ABOUT THE MOLECULE

• APV-527 is a bispecific antibody that targets the immune co-stimulatory receptor 4-1BB and the tumor-associated antigen 5T4.
• The molecule is designed to target 5T4-expressing cancer cells by stimulating 4-1BB on both activated T cells and natural killer cells.
• APV-527 was designed to overcome limitations of the 1st generation 4-1BB monospecific mAbs:
  • Clinical Activity: 5T4-dependent, 4-1BB signaling confers T cell and NK cell stimulation at the tumor site
  • Safety: Conditional 4-1BB agonism is only active upon simultaneous binding to 4-1BB and 5T4, preventing peripheral immune cell activation in non-tumor tissues, which may improve safety profile in contrast to potential unspecific activation of 4-1BB with monospecific mABs, which trigger activation without a conditional second target activation.

PHASE 1 TRIAL DESIGN

The fully enrolled Phase 1 trial was conducted as a multi-center, multi-cohort, open-label dose-escalation trial that included administration of ALG.APV-527 in six escalating dose levels in a 3+3 design*. The trial enrolled adult patients with multiple solid tumor types/histologies likely to express the 5T4 antigen. ALG.APV-527 was administered intravenously once every two weeks and assessed the safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of ALG.APV-527.

*The 3+3 design proceeds in cohorts of three patients treated at increasing dose levels. Dose escalation stops when at least two out of three or six patients experience dose limiting toxicities (DLTs) at that dose level.

Clinical Highlights

Safety and Tolerability

• APV-527 demonstrated positive safety and tolerability across all cohorts
• No serious liver toxicity, a common side effect of other 4-1BB targeting treatments that can cause patients to discontinue dosing, was observed
• The drug was well tolerated across all dose levels

Clinical Activity/Efficacy

• Nine of 16 efficacy evaluable patients (56%) achieved stable disease (SD)
  • One colon cancer patient achieved SD for more than six months
  • The longest SD duration was in a breast cancer patient who entered the study with progressive disease, achieved stable disease and remained on study for >11 months. This patient successfully transitioned to a higher dose level twice

Evidence of biological activity of ALG.APV-527

• APV-527 could be measured in all patients. Serum concentrations of ALG.APV-527 were proportional to the administered dose
• Analysis of biomarkers in the serum of treated patients including soluble 4-1BB (surface protein found on certain immune cells) confirm biological activity of ALG.APV-527
• Analysis of biomarkers in biopsies (including the 5T4 target cells and CD8 T cancer killer cells are consistent with immune activation in the tumor microenvironment). This observation consistent with ALG.APV-527 expected MOA.