BerGenBio

Regulatory Filings • Jan 9, 2018

BerGenBio meets first efficacy endpoint in phase II trial with selective AXL inhibitor BGB324 (bemcentinib) in NSCLC

BerGenBio meets first efficacy endpoint in phase II trial with selective AXL inhibitor BGB324 (bemcentinib) in NSCLC

Trial aims to evaluate the effectiveness of BGB324 (bemcentinib) in preventing

and reversing resistance to targeted therapy

Bergen, Norway, January 9, 2018 - BerGenBio ASA

(OSE:BGBIO) (http://www.bergenbio.com), a clinical-stage biopharmaceutical

company developing novel, selective Axl kinase inhibitors as a potential

cornerstone of combination cancer therapy, announces that the first efficacy

endpoint has been met in its phase II clinical trial evaluating BGB324

(bemcentinib), a selective AXL inhibitor, in combination with erlotinib in

patients with advanced non-small cell lung cancer (NSCLC) who have progressed on

an approved EGFR inhibitor (ClinicalTrials.gov Identifier: NCT02424617).

The trial (known as BGBC004) is designed to test the hypothesis that selective

AXL inhibition with the once-daily oral small molecule bemcentinib may reverse

and prevent resistance to erlotinib, a therapy targeting constitutively active

epidermal growth factor receptor (EGFR) signalling - a pathway frequently

upregulated in cancers, particularly NSCLC. The trial is enrolling patients with

activating EGFR mutations across three settings:

· Arm A is designed to determine the daily dose of bemcentinib that can be

safely administered in combination with erlotinib in patients who have received

prior erlotinib therapy. This arm is completed and a recommended phase II dose

has been established.

· Arm B follows a Simon-like two-stage design evaluating the ability of

bemcentinib to restore sensitivity to EGFR targeted therapy when given in

combination with erlotinib in patients who have progressed on prior therapy with

an approved EGFR inhibitor and that are negative for the T790M mutation. This

arm has successfully completed its first stage (announced today). The initial

endpoints of the first stage of Arm B were exceeded. An overall disease control

rate of 33% was reported in patients who completed at least one cycle of

treatment (n=9) thus providing preliminary proof of concept that bemcentinib can

restore sensitivity to EGFR targeted therapy in some patients.

· Arm C is designed to evaluate the ability of bemcentinib to prevent acquired

resistance to EGFR targeted therapy when given in combination with erlotinib

first line. This arm is recruiting patients with interim results expected mid

-2018.

The Company expects to present clinical data from this study at an international

cancer conference during 2018.

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "Meeting this

initial clinical endpoint in this very challenging patient population, who have

already progressed on prior EGFR targeted therapy and who do not have a T790M

resistance mutation, is an important proof of concept for our hypothesis that

bemcentinib, our selective oral AXL inhibitor, may be effective in restoring

sensitivity to targeted therapy. Two patients in Arm B continue on study and are

experiencing sustained disease control and one patient in Arm A is approaching

their two-year anniversary on bemcentinib in combination with erlotinib and is

asymptomatic. The BGBC004 trial forms an integral part of our strategy to

evaluate bemcentinib as a cornerstone of cancer therapy with targeted-, immune-

and chemotherapy. Bemcentinib is currently being evaluated in two other clinical

trials in NSCLC, in combination with immune- and chemotherapy; the initial

positive chemo combination data were reported in December 2017. Further phase II

combination trials with bemcentinib are ongoing in breast cancer, melanoma and

acute myeloid leukaemia and we look forward to reporting progress across our

broad phase II clinical trial programme at upcoming medical congresses."

About EGFR mutation driven NSCLC and targeted EGFR inhibitors

Lung cancer is the leading cause of cancer death among both men and women and it

is estimated that around 200,000 new cases of non-small cell lung cancer (NSCLC)

will be diagnosed in the US in 2018[1]. 15-20%[2] of NSCLC cases are EGFR mutant

(EGFRm) leading to constitutively active epidermal growth factor receptor (EGFR)

signalling driving the growth of tumour cells. This signalling pathway can be

effectively blocked using targeted EGFR tyrosine kinase inhibitors (EGFR TKIs).

However, virtually all patients ultimately acquire resistance to EGFR TKIs

leading to disease progression: the median progression free survival of patients

receiving first line EGFR inhibitors erlotinib or gefitinib is 10.2 months[3].

Resistance is driven by either the acquisition of additional mutations (e.g. the

EGFR T790M mutation) or - in up to half of the patients - bypass

mechanisms[4],[5],[6]. While third generation EGFR inhibitors targeting the

T790M mutation have shown good results, novel treatments overcoming resistance

in T790M negative patients are urgently needed. Additionally, strategies to

prevent or delay resistance in NSCLC EGFRm patients receiving first line EGFR

inhibitors are a major unmet need.

