Cypherpunk Technologies (CYPH) Piper Sandler 36th Annual Healthcare Conference summary

Key program updates and clinical progress

• Lead program DKN-01 is advancing in two phase 2 trials: first-line gastric cancer (DisTinGuish) and second-line colorectal cancer (DeFianCe).

• Patient data from both trials are maturing, with key readouts expected late 2024 to mid-2025.

• DKN-01 targets DKK1, a protein linked to poor prognosis and immune suppression in several cancers.

• Combination strategies with chemo, PD-1 inhibitors, and anti-angiogenic agents are central to ongoing studies.

• Expansion into additional indications like endometrial, breast, and lung cancer is under consideration.

Gastric cancer (DisTinGuish study)

• Consistent efficacy observed across monotherapy and combination settings, especially in patients with high DKK1 expression.

• Part A showed strong response rates and survival in a U.S.-only, low PD-L1 population.

• Part C is a global, randomized trial with results expected late 2024 or early 2025.

• Subgroup analyses by DKK1 and PD-L1 expression are critical for interpreting outcomes.

• FDA may restrict PD-1/chemo use to higher PD-L1 patients, highlighting unmet need in low PD-L1 groups.

Colorectal cancer (DeFianCe study)

• DKN-01 plus chemo and BEV showed a 33% response rate in part A, exceeding historical benchmarks.

• Stronger efficacy noted in left-sided and rectal cancers, linked to Wnt signaling biology.

• Part B completed enrollment in September; top-line data expected mid-2025.

• Subgroup analyses will focus on DKK1 levels and consensus molecular subtypes (CMS2, CMS4).

• New mechanisms are needed for broader CRC populations beyond niche mutations.