Science

IL-21 Agonist Antibody – PIO-001

Pio Tx is developing a mAb agonist of IL-21 (PIO-001) that binds to and enhances the activity of endogenous human IL-21.

This novel approach of selective enhancement of cytokine function allows for a safer, more convenient therapeutic approach with the established developability path of mAbs, which is aligned with current IO treatment regimens. The aforementioned qualities allow development of a ‘First in Class’ treatment based on mechanism of action in the IO space.

PIO-001 has the potential to:

  • Amplify IL-21 activity at sites of endogenous production (e.g. tumour microenvironment or tumour draining lymph node)
  • Be combined with standard of care and immunotherapies such as checkpoint inhibitors thereby increasing their applicability and/or efficacy
  • Amplify or sustain CAR-T cell activity

Treatment with PIO-001 can be differentiated from systemic treatment with recombinant IL-21 as it has the potential to:

  • Act locally, proportionally, and directly at sites of endogenous IL-21 production, thereby minimising any likelihood of dose-limiting toxicities and/or adverse events
  • Have an improved therapeutic index compared to recombinant IL-21
  • Avoid formation of neutralizing anti-IL-21 antibodies which have been observed in the clinic with recombinant IL-21 administration
  • Have a more convenient dosing schedule compared to recombinant IL-21

Pio Tx has optimized and validated a suite of functional assays utilizing cell lines and primary cells, that demonstrate that PIO-001 can agonise the activity of IL-21. PIO-001 does so by increasing the potency (EC50) of IL-21 activity.

PIO-001 Binds to, and Amplifies the Function of, Endogenously Produced and Localized IL-21