Engineered Small Molecules

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

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.

Our approach



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.



Masahiko Hayakawa, Ph.D.

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.”


David Barrett, Ph.D.

Head, Engineered Small Molecules-US/UK*

David Barrett, Ph.D.
*: subsidiaries of ESM

David Barrett has spent his career working in Japan and the UK with Astellas. He has extensive expertise in infectious diseases and oncology, project management and a track record of delivering quality, differentiated development candidates to the pipeline and market. He previously led the Mitobridge Division at Astellas.

Message from David

“We are committed to delivering important new therapeutic options for patients in need. We are focused on creating assets for difficult-to-treat diseases by leveraging and exploiting the clear potential of induced-proximity concepts to deliver next-generation engineered small molecules to patients.”


Conference Presentation*

  • Presentation Title:KRAS G12D degrader: ASP3082
    Japanese Foundation for Cancer Research-International Symposium on Cancer Chemotherapy

    December 13-14, 2023
    Miraikan - The National Museum of Emerging Science and Innovation
    Tokyo, Japan
  • Presentation Title:Discovery of Novel Kras Degraders
    6th Targeted Protein Degradation Summit

    October 30-November 2, 2023
    The Westin Copley Place
    Boston, MA, USA
  • Presentation Title:Discovery of the first clinical KRAS (G12D) degrader ASP3082
    2nd Targeted Protein Degradation Conference in Japan

    July 26-27, 2023
    Shonan iPark
    Fujisawa, Japan
  • Presentation Title: Novel KRAS G12D degrader ASP3082 demonstrates in vivo dose-dependent KRAS degradation, KRAS pathway inhibition and anti-tumor efficacy in multiple KRAS G12D mutated cancer models
    Abstract 5735: Novel KRAS G12D degrader ASP3082 demonstrates in vivo, dose-dependent KRAS degradation, KRAS pathway inhibition, and antitumor efficacy in multiple KRAS G12D-mutated cancer models | Cancer Research | American Association for Cancer Research (

    April 14-19, 2023
    Orange County Convention Center
    Orlando, FL, USA
  • Presentation Title: ASP3082, a First-in-class novel KRAS G12D degrader, exhibits remarkable anti-tumor activity in KRAS G12D mutated cancer models

    October 26-28, 2022
    Barcelona International Convention Centre (CCIB)
    Barcelona, Spain

*The compound discussed is investigational and has not received regulatory approval

Media Coverage


To further enhance our research capabilities and portfolio, we are partnering or looking for potential partners in biotech and academia in the following areas:

  • Novel TPD platform technology
  • Novel induced proximity technology
  • Research programs based on induced proximity technology
  • New technology to identify shallow pocket binders for undruggable targets


We are excited to work with those who are interested in providing new value to patients through induced proximity technology, such as targeted protein degradation.

Please check out our open positions and contact us if you are interested in joining our team.


Astellas Engineered Small Molecules US, Inc.
441 Morgan Ave, Cambridge, Massachusetts 02141, USA
Email: [email protected]

Astellas Engineered Small Molecules U.K. Ltd.
Merrifield Centre, Rosemary Lane, Cambridge, CB1 3LQ, United Kingdom
Tel: +44(0) 1223 247000
Email: [email protected]
Registered in England & Wales number: 08328823
Registered office as above