visugromab (CTL-002) / CatalYm - LARVOL DELTA

Trial Investigating Visugromab and Nivolumab With or Without Docetaxel in 2L Treatment of Participants With Metastatic NSCLC (clinicaltrials.gov) - P2 | N=131 | Recruiting | Sponsor: CatalYm GmbH

New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

CatalYm today announced that the first patient has been dosed in the randomized Phase 2b GDFATHER‑NSCLC‑02 (GDF‑15 Antibody‑MediaTed‑Human‑Effector‑T‑Cell Relocation) trial (NCT07246863) (Businesswire) - "The randomized, multi-arm Phase 2b GDFATHER-NSCLC-02 trial will enroll approximately 131 patients across multiple sites in the US, EU and Switzerland."

Trial status • Non Small Cell Lung Cancer

Decoding GDF15: Impact on prostate cancer metabolism, chemoresistance, and clinical applications. (PubMed, Chin Med J (Engl)) - "Clinically, GDF15 has shown potential as a biomarker, offering diagnostic precision and prognostic value, particularly when combined with established markers such as prostate-specific antigen. The review concludes with a discussion on several monoclonal antibodies targeting GDF15 in clinical trials, such as AV-380, NGM120, Visugromab, and AZD8853, highlighting promising strategies for novel therapies and precision medicine."

Journal • Cachexia • Genito-urinary Cancer • Metabolic Disorders • Oncology • Prostate Cancer • Solid Tumor • GDF15

GDFATHER-01 trial longterm follow-up: GDF-15 neutralization combined with nivolumab can enable deep, longterm remission in heavily pretreated, anti-PD1/-L1 relapsed/refractory major solid tumor types (SITC 2025) - P1/2 | "A blinded copy of the written informed consent is available for review by the Editor of this journal.Abstract 519 Figure 1Request permissionsWaterfall plot: BoR in nsqNSCLC, UC and HCC. BoR as per RECIST 1.1 in 77 advanced/metastatic nsq-NSCLC, UC and HCC patients that had exhausted available treatment options including an approved anti-PD1/PD-L1 treatment and received the experimental anti-GDF-15 antibody visugromab and nivolumab"

Clinical • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • GDF15

GDFATHER-01 trial longterm follow-up: GDF-15 neutralization combined with nivolumab can enable deep, longterm remission in heavily pretreated, anti-PD1/-L1 relapsed/refractory major solid tumor types (SITC 2025) - P1/2 | "A blinded copy of the written informed consent is available for review by the Editor of this journal.Abstract 519 Figure 1Request permissionsWaterfall plot: BoR in nsqNSCLC, UC and HCC. BoR as per RECIST 1.1 in 77 advanced/metastatic nsq-NSCLC, UC and HCC patients that had exhausted available treatment options including an approved anti-PD1/PD-L1 treatment and received the experimental anti-GDF-15 antibody visugromab and nivolumab"

Clinical • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • GDF15

A blinded, exploratory phase II trial of nivolumab and the GDF-15 neutralizing antibody visugromab or placebo as neoadjuvant treatment of patients with muscle-invasive bladder cancer (MIBC): Primary results of the GDFather-NEO trial (ESMO 2025) - P2 | "Conclusions In anti-PD(L)-1-naïve MIBC, GDF-15 blockade by visugromab tripled the effect size of nivolumab in neoadjuvant therapy, with excellent tolerability. N/V combination warrants further investigation in larger neoadjuvant trials with a tumor response-guided bladder preservation approach."

Clinical • Late-breaking abstract • P2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • GDF15

GDFATHERHCC01: Visugromab, Nivolumab and a Tyrosine Kinase Inhibitor (TKI) Compared to Double Placebo and a TKI in Unresectable or Metastatic Hepatocellular Carcinoma Post Anti-PD-(L)1 Failure (clinicaltrials.gov) - P2 | N=104 | Not yet recruiting | Sponsor: CatalYm GmbH

New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor

Long-term follow-up GDFATHER-01 trial: GDF-15 neutralization combined with nivolumab can enable deep, long-term remission in heavily pretreated, anti-PD1/-L1 relapsed/refractory non-squamous non-small cell lung cancer (NSCLC), urothelial cancer (UC) and hepatocellular cancer (HCC) (ESMO 2025) - P1/2 | "Conclusions In 77 heavily pre-treated, by strict criteria anti-PD-1/-L1 relapsed/refractory nsq NSCLC, UC and HCC pts, V+N treatment induced very durable and deep long-term response, with 61.5% (8/13) of responders achieving confirmed CR or CMR. GDF-15 neutralization by V may overcome ICI resistance and enable long-term immunologic tumor control in metastatic nsq NSCLC, UC and HCC."

