TH9619 / One-carbon Therapeutics - LARVOL DELTA

Somatic Mutation Profile in Normal Tissue Adjacent to Tumor in Colorectal Carcinoma Patients: Functional Effect on Gene Expression and Potential Implications for Precision Medicine. (PubMed, Cancers (Basel)) - "APC mutations were associated with more marked down-regulation of APC, SLC26A3, SELENBP1, KRT20, and CXCL14, and more marked up-regulation of MMP1, MMP12, MTHFD1L and MTHFD2, the latter two suggesting the folate pathway as a potential therapeutic target. For the first time, we document a comprehensive SM profile of normal colon tissue adjacent to tumors in CRC patients and observe its functional effect on differential gene expression in matched tumor tissue to identify potential therapeutic applications in precision medicine."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • APC • ARID1A • BRCA2 • CXCL14 • DHFR • KMT2C • KRT20 • MAP3K1 • MMP1 • MSH6 • MTHFD2 • PIK3CA • PTEN • SELENBP1

Targeting NFATc1-regulated MTHFD2 one-carbon metabolism to suppress sustained T-cell-mediated inflammation in rheumatoid arthritis. (PubMed, Signal Transduct Target Ther) - "Proteomic profiling reveals that TH9619 elicits a distinct molecular response in patients' T cells, divergent from the currently used anti-folate therapy, particularly in inadequate responders. These findings use RA as the proving ground to establish NFATc1-mediated MTHFD2 activation as a critical regulator of sustained T-cell-driven inflammation and support selective MTHFD1/2 inhibition as a novel, mechanism-based therapeutic strategy for RA."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • FOXP3 • MTHFD2 • NFATC1

A phase 1/2 first-in-human study of TH9619 in patients with advanced refractory solid tumors (ODIN). (ASCO 2026) - P1/2 | "The ODIN phase 1/2 study is actively enrolling across leading academic and clinical research centres in the United Kingdom, France, and Spain, with expansion planned across additional European sites in the coming months. As of this submission, dose escalation is ongoing."

Clinical • First-in-human • Metastases • P1/2 data • Colorectal Cancer • Gastric Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • MTHFD2

One-carbon Therapeutics AB…announced today the closing of an oversubscribed 153 million SEK ($16.2 million) private placement financing round supported by current and new investors and private Swedish family offices. (Drug Discovery News) - "One-carbon Therapeutics will use the net proceeds from the private placement to strengthen its financial position and expand its ongoing Phase 1/2 ODIN clinical study of TH9619, an MTHFD1/2 inhibitor, thereby further accelerating its momentum through a data-driven strategy."

Financing • Colorectal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

ODIN: Phase 1/2 Study to Evaluate TH9619 in the Treatment of Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=43 | Recruiting | Sponsor: One-carbon Therapeutics AB

New P1/2 trial • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

MTHFD1/2 inhibitor TH9619 in combination with PD-L1 blockade in NSCLC (CIMT 2025) - "Our data demonstrate that TH9619 can work in combination with the PD-L1 inhibitor Atezolizumab in the LL2 murine lung cancer model, and we investigate PD-L1 expression and CD8+ T cell infiltration by flow cytometry and immunofluorescence. This report investigates if TH9619 may enhance the therapeutic efficacy of immunotherapies targeting the PD-1/PD-L1 pathway."

Combination therapy • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • MTHFD2