Advancing the science of what's next in oncology and hematology.

INNOVATING

Platform Overview

Aptevo is a clinical stage biotechnology company focused on development of novel immunotherapies using our proprietary ADAPTIR™ and ADAPTIR-FLEX™ platform technologies.

ADAPTIR and ADAPTIR-FLEX protein therapeutics have been designed to achieve a variety of biological mechanisms such as:

  • Redirected T-cell cytotoxicity (RTCC) against solid or hematologic tumor indications, demonstrated in several preclinical studies
    • –  CD3 agonism with the potential for potent anti-tumor responses but with reduced cytokine release and potential to improve drug tolerability and potency
  • Dual agonism of T-cell co-receptors (4-1BB and OX40) with potential to amply anti-tumor responses of tumor-specific T-cells

ADAPTIR and ADAPTIR-FLEX candidates have potential advantages over other immunotherapeutic and bispecific T-cell technologies:

  • Based on an immunoglobulin backbone including the hinge-Fc to enable use of antibody-like manufacturing processes and potential to extend serum half-life to improve ease of administration
  • Unique anti-CD3 domain that has demonstrated reduced cytokine release in preclinical studies compared to acompetitor candidate generated in-house. Potential to improve a patient’s tolerability to drug and improve therapeutic responses as compared to competitor responses
  • Potential to incorporate multiple functional domains to the ADAPTIR and ADAPTIR-FLEX candidate including antibody-derived binding domains, soluble receptors or modified cytokines

Built for Novel Activity, Therapeutic Opportunities

  • ADAPTIR and ADAPTIR-FLEX molecules can be built to produce different potential modes of action by design or upon request, with potential application for developing drug candidates in immuno-oncology, autoimmunity, inflammation and others
  • ADAPTIR and ADAPTIR-FLEX molecules are comparable in size to an IgG antibody but can bind to up to four possible targets
  • Mutations can be incorporated in the Fc region to eliminate or enhance Fc-effector function
  • Our expertise makes us uniquely positioned to develop ADAPTIR and ADAPTIR-FLEX candidates for treatment of cancer, hematological disorders, autoimmunity or infectious disease
  • We actively seek opportunities to develop novel ADAPTIR or ADAPTIR-FLEX bispecific molecules with pharmaceutical partners

Current Candidates

The ADAPTIR platform technology enables the design of both mono- and bispecific bi-valent protein therapeutics.

  • APVO436: A clinical stage bispecific candidate in development for treatment of AML and MDS: designed to redirect CD3-expressing T cells to kill CD123-positive tumors for treatment of AML and MDS
  • ALG.APV-527: A preclinical program designed to target 4-1BB, a costimulatory receptor, expressed on activated T cells and natural killer cells, only when engaged with 5T4, a solid tumor antigen, expressed on multiple solid tumors
  • APVO603: A preclinical program designed to target costimulatory receptors 4-1BB and OX40, with potential to stimulate T-cell and NK-cell immune responses for treatment of multiple solid tumor indications

The ADAPTIR-FLEX platform expands on the ADAPTIR technology and enables design of protein therapeutics with different specificity and valency. This includes, but is not limited to, building proteins that interact with two or more targets, two or more epitopes on a target, and as monovalent or multivalent binding to potentially improve specificity and potency.

  • APVO442: A bispecific protein that binds to PSMA with high affinity and CD3 with low affinity for the potential treatment of prostate cancer.
Characteristic Technology
ADAPTIR ADAPTIR-FLEX
Drug Targeting Bind up to two targets Bind up to four targets
Genetic and Structural Format Single gene that assembles into a homodimer based on an IgG1 backbone Two genes that form hetero dimerusing “Knob-in-Hole” mutations
Half-life Contains IgG1 Fc – Demonstrated antibody-like half-life in mice
Effector function Fc mutations may be utilized to eliminate or enhance effector function
Manufacturing Antibody-like manufacturing processes
Current Pipeline Candidates APVO436 (CD123 x CD3)
ALG.APV-527 (41BB x 5T4)
APVO603 (41BB x OX40)		 APVO442 (PSMA x CD3)