What question did this study set out to answer?

The aim is to develop a scalable process for creating a heterobifunctional BTK degrader.

April 1, 2026Organic Process Research & Development0 citations

Early Process Development of a Heterobifunctional Protein Degrader

MHMichael C. HaibachCentre for Process Innovation RKRussell C. KlixCentre for Process Innovation SPSarma PullelaCentre for Process Innovation

Key Points

The aim is to develop a scalable process for creating a heterobifunctional BTK degrader.
Optimized discovery synthesis for scalability.
Implemented selective optimization of reaction conditions.
Utilized modeling and high-throughput experimentation.
Addressed scale-up challenges relevant to the API class.
Achieved an average yield of 86% over the final four stages of the FIH process.
Successfully prepared sufficient API for GLP-Tox studies (600 g) and planned FIH studies (5.7 kg).

Abstract

We present the process development of 1, a heterobifunctional Bruton’s Tyrosine Kinase (BTK) degrader. Optimization and reorganization of the discovery synthesis resulted in a scalable process suitable for preparation of API for the GLP-Tox (600 g) and planned FIH studies (5.7 kg). The FIH process achieved an average yield of 86% over the final four stages. Selective optimization of reaction conditions, modeling and high-throughput experimentation were applied strategically to address scale up challenges posed by this novel class of API.

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