Company achieves key milestone in drug discovery for rare bone cancer

18 September 2026 • By Diana Turner • #Cancer Research

Tagged Bone cancer, Chordoma, Oncology, Protein binders, X-Chem

The Chordoma Foundation’s TBXT Challenge was won by X-Chem, securing the company $100,000 in milestone awards.

X-Chem was the first of 26 participating teams to discover a compound that binds Brachyury (TBXT) below the 1 micromolar threshold.

TBXT is a key vulnerability in chordoma, a rare bone cancer with significant unmet treatment need.

Using its Chemomics model, X-Chem was able to successfully identify and generate novel chemical matter that binds to the TBXT protein with remarkable affinity.

The open international Challenge drew teams from 22 companies and four academic groups across nine countries, applying a wide range of approaches to the same difficult target; X-Chem was the first to clear the qualifying threshold.

Karen Lackey, Chief Executive Officer at X-Chem, said: “This work opens an important new path for continued discovery and development around a target that has long been considered exceptionally difficult to drug.”

Because chordoma occurs in the bones of the skull base and spine, it is exceptionally difficult to treat with conventional methods. For years, the master driver protein Brachyury was considered “undruggable” because its smooth surface lacks traditional, deep binding pockets.

There remains a significant need for effective systemic treatments for chordoma. Breaking the 1-micromolar binding threshold represents an important step toward determining whether TBXT can ultimately be addressed therapeutically.

The TBXT Challenge

The Chordoma Foundation launched its TBXT Challenge as a landmark international competition, offering up to $500,000 in prize incentives. Designed as an open-initiative model to spur breakthroughs against Brachyury, the challenge encourages biopharma innovators from both private industry and academia to deploy advanced technologies against this intractable target.

By offering independent biophysical validation through Chordoma Foundation Labs, the initiative aims to de-risk TBXT drug discovery and establish a template for conquering intractable transcription factors across broader oncology. The challenge received support from Biohub and The Mark Foundation for Cancer Research.

“For years, transcription factors like Brachyury have been considered among the most challenging targets in drug discovery – and often called ‘undruggable.’ X-Chem’s result challenges that paradigm,” said Dan Freed, Chief Scientific Officer of the Chordoma Foundation. “It provides crucial proof of concept that potent small-molecule Brachyury binders can be discovered, and we believe it will unlock further advances toward drugs that directly target chordoma’s main Achilles heel. For patients who have long been told that drugging an intractable target in a rare cancer simply can’t be done, this is an important reason for hope.”