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European Lead Factory testimonial: Dirk Finsinger
Dirk Finsinger is Director in Medicinal Chemistry at Merck Healthcare KGaA Darmstadt, Germany. He has significant experience in project work in Oncology and Immunology, increasingly directing his attention to the early pipeline, specifically hit identification techniques, screening approaches and the respective relevant chemical space. In this context he is also actively engaged in collaborative project work and externalization with partners worldwide.
Within the European Lead Factory (ELF), he functions as project lead for Merck and was part of the team setting up ELF over ten years ago. We interviewed Dirk about his experience with the ELF.
Can you elaborate on the motivation for Merck to join this partnership?
At Merck, it was always strongly believed that collaboration has a highly positive impact on developing knowledge and science. Therefore, there was an immediate interest in fostering exchange among scientists from industry, academia, and the SME community. A lot of knowledge can be exchanged pre-competitively and this definitely boosts the overall quality of pharmaceutical research, which at the end benefits patients.
In a sense the ELF was a huge trust building exercise when we explored the various relationships between the participating organisations. While it was not common in the industry at the time to share knowledge between companies, participants quickly discovered that there was much to gain without revealing trade secrets. Building this distinctive network provided inherent value, and benchmarking internal processes, approaches, and thinking were significant drivers for joining this initiative. In retrospect, I can confidently say that it was a success.
The notion of "sharing" persists to this day, and academia and EFPIA continue to adopt an open-minded approach that welcomes new ideas and methodologies. The broad involvement of third parties utilizing the ELF infrastructure to advance their scientific research has shifted mindsets in the community and is poised to endure over time.
What was it that made the ELF compound library and participating in ELF so attractive?
The ELF provided a great opportunity to collaborate with a diverse group of industrial and academic partners. This included learning from each other about general views on hit identification and respective challenges. Moreover, the compilation of a unique library based on the combined experience from the industrial partners, with a broad portfolio in different areas of the indication space, complemented by unbiased design of compounds provided by the SMEs and academia during phase 1 of the ELF provided a source for screening novel targets that was previously unavailable.
What has been the added value of the ELF to your organization?
We quickly made the ELF screening activities one of our pillars of our overall hit finding technologies and used it whenever appropriate. Access to a diverse screening deck, compiled by input from diverse partners, was a strong driver for us. A considerable amount of high quality chemical matter was identified which was explored in multiple phases of the drug discovery process and also stimulated new ideas to modify compounds or paved the way into differentiated chemical space.
Over the course of several years, we integrated screening of the ELF library into our screening strategy. Whenever feasible, we incorporated the ELF to increase our option space in HT Screening, resulting in the addition of chemical matter to our hit sets in many instances.
Additionally, one notable discovery led to further understanding of small molecule binding to the respective biological target and allowed us to derive the clinical candidate compound M4205 (IDRX-42) after just a few optimization cycles.
What are the most important learnings or takeaways from working with the ELF?
Working with the ELF really showed me that overcoming prejudices, having an open mindset and working together can make the difference. In the beginning this was a huge exercise where none of the parties involved knew where the discussions would end. And it was about building trust, especially between EFPIA and academia during the initial discussions. This could mean to deviate from trusted paths and leave a supposed comfort zone, but there was a clear conviction that the basic idea of sharing and working together was a good idea. Partners knew that a complex contractual framework was required to support a trustful relationship. Once those initial steps were taken this led to this successful consortium that perfectly balanced the different interests of all involved.
How do you see the future of small molecule drug discovery now the ELF is wrapping up its activities?
Small molecule research has invariably relied on several approaches to generate hit matter, as requirements may differ across various projects and target spaces. High throughput screening remains a primary pillar, provided we assure that the understanding of how we screen and what chemical space we use is developed. The ELF has been an essential component of HitID for a decade in Europe, and it contributed to a better understanding of how to use and what to expect from HTS in a large group of the scientific community.