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Navigating the Waves of Discovery

Publish Date

02 APR 2024

Author

Felix Hart

Overview

The exhilaration I feel is undeniable when I see data generated by people here, in our team, and know that we are looking at biology never seen before.

Navigating the Waves of Discovery

The connection between adventure and scientific discovery is undeniable. The fascination and excitement felt when diving into the blue depths of the Caribbean is the same as the exhilaration I feel when I see data that is generated by our team here at Merck KGaA, Darmstadt, Germany and know that we’re looking at biology no one has ever seen before.

My journey in the field of cancer research is driven by a profound sense of purpose and a dedication to improving the lives of those affected by cancer. For many, myself included, cancer has touched our lives through close family members and friends fighting this tremendous adversary. Unfortunately, there's a substantial population of cancer patients who don’t respond well, or not at all, to existing treatments. At Merck KGaA, Darmstadt, Germany, we're on a mission to turn more cancer patients into survivors, and we're doing it through ground-breaking research into antibody-drug conjugates (ADCs).

Unlocking the Potential of ADCs

My role is two-fold. I head up an in vitro pharmacology lab that investigates ADCs. ADCs are often referred to as ‘magic bullets’ or ‘guided missiles’ for treating cancer because of their immense potential. These innovative compounds are engineered to deliver highly potent agents directly to cancer cells while sparing healthy ones. ADCs comprise of a special targeting antibody that can recognize cancer cells. A chemical linker connects the antibody to a drug (payload) that’s designed to target fundamental cellular processes. Once this tiny package infiltrates a cancer cell, it destroys it from the inside.

My lab focuses on deciphering critical aspects of how ADCs work. It is fascinating to utilize state-of-the-art technology which allows us to look at, and into, cancer cells to see how ADCs bind and internalize, respectively. In even higher resolution we are able to look into the nucleus to detect DNA damage elicited by a payload specifically delivered by an ADC to cancer cells. We rigorously test various combinations of antibody-payload partners, evaluate the potential of ADCs to mediate bystander effects, and measure their ability to inhibit cancer cell proliferation. We collaborate with numerous teams in-house, as well as academic and industry partners who bring their unique expertise to the table. These collaborations highlight the multidimensional approach to our collective effort to advance cancer treatment.

Guiding Project Teams towards the Clinic

I also lead and collaborate with research discovery project teams, guiding them through the complex path towards clinical development. Managing multidisciplinary teams has taught me the importance of clear and effective communication. Interpreting results may spark new ideas on how to improve what’s available and what has been tested so far. I enjoy brainstorming with talented, like-minded colleagues about follow-ups, which often leads to further experiments or new compound designs and ideas. By continuously sharing our latest discoveries within and between our teams, we keep everyone motivated, involved and open to asking the right questions at the right time.

One of the most rewarding experiences I've had recently was being a part of two ADC projects that started clinical development. It allowed me to see the entire drug discovery journey from start to finish, and I gained invaluable insights throughout this process. This is far from being something I take for granted, as we all know that it requires the right approach/idea, patience, resilience and of course some luck to advance projects or compounds from early discovery up to a first-in-human study. It's a reminder of the real impact our work can have on the lives of those touched by cancer, and it motivates me to continue navigating the waves of discovery in cancer research.

ADCs represent an exciting avenue in cancer research with further technological advancements being explored, and I'm hopeful that in the next two years, we'll see more ADC projects progress to the clinical stage. While the motivation of ADCs to specifically delivery highly potent agents to cancer cells may be simple, turning them into effective medicines is rather complex. Combining the specificity of biologics with the potency of small-molecules requires multidisciplinary teams which I really enjoy working in. This journey is far from over, and I’m thrilled to be part of the teams exploring uncharted cancer biology, as we strive to make tangible differences in the lives of patients and families.

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