After a few months’ delay to refine its clinical strategy the private Norwegian biotech BerGenBio is off the starting blocks, fortified with a recently completed $6m financing round.
Its first ever phase I study has just started testing single ascending doses of BGB324, an oral Axl tyrosine kinase inhibitor – a novel mechanism that caused some excitement among early-stage researchers at the recent Asco meeting. Speaking to EP Vantage at Asco, BerGenBio’s chief executive, Richard Godfrey, said this initial study could validate not only BGB324 but the start-up’s entire technology base.
This technology is focused broadly on endothelial-mesenchymal transition (EMT), a natural process whereby epithelial cells lose cell polarity and adhesion, and gain migratory and invasive properties to become mesenchymal cells. In some cancers this is thought to initiate metastasis, and Axl tyrosine kinase might play a role in this process.
“Axl is a mediator – not the only driver – of EMT,” says Mr Godfrey. BerGenBio’s pipeline also includes other compounds acting on EMT – the company’s work on EMT induction in tumours has given rise to a suite of screening technologies – though the specific targets remain largely undisclosed.
The phase I programme has started a little later than initially hoped, giving BerGenBio time to define an additional clinical role for BGB324 in combination with standard of care (EP Vantage Interview - BerGenBio close to securing Series A funds, December 2, 2011).
Combinations make sense because EMT is thought to drive drug resistance, and so blocking Axl might re-sensitise cells to standard treatment. The phase I trial will evaluate safety and pharmacokinetics and BerGenBio’s clinical biomarker assays, and its adaptive design means the number of subjects has not been specified.
The Axl tyrosine kinase approach has few competitors, and EvaluatePharma reveals only one other company, Tolero Pharmaceuticals, specifically involved in this field. At Asco Tolero presented early data on its two Axl inhibitors, SGI-7079 and TP-0903, suggesting Axl as a target and predictive marker of EGFR-inhibitor resistance in squamous cell head and neck carcinoma.
However, Mr Godrfrey says that “some broad tyrosine kinase inhibitors also likely target Axl. Some are being rebranded as Axl tyrosine kinase inhibitors.” One might be GlaxoSmithKline’s foretinib – a multi-kinase inhibitor of Met and VEGFR2 that at Asco was said also to inhibit Axl.
A phase Ib study of foretinib plus Tykerb in 19 patients with Her2-positive metastatic breast cancer backed the combination approach, although in Glaxo’s case the two agents hit safety issues when given at their standard standalone doses.
Another Asco poster detailed a role for Axl inhibition specifically by BGB324 in acute myeloid leukaemia. “We’ve also had nice early results in NSCLC and pancreatic cancer,” says Mr Godfrey, though he admits that these particularly intractable cancer types have seen many companies try and fail.
The $6m BerGenBio recently raised comes on top of an $8.8m series A round completed in January 2012, and will take the company to the end of phase I. “We will look to raise more, likely at the end of 2013,” says the chief executive.
Surprisingly, the aim is to seek a partner for BGB324 shortly after phase I. This, says Mr Godfrey, is so the appropriate number of phase II studies can be done – and funded. “A first-in-class compound will require quite a comprehensive phase II programme, maybe four to six studies.
“Industry also is looking earlier, and wants to be more involved in phase II work. We have other programmes. We don’t want to be a one-product company.”