Eidos Therapeutics, Inc. announced positive results of its Phase 2 clinical trial studying AG10 in subjects with symptomatic transthyretin (TTR) amyloidosis cardiomyopathy (ATTR-CM). The data were presented in a late-breaking Featured Science oral presentation at the American Heart Association (AHA) Scientific Sessions. AG10 was well tolerated, demonstrated >90% TTR average stabilization at day 28, and increased serum TTR concentrations, a prognostic indicator of survival in ATTR-CM, in a dose-dependent manner. Subject to discussions with regulatory agencies, these data support the advancement of AG10 into Phase 3 pivotal trials planned to be initiated in the first half of 2019. These data demonstrate that AG10 is well tolerated in symptomatic patients with ATTR-CM with clear evidence of drug activity in all actively treated subjects. The consistently high levels of TTR stabilization, in all actively treated subjects and across the entire dosing interval, were correlated with statistically significant and dose-dependent increases in serum TTR concentrations. The company observed normalized serum TTR levels in 100% of patients treated with AG10. This Phase 2 clinical trial was a randomized, double-blind, placebo-controlled, multi-center study that enrolled patients with symptomatic ATTR-CM, both wild-type and mutant. Eligible patients had confirmed ATTR-CM and NYHA Class II or III symptoms, and at least one prior heart failure hospitalization or active treatment for chronic heart failure. The 49 enrolled subjects were randomly assigned in a 1:1:1 fashion to treatment with placebo, 400 mg AG10 twice daily, or 800 mg AG10 twice daily for 28 days. Results from the study showed the following: The study met its primary objective of establishing that AG10 was well tolerated with no safety signals of potential clinical concern related to the administration of AG10 in symptomatic ATTR-CM patients. One serious adverse event (SAE) of dyspnea deemed unrelated to study drug was observed in one actively-treated subject (3%) and SAEs of atrial fibrillation, congestive heart failure, and cellulitis were observed in two placebo-treated subjects (12%). The overall rate of adverse events (AEs) was 69% in subjects administered 800 mg bid AG10, 63% in subjects administered 400 mg bid AG10, and 88% in subjects administered placebo. As compared to placebo, subjects treated with AG10 demonstrated a statistically significant increase in serum TTR concentrations (p90%, on average), across the dosing interval in all actively treated subjects as measured by established ex vivo assays. 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 amyloidosis, or ATTR. AG10 is currently being studied in an open-label extension of a Phase 2 clinical trial in patients with ATTR cardiomyopathy. AG10 was designed to mimic a naturally-occurring variant of the TTR gene (T119M) that is considered a “rescue mutation” because it has been shown to prevent ATTR in individuals carrying pathogenic, or disease-causing, mutations in the TTR gene. ATTR represents a significant unmet need of a comparatively large patient population in the context of rare genetic diseases with an inadequate current standard of care. There are three distinct diseases that comprise the ATTR family: 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 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. 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.