BridgeBio Pharma, Inc. products

Acoramidis (AG10) is an investigational, orally-administered small molecule designed to potently stabilize tetrameric transthyretin (TTR). Acoramidis?was designed to mimic a?naturally-occurring?variant of the TTR gene (T119M) that is considered a “rescue mutation” because it has been shown to prevent or minimize ATTR in individuals carrying pathogenic, or disease-causing, mutations in the TTR gene. Results from the ongoing Phase 3 study investigating acoramidis for symptomatic transthyretin amyloid cardiomyopathy (ATTR-CM), which includes mortality and cardiovascular-related hospitalizations, are expected in 2023.

Encaleret is an investigational small molecule antagonist of the calcium sensing receptor (CaSR) being studied in disorders of calcium homeostasis, including autosomal dominant hypocalcemia type 1 (ADH1). Individuals with ADH1 have gain-of-function mutations in the CaSR, causing low serum calcium and a range of debilitating symptoms. ADH1 may also lead to relatively high levels of calcium in urine, a condition called hypercalciuria, which can result in impaired kidney function and can cause kidney stone formation. Encaleret has been administered to approximately 1,300 healthy volunteers and osteoporosis patients, demonstrating tolerability and showing clear modification of ADH1 disease drivers, encouraging our investigation of the compound in ADH1 patients. Encaleret is a potential first-in-class CaSR antagonist for ADH1 and initiation of Phase 3 is planned in 2022.

BBP-711 is an orally-administered small molecule inhibitor of glycolate oxidase (GO) that is being developed to treat conditions of excess oxalate, including primary hyperoxaluria type 1 (PH1) and frequent kidney stone formation. In PH1, loss of function mutation in the AGXT gene results in accumulation of glyoxylate, which is converted into oxalate and leads to kidney stones and organ damage. Targeting GO is a clinically validated approach to reduce urinary oxalate by lowering the concentration of glyoxylate. The first-in-human Phase 1 trial of BBP-711 for hyperoxaluria was initiated in May 2021.

Patients with MoCD Type A have mutations in the MOCS1 gene leading to deficient MOCS1A/B dependent synthesis of the intermediate substrate, cPMP. Substrate replacement therapy with fosdenopterin provides an exogenous source of cPMP, which is converted to molybdopterin. Molybdopterin is then converted to molybdenum cofactor, which is needed for the activation of molybdenum-dependent enzymes, including sulfite oxidase (SOX), an enzyme that reduces levels of neurotoxic sulfites.

Infigratinib (BGJ398), is an orally administered, ATP-competitive, FGFR1-3 tyrosine kinase inhibitor in development for the treatment of FGFR-driven conditions, including achondroplasia, a bone growth disorder in children. Overactivating FGFR3 mutations drive downstream MAPK and STAT1 signaling that aberrates growth plate development, thereby causing disproportionate short stature and serious health complications stemming from cranial and spinal defects. Low dose infigratinib has best-in-class potential due to its design to inhibit mutant FGFR3 receptor. In mouse models of achondroplasia, infigratinib demonstrated robust bone growth and clear improvement in cranial and spinal defects. BridgeBio is currently conducting a Phase 2 clinical trial in achondroplasia patients to evaluate the safety and tolerability of low-dose infigratinib, as well as clinical proof-of-concept.

BridgeBio is working to create a potential first-ever systemic treatment for dystrophic epidermolysis bullosa (DEB), a disease caused by loss of function of Collagen 7 (C7) protein. PTR-01 is a C7 protein replacement therapy designed to restore the missing collagen protein (C7) at the root of the disease. Mutations in the gene that encodes C7 enable the epidermis to separate from the dermis. Even minor friction or trauma can cause debilitating blistering, tearing and scarring of the skin, along with severe pain and itching. The disease can also affect the lining of the mouth, esophagus, eye, anus and vagina. BridgeBio completed a Phase 2 clinical trial evaluating safety and tolerability of PTR-01, as well as clinical proof of concept, and has initiated a Phase 2 extension study.

Infigratinib is an orally administered, ATP-competitive, FGFR1-3 tyrosine kinase inhibitor in development for the treatment of FGFR-driven cancers. Multiple Phase 3 clinical trials are currently enrolling; please explore www.clinicaltrials.gov for more information. TRUSELTIQ™ (infigratinib) obtained accelerated approval by FDA, was conditionally approved by Health Canada and received approval in Australia. TRUSELTIQ™ is not approved for use by any other health authority. For the current approval status and more information please visit www.truseltiq.com. In 2022, Helsinn Group gained full, exclusive licensing rights to commercialize high-dose infigratinib worldwide in oncology indications except in mainland China, Hong Kong and Macau. BridgeBio has established a strategic collaboration with LianBio for the development and commercialization of infigratinib in oncology indications in mainland China, Hong Kong and Macau.

BridgeBio is developing SHP2 inhibitors as potentially effective additions to the therapeutic arsenal for difficult-to-treat cancers. SHP2, encoded by the PTPN11 gene, links growth factor signaling with the downstream RAS/ERK/MAPK pathway to regulate cell growth and division. Over-activity of this pathway, often driven by distinct gene mutations, causes or contributes to many human cancers. Inhibiting SHP2 offers a new approach to treat tumors relying on this pathway. SHP2 also suppresses T-cell activity against growing tumors through regulation of the adaptive immune response. SHP2 inhibition may relieve this negative effect, enhancing the patient`s immune response to fight cancer proliferation. A Phase 1 clinical trial is planned (NCT04528836).

RAS is one of the most well-known oncogenic drivers, with approximately 30% of all cancers being driven by RAS mutations, including large proportions of lung, colorectal and pancreatic tumors. BridgeBio’s approach to RAS cancers encompasses multiple “shots on goal” that target both KRAS mutant tumors and those in which RAS activates PI3Ka. We believe two of our approaches have the potential to be first-in-class. In one approach, we have discovered multiple series of direct KRAS G12C dual inhibitors that block both the active and inactive states of KRAS G12C and have shown differentiation from KRAS G12C inactive state inhibitors such as sotorasib and adagrasib. Another approach has led to the discovery of multiple PI3Ka:RAS breakers that are able to block RAS activation of the key oncogenic effector PI3Ka. PI3Ka is the second most altered oncogene in human tumors. 

GPX4 neutralizes toxic free radicals at the lipid membrane, protecting cells from death by ferroptosis. BridgeBio is developing covalent inhibitors of GPX4 designed to induce ferroptosis in cancer cells. BridgeBio has entered into a strategic collaboration with Helsinn to co-develop and co-commercialize a potentially first-in-class inhibitor designed to target glutathione peroxidase 4 (GPX4) with the hope of providing an effective new therapy for patients with difficult-to-treat tumors. Our approach has demonstrated monotherapy activity, reducing tumor volume in a mouse xenograft model of renal cell carcinoma. Recent high profile publications provide preclinical in vivo rationale for monotherapy and combinations with immuno-oncology agents, kinase inhibitors, and chemotherapy. Optimization of oral lead compounds is ongoing.