A new approach to cancer target screening

LSIPR asked chief executive Richard Godfrey.

Cancer is the leading cause of death in Europe: a third of people living there will die from the disease. Improvements in treatments are making it easier to manage, and more people are surviving their cancers.

These days the majority of cancer fatalities are a result of cancer spread (metastasis) and metastatic tumours are often drug-resistant.

“The driver is often the epithelial-mesenchymal transition (EMT) process, where cells break out of a tumour, become stem cell-like, and spread to other parts of the body,” says Richard Godfrey, chief executive of BerGenBio.

BerGenBio’s CellSelect technology, patented in 2007, ‘asks’ the cell what genes are driving EMT. After identifying the genes, BerGenBio validates their role and assuming it’s treatable with drugs, then goes to work in developing drug leads that inhibit the protein and stop EMT.

“We’re about developing cancer drugs, but we’re doing it from a very sophisticated start point of a deep understanding of the biology,” he says.

BerGenBio`s CellSelectRNA technology uses a library of ribonucleic acid (RNA) triggers in phenotypic screens to identify the gene that is driving a certain cellular behaviour. “It’s like having a library of hundreds of thousands of surrogate drug compounds and asking what they do to the cell behaviour,” Godfrey explains.

The very same technology allows BerGenBio to see how drugs would behave in disease models, before the company invests in developing the chemistry.

BerGenBio has one family of patents that covers the CellSelect technology, which Godfrey says has so far withstood prosecution.

These patents cover the CellSelectRNAi process and the application of the information BerGenBio gets from its RNAi studies.

Perhaps surprisingly, Godfrey doesn’t intend to protect BerGenBio’s library of RNAi triggers with patents. That would be “giving away the house”, he says. “They’re trade secrets.”

The company has seven patent families that include 33 patents in all. Most patents cover composition of matter, and the use of drugs leads.

As the field of RNAi is highly specialised, carving out a legitimate space in a patent arena “cluttered” with many older conflicting and overlapping patents is a challenge, says Godfrey.

“There’s limited value in biological discovery, or novel targets, but there’s a great deal of value in first-in-class drugs that address an unmet medical need.”

“What we’ve realised is that the clinical assets, the drugs, are what really drive the value for our company, therefore when drafting patents it’s important to carve out a unique space that aligns with the clinical opportunity, if possible. There is limited value in biological discovery, even novel targets, but there’s a great deal of value in first-in-class drugs that address an unmet medical need. That’s really where we’re putting our effort going forward.”

CellSelect may be used for identifying targets that drive almost any disease. While he is considering licensing the technology to other companies, Godfrey wants first to develop a deeper understanding of cancer.

“We’re quite grounded really, you can’t venture into too many areas, we must stay focused,” he says. “Our focus is to maintain our leadership in understanding the EMT process in cancer.”

BerGenBio’s drug leads are at the development stage, and the lead program BGB324 is poised to start clinical trials.

BGB324 is an oral, highly selective inhibitor of AXL-receptor tyrosine kinase (AXL), which is a mediator in the EMT process.

AXL’s role in the development and spread of cancer was first understood by BerGenBio, using its CellSelect technology. Godfrey says that the recent interest in AXL’s function was a result of the company’s discovery.

“No-one was really working on it before,” he says, “but now Axl inhibition is probably one of the hottest areas in the next generation of cancer therapies, and increasingly companies are developing or trying to develop AXL inhibitors.”

BerGenBio is currently developing a treatment that inhibits AXL with its BGB324 programme, which is poised to enter Phase 1 clinical trials.

When a treatment is found, how will BerGenBio protect it?

“When we discover a novel target, it’s actually quite difficult to IP-protect,” he says, adding that this is “probably right”.

“It’s appropriate that we’re not allowed to protect a gene, because there are a finite number of genes,” he says. “In order to get some IP from a novel biological discovery, you need to file for IP based on the use of the gene or its expression—rather than just trying to block others from working on it and saying ‘this is ours’.”

He says that in any case the strongest, most valuable IP comes from developing a therapy or drug, which can then be sold at some commercial value.

The BerGenBio business model is to understand something very novel in a specific biological process; this is the very beginning of the drug discovery cycle. After the discovery, the company has to act fast to protect it:

“We’ll try to quickly prosecute that biological discovery into a composition of matter that is specific and robust and has the usually 20 or more years of IP life from which we can get some return on our investment,” he says.

Asked for his opinion of the Myriad case, where the patentability of genetic material is being considered at the US Supreme Court, Godfrey says “it’s important that the IP provides some reward for the initial work, but doesn’t prevent future innovation and wellbeing for mankind.”

“I hope that they can find some sort of compromise where the initial discoveries are somehow rewarded, but they don’t block the rest of the world from developing.”

BerGenBio is now working to find more targets that are responsible for driving aggressive drug resistant cancers, for which treatments do not yet exist.

“We’re about to start a clinical development programme,” Godfrey says. “We’ll spend more time and money demonstrating that our drug is safe and effective in human studies, and then we’ll license its forward development. It will be available for license probably this time next year.”

BerGenBio is also preparing to share more of its patents. In mid-2014 the company will be seeking licensing partners.

“We’d be prepared to discuss with potential partners licensing our CellSelect technology if somebody wanted to learn that technology and use it for their own discovery,” he says. More research needs to be done on understanding the mechanisms of many diseases.

There’s a lot going on, he says, though establishing a biotech company takes time:

“The strongest, most valuable IP comes from developing a therapy or drug, which can then be sold at some commercial value.”

“Maybe it’s just typical biotech,” he says. “It takes a few years to get established, to get recognised, to get scientific respect, to build on the initial discoveries so that you’ve got something of value, and then after a few years you need to consolidate and get yourself in a position where you can become commercial.”

What does he think are the most significant challenges facing startup biotech companies?

First is funding. Godfrey says: “Money solves eight out of 10 problems.” The next challenge is finding appropriate human resources, and then, later on in the business life cycle, finding an acceptable exit that satisfies all stakeholders.

And of course, having an IP strategy is essential in the success of a startup, he says.

“We’ve always got our eyes open to the possibility of protecting the work that we’re doing and the prosecution and protection of the work that we’ve done.”

While BerGenBio is focused on developing cancer treatments specifically, its scope is very wide in terms of IP. The business holds patents covering a range of technologies and processes, from the specialised RNAi technologies, compositions of matter, and clinical uses related to compounds and biomarkers.

Having a team that understands the science is also vital. BerGenBio works with several specialist IP firms, and lawyers who are experts in the technology.

“It’s very important that our IP lawyers and counsel are scientifically and technically competent, and even expert, so that they can help us understand what’s unique, valuable, protectable, novel, in what we’ve done and how we can differentiate that from what else is in the literature and in the patent world, and that we can navigate and prosecute the right claims,” Godfrey explains.

BerGenBio works with firms in the US and UK to find expert counsel, who work to syndicate the company’s patents worldwide.

Though he predicts it will be at least another seven years before any programmes make it to the market, before then BerGenBio will file patents and use its technology platform to “produce a pipeline that hopefully has value and clinical benefit for the cancer patient”.

“The value comes from being able to protect everything from an IP point of view,” he says.