science & pipeline

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our product platform

Our drug engineering platform leverages and efficiently translates innovation into therapies that matter.

discover novel genetic disease targets

Well described diseases that can be targeted at their source

Our genetic disease target engine allows us to identify genetic diseases to pursue based on the impact we might deliver for patients
We use computational genomics and statistical genetics, along with systematic disease mapping and partnerships with top academic institutions to identify potential disease-modifying targets
Our team is made up of industry leaders with proven track records who bring decades of scientific insight to the table when selecting genetic disease targets for our pipeline

create medicines with our industry research capabilities

Tailored therapeutic technologies that create potential first or best-in-class medicines

We select a therapeutic approach to target each genetic disease at its source
Our capabilities allow us to work across multiple modalities, including molecular dynamics assisted chemistry, gene therapy, therapeutic proteins and antisense oligonucleotides as well as multiple other technologies, including de novo QGS, NMR trapping and molecular dynamics
Our small, expert teams led by industry veterans focus on addressing the greatest unmet patient needs. We pair each disease with the modality that is suited to maximize patient impact

test our drugs through global development footprint

Broad clinical development capabilities across therapeutic areas and geographies

We have a global clinical development footprint
We have ongoing trials across five different therapeutic areas and over 25 countries
Our patient-centric clinical and regulatory strategies are focused on efficiency and speed and deploys our vast experience across enrollment, protocol quality, site activation, CRO quality and regional performance
We have expert, dedicated R&D teams in each therapeutic area and focused scientific and clinical advisors to guide our programs

deliver our products to patients through commercial infrastructures

Capabilities built to deliver genetic medicines to patients globally

We are building the capabilities and collaborating with partners to deliver our approved products to patients across the globe
We look for new diagnostic partnerships to identify more patients in need of our medicines
We are committed to deepening the early partnerships we have built with patient advocacy groups
We are implementing commercial partnerships in strategic geographics and establishing country-specific Early Access Programs (EAP) and patient assistance programs

We are poised to potentially help 4.5m+ patients across our pipeline

Our platform is delivering:

2approved products

30+programs in our pipeline

30+clinical trials across the globe

The Pipeline

Precision Cardiorenal

Mendelian

Precision Oncology

Gene Therapy

Acoramidis

TTR stabilizer for transthyretin amyloidosis (ATTR)

disease

ATTR-CM, ATTR-PN

genetic source

TTR (transthyretin)

estimated prevalence

>400,000

modality

small molecule

Program summary

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” due to its ability to prevent or minimize ATTR in individuals carrying pathogenic, or disease-causing, mutations in the TTR gene. In mid-2023, BridgeBio announced positive results from a Phase 3 study of acoramidis in ATTR cardiomyopathy, ATTRibute-CM.

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Encaleret

Ca sensing receptor antagonist for autosomal dominant hypocalcemia type 1 (ADH1)

disease

Autosomal dominant hypocalcemia type 1

genetic source

CaSR

estimated prevalence

12,000

modality

small molecule

Program summary

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 initiated its Phase 3 clinical trial at the end of 2022.

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NULIBRY (fosdenopterin)*

Synthetic cPMP for molybdenum cofactor deficiency (MocD) type a

disease

MocD Type A

genetic source

MOCS1

estimated prevalence

100

modality

small molecule

Program summary

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. NULIBRY™ (fosdenopterin) for Injection is a substrate replacement therapy that 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, an enzyme that reduces levels of neurotoxic sulfites. It is the first and only FDA-approved therapy indicated to reduce the risk of mortality in patients with MoCD Type A, and clinical trials have demonstrated that patients treated with NULIBRY or rcPMP had an improvement in overall survival compared to the untreated, genotype-matched, historical control group. In 2022, BridgeBio announced an asset acquisition agreement for NULIBRY with Sentynl Therapeutics, Inc. Sentynl gained full, exclusive licensing rights to ongoing development and commercialization of NULIBRY in the U.S. and is responsible for developing, manufacturing and commercializing fosdenopterin globally.

BBP-418

Glycosylation substrate pro-drug for limb-girdle muscular dystrophy type 2I (LGMD2I/R9)

disease

Limb-girdle muscular dystrophy type 2I (LGMD2I/r()

