Overall response rate of 40% with the bemcentinib/KEYTRUDA combination observed in AXL-positive, previously treated NSCLC patients, including PD-L1 negative patients who are not expected to benefit from KEYTRUDA monotherapy
Median PFS of patients receiving the bemcentinib/TARCEVA combination in first line has surpassed that of TARCEVA monotherapy
Encouraging efficacy reported for bemcentinib in combination with docetaxel chemotherapy in patients who had exhausted all available therapy options including anti-PD-(L)1
Phase II trial design revealed combining bemcentinib and KEYTRUDA in previously treated malignant mesothelioma, funded by the British Lung Foundation with support from Merck Sharp and Dohme Limited and BerGenBio ASA
Data presented at the 19th Annual World Conference on Lung Cancer
Bergen, Norway, 25 September 2018: BerGenBio ASA (OSE:BGBIO) presented clinical data from its phase II programme with bemcentinib, a first-in-class highly selective oral AXL inhibitor, in non-small cell lung cancer (NSCLC) at the 19thWorld Conference on Lung Cancer (WCLC) in Toronto, Canada (23-26 September 2018).
Richard Godfrey, CEO of BerGenBio, commented: "We are extremely encouraged by the data presented at WCLC today. The expanded results from our study combining bemcentinib with the blockbuster immunotherapy KEYTRUDA were particularly promising. In this study, we saw increased response rates in tumours that were positive for AXL versus those that were not. Importantly, we also saw positive responses in tumours that had low or no PD-L1 expression, where we would expect to see little or no effect from KEYTRUDA therapy alone. We are now advancing this study into the second expansion stage.
"Lung cancer remains the largest cancer killer and, despite recent advances with immune-, targeted and combination therapies, many patients are still not benefitting from these treatments. By selectively inhibiting AXL activity with bemcentinib, we aim to block a fundamental survival mechanism that enables cancer cells to evade the immune system and become resistant to therapy. We believe that this approach has the potential to improve patient outcomes to treatment with established and emerging therapies. The encouraging clinical data presented at WCLC investigating bemcentinib with the three major treatment approaches in advanced lung cancer strengthens our belief in bemcentinib and we look forward to providing further updates at leading medical conferences."
The posters presented at WCLC are available on the BerGenBio website in the Investors / Presentations section (https://www.bergenbio.com/investors/presentations/) and a summary of key findings is provided below.
Ph II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Pembrolizumab in Patients with Advanced NSCLC(BerGenBio study reference: BGBC008), James Lorens et al
The BGBC008 study is investigating whether adding bemcentinib to KEYTRUDA (pembrolizumab) in previously treated, PD-L1 unselected and immunotherapy naïve patients with advanced adenocarcinoma of the lung is well tolerated and improves patient outcomes. The study will also assess the combination in the subset of PD-L1 negative patients for whom KEYTRUDA is not indicated. A total of 48 patients across two stages will be enrolled.

• The first stage is fully enrolled with 24 patients, of which 7 remain on treatment or in follow-up 
• The biomarker analysis revealed that: 
• 10 of 21 evaluable patients were AXL positive (48%)
• Of 20 patients evaluated for PD-L1 expression, 11 (55%) were PD-L1 negative, 7 (35%) were weakly positive and 2 (10%) were strongly positive 
• 40% overall response rate (ORR) was reported in AXL-positive patients with a disease control rate (DCR) of 70%
• 7 of 10 patients with no PD-L1 expression showed clinical benefit, of which there were 3 PRs (ORR 30%) and 4 SD (DCR 70%). This compares with an ORR of 9% in the Keynote-001 study of KEYTRUDA monotherapy in PD-L1 negative patients

+————————————+——+——+——+——-+——-+
| |PR (n)|SD (n)|PD (n)|ORR (%)|DCR (%)|
+————————————+——+——+——+——-+——-+
|Intention-to-treat population (n=24)| 5 | 8 | 10 | 21 | 54 |
+————————————+——+——+——+——-+——-+
|AXL positive patients (n=10) | 4 | 3 | 3 | 40 | 70 |
+————————————+——+——+——+——-+——-+
|AXL negative patients (n=11) | 1 | 4 | 5 | 9 | 45 |
+————————————+——+——+——+——-+——-+

PR: partial response, SD: stable disease, PD: progressive disease.

