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Start-Up to Discover Proteins for Difficult Drug Targets

Chemical atom model

(Fernando Zhiminaicela, Pixabay. https://pixabay.com/illustrations/chemical-molecular-atom-medicine-3086130/)

28 Jan. 2022. A new biotechnology company designing proteins in the lab for difficult drug targets in a range of diseases is raising $100 million in venture funds. Septerna Inc. in South San Francisco is formed and incubated by life science investor Third Rock Ventures, and based on research at Duke University and Monash University in Australia.

Septerna seeks to discover and design small molecule or low molecular weight drugs addressing G protein-coupled receptors, or GPCRs, found on cell surface membranes, and targets for about one in three current prescription drugs, such as antihistamines, ulcer drugs, and beta blockers to treat heart conditions. Yet as the company notes, the vast majority of these drugs today address only six sub-families of GPCRs, leaving out more than 85 percent of potential targets.

Robert Lefkowitz, professor of biochemistry and medicine at Duke University in Durham, North Carolina and co-founder of Septerna, says in a company statement, “the complexity and transmembrane nature of GPCRs have made them difficult to isolate outside of the cell and inaccessible to modern small molecule drug discovery approaches.” Lefkowitz, winner of the Nobel Prize in Chemistry in 2012, is joined as scientific founders by GPCR researchers Arthur Christopoulos, professor of pharmacology, and Patrick Sexton, professor of drug discovery biology, both at Monash University in Melbourne, Australia.

Native functions, structure, and dynamics

Septerna’s Native Complex technology, based on the founders’ research, seeks to recreate the natural world for GPCRs, providing their native functions, structure, and dynamics outside the normal cellular environment. The company says it can isolate, purify, and reconstitute the ligands or binding molecules and supporting signaling proteins found on cell membranes, but outside the cell and in the lab. Septerna says it can screen GPCRs against combinations of ligands and signaling proteins to discover specific receptors previously considered untouchable as drug targets, and with computational techniques and structural biology, design small molecule drugs addressing those receptors.

“Septerna is establishing a new future for GPCR-targeted medicines for patients,” says Septerna CEO and interim president Jeffrey Finer. “We already have strong momentum advancing our pipeline of small molecule drug discovery programs on the path to creating high-impact medicines.” Finer, a Septerna co-founder, is a partner at Third Rock Ventures in San Francisco.

The company is raising $100 million in its first venture funding round, led by Third Rock Ventures. Joining the round are Samsara BioCapital, BVF Partners, Invus Financial Advisors, Catalio Capital Management, Casdin Capital, and Logos Capital. Septerna says the financing will help advance the company’s pipeline across multiple therapeutic areas — endocrine system, central nervous system, inflammation, metabolism — and further develop the Native Complex technology.

Lefkowitz says that technology, “ushers in a new era of drug discovery to reach previously undruggable GPCRs and enable all modern drug discovery technologies to be fully accessible for the GPCR target class.”

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