RESEARCH TRIANGLE PARK, NC, USA I December 18, 2013 I BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) today announced that it has selected two optimized plasma kallikrein inhibitors to advance into preclinical development as potential once-daily, oral treatments for the prevention of hereditary angioedema (HAE) attacks.
The second generation discovery program’s goals of improving selectivity and bioavailability compared to BCX4161 were both met, with no effect on prothrombin time at high concentrations ( > 50 micromolar), and oral fraction absorbed exceeding 25%. Similar to BCX4161, these BioCryst discovered compounds demonstrate sub-nanomolar potency on the isolated enzyme and single digit nanomolar potency in suppressing kallikrein activity in an ex vivo activated human plasma kallikrein inhibition (aPKI) assay. Plasma concentrations of each of the optimized compounds exceeded the aPKI assay EC80 concentration at 24 hours after a single oral dose of 10 mg/kg in rats, indicating suitability for once-daily dosing.
“We are pleased with the outcome of our discovery program for second-generation plasma kallikrein inhibitors,” said Yarlagadda S. Babu, Ph.D., Senior Vice President, Drug Discovery at BioCryst. “We look forward to evaluating nonclinical safety in the preclinical development phase, and to providing updates regarding our progress towards our goal of developing a once-daily prophylactic therapy for hereditary angioedema.”
About BCX4161
Discovered by BioCryst, BCX4161 is a novel, selective inhibitor of plasma kallikrein in Phase 2 development for prevention of attacks in patients with hereditary angioedema. By inhibiting plasma kallikrein, BCX4161 suppresses bradykinin production. Bradykinin is the mediator of acute swelling attacks in HAE patients.
About Hereditary Angioedema
HAE is a rare, severely debilitating and potentially fatal genetic condition that occurs in about 1 in 10,000 to 1 in 50,000 people. HAE symptoms include recurrent episodes of edema in various locations, including the hands, feet, face, genitalia and airway. In addition, patients often have bouts of excruciating abdominal pain, nausea and vomiting that are caused by swelling in the intestinal wall. Airway swelling is particularly dangerous and can lead to death by asphyxiation. Further information regarding HAE can be found at www.haea.org.
About BioCryst Pharmaceuticals
BioCryst Pharmaceuticals designs, optimizes and develops novel small molecule drugs that block key enzymes involved in infectious and inflammatory diseases, with the goal of addressing unmet medical needs of patients and physicians. BioCryst’s core development programs include BCX4161 and two next generation oral inhibitors of plasma kallikrein for hereditary angioedema; peramivir, a viral neuraminidase inhibitor for the treatment of influenza; and BCX4430, a broad spectrum antiviral for hemorrhagic fevers. For more information, please visit the Company’s website at www.BioCryst.com.
SOURCE: BioCryst Pharmaceuticals
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RESEARCH TRIANGLE PARK, NC, USA I December 18, 2013 I BioCryst Pharmaceuticals, Inc. (NASDAQ:BCRX) today announced that it has selected two optimized plasma kallikrein inhibitors to advance into preclinical development as potential once-daily, oral treatments for the prevention of hereditary angioedema (HAE) attacks.
The second generation discovery program’s goals of improving selectivity and bioavailability compared to BCX4161 were both met, with no effect on prothrombin time at high concentrations ( > 50 micromolar), and oral fraction absorbed exceeding 25%. Similar to BCX4161, these BioCryst discovered compounds demonstrate sub-nanomolar potency on the isolated enzyme and single digit nanomolar potency in suppressing kallikrein activity in an ex vivo activated human plasma kallikrein inhibition (aPKI) assay. Plasma concentrations of each of the optimized compounds exceeded the aPKI assay EC80 concentration at 24 hours after a single oral dose of 10 mg/kg in rats, indicating suitability for once-daily dosing.
“We are pleased with the outcome of our discovery program for second-generation plasma kallikrein inhibitors,” said Yarlagadda S. Babu, Ph.D., Senior Vice President, Drug Discovery at BioCryst. “We look forward to evaluating nonclinical safety in the preclinical development phase, and to providing updates regarding our progress towards our goal of developing a once-daily prophylactic therapy for hereditary angioedema.”
About BCX4161
Discovered by BioCryst, BCX4161 is a novel, selective inhibitor of plasma kallikrein in Phase 2 development for prevention of attacks in patients with hereditary angioedema. By inhibiting plasma kallikrein, BCX4161 suppresses bradykinin production. Bradykinin is the mediator of acute swelling attacks in HAE patients.
About Hereditary Angioedema
HAE is a rare, severely debilitating and potentially fatal genetic condition that occurs in about 1 in 10,000 to 1 in 50,000 people. HAE symptoms include recurrent episodes of edema in various locations, including the hands, feet, face, genitalia and airway. In addition, patients often have bouts of excruciating abdominal pain, nausea and vomiting that are caused by swelling in the intestinal wall. Airway swelling is particularly dangerous and can lead to death by asphyxiation. Further information regarding HAE can be found at www.haea.org.
About BioCryst Pharmaceuticals
BioCryst Pharmaceuticals designs, optimizes and develops novel small molecule drugs that block key enzymes involved in infectious and inflammatory diseases, with the goal of addressing unmet medical needs of patients and physicians. BioCryst’s core development programs include BCX4161 and two next generation oral inhibitors of plasma kallikrein for hereditary angioedema; peramivir, a viral neuraminidase inhibitor for the treatment of influenza; and BCX4430, a broad spectrum antiviral for hemorrhagic fevers. For more information, please visit the Company’s website at www.BioCryst.com.
SOURCE: BioCryst Pharmaceuticals
Post Views: 145
