Background

For over 20 years, G-CSF has been an effective treatment for increasing numbers of neutrophils and white blood cell count. However, despite this therapy, chemotherapy induced neutropenia continues to be a problem with infections, febrile neutropenia and associated deaths.

Technology Overview

The combination of Am80 (Tamibarotene) and G-CSF will provide therapeutic benefit to patients suffering from neutropenia beyond G-CSF alone. Am80, an oral retinoic acid derivative, promotes neutrophil maturation significantly better than G-CSF and effectively differentiates a GCSF-induced immature granulocytes into mature neutrophils. Unlike G-CSF, Am80 promotes the production of differentiated neutrophils that closely mimic fully mature neutrophils. Am80-induced neutrophils exhibit cellular morphology and functional reactive oxygen species (ROS) production characteristic of mature neutrophils. Together, Am80 and G-CSF work synergistically to provide sufficient numbers of mature neutrophils to combat infection and promote survival. 

Further Details

• Blood. 2013 Feb 7;121(6):996-1007 Retinoid agonist Am80-enhanced neutrophil bactericidal activity arising from granulopoiesis in vitro and in a neutropenic mouse model
• EMBO 2016 Mol Med 8(11): 1340-1359  Am80‐GCSF synergizes myeloid expansion and differentiation to generate functional neutrophils that reduce neutropenia‐associated infection and mortality
• Pharmacology & Therapeutics Available online 27 August 2019, Strategies to generate functionally normal neutrophils to reduce infection and infection-related mortality in cancer chemotherapy

Benefits

• Drug repurposing allows shortened development timeline, API and Drug Master File available 
• Shortened duration of cancer chemotherapy induced neutropenia (CCIN)
• Lowers risk of both fungal and bacterial infection in patients suffering from CCIN 

Applications

• Am80 used in combination with G‑CSF biosimilar for CCIN serves to differentiate from other G‑CSF biosimilars on the market
• Breast cancer and AML patients with CCIN identified as target patient populations for clinical proof of concept

Opportunity

Looking for a licensee and development partner, preferably with an approved biosimilar G‑CSF or one in clinical development.