Bemcentinib is a first-in-class, selective, oral once-a-day inhibitor of AXL receptor tyrosine kinase (AXL) a promising therapeutic target for serious diseases. In cancer, recent studies have revealed a central role of AXL signaling in tumor proliferation, survival, metastasis, and resistance to therapy. AXL is also known to play an important role in transporting viruses into cells and once in the cell, AXL signaling promotes the engulfment of the virus increasing infectivity. BerGenBio is pursuing clinical development alone and in collaboration in the following indications: in Non-Small Cell Lung Cancer (NSCLC), hospitalized COVID-19 patients.
Clinical Development in NSCLC
AXL expression has been established as a negative prognostic factor in a large variety of cancers, with particularly compelling evidence in NSCLC. BerGen Bio is studying bemcentinib in combination with the current standard of care treatments in two key clinical settings:
1. NSCLC patients with a mutation in the STK11 gene
Certain genes when mutated can cause rapid tumor cell growth and/or resistance to therapy. Mutations to the STK11 gene occur in approximately 20% of NSCLC patients and have been shown in preclinical models to confer significant resistance to commonly employed immune checkpoint inhibitor treatments. Preclinical data and preliminary clinical indicate that bemcentinib when combined with an anti-PD1 antibody therapy may reinvigorate the ability of patients who harbor the STK11 mutation to generate tumor killing T-cells, potentially improving response to treatment in this large, underserved population.
2. 2nd Line NSCLC
In collaboration with Merck & Co, BerGen Bio is conducting an ongoing Phase 2 study in recurrent NSCLC to study bemcentinib in combination with Keytruda®, the leading immune checkpoint inhibitor (ICI) therapy in NSCLC. The study includes patients who have relapsed following prior ICI &/or chemotherapy treatment. ClinicalTrials.gov Identifier: NCT03184571
Clinical Development in Adult Myeloid Leukemia (AML)
Expression of AXL (the target of bemcentinib) is an adverse prognostic factor in AML. Patients with AXL overexpression have been shown to have worse progression-free survival and poor overall survival. AXL signaling within the cell is associated with immune suppression and resistance to cancer therapies. BerGen Bio is conducting an ongoing Phase 2 study in resistant and refractory AML patients in combination with chemotherapy. ClinicalTrials.gov Identifier: NCT02488408
Non-Small Cell Lung Cancer
Lung cancer is the most prevalent cancer across the world with over 230,000 newly diagnosed cases expected in 2021. Of these, over 80% lung cancers are of NSCLC histology. NSCLC is a severe disease with a 5-year survival for newly diagnosed patients of just 25% (Source: SEER).
Although the use of targeted treatments and immune checkpoint inhibitors (ICI) to treat NSCLC have led to improved patient outcomes and survival beyond what can be obtained with traditional chemotherapy alone, a significant percentage of patients still do not respond to treatment or quickly relapse. BerGen Bio is exploring two different clinical settings for bemcentinib to improve the response to ICI treatment – NSCLC patients with STK11 mutations and 2nd Line (recurrent) NSCLC. This approach allows BerGen Bio to study two important, underserved patient populations with the goal of improving response rates and overall survival.
COVID-19
COVID-19 is the clinical disease manifested as a result of SARS-CoV-2 coronavirus infection which is responsible for the ongoing COVID-19 pandemic. Despite the approval of several therapies directed towards COVID-19, hospitalized patients still face the risk of severe disease (requiring intubation or resulting in death). Preclinical and early clinical data suggest that bemcentinib is potentially useful for the treatment of SARS-CoV-2 infection.
Adult Leukemia (AML)
AML is the most common type of acute leukemias in adults. It is characterized by a rapid proliferation of immature white cells in the bone marrow. This results in an accumulation and subsequent interference with the normal blood cell production, thus leading to complications such as anaemia, infections, and bleeding. AML is diagnosed in over 20,000 patients in the US annually and is rapidly lethal if left untreated. Successful treatment typically requires intensive chemotherapy with or without bone marrow transplantation, however, relapse and resistance are common and frequently difficult to manage. Consequently, there is an urgent need for effective novel therapies in relapsed/refractory patients, and more so in patients who are not eligible for intensive therapy or bone marrow transplant.
