Visugromab

Study targets patients with unresectable or metastatic hepatocellular carcinoma who have progressed following first-line anti-PD-(L)1-based therapy Initiation of the third Phase 2b study of visugromab, expanding development into hepatocellular carcinoma following first and second-line NSCLC programs MUNICH & SAN FRANCISCO--(BUSINESS WIRE)-- CatalYm today announced that the first patient has been dosed in the GDFATHER-HCC-01 trial ( NCT07219459 ). The trial evaluates the company’s lead anti-GDF-15 antibody visugromab in combination with chemoimmunotherapy as a second-line (2L) treatment for patients with unresectable or metastatic hepatocellular carcinoma (HCC). The Phase 2b trial targets patients who have progressed following 1L treatment with an anti-PD-(L)1-based therapy. The trial will assess a treatment strategy combining visugromab with the PD-1 inhibitor nivolumab and the multi-target tyrosine kinase inhibitor (TKI) lenvatinib. The study consists of an open-label safety run-in to confirm the recommended dose for expansion, followed by a randomized, double-blind phase evaluating visugromab plus nivolumab plus lenvatinib versus double placebo plus lenvatinib. Visugromab is a monoclonal antibody that neutralizes Growth Differentiation Factor-15 (GDF-15), an immunosuppressive cytokine exploited by tumor cells to promote immune evasion and resistance to anti-PD-(L)1 therapies. By neutralizing GDF-15, visugromab aims to restore anti-tumor immune responses to improve outcomes in a setting where 5-year overall survival remains as low as 18%. 1 In the exploratory Phase 1/2a GDFATHER trial ( NCT04725474 ), visugromab demonstrated encouraging anti-tumor activity when combined with an anti-PD-1 antibody in advanced-stage, anti-PD-(L)1 relapsed/refractory HCC patients, demonstrating deep and durable responses, with a median duration of response of 21.4 months and a favorable safety profile. “HCC is the third leading cause of cancer-related deaths globally and continues to present immense clinical challenges, especially in patients who progress on immunotherapy,” said Sujata Rao, MD, Chief Medical Officer at CatalYm . “This new trial is designed to combine the immune-restoring properties of visugromab with a checkpoint inhibitor and the standard of care tyrosine kinase inhibitor. With this approach we aim to improve clinical outcomes for HCC patients with limited treatment options.” “Expanding into HCC represents a pivotal step in our strategy to bring visugromab to additional high-need tumor types,” said Scott Clarke, Chief Executive Officer at CatalYm . “Visugromab’s dual potential to restore immune sensitivity and address cancer cachexia, which affects nearly one in four patients with HCC at diagnosis, underpins our approach in this study. By combining our antibody with proven standards of care, we aim to shift the treatment paradigm and ultimately improve survival and quality of life for patients who have few options today.” The GDFATHER-HCC-01 trial is a global, randomized, blinded Phase 2b study enrolling approximately 104 participants across 40 sites in North America, Europe and Asia-Pacific. It consists of two parts: Part 1: An open-label safety run-in assessing the combination of visugromab with nivolumab and lenvatinib to determine the Recommended Dose for Expansion (RDE). Part 2: A randomized and double-blind evaluation of the triple combination versus double placebo plus lenvatinib. The primary endpoint is progression-free survival (PFS) assessed by local investigators. Key secondary endpoints include overall survival (OS), independently assessed PFS, and objective response rate (ORR). The study will also explore visugromab’s potential to mitigate cancer cachexia using the Functional Assessment of the Anorexia and Cachexia Therapy questionnaire (FAACT-ACS), as muscle wasting and weight loss are common in HCC and known to negatively affect treatment tolerance and clinical outcomes. About Hepatocellular Carcinoma Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death worldwide. The five-year survival rate for HCC is only 18%, second lowest among common cancers 1 . While checkpoint inhibitors have become a first-line standard of care, most patients with advanced-stage HCC ultimately experience disease progression or relapse. Treatment options in the second-line setting remain limited, underscoring the urgent need for more effective and well-tolerated therapies. About Visugromab Visugromab is a monoclonal antibody that neutralizes Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant produced by tumors which fosters immunotherapy resistance and drives cachexia in people with cancer. