Rare Daily Staff

BridgeBio Pharma’s subsidiary Eidos Therapeutics has granted Alexion Pharmaceuticals an exclusive license to develop and commercialize in Japan AG10, its small molecule designed to treat the root cause of transthyretin amyloidosis.

Under the terms of their agreement, Eidos will receive an upfront payment of $25 million and an equity investment of $25 million at a premium to the market price upon deal execution, with the potential for additional Japanese-based milestone- and royalty-dependent payments.

Transthyretin amyloidosis (ATTR) is a progressive, fatal disease caused by the accumulation of destabilized and misfolded TTR amyloid due to inherited mutations or aging. It is commonly divided into three distinct categories: wild-type ATTR cardiomyopathy (ATTRwt-CM), mutant ATTR cardiomyopathy (ATTRm-CM), and ATTR polyneuropathy (ATTR-PN). ATTRwt-CM affects about 400,000 patients globally and usually manifests later in life, with median survival of three to five years from diagnosis. ATTR-CM also manifests later in life, affecting about 40,000 patients globally. ATTR-PN, which affects about 10,000 patients globally, can present as early as a patient’s 30s or later. Current standard of care does not slow or stop progression of the disease.

“There is a significant need for new treatments for TTR amyloidosis. We believe AG10 holds promise in its ability to stabilize TTR and halt disease progression,” said John Orloff, executive vice president and head of R&D at Alexion.

AG10 is an experimental, orally-administered small molecule designed to potently stabilize tetrameric transthyretin, or TTR, thereby halting at its outset the series of molecular events that give rise to TTR amyloidosis, or ATTR. It was designed to mimic a naturally-occurring variant of the TTR gene (T119M) that is considered a rescue mutation because co-inheritance has been shown to prevent or ameliorate ATTR in individuals also inheriting a pathogenic, or disease-causing, mutation in the TTR gene.

“The phase 2 study in ATTR-CM suggested that AG10 has the potential to become an important treatment option for the underserved ATTR-CM population,” said Jonathan Fox, president and chief medical officer of Eidos. “The trial showed that AG10 was generally well-tolerated and resulted in near-complete stabilization of TTR, which is known to be correlated with disease severity in ATTR-CM. In the study, AG10 also normalized serum TTR levels, a prognostic indicator of survival in ATTR patients.”

Eidos is currently evaluating AG10 in a phase 3 study in the United States and Europe for ATTR-CM and plans to begin a phase 3 study in ATTR-PN in the second half of 2019.

Photo: Jonathan Fox, president and chief medical officer of Eidos

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