ES002: Clinical-Stage Anti-CD39 Antibody with Best-in-Class Potential

ES002’s dual ATP-adenosine mechanism is a potentially powerful TME regulator and transformative cancer immunotherapy. In preclinical studies ES002 demonstrated significant single agent anti-tumor activity as well as an excellent tolerability profile. ES002 has also shown superior enzymatic inhibition and binding affinity.

The ecto-ATPase CD39 is the rate-limiting enzyme in the ATP-adenosine pathway that plays an important immune regulatory role. The dual ES002 mechanism is designed to reverse immunosuppression by maintaining high levels of immune-stimulatory extracellular ATP while reducing suppressive adenosine. Blocking CD39 is expected to have a strong effect on the inhibition of Treg function, enhancing the killing function of effector T cells. 

An ES002 monotherapy Phase 1 clinical study started in the US in January 2022 and IND clearance from CDE was received in February 2022. 

CD39 Dual ATP-Adenosine Mechanism of Action

• CD39 is pivotal in the conversion of extracellular ATP into AMP, which is then converted downstream by CD73 into immunosuppressive adenosine
• CD39 blockade is expected to maintain extracellular ATP, a key TME inflammatory signal stimulating the immune response
• Blocking CD39 is expected to have a strong effect on the inhibition of Treg function, enhancing the killing function of effector T cells

Key Differentiation

• Differentiated dual ATP-adenosine mechanism of action versus targeting CD73
• Demonstrated high binding affinity and enzymatic inhibition
• Significant in vivo single agent anti-tumor activity and excellent GLP tolerability profile

In vitro and In vivo Properties

• High binding affinity against human and cyno CD39
• Strong enzyme inhibition effect
• Efficient reversal of immunosuppression by adenosine mediated inhibition
  • Promotes IL-18 and IL-1β secretion (anti-CD73 antibodies have not shown this effect)
  • Promotes monocyte maturation and activation
  • Promotes NK cell activation

In vivo:

• Demonstrated a significant single-agent anti-tumor activity in MOLP-8 PBMC humanized mice model

Anti-tumor activity in PBMC humanized mice

Statistically significant reduction in tumor volume observed in all groups treated with ES002 with a dose as low as 0.03mg/kg