Other companies specializing in ADC technology are partnering with pharmaceutical companies. Earlier this year, Spirogen announced
a multiyear collaboration and license agreement with Genentech for the discovery and development of ADCs using Spirogen's
pyrrolobenzodiazepine-based drugs and associated linker technology. Spirogen will be primarily responsible for synthesizing
and manufacturing drug reagents while Genentech will use Spirogen's drug reagents to generate ADCs and evaluate their potential
therapeutic utility. Genentech will have the exclusive license to fully develop and commercialize licensed products that contain
these ADCs.
Mersana Therapeutics, which is developing ADCs using its Fleximer polymer and customizable linker chemistries, formed a $270-million
collaboration with Endo Pharmaceuticals in March 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. In July 2012, Mersana
received $27 million in venture-capital funding, which included investment by Pfizer Venture Investments.
Biotecnol and PolyTherics formed a collaboration last month for the development of multispecific tribody drug conjugates (TDCs).
The companies will combine Biotecnol's tribody technology with PolyTherics' proprietary site-specific linker technologies
to attach cytotoxic payloads to various tribodies for targeted cancer therapy. 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 tumor target. In vitro and in vivo studies conducted by Biotecnol have demonstrated tribodies to have targeting abilities and high tumor-to-blood ratios, which
make them suitable for delivering toxic payloads in certain disease settings. Biotecnol has a portfolio of multivalent antibodies
and capabilities in antibody development and antibody engineering, which will be directed toward this collaboration.
PolyTherics' ThioBridge linker technology is a conjugation technology for creating more stable, less heterogeneous ADCs through
site-specific linkage and rebridging of disulfide bonds. It has been developed to support the conjugation of a range of therapeutic
payloads to antibodies, antibody fragments, or scaffolds through specific sites without impacting functional domains. The
companies will test the potency of the ThioBridge tribody-drug conjugates in preclinical cancer models.
Contract manufacturers expand
Contract API manufacturers offering high-potency manufacturing and related conjugation services are expanding their offerings
in response to increase demand for ADCs and other highly potent compounds. For example, Carbogen Amcis and ADC Biotechnology
recently announced a partnership to provide customers with development and manufacturing services for ADCs. ADC Bio will provide
access to proprietary solid-phase immobilization technologies for conjugation and long-term storage of ADCs, and Carbogen
Amcis will focus on small- to large-scale GMP supply and on the formulation of ADCs.
In October 2012, Fujifilm Diosynth Biotechnologies formed a strategic alliance with Piramal for ADC production whereby the
two parties will offer contract development and manufacture of ADCs. Piramal offers ADC production at its site in Grangemouth,
Scotland. Fujifilm recently announced an expansion of its cGMP manufacturing facilities at its sites in Research Triangle
Park, North Carolina, and Billingham, United Kingdom.
Novasep recently announced an EUR 3 million ($3.9 million) invesment to expand its highly potent API (HPAPI) manufacturing
capabilities at its Le Mans, France, facility. The plant expansion is expected to be fully operational by the beginning of
2013. The new Le Mans facility adds to Novasep's strategy for total synthesis of ADCs, including toxin and mAb production,
mAb-toxin coupling, downstream processing, and formulation.
Lonza recently partnered with the biopharmaceutical company Intellect Neurosciences to provide the future development and
manufacture of Intellect's ADC Conjumab-A. Lonza will supply the preclinical study material for the drug optimization and
drug selection for Intellect's Conjumab-A. The new program includes in vitro and in vivo studies to evaluate both therapeutic and prophylactic potential in age-related macular degeneration testing different chemical
variants manufactured by Lonza.
Patricia Van Arnum is executive editor of Pharmaceutical Technology, 485 Route One South, Bldg F, First Floor, Iselin, NJ 08830 tel. 732.346.3072, pvanarnum@advanstar.com
Twitter@PharmTechVArnum.
References
1. A. Ritter, Pharm. Technol.
36 (1), 42–47 (2012).
2. FDA, "Label for Adcetris, BLA 125338," FDA Approved Drug Products: Drugs@FDA, accessed Dec. 20, 2011.
3. M. Dolsten, presentation at the Barclay 2011 Global Healthcare Conference, Mar. 17, 2011.
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