fresolimumab (GC 1008) / Sanofi - LARVOL DELTA

Mathematical Modeling of Systemic Sclerosis and Its Treatment. (PubMed, Bull Math Biol) - "Since abnormally large densities of myofibroblasts are associated with SSc, clinical studies consider trials that reduce the density of myofibroblasts: imatinib treatment ( ), which promotes apoptosis in myofibroblasts, and SSc by fresolimumab ( ), which inhibits TGF- , a key growth factor of myofibroblasts. We found that with the smallest amount of , decreases over a few months to and remains nearly stable thereafter. The results of the paper could be useful in the design of future clinical trials aimed to decrease the excessive extracellular matrix in SSc patients."

Journal • Fibrosis • Immunology • Scleroderma • Systemic Sclerosis

Genetic Bone Diseases: A Scoping Review of Pathology, Symptoms, Diagnosis, Treatment, and New Horizons. (PubMed, Adv Genet (Hoboken)) - "These treatments include: fresolimumab for osteogenesis imperfecta, small interfering ribonucleic acid (RNA) therapy for Osteopetrosis, denosumab for Paget's disease of bone, vosoritide/recifercept/infigratinib for achondroplasia, mesenchymal stem cell therapy for craniosynostosis, and combination losartan and atenolol therapy for Marfan syndrome. These treatments are generally more recently acknowledged in literature and are either actively undergoing research or require further research to determine their efficacy."

Journal • Review • Genetic Disorders • Orthopedics • Rare Diseases

Artificial Intelligence for Evidence Synthesis of Emerging Biologics to Improve Skeletal Health in Osteogenesis Imperfecta: Systematic Review and Meta-Analysis. (PubMed, J Med Internet Res) - "We conducted a systematic review and meta-analysis of interventional trials of denosumab, setrusumab, teriparatide, romosozumab, and fresolimumab. These findings should be interpreted cautiously given the small and heterogeneous trial base. Taken together, our workflow presented how evidence synthesis may be scaled and operationalized in real-world rare disease research."

Journal • Retrospective data • Review • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Rare Diseases

Collagen-derived biomarkers reveal distinct fibrotic responses among cancer-associated fibroblasts. (PubMed, Sci Rep) - "Notably, TGF-β1 was the primary driver of PRO-C3, PDGF-AB was the primary driver of PRO-C6, while IL-1α and IL-6 had no effect on PRO-C1, PRO-C3 and PRO-C6 levels. Antifibrotic treatments with ALK5i and Fresolimumab effectively reduced collagen biomarkers elevated by TGF-β1 to baseline levels or below.These results underscore the heterogeneity of CAFs in ECM remodeling, highlighting the need for tailored therapeutic strategies to target tumors exhibiting high fibrotic activity."

Biomarker • Journal • Fibrosis • Oncology • CAFs • IL6 • TGFB1

Targeting Transforming Growth Factor β: Development of a Pan-Cancer Theranostic (SNMMI 2026) - "This differential was previously demonstrated in breast, lung, and glioblastoma tumor models using positron emission tomography (PET) imaging with 89Zr-radiolabeled TGFβ-neutralizing antibody, fresolimumab (freso), which was clinically validated and binds to the activated form of TGFβ... As previously demonstrated by 89Zr-freso PET imaging, activated TGFβ is a promising theranostic target. Here, we assessed the therapeutic potential of 177Lu-freso. SPECT/CT imaging and autoradiograms confirmed tumor uptake and retention of 177Lu-freso, which was increased by priming irradiation, and may further enhance the efficacy of 177Lu-freso."

Pan tumor • Brain Cancer • Breast Cancer • Glioblastoma • Oncology • Solid Tumor • TGFB1

In vitro analysis of collagen deposition in lung cancer-associated fibroblasts using clinically validated biomarkers (AACR 2025) - "The pseudo-3D in vitro model using lCAFs and lNFs successfully replicates key aspects of the lung tumor microenvironment, particularly the differential collagen deposition patterns. The model demonstrated that lCAFs exhibit distinct collagen formation responses to TGF-β1, especially in type I and VI collagens, compared to lNFs. Additionally, treatment with ALK5i and Fresolimumab effectively reduced collagen formation, underscoring the model's potential for preclinical anti-fibrotic drug screening."

Preclinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CAFs • TGFB1 • TGFBR1

Pharmacological suppression of cancer associated fibroblast (CAF)-driven tumor fibrosis identified by the PRO-C3 biomarker in NSCLC (ELCC 2026) - "CAFs were treated with the ALK5/TGF-β1 receptor kinase inhibitor (ALK5i) or Fresolimumab (antibody targetingTGF-β) to investigate if the PRO-C3 and collagen deposition could be pharmacologically modified by therapeutic intervention.Results PRO-C3 was produced by lung CAFs after activation with TGF-beta but not PDGF-AB, IL-1 and IL-6 (p<0.0001)...These findings support that modulating CAFs can be monitored in vitro and that treating tumor fibrosis in NSCLC may be achived. Here, PRO-C3 may support drug development efforts already from drug discovery through clinical evaluation."

Biomarker • IO biomarker • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CAFs • IL6 • TGFB1 • TGFBR1

TGF-β Inhibition Through Combinatory Strategies Suppresses Proliferation and Invasiveness in Malignant Pleural Mesothelioma. (PubMed, Int J Mol Sci) - "Data obtained clearly highlighted how TGF-β inhibition, through the silencing or treatment of MPM cells with antibody anti-TGF-β (Fresolimumab), significantly reduces cell proliferation (MTT, PCNA) and prevents metastasis, reducing EMT and decreasing the invasiveness and migration of MPM cells...Taken as a whole, targeting TGF-β will represent a starting point for future improvements in MPM management. This is particularly important as we foresee a growing increase in MPM in the coming years."

Journal • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Pleural Mesothelioma • Solid Tumor • PCNA • TGFB1

Pro-c3 as a circulating biomarker of tumor fibrosis in breast cancer: functional insights from studying cancer associated fibroblasts in vitro (SABCS 2025) - "Elevated pre-treatment PRO-C3 levels have been associated with poor outcomes in metastatic HER2+ breast cancer treated with Trastuzumab (Lipton et al., 2018)...Fibroblasts were stimulated with profibrotic (TGF-β1, PDGF-AB) or inflammatory (IL-1α, IL-6) cytokines, and treated with antifibrotic agents (ALK5i, Fresolimumab) to assess potential changes in PRO-C3. PRO-C3 was elevated intrinsically in CAFs compared to benign fibroblast... PRO-C3 reflects both intrinsic and inducible fibrotic activity in breast CAFs and may serve as a surrogate marker of fibroblast activation in breast tumors. PRO-C3 is a clinically relevant biomarker of tumor fibrosis in breast cancer, with elevated circulating levels associated with poor prognosis. Our data support a fibroblast-derived origin of PRO-C3 and highlight TGF-β1 as a key upstream regulator."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CAFs • HER-2 • IL6 • TGFB1

The role of TGF-β1 in chronic multilobar segmental bronchial stenosis and advances in targeted drug research. (PubMed, Front Pharmacol) - "In recent years, groundbreaking progress has been made in research on therapeutics targeting the TGF-β1 signaling pathway, including monoclonal antibodies (e.g., Fresolimumab), small molecule kinase inhibitors (e.g., Galunisertib, TEW-7197), and novel targeted delivery systems. Furthermore, it proposes future research directions focused on CMBS-specific applications, such as validating these therapeutics in preclinical CMBS models, developing inhaled formulations for localized delivery, establishing biomarker-driven patient stratification, and exploring combination therapies with anti-fibrotic agents. This aims to provide a comprehensive theoretical foundation for elucidating the disease's pathology and developing novel, precise diagnostic and therapeutic strategies for CMBS."

