PolyTherics and Spirogen formed a research collaboration to develop antibody drug conjugates (ADCs) for cancer. The companies will produce the ADCs using PolyTherics’ TheraPEG™ linker technology to site-specifically conjugate Spirogen’s potent pyrrolobenzodiazepines (PBDs) cytotoxic agents to antibodies and antibody fragments.
The companies will test the potency of the resulting ADCs in preclinical models of cancer. PolyTherics and Spirogen will jointly seek partners to develop the most promising ADC candidates that arise from the collaboration.
The agreement comes a week after Spirogen’s majority owner, Celtic Therapeutics, launched a new company with $50 million and 10 Spirogen ADC candidates. “We believe that ADCs will represent a significant medical breakthrough in cancer therapy over the coming decade, and that PolyTherics’ TheraPEG conjugation technology will broaden the applications where our PBD warheads and linkers can create highly potent potentially market-leading ADC candidates,” says Chris Martin, CEO of Spirogen.
PolyTherics has been using its technology for the site-specific conjugation of polymers such as polyethylene glycol (PEG), to any therapeutic peptide or protein including antibodies, antibody fragments, and protein scaffolds. The linker chemistry and novel reagents can be used to produce protein drug conjugates, targeted imaging agents, bispecific proteins, and more stable proteins and peptides with longer half-lives.
Polytherics says that products developed using its technologies have significant product quality and production advantages including better pharmacokinetic and pharmacodynamic profiles, increased product homogeneity, consistency of manufacture, and more cost-effective process economics. PolyTherics has licence agreements with Celtic Pharma and Nuron Biotech and expects products developed using its technologies to be in clinical development in the next 12–24 months.
Spirogen’s PBDs are DNA minor groove binding agents, which bind and cross-link specific sites of DNA of the cancer cell. This blocks the cancer cells’ division without distorting its DNA helix, thus avoiding the common phenomenon of emergent drug resistance. In contrast, many cancer chemotherapeutics distort the structure of DNA resulting in the ability of the cancer cells to develop resistance to further therapy.
Spirogen has been developing its PBD technology for more than 10 years, including a standalone PBD agent already in an NCI-sponsored Phase II study in cisplatin-resistant ovarian cancer. It has a number of industry collaborations including a deal with Genentech. Last week Celtic Therapeutics spun out ADC Therapeutics, which will start out with a portfolio of 10 oncology PBD-based ADC development programs from Spirogen.