On April 25, 2025 Talus Bioscience, a technology-enabled therapeutics company, reported new preclinical data from programs targeting transcription factors in chordoma, non-small cell lung cancer, and advanced prostate cancer (Press release, Talus Bioscience, APR 25, 2025, View Source [SID1234652172]). The data, presented at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, held April 25-30, support Talus Bio’s first-in-class approach to target previously undruggable transcription factors using regulome-scale discovery in live human cells.
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"We built our platform to systematically address transcription factors, a target class long considered out of reach for small-molecule therapeutics," said Alex Federation, PhD, CEO and Co-Founder of Talus Bio. "The data we’re presenting at AACR (Free AACR Whitepaper) show that the approach is working. Our platform has already logged over 50 million protein-compound interactions this year. These results validate our strategy in two difficult oncology indications. Our Brachyury molecules are on track for candidate nomination, and new compounds targeting NONO and AR-V7 show real promise for metastatic castration-resistant prostate cancer. We now have a repeatable model for discovering tractable starting points across transcription factor targets once thought undruggable."
Talus Bio’s technology profiles the regulome, providing a quantitative readout of active transcription factors and other DNA-bound regulators in live, unmodified human cells. The platform can measure over 10,000 regulomes per month and is being deployed to discover and optimize small molecules that modulate transcription factor activity in their native context.
Data presented at AACR (Free AACR Whitepaper) on lead drug candidates highlight the strength of this approach. By combining high-throughput transcription factor profiling with AI-guided chemistry, Talus Bio is accelerating the discovery of modulators for transcription factor targets.
Presentation Highlights
Poster 4036 / 2: Selective inhibition of the transcription factor Brachyury in chordoma and non-small cell lung cancer
Preclinical data presented by Gaelle Mercenne at AACR (Free AACR Whitepaper) showcase the ability of a novel covalent small molecule, TAL61, to effectively modulate Brachyury activity in patient-derived xenograft (PDX) models of chordoma:
TAL61 demonstrated significant efficacy in reducing tumor burden in PDX chordoma models with durable tumor suppression post-treatment
TAL61 exhibited low toxicity and high tolerability with daily dosing
Additionally, TAL61 decreased tumor burden by more than 50% in in vivo models of Brachyury-positive non-small cell lung cancer (NSCLC)
Poster 6991 / 20: Targeting NONO as a therapeutic strategy for metastatic castration-resistant prostate cancer (CRPC)
Preclinical data presented by Brian McEllin support an emerging modality targeting NONO to disrupt both AR and ARv7 transcription as an emerging treatment for metastatic castration-resistant prostate cancer:
A targeted search of Talus Bio’s proprietary compound database identified covalent small molecules for lead optimization
Compound treatment reduced mRNA and protein levels of AR and ARv7 in prostate cancer cells
Active compounds show abrogate AR and ARv7 gene expression programs in castration-resistant prostate cancer models
Poster 4496 / 7: Small molecule inhibition of previously "undruggable" transcription factors with AI-guided functional proteomics
Data presented by Alex Federation at AACR (Free AACR Whitepaper) highlight the regulome sequencing platform as a drug discovery engine for previously intractable transcription factors:
The assay provides a quantitative, time-resolved readout of drug-induced changes in transcription factor activity, capturing protein:genome interactions for thousands of proteins simultaneously
This approach enables small molecule screening in physiologically relevant contexts, where transcription factors fold, assemble, and function as they do in human disease
AI-guided hit discovery using this technology has enabled discovery and optimization for inhibitors of Brachyury, AR-V7, and STAT3
Talus Bio’s foundational AI model has helped identify over 30 tractable compounds against validated transcription factor targets in cancer and other diseases. The company is actively pursuing co-development opportunities with partners to accelerate these discoveries into the clinic. Connect with the team to learn more about partnerships and collaborations.