Cypherpunk Technologies Inc. · NASDAQ:CYPH

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

50 slides from Cypherpunk Technologies's investor presentation, Jun 23, 2025

  1. Slide 1: Leap Therapeutics Company Presentation

    company presentation LEAP THERAPEUTICS June 23, 2025

  2. Slide 2: Forward looking statements

    Forward looking statements 2 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, clinical tri

  3. Slide 3: Pipeline

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

  4. Slide 4: Sirexatamab (DKN-01) Anti-DKK1 monoclonal antibody

    SIREXATAMAB (DKN-01) Anti-DKK1 monoclonal antibody

  5. Slide 5: The role of DKK1 in cancer

    The role of DKK1 in cancer 5 Tumor CKAP4 Angiogenesis Akt PI3K Cancer cell Cancer cells DKK1 is produced and secreted by cancer cells, and functions on several tumor pathways and nearby immune cells. Enhances the suppressive activity of MDSCs and M2 macrophages. Reduces NK cell activity and T-cell i

  6. Slide 6: DKK1 production from multiple sources can drive tumor growth

    DKK1 production from multiple sources can drive tumor growth 6 Tumor DKK1 DKK1 Bone DKK1 high DKK1 low Blood vessel ELISA Enzyme-Linked Immunosorbent Assay DKK1 RNA from the tumor is measured by RNAscope DKK1 protein in circulation is measured by ELISA

  7. Slide 7: Activity of sirexatamab (DKN-01) to treat cancer

    Activity of sirexatamab (DKN-01) to treat cancer 7 CKAP4 Angiogenesis Akt PI3K Cancer cell Cancer cells Tumor Cancer cell DKK1 Sirexatamab (DKN-01) treatment neutralizes DKK1 and stimulates an immune mediated anti-tumor response. sirexatamab (DKN-01) Activates NK cells, reprograms macrophagesinto th

  8. Slide 8: Sirexatamab (DKN-01) Colorectal cancer

    SIREXATAMAB (DKN-01) Colorectal cancer

  9. Slide 9: 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

  10. Slide 10: Bevacizumab benchmark studies demonstrate need for new options

    Bevacizumab benchmark studies demonstrate need for new options for today’s heterogeneous second-line patient population ML18147 409 5.4% E3200 286 22.7% SLAVE 228 25.7% Bevacizumab + Chemo Bevacizumab + Chemo Bevacizumab + Chemo* *SLAVE included N=198 left sided CRC patients. This subgroup has an OR

  11. Slide 11: DeFianCe study design

    DeFianCe study design 11 Randomized phase 2 study of FOLFIRI/FOLFOX and bevacizumab +/- sirexatamab (DKN-01) as second-line treatment of advanced colorectal cancer Primary: PFS (Investigator assessed) Secondary: • ORR • OS Sirexatamab (DKN-01) + SOC chemotherapy (FOLFIRI or mFOLFOX6) + bevacizumab S

  12. Slide 12: Part B population demographics

    Part B population demographics 12 N=188 Experimental Arm N=94 n (%) Control Arm N=94 n (%) Male 64 (68) 52 (55) Female 30 (32) 42 (45) Age, mean (min, max) 59.6 (33, 84) 58.7 (29, 84) Geography United States 41 (44) 40 (43) South Korea 50 (53) 45 (48) Germany 3 (3) 9 (10) Tumor Sidedness Right 24 (2

  13. Slide 13: Part B population

    Part B population 13 N=188 Experimental Arm N=94 n (%) Control Arm N=94 n (%) Liver metastasis Yes 73 (78) 65 (69) No 21 (22) 29 (31) Lung metastasis Yes 46 (49) 48 (51) No 48 (51) 46 (49) RAS Mutated# Yes 44 (47) 54 (57) No 36 (38) 26 (28) Unknown 14 (15) 14 (15) Prior Systemic Therapy- 5FU based O

  14. Slide 14: Part B overall safety summary

    Part B overall safety summary 14 N=179 Experimental arm (n=91) n (%) Control Arm (n=88) n (%) Any TEAE 91 (100) 88 (100) Regimen-related TEAE 90 (99) 86 (98) ≥ Grade 3 TEAE 53 (58) 58 (66) Regimen-related ≥ Grade 3 TEAE# 50 (55) 49 (56) Any SAE 19 (21) 17 (19) Regimen-related SAEs* 12 (13) 4 (5) AEs

