CatalYm to Present Initial Data of First-in-Human Trial of GDF-15 Neutralizing Antibody CTL-002 

CatalYm GmbH recently announced that their abstract with first interim data from the Phase 1 clinical trial investigation CTL-002 as monotherapy and in combination with a checkpoint inhibitor (the GDFATHER-Trial) has been selected by ASCO for a poster presentation. The 2021 Annual Meeting of the American Society of Clinical Oncology will be held virtually from June 4-8.

The poster A Phase 1, First-in-Human Clinical Trial of the GDF-15 Neutralizing Antibody CTL-002 in Subjects With Advanced-Stage Solid Tumors (ACRONYM: GDFATHER), Abstract TPS2658, will present CatalYm’s first-in-human, two-part, open-label Phase 1 clinical trial of CTL-002, a neutralizing antibody targeting GDF-15. GDF-15 is a factor that is secreted by several major tumor entities and interferes with effector T cell recruitment. In the GDFATHER-trial, patients with advanced-stage, solid tumors who have not responded or stopped responding to anti-PD-1/PD-L1 therapy are treated with CTL-002 as monotherapy and followed by combination with an anti-PD-1 antibody. The first patient was enrolled in December 2020.

The poster presentation with initial interim data will be available from 3:00 pm CEST (9:00 am EDT) on June 4, Track: Developmental Therapeutics – Immunotherapy.

“It is an exciting opportunity to present our trial at ASCO,” noted Prof. Dr. Eugen Leo, Chief Medical Officer of CatalYm. “Our tailored ‘mono-followed-by-combination’ trial design allows all participating patients to access a promising, novel antibody combination therapy from the very start of the clinical trial, resulting in great patient and Investigator interest in trial participation.”

Dr. Christine Schuberth-Wagner, Chief Scientific Officer of CatalYm, added “With recent external confirmation of GDF-15 being a key player in the I/O-space by third parties, we are delighted to see our data receiving the appropriate attention bringing GDF-15 in the spotlight of the I/O world. This validates our concept that blocking GDF-15 can make anti-PD1 therapy more effective.”

Dr. Phil L’Huillier, Chief Executive Officer of CatalYm, concluded “We strongly believe that neutralizing GDF-15 is one of the key immune restorative mechanisms in a broad range of tumors and could substantially improve the efficacy of anti-PD1/-PD-L1 checkpoint inhibitors and other immune agonists. Our Phase 1 trial is well underway with the third cohort ongoing as planned. We are very excited about the rapid overall progress of our program and are eager to see the definitive biomarker and clinical results of this promising clinical trial unfolding.”

An additional abstract on GDF-15 preclinical data will appear in the 2021 ASCO Annual Meeting Proceedings, a Journal of Clinical Oncology supplement. The abstract Tumor-Derived GDF-15 to Suppress T-lymphocyte Recruitment to the Tumor Microenvironment Resulting in Resistance to ANTI-PD-1 Treatment, Abstract e14532, is also available on the ASCO meeting website.

It describes in vitro and in vivo as well as translational data showing that elevated GDF-15 levels block T cells from infiltrating tumor tissues and are predictive for shorter OS of patients. CTL-002, which neutralizes GDF-15, can restore the ability of T cells to enter the tumor and may thus improve responses to anti-PD1 therapy in patients with high GDF-15 levels.

CTL-002 is a humanized, monoclonal antibody designed to neutralize the tumor-produced Growth Differentiation Factor-15 (GDF-15). High concentrations of GDF-15 in the serum and tumor-microenvironment help the tumor evade the immune system and are associated with resistance to current therapies.

CTL-002 addresses three of the tumor’s immune suppressive mechanisms all involving the inhibitory effect of GDF-15 on the immunostimulatory LFA-1/ICAM-1 interaction. By neutralizing GDF-15, CTL-002 is expected to enhance infiltration of immune cells into the tumor, improve priming of T cells by dendritic cells and improve tumor killing by T cells and NK cells.

The GDFATHER trial (GDF-15 Antibody-mediaTed Effector cell Relocation) is a Phase 1, first-in-human, multicenter, two-part (part A: dose escalation and part B: cohort expansion) clinical trial of intravenous (IV) administration of CTL-002 as monotherapy and in combination with an anti-PD-1 checkpoint inhibitor in patients with advanced-stage solid tumors, that relapsed post or were refractory to a prior anti-PD-1/PD-L1 therapy. The primary objectives of the study are to characterize the safety and tolerability of CTL-002 and to explore the preliminary anti-tumor activity of CTL-002 in the expansion cohorts. More information on trial can be found at https://clinicaltrials.gov.

CatalYm is a biopharmaceutical company developing novel cancer immunotherapies targeting Growth-and-Differentiation Factor 15 (GDF-15). Apart from its established role in cachexia, GDF-15 has been associated with immunosuppression in tissues and tumors and a rapidly growing body of literature supports the concept that GDF-15 is a major T cell repellent. CatalYm aims to neutralize GDF-15 to turn “cold” tumors “hot” and thereby substantially improving the efficacy of established immunotherapy such as anti-PD1/-PD-L1 checkpoint inhibitors. The company’s lead product candidate CTL-002, a neutralizing GDF-15 antibody, is currently under clinical evaluation in a two-part, open-label, multicenter, Phase 1 clinical trial (GDFATHER trial).

The company was founded in 2016 as a spin-off from the Julius-Maximilians-University of Würzburg based on the innovative research work of Prof. Dr. Joerg Wischhusen. CatalYm is led by a seasoned senior executive team with substantial IO drug development as well as deal making experience and backed by international venture capital investors, eg, Forbion and BioGeneration Ventures, Vesalius Biocapital III, Novartis Venture Fund, Wachstumsfonds Bayern and coparion. CatalYm received financial support from the EIF via the EIB-EIF Co-investment Facility, backed by the European Union through the European Fund for Strategic Investments (EFSI).