SHANGHAI – Beigene Co. Ltd. is betting its Bruton's tyrosine kinase inhibitor, BGB-3111, has world-class potential and is gearing up for proof-of-concept trials in the U.S. to find out. The company just received approval for its investigational new drug application from the FDA and is beginning to build up its U.S.-based operation to support the upcoming trials.

Although it marks the company's first foray stateside, it is not the first trial outside of China.

BGB-3111 initially went to Australia for first-in-human trials 10 months ago, in a multicenter, open-label, dose-escalation study to assess the safety, tolerability, pharmacokinetic (PK) properties and antitumor activity of the candidate as a single agent. (See BioWorld Today, Sept. 10, 2014.)

Not disclosing the results of the trial at this time, Beigene's co-founder and CEO, John Oyler, told BioWorld Today that "we believe we have a very potent molecule with great PK, a more selective molecule that should have the benefit of doing what it is supposed and not doing anything it is not supposed to. It certainly warrants a global drug development plan."

The U.S. trial will be an expansion study with key objective of determining the maximum tolerated phase II dose, PK and preliminary antitumor activity in a variety of human tumors.

While going to Australia is often a bid to get started in the clinic while waiting for clinical trial application approval in China, going to the U.S. this time around is not about saving time as much as it is developing a global plan for BGB-3111, a drug that Beigene said has the best-in-class potential.

The company is hopeful BGB-3111 will be safer and more efficacious than the "marketing-leading BTK," Imbruvica (ibrutinib), which attracted industrywide attention recently for a $21 billion price tag commanded in the buyout of its developer, Pharmacyclics Inc., by Abbvie Inc., of Chicago. (See BioWorld Today, March 6, 2015.)

Ibruvica is approved for three blood cancers, all under the FDA's breakthrough category, with potential for more indications.

Although more Chinese companies are beginning to consider or are entering the U.S. regulatory pathway with their assets, it is still early days for the industry. China has had little success bringing world-class drugs to market, in China or elsewhere. But Beigene could be a contender to change that narrative.

The firm is well funded to bankroll global ambitions. Over the last six months, in two venture capital rounds, it raised a total of $172 million in financing. And, in 2013, it licensed out global rights to two candidates to Merck KgaA for a reported total deal value of $465 million, giving the company a steady stream of licensing payments. (See BioWorld Today, May 19, 2015.)

Beigene also has the management and scientific talent to match that stellar bank account.

Oyler is a former McKinsey consultant and serial entrepreneur who sold his China-based clinical research organization (CRO) business, Bioduro, to PPD Inc., of Wilmington, N.C., for a reported $77 million in 2009.

Beigene's other co-founder and chairman, Xiaodong Wang, is an eminent scientist, the architect and director of China's esteemed National Institute of Biological Sciences, as well as a member of the National Academy of Science in the U.S. and the former Howard Hughes investigator, distinguished chair of Biomedical Sciences and professor of Biochemistry at University of Texas-Southwestern.

BTK AND PD-1 UNDER ONE ROOF

It is no surprise that talent and money flock to promising assets, and Beigene is sitting on two potentially game-changing therapies: the BTK inhibitor BGB-3111 and a programmed death-1 (PD-1) antibody, BGB-A317, which initiated phase I trials in Australia earlier this month. (See BioWorld Today, June 10, 2015.)

Rounding out a total of four assets in the clinic, all self-discovered, the company is also testing BGB-290, an investigational PARP inhibitor, and BGB-283, a second-generation BRAF inhibitor. There are expectations that another candidate will enter the clinic this year.

Few companies have managed to have that line-up of assets not just under one roof but also already on the way in the clinic, providing the small company with some distinct advantages. "Our vision, like most oncology companies today, is that the true solutions of tomorrow are all going to be combinations," said Oyler.

While Oyler said BGB-3111 has shown promising results as a single agent, the company vision is focused on combination therapies, bringing together targeted therapies such as BGB-3111 with immuno-oncology targets such as PD-1 and PD-L candidates, in a science-driven way.

"Blood cancer is one opportunity," said Oyler, when asked about what indications the firm is pursuing for BTK-3111, though he added that "there are additional indications that are of interest that we believe will be exciting from a combination perspective, including solid tumors, and including PD-1 oncology therapeutics. Given the fact we have both the PD-1 and BTK, that makes us one of the few organizations that can effectively pursue that without the encumbrances of partner companies."

NOT GIVING UP ON CHINA

Beigene's efforts will continue apace in China, taking the strategy of preparing for the worst-case regulatory timeline but hoping for the best.

"We view China as no different than the U.S.; it is a younger regulatory system and it will take some time," said Oyler. "But we think there is an ability right now, without regulatory change, to move drugs forward in China.

"We would love to see things move faster," he said. But "even if it does not, there is a path. A couple of companies have gone through that path, and we are hopefully well on our way."