– Interim data from healthy individuals, reported earlier this year, showed that BBP-671 was detected in plasma and cerebrospinal fluid (CSF) at concentrations above predicted therapeutic thresholds, suggesting the compound has the potential to impact key systemic and neurological complications of PA and MMA

– BridgeBio is in active discussions with regulators and expects to launch a pivotal Phase 2/3 clinical study of BBP-671 in pantothenate kinase-associated neurodegeneration (PKAN) in 2023

– If successful, BBP-671 has potential to be a best-in-class therapy for PA, MMA, and PKAN patients, as well as the first approved oral therapy for the treatment of systemic complications caused by CoA deficiencies

PALO ALTO, CA, USA I August 18, 2022 I BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, today announced that the first patient has been dosed in its Phase 1 clinical trial of BBP-671, an investigational oral therapy being developed for the potential treatment of conditions caused by coenzyme A (CoA) deficiencies. 

BBP-671 is an investigational oral therapy intended to increase CoA levels by allosterically modulating pantothenate kinases, key enzymes in the CoA biosynthesis pathway. It is being developed as a potential therapy for diseases in which CoA metabolism is deficient, including propionic acidemia (PA), methylmalonic acidemia (MMA), and pantothenate kinase-associated neurodegeneration (PKAN). PA, MMA, and PKAN affect an estimated 7,000 patients in the United States and European Union collectively, with PA and MMA typically diagnosed in early infancy. BBP-671 is based on breakthrough scientific developments from St. Jude Children’s Research Hospital in Memphis, Tennessee. 

The first-in-human Phase 1 study of BBP-671 is a single- and multiple-ascending dose study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of BBP-671. The first part of the study evaluated BBP-671 in healthy individuals and the second part of the study is evaluating BBP-671 in PA and MMA patients. Positive interim data from healthy individuals were reported earlier this year. 

The first patient dosed in the second part of the trial has PA. In this part of the study, up to eight PA patients and eight MMA patients will receive BBP-671. Safety and tolerability will be assessed, as well as the PK and PD of BBP-671 using validated bioanalytical assays. A wide range of disease-related biomarkers with potential clinical relevance will be monitored during the study and compared to baseline values. The potential use of biomarkers for PA and MMA as surrogate endpoints in clinical trials for metabolic diseases is a subject of active discussion among key opinion leaders in the field.1 

“We are eager to advance the trial of BBP-671 in the hope that it will provide a positive improvement for patients, valuable data, and ultimately lead to a meaningful therapy for patients who currently have no approved treatment options,” said Zineb Ammous, M.D., clinical geneticist and Medical Director of The Community Health Clinic in Topeka, Indiana, which specializes in rare genetic conditions. 

PA and MMA are rare metabolic disorders caused by mutations in genes that impact the development of enzymes that participate in amino acid metabolism, leading to life-threatening metabolic decompensations, as well as long-term complications involving multiple organ systems, including the heart, pancreas, kidney, liver, and brain. The current standard of care includes dietary restrictions, supplementation, and sometimes liver and/or kidney transplantation but unmet need remains high due to the long-term and life-threatening impact of these diseases. 

“Currently, the majority of individuals with PA and MMA are being diagnosed through newborn screening and are on a strict diet and regimen of supplements and medications. PA and MMA patients experience life-threatening metabolic decompensations, as well as many other serious complications as a result of their disease. We are hopeful that by creating a therapy designed to target the disease by modulating fundamental metabolic pathways, we may be able to treat a condition that impacts young people so early in their lives.,” said Jerry Vockley, M.D., Ph.D., Chief of Genetic and Genomic Medicine and Director of the Center for Rare Disease Therapy at the University of Pittsburg Medical Center (UPMC) Children’s Hospital of Pittsburgh, Pennsylvania.  

Initial data from the second part of this clinical trial are expected in the first half of 2023. The company also plans to initiate a pivotal Phase 2/3 clinical study in PKAN in 2023.  

“We are excited by biomarker changes observed with BBP-671 in a preclinical study using a mouse model for PA, which were associated with improved survival.  Individuals diagnosed with PA and MMA and their families currently have no treatment options beyond dietary management and liver and/or kidney transplant, and we hope that BBP-671 may represent a novel therapeutic strategy for these diseases.” said Uma Sinha, Ph.D., Chief Scientific Officer of BridgeBio. 

More information about the ongoing Phase 1 clinical trial of BBP-671 (study number NCT04836494) can be found here on the ClinicalTrials.gov website.  

Longo, N. et al. Journal of Inherited Metabolic Disease. 2022;45:2. 

About BridgeBio Pharma, Inc. 
BridgeBio Pharma, Inc. (BridgeBio) is a commercial-stage biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn and Twitter

SOURCE: BridgeBio Pharma