NextGen CTLA-4 (AGEN1181)

Positioning recent PD-1s and PD-L1s for market leadership

AGEN1181 – Status

  • In clinical trials as monotherapy and in combination with PD-1
  • Clinical activity seen at low doses in patients refractory to other therapies
  • Potential to triple patient population responding to Yervoy®

AGEN1181 can significantly expand the markets of PD-1s and PD-L1s

  • Leading PD-1 antibodies (Keytruda & Opdivo) have combined annual revenues of $20B
  • Higher efficacy potential of AGEN1181 in combination with PD-1s or PD-L1s can expand the market for recently launched products

Why is CTLA-4 critically important?

  • CTLA-4 is the main driver of initiation of immune response and memory
  • PD-1 is an important driver of an existing or new immune response

What must an optimal CTLA-4 antibody do?

  • Enhance T cell priming, activation, and proliferation
  • Promote the generation of memory T cells for durable anti-tumor immune response
  • Deplete intratumoral Tregs that drive broad immune suppression – Tregs are associated with poor prognosis

The need for a NextGen CTLA-4

  • First generation anti-CTLA-4 antibody, Yervoy®, has achieved unprecedented durable responses in 20% of metastaic melanoma patients
  • Agenusí NextGen CTLA-4 antibody is designed to triple the responder population to 60%
  • Drive deeper responses for an ideal combination partner to PD-1s, PD-L1s and other combination agents

AGEN1181 addresses the limitations of first generation CTLA-4 Antibodies

  • By counteracting a key immune blocker, regulatory T cells (Tregs), for improved immune activity
  • By addressing 40% of patients unresponsive to Yervoy® who have a genetic polymorphism – AGEN1181 is specifically engineered to address this condition
  • By optimizing structure which allows FcγRIIIA engagement for higher activity at lower doses
  • By promoting T cell priming and depletion of Tregs through our Novel Fc engagement