CatalYm has announced groundbreaking preclinical data demonstrating that its clinical-stage antibody visugromab can significantly enhance the anti-tumor activity of antibody-drug conjugates (ADCs). The findings will be presented at the American Association for Cancer Research (AACR) Annual Meeting in Chicago, taking place April 25-30, 2025.
The research reveals a novel approach to overcoming cancer therapy resistance by targeting Growth Differentiation Factor 15 (GDF-15), a tumor-derived immunosuppressant. According to the study, several clinically validated ADCs consistently triggered GDF-15 expression in tumor cells, suggesting this may represent a previously unrecognized resistance mechanism to ADC therapy.
"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," explained 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."
Mechanism of Action and Study Findings
The study investigated both in vitro and in vivo models across multiple solid tumor types. Researchers observed that ADC treatment induced GDF-15 release from tumor cells, leading to elevated serum levels and reduced ADC efficacy. When ADC treatment was combined with GDF-15 neutralization via visugromab, anti-tumor responses improved significantly.
Key outcomes of the combination therapy included:
- Reduced tumor growth
- Enhanced infiltration of T cells into the tumor microenvironment
- Increased activation of myeloid cells in the tumor
- Improved overall efficacy of ADC treatments
The study specifically examined ADCs with different mechanisms of action, including those based on topoisomerase I and microtubule inhibitors, with consistent results across these different classes.
Building on Previous Clinical Success
These preclinical findings complement existing clinical evidence from CatalYm's GDFATHER-1/2a trial (GDF-15 Antibody-mediaTed Human Effector T Cell Relocation Phase 1/2a Trial; NCT04725474), recently published in Nature. That study demonstrated visugromab's ability to induce deep and durable responses in patients with relapsed or refractory solid tumors who had progressed on prior anti-PD-1/PD-L1 therapies.
Scott Clarke, Chief Executive Officer at CatalYm, highlighted the significance of these findings: "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."
Beyond its primary role in restoring anti-tumor immune responses, visugromab has also shown potential to mitigate cancer-associated cachexia, a debilitating condition characterized by severe weight loss and muscle wasting that affects many cancer patients.
Ongoing Clinical Development
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
- Hepatocellular carcinoma
- Neoadjuvant treatment in urothelial cancer in combination with standard of care
The company's poster presentation at AACR will take place on April 29, 2025, from 9:00 AM to 12:00 PM CT in Section 36, with abstract number 4777/13 titled "GDF-15 neutralization enhances the therapeutic activity of antibody-drug conjugates."
About Visugromab and Its Mechanism
Visugromab is a monoclonal antibody that neutralizes tumor-derived GDF-15, which acts as a local immunosuppressant that fosters resistance to immunotherapy. By neutralizing GDF-15, visugromab reverses key cancer resistance mechanisms, reinstating efficient anti-tumor responses through several mechanisms:
- Re-enabling immune cell activation
- Promoting immune cell proliferation
- Inducing interferon-γ production
This first-in-class anti-GDF-15 antibody has shown promising results 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 patients with relapsed and refractory metastatic solid tumors when used in combination with anti-PD-1 treatment.
About CatalYm
Founded in 2016 and headquartered in Munich, Germany, with additional operations in San Francisco, USA, CatalYm is focused on developing novel immunotherapies for cancer treatment. The company is backed by a consortium of leading international investors including Canaan Partners, Bioqube Ventures, Forbion, Omega Funds, Gilde Healthcare, Jeito Capital, Novartis Venture Fund, and several others.
The company's approach represents a potentially significant advancement in addressing the challenge of treatment resistance, which remains one of the most significant hurdles in cancer therapy. By targeting GDF-15, CatalYm is exploring a novel pathway to enhance the effectiveness of both established and emerging cancer treatments, potentially offering new hope for patients with difficult-to-treat solid tumors.
