Cypherpunk Technologies (CYPH) Study Result summary

Sirexatamab (DKN-01) Mechanism and Rationale

• Sirexatamab is an anti-DKK1 monoclonal antibody that neutralizes DKK1, stimulating immune-mediated anti-tumor responses and reducing angiogenesis and oncogenic signaling.

• DKK1 is produced by cancer cells, enhances immunosuppression, and promotes tumor growth and angiogenesis.

DeFiance Study (Colorectal Cancer, Part B) Design and Population

• Randomized phase II global trial: 188 patients with advanced CRC received FOLFIRI/mFOLFOX6 + bevacizumab ± sirexatamab as second-line therapy; demographics balanced, 77% had left-sided tumors, 51% enrolled from South Korea.

• Patients were stratified by tumor sidedness and prior bevacizumab exposure; 50% were VEGF-naive.

• Key subgroups included DKK1-high, VEGF-naive, EGFR-experienced, and RAS wild-type patients.

• All patients had at least three months of follow-up, with a mean study duration of six months.

• Safety profile was similar between experimental and control arms, with no increase in high-grade adverse events.

DeFiance Study Results

• Sirexatamab plus bevacizumab and chemotherapy achieved a 35% ORR vs. 23% in the control arm for second-line CRC patients.

• ORR benefit was consistent across subgroups: 38% in left-sided tumors, 51% in VEGF-naive, 54% in EGFR-experienced, and 43% in RAS wild-type patients.

• DKK1 biomarker levels strongly correlated with clinical activity; ORR reached 48% in upper-quartile DKK1 patients.

• Early separation of PFS curves was observed in several subgroups, especially those with high DKK1; PFS data are maturing.

• Sirexatamab combination was well-tolerated, supporting plans for a registrational Phase 3 trial in second-line CRC.