Our Science ++ Overview

Our PRODEGY (Protein Degrader Technology) platform was designed as a new and powerful targeted protein degradation drug discovery engine. Our platform was built on our expertise in modulating Cereblon and includes proprietary solutions and unique tools for targeted protein degrader (TPD) drug design.

Innovative modulation of Cereblon to create first-in-class TPD product candidates

Our Science ++ Targeted Protein Degradation

Combining the precision of gene-based knock-down approaches with the advantages of small molecule oral bioavailability, broad tissue penetration and reversibility

Targeted protein degradation is a rapidly expanding therapeutic modality focused on the selective removal of disease-enabling proteins. Aberrant proteins are a key driver of a wide range of diseases including cancer and inflammatory and neurologic diseases. Targeted protein degradation has the potential to degrade proteins that have otherwise been difficult to modulate by conventional small molecule inhibitors.

Our founders are pioneers in the field of protein degradation, having led the discovery and development of the ImmunoModulatory imide Drugs (IMiDs) — REVLIMID® (lenalidomide) and POMALYST® (pomalidomide).

Our Science ++ PRODEGY Platform for Next Generation Targeted Protein Degraders

We have applied our expertise in Cereblon modulation to carefully build our platform to accelerate the discovery and development of highly precise targeted protein degraders. Our PRODEGY platform leverages the following key advantages:

Innovative modulation of Cereblon via customized computational chemistry methods and molecular structure-activity analytics

These capabilities enable us to modulate Cereblon in new ways to create potential first-in-class TPD product candidates with attractive drug-like qualities.

Our team has spent years understanding how to modulate our E3 ligase of choice – Cereblon – to optimize the design of our TPDs.

Building on our experience with IMiDs, we know that small changes in chemical structure have profound effects on protein targeting, efficacy and safety profiles.

This understanding allows us to design rapid, deep, potent and durable degraders for a range of target proteins of interest.

Broad library of patent-protected Cereblon binders

This library comprises over 4,000 small molecules rationally designed to bind Cereblon, is built on more than 25 chemical scaffolds and represents one of the broadest portfolios of issued U.S patents covering targeted protein degradation. The library can be directed towards the design of novel molecular glues, bifunctional degraders and hybrid degraders.

Proprietary screening methodology and tools designed to accelerate the identification of highly precise development candidates in an efficient manner

Our PRODEGY platform integrates a wide range of structure-based computational tools and machine-learning algorithms with a portfolio of biological assays, screening methodologies and high-throughput synthesis capabilities – all designed to accelerate the identification of highly precise development candidates in an efficient manner.

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Using our PRODEGY platform, we have designed molecular glues, bifunctional degraders and hybrid degraders. This gives us the ability to apply our platform to develop degraders for a very broad range of target proteins and the flexibility to select the most appropriate molecular design for each target.

Precision protein degradation therapeutics enabled by Cereblon

Our Science ++ PRODEGY Platform for Next Generation Targeted Protein Degraders

Molecular glues. Our molecular glues bind to Cereblon, induce a conformational change in Cereblon that enables a direct protein-protein interaction with the target protein (neosubstrate) and lead to its ubiquitination and subsequent proteasomal degradation. Without the molecular glue, these neosubstrates would not be recognized by Cereblon. We design molecular glues to produce specific surface changes in Cereblon to enable binding and ultimately degradation of therapeutically relevant protein targets. Through specific design efforts, we are able to design molecular glues to degrade more than one neosubstrate.

Our Science ++ PRODEGY Platform for Next Generation Targeted Protein Degraders

Bifunctional degraders. Our bifunctional degraders are designed to bind to a target protein and concomitantly bind to Cereblon to induce the target protein’s degradation. Our library of Cereblon binders serves as a critical anchor for the design of bifunctional degraders. Although bifunctional degraders require that the target have a small molecule binding pocket, binding with high affinity is not required as it is with conventional inhibitors. In this way, bifunctional degraders also expand the universe of potential protein targets beyond those with pockets where small molecules can bind with high affinity.

Our Science ++ PRODEGY Platform for Next Generation Targeted Protein Degraders

Hybrid degraders. These molecules are engineered to function as both molecular glues and bifunctional degraders. A single hybrid degrader can degrade both neosubstrates and target proteins with binding pockets and thereby significantly broaden the range of proteins that can be concurrently targeted.

Our Science ++ Publications & Presentations

Jun 2022 | biotheryx
Safety and efficacy of casein kinase 1α and cyclin dependent kinase 7/9 inhibition in patients with relapsed or refractory AML: A first-in-human study of BTX-A51
ASCO | Ball et al.
The full abstract will be available once published on the ASCO website
Jun 2022 | biotheryx
BTX-1188, a first-in-class dual degrader of GSPT1 and IKZF1/3, for treatment of acute myeloid leukemia (AML) and solid tumors
ASCO | Hoskote Chourasia, Majeski et al.
The full abstract will be available once published on the ASCO website