Cypherpunk Technologies Inc. · NASDAQ:CYPH
Cypherpunk Technologies — Leap Therapeutics — Corporate Update (March 2025)
42 slides from Cypherpunk Technologies's corporate update, Mar 26, 2025
Slide 1: Leap Therapeutics Company Presentation
company presentation LEAP THERAPEUTICS March 26, 2025
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
Slide 3: Developing biomarker-targeted antibody therapies for cancer patients
Developing biomarker-targeted antibody therapies for cancer patients 3 Lead program preparing for Phase 3 CRC clinical trials – sirexatamab (DKN-01) targeting DKK1 Statistically Significant ORR and PFS in 2L CRC patients with high DKK1 levels or are VEGF-naïve Biomarker strategy, focus on CRC $42.7M
Slide 4: Pipeline
Pipeline 4 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
Slide 5: Sirexatamab (DKN-01) Anti-DKK1 monoclonal antibody
SIREXATAMAB (DKN-01) Anti-DKK1 monoclonal antibody
Slide 6: The role of DKK1 in cancer
The role of DKK1 in cancer 6 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
Slide 7: DKK1 production from multiple sources can drive tumor growth
DKK1 production from multiple sources can drive tumor growth 7 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
Slide 8: Activity of sirexatamab (DKN-01) to treat cancer
Activity of sirexatamab (DKN-01) to treat cancer 8 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
Slide 9: Sirexatamab (DKN-01) Colorectal cancer development
SIREXATAMAB (DKN-01) Colorectal cancer development
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
Slide 11: Bevacizumab benchmark studies demonstrate need for new options in second-line
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
Slide 12: DeFianCe study design
DeFianCe study design 12 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
Slide 13: DKK1 Biomarker Population
DKK1 BIOMARKER POPULATION
Slide 14: 32% higher response rate with sirexatamab by Investigator Assessment
32% higher response rate (48% vs 16%) with sirexatamab by Investigator Assessment DKK1-high subgroup – upper quartile 14 Response Sirexatamab Experimental N=25 Control N=19 n (%) n (%) CR 0 (0) 0 (0) PR 12 (48) 3 (16) ORR 95% CI 48% (27.8, 68.7) 16% (3.4, 39.6) p value p=0.0067 SD 11 (44) 12 (63) DC
Slide 15: 32% higher response rate with sirexatamab by Investigator Assessment
32% higher response rate (48% vs 16%) with sirexatamab by Investigator Assessment DKK1-high subgroup – upper quartile 15 Response Sirexatamab Experimental N=25 Control N=19 n (%) n (%) CR 0 (0) 0 (0) PR 12 (48) 3 (16) ORR 95% CI 48% (27.8, 68.7) 16% (3.4, 39.6) p value p=0.0067 SD 11 (44) 12 (63) DC
Slide 16: 35% higher response rate with sirexatamab by BICR
35% higher response rate (40% vs 5%) with sirexatamab by BICR DKK1-high subgroup – upper quartile 16 Response Sirexatamab Experimental N=25 Control N=19 n (%) n (%) CR 1 (4) 0 (0) PR 9 (36) 1 (5) ORR 95% CI 40% (21.1, 61.3) 5% (0.1, 26.0) p value p<0.001 SD 11 (44) 10 (53) Non-CR / Non-PD 1 (4) 1 (5
Slide 17: 3.5 month longer Progression-free Survival with sirexatamab
3.5 month longer Progression-free Survival with sirexatamab DKK1-high subgroup – upper quartile 17 • Statistically significant improvement in PFS • Median: 9.36 vs. 5.88 m • HR 0.46 • p = 0.0248 • 10 Experimental Arm patients remain on study drug vs. 1 Control Arm
