Kura Oncology (KURA) Investor update summary

Clinical data highlights

• Darlifarnib combined with adagrasib demonstrated confirmed objective response rates of 67% in pancreatic cancer, 50% in non-small cell lung cancer, and 29% in KRAS inhibitor-naïve colorectal cancer, with tumor shrinkage in 77% of all patients and 94% of KRAS inhibitor-naïve patients.

• Enhanced clinical activity was observed in KRAS-mutant tumors, with response rates exceeding historical controls for single-agent therapies and durable responses, especially in pancreatic cancer.

• The combination was well tolerated, with manageable safety profile; most common adverse events included diarrhea, nausea, anemia, and neutropenia, with dose interruptions and reductions considered manageable.

• Clinical activity was seen in both KRAS inhibitor-naïve and pretreated patients, with ongoing responses and a significant proportion of patients remaining on treatment.

Translational and preclinical insights

• Preclinical studies show darlifarnib enhances the efficacy of all classes of RAS inhibitors by sustaining mTORC1 suppression and overcoming resistance, including in previously resistant or relapsed settings.

• Mechanistically, darlifarnib inhibits RHEB farnesylation, leading to sustained mTORC1 blockade and potentiation of RAS inhibitor efficacy.

• The combination approach is effective across mutant-selective, pan-KRAS, and multi-selective RAS inhibitors, supporting broad applicability.

• Data support further evaluation of darlifarnib with both approved and investigational targeted therapies, including in earlier line settings.

Development strategy and next steps

• A platform trial is being operationalized to evaluate darlifarnib in combination with various KRAS, pan-RAS, and other targeted agents across multiple tumor types, starting with pancreatic cancer.

• The first planned combination is darlifarnib plus daraxonrasib in KRAS-mutant pancreatic cancer, entering Phase 1a in early 2027.

• Ongoing Phase 1b expansion with cabozantinib in RCC and planned Phase 1a escalation with daraxonrasib in 2L+ PDAC, with pivotal trials anticipated to initiate between 2027 and 2028.

• The platform trial design allows for parallel evaluation of combinations and rapid expansion into new indications and partners.

• Additional combinations and indications will be evaluated within the platform study, with successful regimens advancing to dedicated registrational studies.