Innovations from discovery to the clinic

Posted on: 14/12/2017

ADC community discussed the latest developments in the field

High Potency ADCS: from discovery to the clinic

The Knowledge Transfer Network hosted an event with MedImmune Cambridge and sponsored by ADCBio and Glythera bringing together the antibody drug conjugate (ADC) community to present the latest advances in the field as well as providing opportunity to network.

Paul Varley, VP Biopharmaceutical Development at MedImmune, opened the meeting as our host, and highlighted that, building on their respective strengths, MedImmune and AstraZeneca are well placed to be at the forefront of ADC development. The first session focussed on some aspects of the UK Innovation landscape, including the KTN itself, with Sarah Goulding giving an overview of the role we have in supporting industry in the UK. Mike Sullivan from Innovate UK updated on the recent funding opportunities relevant to the attendees and the scope of the Industrial Strategy Challenge Fund (ISCF), as well as a request to the audience for input on target areas for Wave 3 of the ISCF. The role that the Medicines Manufacturing Industrial Partnership (MMIP) plays in this area was outlined by Kit Erlebach from FujiFilm Diosynth Biotechnologies. He stated that ADCs are an example of complex medicines which MMIP have identified as an opportunity for the UK to become a world leader, and with the right environment hopefully the UK can capture investment and jobs in the future.

Dave Simpson from Glythera was the chair for the day and introduced his company colleague Ian Evetts. Ian provided an excellent overview of the current state of the ADC landscape, indicating the strength of interest and pipeline across the globe from key players in the market. He highlighted that despite some clinical failures, the number of ADC companies and clinical trials are rising and that innovation is addressing the issues with some of the earlier generation ADCs. Next, Deyarina Gonzalez from Swansea University presented the work of her group on developing ADCs against the receptor of advanced glycation endproduct (RAGE) for the treatment of gynaecological cancers. This included collaboration with ADCBIO on payloads.

Jenny Thirlway from Glythera presented on linker technology developed by her company. The technology, called PermaLink®, has improved stability, efficacy and tolerability as compared to maleimide linker technology in vitro and in vivo. In addition, Jenny presented data on novel payloads targeting CDK11 and inducing apoptosis in cancer cells.

Toni Georgiou from ADCBIO spoke about process development of ADCs enabled by a novel solid phase conjugation technology platform developed there. The platform, called Lock-Release, was shown to be amenable to a variety of different conjugation approaches and fully scalable. Data was presented which showed product quality advantages over standard solution phase methods where aggregation and toxin removal are problematic.  Lock-Release has the potential to be an enabling technology for difficult to manufacture ADCs.

Jeremy Parker (AstraZeneca) and Nick Bond (MedImmune), discussed their companies’ pipeline of eight ADCs, three of which are in clinical phase. Jeremy talked about their proprietary portfolio of payloads either developed by Spirogen (PBDs) or AstraZeneca (tubulysins) and the complexity of their manufacture both in terms of the number of synthesis steps and the containment facilities required. Nick talked about the process of assembling the complete ADC as well as the analyses carried out.

Kendall Morrison from US-based Agensys came over specifically to attend and present at the event. He told delegates about a well-tolerated ADC completely developed by the company and targeting FLT3, one of the five Agensys ADCs currently in clinical trials. The linkage technology that provides the stable link between toxin uses the Ambrx technology, introducing a non-natural amino acid into the antibody, which is used to link the payload to.

In our final session, Marcel Kuiper from the KTN facilitated a panel Q&A with many of our speakers. Key messages included the standing of academic and industrial ADC activities in the UK on the world stage, the lack of specialist high containment GMP facilities for ADCs in the UK and the establishment of an ADC focus group in the UK. Overall other key messages emerging from discussions were that there is much space for innovation in this field, from synthesis of payloads, to novel conjugation technologies, to the analytics needed and regulatory approaches to take these products through the clinic and into patients.

Commenting on the event, Paul Varley from MedImmune said:

“We were very pleased to host the ADC meeting organised by the Knowledge Transfer Network as it enabled the ADC community in the UK to come together and hear about the latest developments in the field, as well as provide opportunities to network and start new collaborations that may get innovations to market quicker.”

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