San Diego’s Ambrx, co-founded in 2003 by the prominent chemist Peter Schultz (who remains on its board), has advanced its technology for antibody-drug conjugates by forging a series of drug discovery and development partnerships with Big Pharmas like Merck, Eli Lilly, Astellas, and Bristol-Myers Squibb.
Now, in what a spokeswoman calls a “significant departure” from its previous collaborations, Ambrx says it has formed a collaboration with China’s Zhejiang Medicine to develop and commercialize ARX788, a preclinical antibody drug conjugate that targets HER2-positive metastatic breast cancer.
Ambrx CEO Lawson Macartney, a Scot who joined Ambrx in January from Shire’s specialty pharmaceutical business in Switzerland, told me by phone yesterday that financial terms of the deal with Zhejiang were not being disclosed. Still, he allowed that “there are financial considerations” for Ambrx.
The big difference in this deal is that Zhejian will bear the drug development costs going forward, according to Simon Allen, Ambrx’ chief business officer. If ARX788 makes it through clinical trials and all the way through regulatory approval, Zhejiang would get commercial rights to the drug in China, while Ambrx would retain commercial rights everywhere outside of China, and also would get royalties on product sales in China. It’s a deal that helps advance a potentially lucrative anti-cancer drug without a huge investment by Ambrx (limiting the company’s financial risks) and still preserves commercialization rights outside China for Ambrx, Allen said.
But how lucrative would such a drug be? ARX788 is targeting a type of advanced breast cancer already well-served by Roche-Genentech’s trastuzumab (Herceptin) and another antibody-drug conjugate known as T-DM1, or ado-trastuzumab emtansine (Kadcyla), that won FDA approval in February. Ado-Trastuzuman emtansine is intended for patients who previously received trastuzumab and a taxane, separately or in combination.
Nevertheless, Macartney said he believes the Ambrx technology imbues site-specific antibodies with toxicity that would compare well against Herceptin.
The technology has been described as “empowered” or “armed” antibodies, and compared to both smart bombs and the Trojan Horse. The general concept is to attach a toxic payload to an antibody that is known to bind to a specific target on tumor cells, Macartney said. Ambrx takes an approach that optimizes the antibody-drug conjugate even more, by synthesizing an amino acid that precisely attaches the toxic payload to the antibody so it won’t break off or get in the way when the amino acid binds to tumor cells. “We can design exactly where we want [the antibody] to stick the payload,” Macartney said.
When the previous CEO, Steve Kaldor, left in 2010, Xconomy’s Luke Timmerman reported that Ambrx had raised more than $106 million in venture capital—-and Macartney told me the company has not raised any additional funding from VCs.
But the company has secured additional funding through its partnership deals, Macartney said. The deal that Ambrx struck last year with Merck (NYSE: MRK), for example, called for the New Jersey pharmaceutical giant to pay $15 million upfront, another $288 million in milestone payments, and an undisclosed royalty rate on worldwide sales of any drugs that might come from the collaboration.
Under its agreement with Ambrx, China’s Zhejiang will manufacture the product for clinical and commercial supplies on a global basis. China’s WuXi PharmaTech, a contract research giant, will provide integrated services for ARX788, including the development and manufacturing of the toxin, antibody, and antibody-drug conjugate, as well as pre-clinical development and clinical trials.
“This collaboration allows Ambrx to further extend our pipeline of ADCs (antibody-drug conjugates) and gain access to the China market through our partnership with [Zhejiang],” Macartney said. “Our experience with site-specific ADC technology has shown that we have the potential to create best-in-class therapeutic candidates, and we look forward to advancing ARX788 into the clinic to understand its full potential.”
The company’s product pipeline identifies 11 antibody-drug conjugates, but it’s worth noting that at the request of some of its pharmaceutical partners, Ambrx has not identified all of its drug discovery and development partnerships. So it’s possible that the San Diego biotech’s product pipeline could be bigger than the company has disclosed.