Beyond the R&D Pharma Walls: Safari visit of Middle Eastern and African Researchers

Not many academic researchers have had the opportunity to visit the Pharma R&D facilities and interact directly with the active scientists. Academic researchers wonder what lies behind the walls of Pharma R&D and how its scientists operate. On a rare occasion, AbbVie organised a three-day trip for 14 selected researchers from the Middle East (Saudi Arabia, UAE, Kuwait, and Iraq) and Africa (Algeria, Egypt, and South Africa) to visit its research facility. During the visit, the company’s scientists gave an overview of the drug discovery and development process, covering both small molecules and biologicals, in the form of an antibody drug conjugate.

In the discovery part, the scientists described the process of target identification using several approaches, including studying patient samples with exome and whole-genome sequencing to dissect the possible biological pathways involved in the malignancy. The plausible biological mechanism needs to be validated by targeting the involved targets using small molecules, CRISPR, peptides, and other tools to pinpoint the most likely target(s). The scientists gave a real example of their ongoing projects with real data.

Such an approach gave us a real sense of how the work is being planned and carried out, with milestones, across several platforms. The presenting scientists all agree that the most critical part in any drug discovery project is the identification of the target(s), a step that needs both deep understanding of disease biology, skilled scientists who can overcome any technical challenge to answer the question being addressed as well as the availability of the cutting-edge technology to carry out the work in a very speedy manner.

Once this step is successfully carried out and the potential target is identified, the next step is to screen the large set of over 2 million small molecules using high-throughput screening or to generate antibodies to the target, a phase called the HIT identification. This step is followed by HIT optimisation and candidate selection, carried out by the genius medicinal chemists for small molecules and by the protein modellers for the antibody-based approach. This process can take up to 6 years, followed by another 6 years in clinical development, and the whole process can cost over 1 billion US dollars.

The visit allowed us to learn about the CRISPR technology used in CAR-T cell-based cancer therapy and gene therapy for rare diseases. The rate of rare diseases is high in the Arab world and Africa, and the affected population in this region represents up to 6% of the global population due to consanguineous marriage. This later represents 25-60% in the Arab world and makes it a leading cause of infant death in a few Gulf nations. The most prevalent diseases are thalassaemia, sickle cell disease, Gaucher's disease, and Fabry disease. Saudi Arabia, represented by the Ministry of National Guard Health Affairs (MNGHA), is the first authorised treatment centre to use the CRISPR-based therapy for sickle cell disease. It provides Casgevy (exagamglogene autotemcel) for eligible patients with sickle cell disease aged 12 years and older. Casgevy is the first approved therapy in the U.S. that uses the innovative CRISPR gene-editing tool. Moreover, a number of centres across the Arab world and Africa are treating cancer patients with CAR-T cells generated using CRISPR technology. During our visit, we learnt how the pharma companies are adopting CRISPR technology to develop innovative therapies for unmet medical needs.

The most interesting part of the program is visiting the real R&D Pharma labs, “Beyond the walls,” where the whole work is being carried out. We found well-organised labs and highly skilled, experienced scientists ready to take on any challenging tasks. The most exciting part was visiting the simple fume hood and chemistry setting where the JAK1 inhibitor upadacitinib, sold under the brand name RINVOQ, was first discovered and synthesised. The setting was preserved as a living chemistry museum where the reaction leading to RINVOQ discovery was made, with even the chart of the chemistry synthesis.

RINVOQ is a selective inhibitor of Janus kinase 1 (JAK1) used to treat a variety of immune-mediated inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and Crohn’s disease. The visit also included the GMP facility for scaling up ADC therapies used to treat various diseases. It ended with a half-day discussion on the best approach to increase the appeal of clinical trials in the Middle East and Africa, making the region a global hub.

The final day was dedicated to a workshop bringing together all participants and organisers. The workshop focused on the methods and resources needed to develop research in African and Middle Eastern countries. The discussion was very rich and fruitful, identifying the needs and resources of different countries in the region. We concluded that Pharmaceutical companies need to collaborate with scientific leaders in these countries to improve access to research.

In summary, such a visit will be a long-lasting memory for all of us, guiding us to follow the Pharma R&D footsteps in setting up Drug Discovery and Development programs. Access to the Pharma R&D facilities of various pharmaceutical companies should be opened to academicians to boost Pharma-Academia collaboration, which is essential for discovering innovative therapies to address unmet medical needs.

It is important to consider researchers from the developing world, including Africa, South America, Asia, and the Middle East.

1 King Abdullah International Medical Research Center (KAIMRC), KSAU-HS, MNGHA, Riyadh, Kingdom of Saudi Arabia

2 Ministry of Pharmaceutical Industry, Algiers, Algeria

3 Health Life Science, Department of Health, Abu Dhabi, United Arab Emirates

4 Benimessous University Hospital, Algiers, Algeria

5 Amiri Hospital, Kuwait