The Application of Eribulin in ADC Field
Eribulin is a synthetic analogue of the macrocyclic polyether halichondrin B, which was originally isolated from the Asian sea sponge Halichondria okadai. Eribulin mesylate, marketed as Halaven, is approved in the US for the treatment of metastatic breast cancer in patients who have received at least two prior treatment regimens that include an anthracycline and a taxane.
Fig.1 Eribulin is a fully synthetic macrocyclic ketone analogue of halichondrin B
Eribulin-based Payload
Eribulin was first used as antibody-drug conjugate payload is in Eisai’s MORAb-202, which targeting FRα positive solid tumors.
In 2021, Eisai has published they performed further characterization of MORAb-202 and investigated whether it exhibited antitumor effect and a mode of action in triple-negative breast cancer (TNBC) patient–derived xenograft (PDx) models with low and high folate receptor alpha (FRα) expression, with the aim to find a new therapeutic option for TNBC patients[1-2]. At 2022 ASCO annual meeting platinum-resistant ovarian cancer (PROC) phase I clinical data published by Eisai showed an objective response rate (ORR) of 52.4% and stable disease (SD) of 42.9% , confirming that it is indeed the best-in-class FRα ADC. The followings are three eribulin-based payload in clinical trial, one is from Eisai and the others are from Bliss.
Fig 2. Eribulin-based payload in current pipeline
Advantages of Eribulin-based Payload:
● Subnanomolar in vitro anti-mitotic activity
● Additional non-mitotic anti-tumor activity
● Less peripheral neuropathy clinically
● Well-understood toxicity profile
● Amenable to multiple linker chemistries
Our Eribulin Production Capacity
• Breakthrough optimization of key steps in the total synthesis
• Completed 100g GMP process verification and stability test of Eribulin mesylate and advanced intermediates
• Any single impurity < 0.1 %
• Provide stable supply of 100 grams of Eribulin advanced intermediates and API(GMP or non-GMP)
• The technical team is submitting European ASMF, US FDA DMF submission and Chinese API applications
Reference:
[1] Mol. Cancer Ther., 2018, 17, 2665-2675.
[2] Cancer Science, 2021, 112, 2467-2480.