Instead, McConnell looked for someone to team up with. US researcher Dr. Stephen Fesik from Vanderbilt University in Nashville fit the profile. Fesik had been researching KRAS there since 2009 and had developed a new technology: fragment-based drug discovery, an innovative approach that can find drugs for the toughest targets. Fesik had advanced this approach at the pharmaceutical company Abbott Laboratories (now AbbVie), where he had been working from 2000 to 2009 as the head of cancer research. He is considered a pioneer in his field; Fesik and colleagues at Abbott developed a medication, which is used to treat leukemia.
When McConnell called Fesik in 2013, he was unsurprised, because many pharmaceutical companies consulted him regularly. Fesik flew to Vienna for two days – and was met with a storm of questions from Boehringer Ingelheim’s researchers. “It was very clear to me that they truly wanted to change something.” What impressed him even more, was the fact that Boehringer Ingelheim was truly interested in a serious exchange. Other companies had invited Fesik to agree with their ways of doing things. In Vienna, the situation was different. “They wanted my opinion, and they have implemented my advice.”
The initial consulting service turned into a formal cooperation between Boehringer Ingelheim and Vanderbilt University which is now entering its seventh year. Today, Fesik and McConnell are working together to shut off KRAS entirely. They pursue this by searching for structures to serve as “keys” that fit exactly into the “locks” on the surface of the KRAS protein. Thanks to highly sensitive biophysical measurement methods, they can precisely examine nearly every molecule that binds to the protein’s surface. Using X-ray crystallography, they can view the “keys” and “locks” all the way down to the atomic level. Thanks to this cooperation with Fesik, Boehringer Ingelheim has discovered not just one but a number of such “keys” to KRAS and other cancer-causing proteins.
The two pioneers agree that they would never have made it so far on their own. While McConnell knew that he needed to blaze entirely new trails, Fesik needed Boehringer Ingelheim’s manpower. Working together, the two of them realized that they needed to combine the KRAS inhibitors with other medications to achieve real options for treatment. In September 2019, Boehringer Ingelheim entered into a partnership with the Indian pharmaceutical company Lupin, which had developed what is known as a MEK inhibitor.