Mendelian
Targeted Oncology
Gene Therapy

Mendelian

Pre-clinical
Phase 1
Phase 2
Phase 3
Commercial
NULIBRY (fosdenopterin)

Synthetic cPMP for MOCD Type A

patients (us + eu)

100

disease

Molybdenum cofactor deficiency (MocD) Type A

genetic source

MOCS1

program overview

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.

Acoramidis

TTR Stabilizer for ATTR-CM

patients (us + eu)

>400,000

disease

ATTR-CM, ATTR-PN

genetic source

TTR (transthyretin)

program overview

Acoramidis is an investigational small molecule being studied to potently stabilize transthyretin (TTR) and slow or halt the progression of TTR amyloidosis (ATTR). Acoramidis was designed to mimic the structure of the naturally occurring T119M mutation that protects carriers of known pathogenic variants from developing ATTR. Acoramidis has been well-tolerated and demonstrated near complete TTR stabilization in pre-clinical, Phase 1, and Phase 2 studies. The efficacy and safety of acoramidis is currently being investigated in Phase 2 and Phase 3 studies.

Patidegib topical gel

Topical HH Inhibitor (Patidegib) for Gorlin Syndrome

patients (us + eu)

120,000

disease

Gorlin syndrome, Frequent basal cell carcinoma

genetic source

PTCH1 (patched-1, a smoothened inhibitor)

program overview

Patidegib topical gel is designed to selectively replace and/or augment the function of Patched (Ptc), a naturally occurring hedgehog signaling pathway inhibitor, by blocking the Smoothened (Smo) protein. Acting as a tumor suppressor, patidegib is designed to allow cells to function normally and limit the overproduction of tumors found in patients with Gorlin Syndrome and High Frequency Basal Cell Carcinoma. Because oral formulations for this treatment typically have serious systemic side effects which cause many patients to discontinue treatment, patidegib is formulated as a topical gel to reduce its side effect profile due to its minimal systemic exposure. BridgeBio is currently investigating the safety and efficacy of patidegib in patients with Gorlin Syndrome in a Phase 3 clinical trial.

Low-dose infigratnib

FGFR1-3 inhibitor for achondroplasia

patients (us + eu)

55,000

disease

Achondroplasia

genetic source

FGFR

program overview

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.

Encaleret

Ca sensing receptor antagonist for Autosomal Dominant Hypocalcemia Type 1

patients (us + eu)

12,000 / 200,000

disease

Autosomal Dominant Hypocalcemia Type 1 / Hypoparathyroidism

genetic source

CaSR

program overview

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 a Phase 2 clinical trial is currently enrolling.

BBP-589

Recombinant Collagen 7 for rDEB

patients (us + eu)

1,500

disease

Dystrophic Epidermolysis Bullosa (DEB)

genetic source

COL7A1 (collagen 7)

program overview

BridgeBio is working to create a first-ever systemic treatment for recessive dystrophic epidermolysis bullosa (RDEB), 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. In an ongoing Phase 1/2 clinical trial in adult RDEB patients, BridgeBio is evaluating safety and tolerability of PTR-01, as well as clinical proof of concept.

BBP-418

Glycosylation Substrate Pro-drug for LGMD2i

patients (us + eu)

7,000

disease

Limb-Girdle Muscular Dystrophy 2i (LGMD2i)

genetic source

FKRP

program overview

BridgeBio is investigating the first-ever oral disease-modifying treatment for limb girdle muscular dystrophy type 2i (LGMD2i) – BBP-418 (ribitol), which preclinical studies have shown is converted into the phosphorylated substrate that is inefficiently added to the alpha-dystroglycan “shock absorber” protein by the mutated FKRP gene product. Dysfunctional alpha-dystroglycan leads to progressive leg and arm muscle weakness, and in some cases severe respiratory and cardiovascular compromise. Currently, people with LGMD2i have symptomatic and palliative treatment options only, such as walking assists and ventilatory support, but no disease-modifying therapies exist. The safety, pharmacokinetics and tolerability of BBP-418 is being investigated in healthy volunteers in a Phase 1 clinical trial.

