Q&A: How an academic-industry alliance is reshaping the way research can lead to new medicines
ӳý researchers Matthew Meyerson and Heidi Greulich describe how they and Bayer scientists developed the first FDA-approved cancer drug to come from a ӳý scientific discovery.
Highlights
- A lung cancer drug recently approved by the FDA is the result both of by ӳý scientists two decades ago, and of a unique, years-long partnership between ӳý and Bayer Healthcare Pharmaceuticals.
- The ӳý-Bayer team overcame many scientific challenges to develop the new medicine.
- This is a research success story that shows how two decades of basic cancer research and long-term collaboration between academia and industry can generate new treatments for patients.
The FDA’s recent accelerated approval of a lung cancer drug is not only a milestone for the ӳý — it also shows how academic scientists with deep knowledge in cancer biology and industry experts in drug development working closely together over many years can solve the numerous challenges involved in making a new medicine.
The drug from Bayer Healthcare Pharmaceuticals, sevabertinib, is the first FDA-approved cancer treatment to come from a ӳý discovery, and is the result of a unique and more than decade-long alliance between ӳý and Bayer scientists. To learn more about how the drug was developed, the challenges that nearly stalled the effort, and the future outlook for new cancer drugs, we spoke with ӳý team leaders Matthew Meyerson, an institute member at the ӳý, the Charles A. Dana Chair in Human Cancer Genetics at Dana-Farber Cancer Institute, and professor of genetics and medicine at Dana-Farber and Harvard Medical School, and Heidi Greulich, an institute scientist and senior group leader in the ӳý’s Cancer Program.
What scientific discoveries led to the development of this new treatment?
Matthew Meyerson: If we go back to the year 2000, there were really no medical treatment options for patients with metastatic lung cancer. This changed with the beginning of genomic studies of lung cancer. In 2004, my colleagues Bill Sellers and Bruce Johnson and I our discovery that many lung tumors harbored mutations in the epidermal growth factor receptor (EGFR) gene. This helped solve the mystery of why the early targeted treatments that inhibited EGFR worked so well for some patients. We soon saw an explosion of new treatment options that targeted EGFR and other genes. Today, thanks to these medicines, some lung cancer patients with metastatic disease can survive ten years or more, which was unimaginable before these genomic discoveries. But not all patients have benefited.
Heidi Greulich: Twenty years ago, Matthew and I discovered that tumors from some patients who didn’t respond to EGFR inhibitors carried particular mutations in the EGFR gene known as “exon 20 insertions.” Those mutations were also found in the related gene for HER2. We knew that we would need something different to treat these patients, but the opportunity to develop a therapeutic for these patients didn't present itself until 10 years later when we started the ӳý-Bayer collaboration.
How did the ӳý and Bayer work together to develop sevabertinib?
MM: Collaborations between academia and industry play a huge role in driving forward medical research across many fronts, including cancer research. Academic research is the most likely to create truly novel breakthroughs that can become the basis for drug discovery in the long term, while industry has the capabilities to develop, engineer, and test new drugs at a very large scale. Marrying these capabilities provides a special opportunity to bring new treatments, new diagnoses, and new options for patients everywhere.
HG: Each party brought different expertise to the table and we worked together as a cohesive project team. At the ӳý, we brought genomics expertise, deep knowledge of lung cancer biology, and a little bit of the “outside-the-box” kind of thinking to the project. Bayer brought the drug discovery, medicinal chemistry, and pharmacology expertise, in addition to capabilities for launching and running clinical trials.
ӳý team members Kristyna Kotynkova (left) and Gizem Uzunbas (right) contributed to the research that led to sevabertinib's approval.
Contributions to this project were also made by colleagues in the ӳý’s technology platforms, including the Genetic Perturbation Platform, the Center for the Development of Therapeutics, and the Proteomics Platform, and by colleagues in the ӳý’s Cancer Program.
What were some of the challenges you faced in developing this new medicine?
HG: We encountered many challenges during the course of this project, so it wasn't smooth sailing all the way through. In fact, when we started the project, there were no cellular models available so we had to come up with a cellular assay that we could use to test early compounds.
Our initial cell assay was unstable, but heroic efforts from senior research associate Bethany Kaplan helped to stabilize the assay so that it was robust enough for compound testing. In addition, our chemistry colleagues at Bayer worked for years to improve the potency, selectivity, and stability of the compounds to eventually develop sevabertinib.
How did two decades of basic cancer research contribute to the development of the new drug?
MM: The development of sevabertinib is a real testament to the power of long-term collaborative partnerships. Heidi and I have been working together on EGFR and HER2 for 22 years now, and we've developed a lot of knowledge of these molecules and how they behave. Before that, Bill Sellers and I worked to explore alterations of tyrosine kinase enzymes in human cancer that led to the EGFR discovery. And going back even further, Bill and ӳý director Todd Golub and I worked to understand what happens in the genomes of human cancers more broadly. These long-term scientific collaborations and all the biological insight that came from them, along with our deep and continued commitment to solving the same problems, have really helped us to get to where we are today with the development of sevabertinib.
What’s next for sevabertinib and similar efforts?
MM: It is an extraordinary time to make many new treatments for patients with cancer and other diseases as well. The success of sevabertinib is a real proof-of-concept that we can do this again. If we can keep targeting the genomic causes of cancer in a disciplined and persistent way, we will continue making further advances in cancer treatment, so it’s important that we keep this momentum going forward. Here at the ӳý, with our industry partners, we could do this again, not just once, not just twice, but many, many more times, and I’m looking forward to our opportunities to do that.
Seeing this effort come to fruition after so many years of hard work, what are your reflections on this milestone?
MM: As a cancer researcher, it's just an incredible honor and privilege to be part of a team that has brought forward a new medicine that can help people with the terrible disease of lung cancer.
HG: Not all academic scientists have the opportunity to initiate and execute a drug discovery project that directly benefits patients, so we’ve been incredibly fortunate in this respect. The development of sevabertinib is also really meaningful for me personally. Both my parents passed away from cancer, and my father from lung cancer in particular. So the fact that I've made a contribution to help other lung cancer patients resonates with me and makes me really glad I come to work every day at the ӳý.
