The last two decades have seen an unprecedented expansion in the study of human biology, with advances in human genetics, cancer genomics, stem cell biology, bioinformatics and systems biology all paving the way for new therapies. In the future, advances not only in medicinal chemistry but in areas such as protein engineering, antibody drug conjugates (ADCs), bispecifics and immunotherapies will bring new targets into reach.
Explore some of the technologies and platforms we are using to discover and develop innovative medicines.
One way to enhance the therapeutic potential of antibodies is to combine, or “conjugate,” them with small molecule drugs, which enhances the antibody’s ability to target a specific antigen. Another way to boost the therapeutic potential of antibodies is to use a technology that allows the generation of a dual-specific antibody to target two antigens (also called a dual-variable domain [DVD] antibody).
Our bispecific platform is a technology that holds great promise. In the past, this has been referred to as DVD platform. In fact, this platform is capable of producing a wide range of different bispecific formats and DVD is just a small portion. These bispecific formats have a broad range of protein binding and biologic characteristics.
In oncology, we view our bispecific platform as a path to new biology rather than simply to combination therapy. For example, we are studying the uses of our bispecifics to enhance the performance of ADCs. In pre-clinical systems, we can show that a bispecific that binds to two portions of the same molecular target is taken up in the cancer cells better than a traditional ADC. This could deliver a greater toxin load, thereby enhancing efficacy.
Similarly, a bispecific that binds to two molecular targets from the same cancer cell can be used to increase tumour specificity, allowing us to prosecute targets that had some degree of expression in normal tissue. With our bispecific platform, we are able to create a wide range of protein constructs, ultimately leading to new biology with different mechanisms of action.
We are exploring several new methods for delivering medicines that are more precise and impactful. From reducing the effect of chemotherapy on healthy cells to opening new avenues for treating neurodegenerative diseases, our research on innovative, targeted drug delivery aims to change the way disease is treated.
ADCs represent a proven technology platform that delivers a therapeutic agent directly to where it’s needed using precise targeting of an antibody.
An ADC takes a highly potent toxin, one that is too potent to be administered systemically, and couples it to a monoclonal antibody so that it can be delivered directly to cancer cells, sparing normal tissue. The idea behind ADCs is not new, but it is only recently that the progress in target identification, antibody engineering, linker chemistry and toxin technology have come together to make this a promising platform.
Our strength in discovering and developing highly specific monoclonal antibodies and our experience in small molecule chemistry and analytics make ADCs a strong focus area of development for AbbVie.
Cancer stem cells are the roots of a tumour. They initiate and perpetuate tumour growth and are more resistant to chemotherapy and radiation therapies. Cancer stem cells are the tumour cells that metastasise, causing cancer to spread throughout the body.
With work initiated by Stemcentrx, our therapies are engineered to target cancer stem cells, subsequently delivering a potent drug that can kill them. We believe that targeting and eliminating cancer stem cells will enable long-term patient survival.
The complex and intricate system of cells that carries blood to the brain and spinal cord tissue is difficult to penetrate with biologic medicines. That’s why we are exploring new ways to cross the blood-brain barrier with nanoparticles and protein capsules. These innovative drug delivery systems may lead to advances in discovering and developing new medicines to treat diseases of the brain, like Alzheimer’s and Parkinson’s.
As we better understand human biology, we can also leverage the body to uncover new ways to fight disease. Cancer and immune-mediated diseases are two areas where recent research is showing how new solutions might come from within.
In oncology, we want to turn up the immune system to attack tumours, while for immunological diseases, we want to turn it down because it’s doing damage by attacking normal tissue inappropriately. The key to treating both types of diseases may involve immunotherapies.
For example, there is a constant battle between the immune system and tumours. Tumours use various mechanisms to avoid destruction by immune cells. One of the ways they do this is by engaging checkpoint receptors on immune cells. Checkpoint molecules are on-off switches in immune cells and their activation blocks an immune response to target what is identified as “foreign” in the body. When tumours engage these checkpoints, it makes it difficult for immune cells to identify the tumour as something they need to attack, thereby dampening their activity. The biggest breakthrough in immunotherapy in recent years came when scientists discovered that disrupting these checkpoint receptors can activate immune cells and result in antitumour responses.
The anti-tumour activity of checkpoint inhibitors teaches us that tumours can be controlled by the immune system, but checkpoint blockade is only one approach. We have been looking at various approaches beyond checkpoint inhibitors for several years.
There has been an increased emphasis on the gut microbiome in recent years. Bacteria and microorganisms in our gastrointestinal tract perform critical functions like digestion and vitamin production, and the ability to easily reprogramme bacteria to perform other functions, thereby changing the way researchers tackle serious diseases. Together with Synlogic, we are studying the gut microbiome to develop new medicines for treating inflammatory bowel disease.
Our medicines are only as effective as our ability to deliver them. We continue to look for new ways to ensure our discoveries can be manufactured and delivered to patients safely and with the highest quality.
Success in biologics manufacturing is largely measured by product reproducibility. Through sophisticated cell line development, cell culture manufacturing and quality control, we overcome the complexity of large molecule manufacturing to deliver consistent drug performance. Our expertise in biologics is rooted in having developed the first fully human monoclonal antibody. Today, our biologics manufacturing team continues to be leaders in the field, providing scientific support for all aspects of our manufacturing. Our team partners with R&D and our contract manufacturing clients to scale up and transfer new products into commercial manufacturing sites, troubleshoot technical problems associated with product manufacturing or laboratory tests and identify and implement process enhancements to increase yields or throughput. We support chemical and fermentation drug substances, sterile and non-sterile drug products, analytical test methods and devices as enablers of drug delivery.
A common problem in drug research occurs when a medicine won’t dissolve in water and, therefore, cannot be absorbed in the body. We have found a way to use the same melt extrusion techniques that have been used in industrial settings for centuries and apply them to medicine, opening possibilities for the formulation of new drugs to treat patients with a variety of diseases, from viral infections to cancer.