MUNICH, Germany I October 26, 2023 ICatalYm today announced that the first patient has been dosed in the Phase 2 clinical trial, GDFather-NEO (NCT06059547), evaluating its lead anti-GDF-15 antibody candidate, visugromab, in combination with neoadjuvant immunotherapy (nivolumab, aPD-1 inhibitor) in muscle invasive bladder cancer (MIBC). The exploratory study expands visugromab’s clinical Phase 2 evaluation to a therapeutic front-line setting, building on the positive results from the ongoing GDFather-2 (NCT04725474) trial in last-line metastatic patients with a range of advanced, treatment-resistant solid tumors.

“Visugromab offers a very distinct mechanism of action that has the potential to break key immunotherapy resistance mechanisms preventing aPD-1 therapy to fully deliver,” commented Prof. Dr. Andrea Necchi, Director of Genitourinary Medical Oncology at IRCCS San Raffaele Hospital and Principal Investigator of the study. “Based on the encouraging efficacy signs achieved with the visugromab-nivolumab combination in the last-line setting, we are looking forward to exploring this new approach in the front-line setting to open new avenues for the treatment of early-stage bladder cancer.”

“This study provides us with the first opportunity to evaluate visugromab in an earlier clinical setting and allows us to gain a deeper understanding of its immunosupportive activity. It will also offer us expanded reference data on response-predictive biomarkers and provide further insights into visugromab’s extensive therapeutic potential for patients with hard-to-treat cancers that have built immune-resistance mechanisms,” added Dr. Phil L’Huillier, Chief Executive Officer at CatalYm.

The exploratory, controlled GDFATHER-NEO Phase 2 study is assessing the safety and initial signs of clinical efficacy of a combination treatment of nivolumab plus visugromab compared to nivolumab plus placebo in patients with MIBC who are set to undergo radical cystectomy and cannot or refuse to receive cisplatin-based chemotherapy. In addition, the study will provide data on potential response-predictive biomarkers for patient stratification. The trial will be led from Milan, Italy, and will enroll 30 patients in a 1:1 setting at four sites in Italy.

About the GDFATHER-2 Trials

The GDFATHER-2 trials (GDF-15 Antibody-mediaTed Human Effector cell Relocation Phase 2) (NCT04725474) are ongoing first-in-human Phase 2a cohorts investigating the effect of visugromab (CTL-002) as monotherapy and/or in combination with a PD-1 checkpoint inhibitor in patients with various advanced-stage, relapse/refractory solid tumors and the new biomarker-selected cohort. The study consists of two segments with a total of up to seven cohorts, enrolling up to 164 patients in Simon-2-stage designs to confirm a certain response rate within each tumor type. Five cohorts are within tumor types with anti-PD1/-L1 label, recruiting patients that either were refractory to or relapsed post prior anti-PD1/-L1 treatment. One cohort entails treatment of an anti-PD1/-L1 naïve tumor type in an indication without anti-PD1/-L1 approval and one tumor-agnostic cohort evaluates patient-selection based on two novel predictive biomarkers. In addition the company is also evaluating visugromab in an exploratory Phase 2 study GDFather-NEO (NCT06059547) 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.