ginisortamab (UCB6114) / UCB - LARVOL DELTA

CRUK: Phase II trial of ginisortamab with (1) 1st-line gemcitabine + nab-paclitaxel (AG) or (2) MEK inhibitor as maintenance therapy in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC). (ASCO-GI 2026) - P1/2 | "This study is funded and sponsored by Cancer Research UK in collaboration with UCB. The EU CT Number is 2024-514129-43, and the IRAS Identifier is 1007925."

Clinical • First-in-human • Metastases • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CA 19-9 • SMAD4

A dose-finding population pharmacokinetic/pharmacodynamic model of ginisortamab, an anti-gremlin-1 monoclonal antibody, in patients with solid tumours. (PubMed, Br J Clin Pharmacol) - P1/2 | "This population PK/PD model adequately described ginisortamab PK and binding to serum gremlin-1 in patients with advanced solid tumours. Dose simulations informed the level of gremlin-1 suppression and supported further clinical evaluation of several dosing regimens."

Journal • PK/PD data • Oncology • Solid Tumor

Phase 1 dose-optimization study evaluating the safety of ginisortamab (UCB6114), an anti-gremlin-1 monoclonal antibody (mAb) with first-in-class potential, as monotherapy in advanced solid tumors (AACR 2025) - P1/2 | "ONC001 (NCT04393298) is a first-in-human, nonrandomized, open-label, Phase 1/2 study assessing ginisortamab ± standard of care (SoC) in advanced solid tumors; results from Part A (monotherapy dose-escalation) have been reported previously.1 We present primary (safety), secondary (pharmacokinetics), and exploratory (biomarker, efficacy) endpoints from Part A1 (monotherapy dose-optimization); patients (pts) were aged ≥18 years with advanced disease resistant or refractory to SoC; ginisortamab was administered as 1 of 4 intravenous dose schedules (2000 mg Q2W 30- or 60-min infusion, 4000 mg Q4W 120-min, 28-day cycle; 3000 mg Q3W 90-min 21-day cycle). In total, 32 pts received ≥1 ginisortamab dose (n=8 for each dose schedule); median age 63 (39-82) years, 59% male, median prior anti-cancer therapies 3.5 (1-8); most common tumor type colorectal adenocarcinoma (81%). In total, 32 pts received ≥1 ginisortamab dose (n=8 for each dose schedule); median age 63 (39-82)..."

Clinical • First-in-human • Metastases • Monotherapy • P1 data • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • SMAD1

Antibody-mediated blockade of gremlin-1 in combination with gemcitabine or MEK inhibition in a genetically engineered mouse model of pancreatic cancer. (ASCO-GI 2026) - " We used a genetically engineered mouse model of pancreatic cancer to evaluate the therapeutic effect of antibody-mediated inhibition of gremlin-1 (Ab7326) alone, or in combination with gemcitabine or a MEK 1/2 inhibitor (selumetinib or UCB-554). Blocking gremlin-1 in combination with gemcitabine or MEK inhibition may have benefit in the treatment of pancreatic cancer. Ginisortamab is now in a Phase 2 clinical trial in patients with PDAC."

Combination therapy • Preclinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS • MAP2K1 • PDX1

