CI (26.4, 49.7) (18.0, 40.7) p value p=0.1245 SD 35 (48) 37 (55) DCR 86.1% 83.6% PD 6 (8) 6 (9) No assessment 4 (5) 5 (7)

  36. Slide 36: Overall Survival

    Overall Survival Liver Mets subgroup • OS trending advantage for sirexatamab • 21 deaths Control Arm vs. 17 deaths Experimental Arm • Median: Not Yet Reached vs. 15.74 months • HR 0.69 • p = 0.1305 36

  37. Slide 37: ~2.6 months longer Progression-free Survival with sirexatamab

    ~2.6 months longer Progression-free Survival with sirexatamab Liver Mets subgroup without prior VEGF • Nearly 3 month improvement favoring the Experimental Arm in patients with liver mets and no prior anti-VEGF exposure • Median: 10.94 vs. 8.31 months • HR 0.59 • p = 0.0379 37

  38. Slide 38: 29% higher response rate with sirexatamab

    29% higher response rate with sirexatamab Liver Mets subgroup without prior VEGF Sirexatamab Control Experimental N=33 N=38 Response n (%) n (%) CR 0 (0) 1 (3) PR 21 (64) 12 (32) ORR 63.6% 34.2% p value p=0.0048 SD 10 (30) 19 (50) DCR 93.9% 84.2% PD 0 (0) 4 (11) No assessment 2 (6) 2 (5) 38

  39. Slide 39: Sirexatamab enhanced outcomes in patients with liver & lung mets

    Sirexatamab enhanced outcomes in patients with liver & lung mets Patients with Both Liver and Lung Mets and no prior anti-VEGF • More advanced, poorer prognostic groups perform well on sirexatamab • Anti-VEGF naïve patients with both liver and lung mets • ORR: 86.7% v 7.7% (p<0.001) • DCR: 100% v 76

  40. Slide 40: Market opportunity

    MARKET OPPORTUNITY leaptherapeutics

  41. Slide 41: Large potential colorectal cancer market opportunity

    Large potential colorectal cancer market opportunity First-Line Treated Patients for Advanced Disease US: 45,000 patients Largest 7 non-US markets: 265,000 patients ~5% ~10% ~10% ~25% ~50% HER2- RAS/BRAF amplified + BRAF MSI-H wt Other RAS/BRAF V600E Left Sided wt encorafenib + EGFR HER2 agent Check

  42. Slide 42: Sirexatamab ORR is enhanced by increasing DKK1 across biomarker subgroups

    Sirexatamab ORR is enhanced by increasing DKK1 across biomarker subgroups All Patients DKK1-High (upper median) DKK1-High (upper quartile) Group Sirexatamab Control Sirexatamab Control Sirexatamab Control Experimental Experimental Experimental ITT 35.1% 26.6% 38.0% 23.7% 44.0% 15.8% VEGF-naïve 55.1%

  43. Slide 43: Summary of final results

    Summary of final results • Circulating DKK1 is a negative prognostic factor in CRC and is elevated in patients with advanced mCRC; Sirexatamab, a first in class antibody neutralizes DKK1. • Sirexatamab was safe and well tolerated in combination with chemotherapy and bevacizumab. • Positive trend in

  44. Slide 44: FL-501 Anti-GDF-15 monoclonal antibody

    FL-501 Anti-GDF-15 monoclonal antibody

  45. Slide 45: The role of GDF-15 in cachexia and cancer

    The role of GDF-15 in cachexia and cancer Circulating GDF-15 triggers its Blood stream effects by binding to its receptor (GFRAL) in the hindbrain GDF-15 Stressed сells GDF-15 Immuno- Hyperemesis suppression gravidarum in cancers GDF-15 expression leads to an immuno- suppressive TME Other Respiratory

  46. Slide 46: FL-501 mechanism of action

    FL-501 mechanism of action Blood stream GDF-15 Stressed сells Immuno Improved stimulation maternal health in tumor microenvironment FL-501 Pulmonary improvement Weight gain, normal appetite, improved Renoprotective GFRAL muscle mass effects 46

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