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by re-enabling immune cell activation, proliferation and induction of interferon-γ. In addition, visugromab also mitigates cancer cachexia, a severe condition affecting a significant number of advanced cancer patients by inhibiting the activation of the GFRAL pathway in the brainstem, a key driver of weight loss and appetite suppression in cancer patients. About CatalYm CatalYm is developing visugromab, a first-in-class anti-GDF-15 antibody, in solid tumors and cachexia. In its first-in-human Phase 1/2a study, visugromab demonstrated deep and durable anti-tumor efficacy with long-lasting objective responses in relapsed and checkpoint refractory metastatic solid tumor patients in combination with anti-PD-1 treatment. In addition, data from the same study demonstrated that visugromab can significantly counteract the effects of cachexia in these patients. This data was published in Nature and presented at the International Conference on Sarcopenia, Cachexia & Wasting Disorders. CatalYm is now advancing visugromab into multiple Phase 2b studies including first-line metastatic non-squamous NSCLC ( NCT07098988 ), second-line metastatic non-squamous NSCLC ( NCT07246863 ), and second-line hepatocellular carcinoma ( NCT07219459 ). Founded in 2016 and based in Munich, Germany and San Francisco, USA, CatalYm is backed by leading international investors including Canaan Partners, Omega Funds, Bioqube Ventures, Forbion, Jeito Capital, Brandon Capital, Gilde Healthcare, Novartis Venture Fund, Vesalius, Bayern Kapital, BioGeneration Ventures, and Coparion. 1 National Institute of Health, Hepatocellular Carcinoma , retrieved on January 14, 2026 Contacts CatalYm GmbH Clinton Musil, CFO and CBO info@catalym.com Media Inquiries Trophic Communications Dr. Stephanie May or Anja Heuer Phone: +49 171 185 56 82 or +49 151 106 199 05 catalym@trophic.eu

MUNICH & SAN FRANCISCO--(BUSINESS WIRE)--CatalYm today announced that the first patient has been dosed in the randomized Phase 2b GDFATHER‑NSCLC‑02 (GDF‑15 Antibody‑MediaTed‑Human‑Effector‑T‑Cell Relocation) trial (NCT07246863). The trial evaluates the company’s lead anti-GDF-15 antibody visugromab as a second-line treatment in patients with metastatic non-squamous non-small cell lung cancer (nsq NSCLC) who have progressed following initial systemic treatment including an approved immune checkpoint inhibitor. The trial will assess multiple treatment strategies combining visugromab with an anti-PD-1 antibody and the chemotherapy docetaxel, including a chemo-free regimen. Standard-of-care chemotherapy alone will serve as the control arm. The trial consists of a safety run-in followed by a randomized phase evaluating visugromab in the different combination regimen settings. Visugromab is a humanized, monoclonal antibody that targets Growth Differentiation Factor-15 (GDF-15), a tumor-derived cytokine known to drive immune suppression and resistance to anti-PD-(L)1 therapies. In the exploratory Phase 1/2a GDFATHER trial (NCT04725474), visugromab demonstrated encouraging anti-tumor activity when combined with an anti-PD-1 antibody in advanced-stage, anti-PD-(L)1 relapsed/refractory NSCLC patients, demonstrating deep and durable responses, with a median duration of response of 32.2 months and a favorable safety profile. In addition to its ability to restore immune activation, visugromab also showed potential to alleviate cancer cachexia, a severe condition limiting treatment tolerability and responsible for 20-40% of cancer deaths.1 “The decision to evaluate visugromab in second-line nsq NSCLC, in addition to the first-line setting, was driven by the strength of our Phase 1/2a data in heavily pretreated patients, where we observed deep and durable responses well beyond those typically seen with other therapies in this setting,” said Sujata Rao, MD, Chief Medical Officer at CatalYm. “By neutralizing GDF-15, a key driver of immune suppression, visugromab may overcome resistance, restore responsiveness to immunotherapy and extend