Sutro Biopharma, a biopharmaceutical company developing a new generation of protein therapeutics utilizing a cell-free protein synthesis technology, presented the first scientific data involving a dual-warhead antibody-drug conjugate (ADC). The data was presented at the World ADC Summit being held in San Francisco, California, USA, October 14 – 17, 2013.

Trevor Hallam, Ph.D., chief scientific officer of Sutro, reported the data in a presentation titled “Producing Homogeneous ADCs with Combination Warheads,” demonstrating that scientists can combine two or more mechanistically diverse warheads precisely in a single ADC. As a result, next-generation Antibody-drug conjugates have the potential to efficiently kill tumors while limiting their ability to develop resistance to the cytotoxic conjugates.


Current antibody-drug conjugates in development have immense promise, but they are limited by the fact that they are structurally heterogeneous populations in which the position and number of conjugated linkers and warheads vary significantly.


“This data shows our technology can take ADCs a stage further, in this case enabling the creation of dual-warhead ADCs with two different cytotoxic agents attached to the targeting antibody, which may address the challenge of drug resistance in cancer,” Hallam noted “The ability to create a unique ADC has the potential to expand the number of cancers that can be treated using this type of drug.”

MabPlex
 

A new generation ADCs
Following the successful launch of brentuximab vedotin (Adcetris™, Seattle Genetics/Takeda/Millennium) and ado-trastuzumab emtansine (Kadcyla™, Genentech/Roche) the industry has begun to focus on new generations of antibody-drug conjugates that promise to be even more precise and effective at delivering cytotoxic “warheads” to tumors. Central to these approaches has been the optimization of new generation ADCs using technologies to conjugate the cytotoxic payloads precisely, resulting in a product containing a single homogeneous molecular species, rather than the mixture of species that comprise the approved ADCs to date.

Multiple partnerships
Current antibody-drug conjugates in development have immense promise. However, they are limited by the fact that they are structurally heterogeneous populations in which the position and number of conjugated linkers and warheads vary significantly. Such heterogeneity prevents the definition of structure-activity relationships (SARs). Consequently, using traditional ADC technologies prevents researchers from discovering and developing candidates with optimal therapeutic indices and can result in products with unpredictable and sub-optimal pharmacokinetic properties, stability and efficacy.

Scientists at Sutro are developing a new generation of antibody drug conjugate therapeutics and bifunctional antibody-based therapeutics for targeted cancer therapies. These expectation is that these therapeutics will significantly extend the clinical impact of current oncology therapeutic approaches and are beyond what can be envisioned with current, cell-based expression technologies.

As part of their strategy, the company has formed multiple partnerships with biopharma companies utilizing its technology, including a collaboration with Celgene Corporation to design and develop novel ADCs and bispecific antibodies as well as manufacture a proprietary Celgene antibody, and a partnership with Pfizer for the research, development and commercialization of novel peptide-based therapeutics.


Last editorial review: October 15, 2013.

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