About Us
The Engineered Small Molecules (ESM) team is dedicated to advancing Targeted Protein Degradation (TPD) and other induced proximity technology, expanding our small molecule capabilities.
Our goal is to create novel drugs targeting refractory diseases such as cancers dependent on aberrant proteins that historically have been considered undruggable.
ESM team is a new organization established in April 2024 by the merger of TPD and the Mitobridge Division, comprised of Mitobridge, Inc. (now Astellas Engineered Small Molecules US, Inc.) and Nanna Therapeutics Ltd. (now Astellas Engineered Small Molecules U.K. Ltd.).
*Learn more about Astellas’ Primary Focus TPD here
Our Approach
We focus on induced proximity technology such as TPD, which leverages heterobifunctional chemical molecules. TPD promotes ubiquitination of target proteins by inducing the proximity between target proteins and E3 ubiquitin ligases, leading to protein degradation by the proteasome.
Conventional small molecule drugs require a functional deep pocket in the target protein. TPD molecules, however, only weakly bind to a shallow pocket on the target protein, catalytically inducing the proximity of the target protein to the E3 ligase, and selectively degrading the target protein. TPD can be applied to a wider range of proteins, including historically undruggable proteins, because it can use shallow pockets normally present in most proteins.
ASP3082
Applying the concept of TPD we have discovered ASP3082, a first-in-class and selective KRAS G12D degrader. Phase I clinical trials are underway in the U.S. to study the efficacy and safety of the drug for pancreatic cancer, colorectal cancer, and lung cancer with KRAS G12D mutation.
Teams
Head, Engineered Small Molecules
Masahiko Hayakawa, Ph.D.
Masahiko Hayakawa has led research activities in the field of oncology and urology, creating multiple clinical and launched products. He assumed the Executive Director role in Modality Management in 2018, and the Head of Targeted Protein Degradation in 2019. He has been in his present position since April 2024.
Message from Masahiko
“Our goal is to deliver new therapeutic options to patients suffering from refractory diseases that have been difficult to treat with conventional drug therapies. We are committed to helping these patients with unmet medical needs.”
Head, Engineered Small Molecules-US/UK*
David Barrett, Ph.D.
*: subsidiaries of ESM