From AZ to VC: Tracing Our Industry’s Recent Evolution Through A Career

Our Drug Hunter subscribers at Curie.Bio recently made headlines with the launch of their new >$500M venture fund with a new model for early-stage biotech financing to help founders launch therapeutics companies. Curie.Bio intends to act not only as an investor, but also as a day-to-day operating partner to help founders choose targets, design experiments, interview & select drug discovery vendors (now including Drug Hunter Premium!), and beyond. It is an interesting concept that could parallel the tech world’s famous Y-Combinator program for nurturing startups.

Curie.Bio’s founders, including prolific biotech investor Alexis Borisy, serial entrepreneur Zach Weinberg, and chief scientist Christoph Lengauer, are backing up their ability to offer differentiated support by stacking their team with biotech and pharma veterans like Sue Wee and Andy Garner.

This week, Alexis reached out to let us know about a new, truly impressive CSO Partner that we’re sure readers will recognize: Chris De Savi. Chris is an expert practitioner of drug discovery and drug discovery executive who is deeply passionate about delivering high-quality and differentiated medicines to patients. He’s contributed to several molecules highlighted here on Drug Hunter, including Blueprint Medicines’ next-generation EGFR molecule, BLU-945, AstraZeneca’s CDK9 inhibitor, AZD4573, and AZ’s oral SERD program.

Chris shared his journey with us from total synthesis at Cambridge University to game-changing degraders at Kymera Therapeutics, and shares why he made the jump to Curie.Bio.

A Passion for Drug Discovery Ignited by A Natural Product

Today, Chris’s CV reads with a litany of drug discovery achievements. He’s won award after award at AstraZeneca, lauded by colleagues as “one of the most motivated and driven people” they’ve ever worked with, and has contributed to at least nine compounds to reach clinical testing – a remarkable feat in an industry where many can go their entire careers without seeing more than one. Like many successful R&D innovators in America, he’s also an immigrant, in both the traditional sense (completing his education in Australia) and a scientific sense. 

Like many drug discovery professionals, Chris’s scientific training wasn’t in biology, pharmacology, or anything to do with drugs, but with the fundamental study of how molecules work and how to make them. Chemists may be surprised to learn that Chris was working on asymmetric desymmetrization of aromatic compounds and biocatalysis as early as 1998 in Australia, many years before these topics became hot topics in both academia and industry. It wasn’t until he made the scientific pilgrimage around the world to the UK that he experienced the excitement of making molecules that could be biologically meaningful.

As a post-doc at Cambridge’ famed University Chemical Laboratory on Lensfield Road, which has now unintentionally trained countless pharma R&D leaders worldwide, he had his “first true drug discovery experience synthesizing laulimalide, a microtubule stabilizer natural product.” Like many other natural products of academic research interest at the time, laulimalide has a similar mechanism to blockbuster chemotherapy paclitaxel (Taxol) – binding to tubulin, enhancing microtubule assembly and stabilization, and inhibiting cancer cell proliferation. The cancer drug discovery landscape at that time, in 1999-2001, was just starting to make the monumental paradigm shift from searching for more cytotoxic chemotherapies like Taxol to investing heavily in more targeted therapies like imatinib and other tyrosine kinase inhibitors.

The then-interest in cytotoxic chemotherapies the challenge of making molecules as complex as laulimalide seem worthwide. It took Chris two years to get the first samples of the compound, after an arduous 27 total reactions. Synthetic chemists know that successfully synthesizing a molecule this complex is a significant achievement.

laulimalide potent microtubule-stabilizing anticancer agent

A Start on AurB at AZ

It was likely impossible for Chris not to sense the massive, industry-wide shift then taking place to targeted therapy research. Rather than continue researching natural product synthesis in academia, he decided to make the move to pharma R&D. “My industrial drug discovery career started in 2001 as a medicinal chemist at AstraZeneca” – “Aye-Zee” to Americans and “Aye-Zed” to Commonwealthers like Chris.

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