12 September 2019 - - US-based drugmaker Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) and BridgeBio Pharma, Inc.'s (NASDAQ: BBIO) subsidiary Eidos Therapeutics, Inc. (NASDAQ: EIDX) have inked an agreement that grants Alexion an exclusive license to develop and commercialize AG10 in Japan, the companies said.

AG10 is a small molecule designed to treat the root cause of transthyretin amyloidosis destabilized and misfolded transthyretin protein by binding and stabilising TTR in the blood.

Eidos is currently evaluating AG10 in a Phase 3 study in the US and Europe for ATTR cardiomyopathy (ATTR-CM) a progressive, fatal disease caused by the accumulation of misfolded TTR amyloid in the heart and plans to begin a Phase 3 study in ATTR polyneuropathy (ATTR-PN) a progressive, fatal disease caused by the accumulation of misfolded TTR amyloid in the peripheral nervous system.

Under the terms of the agreement, Alexion will acquire an exclusive license for the clinical development and commercialization of AG10 in Japan.

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

AG10 is an investigational, 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.

In a Phase 2 clinical trial in patients with symptomatic ATTR-CM, AG10 was generally well tolerated, demonstrated greater than 90% average TTR stabilisation at Day 28, and increased serum TTR concentrations, a prognostic indicator of survival in a retrospective study of ATTR-CM patients, in a dose-dependent manner.

AG10 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.

To the company's knowledge, AG10 is the only TTR stabiliser in development that has been observed to mimic the stabilising structure of this rescue mutation.

The Phase 3 ATTRibute-CM study of AG10 in patients with ATTR-CM is underway in the United States and Europe.

Part A of the study will assess the change from baseline in six-minute walk distance at 12 months.

Part B of the study will evaluate reduction in all-cause mortality and frequency of cardiovascular-related hospitalisations will be evaluated at 30 months.

In addition, Eidos plans to initiate a Phase 3 study of AG10 in ATTR polyneuropathy (ATTR-PN) in the second half of 2019.

There is significant medical need in transthyretin amyloidosis given the large patient population and an inadequate current standard of care.

ATTR is caused by the destabilisation of TTR due to inherited mutations or aging and is commonly divided into three distinct categories: wild-type ATTR cardiomyopathy (ATTRwt-CM), mutant ATTR cardiomyopathy (ATTRm-CM), and ATTR polyneuropathy (ATTR-PN).

The worldwide prevalence of each disease is approximately 400,000 patients, 40,000 patients and 10,000 patients, respectively.

All three forms of ATTR are progressive and fatal. For patients with untreated ATTRwt-CM and ATTRm-CM, symptoms usually manifest later in life (age 50+), with median survival of three to five years from diagnosis. ATTR-PN either presents in a patient's early 30s or later (age 50+), and results in a median life expectancy of five to ten years from diagnosis for untreated patients.

Progression of all forms of ATTR causes significant morbidity, impacts productivity and quality of life, and creates a significant economic burden due to the costs associated with progressively greater patient needs for supportive care.

Alexion is a global biopharmaceutical company focused on serving patients and families affected by rare diseases through the discovery, development and commercialization of life-changing therapies.

As a leader in complement biology and inhibition for more than 20 years, Alexion has developed and commercialises two approved complement inhibitors to treat patients with paroxysmal nocturnal hemoglobinuria as well as the first and only approved complement inhibitor to treat atypical hemolytic uremic syndrome, anti-acetylcholine receptor antibody-positive generalized myasthenia gravis and neuromyelitis optica spectrum disorder (NMOSD).

Alexion also has two highly innovative enzyme replacement therapies for patients with life-threatening and ultra-rare metabolic disorders, hypophosphatasia and lysosomal acid lipase deficiency (LAL-D).

In addition, the company is developing several mid-to-late-stage therapies, including a second complement inhibitor, a copper-binding agent for Wilson disease and an anti-neonatal Fc receptor antibody for rare Immunoglobulin G -mediated diseases as well as several early-stage therapies, including one for light chain amyloidosis and a second anti-FcRn therapy.

Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on the core therapeutic areas of hematology, nephrology, neurology, and metabolic disorders.

Alexion has been named to the Forbes' list of the World's Most Innovative Companies seven years in a row and is headquartered in Boston, Massachusetts' Innovation District.

The company also has offices around the globe and serves patients in more than 50 countries.

BridgeBio was founded in 2015 to identify and advance transformative medicines to treat patients who suffer from Mendelian diseases, which are diseases that arise from defects in a single gene, and cancers with clear genetic drivers.

BridgeBio's pipeline of over 15 development programmes includes product candidates ranging from early discovery to late-stage development.

Eidos is a BridgeBio Pharma subsidiary focused on addressing the large and growing unmet need in diseases caused by transthyretin amyloidosis. Eidos is developing AG10, a potentially disease-modifying therapy for the treatment of ATTR.