Oncology Translational Science

A patient-centric translational strategy

In the pharmaceutical industry, the success rate of drug candidates in clinical trials is less than 10%. The primary reason for this is the difficulty in translating safety and efficacy data from non-clinical to clinical phases. Translational science, with the aid of Molecular Biology and Molecular Pathology/Histopathology, helps us to decode which patients are likely to respond to treatment, what factors contribute to their response, and what we can learn about the drug mode of action in the process. Together with experts across Boehringer Ingelheim, we have developed a patient-centric strategy to identify the required dose to induce the desired therapeutic effect and target the appropriate patient populations. This also improves the quality and strategy of our translation projects with a transparent approach for risk evaluation and mitigation, all aiming to increase the likelihood of clinical success.

Our Molecular Biology and Molecular Pathology/Histopathology teams play key roles to discover biomarkers in pre-clinical settings that can be assessed in minimally invasive manners, while providing maximal understanding of patient biology during clinical trials. Our activities help us understand how each patient’s response to therapy is influenced by their molecular profile and target expression. Every patient is unique, which is reflected in their genetic make-up, epigenome and immunoprofile. These complex features have shifted our research focus and development towards a more patient-centric approach.

Translational science is the heart of our patient-centric approach to drug discovery research. The intimate connection of fundamental basic research and applied sciences is key to supporting project teams and developing high-quality treatments for patients, quickly.

 Finding novel biomarkers

Biomarkers are often used in clinical studies to objectively measure and evaluate biological processes or responses to an intervention or treatment. Measuring biomarker changes in response to a potential drug allows us to assess a drug’s mode of action and efficacy.

Our committed team of scientists combines and analyses all relevant data, ranging from existing literature and databases to pre-clinical research and clinical trial-derived data to identify new biomarkers that can track the biological or clinical changes a drug induces. Once potential biomarkers have been identified, they need to be validated. This means testing the potential biomarker in lab conditions to see if it consistently indicates the presence, stage, or progression of cancer. This step often involves comparing samples from cancer patients with samples from healthy individuals to confirm that the biomarker is not present in the latter. Upon validation, a confirmed biomarker is implemented and applied in clinical trials.

Collaboration is key

Boehringer Ingelheim is investing in cutting-edge biomarker discovery research through collaborations with centres of translational science excellence that combine early science with access to patient-derived samples and data. In the Regional Center Vienna (RCV), we are collaboration with the Cancer Research UK Manchester Institute focusing on target distribution, primary co-cultures and predictive biomarkers of therapy response. Furthermore, the partnership with CBmed enables Boehringer Ingelheim to identify and validate biomarkers for projects across its growing cancer pipeline. This will further support our efforts to increase the success rate of our clinical development by translating research discoveries into actionable insights for the clinic. It will also enable us to further expand our pipeline to achieve our goal of transforming the lives of people living with cancer.

Publications

1. Kim D, Herdeis L, Rudolph D, Zhao Y, Böttcher J, Vides A, Ayala-Santos CI, Pourfarjam Y, Cuevas-Navarro A, Xue JY, Mantoulidis A, Bröker J, Wunberg T, Schaaf O, Popow J, Wolkerstorfer B, Kropatsch KG, Qu R, de Stanchina E, Sang B, Li C, McConnell DB, Kraut N, Lito P. Pan-KRAS inhibitor disables oncogenic signalling and tumour growth. Nature. 2023 Jul;619(7968):160-166. doi: 10.1038/s41586-023-06123-3.
2. Kofink C, Trainor N, Mair B, Wöhrle S, Wurm M, Mischerikow N, Roy MJ, Bader G, Greb P, Garavel G, Diers E, McLennan R, Whitworth C, Vetma V, Rumpel K, Scharnweber M, Fuchs JE, Gerstberger T, Cui Y, Gremel G, Chetta P, Hopf S, Budano N, Rinnenthal J, Gmaschitz G, Mayer M, Koegl M, Ciulli A, Weinstabl H, Farnaby W. A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo. Nat Commun. 2022 Oct 10;13(1):5969. doi: 10.1038/s41467-022-33430-6.
3. Tontsch-Grunt U, Traexler PE, Baum A, Musa H, Marzin K, Wang S, Trapani F, Engelhardt H, Solca F. Therapeutic impact of BET inhibitor BI 894999 treatment: backtranslation from the clinic. Br J Cancer. 2022 Aug;127(3):577-586. doi: 10.1038/s41416-022-01815-5.
4. Hofmann MH, Gmachl M, Ramharter J, Savarese F, Gerlach D, Marszalek JR, Sanderson MP, Kessler D, Trapani F, Arnhof H, Rumpel K, Botesteanu DA, Ettmayer P, Gerstberger T, Kofink C, Wunberg T, Zoephel A, Fu SC, Teh JL, Böttcher J, Pototschnig N, Schachinger F, Schipany K, Lieb S, Vellano CP, O'Connell JC, Mendes RL, Moll J, Petronczki M, Heffernan TP, Pearson M, McConnell DB, Kraut N. BI-3406, a Potent and Selective SOS1-KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition. Cancer Discov. 2021 Jan;11(1):142-157. doi: 10.1158/2159-8290.CD-20-0142.
5. Hipp S, Voynov V, Drobits-Handl B, Giragossian C, Trapani F, Nixon AE, Scheer JM, Adam PJ. A Bispecific DLL3/CD3 IgG-Like T-Cell Engaging Antibody Induces Antitumor Responses in Small Cell Lung Cancer. Clin Cancer Res. 2020 Oct 1;26(19):5258-5268. doi: 10.1158/1078-0432.CCR-20-0926.