Slide 18: Sirexatamab significantly improved Overall Survival
Sirexatamab significantly improved Overall Survival DKK1-high subgroup – upper quartile 18 • Statistically significant improvement in OS • 8 deaths Control Arm vs. 1 death Experimental Arm • Median: Not Yet Reached vs. 9.49 m • HR 0.09 • p = 0.0018
Slide 19: Sirexatamab statistically significant benefit across endpoints (upper quartile)
Sirexatamab statistically significant benefit across endpoints DKK1-high subgroup – upper quartile 19 Sirexatamab Experimental Arm (n=25) Control Arm (n=19) ORR by IA 48.0% 15.8% p = 0.0067 ORR by BICR 40.0% 5.3% p < 0.001 Median PFS 9.36 months 5.88 months HR 0.46 95% CI: 0.21, 1.02 p = 0.0248 Even
Slide 20: Sirexatamab statistically significant benefit across endpoints (upper median)
Sirexatamab statistically significant benefit across endpoints DKK1-high subgroup – upper median 20 Sirexatamab Experimental Arm (n=50) Control Arm (n=38) ORR by IA 40.0% 23.7% p = 0.0467 ORR by BICR 40.0% 10.5% p < 0.001 Median PFS 7.66 months 7.23 months HR 0.57 95% CI: 0.33, 0.99 p = 0.0218 Event
Slide 21: No Prior Anti-VEGF Population
NO PRIOR ANTI-VEGF POPULATION
Slide 22: Sirexatamab improved ORR by 22% by Investigator Assessment
Sirexatamab improved ORR by 22% (55% vs. 33%) by Investigator Assessment No prior anti-VEGF subgroup 22 Sirexatamab Experimental N=49 Control N=46 Response n (%) n (%) CR 0 (0) 2 (4) PR 27 (55) 13 (28) ORR 95% CI 55% (40.2, 69.3) 33% (19.5, 48.0) p value p=0.0116 SD 19 (39) 24 (52) DCR 94% 85% PD 0
Slide 23: Sirexatamab improved ORR by 22% by Investigator Assessment
Sirexatamab improved ORR by 22% (55% vs. 33%) by Investigator Assessment No prior anti-VEGF subgroup 23 Sirexatamab Experimental N=49 Control N=46 Response n (%) n (%) CR 0 (0) 2 (4) PR 27 (55) 13 (28) ORR 95% CI 55% (40.2, 69.3) 33% (19.5, 48.0) p value p=0.0116 SD 19 (39) 24 (52) DCR 94% 85% PD 0
Slide 24: Sirexatamab doubled ORR as assessed by BICR
Sirexatamab doubled ORR 45% vs. 22% as assessed by BICR No prior anti-VEGF subgroup 24 Response Sirexatamab Experimental N=49 Control N=46 n (%) n (%) CR 0 (0) 2 (4) PR 22 (45) 8 (17) ORR 95% CI 45% (30.7, 59.8) 22% (11.0, 36.4) p value p=0.0066 SD 20 (41) 24 (52) Non-CR / Non-PD 2 (4) 1 (2) DCR 90%
Slide 25: 2.6 month longer Progression-free Survival with sirexatamab
2.6 month longer Progression-free Survival with sirexatamab No prior anti-VEGF subgroup 25 • Statistically significant improvement in PFS • Median: 10.94 vs. 8.34 m • HR 0.59 • p = 0.0386 • 23 Experimental Arm patients remain on study drug vs. 8 Control Arm
Slide 26: Overall Survival No prior anti-VEGF subgroup
Overall Survival No prior anti-VEGF subgroup 26 • Early advantage in OS with limited number of events • 4 deaths Control Arm vs. 1 death Experimental Arm • Median: Not Yet Reached vs. Not Yet Reached • HR 0.22 • p = 0.0719
Slide 27: Sirexatamab statistically significant benefit across endpoints
Sirexatamab statistically significant benefit across endpoints No prior anti-VEGF subgroup 27 Sirexatamab Experimental Arm (n=49) Control Arm (n=46) ORR by IA 55.1% 32.6% p = 0.0116 ORR by BICR 44.9% 21.7% p = 0.0066 Median PFS 10.94 months 8.34 months HR 0.59 95% CI: 0.32, 1.07 p = 0.0386 Event-Fre
