Underdog Launches With $4M to Target “Toxic” Form of Cholesterol

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Underdog Pharmaceuticals has launched with nearly $4 million in seed funding to develop treatments for atherosclerosis, a progressive condition in which arteries become clogged with substances such as fats and cholesterol, which restricts blood flow.

Based in Mountain View, CA, Underdog is a spinout of the nonprofit SENS Research Foundation (SRF). Matthew O’Connor and Michael Kope, SRF’s former vice president of research and founding CEO, respectively, are co-founders.

The seed round brought in $3.95 million, which the company plans to use in the next 18 months. It will need to raise another round to advance the drug candidates it develops into human testing, says O’Connor, who, with Kope, holds the title of co-CEO.

The company is targeting “really bad” cholesterol, 7-ketocholesterol, a broadly toxic damaged cholesterol with no useful biological function, O’Connor explains. In addition to atherosclerosis, the fatty substance is involved in other age-related diseases, such as macular degeneration and Alzheimer’s disease, for which the company may also look to develop treatments.

Underdog’s overall strategy is to modify existing drugs, though O’Connor notes the company’s new cyclodextrins are highly engineered.

“One benefit to working with this class of molecule is that a lot is known about the properties of the core drug, including how it is metabolized and we’ve carefully studied what kinds of structures and modifications are key to making it safe,” he says. “At their core, cyclodextrins are natural compounds that have been studied for many decades so there is a large body of literature that has been written about their chemistry and biology.”

As for the next steps, the company is scaling up its in vivo work and expects to finalize at least one lead drug in the next six months.

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