tilvestamab (BGB149) / BerGenBio - LARVOL DELTA

Revealing the mechanism of Tilvestamab in treating cancer from a single-molecule perspective using atomic force microscopy. (PubMed, Anal Chim Acta) - "Our study reveals that tilvestamab's anti-cancer efficacy arises from superior kinetic stability in AXL binding and direct modulation of cellular biomechanics. By enhancing membrane rigidity, tilvestamab impairs cancer cell migration and proliferation-key drivers of metastasis. These findings provide the biomechanical rationale for tilvestamab's therapeutic activity, positioning it as a promising agent for targeting AXL-dependent cancers through mechanopharmacological mechanisms."

Journal • Lung Cancer • Oncology • Solid Tumor • GAS6

Paratope mapping of tilvestamab, an anti-AXL function-blocking antibody, using high-throughput bacterial expression of secreted scFv-ompY fusion proteins. (PubMed, Biosci Rep) - "Glu2 near the N terminus of AXL is essential for binding. The data give a structural view into the AXL-tilvestamab complex and allow for further optimisation of the binding interface."

Journal • Oncology • AXL

A phase 1b, multicentre, dose escalation, safety and pharmacokinetics study of tilvestamab (BGB149) in relapsed, platinum-resistant, high-grade serous ovarian cancer (PROC) patients (Nature) - P1 | N=16 | NCT04893551 | Sponsor: BerGenBio ASA | "Patients received tilvestamab in three dose levels (1 mg/kg, 3 mg/kg and 5 mg/kg) via IV infusion every 2 weeks...Median treatment duration was 6.1 weeks. Grade 3 or higher treatment-emergent adverse events occurred in 62.5% patients, but none were tilvestamab-related. Common events included fatigue (38%), anorexia (38%) infections (31%), anaemia (25%) and dyspnoea (25%). No objective responses were observed, but 7 (44%) had stable disease at 6 weeks. PK showed dose-proportional exposure and steady-state by the second dose. Pharmacodynamic analyses revealed reduced fibrosis-related gene signatures and AXL protein expression. Epithelial-mesenchymal transition reversal was seen in 2 patients."

P1 data • Platinum resistant • Ovarian Cancer

PHASE I TRIAL OF TILVESTAMAB, A FUNCTION-BLOCKING ANTIBODY INHIBITING AXL, IN PLATINUM-RESISTANT/REFRACTORY HIGH GRADE SEROUS OVARIAN CANCER (PROC). (IGCS 2023) - "Of sixteen pts enrolled, 10 had tumors of Mesenchymal subtype pretreatment. Mean (SD) duration on therapy was 10.5 (±6.3) weeks. No adverse clinical or laboratory signals were noted; tilvestamab exhibited dose-proportional PK."

P1 data • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Refractory Ovarian Cancer • Solid Tumor • MUC16 • PROC

BGB149-102: A Study of Tilvestamab (BGB149) in Relapsed, Platinum-resistant, High-grade Serous Ovarian Cancer (HGSOC) Participants (clinicaltrials.gov) - P1b | N=16 | Terminated | Sponsor: BerGenBio ASA | N=24 ➔ 16 | Trial completion date: Dec 2023 ➔ Jun 2022 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2023 ➔ Jun 2022; After completion of all planned dose levels in the dose escalation phase, the sponsor decision was not to continue with expanding the cohorts of any of the dose levels, using the existing study design.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

AXL targeting by a specific small molecule or monoclonal antibody inhibits renal cell carcinoma progression in an orthotopic mice model. (PubMed, Physiol Rep) - "Remarkably, their in vivo antitumor effectiveness was not significantly enhanced by concomitant administration of a multi-target tyrosine kinase inhibitor. Bemcentinib and tilvestamab qualify as compounds of potentially high clinical interest in AXL overexpressing RCC."

Journal • Preclinical • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • AXL • GAS6 • VIM

PRECLINICAL BEMCENTINIB AND TILVESTAMAB DATA PRESENTED AT EAU 2021 (Cision) - “BerGenBio…announces that preclinical data from a study investigating the anti-tumor efficacy of BerGenBio’s AXL-inhibitors bemcentinib and tilvestamab in renal cell carcinoma (RCC) was presented at the European Association of Urology 2021 virtual congress. Data from the study, conducted by researchers at the University of Bergen, Department of Clinical Medicine, showed that both bemcentinib and tilvestamab prevented Gas6-induced AXL phosphorylation in vitro and effectively prevented tumour growth in an orthotopic RCC xenograft model in vivo.”

Preclinical • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma

"PRECLINICAL BEMCENTINIB AND TILVESTAMAB DATA PRESENTED AT EAU 2021 https://t.co/CSwOQdPuUD" (@CisionNews)

Preclinical

[VIRTUAL] TILVESTAMAB, A FUNCTION-BLOCKING MONOCLONAL ANTIBODY INHIBITOR OF AXL RTK SIGNALLING, LIMITS THE ONSET OF RENAL FIBROTIC CHANGES IN HUMAN KIDNEYS EX VIVO (ERA-EDTA 2021) - "When combined with the lower of two doses of the ACE inhibitor enalapril, the lowest dose of tilvestamab synergized to reduce αSMA levels further as well as reducing secreted Collagen 1a1. AXL expression is induced in key cell populations during development of kidney fibrosis supporting AXL as a novel target in CKD. Tilvestamab represents a promising strategy for the pharmacologic intervention of kidney fibrosis, and the potential synergy with current reno-protective therapies warrants further exploration."

Preclinical • Chronic Kidney Disease • Diabetes • Fibrosis • Hypertension • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • AXL • COL1A1 • GAS6 • VIM

A Study of Tilvestamab (BGB149) in Relapsed, Platinum-resistant, High-grade Serous Ovarian Cancer (HGSOC) Participants (clinicaltrials.gov) - P1b; N=24; Recruiting; Sponsor: BerGenBio ASA

Clinical • New P1 trial • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor

BERGENBIO ANNOUNCES START OF PHASE 1B TRIAL OF ANTI-AXL ANTIBODY TILVESTAMAB (BGB149) (Cision) - “BerGenBio…announces the first patient dosed in an international Phase Ib trial investigating its first-in-class fully humanised anti-AXL monoclonal antibody, tilvestamab (BGB149). The objective of the study is to confirm safety, tolerability and determine a recommended phase II dose (RP2D) for use in subsequent clinical trials.”

Trial status • Gynecologic Cancers • Oncology • Ovarian Cancer