First Clinical Study for Compound From Company’s Potential Best-in-Class NEP Inhibitor Development Program; Compound Designed for Broad Use in Major Cardiovascular and Renal Diseases
DUBLIN, Ireland I December 8, 2015 I Theravance Biopharma, Inc. (NASDAQ: TBPH) (“Theravance Biopharma” or the “Company”) today announced dosing of the first subject in a Phase 1 clinical trial of TD-0714, the lead drug candidate in the Company’s neprilysin (NEP) inhibitor program. This program is designed to develop best-in-class selective NEP inhibitors for the treatment of a range of major cardiovascular and renal diseases, including acute and chronic heart failure, hypertension and chronic kidney diseases such as diabetic nephropathy.
TD-0714 is an internally-discovered selective inhibitor of NEP, the enzyme responsible for degradation of natriuretic peptides ANP, BNP and CNP. By inhibiting NEP, TD-0714 elevates the levels of these peptides, which may exert protective cardiac and renal effects including vasodilation, diuresis, natriuresis, reversal of maladaptive changes in heart, blood vessels and kidney, prevention of fibrosis, and prevention of end-organ damage. Theravance Biopharma has specifically designed TD-0714 to possess certain key features, including low renal clearance, the potential to be administered once daily, and the flexibility to be combined with other approved and investigational drugs.
The Phase 1 trial is a randomized, double-blind, placebo-controlled, single-ascending dose study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of TD-0714. The single-center study’s primary endpoints will be the safety and tolerability of TD-0714 in healthy adults. Key secondary endpoints are designed to assess the potential for once-daily dosing and include an assessment of the pharmacodynamics of TD-0714 and the pharmacokinetic half-life. Investigators will also assess TD-0714’s potential for low levels of renal clearance.
“The initiation of this first-in-human clinical trial is the next step in our efforts to develop a best-in-class collection of NEP inhibitors with the flexibility to be combined with a range of other mechanistic classes to potentially deliver enhanced outcomes to patients with a range of cardiovascular and renal diseases. Importantly, our preclinical data presented at the 2015 American Heart Association conference support our belief that several of our NEP inhibitors have attractive biological and pharmacokinetic properties with significant therapeutic potential,” said Mathai Mammen, M.D., Ph.D., Senior Vice President, Research and Development of Theravance Biopharma. “We believe TD-0714 is an exciting compound with uniquely designed characteristics. In addition, it is just the first in a series of novel NEP inhibitors that have been created at Theravance Biopharma. We are working aggressively to advance additional compounds from this program into the clinic and look forward to achieving key development milestones with those drug candidates as well.”
Results from preclinical studies involving several of Theravance Biopharma’s NEP inhibitors were recently presented at the American Heart Association Scientific Sessions 2015. Findings demonstrated that the Company’s NEP inhibitors are potent and selective inhibitors of neprilysin and demonstrated sustained levels of target engagement over 24-hours after a single oral dose in rats. Data also demonstrated that the compounds produced robust and long-lasting cardiovascular effects in rats that were equivalent to or greater than sacubitril, the NEP inhibitor component of Entresto™, which was recently approved by the United States Food and Drug Administration (FDA) for the treatment of patients with reduced-ejection fraction chronic heart failure. Additionally, in the preclinical studies Theravance Biopharma’s compounds were orally bioavailable and demonstrated levels of renal clearance that were low as compared to sacubitril.
About Neprilysin (NEP) Inhibition
Neprilysin (NEP) is an enzyme that degrades natriuretic peptides. These peptides play a protective role in controlling blood pressure and preventing cardiovascular tissue remodeling. Research suggests that inhibiting NEP may result in clinical benefits for patients, including diuresis, control of blood pressure, and reversing maladaptive changes in the heart and vascular tissue in patients with congestive heart failure. Based on this activity, NEP inhibitors may have the potential to treat a range of major cardiovascular and renal diseases, including acute and chronic heart failure, resistant hypertension and chronic kidney disease. In the United States alone, there are roughly six million patients diagnosed with chronic heart failure and approximately one million acute heart failure patients hospitalized annually. Additionally, there are six million Americans affected by resistant hypertension and 26 million with chronic kidney disease.1
About Theravance Biopharma
The mission of Theravance Biopharma (NASDAQ: TBPH) is to create value from a unique and diverse set of assets: an approved product; a development pipeline of late-stage assets; and a productive research platform designed for long-term growth.
Our pipeline of internally discovered product candidates includes potential best-in-class opportunities in underserved markets in the acute care setting, representing multiple opportunities for value creation. VIBATIV® (telavancin), our first commercial product, is a once-daily dual-mechanism antibiotic approved in the US, Europe and certain other countries for certain difficult-to-treat infections. Revefenacin (TD-4208) is an investigational long-acting muscarinic antagonist (LAMA) being developed as a potential once-daily, nebulized treatment for chronic obstructive pulmonary disease (COPD). Axelopran (TD-1211) is an investigational potential once-daily, oral treatment for opioid-induced constipation (OIC). Our earlier-stage clinical assets represent novel approaches for potentially treating diseases of the lung and gastrointestinal tract and infectious disease. In addition, we have an economic interest in future payments that may be made by Glaxo Group Limited or one of its affiliates pursuant to its agreements with Theravance, Inc. relating to certain drug development programs, including the combination of fluticasone furoate, umeclidinium and vilanterol (the “Closed Triple”).
With our successful drug discovery and development track record, commercial infrastructure, experienced management team and efficient corporate structure, we believe that we are well positioned to create value for our shareholders and make a difference in the lives of patients.
