– BBP-711 led to near complete inhibition of glycolate oxidase throughout the dosing period and greater than 10-fold increases in plasma glycolate, suggesting it has the potential to be both a best-in-class therapy and the first oral therapy for PH1 and recurrent kidney stone formers

– Based on the tolerability and potency of the oral therapy, BridgeBio has met with regulators and intends to initiate a Phase 2/3 pivotal study by the end of 2022

– At the end of 2022, BridgeBio also intends to launch a Phase 2 study of BBP-711 in adult recurrent kidney stone formers, which affects an estimated 1.5 million individuals in the United States and European Union

PALO ALTO, CA, USA I June 27, 2022 I BridgeBio Pharma, Inc. (Nasdaq: BBIO), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, today announced positive Phase 1 data for BBP-711 in healthy volunteers, supporting the development of the investigational therapy for patients with primary hyperoxaluria type 1 (PH1) and recurrent kidney stone formers. The data were shared in a feature oral presentation at European Society for Pediatric Nephrology (ESPN) 2022, taking place in Ljubljana, Slovenia.

BBP-711 is an orally-administered small molecule inhibitor of glycolate oxidase (GO) that is being developed to treat conditions of excess oxalate. Overproduction of oxalate in hyperoxaluria, including PH1 and recurrent kidney stone formers with elevated oxalate, can lead to kidney stone formation, nephrocalcinosis and renal impairment. PH1 affects an estimated 5,000 patients in the United States and European Union, while recurrent stone formers are much more common, affecting an estimated 1.5 million individuals in the United States and European Union.

“PH1 is a severe genetic condition with a high degree of morbidity, including kidney stones, calcification in the kidneys and deposition of calcium oxalate in many vital organs. Despite major advances in the field of hyperoxaluria, PH1 remains a disease with high unmet medical need in many parts of the world,” said Scott Adler, M.D., chief medical officer and vice president of clinical development at Cantero Therapeutics, the BridgeBio affiliate developing BBP-711. “These data are encouraging for patients with PH1 as BBP-711 could become a novel oral therapy to prevent hyperoxaluria and its long-term consequences.”

BBP-711 was evaluated in a two-part, randomized, double-blinded, placebo-controlled, ascending dose Phase 1 study with 92 healthy volunteers. The Phase 1 data included:

  • The pharmacokinetic (PK) parameters demonstrated that the drug was rapidly absorbed with a time to maximum concentration of ~2.5 hours and an elimination half-life of ~26 hours, supportive of once-daily dosing
  • The results showed rapid and clinically meaningful pharmacodynamic (PD) increases in plasma glycolate of 10-15-fold above baseline levels, the highest response publicly reported to date of any GO-targeting agent tested in healthy volunteers
  • PK-PD modeling of this data predicts that near-complete inhibition (maximal inhibition of > 95%) of GO can be sustained throughout the dosing period
  • BBP-711 was well-tolerated with evaluated single doses 40 to 3,000 mgs and multiple doses of 75 to 1000 mgs. Treatment emergent adverse events were low in frequency (15-34%) and mild or moderate, with no changes in clinical laboratory measures, ECG, or vital signs observed

Based on the data, BridgeBio intends to initiate a Phase 2/3 study in PH1. The study is expected to consist of two parts: Part A will include a dose-finding period to identify a well-tolerated therapeutic dose for Part B; Part B will be a randomized, placebo-controlled trial. Key secondary endpoints include absolute change from baseline in 24-hour UOx excretion corrected for body surface area (BSA) and percentage of participants with 24-hour UOx below upper limit of normal (ULN).

“PH1 is a severe and progressive genetic disease. It is often undiagnosed or misdiagnosed in infancy, childhood, adolescence and adulthood and can lead to intensive dialysis or kidney and liver transplantation,” said Kim Hollander, executive director of the Oxalosis and Hyperoxaluria Foundation. “We are encouraged by the potential of an oral therapy for people living with this serious genetic condition. It provides hope to patients praying for a new treatment option, seeking to alleviate the burden of medical care management and achieve an improved quality of life.”

The Company also intends to launch a proof-of-concept Phase 2 study in adult recurrent kidney stone formers with elevated urinary oxalate excretion at the end of 2022, pending discussions with regulatory agencies. Additional studies are planned to address all patients with hyperoxaluria including patients less than six years of age and patients with impaired renal function.

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