Phase I/II dose-escalation study evaluating ginisortamab (UCB6114), an anti-gremlin-1 monoclonal antibody (mAb) with first-in-class potential, in combination with 5-fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) in advanced solid tumours (ESMO 2025) - P1/2 | "Median (95% confidence interval) progression-free survival was 4.0 months (1.8, 5.7). Table: 841P n patients (%) [N events] 500 mg + mFOLFOX6 (n=5) 1000 mg + mFOLFOX6 (n=3) 2000 mg + mFOLFOX6 (n=7) Total (N=15) DLT 0 0 0 0 Any TEAE 5 (100) [153] 3 (100) [43] 7 (100) [78] 15 (100) [274] Any serious TEAE 5 (100) [14] 1 (33) [4] 2 (29) [2] 8 (53) [20] TEAE related to ginisortamab regardless of relation to mFOLFOX6 4 (80) [51] 3 (100) [11] 6 (86) [15] 13 (87) [77] Grade ≥3 5 (100) [21] 3 (100) [10] 6 (86) [11] 14 (93) [42] TEAE leading to delay in ginisortamab infusion 2 (40) [3] 0 5 (71) [7] 7 (47) [10] TEAE leading to ginisortamab + mFOLFOX6 discontinuation 1 (20) [1] 1 (33) [1] 1 (14) [1] 3 (20) [3] TEAE leading to study discontinuation 1 (20) [1] 1 (33) [1] 1 (14) [1] 3 (20) [3] TEAE leading to death 0 1 (33) [1] 1 (14) [1] 2 (13) [2] Conclusions Safety, PK and efficacy data in this heavily pre-treated cohort support further studies of ginisortamab 2000 mg iv Q2W..."

Combination therapy • Metastases • P1/2 data • Colorectal Adenocarcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase I/II dose-escalation study evaluating ginisortamab (UCB6114), an anti-gremlin-1 monoclonal antibody (mAb) with first-in-class potential, in combination with trifluridine/tipiracil (TFD/TPI) in advanced solid tumours (ESMO 2025) - P1/2 | "Median (95% confidence interval) progression-free survival was 1.9 months (1.7, 4.0). Table: 838P n patients (%) [N events] 500 mg + TFD/TPI (n=9) 1000 mg + TFD/TPI (n=4) 2000 mg + TFD/TPI (n=8) Total (N=21) DLT 1 (11) [1] 0 1 (13) [1] 2 (10) [2] Any treatment-emergent adverse event (TEAE) 9 (100) [152] 4 (100) [81] 8 (100) [113] 21 (100) [346] Any serious TEAE 4 (44) [8] 2 (50) [2] 4 (50) [7] 10 (48) [17] TEAE related to ginisortamab regardless of relation to TFD/TPI 8 (89) [58] 3 (75) [11] 6 (75) [28] 17 (81) [97] Grade ≥3 5 (56) [23] 3 (75) [10] 7 (88) [21] 15 (71) [54] TEAE leading to delay in ginisortamab infusion 3 (33) [6] 2 (50) [4] 1 (13) [1] 6 (29) [11] TEAE leading to ginisortamab + TFD/TPI discontinuation 2 (22) [5] 0 0 2 (10) [5] TEAE leading to study discontinuation 0 0 0 0 TEAE leading to death 0 0 0 0 Conclusions Safety, PK and efficacy data in this heavily pre-treated cohort support further studies of ginisortamab 2000 mg iv Q2W (or a dosing..."

Combination therapy • Metastases • P1/2 data • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor

ONC001: A Study to Assess the Safety, Pharmacokinetics and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=95 | Completed | Sponsor: UCB Biopharma SRL | Active, not recruiting ➔ Completed

Metastases • Trial completion • Breast Cancer • Colorectal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Discovery of ginisortamab, a potent and novel anti-gremlin-1 antibody in clinical development for the treatment of cancer. (PubMed, MAbs) - P1/2 | "Furthermore, in a human CRC - fibroblast co-culture system where gremlin-1 is produced by the fibroblasts, ginisortamab restored BMP signaling in both the CRC cells and fibroblasts, demonstrating its activity in a relevant human tumor microenvironment model. The safety and efficacy of ginisortamab are currently being evaluated in a Phase 1/2 clinical trial in patients with advanced solid tumors (NCT04393298)."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

ONC001: A Study to Assess the Safety, Pharmacokinetics and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=95 | Active, not recruiting | Sponsor: UCB Biopharma SRL | Recruiting ➔ Active, not recruiting | N=250 ➔ 95 | Trial completion date: Feb 2024 ➔ May 2024 | Trial primary completion date: Feb 2024 ➔ May 2024

