Tempest Therapeutics (TPST) Study Update summary

Study background and rationale

• Amezalpat (TPST-1120) is a first-in-class PPAR-alpha antagonist targeting both tumor and immune suppressor cells, designed for difficult-to-treat tumors, including immune cold and beta-catenin mutated cancers.

• Earlier phase I data showed clinical benefit as monotherapy and in combination with checkpoint inhibitors.

• Liver cancer was prioritized due to high PPAR-alpha expression and promising early results.

• Beta-catenin mutations, which upregulate PPAR-alpha, may enhance response to amezalpat.

Study design and patient population

• Global randomized phase 1b/2 trial in first-line unresectable/metastatic HCC, comparing amezalpat plus atezolizumab/bevacizumab to standard of care across 26 sites in 7 countries.

• 70 patients randomized: 40 in the amezalpat arm, 30 in control, with balanced demographics and baseline characteristics.

• Primary endpoint was confirmed objective response rate; secondary endpoints included progression-free survival, overall survival, and safety.

• Stratification factors and eligibility criteria aligned with prior registrational studies.

Efficacy and survival outcomes

• Median overall survival in the amezalpat arm was 21 months versus 15 months in control, a six-month improvement.

• Hazard ratio for OS was 0.65, indicating a 35% reduction in risk of death.

• Confirmed objective response rate was 30% for amezalpat versus 13.3% for control; PFS HR was 0.8 (median 7 vs. 4.27 months).

• 50% of amezalpat patients remain in survival follow-up, compared to 30% in control.

• Early and sustained separation of survival curves observed, with benefit seen as early as three months.