visugromab (CTL-002) / CatalYm - LARVOL DELTA

FL-501 is a potential best in class GDF-15 inhibitor with extended half-life and potent anti-cachexia activity in preclinical models (AACR 2025) - "In this therapeutic model, mice were treated with cisplatin (5 mg/kg) alone or in combination with either FL-501 or ponsegromab...Further, the targeted inhibition of GDF-15 with FL-501 was able to effectively reverse characteristics of cancer cachexia in multiple pre-clinical models. Taken together, these findings support the continued evaluation of FL501 and its progression into the clinic."

Preclinical • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • GDF15

CatalYm to Present New Data Demonstrating GDF-15 Blockade Enhances Efficacy of Antibody-Drug Conjugates at AACR 2025 (Businesswire) - "Preclinical in vitro and in vivo data show enhanced anti-tumor activity when combining visugromab, a GDF-15-neutralizing antibody candidate, with approved antibody-drug-conjugate (ADC) treatment....The study showed that several clinically validated ADCs, including topoisomerase I and microtubule inhibitor-based regimens, consistently triggered GDF-15 expression, suggesting a potential resistance mechanism to ADC therapy. Across in vitro and in vivo models of multiple solid tumor types, ADC treatment induced GDF-15 release from tumor cells, leading to elevated serum levels and reduced ADC efficacy. Combining ADC treatment with GDF-15 neutralization improved anti-tumor responses, resulting in reduced tumor growth and enhanced infiltration and activation of T cells and myeloid cells in the tumor microenvironment."

Preclinical • Solid Tumor

GDF-15 neutralization enhances T cell infiltration in solid tumor models (ITOC 2025) - "Additionally, GDF-15 neutralization in the tebentafusp model was associated with increased infiltration of activated antigen-presenting cells, as evidenced by elevated numbers of CD80 and CD86-expressing dendritic cells and macrophages. Conclusions Our findings identify GDF-15 as a potential barrier to effective T cell infiltration in solid tumors and suggest that its neutralization may enhance T cell-based therapies by promoting T cell extravasation and facilitating the recruitment and activation of antigen-presenting cells in the tumor microenvironment, potentially expanding the application of these therapeutic modalities beyond their current limitations."

Preclinical • Hematological Malignancies • Melanoma • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD80 • CD86 • GDF15

GDFather-NEO: Neoadjuvant Immunotherapy Combined With the Anti-GDF-15 Antibody Visugromab to Treat Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: CatalYm GmbH | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2026 ➔ Sep 2026 | Trial primary completion date: Apr 2025 ➔ Aug 2025

Enrollment closed • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

GDF-15 blockade: A multi-directional approach to potentiate cancer immunotherapy and alleviate cancer cachexia. (PubMed, Clin Transl Med) - No abstract available

Journal • Cachexia • Oncology • GDF15

CatalYm Appoints Scott Clarke CEO as Company Initiates Global Phase 2b Clinical Development Program for Visugromab (Businesswire) - "CatalYm today announced the appointment of Scott Clarke as Chief Executive Officer. Mr. Clarke brings over two decades of executive leadership experience in driving company growth, developing products, and shaping and executing transactions in the biopharmaceutical industry. He takes the helm as CatalYm enters a new stage of corporate and clinical development, including the initiation of a broad Phase 2b program for its lead candidate, visugromab, in non-squamous non-small-cell lung cancer and additional tumor indications. Based in the US, he will oversee both EU and US operations."

Commercial • New P2b trial • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor

CatalYm Highlights Visugromab’s Potential to Treat Cachexia in Cancer Patients at International SCWD Conference (Businesswire) - P1/2a | N=274 | GDFATHER (NCT04725474) | Sponsor: CatalYm GmbH | "Preclinical and clinical data from the CatalYm’s ongoing GDFATHER Phase 1/2a study (GDF-15 Antibody-mediaTed Human Effector T Cell Relocation Phase 1/2a Trial; NCT04725474) demonstrate that visugromab, a humanized monoclonal antibody targeting GDF-15, can significantly counteract the effects of cachexia. By neutralizing GDF-15, visugromab inhibits the activation of the GFRAL pathway in the brainstem, a key driver of weight loss and appetite suppression in cancer patients...A distinct subgroup of patients in the GDFATHER Phase 1/2a trial that entered the trial with manifest cachexia and elevated GDF-15 levels experienced meaningful weight gain during combination treatment of visugromab and nivolumab...In xenograft mouse models with GDF-15 overexpression, visugromab effectively inhibited the GFRAL/Erk1/2 pathway, reversing weight loss and restoring normal food intake."

