“It Always Seems Impossible Until It’s Done”
Contrary to popular belief, pharma is incredibly competitive, with dozens of companies often working on the same hot target at the same time. What sets pharma apart from the outside world though, is how deeply we respect our competitors and other scientists when they succeed at cracking technical challenges.
Here, Dr. Romyr Dominique tells us about what’s inspired him in his 17 years in our industry. Though he's never worked at Abbott or Amgen, he has tremendous respect for the scientists there and their alumni.
About Romyr
Romyr’s spent nearly a decade at Roche in Nutley, NJ, had short stints at a small biotech and in academia, and currently is a Senior Principal Scientist at PMV Pharmaceuticals, where he’s been for the last 7 years. He completed his postdoctoral fellowship at TSRI and PhD in chemistry at the University of Ottawa.
“My path to drug discovery has not been a straight line and it shaped as I was moving,” says Romyr. Initially interested in medicine to help people, he went to college to study biochemistry. While enzymatic pathways and molecular biology were interesting, he fell in love with organic chemistry. “Organic chemistry really struck some chords that still resonate with me today. I was amazed by how electrons moved to explain reaction mechanisms, and by the total syntheses of natural products that were not only ‘tours de force’ but pieces of art.”
After years of working with many different drug hunters, he finally felt like a drug hunter himself. He loves the term, “drug hunter,” because in every project the search for a target product profile is more like a hunter’s pursuit following an SAR trail than the reading of a blueprint.
Inspired by Venetoclax
“The discovery of venetoclax is one of the most inspirational drug discovery stories to me,” says Romyr. “The scientists at Abbott were faced with a challenging target, the anti-apoptotic protein Bcl-2,” which acts through protein-protein interactions (PPIs).
“To identify their starting point, Abbott’s scientists developed a technique called SAR by NMR.” They not only found a starting point to an approved blockbuster cancer drug, but laid the groundwork for a new field of drug discovery. “Through the development of SAR by NMR, a new platform was born which is known as fragment-based drug discovery (FBDD). Since then, several biotech companies have emerged using this technology, and multiple molecules originating from fragments have been FDA-approved or entered trials, including the first KRAS inhibitor, Amgen’s sotorasib.”
This success story highlights how one team of drug hunters’ pursuit of new leads can lead to new technologies employed by everyone. “As we address more ‘undruggable’ targets, I am hopeful that new technology will emerge to expand our arsenal of drug hunting tools.”
Platforms for the Undruggable
“I am most excited about all the platforms that go after undruggable targets,” says Romyr. “Only 2% of human proteins interact with currently approved drugs. When one thinks of the vast numbers of targets considered undruggable, one realizes there is plenty of work and job security for drug hunters!” Platforms like targeted covalent inhibition, PROTACs, and fragment-based drug discovery all get him excited about the future.
“It Always Seems Impossible Until It’s Done”
“There are several inspirational drug discovery stories I could think of because discovering a drug is a very difficult endeavor,” Romyr said. “However, the most recent success story that is really inspiring to me is the discovery of sotorasib. For the longest time, KRAS was considered an undruggable target, but in 2021, sotorasib (AMG510) was approved.”
The decades of research in the KRAS field by the drug discovery community reflects the relentless mentality drug hunters have: “It always seems impossible until it’s done.” (Nelson Mandela)
Thank you Romyr for sharing what inspires you, and thank you to all the drug hunters who've inspired future generations!
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