RRx-001, a downregulator of the CD47- SIRPα checkpoint pathway, does not cause anemia or thrombocytopenia

ABSTRACT

Introduction: The CD47 and SIRPα checkpoint pathway has garnered much interest within the anti-cancer research community, with multiple experimental checkpoint inhibitors targeting CD47 and SIRPα in development. The use of such checkpoint inhibitors may however be limited by hematologic toxicity.

Areas covered: We report on RRx-001, the first known small molecule downregulator of CD47 and SIRPα, which has shown a lack of hematologic toxicity in clinical trials.

Expert opinion: RRx-001 is the first reported small molecule downregulator of CD47 and SIRPα and lacks any notable hematologic or systemic toxicity as demonstrated in clinical trials to date. Small molecule RRx-001 could be used in combination with or in place of CD47 targeting antibodies for anti-cancer treatment.

KEYWORDS:

• Oncology
• immunotherapy
• checkpoint inhibitor
• CD47
• SIRPα
• PPAR-γ
• antibody
• small molecule

Article highlights

• Multiple CD47 and SIRPα targeting checkpoint inhibitors are in various stages of preclinical and clinical development.

• Most of these antibodies are characterized by some degree of hematologic toxicity.

• We report on RRx-001, a Phase 3 small molecule dual downregulator of CD47 and SIRPα which has demonstrated a lack of hematologic or other toxicity in clinical trials.

• Small molecule RRx-001 is under clinical investigation for the treatment of multiple solid tumor types with planned trials in hematologic malignancies.

Additional information

Funding

This paper was not funded.