Slide 28: Intent-to-Treat Population
INTENT-TO-TREAT POPULATION
Slide 29: Sirexatamab improved ORR by 10% by Investigator Assessment
Sirexatamab improved ORR by 10% (36% vs. 26%) by Investigator Assessment Intent-to-Treat (ITT) population 29 Sirexatamab Experimental N=94 Control N=94 Response n (%) n (%) CR 0 (0) 2 (2) PR 34 (36) 22 (23) ORR 95% CI 36% (26.5, 46.7) 26% (17.0, 35.6) p value p=0.0536 SD 47 (50) 55 (59) DCR 86% 84%
Slide 30: Sirexatamab improved ORR by 10% by Investigator Assessment
Sirexatamab improved ORR by 10% (36% vs. 26%) by Investigator Assessment Intent-to-Treat (ITT) population 30 Sirexatamab Experimental N= 94 Control N= 94 Response n (%) n (%) CR 0 (0) 2 (2) PR 34 (36) 22 (23) ORR 95% CI 36% (26.5, 46.7) 26% (17.0, 35.6) p value p=0.0536 SD 47 (50) 55 (58) DCR 86% 84
Slide 31: Sirexatamab improved ORR by 17% assessed by BICR
Sirexatamab improved ORR by 17% (33% vs. 16%) assessed by BICR Intent-to-Treat (ITT) population 31 Response Sirexatamab Experimental N=94 Control N=94 n (%) n (%) CR 1 (1) 2 (2) PR 30 (32) 13 (14) ORR 95% CI 33% (23.6, 43.4) 16% (9.2, 25.0) p value p=0.0023 SD 46 (49) 51 (54) Non-CR / Non-PD 2 (2) 4
Slide 32: Tail population advantage in Progression-free Survival
Tail population advantage in Progression-free Survival Intent-to-Treat (ITT) population 32 • Separation after the median indicates tail population showing advantage in PFS • Median: 7.82 vs. 8.31 m • HR 0.83 • p = 0.1809 • With 10 additional Experimental Arm patients on study drug compared to Contro
Slide 33: Overall Survival Intent-to-Treat population
Overall Survival Intent-to-Treat (ITT) population 33 • OS not mature due to limited number of events • 13 deaths Control Arm vs. 10 deaths Experimental Arm
Slide 34: Sirexatamab benefit across ORR endpoints, survival data still to mature
Sirexatamab benefit across ORR endpoints, survival data still to mature Intent-to-Treat (ITT) population 34 Sirexatamab Experimental Arm (n=94) Control Arm (n=94) ORR by IA 36.2% 25.5% p = 0.0536 ORR by BICR 33.0% 16.0% p = 0.0023 Median PFS 7.82 months 8.31 months HR 0.83 95% CI: 0.56, 1.24 p = 0.1
Slide 35: Market Opportunity
MARKET OPPORTUNITY
Slide 36: 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
Slide 37: Potential Phase 3 Trial: 2nd Line Metastatic CRC
Potential Phase 3 Trial: 2nd Line Metastatic CRC 37 Primary Endpoint • BICR assessed Objective Response Rate (Accelerated Approval) • Overall Survival (Confirmatory Endpoint) Potential patient populations • DKK1-high • Anti-VEGF naïve Chemo + bev + placebo Patient Enrollment Chemo + bev + sirexatama
Slide 38: Summary of preliminary results
Summary of preliminary results 38 • Statistically significant improvement in ORR, PFS, and OS in DKK1-high (upper quartile) patients and the DKK1-high (upper median) patients • Represent 25%-50% of the global 2L CRC market • Statistically significant improvement in ORR and PFS in VEGF-naïve patients
Slide 39: FL-501 Anti-GDF-15 monoclonal antibody
FL-501 Anti-GDF-15 monoclonal antibody
Slide 40: 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
Slide 41: 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 41
Slide 42: Leap Therapeutics
company presentation LEAP THERAPEUTICS March 26, 2025