  15. Slide 15: Treatment Emergent Adverse Events occurring in ≥10% of subjects

    Treatment Emergent Adverse Events occurring in ≥10% of subjects 15 • Most frequently reported AE overall is neutropenia (55%) and reported in (57%) on Experimental Arm and (52%) on Control Arm; ≥ Grade 3 were comparable at 37% vs 33%, respectively. • Experimental Arm had more asthenia (19 vs 8%) rep

  16. Slide 16: Intent-to-Treat Population

    INTENT-TO-TREAT POPULATION

  17. Slide 17: Progression-free Survival maturing, ~1 month advantage at median

    Progression-free Survival maturing and now showing ~1 month advantage at median Intent-to-Treat (ITT) population 17 • PFS continues to mature and now shows ~1 month advantage • Median: 9.2 vs. 8.3 m • HR 0.84 • p = 0.1749 (pre-defined SAP primary endpoint p = 0.10) • 6 additional Experimental Arm pa

  18. Slide 18: Sirexatamab improved ORR by 8% (35% vs. 27%)

    Sirexatamab improved ORR by 8% (35% vs. 27%) Intent-to-Treat (ITT) population 18 Sirexatamab Experimental N=94 Control N=94 Response n (%) n (%) CR 0 (0) 3 (3) PR 33 (35) 22 (23) ORR 95% CI 35.1% (25.5, 45.6) 26.6% (18.0, 36.7) p value p=0.1009 SD 48 (51) 54 (57) DCR 86.2% 84.0% PD 6 (6) 7 (7) No as

  19. Slide 19: Sirexatamab improved ORR by 13% assessed by BICR

    Sirexatamab improved ORR by 13% (33% vs. 20%) assessed by BICR Intent-to-Treat (ITT) population 19 Response Sirexatamab Experimental N=94 Control N=94 n (%) n (%) CR 1 (1) 2 (2) PR 30 (32) 17 (18) ORR 95% CI 33.0% (23.6, 43.4) 20.2% (12.6, 29.8) p value p=0.0203 SD 47 (50) 50 (53) Non-CR / Non-PD 2

  20. Slide 20: Overall Survival

    Overall Survival Intent-to-Treat (ITT) population 20 • OS not mature due to limited number of events • 19 deaths Control Arm vs. 16 deaths Experimental Arm

  21. Slide 21: DKK1 Biomarker Population

    DKK1 BIOMARKER POPULATION

  22. Slide 22: 3.5 months longer Progression-free Survival with sirexatamab

    3.5 months longer Progression-free Survival with sirexatamab DKK1-high subgroup – upper quartile 22 • Statistically significant improvement in PFS • Median: 9.36 vs. 5.88 m • HR 0.47 • p = 0.0237 • 7 Experimental Arm patients remain on study drug vs. 1 Control Arm

  23. Slide 23: 28% higher response rate (44% vs 16%) with sirexatamab

    28% higher response rate (44% vs 16%) with sirexatamab DKK1-high subgroup – upper quartile 23 Response Sirexatamab Experimental N=25 Control N=19 n (%) n (%) CR 0 (0) 0 (0) PR 11 (44) 3 (16) ORR 95% CI 44.0% (24.4, 65.1) 15.8% (3.4, 39.6) p value p=0.0149 SD 12 (48) 12 (63) DCR 92.0% 78.9% PD 2 (8)

  24. Slide 24: 28% higher response rate by Investigator Assessment

    28% higher response rate (44% vs 16%) with sirexatamab by Investigator Assessment DKK1-high subgroup – upper quartile 24 Response Sirexatamab Experimental N=25 Control N=19 n (%) n (%) CR 0 (0) 0 (0) PR 11 (44) 3 (16) ORR 95% CI 44.0% (24.4, 65.1) 15.8% (3.4, 39.6) p value p=0.0149 SD 12 (48) 12 (63

  25. Slide 25: 24% higher response rate (40% vs 16%) by BICR

    24% higher response rate (40% vs 16%) with sirexatamab by BICR DKK1-high subgroup – upper quartile 25 Response Sirexatamab Experimental N=25 Control N=19 n (%) n (%) CR 1 (4) 0 (0) PR 9 (36) 3 (16) ORR 95% CI 40.0% (21.1, 61.3) 15.8% (3.4, 39.6) p value p= 0.0301 SD 11 (44) 9 (47) Non-CR / Non-PD 1

