Cypherpunk Technologies Inc. · NASDAQ:CYPH
Cypherpunk Technologies — Leap Therapeutics — ESMO Congress 2025
13 slides from Cypherpunk Technologies's conference presentation, Oct 20, 2025
Slide 1: DeFianCe Trial: Randomized phase 2 trial of sirexatamab plus bevacizumab and chemotherapy
DeFianCe Trial: A randomized phase 2 trial of sirexatamab (DKN-01) plus bevacizumab and chemotherapy versus bevacizumab and chemotherapy as second-line therapy in advanced microsatellite stable (MSS) colorectal cancer (CRC) Z.A. Wainberg1, S.-W. Han2, J.G. Kim3, C. Devoe4, J. Strickler5, K.-W. Lee6,
Slide 2: Declaration of Interests
DECLARATION OF INTERESTS • Consulting: Alligator Therapeutics, Amgen, AstraZeneca, Arcus, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo Company, Eli Lilly and Company, EMD Serono, Roche AG, Genentech, Ipsen, Johnson & Johnson, Merus N.V., Merck, Novartis, Novocure, Pfizer, Servier, Vera
Slide 3: Sirexatamab inhibits DKK1, a poor prognostic factor and key driver of CRC
Sirexatimab inhibits DKK1, a poor prognostic factor and key driver of CRC • Metastatic CRC is highly associated with alterations in the wnt signaling pathway. • DKK1 is a key regulator of wnt signaling and implicated in disease progression, metastasis and angiogenesis. • Circulating levels of DKK1 a
Slide 4: DeFianCe study design
DeFianCe study design A randomized, open label, global phase 2 trial of sirexatamab plus bevacizumab and chemotherapy versus bevacizumab and chemotherapy as second-line therapy in mCRC Sirexatamab + SOC chemotherapy (FOLFIRI or mFOLFOX6) Key eligibility criteria: + bevacizumab • One prior 5-FU based
Slide 5: Baseline Demographics of DeFianCe Trial
Baseline Demographics of DeFianCe Trial N=188 Experimental Arm N=94 n (%) Control Arm N=94 n (%) Male 64 (68) 52 (55) Age, mean (min, max) 59.6 (33, 84) 58.7 (29, 84) Region United States 41 (44) 40 (43) South Korea 50 (53) 45 (48) Germany 3 (3) 9 (10) Tumor Sidedness Right 24 (25) 23 (25) Left 70 (
Slide 6: Progression-free Survival and Overall Response Rate
Progression-free Survival and Overall Response Rate Intent-to-Treat (ITT) population – Investigator Assessment Sirexatamab • Median: 9.2 months • Event-free rate favors Experimental Control N=94 N=94 sirexatamab vs. 8.3 sirexatamab arm beginning at Response n (%) n (%) months control arm month 9 (53
Slide 7: Sirexatamab significantly improves PFS and OS in DKK1-high patients
Sirexatamab significantly improves PFS and OS in DKK1-high patients DKK1-high subgroup – Upper Median – Investigator Assessment Progression free survival • Median: 9.03 mos vs. 7.06 mos • HR 0.61 (0.37, 1.0) • p = 0.0255 Overall survival Sirexatamab Control Experimental N=50 N=38 Response n (%) n (%
Slide 8: Safety of sirexatamab
Safety of sirexatamab Overall TEAE profile is similar between the two arms suggesting the addition of sirexatamab does not adversely impact the safety profile of the combinatorial agents. # Only regimen related ≥ Grade 3 occurring in >10% in either arm was neutrophil count decreased * SAEs assessed
Slide 9: Conclusions
Conclusions •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 the overall popu
Slide 10: Acknowledgements
Acknowledgements • All the patients and family who participated in the study and made it possible • The clinical study teams who participated in the study • Leap Therapeutics (Cambridge, MA) • All authors who contributed to and approved the presentation • Investigators: United States South Korea Ger
Slide 11: Backup
Backup Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
Slide 12: DKK1 production from multiple sources can drive tumor growth and is associated with poor prognosis
DKK1 production from multiple sources can drive tumor growth and is associated with poor prognosis in colorectal cancer DKK1 DKK1 Bone Blood vessel Tumor DKK1 protein in circulation DKK1 RNA from the tumor is is measured by SomaScan and measured by RNAscope ELISA DKK1 high DKK1 low SomaScan platform
Slide 13: Sirexatamab activity is enhanced with increasing thresholds of baseline DKK1
Sirexatamab activity is enhanced with increasing thresholds of baseline DKK1 All Patients DKK1-High (upper median) DKK1-High (upper quartile) Endpoint Sirexatamab Control Sirexatamab Control Sirexatamab Control Experimental Experimental Experimental n=94 n=94 n=50 n=38 n=25 n=19 ORR 35.1% 26.6% 38.0