Shaken by An Unexpected Patient Connection

with Julien Lefranc 

We asked one of our reviewers, Julien Lefranc, about what inspires and excites him about drug discovery. Here, he tells us about an unexpected, moving connection with a cancer patient, and what drives him to work every day.

About Julien

Julien is a Principal Scientist at Merck KGaA in Darmstadt and is a member of the Early Career Advisory Board at ChemMedChem. Julien Lefranc studied chemistry in Marseille and Montpellier before carrying out his PhD in Manchester with Prof. Jonathan Clayden, working on organolithium reactions. In 2012, he moved to Germany for a post-doctoral stay with Prof. Dirk Trauner working on natural products synthesis, and started his industrial career in 2014 with Bayer in Berlin where he worked on several oncology projects. In 2020, he was promoted to Senior Scientist in Medicinal Chemistry at the Innovation Campus Berlin. He assumed his current position in 2021.

Drug Hunter Featured Reviewer: Julien Lefranc, Principal Scientist at Merck KGaA. Started career at Bayer, Berlin. Early Career Advisory Board at ChemMedChem

Unexpected Connection with a Patient

“I have been fortunate enough to see the first project I ever worked on enter clinical trials,” said Julien. “A few years later we published a medicinal chemistry paper to explain how we discover our clinical candidate…” 

“With the increasing use of social media in science, I was happy to share the publication on Twitter. A few days later I received a message from a patient that was part of our clinical studies, who saw my post.”

“I have been fortunate enough to see the first project I ever worked on enter clinical trials. ...I was happy to share the publication on Twitter. A few days later I received a message from a patient that was part of our clinical studies ...she was diagnosed with breast cancer..."

“We exchanged messages and she then told me her story and about how she was diagnosed with breast cancer. She was an incredible woman and kept on thanking me/us for the job we do and saying how grateful she was for new treatments and how much hope these molecules give to the patients and their families. It’s quite rare for a medicinal chemist to discuss with patients and even rarer with patients that are being treated with a drug you discover.”

“This exchange has shaken me for a long time afterwards and still plays a very important role in my everyday work.”

"She...kept on thanking me/us for the job we do and saying how grateful she was for new treatments and how much hope these molecules give to the patients and their families." "This exchange has shaken me for a long time afterwards and still plays a very important role in my everyday work."

Inspired by KRAS inhibitors

Throughout his career Julien has been amazed by the development of KRAS inhibitors. He started his medicinal chemistry career in 2014, just after the landmark paper from Kevan Shokat identifying a small molecule inhibitor that binds covalently to KRAS G12C was published. At that time KRAS was considered undruggable. Only seven years later, the first KRAS G12C inhibitor, Sotorasib (Lumakras™), was approved by the FDA.

Julien is inspired by the discovery of KRAS inhibitors. In the last decade Julien has witnessed the KRAS protein go from being considered “undruggable” to becoming a highly pursued drug target, leading to the first-in-class approval of sotorasib (Lumakras, structure shown) in 2021 for the treatment of solid tumors with KRAS mutations, including non-small cell lung cancer

New Methods to Target the “Undruggable”

Today Julien is excited about targeted protein degradation, an emerging strategy to target proteins that have been considered “undruggable” in the past, or difficult to target with small molecule drugs. Proteolysis-targeting chimera (PROTAC) protein degraders utilize the ubiquitin–proteasome system to mark a protein for degradation. In 2019 the first PROTAC drugs entered into clinical trials, ARV-110 (NCT03888612) and ARV-471 (NCT04072952), almost 20 years after the first small molecule PROTAC was reported in 2001

“I am very much looking forward to the evolution of the degrader field. The first PROTACs are currently in clinical trials and there is a lot to come. This can really provide the patients with new options for therapies.” with structure of ARV-471

“He DIdn’t Know it Was Impossible So He Did It”

All new drugs start with a thought – some are very plausible ideas, while others are initially considered impossible. Julien’s favorite quote to apply about science is:

“He didn’t know it was impossible so he did it.” – Mark Twain

As new generations of scientists take on old drug discovery challenges with emerging technologies, new strategies, and a healthy dose of naivety to past failures, we are bound to unlock more serendipitous breakthroughs.

Julien’s favorite quote to apply in science:  “He didn’t know it was impossible so he did it.” -Mark Twain

Thank you Julien and all drug discovery scientists and leaders for your contributions to healthcare!

If you want to read more from industry leaders, check out our other interviews:

Feel the same way, or have something else to share? Please get in touch!

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