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, aiming for a dual mechanism in cancer and immune modulation.

• The drug is designed for difficult-to-treat tumors, including immune cold tumors and those with beta-catenin mutations.

• 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 I-B/2 study in first-line unresectable/metastatic HCC, operationalized by Roche, across 26 sites in 7 countries.

• Patients randomized to amezalpat plus atezolizumab/bevacizumab or standard of care (atezolizumab + bevacizumab).

• 40 patients in the amezalpat arm, 30 in the control arm; demographics were balanced, with some numerical differences favoring control.

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

• Primary endpoint was confirmed objective response rate (ORR); secondary endpoints included PFS, OS, and safety.

Efficacy and survival outcomes

• Median overall survival (OS) in the amezalpat arm exceeded 21 months, a six-month improvement over the 15 months in the control arm; hazard ratio for OS was 0.65.

• Confirmed ORR was 30% in the amezalpat arm versus 13.3% in control; PFS HR was 0.8 (median 7 vs. 4.27 months).

• 50% of amezalpat patients remained in survival follow-up, compared to 30% in control at data cut.

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

• Efficacy was observed in both immune "cold" and "hot" tumors, and in B-catenin mutant and wild-type populations.