Partnering in Antibody Drug Conjugates - Pharmaceutical Technology

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Partnering in Antibody Drug Conjugates
The promise of antibody drug conjugates is creating a network of partners among large pharma companies and specialized players.

Pharmaceutical Technology
Volume 36, Issue 11, pp. 50-51

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,


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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