• 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

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 cancers¹. 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 https://www.ncbi.nlm.nih.gov/books/NBK559177/, retrieved on January 14, 2026

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