“Rewriting the manual” for precision medicine

“Rewriting the manual” for precision medicine

Precision medicine puts the patient at the center of healthcare, using a variety of tools to develop tailored and targeted therapies and diagnostics.

Promising to “revolutionize” the landscape of modern medicine, precision medicine requires in-depth knowledge of the molecular underpinnings of healthy and diseased states. Advances in molecular biology techniques and bioinformatics platforms help provide this knowledge, equipping researchers and physicians with the tools to implement precision medicine approaches in different disease areas.

So far, oncology – the field of cancer research and treatment – ​​has arguably benefited the most from precision medicine. However, pharmaceutical and biotech company AstraZeneca believes that precision medicine will “rewrite the manual” for the diagnosis and treatment of chronic diseases. Technology networks recently had the pleasure of speaking with Mark FidockVice President of Diagnostic Development, Precision Medicine at AstraZeneca, to find out how the company is “rising to the challenge” of delivering precision medicines for chronic diseases.

Molly Campbell (MC): Can you talk about some of the ways AstraZeneca is actively pursuing precision medicine?

Mark Fidock (MF): I think an interesting metric is that when we look at our portfolio, over 90% of it has a precision medicine strategy. Precision medicine as a strategy and as a discipline really encompasses the entire spectrum of drug research and development. This includes finding new targets – which requires the use of cutting-edge methods available – advancing and innovating new technologies and, of course, driving for better patient outcomes and a healthier healthcare system. sustainable.

Oncology is one of the areas in which we have made major advances. AstraZeneca has already completed more than 50 regulatory-approved companion diagnostics in a variety of indications and in a variety of different specimen types. This has made it possible to develop innovative targeted therapies and benefit millions of cancer patients worldwide.

The work and success we have had in oncology has almost produced a “framework” for which we can develop precision medicine approaches for chronic disease. However, we need to recognize that chronic diseases are biologically complex, of very heterogeneous origin, so a key priority in this space is to investigate the ways in which precision medicine can be deployed and used, which increases our understanding of the disease and leads to better patient care. results.

The opportunity in the field of precision medicine is huge, especially for chronic diseases. We are now in a time where, thanks to precision medicine, we are rewriting the textbooks for many indications and changing the way we ultimately treat patients.

MC: Let’s talk more about tools and technologies. What are the main technological developments that help us understand the biology of diseases and use this information to adapt treatments?

FM: One of the key technology areas (in which AstraZeneca is a leader) is genomics research. Our in-house genomics research center aims to sequence 2 million genomes by 2026 – which, of course, isn’t that far away now. Using highly innovative bioinformatics analysis methods, the groups behind this project are looking for rare variants associated with diseases. In doing so, they uncover new biological insights into disease, discover new therapeutic targets, and describe diseases in a much more granular – almost molecular – or genetic way.

This creates opportunities for the development of targeted therapies for different segments of a particular disease.

Key examples include the discovery of new targets in respiratory and immunological diseases, cardiovascular research, and renal and metabolic diseases. One of AstraZeneca’s areas of focus is pulmonary fibrosis, and the group previously published the discovery of a gene called SPDL1 identified in idiopathic pulmonary fibrosis.

The SPDL1 The gene encodes a protein known as “Spindly” which is responsible for signaling during cell division. Previously, this gene had not been described in relation to idiopathic pulmonary fibrosis. The identification of a new mechanism underlying the disease opens the door to new therapeutic discoveries.

In cardiomyopathy, the group also published a conclusion on the NTT embarrassed. These two examples are key examples of how genomic techniques can be used to inform our understanding of disease. These publications have been widely distributed within the scientific community.

The NTT The gene codes for a protein called “titin”. Truncated variants of the gene contribute to about 15-25% of cases of non-ischemic dilated cardiomyopathy, a condition in which the left ventricle enlarges.

MC: Can you tell us about the importance of biomarkers in precision medicine? How are they used to identify patients and develop targeted therapies?

