Former Onyx CEO leads Yumanity to challenge neurodegenerative diseases

Matthew Herper at Forbes has a really interesting story yestoday. Tony Coles, the former CEO of Onyx Pharmaceuticals, is starting a new company called Yumanity Therapeutics to develop new drugs for neurodegenerative diseases (e.g., Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis).  Yumanity is initially being funded by Tony Coles who received more than $57 million from the Onyx deal, but a funding round is expected to close early next year.

Previously, Onyx successfully developed three anti-cancer agents (sorafenib, regorafenib, and carfilzomib), and was finally acquired by Amgen for $10.4 billion in 2013. Not long ago, Raymond Deshaies and Larry Lasky who discovered carfilzomib and co-founded Proteolix (acquired by Onyx in 2009) launched a biotech startup called Cleave Biosciences to develop p97 inhibitor CB-5083.

Yumanity’s technologies came from professor Susan Lindquist who is a pioneer in the study of protein folding and was awarded the National Medal of Science in 2010. In November 2013, two studies from Susan Lindquist’s laboratory, published in Science[1,2], established engineered yeast cells that are amenable to high-throughput screening.

They screened ~190,000 compounds and found that an N-Aryl Benzimidazole (NAB) could reverse diverse phenotypes caused by α-synuclein, a key protein associated with several neurodegenerative diseases. Further experiments showed that NAB promotes endosomal transport dependent on Rsp5/Nedd4, whereas α-synuclein disrupts it. Finally, they demonstrated that NAB2 reversed pathologic phenotypes in neurons derived from iPS cells of patients who are at high risk of developing Parkonson’s disease dementia.

While it is widely known that α-synuclein accumulates in the brains of patients with Parkinson’s disease, it is still unclear whether α-synuclein is acting alone. Preclinical testing in animal models will be eagerly awaited.

[1] Science. 2013, 342(6161), 979-983.

[2] Science. 2013, 342(6161), 983-987.

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Developers of carfilzomib take another shot at multiple myeloma

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