Cypherpunk Technologies (CYPH) Status Update summary

Current treatment landscape and unmet needs in colorectal cancer

• Standard care for advanced colorectal cancer relies on FOLFOX or FOLFIRI with bevacizumab, with few new agents introduced in the past two decades.

• Most patients lack actionable biomarkers, limiting the use of targeted therapies.

• Bevacizumab remains the entrenched standard globally due to tolerability and survival data.

• Second-line therapy typically continues bevacizumab with irinotecan-based regimens, but durability is limited.

• There is a significant need for new therapies to improve outcomes beyond current angiogenesis inhibitors.

Sirexatamab (DKN-01) clinical experience and rationale

• Sirexatamab is well tolerated as a single agent and in combination, with no major safety concerns in 20-30 treated patients.

• Early data suggested a biomarker-driven approach targeting DKK1, a secreted protein linked to poor prognosis.

• Anecdotal experience indicates some patients have longer disease control than expected with standard care.

DEFIANCE study design and key results

• The DEFIANCE phase 2 study enrolled 188 metastatic colorectal cancer patients, all microsatellite stable and BRAF negative, post one prior therapy.

• In the intent-to-treat population, Sirexatamab improved overall response rate by 10.7% (36.2% vs. 25.5%).

• The experimental arm showed a higher proportion of patients remaining on therapy, suggesting durable benefit.

• Progression-free survival (PFS) curves are separating over time, with optimism for a significant PFS advantage.