Pipeline

F-627 RyzneutaTM
Introduction

RyzneutaTM is intended to treat chemotherapy-induced neutropenia (CIN) in patients in cancer. Phase III head-to-head trials against Neupogen (filgrastim) and Neulasta (peg-filgrastim) have been successfully completed for China and global (US, Europe included) markets respectively. F-627 is a recombinant fusion protein containing human granulocyte colony-stimulating factor (G-CSF) and the crystallizable fragment domain of human IgG2 (Fc). F-627 is expressed in Chinese Hamster Ovary (CHO) cells. F-627 exists as a homodimer. G-CSF binds to specific G-CSF receptors (G-CSFR) on the cell surface and influences the survival, proliferation, and differentiation of all cells in the neutrophil lineage, from haemopoietic stem cell through mature neutrophil.

rhG-CSFs for CIN

Due to their short serum half-life, patients receiving the first generation short-acting G-CSF products, such as filgrastim, require 5 daily administrations every chemotherapy cycle. The dosing frequency for patients receiving the second generation long-acting G-CSF, such as peg-filgrastim, is reduced to once per chemotherapy cycle owing to their extended serum half-life. The once-per-chemotherapy cycle administration greatly improved patient compliance, convenience, and ultimately therapeutic efficacy. F-627 is a fully biodegradable long-lasting G-CSF-Fc protein that provides patients with all the benefits from second generation G-CSF products.

Chemotherapy Induced Neutropenia (CIN) Market

CIN is a disease commonly occurring during current cancer treatments. It impacts millions of patients globally, is potentially life-threatening and generally requires medical intervention. The global CIN market is estimated to be at $7.0 billion with about >85% of patients are still on the first generation of rhG-CSFs, and less than 15% of patients are using the second generation of rhG-CSFs.

F-627 has a unique potential to compete in the CIN global market, due to its unique dimeric fusion protein structure, which does not require pegylation, observed safety benefits and robust manufacturing process.

Clinical Development Status

The completed clinical studies for F-627 include two Phase I studies in healthy men, and three Phase IB and two Phase II studies in women with breast cancer receiving various chemotherapies. The patient follow-up in China, US and EU Phase III has been completed and the clinical study reports are in preparation. The status of clinical development for F-627 is shown in Table 1.

F-627 drug substance for Phase III clinical development was manufactured in Evive’s cGMP production facility. F-627 drug product was manufactured in a cGMP facility located in the US or China.

StudySubjectObjectiveCountryStatus
Ph IHealthy menSafety & PKAustraliaCompleted
Ph IHealthy menSafety & PKAustraliaCompleted
Ph IbWomen with breast cancerSafety & PKChinaCompleted
Ph IbWomen with breast cancerSafety & PKChinaCompleted
Ph IbWomen with breast cancerSafety & PKChinaCompleted
Ph IIWomen with breast cancerSafety & EfficacyUS, EuropeCompleted
Ph IIWomen with breast cancerSafety & EfficacyChinaCompleted
Ph IIIWomen with breast cancerSafety & EfficacyChinaCompleted
Ph III (04)Women with breast cancerSafety & EfficacyUS, EuropeCompleted
Ph III (05)Women with breast cancerSafety & EfficacyUS, EuropeTopline results