FM: I think the opportunity space for precision medicine in all of the disease indications that AstraZeneca is exploring is huge. It will improve our ability to rewrite the medical textbooks that doctors use to understand, diagnose and treat disease.

How do we do this? A critical aspect of precision medicine is identifying predictive biomarkers, which is achieved through information gathered through genomic studies and other means. Predictive biomarkers provide the opportunity to enroll the right patients in our clinical trials and develop targeted companion diagnostics and treatment approaches in the most appropriate way.

In disease areas where we already have several targeted treatment options, we have also identified biomarkers to select patients. An example is in non-alcoholic steatohepatitis (NASH) where A second example is IL33 – a cytokine that is seen and elevated in many different indications, from asthma to diabetic kidney disease and even in COVID-19.

These are areas where the biomarker – and the scientific research surrounding the biomarker – helps us identify the right patients, allowing us to direct where our targeted therapies will have the most beneficial clinical outcomes.

MC: Can you talk about the importance of collaboration in the field of precision medicine? How does AstraZeneca pursue collaborative projects?

FM: AstraZeneca works in a very collaborative waywith numerous collaborations established in each of the different research spaces in which we choose to operate.

We need to develop companion diagnostics that are scalable and have global reach, so that they not only align with our targeted treatments, but are also analytically and clinically validated and demonstrate patient benefits. We have built global partnerships to provide these tests that can be marketed, which really allows maximum access for patients. It also ensures that these diagnostics are used consistently within regulatory requirements in all regions of the world where they will be used.

Through one of our collaborations with Almac, we are developing and validating companion diagnostic tests for patient selection in a variety of different clinical trials for a range of therapeutic areas, such as chronic kidney disease, NASH and respiratory diseases. This is a solid framework that we can adapt for use with other ongoing collaborations, such as our work with Roche diagnosticsamong others.

In terms of challenges, when you’re innovative, leading in a space, and creating information that “rewrites the rules” and “rewrites” the ways in which treatments are derived, there will of course be challenges. I think we can all agree that health is a fundamental right that we should everything have access, and that it should be inclusive and tailored to the individual. We believe that precision medicine will be an essential part of this offer, that it will improve health and that it will improve health equity. We need to have discussions to ensure that all health systems can fully embrace this approach in clinical practice, which is achieved through interactions, partnerships, and participation in symposia and summits. We recently spoke at the World Health Summit, and AstraZeneca aims, with panels of external leaders from different diagnostic organizations, to discuss policy and consider ways in which we can help bring new approaches to clinical community and health care facilities.

MC: Looking at the future of precision medicine, what are AstraZeneca’s top priorities for precision medicine? What do you think this space will look like in, say, 10 to 15 years?

FM: The more we use precision medicine in the area of ​​chronic diseases, and the more science really begins to uncover how these complex chronic diseases are derived and their etiology, the more we can seek to develop new therapeutic modalities.. We can identify the right patient populations for diagnostics to target treatments, and ultimately that will produce much better patient outcomes in the long run.

What will it look like in the future? I think a key objective is to ask: how do we introduce new diagnostics into clinical practice? How to bring precision medicine to the patient? The future is patient comfort. One day it would be fantastic to be able to bring molecular diagnostic devices into the home, so that patients can monitor their illnesses as they arise. This will involve bringing digital advances – such as advances in artificial intelligence (AI) – to the various areas of precision medicine. How do we do this? How do we use digital media to derive actionable diagnostic data, where patients can take a diagnostic test in their own environment, this data is then shared with their treating physician enabling decisions and discussions in the interest patients ? These will be important considerations.

A big part of the future is to further develop the scientific understanding of chronic disease and bring together all the learnings we’ve had in precision medicine and maximize patient outcomes. The future of precision medicine is having a deep understanding of chronic disease at the molecular, genetic or metabolic level, so that we can truly ensure that the patient is at the heart of it all, and that they can have the advantage and convenience of precision medicine in the future.

Mark Fidock, Vice President of Diagnostics Development, Precision Medicine at AstraZeneca, spoke with Molly Campbell, Senior Science Writer for Technology Networks.

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