Straight A's with ADCs
May 2013
by Kelsey Kaustinen  |  Email the author


TOKYO—In a deal that is as matched in expertise and technology as it is in alliteration, Astellas Pharma Inc. and Ambrx Inc. have announced a collaboration to discover and develop novel antibody drug conjugates (ADCs) against oncology targets.  
Per the terms of the collaboration, Astellas will pay Ambrx $15 million up front, with the potential for an additional $285 million in near- and long-term research, development, regulatory and sales milestones for an undisclosed number of oncology targets. A fraction of the milestones, in addition to royalties on net sales, will be contingent on the successful commercialization of any products that result from this collaboration. Astellas will gain worldwide rights to develop and commercialize ADCs for oncology. The specific oncology targets were not disclosed.
"Agensys Inc., an affiliate of Astellas which specializes in therapeutic antibody research and development in cancer, has significant experience with ADCs as oncology therapeutics and is looking to further expand its capabilities in this area," Dr. David Stover, senior vice president and Agensys site head, said in a press release. "Ambrx offers a novel approach to allow creation of site-specific and highly stable conjugations that have the potential to further optimize drug delivery to tumor cells."
The collaboration represents the first time the two companies have worked together, and Dr. Lawson Macartney, CEO of Ambrx, says the agreement is built on a mutual attraction. Astellas, he notes, "has a fabulous reputation in being a leading company in the oncology space," and Ambrx brings with it the specificity of its proprietary technology.
"As part of their expertise in oncology, Astellas, through their subsidiary Agensys, actually have multiple antibody drug conjugate molecules in the clinic," adds Dr. Ho Sung Cho, chief technology officer at Ambrx. "And so we thought that by bringing on a partner that also had specific expertise in this novel modality, they could truly value what we can create together, and so we look forward to enabling them to put additional molecules into clinical evaluation."  
ADCs are composed of an antibody and a payload drug, and enable targeted delivery of drugs. Ambrx's approach combines site-specific conjugation technology with proprietary payloads and links, and the company notes on its website that "by using conjugation chemistries that are orthogonal to the native 20 amino acids, we create antibody conjugates with unprecedented homogeneity with respect to the site of drug attachment."  
The company's ADCs have been shown in preclinical usage to have high potency and a wider therapeutic index than ADCs created with conventional non-specific conjugation.
Macartney notes that traditionally ADCs have not always been successful because the antibodies have been conjugated with the drug attached wherever it could get purchase, with the result that sometimes the payload would obstruct the interaction between the antibody and the tumor-specific molecule. Ambrx's approach, what he calls "medicinal chemistry for proteins," allows them to place a unique molecule—what they call a non-natural amino acid—at very specific points along the antibody, which allows them to "increase the potency and minimize the side effects."
"That balance, between therapeutic effects and side effects, that's what we call the therapeutic window. You want that window to be as wide as you can, and we believe that we optimize the therapeutic window for any given antibody drug conjugate," says Macartney.
Ambrx has other large industry partnerships underway that Macartney says are progressing "absolutely on track." Ambrx is working with Bristol-Myers Squibb Co., in a partnership that began in September 2011, on two biologics. One, ARX618, is based on Ambrx's research in Fibroblast Growth Factor 21 and is being developed in diabetes, and the other is based on the Relaxin hormone, which is currently under development for the treatment of heart failure. Ambrx is also collaborating with Merck, in a deal that was announced last June. The two companies are developing biologic drug conjugates against undisclosed targets.
Code: E051303

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