Editor’s (re)View: Sutro, Boehringer reach ADC manufacturing milestone with large-scale GMP production
Antibody-drug conjugates (ADCs), which combine the specificity of monoclonal antibodies with the potency of cytotoxic drugs, are not a new modality for targeting and killing cancer cells. What is new is the recent investment that biotech and Big Pharma companies have made to improve ADC linker and payload technologies and overcome the toxicity challenges.
Sutro Biopharma, a South San Francisco clinical-stage company, has been making ADCs since 2011. When Bill Newell became CEO of Sutro in 2009, he asked his staff what they could make in-house. At that point, the company couldn’t make antibodies. However, that soon changed.
More recently, Sutro has been working on demonstrating that ADCs built with its proprietary cell-free expression technology can be manufactured by a third party at commercial scale under GMP conditions. Fast-forward to this week, Sutro has achieved what it claims are first-in-class cell-free capabilities at a commercial scale with biopharma partner Boehringer Ingelheim.
Working with Boehringer Ingelheim’s contract manufacturing arm, BioXcellence, the companies used the cell-free platform to produce Sutro’s lead asset luvelta, a Tubulin FRα-targeting ADC being developed to treat patients with advanced-stage ovarian cancer and other cancers. “All batches of luvelta manufactured in 4,500 L at Boehringer’s large-scale manufacturing facility in Vienna, Austria, met the product quality criteria required for the use in clinical studies,” the companies announced.
Sutro’s platform is based on company founder and Stanford University professor James Swartz’s patented Open Cell-Free Synthesis technology. The challenge, according to Newell, was making it robust enough to scale on an industrial level of commercial production. He credited Swartz with putting the “underlying processes in place that allowed that scalability.”
According to Sutro, the production of proteins using its cell-free system can be scaled rapidly from sub-1mL to manufacturing scale. Newell told investors at the company’s ADC research forum in October that the company’s protein synthesis platform is “an elegant solution for what has been a longtime challenge in the biotechnology industry — the production of complex biologics using cell-bound techniques.”
The biotech industry has invested billions of dollars to produce large molecules, such as antibodies, using Chinese hamster ovary (CHO) cells. Conventional ADCs are made using CHO cells, while Sutro’s cell-free platform enables the precise design of a wide range of features that Newell contends are not possible with other platforms. “It’s the flexibility of not having to be limited by the cell’s need to continue to replicate,” he said.
Sutro’s competitors “are 20 years behind in terms of scalability,” according to Newell. While Sutro is focused on ADCs, he said the company’s cell-free platform is highly flexible in terms of its ability to make different kinds of large molecules beyond just antibodies, including vaccines.
“We could offer this and sell it to everybody and teach them how to do it — but then, we would enable hundreds of competitors,” Newell said. “If you want to be part of this design advantage, come and collaborate with us.”