visugromab (CTL-002) / CatalYm - LARVOL DELTA

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

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

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

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 (NEO-GDFATHER). (ASCO-GU 2023) - "Translational research includes evaluation of immunologic parameters in the tumor, other immune-correlates and molecular profiles, as well as evaluation of treatment-emergent cytokine and chemokine profiles in peripheral blood. * Melero et al., Annals of Oncology (2022) 33 (suppl_7): S331-S355."

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

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

Initial results from the phase 2A trial of visugromab (CTL-002) + nivolumab in advanced/metastatic anti-PD1/-L1 relapsed/refractory solid tumors (The GDFATHER-TRIAL). (ASCO 2023) - P1/2 | "These initial phase 2a results demonstrate promising clinical activity for the combination of visugromab and nivolumab in heavily pretreated anti-PD1/-PD-L1 refractory/relapsed solid tumor patients across various indications, including induction of confirmed partial and complete responses. Extensive biomarker evaluations are ongoing to further evaluate potential response-predictive markers identified during phase 1 development. Clinical trial information: NCT04725474."

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

GDFATHER-01: First-in-Human Study of the GDF-15 Neutralizing Antibody Visugromab (CTL-002) in Patients With Advanced Cancer (GDFATHER) (clinicaltrials.gov) - P1/2 | N=263 | Active, not recruiting | Sponsor: CatalYm GmbH | Trial completion date: Oct 2027 ➔ Apr 2030 | Trial primary completion date: Oct 2025 ➔ Apr 2028

Checkpoint inhibition • First-in-human • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

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

Enrollment open • Cachexia • Oncology

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

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

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