New data: Visugromab targets ADC resistance mechanism

CatalYm has announced new preclinical data showing that its lead clinical-stage antibody, visugromab, can significantly enhance the effectiveness of antibody-drug conjugates (ADCs) by neutralising Growth Differentiation Factor 15 (GDF-15), a key driver of treatment resistance.

ADCs are an increasingly important class of cancer therapies, known for their precision and potency in treating solid tumours. However, many patients develop resistance, limiting long-term benefit. CatalYm’s latest study reveals that ADCs themselves may trigger the release of GDF-15, a protein linked to immune suppression and tumour progression.

The research showed that several clinically validated ADCs, including those based on topoisomerase I and microtubule inhibitors, consistently induced GDF-15 expression in tumour cells. This response was observed across multiple solid tumour types, both in vitro and in vivo, and was associated with reduced therapeutic efficacy.

Visugromab restores immune response and boosts anti-tumour activity

By neutralising GDF-15, visugromab was able to reverse this resistance mechanism, leading to significantly improved anti-tumour responses. The combination of visugromab with ADC therapy not only slowed tumour growth but also enhanced immune cell infiltration and activation in the tumour microenvironment, which are key factors in durable treatment success.

“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 Dr Christine Schuberth-Wagner, Chief Scientific Officer at CatalYm. “By blocking GDF-15, visugromab restores anti-tumour immune activity and enhances treatment efficacy, underscoring its potential as a versatile combination partner across a broad spectrum of cancer therapies beyond immunotherapies.”

Building on strong clinical evidence

These preclinical insights expand on results from CatalYm’s ongoing GDFATHER-1/2a Phase I/IIa trial (NCT04725474), recently published in Nature. The clinical data demonstrated that visugromab can induce deep and durable responses in patients with advanced solid tumours, particularly those who no longer respond to PD-1/PD-L1 checkpoint inhibitors. The drug also showed potential in addressing cancer-associated cachexia, a severe complication affecting many cancer patients.

Broad clinical development underway

CatalYm is currently conducting a global Phase IIb development program evaluating visugromab in non-squamous non-small-cell lung cancers and hepatocellular carcinoma, in addition to neoadjuvant treatment for urothelial cancer in combination with standard of care.

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