High hopes for high potency solutions

The world-wide number of pre-clinical drugs under development over 2017-2018 increased from 7493 to 8040, a whopping 7.3% ⁽¹⁾. The largest class of these drugs, synthetic chemicals, increased from 7855 to 7992 throughout the same period. The second largest, antibody drugs, similarly showed considerable growth from 1687 to 1809 (7.2%). Overall the largest therapeutic class, which many of these drugs belong, is anticancer drugs, accounting for growth of 7.6% from 4845 in 2017 to 5212 in 2018.

Antibody-drug conjugates or ADCs are an important class of highly potent biopharmaceutical drugs designed to treat people with cancer. They aim to target diseased tissue and deliver the drug to where it is needed. ADCs usually involve an antibody that targets cancer cells, linked to a cytotoxic drug. The drug is often called a payload; it and the linker are made synthetically. Many non-ADC anticancer drugs are also cytotoxic. With the strong growth in antibody drugs and anticancer drugs it is clear that the growing market needs suppliers with the appropriate expertise and facilities.

According to Grand View Research, the global antibody drug conjugates market size was valued at USD 1.57 billion in 2017 and is projected to register a compound annual growth rate of 25.9% over the period to 2025. Major advancements in linker technology coupled with extensive R&D activities are expected to drive the market.

There are currently four ADCs approved by the US Food and Drug Administration. The most recent to become commercially available is from Pfizer – Besponsa™ for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL). According to the ADC Review there are some 175 investigational ADCs in development – from early discovery to pivotal, late stage, clinical phase III studies.

The future of ADCs as a powerful tool in the targeted treatment of cancer is focused on four areas – choosing the target antigen, increasing the potency of the cytotoxic cargo, improving the properties of the linker, and reducing drug resistance.

Due to their inherent properties, traditional chemistry laboratories are not a suitable setting in which to synthesise and isolate highly potent drugs. It is unsafe to make these products without the necessary High Potency handling facilities. That explains why Apex Molecular recognised the need to build facilities to make and handle High Potency Active Pharmaceutical Ingredients or HPAPIs. A clean room facility with negative pressure isolator was constructed and operates at OEL < 1ng.m3 as an 8-hour time weighted average (TWA), as demonstrated through containment testing using a non-toxic surrogate. This allows containment of the most potent HPAPIs. Further specialist facilities including a chemistry laboratory and an independent air handling system that operates under a negative pressure cascade, and technical expertise back up this important niche service offering. Moreover, facilities are not enough and the appropriate project management and specialist staff training are needed to develop, implement and monitor suitable safety protocols.

As part of the service Apex Molecular offers a selection of ADC related products available from stock, both toxins (e.g. Duocarmycins, Pyrrolobenodiazepines or PBDs) and linkers (e.g. cleavable peptide derivatives such as Boc-Val-Ala-PAB-PNP).

As the Pre-Clinical market for cytotoxic and ADC related products grows, the supply side is sure to follow. Apex Molecular is one of the companies aiming to be part of that growth.

¹ Pharmaprojects Pharma R&D Annual Review 2018