the benefit of anti-PD-1 agents. Its additional potential to mitigate cancer cachexia and support tolerance to chemotherapies and other anti-cancer regimens offers a distinct advantage in this difficult-to-treat population.” “We are expanding visugromab’s development into key settings where immune resistance severely limits treatment options,” said Scott Clarke, Chief Executive Officer at CatalYm. “Second-line nsq NSCLC is a particularly challenging indication with limited benefit from current standard-of-care. This trial builds on the compelling rationale for GDF-15 neutralization and is part of our late-stage development program to deliver visugromab’s potential to patients in urgent need of better solutions.” The randomized, multi-arm Phase 2b GDFATHER-NSCLC-02 trial will enroll approximately 131 patients across multiple sites in the US, EU and Switzerland. Following the safety run-in, patients will be randomized into one of four treatment arms: Visugromab + anti-PD-1 inhibitor + chemotherapy Visugromab + anti-PD-1 inhibitor (chemo-free) Visugromab (at lower dose) + anti-PD-1 inhibitor + chemotherapy Chemotherapy alone (control) The primary endpoint of the study is objective response rate (ORR) defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints include duration of response (DOR), progression-free survival (PFS), overall survival (OS), participant weight course over time and safety-related measures. About NSCLC Lung cancers remain the leading cause of cancer-related mortality globally and non-small cell lung cancers (NSCLCs) account for approximately 87% of the 210,000 annual lung cancer diagnoses in the US2. Five-year survival rates in the US for non-squamous NSCLC are low: 12.8% for adenocarcinoma and 5.1% for large-cell carcinoma3. 70-85% of NSCLC patients either exhibit primary resistance to PD-1 blockade or develop acquired resistance to immunotherapy4, emphasizing the need for innovative approaches to overcome immunotherapy resistance. About Visugromab Visugromab is a monoclonal antibody that neutralizes Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant produced by tumors which fosters resistance and drives cachexia in people with cancer. Neutralizing GDF-15 with visugromab reverses key cancer resistance mechanisms to reinstate an efficient anti-tumor response by re-enabling immune cell activation, proliferation and induction of interferon-γ. In addition, visugromab also mitigates cancer cachexia, a severe condition affecting a significant number of advanced cancer patients by inhibiting the activation of the GFRAL pathway in the brainstem, a key driver of weight loss and appetite suppression in cancer patients. About CatalYm CatalYm is developing visugromab, a first-in-class anti-GDF-15 antibody, in solid tumors and cachexia. In its first-in-human Phase 1/2a study, visugromab demonstrated durable anti-tumor efficacy with long-lasting objective responses in relapsed and refractory metastatic solid tumor patients in combination with anti-PD-1 treatment. In addition, data from the same study demonstrated that visugromab can significantly counteract the effects of cachexia in these patients. This data was published in Nature and presented at the International Conference on Sarcopenia, Cachexia & Wasting Disorders. CatalYm is now advancing visugromab into multiple Phase 2b studies including first-line metastatic non-squamous NSCLC (NCT07098988), second-line metastatic non-squamous NSCLC (NCT07246863) and cachexia (NCT07112196). Founded in 2016 and based in Munich, Germany and San Francisco, USA, CatalYm is backed by leading international investors including Canaan Partners, Omega Funds, Bioqube Ventures, Forbion, Jeito Capital, Brandon Capital, Gilde Healthcare, Novartis Venture Fund, Vesalius, Bayern Kapital, BioGeneration Ventures, and Coparion. 1 Fearon K. et al. Lancet Oncol. 2011;12(8):489–495. 2 American Cancer Society, Key Statistics for Lung Cancer, 2025: https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html, retrieved on Aug. 06, 2025 3 https://seer.cancer.gov/ 4 Mariniello A, Borgeaud M, Weiner M, Frisone D, Kim F, Addeo A. Primary and Acquired Resistance to Immunotherapy with Checkpoint Inhibitors in NSCLC: From Bedside to Bench and Back. BioDrugs. 2025 Mar;39(2):215-235. doi: 10.1007/s40259-024-00700-2. Epub 2025 Feb 15. PMID: 39954220; PMCID: PMC11906525.