TAL61 / Talus Bio - LARVOL DELTA

Targeting Brachyury with small molecules: A new therapeutic paradigm for chordoma and neuroendocrine carcinomas (AACR 2026) - "To overcome these barriers, we developed TF-Scan, a proteome-wide mass spectrometry platform that directly quantifies TF chromatin occupancy in live cells, enabling functional assessment and therapeutic targeting of TFs that were previously considered undruggable.Using TF-Scan, we discovered TAL61, a first-in-class covalent small-molecule hit that selectively binds TBXT and displaces it from chromatin...Ongoing work using cancer cell lines and patient-derived organoids is defining TBXT dependency in these diseases, suggesting that TBXT may serve as a broader lineage survival factor.Together, these results establish TF-Scan as a powerful TF drug discovery- platform and demonstrate the feasibility of pharmacologically targeting TBXT. Our covalent inhibitors show potent, selective antitumor activity in chordoma and point to new therapeutic opportunities in neuroendocrine cancers lacking targeted treatments."

Chordoma • Embryonal Tumor • Endocrine Cancer • Lung Cancer • Merkel Cell Carcinoma • Neuroendocrine Carcinoma • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Small Cell Lung Cancer • Solid Tumor

Selective inhibition of the transcription factor Brachyury in chordoma and non-small cell lung cancer (AACR 2025) - "We tested our lead compound in a model of NSCLC and were able to significantly decrease tumor burden by more than 50% and visualize additive effects while doing combination with a chemotherapy agent.We are conducting other studies to further characterize TAL61 and uncover new cancer indications where TBXT plays a key role. The development of TF-Scan represents a paradigm shift in drug discovery, enabling the identification of compounds capable of disrupting targets that were previously inaccessible to conventional approaches."

Breast Cancer • Chordoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Osteosarcoma • Solid Tumor

Poster 4036 / 2: Selective inhibition of the transcription factor Brachyury in chordoma and non-small cell lung cancer (Businesswire) - "Preclinical data presented by Gaelle Mercenne at AACR 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)."

Preclinical • Chordoma • Non Small Cell Lung Cancer