P1/2 data • Preclinical • Cachexia • Solid Tumor

Neutralizing GDF-15 can overcome anti-PD-1 and anti-PD-L1 resistance in solid tumours. (PubMed, Nature) - P1/2 | "In a first-in-human phase 1-2a study (GDFATHER-1/2a trial, NCT04725474 ), patients with advanced cancers refractory to anti-PD-1 or anti-PD-L1 therapy (termed generally as anti-PD-1/PD-L1 refractoriness) were treated with the neutralizing anti-GDF-15 antibody visugromab (CTL-002) in combination with the anti-PD-1 antibody nivolumab. Increased levels of tumour infiltration, proliferation, interferon-γ-related signalling and granzyme B expression by cytotoxic T cells were observed in response to treatment. Neutralizing GDF-15 holds promise in overcoming resistance to immune checkpoint inhibition in cancer."

IO biomarker • Journal • Genito-urinary Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • GDF15 • GZMB • IFNG

CatalYm’s Visugromab Phase 1/2a Data Demonstrating Clinical Proof-of-Concept for Reversing Resistance to Checkpoint Inhibitors through GDF-15 Neutralization Published in Nature (Businesswire) - P1/2a | N=274 | GDFATHER (NCT04725474) | Sponsor:CatalYm GmbH | "The matured results from the Phase 2a indication-specific cohorts for NSCLC, UC, and all HCC so far treated show the following Objective Response Rates (ORR) based on strict RECIST 1.1 criteria: non-squamous NSCLC: ORR of 19.0% (4/21), with 2 partial responses (PR) and 2 complete responses (CR); UC: ORR of 18.5% (5/27), with 4 PR and 1 CR; HCC: interim ORR of 20.0% (4/20), with 3 PR and 1 CR...More than half of all responders in the NSCLC and UC cohorts of the trial experienced a response depth on study treatment as per RECIST 1.1 criteria that had not been reached on their prior anti-PD1/PD-L1 treatment that was mostly administered as first-line treatment and in combination with chemotherapy....In a subgroup of patients that had combined manifest cachexia, a similar effect on weight gain was observed as demonstrated for another GDF-15 inhibitor in a recent cachexia trial."

P1/2 data • Cachexia • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Urothelial Cancer

GDFather-NEO: Neoadjuvant Immunotherapy Combined With the Anti-GDF-15 Antibody Visugromab to Treat Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: CatalYm GmbH | Trial completion date: Aug 2025 ➔ Apr 2026 | Trial primary completion date: Aug 2024 ➔ Apr 2025

Combination therapy • Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

The impact of the expression level of growth differentiation factor 15 in tumor tissue on the response to immunotherapy in non-small cell lung cancer. (PubMed, BMC Cancer) - "Elevated GDF-15 expression in NSCLC tumor tissues is associated with poorer response to nivolumab, suggesting that GDF-15 is a potential prognostic biomarker for immunotherapy efficacy. These findings warrant further validation through prospective studies to optimize treatment strategies for NSCLC patients."

Biomarker • IO biomarker • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • GDF15 • TGFB1

First-in-Human Study of the GDF-15 Neutralizing Antibody Visugromab (CTL-002) in Patients With Advanced Cancer (GDFATHER) (clinicaltrials.gov) - P1/2 | N=274 | Active, not recruiting | Sponsor: CatalYm GmbH | Recruiting ➔ Active, not recruiting

Checkpoint inhibition • Combination therapy • Enrollment closed • Metastases • Monotherapy • Oncology • Solid Tumor

CatalYm Announces New Financing of $150M to Support Broad Phase 2b Development Program for Visugromab (Businesswire) - "CatalYm today announced the completion of a $150 million Series D financing. The oversubscribed round was led by new investors, Canaan Partners and Bioqube Ventures, and joined by Forbion's Growth Opportunities Fund ('Forbion Growth'), Omega Funds and Gilde Healthcare. Existing investors Jeito Capital, Brandon Capital Partners, Novartis Venture Fund and Vesalius Biocapital III also participated in the round. The proceeds will fund the expansion of the company’s broad Phase 2b development of visugromab into randomized Phase 2b studies in select checkpoint naïve frontline and second-line treatment settings."