BBP-681

Topical PI3Ka Inhibitor for VM & LM

patients (us + eu)

117,000

disease

Venous Malformations

genetic source

PI3Ka

program overview

Venous and lymphatic malformations (VM and LM, respectively) are congenital vascular anomalies caused by mosaic somatic gain-of-function mutation in either the TEK or PIK3CA genes. These malformations cause a number of clinical complications including pain, bleeding and impairment of the function of the affected area. BridgeBio’s investigational approach focuses on getting the right medicine to the right tissue by delivering a PI3Kα inhibitor to the skin and structures close beneath. VT30 topical gel is designed to target the right tissue – the network of malformed vasculature lying just underneath the skin. Preclinical studies showed that once VT30 crosses the skin, it is cleaved by naturally occurring enzymes to produce VT10, a potent inhibitor of PI3Kα. BridgeBio’s local transdermal approach is designed to deliver the drug directly to the cutaneous lesion, bypassing the need for systemic administration. BridgeBio is currently preparing to begin a Phase 1/2 clinical trial in patients with VM/LM.

BBP-711

GO Inhibitor for Primary Hyperoxaluria 1

patients (us + eu)

5,000 / 1.5M

disease

Primary Hyperoxaluria Type 1

genetic source

AGXT

program overview

BBP-711 is an orally available 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. BridgeBio is currently conducting preclinical studies to support regulatory filings required to initiate a first-in human trial.

BBP-671

PanK Activator for PKAN & Organic Acidemias

patients (us + eu)

7,000

disease

Pantothenate kinase-associated neurodegeneration (PKAN), CASTOR

genetic source

PANK2 (pantothenate kinase)

program overview

Coenzyme A (CoA) plays a crucial role in energy metabolism and is implicated in a large number of disorders, including ultra-rare diseases like pantothenate-kinase associated neurodegeneration, or PKAN, and organic acidurias (OAs). BBP-671 is a novel small-molecule approach designed to modulate Coenzyme A (CoA) levels by leveraging recent research about the CoA synthetic pathway. While PanK2 is inactivated in PKAN patients, other isoforms known as PanK1 and PanK3 are still active. This leads to decreased PanK activity and impaired CoA synthesis. Conversely, in organic acidurias, build-up of metabolic intermediates can inhibit the activity of all three isoforms of PanK and impair CoA synthesis. Early experiments have shown that our small molecules can bind to all three PanK isoforms, prevent feedback inhibition, and thereby increase PanK activity and increase CoA synthesis. BridgeBio is currently conducting preclinical studies to support regulatory filings required to initiate a first-in human trial.

BBP-561

KLK 5/7 Inhibitor for Netherton Syndrome

patients (us + eu)

11,000

disease

Netherton

genetic source

SPINK5 (LEKT1, a kallikrein 5/7/14 inhibitor)

program overview

BBP-561 is an investigational treatment for Netherton Syndrome (NS), a debilitating condition of severe skin inflammation, scaling, and allergy with no available disease-modifying therapies. BBP-561 is a topical small molecule dual inhibitor of serine proteases, KLK5 and KLK7, whose regulation is compromised by loss-of-function mutation in the SPINK5 gene that causes NS. In a mouse model of NS, combined knockout of KLK5 and KLK7, but not either gene alone is required to fully rescue the disease phenotype, suggesting best-in-class potential of our dual inhibitor approach. BridgeBio is currently conducting preclinical studies to support regulatory filings required to initiate a first-in human trial.

BBP-472

PI3KB inhibitor for PTEN Autism

patients (us + eu)

120,000

disease

PTEN Autism

genetic source

PTEN

program overview

BBP-472 is a novel treatment designed to balance kinase signaling in the brain for the treatment of children with autism-spectrum disorders (ASD) characterized by loss of function in the PTEN protein. This program, currently in the lead-finding phase, is focused on advancing a brain-permeable, isoform selective, inhibitor of PI3KB, a kinase shown to signal unabated in the absence of PTEN. Although PI3KB inhibitors designed to stay out of the brain are being tested experimentally for cancer indications, a PI3KB inhibitor engineered for brain penetrance has not been advanced to date, representing a major unmet need for this pediatric population.

