Innovation in an Era of Transformation

One of my core beliefs is that we are at a hinge moment in the biopharmaceutical industry, where we are seeing profound changes in drug discovery and development powered by the union of technology and biotechnology.

At @Amgen we have been preparing for this moment for over a decade, leveraging our expertise in collecting and analyzing human data, developing multispecific drugs and investing in the power of artificial intelligence (AI) and other technologies to create the next generation of biologics.

We have been applying this expertise in Research to target diseases with high unmet need where we feel we can bring the most value to patients. These areas are in:

·??????Inflammation: Particularly in the areas of dermatology, respiratory disease, gastroenterology and rheumatology

·??????Cancer: In both solid and hematologic oncology

·??????General medicine: Including cardiovascular disease and metabolism

Since 2012 we have been building a human data resource that now comprises 2.5 million genotypes from around the world, including more than 350,000 whole genomes, 18,000 transcriptomes and 100,000 proteomes, coupled with phenotypic data for over 10,000 traits across 2.5 million individuals. All told, we have an incredible 100 petabytes (PB), or 100,000,000 gigabytes of data. To put this into context, the movie?Avatar?needed?about 1 PB of storage?to render those groundbreaking graphics. With this data at our disposal, 65% of our inflammation and general medicine portfolios already benefit from genetic validation. We also have access to large swaths of de-identified real-world data through partnerships in Utah, the UK and elsewhere. These data help us select the right target for the right patient and provide the most benefit from our therapies, so we can lead the way into the era of precision medicine. Our human data capabilities already inform almost all our programs that enter clinical development.

Using many of the insights we have gained from human data, we are accelerating our research in multispecific therapeutics, led by my colleague @Ray Deshaies, Senior Vice President of Global Research. This new modality has the potential to drug what was once thought to be “undruggable.” But we can’t do it alone. Our internal capabilities complement external innovation that includes acquisitions such as Nuevolution, now Amgen Research Copenhagen, whose DNA encoded library technology is enabling us to find drugs that bind targets of interest more quickly and efficiently. More recently we acquired Teneobio, whose more compact, single chain antibodies are allowing us to build highly sophisticated multispecific molecules. And in 2022 we announced partnerships with Arrakis Therapeutics and Plexium, companies that are working on drugs that use the principle of induced proximity to bring together otherwise undruggable targets with RNA, protein and other degradation mechanisms found naturally in the cell.

Leading the way in large molecule development is @Alan Russell, Vice President of Biologics. His team is building our in silico protein research platform that uses computer modeling, AI and machine learning for improved target discovery and drug design. Thanks to advances like Google’s AlphaFold and RoseTTA fold from the Institute for Protein Design at the University of Washington, science is finally connecting a protein’s sequence to its structure and function. This new knowledge will allow us to move toward a new generation of protein drug design. We are now progressing from iterative cycles, where we repeatedly test potential therapeutics until we obtain a marketable molecule, to a more generative approach that uses machine learning and automation, as well as vast amounts of data from past molecular discoveries to design products at speeds previously unheard of. To help us in these endeavors, we have partnered with Generative Biomedicines to leverage its AI-powered protein engineering platform. Amgen's combined wet and dry lab generative biology capabilities have already cut in half antibody discovery timelines, doubled protein engineering success rates and reduced protein engineering timelines by approximately 70%.

Everything we do in R&D at Amgen is guided by our strategic vision, which is to benefit patients and societies through transformative medicines. To accomplish this, we aim to be the first and the best at making groundbreaking discoveries that bring as much value to patients as possible. By investing in an innovative research engine that includes human data, multispecifics and next-generation biologics, we are ready for the convergence of biology and technology that I believe will fuel the industry well beyond this current decade and change the practice of medicine.

For more information on Amgen’s strategy and cautionary statement regarding forward-looking statements, please see our Business Review Meeting webcast.

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