Ph I/II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Erlotinib in Patients with EGFRm NSCLC (BerGenBio study reference: BGBC004), Lauren Byers et al

TARCEVA (erlotinib) is indicated for NSCLC that is driven by a mutation in the EGFR gene, the most common mutation in NSCLC. Although response rates to TARCEVA are high initially, nearly all patients develop resistance over time. The BGBC004 study is designed to test if adding bemcentinib to TARCEVA in first- or second-line EGFR mutation-driven NSCLC may prevent or reverse acquired resistance to TARCEVA, respectively. 

• Patient recruitment into BGBC004 is complete, with 39 patients enrolled across three arms
• Arm A – a safety cohort – confirmed a bemcentinib phase II dose (200mg daily) that was well tolerated in combination with full dose TARCEVA over extended periods of time (over two years and ongoing)
• Arm B is designed to test whether the addition of bemcentinib to TARCEVA in second line may reverse disease progression in patients whose cancer has become resistant to erlotinib treatment. Arm B met its first primary endpoint, with tumour shrinkage and objective response observed in patients who were negative for the T790M resistance mutation and thus not eligible for any approved targeted therapy (ORR of 20% and a DCR of 40% including 1 PR and 1 SD out of five T790M negative patients)
• Arm C is designed to evaluate the ability of bemcentinib to prevent acquired resistance to TARCEVA and improve outcomes in patients who had been responding/stable to first-line TARCEVA therapy. Arm C reported tumour shrinkage in 6 of 9 patients (67%). Importantly, median Progression-Free Survival (PFS), while not mature, had already surpassed median PFS for TARCEVA monotherapy given as a first-line treatment of 10 months.

A Ph I/II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) with Docetaxel in Patients with Previously Treated NSCLC (BerGenBio study reference: BGBIL005), David Gerber et al

Single agent chemotherapy is the last treatment option for NSCLC patients if they fail targeted, immune- and platinum-based chemotherapy regimes. Around 10% of patients show responses to docetaxel single agent chemotherapy with a median PFS of 3-4 months commonly reported. The investigator-sponsored study BGBIL005 is designed to evaluate if combining bemcentinib with docetaxel chemotherapy is safe and can improve outcomes in up to 30 NSCLC patients who have failed up to three lines of therapy. 

• Among 11 patients evaluated, the combination was generally well tolerated and 2 PRs (18%) and 6 SDs (55%) were reported

A Phase II Study of Oral Selective AXL Inhibitor Bemcentinib (BGB324) in Combination with Pembrolizumab in Patients with Malignant Mesothelioma (trial not active yet), Dean Fennell et al

The poster described a proposed design for an investigator-sponsored trial (MiST3) evaluating bemcentinib in combination with KEYTRUDA in patients with relapsed malignant mesothelioma. Mesothelioma is a cancer that develops from the thin layer of tissue that covers many of the internal organs and most commonly affects the lining of the lungs and chest wall. 

– END –

About WCLC

The 19th World Conference on Lung Cancer (WCLC 2018) is the leading meeting on Thoracic Oncology. It is organised by the International Association for the Study of Lung Cancer and will gather more than 7,000 international delegates. WCLC 2018 will take place in Toronto Canada, 23 – 26 September 2018. https://wclc2018.iaslc.org/ 

About the BGBC008 trial

The BGBC008 trial is a phase II multi-centre open-label study of bemcentinib in combination with KEYTRUDA (pembrolizumab) in previously treated, immunotherapy naïve, patients with advanced adenocarcinoma of the lung, the most common form of non-small cell lung cancer (NSCLC). The objective of the trial is to determine the anti-tumour activity of this novel drug combination and responses will be correlated with biomarker status (including AXL kinase and PD-L1 expression).

