Cypherpunk Technologies (CYPH) 43rd Annual J.P. Morgan Healthcare Conference 2025 summary

Corporate and clinical program updates

• Announced the generic name for lead antibody DKN-01 as sirexatamab, focusing on biomarker-driven oncology drug development.

• Completed enrollment in two randomized controlled trials for sirexatamab in first-line gastric and second-line colorectal cancer; initial data from both expected in Q1 2025.

• Cash position of $62.8M as of September 30, 2024, providing runway into Q2 2026 after a $40 million financing led by Gilead.

• Advanced FL-501, an anti-GDF15 antibody, into preclinical development with plans to share initial data in early Q2 and move to clinical trials in H1 2026.

• Sirexatamab demonstrated single-agent activity in endometrial cancer, supporting an investigator-sponsored trial in combination with Keytruda.

Scientific rationale and biomarker strategy

• DKK1 is a key driver of tumor proliferation, metastasis, angiogenesis, and immune suppression; high DKK1 correlates with poor outcomes.

• Sirexatamab targets and removes free DKK1, aiming to reverse its pro-tumorigenic effects, reprogram macrophages, and enhance immune response.

• Two assays developed to measure DKK1: one for plasma and one for tumor RNA, both implemented in current trials.

• Biomarker-driven approach underpins patient selection and trial stratification, especially for DKK1 and PD-L1 expression.

• Sirexatamab’s mechanism supports combination with VEGF inhibitors and immunotherapies due to its impact on angiogenesis and immune modulation.

Colorectal cancer clinical data and strategy

• DeFiance study Part A showed a 33% overall response rate and 93% disease control rate in second-line colorectal cancer, exceeding benchmarks.

• Left-sided tumors had a 38% response rate and 100% disease control; bevacizumab-naive patients showed a 53% response rate.

• Median duration of response was 9.92 months; left-sided tumors had longer PFS (8.6 months), and bevacizumab-naive group had PFS of 8.05 months.

• Randomized Part B completed enrollment of 188 patients, stratified by tumor-sidedness and prior bevacizumab exposure; primary endpoint is progression-free survival.

• Data will inform optimal populations for phase III development, with potential to move into first-line therapy if results are favorable.