Glythera demonstrates improved activity and safety of PermaLink®-based ADC

Appoints Scientific Advisory Board

  • Significantly improved tolerability of ADCs incorporating highly potent toxins

  • Efficacy outperforms industry-standard ADC technology

  • Development of proprietary ADC pipeline supported by key industry appointments to SAB-

Glythera Limited (‘Glythera’), the next generation Antibody Drug Conjugate (‘ADC’) development company, today provides further evidence that PermaLink®, its proprietary non-maleimide conjugation platform, enables the production of ADCs with potentially greater clinical utility than current industry-standard conjugation technologies.

ADCs are rapidly gaining ground as an important tool in the fight against cancer by specifically delivering highly potent toxins to tumour cells and limiting damage to healthy tissues. However, clinical utility depends on the stability of the conjugation chemistry; the current industry-standard maleimide approach is prone to the premature release of toxic payloads, thus limiting the dose that can be administered safely to patients and, subsequently, reducing ADC therapeutic index. Glythera’s PermaLink® is an alternative conjugation chemistry platform with greater stability and delivery metrics.

In recent in vivo studies, PermaLink®-based ADCs, have been shown to provide a near 100% improvement in tolerability when compared with equivalent maleimide-based ADCs, as well as enhanced tumour-cell killing and an overall improvement in tumour response in xenograft models. This combination of improved tolerability and efficacy of PermaLink® based ADCs will enable the safer use of higher-potency toxins for enhanced therapeutic utility.

Glythera is developing a portfolio of next-generation PermaLink® ADCs, focused on difficult-to-treat cancers. These combine unique high-potency toxins with novel antibodies. The Company is assessing and developing a broad range of innovative, highly potent toxin payloads from numerous toxin classes – including known and new mechanisms. In addition, Glythera is collaborating with its partners to evaluate a range of clinically important antibody targets and intends to identify its first clinical candidate before the end of 2018.

In another significant step, Glythera has appointed a Scientific Advisory Board to support and advance the Company’s industry-leading ADC development pipeline, with its first appointments being Dr Morris Rosenberg and Dr Robert Lutz. Dr Rosenberg has over 15 years in the ADC field, most notably as Vice President of Process Sciences at Seattle Genetics Inc., whilst Dr Lutz spent 23 years with Immunogen Inc., culminating in his role as Vice President of Translation Research and Development. Glythera hopes to announce further key appointments to its SAB in due course.

Dr Robert Lutz commented:

"The PermaLink® conjugation technology provides a highly selective and safe alternative to the current maleimide chemistries, whilst reducing the significant risk associated with de-drugging of potent toxins and adverse events in the clinic."

Dr Morris Rosenberg added:

"Glythera has accessed an impressive range of novel approaches to on-market toxins which meets the industry’s current need for ADCs that can address difficult-to-treat solid tumours with highly potent toxin payloads."

Dr Dave Simpson, CEO of Glythera, said:

"Glythera continues to add significant value to the ADC field, not only by improving the safety and efficacy of ADC targets in its partners development pipelines, but by accessing highly potent toxins and clinically important monoclonal antibodies for the development of our own next-generation ADC portfolio focused on improving the lives of patients living with difficult-to-treat cancers."