On April 25, 2025 CatalYm reported 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) (Free AACR Whitepaper) Annual Meeting, taking place in Chicago, IL, April 25-30, 2025 (Press release, Catalym, APR 25, 2025, View Source [SID1234652140]). 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 (Free AACR Whitepaper) Annual Meeting website.

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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.