Third Rock Ventures Launches Revolution Medicines with $45M to Advance Modular Synthesis of Natural Drugs

Editor’s Note: The healthcare news website MedCity News recently published an article introducingThird Rock’s efforts in the modular synthesis of natural products,VCBeat has compiled the original article, aiming to introduce some of the latest developments in this field. Original textBy Meghana Keshavan, a graduate of Pennsylvania State University with a focus on biochemistry and molecular biology, who has been covering biotechnology and healthcare for the San Diego Business Journal for the past year and a half.Nature is undoubtedly an extremely rich source of medicinal compounds. Research has shown that drug compounds secreted by sponges possess highly complex chemical structures. When these pharmaceutical compounds are used in humans, they become a double-edged sword.

Recently, Third Rock Ventures secured $45 million in venture capital to establish a new company, “Revolution Medicines,” in the San Francisco Bay Area, aiming to develop drugs by fine-tuning nature. CEO Mark Goldsmith interprets the company’s name as “redesigning evolution,” reflecting Revolution Medicines’ intent to optimize therapeutic efficacy without side effects by modifying naturally occurring compounds.

It has been demonstrated that complex molecules found in nature can actually be simplified into modular structures, which can then be assembled as needed to create specific drugs.

This technology originates from Martin Burke, a chemist at the University of Illinois. He established optimal reaction conditions that enable the modular synthesis of pharmaceuticals. A year ago, Burke published his drug manufacturing process in Nature, demonstrating to the world how certain drug structures can be assembled like IKEA furniture:

Intrinsically modular peptides, oligonucleotides, and oligosaccharides have been utilized as synthetic platforms in a broad sense. Importantly, most small-molecule natural products are biosynthesized through the iterative coupling of bifunctional building blocks. This suggests that many small molecules likewise possess intrinsic modularity corresponding to systematic building blocks.

Martin Burke “This platform enables scientists to deconstruct complex natural compounds and break them down into simple structural units—‘just like LEGO bricks,’ says Goldsmith. Once the unnecessary components are removed, these molecular subunits can be reassembled via carbon-carbon bonds to create more effective drugs. Burke has also uploaded videos to YouTube describing this workflow.”Click to Watch, requires bypassing the Great Firewall)

Burke’s research has been applied to amphotericin B. Amphotericin B is an effective antifungal drug that has remained free from resistance for 50 years; however, it is highly toxic and causes significant renal cell injury. By applying Burke’s method, the amphotericin complex was first deconstructed, then the components responsible for renal cell injury were removed, and finally, the molecule was reassembled. The resulting recombinant drug retains potent fungicidal activity, while preclinical trials have demonstrated that this version is harmless to humans.

When discussing Revolution Medicines’ ambitions beyond antifungal drugs, Goldsmith revealed, “It’s a multi-billion-dollar market,” yet remained evasive, adding, “We are considering starting with all known natural compounds.”

The company is also actively seeking drug candidates amenable to deconstruction across a broad spectrum. Its efforts are primarily focused on three areas: antifungal agents, antibacterial and antibiotic drugs, and existing therapeutics that can be further optimized using the Revolution platform (such as the chemotherapy drug paclitaxel).

What is certain is that the ideal drug candidate will align perfectly with Burke’s structural unit approach. As for how long the $45 million funding will sustain Revolution Medicines’ operations, and which indications the company is currently most interested in, Goldsmith chose to remain silent. Admittedly, the company’s future development involves far more than just securing licenses. This round of financing will be used to optimize and industrialize its platform, as well as to bolster its pipeline, ensuring that the development of all drugs is conducted entirely in-house.

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