X-Chem Named First Winner of Chordoma Foundation TBXT Challenge with Discovery of Novel Binder for Untreatable Bone Cancer Target

Groundbreaking synergy of DEL screening and computational chemistry yields the first compound to meet the TBXT Challenge’s submicromolar binding threshold for brachyury (TBXT)

WALTHAM, Mass., Sept. 16, 2026 (GLOBE NEWSWIRE) -- X-Chem, a pioneer in DNA-Encoded Library (DEL) technology and computational drug discovery, today announced it has won the Chordoma Foundation’s TBXT Challenge, securing $100,000 in milestone awards. The company 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.

Winning the challenge provides powerful third-party validation of X-Chem’s proprietary Chemomics model, an advanced framework that integrates physical screening of over 150 billion DEL compounds with machine learning models, 3D pharmacophore modeling and expert medicinal chemistry design. Through this multi-layered approach, 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.

"The TBXT result is a powerful demonstration of what scientific excellence across our platform and team can accomplish against targets the industry has struggled with for decades,” said Karen Lackey, Chief Executive Officer at X-Chem. “By combining the scale and richness of DEL data with AI/ML, computational science and deep chemistry expertise, we identified promising chemical matter against a key vulnerability in chordoma. This work opens an important new path for continued discovery and development around a target that has long been considered exceptionally difficult to drug.”

The Challenge

Chordoma is a devastating diagnosis. Because it 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 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.”

The Approach

Unlike traditional high-throughput screening (HTS) methods that have historically struggled against smooth protein surfaces lacking obvious binding pockets, the Chemomics approach screened its DEL containing more than 150 billion compounds and identified roughly 73,000 compounds with a signal of possible binding. From there, the team used computational analysis and machine learning, in combination with medicinal chemistry expertise, to prioritize 76 compounds for independent laboratory testing by the Chordoma Foundation using full-length human TBXT protein in surface plasmon resonance (SPR) binding assays.

One compound met the challenge’s winning threshold. Multiple rounds of testing at Chordoma Foundation Labs confirmed that it binds to brachyury at concentrations below the 1 micromolar Challenge threshold. That compound also passed an independent expert chemistry review which verified that its chemical structure meets criteria regarding suitability for further drug development.

“With TBXT, our goal was not just to find a single binding hit, but to build a predictive data foundation that could guide the discovery process,” said Matthew Clark, X-Chem’s President and Chief Scientific Officer. “The quality and chemical diversity of our DEL libraries gave us a rich starting dataset, and by combining that data with DEL2PH4 pharmacophore modeling, HITMiner machine learning and experimental feedback, we were able to prioritize multiple chemical approaches and identify validated TBXT binders. That ability to learn from the full dataset and continually improve our decisions is especially important for hard-to-drug transcription factors, where traditional discovery approaches have often fallen short.”

Next Steps

The TBXT Challenge marks an important milestone in the program and establishes a strong foundation for the next phase of discovery. X-Chem will continue characterizing and advancing the chemical matter identified through the effort, with work focused on building a deeper understanding of the compounds and their potential to support future TBXT-directed drug discovery.

About X-Chem

X-Chem is a leading provider of innovative solutions in early-stage drug discovery. By combining massive-scale DNA-Encoded Library (DEL) screening, computational sciences and deep chemistry expertise, X-Chem empowers biopharma partners to unlock challenging targets and accelerate the delivery of transformational medicines to patients. For more information, visit https://www.x-chemrx.com/.

Media Contact:
Alli Cooke
616.258.5769
alli.cooke@llyc.global

About Chordoma Foundation

The Chordoma Foundation is a nonprofit organization that serves the needs of the worldwide chordoma community, and partners with healthcare providers, scientists, and companies to improve the lives of those affected by chordoma and lead the search for a cure. For more information, visit https://www.chordomafoundation.org/.

Media Contact:
Sara Nick
651-895-5454
sara@chordoma.org