From HIV to CAR-T: “Here is the model through which Gilead’s research focuses on the science of connections”

In virology, decades of research have led to the creation of an extensive library of molecules and a deep understanding of the biological mechanisms underpinning many diseases. Over time, this ever-growing body of scientific knowledge has served as a starting point for exploring new therapeutic applications, by identifying biological processes common to different diseases. ‘When we fully understand these mechanisms, we can develop innovative therapies capable of targeting the processes that cause disease, moving beyond the traditional distinction between organs and between medical specialities,’ explains Dietmar Berger, Chief Medical Officer at Gilead Sciences. “This is the direction in which biomedical research is moving today, increasingly focused on studying the biological mechanisms shared by diseases that medicine has traditionally addressed in separate fields.”

This approach is based on a different way of designing drugs: rather than developing each molecule from scratch, researchers are developing molecular platforms that can be adapted to different biological targets, leading to new therapeutic applications. In cell therapies, for example, the process by which the patient’s lymphocytes are modified remains the same, whilst the part of the receptor that directs them towards a specific tumour changes; thus, from a single foundation, multiple generations of treatments for different diseases can be developed. The same logic underpins the development of so-called ADCs, Antibody-Drug Conjugates, one of the fields in which cancer research is advancing most rapidly. The research approach of the biopharmaceutical company Gilead is a concrete example of this model: originating in the field of virology, with the development of the first innovative therapies against HIV and viral hepatitis, it has progressively applied the knowledge gained in this field to oncology and inflammatory diseases, to the extent that today it has the broadest clinical development pipeline in its history (since 1987), with over 50 research and development programmes already in clinical trials – spread across the three areas – and more than 100 projects in the early stages.

“We are gaining an ever-better understanding of diseases, their mechanisms and targets, and we can apply what we learn in one area to others,” continues Berger. “In the coming years, research will need to focus on the commonalities between different diseases, using scientific and technological platforms to transform this knowledge into new therapies.” The immune system is involved in different ways depending on the therapeutic area. In infections such as HIV, research focuses on controlling the virus and its persistence in the body, whilst in other areas the work centres on regulating the immune response. ‘In oncology, the aim is to stimulate the immune system so that it recognises and eliminates the tumour, whilst in inflammatory diseases the objective is to dampen its hyperactivity, learning to bring the response back within appropriate levels,’ observes Berger.

One of the most striking examples of the potential to transfer scientific knowledge from one disease to another is HIV, an area in which Gilead has always been active (today, around 75 per cent of people living with the virus worldwide receive treatment developed through the company’s work). “The most effective treatments for HIV today act simultaneously on two or three targets of the virus, and this approach has made all the difference,” says Berger. “It is precisely the study of the immunological consequences associated with this infection that has paved the way for different treatment strategies and, in the long term, for the search for a cure.”

The transition from this approach to clinical practice is also made possible by tools that allow the disease to be observed in a level of detail that was unattainable until recently. We have moved from analysing a single gene – and the protein it encodes – to sequencing the entire genome, which, in various forms of cancer, enables us to identify the different factors driving the disease in individual patients. Artificial intelligence enables us to synthesise the scientific literature produced worldwide, to design molecules tailored to a specific target, and to identify patients who share the same underlying mechanism. When applied to the analysis of medical images, has made decisions on progressing from phase 2 to phase 3 of clinical trials 50 per cent faster. ‘AI is a tool capable of generating insights from quantities of data that were once impossible to analyse, whilst defining the actions to be taken and interpreting the results remain the researcher’s tasks,’ explains Berger. “Since models are trained on existing data, exploring uncharted territory requires human creativity, which artificial intelligence can support without replacing it.”