“My ultimate goal is to cure cancer”

Drug discovery is hard - Oncology, particularly, is one of the most challenging areas of medicine. It requires passionate and resilient individuals that have the courage to be bold, take risks and face setbacks with an unwavering optimism. Norbert Kraut is one such individual, whose relentless efforts have given rise to some of Boehringer's most advanced assets in oncology.

Norbert has dedicated over two decades to cancer research at Boehringer Ingelheim. With his team in Vienna, he is driving the discovery of new treatments for people living with hard-to-treat cancers. Even prior to taking up the reins as the Global Head of Cancer Research in 2014, Norbert was determined to go after the high-hanging fruits.

“We’re working on the most impactful, but also most challenging, cancer drivers: those that have already been drugged but would benefit from further improvements in potency and selectivity, and those that have remained undrugged for decades. We are also exploring completely new targets in areas of high unmet patient need.” Norbert explains.

His drug discovery programs include addressing alterations in the p53, HER2 and KRAS pathways, which account for more than half of all cancers ^1–4.

“Targeting of the p53 and HER2 pathways with new chemistries comes with several challenges, but great potential. We were determined to push the boundaries to hopefully raise the bar for patients.”

The challenges continue with KRAS – the holy grail of drug discovery. Scientists have been going after the “Everest of oncogenes” for the past four decades ².

“Our long-term commitment to the patient’s needs allows us to stay focused on tackling major scientific challenges in a variety of ways. But we can’t always do it alone. We need a diversity of minds to be successful.”

Norbert is working together with Piro Lito's lab at the Memorial Sloan Kettering Cancer Center to target a broad range of KRAS Mutations. Their recent publication in Nature is paving the way to potentially address extensive unmet needs of people with KRAS-driven cancers ⁵. 

Norbert, what progress have you seen in the way we are discovering new targets and treatments in the oncology space?

Precision medicine has become an integral part of our strategy. We need to deeply understand the biology and genetics of a tumor and leverage innovations in drug discovery and data analytics to find new and improved ways to tackle cancer. 

We have significantly expanded our capabilities in generating, accessing, and analyzing data from large-scale functional screenings in cancer models, as well as from patients through biobanks, clinical data, and consortia. By employing new computational approaches to these datasets, we can generate a comprehensive landscape of cancer drivers and other key cancer dependencies.

We can also identify biomarkers that help us build strong hypotheses about which patient populations would most benefit from our compounds. This can not only increase the likelihood of success in the clinic, but also guide the expansion to further indications. These biomarkers can also assist in dose selection, demonstrate mode-of-action, guide potential combinations, monitor resistance mechanisms, and inform the next generation of treatments.

We are exploring and investing in several new therapeutic modalities and platform technologies. What benefits can they bring to patients?

We take an open-minded approach to modalities. We first start with what the patient needs and then harness the biology to reveal insights that inform our decision-making on the modality. We have a series of cutting-edge therapeutic modalities and platforms available to us which give us the opportunity to address targets and disease mechanisms that were previously not possible through more conventional methods. Importantly, they also allow us to tackle key cancer targets with improved precision, efficacy, safety, and in the end, make a difference for people with cancer. 

Ultimately, our technology platforms enable us to build combinations of therapies with complementary approaches. This is based on our knowledge that cancer is a complex and heterogeneous disease and requires a holistic approach to drive long-term response in patients.

What has been driving you all these years?

I come to work every day because my ultimate goal is to cure cancer. Nearly all of us have somehow been impacted by this disease. This moves us to something bigger than just a job. It gives us the determination and inspiration to connect and team up to accelerate life-changing science.

Losing my mentor, and later my mother, very quickly to cancer, has given me a strong sense of urgency. We need to bring better treatments to the hands of patients as fast as we can, but also work together to ensure equal access to these innovations.

What do you like most about doing research at Boehringer Ingelheim?

The people and our unique culture of innovation are what sets us apart. I’ve had the privilege of working with remarkable colleagues and partners, who share my passion for science, dedication to patients, and relentless persistence to seek the next generation of medicines. 

Our independent structure fosters a long-term commitment to the patient’s greatest needs but also allows us to live our curiosity as scientists and advance the science. I believe that altogether these produce the spark that makes innovation happen.

Our commitment to oncology 

At Boehringer Ingelheim, we have made a generational commitment to transforming cancer care, with the ultimate goal of curing a range of cancers.  We are investigating cancer cell-directed therapies that target key cancer drivers and hallmarks to directly kill cancer cells. In parallel, within immuno-oncology therapies, we are exploring new ways of directing and boosting the immune system against cancer cells. We believe that it is the smart combination of these approaches that could offer the greatest benefit for people living with cancer. 

References

1. Wang, H., Guo, M., Wei, H. & Chen, Y. Targeting p53 pathways: mechanisms, structures, and advances in therapy. Signal Transduct. Target. Ther. 8, 1–35 (2023).
2. Hofmann, M. H., Gerlach, D., Misale, S., Petronczki, M. & Kraut, N. Expanding the Reach of Precision Oncology by Drugging All KRAS Mutants. Cancer Discov. 12, 924–937 (2022).
3. Wilding, B. et al. Discovery of potent and selective HER2 inhibitors with efficacy against HER2 exon 20 insertion-driven tumors, which preserve wild-type EGFR signaling. Nat. Cancer 3, 821–836 (2022).
4. Lorusso, P. et al. The MDM2–p53 Antagonist Brigimadlin (BI 907828) in Patients with Advanced or Metastatic Solid Tumors: Results of a Phase Ia, First-in-Human, Dose-Escalation Study. Cancer Discov. 13, 1802–1813 (2023).
5. Kim, D. et al. Pan-KRAS inhibitor disables oncogenic signalling and tumour growth. Nature 619, 160–166 (2023).