About the BGBC004 trial

The BGBC004 trial is a phase I/II multi-centre open-label study of BGB324 in

combination with erlotinib in patients with EGFR mutation driven 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 mutation

as well as prevention of resistance in patients receiving the EGFR inhibitor

erlotinib first line. Patients are currently being enrolled at centres across in

the US. For more information please access trial NCT02424617 at

www.clinicaltrials.gov.

About BerGenBio ASA

BerGenBio ASA is a clinical-stage biopharmaceutical company focused on

developing a pipeline of first-in-class Axl kinase inhibitors as a potential

cornerstone of combination cancer therapy. The Company is a world leader in

understanding the essential role of Axl kinase in mediating cancer spread,

immune evasion and drug resistance in multiple aggressive haematological and

solid cancers.

BerGenBio's lead product, BGB324 (bemcentinib), is a unique and highly

selective, potent and orally bio-available small molecule Axl inhibitor,

currently in four Company sponsored phase II clinical trials in major cancer

indications, with read-outs anticipated in the second half of 2018. It is the

only selective oral Axl inhibitor in clinical development.

The Company sponsored clinical trials are:

· BGB324 as a single agent and combination therapy in acute myeloid leukaemia

(AML) / myeloid dysplastic syndrome (MDS)

· BGB324 with TARCEVA® (erlotinib) in advanced EGFR mutation driven non-small

cell lung cancer (NSCLC)

· BGB324 with KEYTRUDA® (pembrolizumab) in advanced adenocarcinoma of the

lung, and

· BGB324 with KEYTRUDA in triple negative breast cancer (TNBC).

The clinical trials combining BGB324 with KEYTRUDA in adenocarcinoma of the lung

and TNBC are conducted in collaboration with Merck & Co. Inc. (MSD), through a

subsidiary.

In addition, a number of investigator-sponsored trials are underway, including a

trial to investigate BGB324 with either MEKINIST® (trametinib) plus TAFINLAR®

(dabrafenib) or KEYTRUDA in advanced melanoma, as well as a trial combining

BGB324 with docetaxel in advanced NSCLC.

BerGenBio is simultaneously developing a companion diagnostic test to identify

patient subpopulations most likely to benefit from treatment with BGB324. This

will facilitate more efficient registration trials and support a precision

medicine based commercialisation strategy.

The Company is also developing a diversified pre-clinical pipeline of drug

candidates, including BGB149, an anti-AXL monoclonal antibody.

For further information, please visit: www.bergenbio.com

KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary

of Merck & Co., Inc., Kenilworth, NJ, USA, TARCEVA® is a registered trademark of

OSI Pharmaceuticals, LLC., marketed by Roche-Genentech. TAFLINAR® is a

registered trademark of Novartis International AG and MEKINIST® is a registered

trademark of GSK plc.

-Ends-

Contacts

Richard Godfrey

CEO, BerGenBio ASA

+47 917 86 304

Tom Henrik Sundby

Finance Director, BerGenBio ASA

+47 477 54 415

tom.sundby@bergenbio.com

Media Relations

David Dible, Mark Swallow, Marine Perrier

Citigate Dewe Rogerson

bergenbio@citigatedewerogerson.com

+44 207 638 9571

This information is subject to the disclosure requirements pursuant to section 5

-12 of the Norwegian Securities Trading Act.

References

[1] American Cancer Society - Lung Cancer Statistics -

https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/key

-statistics.html, accessed January 2018

[2] Siegelin M et al. Epidermal growth factor receptor mutations in lung

adenocarcinoma. Nature (2013)

[3] Ramalingam S, et al. Osimertinib vs SoC EGFR-TKI as First-Line Treatment in

Patients with EGFRm Advanced NSCLC (FLAURA). Presented at the European Society

for Medical Oncology (ESMO) 2017 Congress, 8-12 September 2017, Madrid, Spain.

[4] Yu HA, et al. Analysis of Tumour Specimens at the Time of Acquired

Resistance to EGFR-TKI Therapy in 155 Patients with EGFR-Mutant Lung Cancer.

Clin Cancer Research. (2013)

[5] Chong CR et al. The quest to overcome resistance to EGFR-targeted therapies

in cancer. Nature (2013)

[6] Husain H et al. Strategies to Overcome Bypass Mechanisms Mediating Clinical

Resistance to EGFR Tyrosine Kinase Inhibition in Lung Cancer. Molecular Cancer

Therapeutics (2017)