Journal • Review • Asthma • Chronic Cough • Chronic Obstructive Pulmonary Disease • Cough • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • Tuberculosis • TGFB1

Artificial Intelligence in Evidence Synthesis: A Systematic Review and Meta-Analysis of Emerging Biologics for Improving Skeletal Health in Osteogenesis Imperfecta (ISPOR-EU 2025) - "OBJECTIVES: We aimed to systematically evaluate the effectiveness and safety of biologics in patients with Osteogenesis imperfecta (OI), integrating Artificial Intelligence (AI)-assisted assessment to enhance the rigor and efficiency of evidence synthesis. We conducted a systematic review and meta-analysis of trials assessing denosumab, setrusumab, teriparatide, and fresolimumab. Denosumab and setrusumab demonstrate promising efficacy in improving lumbar spine aBMD in OI, though current evidence does not support a definitive benefit of biologics in reducing fracture risk. GPT-4o supports evidence synthesis by improving screening efficiency and quality assessment, offering a scalable solution to reduce human workload. However, human oversight remains essential for tasks requiring contextual understanding and clinical reasoning."

Retrospective data • Review • Endocrine Disorders • Genetic Disorders • Metabolic Disorders • Musculoskeletal Diseases • Orthopedics • Pediatrics

Identification of anoikis-related genes in heart failure: bioinformatics and experimental validation. (PubMed, Hereditas) - "These findings suggest that Tln1 and TGFβ2 may play important roles in HF development through the regulation of anoikis and may serve as therapeutic targets for HF."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • TGFB1 • TGFB2 • TLN1

Predictive Biomarkers for Response to TGF- β Inhibition in Resensitizing Chemo(radiated) Esophageal Adenocarcinoma. (PubMed, Pharmacol Res) - "TGF-β inhibitors fresolimumab and A83-01 were employed to inhibit EMT, and mesenchymal markers were quantified via flow cytometry to assess efficacy...Our findings reveal a distinct gene expression pattern associated with the response to TGF-β inhibition in chemo(radiated) EAC. The identified DEGs and predictive markers may assist patient selection in clinical studies investigating TGF-β targeting."

Biomarker • Journal • Esophageal Adenocarcinoma • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • TGFB1

Current and Developing Pharmacologic Agents for Improving Skeletal Health in Adults with Osteogenesis Imperfecta. (PubMed, Calcif Tissue Int) - "Several therapeutics, including teriparatide, setrusumab, anti-TGF-β antibodies, and allogeneic stem cells, are being studied in clinical trials. Preclinical studies involving Dickkopf-1 antagonists present promising data in non-OI bone disease, and could be useful in OI. Research is ongoing to improve therapeutic options for adults with OI and clinical trials involving gene-editing may be possible in the coming decade."

Journal • Review • Genetic Disorders • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology • DKK1 • TGFB1

In-silico prediction of TGF-β1 non-synonymous variants and their impact on binding affinity to Fresolimumab. (PubMed, J Biomol Struct Dyn) - "Among them, the E35D variant significantly destabilized the TGF-β1 protein structure, resulting in rearrangement in the binding site and affecting the interactions with the Fresolimumab. This study identified four variants that can affect the TGF-β1 protein structure and result in functional consequences such as impaired response to Fresolimumab.Communicated by Ramaswamy H. Sarma."

Journal • Fibrosis • Immunology • Oncology • TGFB1

SABR-ATAC: A Trial of TGF-beta Inhibition and Stereotactic Ablative Radiotherapy for Early Stage Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=24 | Completed | Sponsor: Stanford University | Trial completion date: Dec 2021 ➔ Mar 2023 | Trial primary completion date: Dec 2021 ➔ Mar 2023

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Immune evasion mechanisms in melanoma resistant to targeted- and/or immunotherapy (AACR 2018) - P1,P1b/2; "...Of interest, a study has shown some efficacy of targeting the TGFB pathway by fresolimumab (a human monoclonal antibody against TGFB1-3) in melanoma (Clinical Trial ID: NCT0035646017). Another study currently combines nivolumab (anti-PD-1) with galunisertib (a TGFBR type I/II small molecule inhibitor) in multiple solid tumors (NCT02423343)...This implies that the tumor cell-intrinsic up-expression of IPRES-related genes is regulated at the epigenetic level. In summary, we anticipate that our study will lead to novel insights into the determinants and/or bottlenecks of effective and durable anti-tumor responses by tumor-specific T-cells in order to pave the way to a new combination therapies in human melanoma patients."