SOURCE: Theravance Biopharma
Post Views: 216
First Clinical Study for Compound From Company’s Potential Best-in-Class NEP Inhibitor Development Program; Compound Designed for Broad Use in Major Cardiovascular and Renal Diseases
DUBLIN, Ireland I December 8, 2015 I Theravance Biopharma, Inc. (NASDAQ: TBPH) (“Theravance Biopharma” or the “Company”) today announced dosing of the first subject in a Phase 1 clinical trial of TD-0714, the lead drug candidate in the Company’s neprilysin (NEP) inhibitor program. This program is designed to develop best-in-class selective NEP inhibitors for the treatment of a range of major cardiovascular and renal diseases, including acute and chronic heart failure, hypertension and chronic kidney diseases such as diabetic nephropathy.
TD-0714 is an internally-discovered selective inhibitor of NEP, the enzyme responsible for degradation of natriuretic peptides ANP, BNP and CNP. By inhibiting NEP, TD-0714 elevates the levels of these peptides, which may exert protective cardiac and renal effects including vasodilation, diuresis, natriuresis, reversal of maladaptive changes in heart, blood vessels and kidney, prevention of fibrosis, and prevention of end-organ damage. Theravance Biopharma has specifically designed TD-0714 to possess certain key features, including low renal clearance, the potential to be administered once daily, and the flexibility to be combined with other approved and investigational drugs.
The Phase 1 trial is a randomized, double-blind, placebo-controlled, single-ascending dose study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of TD-0714. The single-center study’s primary endpoints will be the safety and tolerability of TD-0714 in healthy adults. Key secondary endpoints are designed to assess the potential for once-daily dosing and include an assessment of the pharmacodynamics of TD-0714 and the pharmacokinetic half-life. Investigators will also assess TD-0714’s potential for low levels of renal clearance.
“The initiation of this first-in-human clinical trial is the next step in our efforts to develop a best-in-class collection of NEP inhibitors with the flexibility to be combined with a range of other mechanistic classes to potentially deliver enhanced outcomes to patients with a range of cardiovascular and renal diseases. Importantly, our preclinical data presented at the 2015 American Heart Association conference support our belief that several of our NEP inhibitors have attractive biological and pharmacokinetic properties with significant therapeutic potential,” said Mathai Mammen, M.D., Ph.D., Senior Vice President, Research and Development of Theravance Biopharma. “We believe TD-0714 is an exciting compound with uniquely designed characteristics. In addition, it is just the first in a series of novel NEP inhibitors that have been created at Theravance Biopharma. We are working aggressively to advance additional compounds from this program into the clinic and look forward to achieving key development milestones with those drug candidates as well.”
Results from preclinical studies involving several of Theravance Biopharma’s NEP inhibitors were recently presented at the American Heart Association Scientific Sessions 2015. Findings demonstrated that the Company’s NEP inhibitors are potent and selective inhibitors of neprilysin and demonstrated sustained levels of target engagement over 24-hours after a single oral dose in rats. Data also demonstrated that the compounds produced robust and long-lasting cardiovascular effects in rats that were equivalent to or greater than sacubitril, the NEP inhibitor component of Entresto™, which was recently approved by the United States Food and Drug Administration (FDA) for the treatment of patients with reduced-ejection fraction chronic heart failure. Additionally, in the preclinical studies Theravance Biopharma’s compounds were orally bioavailable and demonstrated levels of renal clearance that were low as compared to sacubitril.
About Neprilysin (NEP) Inhibition
Neprilysin (NEP) is an enzyme that degrades natriuretic peptides. These peptides play a protective role in controlling blood pressure and preventing cardiovascular tissue remodeling. Research suggests that inhibiting NEP may result in clinical benefits for patients, including diuresis, control of blood pressure, and reversing maladaptive changes in the heart and vascular tissue in patients with congestive heart failure. Based on this activity, NEP inhibitors may have the potential to treat a range of major cardiovascular and renal diseases, including acute and chronic heart failure, resistant hypertension and chronic kidney disease. In the United States alone, there are roughly six million patients diagnosed with chronic heart failure and approximately one million acute heart failure patients hospitalized annually. Additionally, there are six million Americans affected by resistant hypertension and 26 million with chronic kidney disease.1
About Theravance Biopharma
The mission of Theravance Biopharma (NASDAQ: TBPH) is to create value from a unique and diverse set of assets: an approved product; a development pipeline of late-stage assets; and a productive research platform designed for long-term growth.
Our pipeline of internally discovered product candidates includes potential best-in-class opportunities in underserved markets in the acute care setting, representing multiple opportunities for value creation. VIBATIV® (telavancin), our first commercial product, is a once-daily dual-mechanism antibiotic approved in the US, Europe and certain other countries for certain difficult-to-treat infections. Revefenacin (TD-4208) is an investigational long-acting muscarinic antagonist (LAMA) being developed as a potential once-daily, nebulized treatment for chronic obstructive pulmonary disease (COPD). Axelopran (TD-1211) is an investigational potential once-daily, oral treatment for opioid-induced constipation (OIC). Our earlier-stage clinical assets represent novel approaches for potentially treating diseases of the lung and gastrointestinal tract and infectious disease. In addition, we have an economic interest in future payments that may be made by Glaxo Group Limited or one of its affiliates pursuant to its agreements with Theravance, Inc. relating to certain drug development programs, including the combination of fluticasone furoate, umeclidinium and vilanterol (the “Closed Triple”).
With our successful drug discovery and development track record, commercial infrastructure, experienced management team and efficient corporate structure, we believe that we are well positioned to create value for our shareholders and make a difference in the lives of patients.
SOURCE: Theravance Biopharma
Post Views: 216
