A: There has never been a better time to invest in large initiatives in human genetics research. The successes of the first era of the human genome revolution created a great foundation for today’s discoveries. Technology development has enabled unprecedented scale and the ability to link genomic data to high quality clinical data. The current era of genomic discovery has tremendous potential and will fuel the next wave of great scientific and medical advances.

A: Geisinger has been a terrific partner and a cornerstone of our genetics program at Regeneron. They pioneered the innovative use of electronic health records, biobanking, and genomic medicine, making them the ideal partner for a large-scale genomics initiative. The relationship brings together two like-minded organizations focused on making genomic data medically actionable and translating genetic discoveries into improved patient outcomes.

At the time, it might have been considered somewhat of an unconventional partnership between a health provider organization and a biotech partner, but what initially brought us together was a shared vision and aspiration to implement genomics at an unprecedented scale and in a transformative way. When the partnership was first imagined, the goal was to sequence at least 100,000 individuals and that in the near future everyone (several million people) at Geisinger would have the opportunity to join the study.

Through our shared mission, the collaboration has allowed Geisinger to improve individualized patient care by having qualified providers and genetic counselors validate and return medically actionable information to patients. Meanwhile, the RGC has been able to create a robust database from which to analyze genomic data, making meaningful associations between genes and diseases, ultimately leading to new drug targets and the ability to help guide the development of our therapeutics.

A: The RGC and Geisinger have published many findings in peer-reviewed journals, scientific and medical conferences, and are committed to sharing findings with the scientific community. Further, as part of a recent study published inScience, Geisinger and RGC have publicly released allele frequencies from the first 50,000 sequenced participants. In the long-term, the anticipated benefit is of course the improvement of patient outcomes and the potential development of new and improved medicines based on the early research findings that we are seeing today.

A: The RGC has been wildly successful for Regeneron delivering results and discoveries that advance our science and drug development pipeline. We have fully integrated human genetics into every function and in the evaluation of every target and therapeutic. It has become an essential component of how we conduct our everyday R&D activities. We have advanced dozens of genes from our genetics discoveries into early stages of research and target evaluation. We have identified numerous targets in many diseases, including chronic liver diseases, diabetes, heart failure, depression, asthma and COPD.

We also ask questions about existing targets and development programs, enabling us to provide important new insights guiding our development strategy. For instance, we recently reported that we have identified loss of function mutations in the ANGPTL3 gene (the target of one of our late stage antibodies) that confer protection from coronary heart disease. Similarly, a recent publication of ours highlighted the discovery that inactivating mutations of the ANGPTL4 gene are associated with a significantly reduced risk of coronary heart disease; these same mutations also reduce the risk of diabetes. Many of our findings are already being used to inform Regeneron’s R&D programs, with the ultimate goal of developing treatments for patients in need. There’s much more to come.

A: Challenges and opportunities present themselves in all of these areas with large-scale genetics initiatives. One of the major challenges is securing high quality phenotypic data, which is paramount in understanding the effects of genetic mutations on disease. Further, large sample sizes are needed to detect and replicate these effects for rare genetic mutations, where many of the most informative genetic mutations occur. There are significant informatics and computational challenges related to handling and analyzing large datasets as well as interpreting many of the millions of genetic mutations that we observe. Advances in these fields will be critical to unlock future genomic discoveries. Perhaps most importantly, we believe that these genetics initiatives must be fully integrated with capabilities for biological and clinical validation to truly extend genetics research discoveries into translational opportunities that impact patients and human health.