PALO ALTO, Calif., Sept. 28, 2017 /PRNewswire/ -- Eidos Therapeutics, a subsidiary of BridgeBio Pharma, today announced dosing of the first healthy adult cohort in the first-in-human, Phase 1 clinical trial of AG10 (NCT03294707). Eidos is developing AG10 as a targeted therapeutic for transthyretin (TTR) amyloidosis (ATTR). Eidos' first clinical trial will evaluate AG10's overall safety, tolerability and pharmacokinetic profile. Further, the trial aims to provide evidence of dose-dependent TTR stabilization as proof of therapeutic mechanism. The company also announced the appointment of Camille Landis as chief business officer.
There are no FDA-approved therapies indicated for the treatment of ATTR. This debilitating, progressive and fatal disease causes both cardiomyopathy (heart muscle disease resulting in heart failure) and polyneuropathy (nervous system damage affecting movement, sensation and control of blood pressure and digestion). ATTR is believed to affect at least 250,000 people worldwide and is caused by the accumulation of misfolded and aggregated TTR in affected tissues. AG10's potent, specific binding and stabilization of TTR suggest the potential to alter the progressive clinical deterioration in patients with ATTR.
"AG10 was rationally designed to potently stabilize TTR, targeting the disease at its source by preventing the formation of disease-causing amyloid fibrils," said Jonathan Fox, M.D., Ph.D., the company's president and chief medical officer. "Unlike other TTR stabilizers, AG10's highly selective binding mechanism mimics the super-stabilizing effects of the disease-suppressing T119M mutation that protects some individuals against ATTR. Our prediction is that AG10 will effectively slow or even halt the clinical progression of the disease. This trial is the first step in a journey to making AG10 a safe and effective therapy for patients with ATTR."
Following the successful completion of this first clinical trial, Eidos will advance AG10 into subsequent studies in symptomatic patients with ATTR. The initial trial will employ both single and multiple doses and will document dose-related blood concentrations of AG10 and its activity in stabilizing TTR tetramers. The study is designed to provide the data needed for selecting optimal doses for subsequent studies in patients with symptomatic transthyretin amyloid cardiomyopathy (ATTR-CM) and/or polyneuropathy (ATTR-PN).
Camille Landis joins the senior management team of Eidos as chief business officer to lead the company's corporate development and financing activities. Ms. Landis joins Eidos Therapeutics from Relypsa where she was vice president of corporate development. While at Relypsa, she was responsible for building and leading corporate development, alliance management, and strategic planning. She led the sale process of Relypsa to Galencia for $1.5B and supported the company's IPO and financing activities which raised over $475M. She also led Relypsa's global partnering effort that resulted in a $165M licensing agreement with Vifor Fresenius Medical Renal Pharma and a co-detailing agreement with Sanofi. Additionally, Ms. Landis served on Relypsa's executive leadership team and led the company's annual strategic planning process. She earned her M.B.A from Haas School of Business and her B.A. in biology from the University of St. Thomas.
"Eidos is pursuing a highly targeted approach to treat this devastating disease," said Ms. Landis. "The preclinical data is scientifically compelling and strongly supported our initiation of clinical testing. I will strive to help the team build the company to ensure our potentially disease-modifying medicine reaches as many patients as possible in a timely manner."
AG10 is a small molecule that selectively and potently binds and stabilizes the tetrameric protein transthyretin, preventing its dissociation into disease-causing monomers. AG10 was discovered and initially developed by Eidos' co-founders Isabella Graef, M.D. and Mamoun Alhamadsheh, Ph.D., at Stanford University and the University of the Pacific, respectively.
About transthyretin amyloid cardiomyopathy (ATTR-CM)
ATTR-CM is a progressive, fatal disease caused by the accumulation of misfolded ATTR fibrils in the heart. These deposits are toxic to cardiac muscle cells and limit the heart's ability to fill completely during relaxation, leading to progressive and fatal heart failure.
Approximately 240,000 people worldwide suffer from ATTR cardiomyopathy, though the patient population may be underestimated due to its rarity and confusion with more common forms of heart failure. Most patients are diagnosed after age 60, when the disease is already advanced and may progress rapidly.
Some patients are predisposed to ATTR cardiomyopathy due to mutations in the gene that encodes TTR. The most prevalent of these mutations, V122I TTR, is carried by 3.4% of African Americans.
There are no FDA-approved medications for the treatment of ATTR cardiomyopathy.
About transthyretin amyloid polyneuropathy (ATTR-PN)
ATTR polyneuropathy is a progressive, fatal disease caused by the accumulation of TTR amyloid in the peripheral nervous system. These deposits cause nerve damage that impairs patients' ability to move (motor function) and feel (sensory function), and control heart rate, blood pressure and digestion (so-called autonomic nervous function). The consequences can include an inability to walk, abnormal pain sensation and severe malnutrition.
Approximately 10,000 people worldwide suffer from ATTR polyneuropathy, with clusters of affected families sharing the same causal mutation, V30M, in regions of Portugal, Japan and Sweden. The onset of disease is bi-modal, either the fourth decade of life or after age 60, but can progress rapidly.
There are no FDA-approved medications for the treatment of ATTR polyneuropathy.
About Eidos Therapeutics
Eidos Therapeutics is a clinical stage biopharmaceutical company based in the San Francisco Bay Area. Eidos is developing AG10 as a targeted therapeutic for transthyretin amyloidosis. The company's singular mission is to improve the lives of patients suffering from this disease. Launched in 2016 after years of research supported by Stanford's TRAM and SPARK programs, Eidos is led by a team of veteran biotechnology executives. Together with patients and physicians, the company aims to bring a safe, effective treatment to market as quickly as possible.
About BridgeBio Pharma
BridgeBio is a clinical-stage biotechnology company developing novel, genetically targeted therapies to improve the lives of patients. The BridgeBio approach combines a traditional focus on drug development with a unique corporate model, allowing rapid translation of early stage science into medicines that treat rare diseases at their source.
Founded in 2015 by a team of industry veterans who previously brought more than a dozen products to market, BridgeBio has built a robust portfolio of nine transformative drug programs that address rare diseases across oncology, cardiology, dermatology and cancer. The drugs are in various phases of development, from pre-clinical to late-stage.
With a commitment to scientific excellence and rapid execution, BridgeBio aims to translate today's discoveries into tomorrow's medicines.
SOURCE Eidos Therapeutics