Financing • Bladder Cancer • Solid Tumor

Effects of neutralization of tumor-derived immunosuppressant GDF-15 on anti-PD-1 activity in anti-PD-(L)1 relapsed/refractory non-squamous NSCLC, urothelial, and hepatocellular cancer. (ASCO 2024) - P1/2 | "In the GDFather ph2a first-in-human visugromab trial, subjects with advanced-stage, anti-PD1/PD-L1 relapsed/refractory (r/r) last-line solid tumors received the GDF-15 neutralizing antibody visugromab (CTL-002) at 10 mg/kg Q2W in combination with nivolumab 240 mg Q2W om three defined expansion cohorts (NSCLC:n=5 2, UC :n=34, HCC: n=16). These analyses presented identify GDF-15 as novel, potent immunosuppressant in the tumor microenvironment of non-sq NSCLC, UC and HCC and identify it as potential key cause for CPI resistance. In heavily pretreated, by strict criteria anti-PD-1/-L1 r/r, late/last-line patients with NSCLC, UC and HCC, neutralization of GDF-15 by visugromab in combination with nivolumab resulted in an ORR of 16.1% (14/87; 11 PR and 3 CR) across these indications and long durability."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • GDF15 • PTPRC

CatalYm Reports Impressive and Lasting Responses Including Multiple Complete Responses in Heavily Pretreated, Late- to Last-Line Metastatic NSCLC, Urothelial and Hepatocellular Cancer Patients Treated with Visugromab/Nivolumab Combination (Businesswire) - P1/2a | N=274 | GDFATHER (NCT04725474) | Sponsor: CatalYm GmbH | "Featuring matured data from the non-small cell lung cancer (NSCLC) and urothelial cancer (UC) cohorts, as well as novel, early data for the hepatocellular carcinoma (HCC) cohort and an additional biomarker cohort, the presentation highlighted that treatment with a combination of CatalYm’s lead candidate, visugromab, combined with the anti-PD-1 antibody nivolumab achieves compelling deep and durable anti-tumoral activity in anti-PD-1/PD-L1 relapsed/refractory patients as defined by strict criteria. The combination of visugromab and nivolumab further demonstrates an excellent safety and tolerability profile. Visugromab is a monoclonal antibody designed to neutralize the tumor-produced Growth Differentiation Factor-15 (GDF-15), a central mediator of immune resistance to cancer therapies."

P1/2 data • Bladder Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer

CatalYm to Present Positive New Phase 2a Follow-up Data on GDF-15 Neutralizing Antibody Visugromab in Advanced NSCLC, Urothelial, and Hepatocellular Cancer at the 2024 ASCO Annual Meeting (Businesswire) - "CatalYm today announced that positive new follow-up results from its ongoing 'GDFATHER' Phase 1/2a trial (GDF-15 Antibody-mediaTed Human Effector Cell Relocation Phase 1/2a) will be featured in an oral presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024 in Chicago...The trial is evaluating CatalYm’s lead GDF-15 neutralizing antibody, visugromab, in combination with immune checkpoint inhibitor nivolumab in late- to last-line, anti-PD-1/PD-L1 relapsed/refractory patients....Now matured data for NSCLC, UC and novel data for hepatocellular cancer (HCC) will be presented."

P2a data • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer

Targeted disruption of tumor-borne GDF-15-mediated immunoresistance restores immune checkpoint inhibitor activity in last-line cancer patients (ITOC 2024) - P1/2 | "In addition, a clean safety profile and substantial durability of response (DoR) in last-line was observed with still maturing mean DoR surpassing 11.5 months (non-sq NSCLC) and 10.4 months (UC). Conclusions In summary, visugromab demonstrates potent and durable clinical efficacy as well as excellent tolerability in combination with nivolumab supporting further clinical development."

Checkpoint inhibition • Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD80 • CD86 • GDF15 • ICAM1 • IFNG • TGFB1

Neutralizing GDF-15 in muscle-invasive bladder cancer (MIBC): A neoadjuvant immunotherapy trial of visugromab (CTL-002) in combination with the anti-PD1 antibody nivolumab (GDFather-Neo). (ASCO-GU 2024) - "* Melero et al., #2501 ASCO Annual Meeting 2023 Oral Abstract Session. Clinical trial information: Not yet available."

