BBP-671 / BridgeBio - LARVOL DELTA

Relief of CoA Sequestration by PANKs Agonist As a Potential Treatment for Acidemias (ENDO 2025) - "Moreover GSC003896 could further reduce C3:C2 ratio, comparing to BBP-671. GenSci compounds exhibit a favorable ADME profiles and are under active IND-enabling study."

Genetic Disorders • Metabolic Disorders • Ophthalmology

Development of Brain Penetrant Pyridazine Pantothenate Kinase Activators. (PubMed, J Med Chem) - "These studies led to the prioritization of three late-stage preclinical lead PANK modulators with improved pharmacokinetic profiles and the ability to substantially increase brain CoA levels. Compound 22 (BBP-671) eventually advanced into clinical testing for the treatment of PKAN and propionic acidemia."

Journal • CNS Disorders

A First in Human, Dose Escalation Study to Evaluate the Safety and Tolerability of BBP-671 in Healthy Volunteers and Patients With Propionic Acidemia or Methylmalonic Acidemia (clinicaltrials.gov) - P1 | N=79 | Terminated | Sponsor: CoA Therapeutics, Inc., a BridgeBio company | N=128 ➔ 79 | Recruiting ➔ Terminated; Slow recruitment

Enrollment change • Trial termination • Genetic Disorders • Metabolic Disorders • Ophthalmology

Pantothenate kinase activation restores brain coenzyme A in a mouse model of pantothenate kinase associated neurodegeneration. (PubMed, J Pharmacol Exp Ther) - "BBP-671 crosses the blood brain barrier to correct the neuron-specific CoA deficiency and improve motor function in a mouse model of pantothenate kinase associated neurodegeneration. The central role of CoA and acetyl-CoA in intermediary metabolism suggests that pantothenate kinase activators may be useful in modifying neurological metabolic disorders."

Journal • Preclinical • CNS Disorders • Dystonia • Metabolic Disorders • Movement Disorders • Parkinson's Disease • Solid Tumor • ANK2

A First in Human, Dose Escalation Study to Evaluate the Safety and Tolerability of BBP-671 in Healthy Volunteers and Patients With Propionic Acidemia or Methylmalonic Acidemia (clinicaltrials.gov) - P1 | N=128 | Recruiting | Sponsor: CoA Therapeutics, Inc., a BridgeBio company | Trial completion date: May 2023 ➔ Dec 2023 | Trial primary completion date: May 2023 ➔ Dec 2023

Trial completion date • Trial primary completion date • Genetic Disorders • Metabolic Disorders • Ophthalmology

Relief of CoA sequestration and restoration of mitochondrial function in a mouse model of propionic acidemia. (PubMed, J Inherit Metab Dis) - "Here, we use a hypomorphic PA mouse model to test the effectiveness of BBP-671 in correcting the metabolic imbalances in PA...Furthermore, the low survival of PA mice is restored to normal by BBP-671. These data show that BBP-671 relieves CoA sequestration, improves mitochondrial function, reduces plasma PA biomarkers and extends the lifespan of PA mice, providing the preclinical foundation for the therapeutic potential of BBP-671."

Journal • Preclinical

A First in Human, Dose Escalation Study to Evaluate the Safety and Tolerability of BBP-671 in Healthy Volunteers and Patients With Propionic Acidemia or Methylmalonic Acidemia (clinicaltrials.gov) - P1 | N=128 | Recruiting | Sponsor: CoA Therapeutics, Inc., a BridgeBio company | Trial completion date: Jan 2023 ➔ May 2023 | Trial primary completion date: Jan 2023 ➔ May 2023

Trial completion date • Trial primary completion date • Genetic Disorders • Metabolic Disorders • Ophthalmology

BBP-671, AN INVESTIGATIONAL MODULATOR OF PANTOTHENATE KINASES, DEMONSTRATES PROOF OF CONCEPT IN A PKAN MOUSE MODEL AND TARGET ENGAGEMENT IN HUMANS (MDS Congress 2022) - P1 | "In a PKAN mouse model, BBP-671 improved both survival and movement. In healthy human subjects, BBP-671 was generally well-tolerated and detected in plasma and CSF at concentrations at which efficacy was observed in dKO mice. Increases in WB acetyl-CoA observed with BBP-671 demonstrated target engagement and proof of mechanism."

Preclinical • CNS Disorders

BBP-671, A Potential First-in-Class, Potent, Allosteric Modulator of Human Pantothenate Kinases, is Well-Tolerated and Deomonstrates Target Engagement in Healthy Volunteers (MDS-PAS 2022) - P1 | "BBP-671 is an oral, potentially first-in-class, novel, potent, allosteric modulator of human PanKs specifically developed for the treatment of diseases associated with CoA deficiency. BBP-671 was safe and well-tolerated following oral dosing in healthy volunteers. BBP-671 was detected in healthy volunteer plasma and CSF."

Clinical • CNS Disorders

A First in Human, Dose Escalation Study to Evaluate the Safety and Tolerability of BBP-671 in Healthy Volunteers and Patients With Propionic Acidemia or Methylmalonic Acidemia (clinicaltrials.gov) - P1 | N=128 | Recruiting | Sponsor: CoA Therapeutics, Inc., a BridgeBio company | Trial completion date: Jul 2022 ➔ Jan 2023 | Trial primary completion date: Jul 2022 ➔ Jan 2023

Trial completion date • Trial primary completion date • Genetic Disorders • Metabolic Disorders • Ophthalmology