On a quest to expand its portfolio of new biologics, Beigene Ltd. has tapped Ambrx Inc. to use the San Diego-based company's platform of site-specific conjugation technologies to identify at least one potential new cancer medicine, with $10 million up front. The Beijing-based company could pay Ambrx up to $19 million more to initiate additional programs, which would add to Beigene's pursuit of externally sourced molecules, such as those it licensed from Zymeworks Inc. in November.

Beigene will gain global rights to develop and commercialize any products that arise from the collaboration. Should the venture succeed, Ambrx could claim up to $446 million from Beigene in further development, regulatory and sales-based milestone payments.

Ambrx was founded in 2003 to commercialize technology from The Scripps Research Institute enabling the genetic engineering of proteins with new amino-acid building blocks. The company has worked with China-based pharmaceutical companies since at least 2013, when it first announced a partnership with Shanghai-based Zhejiang Medicine Co. Ltd. to develop an antibody-drug conjugate targeting HER2-positive breast cancer.

The California company's ties to China deepened in 2015, when a consortium of some of the nation's biggest health care players snapped it up in a bid to accelerate the introduction of innovative therapies to the Chinese market. The deal with Beigene appears to be helping realize at least one promise of that acquisition, the suggestion by then-China Everbright CEO Chen Shuang that "with the support of the cooperation partners, Ambrx's business will expand rapidly in China." (See BioWorld Today, Sept. 23, 2003, and May 27, 2015.)

Today, Ambrx is advancing its own early stage oncology programs and a set of partnered assets with Astellas Pharma Inc. and Bristol-Myers Squibb Co. Until recently, it was also engaged in a partnership with its San Diego-based neighbor Tracon Pharmaceuticals Inc. to develop and commercialize the endoglin antibody TRC-105 (carotuximab) in China. Tracon disclosed a February termination of the partnership in its 10-K filing on March 1.

In its work with Beigene, Ambrx will deploy technologies enabling the incorporation of non-native amino acids into proteins in both E. coli and Chinese hamster ovary cells using its Recode and Eucode platforms, respectively. Recode supports the creation of long-acting therapeutic peptides and proteins and modified antibody and bispecific fragments, according to the company. Eucode is designed for the creation of "both larger and more complex proteins where the function may be critically dependent on the appropriate post-translational modification," the company said.

John Oyler, founder, CEO and chairman of Beigene, called the company's Ambrx deal "another example of our commitment to investing in innovative early stage research – both via our internal resources and capabilities and via collaborations," presumably referencing the company's recent billion-dollar-plus tie-up with Vancouver, British Columbia-based Zymeworks. The pairing, Zymeworks' first regional deal, sent rights to its HER2-targeted bispecific antibodies ZW-25 and ZW-49 in Asia (excluding Japan), Australia and New Zealand to Beigene. Representatives of Beigene and Ambrx were unavailable to discuss their work prior to publication. (See BioWorld, Nov. 28, 2018.)

Ambrx, meanwhile, is moving ahead with it other partnerships. According to Cortellis, in October 2018, BMS initiated an open-label, parallel-group, single-dose, phase II trial of Ambrx-discovered BMS-986036 in Hungary and Czechia in patients with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, to assess the pharmacokinetics, safety and tolerability. That trial is expected to complete in May.