In May 2013, Ambrx, a clinical-stage biopharmaceutical company, partnered with Bristol-Myers Squibb for the discovery and
development of ADCs using Ambrx's protein medicinal chemistry technology. Ambrx will receive an upfront payment of $15 million,
funding for discovery and research activities, potential development, and regulatory and sales milestones of as much as
$97 million per product. BMS will have worldwide rights to develop and commercialize products resulting from the collaboration,
and Ambrx is eligible to receive royalties on sales. In April 2013, Ambrx partnered with Astellas in an ADC deal worth up
to $300 milllion. Ambrx received an upfront payment of $15 million from Astellas and may receive up to $285 million in potential
milestones for an undisclosed number of targets for ADCs in oncology. Ambrx also inked a deal in ADC development with Merck
& Co. in 2012. In June 2013, Ambrx partnered with the Chinese pharmaceutical Zhejiang Medicine (ZMC) to develop and commercialize
ARX788, Ambrx's ADC targeting HER2-positive breast cancer. Ambrx and ZMC will continue the development of ARX788, with ZMC
bearing the ongoing development cost. ZMC will manufacture the drug on a commercial basis. The CRO WuXi PharmaTech will develop
and manufacture the toxin, antibody, and ADC as well as provide preclinical development and clinical trials.
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Seattle Genetics, which partnered with Takeda for developing Adcetris, is collaborating with Genentech, Pfizer, AbbVie (formerly
Abbott), Bayer HealthCare, Progenics, and Genmab for ADCs using Seattle Genetics' proprietary ADC technology. Seattle Genetics'
technology uses synthetic cytotoxic agents, such as E (MMAE) and monomethyl auristatin F (MMAF), and stable linker systems.
In April 2013, Seattle Genetics reported on a newly developed cytotoxic agent, a pyrrolobenzodiazepine (PBD) dimer. PBDs are
a class of highly potent, synthetic DNA-crosslinking agents, and the company presented data on ADCs using the company's site-specific
conjugation technology (EC-mAbs) to link PBDs to mAbs targeted to CD33 and CD70. The company also reported on its preclinical
candidate, SGN-LIV1A, which uses the same proprietary ADC technology as Adcetris and presented research on a new method for
making highly stable linkers, specifically self-stabilizing maleimido-DPR linkers (4).
In June 2013, Genmab and ADC Therapeutics teamed to develop a new ADC product combining Genmab's HuMax-TAC antibody and ADC
Therapeutics' PBD-based cytotoxic and linker technology. In 2012, Spirogen announced a multiyear collaboration and license
agreement with Genentech for the discovery and development of ADCs using Spirogen's PBD-based drugs and associated linker
technology. Spirogen is primarily responsible for synthesizing and manufacturing drug reagents while Genentech is using Spirogen's
drug reagents to generate ADCs and evaluate their potential therapeutic utility. Genentech has the exclusive license to fully
develop and commercialize licensed products that contain these ADCs (3).
Mersana Therapeutics, which is developing ADCs using its Fleximer polymer and customizable linker chemistries, formed a $270-million
collaboration with Endo Pharmaceuticals in early 2012. The Fleximer polymer is customized to improve the pharmacokinetics
of targeting moieties, such as antibody fragments, and also to optimize the quantity of cytotoxic payload carried per targeted
conjugate and the stability of the drug–polymer linkage as well as the targeting moiety–polymer linkage (3). In July 2012,
Mersana received $27 million in venture-capital funding, which included investment by Pfizer Venture Investments. Biotecnol
and PolyTherics formed a collaboration in 2012 for multispecific tribody drug conjugates to use Biotecnol's tribody technology
with PolyTherics' proprietary site-specific linker technologies. Tribody molecules are multispecific antibody products that,
from a single molecule, enable the targeting of two or three tumor antigens in the same disease or two or three epitopes on
the same tumour target. PolyTherics' ThioBridge linker technology is a conjugation technology for creating more stable, less
heterogeneous ADCs through site-specific linkage and rebridging of disulfide bonds (3).
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