Clinical • Genito-urinary Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • GDF15

CatalYm…announced updated long-term data from its ongoing GDFATHER-1/2a trial (NCT04725474) at the European Society of Medical Oncology (ESMO) Congress 2025. (Businesswire) - "Confirmed objective response rates (RECIST 1.1) were 18.2% (4/22) in non-squamous NSCLC, 18.5% (5/27) in urothelial cancer, and 14.3% (4/28) in hepatocellular carcinoma, including 5 complete responses and multiple deep partial responses across cohorts...Median duration of response reached 32.2 months in non-squamous NSCLC, 28.8 months in urothelial cancer, and 19.4 months in hepatocellular carcinoma."

P1/2 data • Hepatocellular Cancer • Lung Non-Squamous Non-Small Cell Cancer • Urothelial Cancer

CatalYm Presents Phase 2 Data in Neoadjuvant Bladder Cancer Demonstrating Substantial Increase of Anti-Tumor Activity for Visugromab in Combination with PD-1 Inhibitor at ESMO (Businesswire) - "Visugromab combined with PD-1 inhibitor, nivolumab, more than quadrupled the rate of pathological Complete Response (pCR; 33.3% vs. 7.1%) and substantially increased Major Pathologic Response (MPR; 66.7% vs. 21.4%) rate compared to nivolumab alone Combination achieved a fourfold increase in radiologic Objective Response Rate (rORR) (60% vs. 14.3%)."

P2 data • Bladder Cancer

CatalYm Announces First Patient Dosed in Phase 2b Trial Evaluating Visugromab in Combination with Chemoimmunotherapy as First-Line Treatment in Metastatic Non-squamous NSCLC (Businesswire) - "The randomized, blinded, placebo-controlled Phase 2b GDFATHER-NSCLC-01 (GDF-15 Antibody-mediaTed Human Effector Cell Relocation) trial will enroll approximately 107 patients across multiple sites in the US, EU and Switzerland."

Trial status • Lung Non-Squamous Non-Small Cell Cancer

CatalYm to Present Primary Results From Phase 2 Neoadjuvant Bladder Cancer Trial in Late-breaking Oral Presentation at ESMO (Businesswire) - "A late-breaking abstract featuring first results from the Phase 2 GDFATHER-NEO trial (NCT06059547) was accepted for oral presentation....Second oral presentation will provide updated data from GDFATHER-01 trial demonstrating deep and durable remissions in heavily pretreated patients."

Late-breaking abstract • P2 data • Bladder Cancer • Urothelial Cancer

Characterization of Growth Differentiation Factor 15 (GDF-15) as a therapeutic target in urothelial carcinoma (DGU 2025) - "A clinical study demonstrated that treatment with an anti-GDF-15 antibody (visugromab) in combination with nivolumab can lead to sustained remissions in otherwise ICI-resistant patients with mUC... The therapeutic target GDF-15 is highly expressed, particularly in molecularly luminal UC. Higher expression is associated with an immunosuppressive TME. Investigation of the association between GDF-15 expression and response to ICI therapies is ongoing."

IO biomarker • Oncology • Solid Tumor • Urothelial Cancer • CD8 • GDF15

The Multifaceted Role of Growth Differentiation Factor 15 (GDF15): A Narrative Review from Cancer Cachexia to Target Therapy. (PubMed, Biomedicines) - "Targeting the GDF15-GFRAL axis appears therapeutically promising: the monoclonal antibody ponsegromab improved cachexia-related outcomes in the PROACC-1 trial, while visugromab combined with nivolumab enhanced immune response in ICI-refractory tumors. Further investigation is warranted to delineate the role of GDF15 across malignancies, refine patient selection, and evaluate combinatorial approaches with existing treatments."

IO biomarker • Journal • Review • Cachexia • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • GDF15

Trial Investigating Visugromab in Combination With Immunochemotherapy in 1L Treatment of Participants With Metastatic NSCLC (clinicaltrials.gov) - P2 | N=107 | Not yet recruiting | Sponsor: CatalYm GmbH

New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

GDFATHER-NSCLC-01: Trial Investigating Visugromab in Combination With Immunochemotherapy in 1L Treatment of Participants With Metastatic NSCLC (clinicaltrials.gov) - P2 | N=107 | Recruiting | Sponsor: CatalYm GmbH | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

VINCIT: Visugromab in Cachexia International Trial (clinicaltrials.gov) - P2/3 | N=518 | Not yet recruiting | Sponsor: CatalYm GmbH

New P2/3 trial • Cachexia • Oncology

Meet the Experts (MASCC-ISOO 2025) - "Targeting GDF-15 in Cancer Cachexia: Design for a Pivotal, Adaptive Phase 2/3 Clinical TrialBlocking the GDF-15-GFRAL axis promises a new era in the management of cancer-associated cachexia, with exciting data in animal models and early clinical trials. Join us to explore this breakthrough approach and to hear about a major new registrational clinical trial of the potent anti-GDF-15 monoclonal antibody visugromab."

Cachexia • Oncology • GDF15

VINCIT: a randomized, double-blind, adaptive Phase 2/3 study of visugromab in cancer-associated cachexia, starting in 2025 (MASCC-ISOO 2025) - "Sponsored by CatalYm GmbH."

Clinical • P2/3 data • Cachexia • Oncology

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