2023 and beyond: revolutionising drug discovery

For drug discovery to advance in 2023, a modern approach to science is needed and we are already seeing success with revolutionary new research paradigms. Research involving multidisciplinary, public-private collaboration and increased patient involvement helped speed vaccines and therapies to the public during the COVID-19 pandemic and has proven to be more productive than traditional approaches to research and development (R&D).  

Multi-disciplinary, public-private collaboration

The traditional therapeutic area (TA)-approach to drug discovery and development is driven by observable and measurable patient symptoms, which are generally observed long after the onset of disease. Scientists working within this paradigm group patients together based upon their symptoms and the organs involved in their illnesses. Treatments are then developed by teams focused on a particular disease state or therapeutic area who work in silos.

As scientific understanding of underlying disease mechanisms has increased, we have learned that diseases, and their symptoms and sequelae can result from multiple biochemical mechanisms and pathways that do not necessarily fit into a single therapeutic area. For example, diabetes research calls for expertise in inflammation, heart failure and neuroscience, at a minimum, to understand how disease mechanisms influence these systems. However, only a few biopharmaceutical companies are doing work in all therapeutic areas that touch any one disease. A focus on a single therapeutic area when developing drugs generally results in therapies that treat everyone with a disease the same way, when the causes of their symptoms can involve very different mechanisms. Human biology is complex, and we must embrace and understand that complexity to develop more effective drugs faster. As the knowledge required to understand any given disease can cut across several disciplines, no one scientist can be proficient in everything that is needed to understand how biological systems interact to cause disease.

Multi-disciplinary partnerships fill this gap. Biopharmaceutical leaders historically have questioned the value of public-private partnerships and often felt they did not provide a concrete return-on-investment. Now, groups like the Biomarkers Consortium and ACTIV, which are led by the Foundation for the National Institutes of Health (FNIH), are pioneering approaches to these partnerships that result in highly productive collaborations that speed new therapies to patients and create new, foundational scientific knowledge that increases the efficiency of pharmaceutical R&D. The partnerships spread risk across collaborating organisations so that no one partner bears the full risk and cost of conducting precompetitive, basic science that does not result in a commercial product. While the science does serve to improve the impact and effectiveness of future products, it is so costly and risky that individual companies might not otherwise be able to conduct such research.

Public-private research partnerships begin with a scientific agenda and set of goals, which are defined by multi-disciplinary teams of funders, biopharmaceutical companies and scientists. Teams include patient advocates, biopharmaceutical companies, government agencies, academic institutions, and non-profit organisations, enabling these groups to work together in a way that would not be available to them under regular circumstances. The collaborative approach means that everyone involved knows exactly what they are paying for, including private sector partners who can use the results generated by the partnership in subsequent proprietary therapeutic development. The output of the work is returned to collaborators in the form of usable knowledge and tools for more efficient development of more effective therapies.

Organisations that oversee and facilitate the public-private partnerships help teams align on shared stakeholder goals while ensuring all disciplines across the scientific spectrum are included in the design and execution of a project. Information derived from these projects is often shared broadly, so that all scientists can incorporate it into their work and patient groups know that there is hope for potential new treatments.

Such partnerships provide benefits to all, and while sharing the risk may be enough incentive to participate, the results of the multidiscipline, multi-partner approach also provide increased scientific rigor, a deeper understanding of the underlying biology, an increase in fundamentally innovative advances, faster drug discovery and fewer “shots in the dark.” All these benefits can reduce the number of late-stage drug development failures and increase the rate of discovery for diseases with unmet need.

The more robust the information is about the disease, the faster and more efficiently we can get new therapies to the patients who need them. In the coming years, this public-private approach will improve hypothesis generation, target validation, and clinical tool and trial design. By adding a more mechanism-based biology approach to the drug discovery process, programmes can pull together vast quantities of data on drug targets that can inform which future work to pursue.

A timely example of this is long COVID. Standard practice would have us generate a treatment for a single symptom of long COVID after conducting a detailed analysis of the affected patient group and positioning them squarely within a single therapeutic area. If the symptom being pursued had appeared prior to the pandemic, that might be a reasonable approach, but because we have a rare opportunity to understand the common element, COVID-19, drug development for long COVID using a therapeutic area approach seems an unlikely pathway to a clinical candidate.

Given what we know about SARS-CoV-2 infections, the most plausible path to a cure for long COVID is understanding how the acute infection could have effects on what appear to be disparate systems. This leads to neuroscience, cardiovascular, immunology, metabolic, and respiratory researchers working closely with patients and industry to understand what happens to the human body after the acute infection has cleared. It is the perfect scenario to serve as a pilot to set up the framework for partnership between these groups and move from basic research to a commercial product.

Increased and earlier patient involvement

Another important trend is increased integration of patients into all aspects of the R&D process. In the past, patients’ thoughts and opinions were only minimally assessed. Bench scientists assumed the information we gathered by talking to physicians was sufficient, and that the mechanisms and underlying biology of a disease was outside the comprehension of a non-science-trained patient. However, this view has changed dramatically, trending toward recognition that patient input can streamline clinical trial design, enabling R&D to focus on the symptoms that have the most significant impact on patient lives. The next steps in this journey will require research approaches to continue evolving but will also require evolution in the thinking of patients themselves.

In my own experience, the non-science-trained public in the US is generally less interested in being involved in scientific research than those in other countries, often for valid reasons that grow out of historical misdeeds. Understudied populations have found their past input has been exploited and thus are wary of getting involved in research. Others feel the information gained from their involvement will be used against them or will not have direct impact on them. There are no easy solutions to these concerns and each needs to be addressed appropriately. But research will not progress in a meaningful way until these populations are involved in every stage and every aspect of R&D. I hope that the evolution of patient engagement allows scientists to spend more time gathering information about disease traits and symptoms directly from patients. While this may require training for the scientific community, the discussions that result can be truly illuminating and have great potential to inform the direction of research.

While these conversations will help remove the invisible barrier between scientists and the public, patients must be willing to put in the time and effort to tell us about their problems or we risk pursuing work that may not be relevant to people’s real lives. This means valuing the inclusion of patients in the R&D conversation in a meaningful way, right from the start. The trends I hope to see in patient engagement include bringing scientists, especially molecular scientists, together with patients to improve the information gathered about disease traits and symptoms through first-person storytelling. This approach can uncover data that patients do not tell their physicians and is the most important new frontier in the partnership space that is likely to grow in coming years.

In the past few years, the pandemic has highlighted many gaps in the public’s understanding of the scientific process, how treatments are developed and how evidence is used to make healthcare decisions. Increased patient engagement in the scientific process will help bridge these gaps. This year, initiatives that began early in the pandemic will begin publishing their findings on the causes of mistrust in science. However, no one group can be responsible for executing the resulting recommendations; the answer is increased partnerships with the public at every stage and more direct interaction with patients. Major, multidisciplinary, public-private partnerships will be necessary to ensure a positive impact and illuminate a path forward.

Dr Joseph Menetski is a Vice President of Research Partnerships at the Foundation for the US National Institutes of Health (FNIH), which is a non-profit organisation that creates and leads public-private partnerships to advance breakthrough biomedical discoveries and improve the quality of people’s lives. Dr Menetski has served in both the public and private sectors, including 12 years at Merck, 11 years at Pfizer and four years at the US National Institutes of Health. Menetski has expertise in biomarkers; molecular biology; biotechnology; respiratory disease and life sciences, with a focus on strong community and social services. He holds a PhD in molecular biology and biochemistry from Northwestern University, US.