Q&A: How an academic-industry alliance is reshaping the way research can lead to new medicines

Contributions to this project were also made by colleagues in the Broad’s technology platforms, including the Genetic Perturbation Platform, the Center for the Development of Therapeutics, and the Proteomics Platform, and by colleagues in the Broad’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 Broad Institute 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 Broad, 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 Broad.