MUNICH--(BUSINESS WIRE)--CatalYm today announced the presentation of two preclinical data sets expanding the mechanistic understanding and clinical application of its lead anti-GDF-15 antibody candidate, visugromab, at the upcoming Society for Immunotherapy of Cancer (SITC) 2023 Annual Meeting in San Diego, USA. The findings will be presented in two poster sessions on Friday, November 3rd, and Saturday, November 4th, and provide further clarification on GDF-15-mediated inhibition of T cell infiltration and highlight the potential of combining visugromab with bispecific T-cell engagers as a novel approach in cancer therapy. Visugromab is currently evaluated in a broad Phase 2 program in combination with anti-PD-1 treatment in multiple solid tumor indications.
“We are advancing our understanding of the underlying molecular mechanisms that are the foundation for GDF-15’s central role in tumor resistance to immunotherapy and visugromab’s potential to reinstate anti-tumor activity and enhance responses,” said Dr. Christine Schuberth-Wagner, Chief Scientific Officer at CatalYm. “The new data for the combination of visugromab with bispecific T-cell engagers provide strong scientific support for a synergistic effect in this novel therapeutic setting. We will further investigate this combination, which could extend durability and improve outcomes for a broad range of cancer patients with high medical need.”
Poster Presentation Identifying SHP-1 as Central Mediator of GDF-15-related T Cell Adhesion Inhibition
The first data set further expands understanding of visugromab’s mechanism of action and the underlying pathways involved in the development of GDF-15-mediated therapy resistance in cancer cells. When investigating the involvement of additional cell adhesion pathway components downstream of GDF-15, SHP-1 was identified as a central mediator of GDF-15-related inhibition of T cell adhesion. SHP-1 is an intracellular tyrosine phosphatase known as a negative regulator of antigen-dependent activation and proliferation of T cells. Inhibition of SHP-1 resulted in abrogation of GDF-15’s inhibitory effect. The researchers confirmed that GDF-15 via SHP-1 inhibits the phosphorylation of ZAP-70, another intracellular tyrosine kinase involved in LFA-1 inside-out activation and T cell receptor signaling. These data connect SHP-1 as a downstream effector to the recently published GDF-15-mediated reduction of high-affinity LFA-1 conformation, leading to impaired endothelial adhesion and transmigration of T cells toward the tumor site.
Poster Presentation Details
Title: SHP-1 is a central mediator of GDF-15 mediated adhesion inhibition in T cells
Presenter: Dr. Christine Schuberth-Wagner
Abstract number: 1049
Date and time: Friday, Nov 3rd, 5:00-6:30pm PDT
Poster Presentation on Visugromab/T-Cell Engager Combination
The second data set supports the expansion of visugromab’s application to combinations with immune cell-engaging therapies, underlining its potential to be a critical component for treatment success in a broad range of anti-cancer regimens. The preclinical analyses investigated a new combination of visugromab with a bispecific T-cell engager (tebentafusp). Anti-tumor activity of bispecific T-cell engagers is dependent on infiltration of effector T cells into the tumor microenvironment. In vivo analyses in a mouse tumor model demonstrated that the combination with visugromab significantly increased the number of intratumoral T cells compared with tebentafusp alone. This indicates a direct positive impact of visugromab’s infiltration-enhancing activity on the anti-tumor activity of bispecific T-cell engaging treatments and provides a strong rationale to further investigate this therapeutic concept.
Poster Presentation Details
Title: GDF-15 neutralizing antibody visugromab increases intratumoral immune cell infiltration to support bispecific T-cell engagers
Presenter: Dr. Christine Schuberth-Wagner
Abstract number: 1196
Date and time: Saturday, Nov 4th, 7:00-8:30pm PDT
CatalYm is investigating its GDF-15-neutralizing antibody visugromab in a broad Phase 2 clinical program, the GDFather (GDF-15 Antibody-mediaTed Human Effector Cell Relocation) trials, in combination with the anti-PD-1 inhibitor nivolumab in patients with advanced solid tumors. First interim data from the Phase 2 (NCT04725474) trial continue to demonstrate a very good safety and tolerability profile and promising early responses in major cancer indications, including non-small cell lung cancer (NSCLC), bladder cancer and hepatocellular carcinoma (HCC). In addition, CatalYm recently announced an exploratory Phase 2 study, GDFather-NEO (NCT06059547), evaluating visugromab in combination with neoadjuvant immunotherapy in first-line muscle-invasive bladder cancer.
About Visugromab (CTL-002)
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 reenabling immune cell activation and tumor infiltration. Visugromab has already demonstrated a good safety profile and potent and durable anti-tumor efficacy in combination with anti-PD-1 treatment in advanced cancer patients The antibody is currently being investigated in ongoing Phase 2 studies in multiple solid tumor indications.
About CatalYm
CatalYm has identified GDF-15 as a key cancer therapy resistance mechanism and is developing a safe and efficacious immune therapy for solid tumors. GDF-15, an immunosuppressant important for feto-maternal tolerance, is hijacked by cancer cells to evade immune system attack. Visugromab, CatalYm’s lead antibody, has demonstrated durable anti-tumor efficacy with long-lasting objective responses in relapsed and refractory metastatic solid tumor patients in combination with anti-PD-1. CatalYm is now advancing to Phase 2b studies to confirm visugromab as a new class of cancer immunotherapy in a broad range of anti-cancer regimens.