Enrollment change • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

ONC001: A Study to Assess the Safety, Pharmacokinetics and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=250 | Recruiting | Sponsor: UCB Biopharma SRL | Trial completion date: Sep 2023 ➔ Feb 2024 | Trial primary completion date: Sep 2023 ➔ Feb 2024

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Phase I dose-escalation study evaluating the safety and tolerability of ginisortamab (UCB6114), a first-in-class anti-gremlin-1 monoclonal antibody (mAb), as monotherapy in advanced solid tumors (AACR 2023) - P1/2 | "Favorable safety and PK/PD data at the maximum dose of 2000 mg and preliminary antitumor activity were observed with the first-in-class anti-gremlin antibody ginisortamab. These data support further evaluation of the efficacy and safety of ginisortamab monotherapy at 2000 mg Q2W, or in combination with standard of care regimens (FOLFOX, trifluridine/tipiracil) in advanced solid tumors."

Clinical • Metastases • Monotherapy • P1 data • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Cancer Research UK reach agreement with UCB (PharmaTimes) - "Cancer Research UK and UCB have announced a clinical development collaboration to advance two of UCB’s investigational oncology antibody candidates through clinical trials. The partnership will concentrate on the development of two investigational antibody candidates – UCB6114 and UCB4594....As part of the collaboration, Cancer Research UK’s Centre for Drug Development will appoint the chief clinical and scientific investigators, and will oversee the design, preparation, sponsorship and delivery of phase 1/2 clinical trials for both candidates."

Licensing / partnership • New P1/2 trial • Oncology

A multi-modular phase I/II study of UCB6114, a first-in-class, fully human IgG4P anti-Gremlin-1 monoclonal antibody, as monotherapy and in combination with mFOLFOX6 or trifluridine/tipiracil, for patients with advanced gastrointestinal (GI) tumors. (ASCO-GI 2022) - P1/2 | "In parts B and C (modified toxicity probability interval design), up to 54 pts with locally advanced or metastatic colorectal, gastric or gastroesophageal junction adenocarcinomas will receive UCB6114 in escalating doses in combination with either mFOLFOX6 (5-fluorouracil, leucovorin and oxaliplatin) or trifluridine/tipiracil, given at SOC dosing and schedules. Enrollment in ONC001 began in July 2020; as of Sept 2021, four dose escalation levels in the monotherapy dose-escalation module (Part A) have been completed without DLT. Recruitment to parts B and C is due to commence in Q4 2021."

Clinical • Combination therapy • Monotherapy • P1/2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

ONC001: A Study to Assess the Safety, Pharmacokinetics and Antitumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=240 | Recruiting | Sponsor: UCB Biopharma SRL | Trial completion date: Jun 2023 ➔ Jan 2024 | Trial primary completion date: Jun 2023 ➔ Jan 2024

Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Binding characteristics and preclinical activity of UCB6114; the first fully human anti-gremlin-1 monoclonal antibody in development for the treatment of cancer (EACR 2022) - P1/2 | "Conclusion UCB6114; the first human, highly selective, IgG4P mAb optimised for activity against human gremlin-1 protein, demonstrated restoration of gremlin-1-ablated BMP signalling. UCB6114 is in a Phase I/II clinical trial in patients with advanced solid tumours (NCT04393298)."

Preclinical • Biliary Cancer • Cervical Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • ID2 • ID3 • TGFB1

A Study to Assess the Safety, Pharmacokinetics and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=222; Recruiting; Sponsor: UCB Biopharma S.P.R.L.; Not yet recruiting ➔ Recruiting; Trial completion date: Feb 2024 ➔ Jun 2023; Trial primary completion date: Feb 2024 ➔ Jun 2023

Clinical • Enrollment open • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

A Study to Assess the Safety, Pharmacokinetics and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=222; Not yet recruiting; Sponsor: UCB Biopharma S.P.R.L.

Clinical • New P1/2 trial • Oncology • Solid Tumor