Glythera-42Antibody Drug Conjugates (ADCs) are monoclonal antibodies attached to biologically active drugs, often developed for use in the treatment of cancer. In today’s blog, Dave Simpson, Glythera CEO, discusses the rapidly growing pipeline of ADCs and the ever increasing demand for manufacturing capacity.

During the past decade the ADC pipeline has grown significantly from only eight distinct ADCs in clinical development in 2008 to over 60 in 2016. Whilst early targets were primarily focused towards the treatment of haematological disorders, the generation of newer ultra-potent toxins and, more recently, improved tumour penetration through alternative scaffolds has accelerated the growth in ADC discovery programmes, especially for the treatment of more difficult to treat solid tumours. This expanding pipeline has been mirrored by an increasing number of majors with an ADC focus as well as need for capability to manufacture.

ADCs are, by their very nature, complex entities, combining antibodies (whole or fragments) with potent toxins via conjugation chemistries and appropriate linkers. Even with the anticipated US $1 billion sales generated by the two currently approved ADCs Adcetris® and Kadcyla® and the rapid expansion of the field, relatively few innovators have elected to manufacture ADCs in-house with over 70% outsourcing their manufacturing to contract manufacturing organisations (CMOs).

Manufacturing houses require both biological capability and high containment cytotoxic facilities designed to handle compounds which have a very low Occupational Exposure Limits (OEL) – whilst maintaining aseptic and GMP compliance.

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Over the last 5 years, the CMO market has shifted dramatically from the manufacturing of blockbusters to specialist care drugs. Given the complexity of ADCs, there is a real prospect for manufacturing-oriented companies to offer specialised services through the provision of innovative solutions to current manufacturing challenges – and this, in turn, demands a highly skilled work force.

On top of the challenges of manufacturing drug substance for a selected antibody, plus a range of linker/payload chemistries, manufacturers face difficulties in generating homogeneous ADC and fill/ finish for the subsequent combination. Significant investment has been made by established CMOs and specialised services providers have emerged to support manufacturing by way of partnered supply chains or “one stop shops”.

With global revenues for contract manufacturing services estimated to reach US $60 million by 2018 – and ADC manufacturing anticipated to represent US $1 billion within the next decade – significant investments have been outlaid for facility expansion and to access broader services through mergers and acquisitions by established CMOs including Lonza, Piramal, Carbogen-Amics and Catalent.

Others have preferred to streamline their manufacturing process whilst broadening their potential client base and their manufacturing repertoire through supply chain partnerships. For example, FUJIFILM Diosynth Biotechnologies and Baxter BioPharma Solutions have signed up with Piramal and SAFC® respectively.

We have also seen the emergence of specialist service providers who support development and, perhaps more critically, provide a cost effective, compliant supply chain for early stage clinical trial material. In the UK Abzena, (formed through the combination of Polytherics and Antitope, and the subsequent acquisition of Pacific GMP and TCRS) has positioned itself as supporting a “bench to bedside” approach to ADCs including cell line development, ADC development and subsequent GMP manufacturing.

Glythera-445Thus, the development of ‘problem solving’ manufacturing platforms has underpinned the opportunity for companies to support ADC development and manufacturing. ADC Biotechnology was founded on proprietary technology which focussed on reducing ADC aggregation during manufacturing, therefore improving product safety profiles whilst accelerating ADC development programme timelines. The Company has recently announced significant investment to allow for the expansion of its facilities and capabilities, including GMP manufacturing of this important – and complicated – product class.

With the continued expansion of the clinical pipeline, the expectation of further approvals and the market opportunity for manufacturing of ADCs, there is no doubt that the industry will continue to see further increase in supply chain partnerships and investment into the expansion of current CMOs including those based within the UK.

Glythera is focussed on the development of next-generation ADCs underpinned by its proprietary conjugation/novel toxin platforms. The company was spun out from Bath University in 2007 and relocated to Newcastle upon Tyne in 2012, through ongoing investment support from IP Group and the North East Technology Fund.