Clinical • Combination therapy • IO biomarker • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • GDF15 • PD-L1

CatalYm Presents Positive Phase 2a Outcome for Visugromab in Advanced NSCLC and Urothelial Cancer at the ESMO Immuno-Oncology Congress 2023 (Businesswire) - P1/2a | N=274 | GDFATHER-2 (NCT04725474) | Sponsor: CatalYm GmbH | "CatalYm announced that maturing Phase 2a results from its ongoing GDFATHER-2 trial...were presented today in an oral presentation at the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2023....The matured results from the NSCLC and UC Phase 2a cohorts included a total of 27 patients in each indication. The Objective Response Rate (ORR) as per RECIST criteria in both the NSCLC and the UC cohorts was 14.8% (4/27, respectively), and 21.1% (4/19) in non-squamous NSCLC. The mean Duration of Response (DoR) has surpassed 11 months in non-NSCLC and 10 months in UC and is further expanding with 6/8 subjects in response continuing on study treatment....CatalYm plans to launch randomized, controlled studies in several major cancer indications in combination with checkpoint inhibitors and standard-of-care in early lines of treatment in the first half of 2024."

New trial • P2a data • Non Small Cell Lung Cancer • Urothelial Cancer

Definitive results for NSCLC and Bladder cancer cohorts in the phase 2a trial of visugromab (CTL-002) in advanced/metastatic anti-PD/PD-L1 relapsed/refractory solid tumors (GDFATHER-trial) (ESMO-IO 2023) - P1/2 | "Here we report definitive results for NSCLC and bladder cancer cohorts of the phase 1/2a trial of the GDF-15 neutralizing antibody visugromab (CTL-002) in combination with nivolumab for treatment of patients that were relapsed/refractory to anti-PD1/-PD-L1 therapy and had exhausted standard-of-care. Confirmed partial and complete responses with significant durability up to and beyond 1 year were observed. Biomarker analyses suggest that visugromab can reinvigorate, enhance and deepen response to checkpoint inhibitors mainly in PD-L1+ patients even after documented prior progression on a seamlessly administered checkpoint inhibitor, being relapsed/refractory to it."

IO biomarker • Metastases • P2a data • Bladder Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • GDF15

GDF-15 neutralizing antibody visugromab increases intratumoral immune cell infiltration to support bispecific T-cell engagers (SITC 2023) - P1/2 | "2 3 Neutralization by clinical stage GDF-15 neutralizing antibody visugromab (CTL-002; GDFather-1/2 trial NCT04725474) restores responsiveness to anti-P(L)1 by increasing extravasation of immune cells into the tumor microenvironment. In a PD study combining tebentafusp with anti-GDF-15 antibody visugromab significantly increased the number of intratumoral T cells in mice. Increasing the number of effector cells in the tumor microenvironment is expected to have a direct positive impact on the anti-tumor activity of different bispecific T-cell engaging treatments."

Immune cell • Melanoma • Oncology • Solid Tumor • GDF15 • ICAM1 • TGFB1

SHP-1 is a central mediator of GDF-15 mediated adhesion inhibition in T-cells (SITC 2023) - P1/2 | "4 This supports neutralization of GDF-15 as a promising new approach to enhance intratumoral T-cell infiltration and to increase antitumoral immune responses. 1 A clinical Ph1/2a study with our GDF-15 neutralizing antibody visugromab in combination with nivolumab is currently ongoing [GDFather-1/2 trial; NCT04725474, abstract 2122]."

Oncology • CXCL12 • CXCL9 • GDF15 • TGFB1 • ZAP70

CatalYm Presents Data at SITC 2023 Annual Meeting Further Unraveling GDF-15-mediated Inhibition of T Cell Adhesion and a New Combination Approach for Visugromab with Bispecific T-Cell Engagers (Businesswire) - "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....Preclinical data identify SHP-1 as a downstream effector of GDF-15-mediated inhibition of T cell adhesion, further elucidating mechanistic details of GDF-15’s role in immunotherapy resistance. Combination of visugromab and bispecific T-cell engager significantly increased the number of intratumoral T cells in a mouse tumor model, providing a strong rationale to further investigate this combination approach."

Preclinical • Oncology

Immuno-suppressive role of tumour-derived GDF-15 on myeloid cells (ESMO 2023) - P1/2 | "By inducing a more pro-inflammatory tumor phenotype, anti-GDF-15 antibodies may synergize with other immunotherapeutic agents. A clinical phase 2 trial combining anti-GDF-15 (CTL-002) with anti-PD-1 (NCT04725474) is ongoing."

IO biomarker • Oncology • Solid Tumor • CD80 • CD86 • GDF15 • IFNG • IL13 • IL4 • TGFB1

CatalYm commences Dosing in a Phase 2 Study with Visugromab in Combination with Neoadjuvant Immunotherapy in Treatment-naive Muscle Invasive Bladder Cancer Patients (Businesswire) - "CatalYm 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."

Trial status • Bladder Cancer