AXL Inhibition Specialist BerGenBio's $24m Private Placement To Fund Pipeline, Trials

BerGenBio CEO says the Norwegian biotech aims, either alone or in partnership, to develop and commercialize its lead asset through to marketing approval in a variety of cancers.

University of Bergen spin-out BerGenBio ASA has raised $24m through a private placement of shares, bringing to around $50m the available cash it can use near-term to progress its pipeline of first-in-class AXL kinase inhibitors as a potential cornerstone of combination cancer therapy

BerGenBio, which believes Axl signaling is a key mechanism of cancer cell survival and progression, has generated research showing that Axl expression correlates with the worst overall survival of cancer patients. The biotech's pipeline focuses on the inhibition of Axl signalling and improving patient outcomes through monotherapy and in combination with other drugs.

BerGenBio's lead product candidate, bemcentinib (formerly BGB324), is the only selective AXL inhibitor in clinical development. A highly selective, potent and orally bio-available small molecule, it is currently in four company-sponsored Phase II clinical trials in major cancer indications, with read-outs expected in 2018. Those company sponsored clinical trials are:

•             Bemcentinib with Tarceva (erlotinib) in advanced EGFR mutation driven non-small cell lung cancer (NSCLC)

•             Bemcentinib with Keytruda (pembrolizumab) in advanced adenocarcinoma of the lung

•             Bemcentinib with Keytruda in triple-negative breast cancer (TNBC)

•             Bemcentinib as a single agent and combination therapy in acute myeloid leukaemia (AML) / myeloid dysplastic syndrome (MDS)

Global Profile Sought Through Placement

BerGenBio's private placement price of NOK40.50 per share was determined in an oversubscribed book-building process which concluded on April 13 and was directed mainly towards institutional investors in the US specialising in the biotechnology sector. The exercise raised NOK187.5m ($24m) in gross proceeds through the issuance of 4,629,246 new shares.

"We wanted with this financing to raise the profile of BerGenBio on the international stage and attract investment from big biopharma players - and we did that," said the biotech's CEO Richard Godfrey. 

"This will allow us to maintain our programs, perhaps expand them a little, and elucidate much of the translational data that we're working on, so that not only can we report out response rates, but also overlay them with translational research that we're doing with patients with tissue samples and understanding the immune profile, the AXL profile, PD-L1 profile of the patients to give a better understanding as to why patients do or don't respond," Godfrey said in an interview with Scrip.

And we're meanwhile developing a companion diagnostic to enrich future trials, so we only attract patients that we think have a high probability of responding," he added.

The group's therapy focus reflects the fact that resistance to conventional and targeted therapy is a major cause of failure of anti-cancer treatment.

Although immune checkpoint inhibitors are mobilizing the innate immune system to combat cancer cells, they have only demonstrated sustainable therapy in a relatively small proportion of cancer patients. "We hope to help checkpoint inhibitors to work better. Checkpoint inhibitors are only really suitable for a relatively small proportion of patients, and they only benefit an even smaller proportion of those patients," Godfrey said.

"In putting our strategy together, we were keen to maintain the combination strategy, so we have several studies running in combination with chemo, several running in combination with target agents, and several running in combination with checkpoint inhibitors," he said, adding: "We're putting equal efforts in all three of those areas because we think the resistance seen in all three approaches can be mediated to a significant extent through the AXL pathway."

Parallel Diagnostics

BerGenBio also develops companion diagnostics aiming to identify cancer patients with Axl positive tumours who are more likely to respond to "personalised medicine" treatment. "We are building a proprietary diagnostics capability that we are advancing in parallel to our pipeline," the CEO said.

For example, companion diagnostics using biomarkers are being developed for the identification of patients predicted to be most suitable for treatment with the bemcentinib / Keytruda combination that BerGenBio is working on with Merck & Co. Inc..

The duo, earlier in April, completed patient enrolment for the first stage of their Phase II clinical trials evaluating bemcentinib in combination with Merck's anti-PD-1 therapy Keytruda as a potential new treatment regimen for advanced lung cancer.

"We have strong data that suggests that patients that do not respond to the checkpoint inhibitors have a rich AXL expression in their tumor.  We must confirm that in these studies, but also of course confirm that by inhibiting AXL we will improve the response rate to Keytruda," Godfrey explained.

Their Phase II trial, called BGBC008, follows a two-stage design: it is an open label, multi-center study of bemcentinib in combination with Keytruda in patients with previously treated advanced non-small cell lung cancer (NSCLC) whose disease is progressing.

The trial, began in October 2017, is designed to evaluate the anti-tumour activity, objective response rate and safety of the combination, and to correlate the patient response with biomarker status, including AXL kinase and PD-L1 expression.  The trial is taking place at more than 12 clinical sites in the US, UK, Norway and Spain.  Interim results are expected during 2018.