Locked and loaded: Glythera signs antibodies & payloads for ADCs

Glythera has set out to develop candidate antibody-drug conjugates (ADCs) for difficult-to-treat cancers using components licensed in separate deals with Iontas and Cancer Research UK.

Under the terms of the Iontas agreement, Glythera will combine toxins from its library with human-based antibodies licensed from Iontas.

Glythera will obtain exclusive rights for Ionta’s target-tested antibodies, in order to construct ADCs with its proprietary conjugation platform, PermaLink.

“PermaLink-based ADCs have been shown to provide a near -100% improvement in tolerability when compared with maleimide-based ADCs in in-vivo models, as well as enhanced tumour cell-killing and an overall improvement in tumour response in xenograft models,” said Glythera.

“The inherent stability of PermaLink permits the use of ultra-potent toxins for ADCs with enhanced efficacy and safety,” said the firm.

Iontas’ chief of business officer Neil Butt told us the antibodies – discovered at its Cambridge, UK facilities – are well suited to the project.

“Iontas can provide panels of antibodies against a defined ADC target and these can be generated to fulfil requirements set by a partner,” he said.

“This increases the chances of a partner obtaining a viable antibody in a shorter time frame,” he added.

Butt told us Iontas is looking for other agreements.

“As we expand the model to other indications and technology areas we see this as one route to future growth and expansion for Iontas,” he said

“Iontas is always looking for innovative ways of expanding and we see this arrangement with Glythera as being one of the several models by which we intend to grow our phage display services,” he added.

UK payloads

In a separate deal, Glythera has licensed the right to use payloads – the drugs linked to antibodies in ADCs – from Cancer Research UK’s library to develop next-generation therapeutics.

Under the terms, Glythera has exclusive access to the charity’s CDK11 inhibitor programme, which it will combine with antibodies using the PermaLink platform.

“The agreement follows a successful period of collaboration between the parties during which the viability of selected low molecular weight CDK11 molecules was demonstrated in relevant ADC models,” said the firm.

According to the company, these PermaLink-generated ADCs will have improved therapeutic index directed towards antigens specific to difficult-to-treat tumours.

“The CDK11 inhibitor programme has identified a series of low molecular weight, synthetically tractable compounds which potently inhibit and are selective against other kinase targets. The series demonstrates highly potent anti-proliferative activity in dividing and non-dividing tumour cells and represents an exciting approach for ADCs,” said the company.

Both Cancer Research UK and Iontas will receive milestone payments for agreement-related ADCs, and Glythera will pay Cancer Research UK an undisclosed up-free and royalties on product sales.

Glythera, who is responsible for the development, manufacturing and commercialisation of the candidates in both deals, hopes to nominate its first ADC by 2019.