For more information please access trial NCT03184571 at www.clinicaltrials.gov.

About the BGBC004 trial

The BGBC004 trial is a phase I/II multi-centre open-label study of bemcentinib in combination with TARCEVA (erlotinib) in patients with EGFR mutation driven (EGFRm) Stage IIIb or Stage IV NSCLC. The trial is designed to evaluate reversal of resistance to EGFR targeted therapy in later line patients who are negative for the T790M resistance mutation (arm B) as well as prevention of resistance to TARCEVA in patients receiving the EGFR inhibitor first line (arm C). 

For more information please access trial NCT02424617 at www.clinicaltrials.gov.

About the BGBIL005 trial

The BGBIL005 trial is an investigator-led phase I/II study of bemcentinib in combination with docetaxel chemotherapy in previously treated, relapsed / resistant NSCLC patients.

For more information please access trial NCT02922777 at www.clinicaltrials.gov.

About the MiST3 trial

The MiST3 trial is an investigator-led phase II study of bemcentinib in combination with KEYTRUDA in patients with relapsed mesothelioma. The trial, which is not active as of September 2018, is sponsored by the University of Leicester (Leicester, UK), and funded by the British Lung Foundation with support from Merck Sharp and Dohme Limited and BerGenBio. Up to 25 patients are planned to be enrolled at 3 clinical research sites in the UK.   

For more information please access trial NCT03654833 at www.clinicaltrials.gov 

About BerGenBio ASA  

BerGenBio is a clinical-stage biopharmaceutical company focused on developing transformative drugs targeting AXL as a potential cornerstone of therapy for advanced and aggressive cancers. 

The company’s proprietary lead candidate, bemcentinib, is a potentially first-in-class selective AXL inhibitor in a broad phase II clinical development programme. Ongoing clinical trials are investigating bemcentinib in multiple solid and haematological tumours, in combination with current and emerging therapies (including immunotherapies, targeted therapies and chemotherapy), and as a single agent.

In parallel, BerGenBio is developing companion diagnostics test to identify patient populations most likely to benefit from bemcentinib; this is expected to facilitate more efficient registration trials and support a precision medicine-based commercialisation strategy.

BerGenBio is based in Bergen, Norway with a subsidiary in Oxford, UK. The company is listed on the Oslo Stock Exchange (ticker: BGBIO). www.bergenbio.com

About AXL

AXL kinase is a cell membrane receptor and an essential mediator of the biological mechanisms that drive aggressive and life-threatening diseases. In cancer, AXL drives tumour survival, treatment resistance and spread, as well as suppressing the body’s immune response to tumours. AXL expression has been established as a negative prognostic factor in many cancers. AXL inhibitors, therefore, have potential value at the centre of cancer combination therapy, addressing significant unmet medical needs and multiple high-value market opportunities.

Contacts

Richard Godfrey, CEO, BerGenBio ASA
+47 917 86 304

Rune Skeie, CFO, BerGenBio ASA
rune.skeie@bergenbio.com
+47 917 86 513

Media Relations in Norway
Jan Petter Stiff, Crux Advisers
stiff@crux.no
+47 995 13 891

International Media Relations
David Dible, Mark Swallow, Marine Perrier, Citigate Dewe Rogerson
bergenbio@citigatedewerogerson.com
+44 207 638 9571

Forward looking statements

This announcement may contain forward-looking statements, which as such are not historical facts, but are based upon various assumptions, many of which are based, in turn, upon further assumptions. These assumptions are inherently subject to significant known and unknown risks, uncertainties and other important factors. Such risks, uncertainties, contingencies and other important factors could cause actual events to differ materially from the expectations expressed or implied in this announcement by such forward-looking statements.

This information is subject to the disclosure requirements pursuant to section 5-12 of the Norwegian Securities Trading Act.