  26. Slide 26: Sirexatamab significantly improved Overall Survival

    Sirexatamab significantly improved Overall Survival DKK1-high subgroup – upper quartile 26 • Statistically significant improvement in OS • 9 deaths Control Arm vs. 3 deaths Experimental Arm • Median: Not Yet Reached vs. 9.66 m • HR 0.19 • p = 0.0037

  27. Slide 27: ~2 months longer Progression-free Survival with sirexatamab

    ~2 months longer Progression-free Survival with sirexatamab DKK1-high subgroup – upper median 27 • Statistically significant improvement in PFS • Median: 9.03 vs. 7.23 m • HR 0.56 • p = 0.0146 • 12 Experimental Arm patients remain on study drug vs. 3 Control Arm patients

  28. Slide 28: 14% higher response rate (38% vs 24%) with sirexatamab

    14% higher response rate (38% vs 24%) with sirexatamab DKK1-high subgroup – upper median 28 Response Sirexatamab Experimental N=50 Control N=38 n (%) n (%) CR 0 (0) 0 (0) PR 19 (38) 9 (24) ORR 38.0% (24.7, 52.8) 23.7% (11.4, 40.2) P value p=0.0706 SD 26 (52) 23 (61) DCR 90.0% 84.2% PD 4 (8) 4 (11) N

  29. Slide 29: 24% higher response rate (40% vs 16%) by BICR

    24% higher response rate (40% vs 16%) with sirexatamab by BICR DKK1-high subgroup – upper median 29 Response Sirexatamab Experimental N=50 Control N=38 n (%) n (%) CR 1 (2) 0 (0) PR 19 (38) 6 (16) ORR 95% CI 40.0% (26.4, 54.8) 15.8% (6.0, 31.3) p value p=0.0039 SD 23 (46) 19 (50) Non-CR / Non-PD 1 (

  30. Slide 30: Sirexatamab significantly improved Overall Survival

    Sirexatamab significantly improved Overall Survival DKK1-high subgroup – upper median 30 • Statistically significant improvement in OS • 11 deaths Control Arm vs. 9 deaths Experimental Arm • Median: Not Yet Reached vs. 14.39 months • HR 0.48 • p = 0.0475

  31. Slide 31: No Prior Anti-VEGF Population

    NO PRIOR ANTI-VEGF POPULATION

  32. Slide 32: 2.9 months longer Progression-free Survival with sirexatamab

    2.9 months longer Progression-free Survival with sirexatamab No prior anti-VEGF subgroup 32 • Statistically significant improvement in PFS • Median: 11.2 vs. 8.34 m • HR 0.61 • p = 0.0383 • 15 Experimental Arm patients remain on study drug vs. 5 Control Arm

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

    Sirexatamab improved ORR by 22% (55% vs. 33%) No prior anti-VEGF subgroup 33 Sirexatamab Experimental N=49 Control N=46 Response n (%) n (%) CR 0 (0) 3 (7) PR 27 (55) 12 (26) ORR 95% CI 55.1% (40.2, 69.3) 32.6% (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 assess

  34. Slide 34: Sirexatamab improves ORR by 19% as assessed by BICR

    Sirexatamab improves ORR by 19% as assessed by BICR No prior anti-VEGF subgroup 34 Response Sirexatamab Experimental N=49 Control N=46 n (%) n (%) CR 0 (0) 2 (4) PR 22 (45) 10 (22) ORR 95% CI 44.9% (30.7, 59.8) 26.1% (14.3, 41.1) p value p=0.0252 SD 21 (43) 23 (50) Non-CR / Non-PD 2 (4) 1 (2) DCR 91

  35. Slide 35: Overall Survival

    Overall Survival No prior anti-VEGF subgroup 35 • Early advantage in OS with limited number of events • 7 deaths Control Arm vs. 4 death Experimental Arm • Median: Not Yet Reached vs. Not Yet Reached • HR 0.47 • p = 0.1069

  36. Slide 36: Liver Mets Population

    LIVER METS POPULATION

  37. Slide 37: 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

  38. Slide 38: 1.8 months longer Progression-free Survival with sirexatamab

    1.8 months longer Progression-free Survival with sirexatamab Liver Mets subgroup 38 • Nearly 2 month and 30% risk reduction favoring the Experimental Arm • Median: 9.03 vs. 7.26 m • HR 0.70 • p = 0.0443 • 14 Experimental Arm patients remain on study drug vs. 6 Control Arm

