On March 5, 2021 BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical need, reported the first patient dosed in an international Phase Ib trial investigating its first-in-class fully humanised anti-AXL monoclonal antibody, tilvestamab (BGB149) (Press release, BerGenBio, MAR 5, 2021, View Source [SID1234578613]).
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The objective of the study is to confirm safety, tolerability and determine a recommended phase II dose (RP2D) for use in subsequent clinical trials. It is a multiple ascending dose study, that will focus on establishing tilvestamab’s
safety profile, tolerability and provide an insight into the dose proportional response with respect to its effectiveness at modulating AXL expression, as determined by BerGenBio’s proprietary cAXL biomarker diagnostic assay.
The study will be conducted in patients with platinum resistant high-grade serous ovarian cancer, in which AXL is frequently strongly over expressed. The research will be conducted at specialist ovarian cancer centres able to perform serial biopsies in these patients, and thereby providing a comprehensive understanding of how tilvestamab modulates AXL expression in real time during a treatment period.
Richard Godfrey, Chief Executive Officer of BerGenBio, said: "We understand that AXL plays an important role in mediating the aggressive nature of this treatment resistant cancer. From our Phase Ia study with tilvestamab that was completed last year, we have an insight into its safety profile, and a safe starting dose for this first-in-patient study. I am particularly excited that we are able to conduct this state-of-the-art study collecting serial biopsies from patients with a similar disease, which will provide high quality data on how tilvestamab modulates AXL expression. This will inform how we can best use tilvestamab in a future Phase II program.
About AXL
AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms underlying life-threatening diseases.
In COVID-19, AXL has two synergistic mechanisms of action, it acts a co-receptor to ACE2, to which the spike protein of the Sars-Cov-2 virus attaches and enters the host cell, and AXL expression is upregulated that leads to suppression of the Type 1 Interferon immune response by host cells and in their environment. Research data confirms bemcentinib inhibits SARS-CoV-2 host cell entry and promotes the anti-viral Type I interferon response.
In cancer, increase in AXL expression has been linked to key mechanisms of drug resistance and immune escape by tumour cells, leading to aggressive metastatic cancers. AXL suppresses the body’s immune response to tumours and drives treatment failure across many cancers. High AXL expression defines a very poor prognosis subgroup in most cancers. AXL inhibitors, such as bemcentinib, therefore, have potential high value as monotherapy and as the cornerstone of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities. Research has also shown that AXL mediates other aggressive diseases including fibrosis.
About Bemcentinib
Bemcentinib (formerly known as BGB324), is a potential first-in-class, potent and highly selective AXL inhibitor, currently in a broad phase II clinical development programme. It is administered as an oral capsule and taken once per day. Ongoing clinical trials are investigating bemcentinib in COVID-19, and multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent. Bemcentinib targets and binds to the intracellular catalytic kinase domain of AXL receptor tyrosine kinase and inhibits its activity.