Tango Therapeutics (TNGX) 3rd Annual Guggenheim Healthcare Innovation Conference summary

Development stage and priorities

• Shifted from discovery-stage operations to a late-stage, pre-submission and pre-commercial organization; priority is executing toward vopimetostat approval.

• Key milestones over the next 12 months: initiate frontline pancreatic cancer study, clarify frontline and second-line regulatory strategies, and define the NSCLC development path.

Combination data and rationale

• Updated ESMO dataset: vopimetostat plus daraxonrasib showed an 82% response rate in 22 pancreatic cancer patients; 4 of 5 NSCLC patients responded, with an 81% response rate across both groups.

• Nine-month PFS rate was 88%; no second-line patients had progressed at the update. No grade 3 rash, stomatitis or mucositis was observed.

• A handful of KRAS G12D patients had entered the daraxonrasib arm, but efficacy was too early to assess; management cited 50% response in G12R patients versus 7% with daraxonrasib monotherapy.

• Management attributed the stronger response profile with daraxonrasib versus zoldonrasib combinations to more effective targeting of the RAS wild-type pathway component.

• Proposed mechanism for lower skin toxicity: vopimetostat-induced phospho-ERK upregulation may counteract daraxonrasib-associated phospho-ERK downregulation in skin.

Pancreatic cancer trial plans

• Frontline Phase III is planned to start in H1 2027; the 1:1 randomized study is designed for 240 patients per arm, comparing vopimetostat plus daraxonrasib with investigator-choice chemotherapy.

• FDA discussions aligned on response rate and PFS as dual primary endpoints, the dose proposal and statistical analysis plan; site and CRO startup activities are underway.

• Dual primary endpoints may allow discussion with FDA about an earlier submission timing; PFS and overall survival analyses are also planned to strengthen the data package.

• Second-line pancreatic cancer remains a priority after frontline startup; a potential FDA strategy discussion was expected before year-end 2026, with an enrollment-open study and accelerated approval options under consideration.

• Supply negotiations with Revolution Medicines for the frontline study were ongoing; continuation is preferred, but management said study startup and execution would proceed without delay if no agreement is reached.