Targeted Oncology

Pre-clinical
Phase 1
Phase 2
Phase 3
Commercial
High-dose infigratinib

FGFR1-3 inhibitor for FGFR3 + cancers

patients (us + eu)

37,000

disease

Fibroblast Growth Factor Receptor

genetic source

FGFR

program overview

Infigratinib (BGJ398), is an orally administered, ATP-competitive, FGFR1-3 tyrosine kinase inhibitor in development for the treatment of FGFR-driven conditions, including cholangiocarcinoma (bile duct cancer) and urothelial carcinoma (bladder cancer). BridgeBio is preparing to submit a New Drug Application to the US Food and Drug Administration for the treatment of cholangiocarcinoma patients who have been previously treated with available therapies. Two Phase 3 clinical trials are currently enrolling, one for adjuvant treatment of invasive urothelial carcinoma with FGFR3 genomic alterations and another for first-line treatment of FGFR2 fusion-positive cholangiocarcinoma.

BBP-398

SHP2 Inhibitor for RTK Cancers

patients (us + eu)

>500,000

disease

Receptor Tyrosine Kinase Cancers

genetic source

PTPN11 (SHP2) and MAPK pathway

program overview

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).

BBP-454

KRAS Inhibitor for KRAS Cancers

patients (us + eu)

>500,000

disease

KRAS+ cancers

genetic source

KRAS

program overview

BridgeBio is developing agents to treat tumors driven by KRAS, the holy grail of targeted oncology for which there are no approved therapies. Our approach encompasses multiple “shots on goal” that target previously unexploited sites in parallel. The three programs focus on all KRAS driver mutations, which occur in 30% of all cancers. BridgeBio is privileged to partner with some of the world’s foremost KRAS researchers at Frederick National Lab and supercomputing experts at Lawrence Livermore National Lab to power our medicinal chemistry.

BBP-954

GPX4 Inhibitor for Multiple Tumors

patients (us + eu)

>500,000

disease

Multiple Tumors

genetic source

--

program overview

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. 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.

Gene Therapy

Pre-clinical
Phase 1
Phase 2
Phase 3
Commercial
BBP-631

AAV5 gene therapy for congenital adrenal hyperplasia (CAH)

patients (us + eu)

>75,000

disease

Congenital Adrenal Hyperplasia

genetic source

CYP21A2

program overview

BBP-631 is an investigational adeno-associated virus (AAV) gene therapy to treat CAH due to 21-hydroxylase deficiency at its source. BBP-631 is designed to deliver a functional copy of the 21-hydroxylase gene and has been shown through multiple animal studies to result in efficient and persistent delivery to the adrenal gland, where hormones are naturally made. If successful, we hope to restore the body’s ability to both make and regulate hormone production, producing the right amount of hormone at the right time— something that is not possible with any treatment on the market or currently in clinical trials. BridgeBio believes a gene therapy has the unique potential to restore the delicate balance of hormone production that is dysregulated in this disease. An Investigational New Drug (IND) application is currently being prepared for the US Food and Drug Administration.

BBP-812

AAV9 gene therapy for Canavan disease

patients (us + eu)

1,000

disease

Canavan Disease

genetic source

ASPA

program overview

BBP-812 is an investigational adeno-associated virus (AAV) gene therapy for Canavan disease, which begins in infancy and progresses rapidly to severe neuromuscular symptoms and early mortality. Using AAV gene therapy, we seek to deliver functional copies of the ASPA gene throughout the body and into the brain, correcting the disease. Proof-of-concept work in Canavan disease mouse models has shown that our approach restores survival and normal motor function in these disease models. An Investigational New Drug (IND) application is currently being prepared for the US Food and Drug Administration.

BBP-815

AAV gene therapy for nonsyndromic hearing loss

patients (us + eu)

10,000

disease

Nonsyndromic hearing loss

genetic source

TMC1

program overview

BridgeBio is developing an investigational AAV gene therapy for hearing loss caused by TMC1 gene mutations, which account for 3-5% of genetic hearing loss. Our goal is to correct the disease by delivering functional copies of the TMC1 gene to hair cells in the cochlea. Published research shows that TMC1 gene therapy rescues hearing in a mouse model of TMC1 hearing loss.

the
pipeline

Every investigational drug in our pipeline represents hope for an important segment of patients in need of a treatment. By targeting the known drivers of genetic diseases, we are applying precision medicine techniques to develop drugs that show promise of becoming safe, effective therapies. Visit publications for selected literature about each program.