IO biomarker • PD(L)-1 Biomarker • Melanoma • Renal Cell Carcinoma

Colocalized targeting of TGF-β and PD-L1 by bintrafusp alfa elicits distinct antitumor responses. (PubMed, J Immunother Cancer) - "BA more effectively blocks TGF-β by targeting TGF-β trap to the tumor via PD-L1 binding. Such colocalized targeting elicits distinct and superior antitumor responses relative to single agent combination therapy."

IO biomarker • Journal • Fibrosis • Immunology • Lung Cancer • Oncology • Solid Tumor • TGFB1

Safety of Fresolimumab in the Treatment of Osteogenesis Imperfecta (clinicaltrials.gov) - P1 | N=11 | Completed | Sponsor: Baylor College of Medicine | Active, not recruiting ➔ Completed | Trial completion date: Aug 2023 ➔ Jul 2022

Trial completion • Trial completion date • Genetic Disorders • COL1A1 • COL1A2

Variability of Proteinuria in Nephrotic Syndrome: GC1008 PH2 Trial in FSGS (ERA-EDTA 2022) - P2 | "These data suggest that labour intensive, cumbersome timed 24-h urine collections should not be performed in clinical trials of nephrotic syndrome patients. Importantly, these data should allow for more precise power and sample size estimates for future interventional clinical trials of nephrotic syndrome."

Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Nephrology • Renal Disease

Safety of Fresolimumab in the Treatment of Osteogenesis Imperfecta (clinicaltrials.gov) - P1 | N=11 | Active, not recruiting | Sponsor: Baylor College of Medicine | Recruiting ➔ Active, not recruiting | N=16 ➔ 11

Enrollment change • Enrollment closed • Genetic Disorders • COL1A1 • COL1A2

Interventions for focal segmental glomerulosclerosis in adults. (PubMed, Cochrane Database Syst Rev) - "Five studies (240 participants) compared cyclosporin with or without prednisone with different comparators (no specific treatment, prednisone, methylprednisolone, mycophenolate mofetil (MMF), dexamethasone). Three small studies compared monoclonal antibodies (adalimumab, fresolimumab) with other agents or placebo. Six single small studies compared rituximab with tacrolimus, cyclosporin plus valsartan with cyclosporin alone, MMF with prednisone, chlorambucil plus methylprednisolone and prednisone with no specific treatment, different regimens of dexamethasone and CCX140-B (an antagonist of the chemokine receptor CCR2) with placebo. The final study (109 participants) compared sparsentan, a dual inhibitor of endothelin Type A receptor and of the angiotensin II Type 1 receptor, with irbesartan...Treatment with cyclosporin for at least six months was more likely to achieve complete remission of proteinuria compared with other treatments but there was considerable imprecision..."

Journal • Review • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Hypertension • Infectious Disease • Nephrology • Renal Disease • Transplantation

Targeting transforming growth factor- β (TGF-β) for treatment of osteogenesis imperfecta. (PubMed, J Clin Invest) - P1 | "Our data confirm that TGF-β signaling is a driver pathogenic mechanism in OI bone and that anti-TGF-β therapy could be a potential disease-specific therapy with dose-dependent effects on bone mass and turnover."

Journal • Dermatology • Genetic Disorders • Immunology • Musculoskeletal Diseases • Orthopedics • Rare Diseases • Rheumatology • TGFB1

SABR-ATAC: A Trial of TGF-beta Inhibition and Stereotactic Ablative Radiotherapy for Early Stage Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=24 | Completed | Sponsor: Maximilian Diehn | Active, not recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Dec 2021

Trial completion • Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

SABR-ATAC: A Trial of TGF-beta Inhibition and Stereotactic Ablative Radiotherapy for Early Stage Non-small Cell Lung Cancer (clinicaltrials.gov) - P1/2; N=24; Active, not recruiting; Sponsor: Maximilian Diehn; Trial completion date: Dec 2021 ➔ Dec 2022; Trial primary completion date: Dec 2020 ➔ Dec 2021

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor