BAL0891: Advancing Cancer Research with Dual Inhibition of TTK and PLK1

Mechanism of Action

The mitotic checkpoint ensures accurate eukaryotic cell division by monitoring the proper segregation of chromosomes. BAL0891 targets two key phosphorylating enzymes involved in this process:

• Threonine Tyrosine Kinase (TTK) : Inhibition by BAL0891 induces mitotic override, where cancer cells proceed to divide prematurely, leading to errors in chromosome segregation.
• Polo-like Kinase 1 (PLK1) : Inhibition results in mitotic block, arresting cells at the G2/M phase and preventing progression to anaphase.

Both mechanisms disrupt the cancer cell cycle, triggering apoptosis and effectively halting tumor growth. BAL0891 is the only molecule currently in development that simultaneously inhibits both TTK and PLK1 positioning it as a potential first-in-class therapeutic.

Ongoing Clinical Development

BAL0891 is undergoing a Phase 1 clinical trial, focusing on dose escalation in patients with relapsed/refractory solid tumors. Key details include:

• Clinical Trial Identifier : NCT05768932
• Current Status : Dose escalation stage, evaluating safety, tolerability, and pharmacokinetics.

Study Design

The study design, highlighting the trial's objectives, endpoints, and dosing schedules, can be accessed via the following link : BAL0891 Study Design.

Scientific Insights

Recent publication in Frontiers in Oncology (Aug 9 2024) highlights the scientific rationale and potential f for dual inhibition therapy.
https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1447807/full