  39. Slide 39: 9% higher response rate with sirexatamab

    9% higher response rate with sirexatamab Liver Mets subgroup 39 Response Sirexatamab Experimental N=73 Control N=65 n (%) n (%) CR 0 (0) 2 (3) PR 27 (37) 16 (25) ORR 95% CI 37.0% (26.0, 49.1) 27.7% (17.3, 40.2) p value p=0.1203 SD 36 (49) 36 (55) DCR 86.3% 83.1% PD 6 (8) 6 (9) No assessment 4 (5) 5

  40. Slide 40: 5% higher response rate with sirexatamab by BICR

    5% higher response rate with sirexatamab by BICR Liver Mets subgroup 40 Response Sirexatamab Experimental N=73 Control N=65 n (%) n (%) CR 1 (1) 2 (3) PR 21 (29) 14 (22) ORR 95% CI 30.1% (20.5, 43.1) 24.6% (11.1, 31.8) p value p=0.233 SD 40 (55) 35 (54) Non-CR / Non-PD 1 (1) 1 (2) DCR 86.3% 80.0% PD

  41. Slide 41: Overall Survival

    Overall Survival Liver Mets subgroup 41 • OS not yet mature but trending advantage for sirexatamab • 16 deaths Control Arm vs. 13 deaths Experimental Arm • Median: Not Yet Reached vs. 15.74 m • HR 0.69 • p = 0.1584

  42. Slide 42: ~3 months longer Progression-free Survival with sirexatamab

    ~3 months longer Progression-free Survival with sirexatamab Liver Mets subgroup without prior VEGF 42 • Nearly 3 month improvement favoring the Experimental Arm in patients with liver mets and no prior VEGF exposure • Median: 11.2 vs. 8.34 m • HR 0.64 • p = 0.0725 • 9 Experimental Arm patients remai

  43. Slide 43: 29% higher response rate with sirexatamab

    43 29% higher response rate with sirexatamab Liver Mets subgroup without prior VEGF Response Sirexatamab Experimental N=34 Control N=36 n (%) n (%) CR 0 (0) 2 (6) PR 21 (62) 10 (28) ORR 95% CI 61.8% (43.6, 77.8) 33.3% (18.6, 51.0) p value p=0.0065 SD 11 (32) 18 (50) DCR 94.1% 83.3% PD 0 (0) 4 (11) N

  44. Slide 44: Market Opportunity

    MARKET OPPORTUNITY

  45. Slide 45: Large potential colorectal cancer market opportunity

    Large potential colorectal cancer market opportunity Global Incidence and Deaths US: 155,000 patients and 53,000 deaths ROW: 1,900,000 patients and 910,000 deaths Second-Line Treated Patients US: 30,000 patients Largest 7 non-US markets: 160,000 patients First-Line Treated Patients for Advanced Dise

  46. Slide 46: Sirexatamab ORR is enhanced by increasing DKK1 across biomarker subgroups

    Sirexatamab ORR is enhanced by increasing DKK1 across biomarker subgroups 46 All Patients DKK1-High (upper median) DKK1-High (upper quartile) Group Sirexatamab Experimental Control Sirexatamab Experimental Control Sirexatamab Experimental Control ITT 35% 27% 38% 24% 44% 16% VEGF-naïve 55% 33% 56% 36

  47. Slide 47: FL-501 Anti-GDF-15 monoclonal antibody

    FL-501 Anti-GDF-15 monoclonal antibody

  48. Slide 48: The role of GDF-15 in cachexia and cancer

    GDF-15 Blood stream Stressed сells Cancer cachexia GDF-15 expression leads to an immuno-suppressive TME Heart failure Decline in renal function Hyperemesis gravidarum GFRAL GDF-15 Other GDF-15 related diseases Circulating GDF-15 triggers its effects by binding to its receptor (GFRAL) in the hindbrai

  49. Slide 49: FL-501 mechanism of action

    GDF-15 Blood stream Stressed сells Weight gain, normal appetite, improved muscle mass Cardioprotective effects Renoprotective effects Improved maternal health GFRAL Immuno stimulation in tumor microenvironment Pulmonary improvement FL-501 FL-501 mechanism of action 49

  50. Slide 50: Leap Therapeutics

    company presentation LEAP THERAPEUTICS June 23, 2025

Leap Therapeutics — Investor Presentation (June 2025) on 6ix