CTL-002, which the company will going forward refer to as visugromab, the recently approved International Nonproprietary Name (INN) by the World Health Organization, is a monoclonal antibody against the novel cancer target Growth and Differentiation Factor 15 (GDF-15). GDF-15 has been shown to play a central role in immune system evasion mechanisms in the tumor microenvironment and its overexpression correlates with reduced immune cell influx into the tumor, suppression of the adaptive immune response and poor outcome including anti-PD1/-L1 treatment resistance.

Visugromab has successfully completed phase 1 development demonstrating excellent tolerability as a monotherapy as well as in combination with a PD-1 checkpoint inhibitor. Initial results from the trial have been presented at the AACR-EORTC-NCI meeting in October 2021 and at the SITC Annual Meeting in Nov 2021. In this dose escalation trial named GDFATHER-1 (GDF-15 Antibody-mediaTed Human Effector cell Relocation phase 1, NCT04725474), several patients with solid tumor indications known to be difficult to treat with immune-oncology (I/O) therapy have shown deep and lasting responses post treatment with visugromab + nivolumab after prior failure of anti-PD1/-L1 therapy. Two of the three responders have already passed the six-month follow-up mark showing lasting and continued responses. The full results from the phase 1 part of the study including biomarker profile correlations are planned to be shared at an upcoming conference in the first half of 2022.

Prof. Ignacio Melero (Center for Advanced Medical Research, CIMA/Pamplona, Spain), Principal Investigator of the GDFATHER-1 trial, commented: “There is mounting evidence from several research groups demonstrating that GDF-15 plays an important role in tumor-mediated immunosuppression across various major solid tumor indications. Visugromab has the potential to neutralize GDF-15 in the tumor microenvironment and to reverse this immunosuppression. The initial signs of efficacy combined with a very safe combination treatment profile even in heavily pretreated patients are very encouraging to me and I look forward to seeing the impact visugromab will have on larger patient populations treated at earlier stages of the disease.”

The initial phase 2a exploration, the GDFATHER-2 trial series, is planned to enroll up to 164 patients across six major solid tumor indications in trial sites in Spain, Germany and Switzerland in a Simon-2-stage design. The study will evaluate the efficacy of visugromab at target dose in combination with the PD-1 checkpoint inhibitor, nivolumab, in six solid tumor indications that were selected based on significant translational research data obtained by CatalYm and the phase 1 results. The first five cohorts will include patients with relapsed/refractory tumors that received PD-1 checkpoint inhibitor treatment prior to this study. The sixth cohort is recruiting PD-1 checkpoint naïve patients. The first results from the phase 2a study are expected in the second half of 2022.

Prof. Eugen Leo, Chief Medical Officer at CatalYm stated: “In 2021, we were able to demonstrate in the GDFATHER-1 trial that treatment with visugromab is not only safe and very well tolerated in a very advanced and heavily pretreated patient population, but we also saw encouraging signs of potent antitumoral activity in previously anti-PD1/-L1 relapsed/refractory patients. Now, in 2022, our goal is to maximize the clinical impact of our lead candidate in a variety of cancer indications both PD-1 refractory and naïve with the phase 2a GDFATHER-2 trial series. Advancing into phase 2a development marks an important scientific and clinical milestone for CatalYm and we are looking forward to sharing further data from our phase 1 trial and early phase 2 data with the scientific and medical community in the near future.”

CatalYm’s CEO, Phil L’Huillier concluded: “Advancing this program into phase 2 at such a fast pace demonstrates the dedication and experience of our clinical operations and translational research team as well as our collaborators and I applaud them for their enormous contributions in making this possible. In light of the exciting emerging preclinical and clinical data for the program we will add further trial segments to our phase 2 program over the course of 2022 to further accelerate visugromab development towards a registration trial.”

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 advanced-stage, relapse/refractory solid tumors. The study consists of two segments with a total of six 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.

About Visugromab (CTL-002)
Visugromab, formerly known as CTL-002, is a humanized, monoclonal antibody designed to neutralize the tumor-produced Growth Differentiation Factor-15 (GDF-15). GDF-15 secretion by the tumor has been shown to prevent T cell migration into the tumor and suppresses T cell function and the adaptive immune response in the tumor microenvironment. This enables the tumor to evade the immune system and become resistant to standard of care and current immunotherapy approaches such as checkpoint inhibitors. Visugromab counteracts these immuno-suppressive mechanisms by neutralizing GDF-15, enhancing the infiltration of immune cells into the tumor, improving both priming of T cells by dendritic cells and tumor killing by T cells and NK cells.