CatalYm to Present New Data Demonstrating GDF-15 Blockade Enhances Efficacy of Antibody-Drug Conjugates at AACR 2025

• Preclinical in vitro and in vivo data show enhanced anti-tumor activity when combining visugromab, a GDF-15-neutralizing antibody candidate, with approved antibody-drug-conjugate (ADC) treatment
• GDF-15 blockade enhances ADC activity, immune cell infiltration, and activation in the tumor
• Findings support continued investigation of GDF-15 neutralization as a potential strategy to overcome cancer therapy resistance for a variety of treatment modalities

MUNICH--(BUSINESS WIRE)--CatalYm today announced the presentation of the first preclinical data demonstrating that the company’s clinical-stage antibody visugromab can improve the anti-tumor activity of antibody-drug conjugates (ADCs). The data will be presented at the American Association for Cancer Research (AACR) Annual Meeting, taking place in Chicago, IL, April 25-30, 2025. The poster will highlight the potential of targeting Growth Differentiation Factor 15 (GDF-15) to enhance the activity and overcome resistance to ADC therapies, which are increasingly used as frontline treatments in several solid tumor indications. The full abstract is available on the AACR Annual Meeting website.

The study showed that several clinically validated ADCs, including topoisomerase I and microtubule inhibitor-based regimens, consistently triggered GDF-15 expression, suggesting a potential resistance mechanism to ADC therapy. Across in vitro and in vivo models of multiple solid tumor types, ADC treatment induced GDF-15 release from tumor cells, leading to elevated serum levels and reduced ADC efficacy. Combining ADC treatment with GDF-15 neutralization improved anti-tumor responses, resulting in reduced tumor growth and enhanced infiltration and activation of T cells and myeloid cells in the tumor microenvironment.

“We are building a broader understanding of GDF-15 as a key resistance mechanism activated by targeted approaches like ADCs as well as the leading immunotherapies like PD-1 inhibitors,” said Christine Schuberth-Wagner, PhD, Chief Scientific Officer at CatalYm. “By blocking GDF-15, visugromab restores anti-tumor immune activity and enhances treatment efficacy, underscoring its potential as a versatile combination partner across a broad spectrum of cancer therapies beyond immunotherapies.”

“ADCs continue to demonstrate potent and specific therapeutic impact, nevertheless resistance is a significant challenge for long-term patient benefit. In addition to our Phase 2 clinical development program, CatalYm will continue to investigate how our GDF-15 neutralizing antibody visugromab can create a novel path to address cancer resistance effectively,” added Scott Clarke, Chief Executive Officer at CatalYm.

The preclinical findings build on clinical evidence from the GDFATHER-1/2a trial (GDF-15 Antibody-mediaTed Human Effector T Cell Relocation Phase 1/2a Trial; NCT04725474), that was recently published in Nature. The data show that visugromab induces deep and durable responses in patients with relapsed or refractory solid tumors who had progressed on prior anti-PD-1/PD-L1 therapies. In addition to restoring anti-tumor immune responses, visugromab also demonstrated the potential to mitigate cancer-associated cachexia. CatalYm is currently conducting a broad, global Phase 2b clinical development program for visugromab, evaluating its effectiveness in earlier treatment lines of non-squamous non-small-cell lung cancer and hepatocellular carcinoma, as well as neoadjuvant treatment in urothelial cancer in combination with standard of care.

Poster details

Session title: “PO.IM01.03 - Antibodies and Antibody-Drug Conjugates”
Abstract title: “GDF-15 neutralization enhances the therapeutic activity of antibody-drug conjugates”
Abstract number: 4777/13
Location: Section 36
Date and time: April 29, 2025, 9:00 AM – 12 PM CT/ 4:00 PM – 7:00 PM CEST

About Visugromab

Visugromab is a monoclonal antibody that neutralizes the tumor-derived Growth Differentiation Factor-15 (GDF-15), a locally acting immunosuppressant fostering immunotherapy resistance. 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.

About CatalYm

CatalYm is developing visugromab, a first-in-class anti-GDF-15 antibody, in solid tumors and other indications. 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 recently published in Nature and presented at the International Conference on Sarcopenia, Cachexia & Wasting Disorders. CatalYm is now advancing visugromab into multiple Phase 2b studies.

Founded in 2016 and based in Munich, Germany and San Francisco, USA, CatalYm is backed by leading international investors including Canaan Partners, Bioqube Ventures, Forbion, Omega Funds, Gilde Healthcare, Jeito Capital, Novartis Venture Fund, Vesalius, Brandon Capital, Bayern Kapital, BioGeneration Ventures, and Coparion.