genetic source

FKRP

estimated prevalence

7,000

modality

small molecule

Program summary

BridgeBio is investigating what could be 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. BridgeBio is investigating what could be the first-ever oral disease-modifying treatment for limb girdle muscular dystrophy type 2I (LGMD2I/R9). BBP-418 (ribitol), which preclinical studies have shown is converted into the phosphorylated substrate that is inefficiently added to the alpha-dystroglycan (αDG) “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/R9 have symptomatic and palliative treatment options only, such as walking assists and ventilatory support, but no disease-modifying therapies exist. BridgeBio is enrolling for its Phase 3 FORTIFY registrational study, which evaluates the safety and efficacy of BBP-418. FORTIFY has a planned interim analysis at 12 months focused on assessing glycosylated αDG as a surrogate endpoint to potentially support an accelerated approval. The North Star Assessment for Dysferlinopathy (NSAD) and secondary endpoints will be evaluated at 36 months, and results are expected to provide confirmatory clinical data. Initial Phase 2 data indicates the potential for BBP-418 to increase glycosylation of αDG and drive functional improvements for patients, as well as reduce CK, a key marker of muscle breakdown. Furthermore, the 90- and 180-day data show improvements on walk tests from baseline, which the Company believes suggests a potential impact on clinical function and on the rate of disease progression. BBP-418 has received Fast Track Designation and Orphan Drug Designation for the treatment of LGMD2i from the FDA and for LGMD from the European Medicines Agency. Initial Phase 2 data indicates the potential for BBP-418 to increase glycosylation of αDG and drive functional improvements for patients, as well as reduce CK, a key marker of muscle breakdown. Furthermore, the 90- and 180-day data show improvements on walk tests from baseline, which the Company believes suggests a potential impact on clinical function and on the rate of disease progression. BBP-418 has received Fast Track Designation and Orphan Drug Designation for the treatment of LGMD2i from the FDA and for LGMD from the European Medicines Agency.

Low-dose infigratinib

FGFR1-3 inhibitor for achondroplasia

disease

Achondroplasia

genetic source

FGFR

estimated prevalence

55,000

modality

small molecule

Program summary

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 the potential to help these patients due to its direct inhibition of the mutant FGFR3 receptor. In mouse models of achondroplasia, infigratinib demonstrated robust bone growth and clear improvement in cranial and spinal defects. BridgeBio recently shared positive Phase 2 results from PROPEL2, a Phase 2 trial of infigratinib in children with achondroplasia. Based on the positive Phase 2 results, BridgeBio has started to enroll children for a pivotal Phase 3 trial and will continue to explore the impact on the medical and functional complications of achondroplasia in future studies of infigratinib.

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BBP-671

PanK activator for pantothenate kinase-associated neurodegeneration (PKAN) & organic acidemias

disease

PKAN, organic acidemias and CASTOR

genetic source

PANK2 (pantothenate kinase)

estimated prevalence

7,000

modality

small molecule

Program summary

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 acidemias (OAs), such as propionic acidemia (PA) and methylmalonic acidemia (MMA). 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 acidemias, 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 believes initial findings from its Phase 1 study of healthy volunteers demonstrate target engagement and proof of mechanism of BBP-671 provided by evidence that BBP-671 can cross the blood brain barrier. Based on these data, BridgeBio intends to move forward with the second part of the Phase 1 clinical study in patients with propionic acidemia and methylmalonic acidemia in the second half of 2022, and plans to initiate a pivotal Phase 2/3 study in PKAN in 2023.

TRUSELTIQ (high-dose infigratinib)*

FGFR1-3 inhibitor for FGFR+ cancers

disease

Fibroblast Growth Factor Receptor

genetic source

FGFR

estimated prevalence

37,000

modality

small molecule

Program summary

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.

BBP-398

SHP2 inhibitor for MAPK/RAS driven cancers

disease

MAPK/RAS driven cancers

genetic source

PTPN11 (SHP2) and MAPK pathway

estimated prevalence

>500,000

modality

small molecule

Program summary

BBP-398 is a SHP2 inhibitor that is being developed 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. BridgeBio is currently advancing its Phase 1 clinical trial in patients with solid tumors driven by mutations in the MAPK signaling pathway, including RAS and receptor tyrosine kinase genes. In May 2022, BridgeBio entered an exclusive license with Bristol Myers Squibb to develop and commercialize BBP-398 in oncology worldwide, except for in mainland China and other Asian markets, which are part of BridgeBio’s separate strategic collaboration with LianBio announced in 2020. Additionally, BridgeBio has a non-exclusive clinical collaboration and supply agreement with Amgen to evaluate the combination of BBP-398 with LUMAKRAS® (sotorasib) in patients with advanced solid tumors with the KRAS G12C mutation. BridgeBio is currently advancing its Phase 1/2 clinical trial in patients with solid tumors with a KRAS G12C mutation. The US FDA also granted Fast Track designation for the investigation of BBP-398 in combination with LUMAKRAS for adult patients with previously treated, KRAS G12C-mutated, metastatic NSCLC.

BBO-8520

KRASG12C dual inhibitor for KRAS cancers

disease

KRAS+ cancers

genetic source

KRAS

estimated prevalence

40,000

modality

small molecule

Program summary

BBO-8520 is a small molecule that directly binds and inhibits KRASG12C in both its active (GTP bound) and inactive (GDP bound) conformations. In binding the active state, BBO-8520 disrupts effector protein binding and downstream oncogenic signaling. To date, BridgeBio has shown this molecule with its novel dual reactivity to be effective in vitro against several resistant mutants that have evolved in response to GDP-inhibitor treatment. In vivo, BBO-8520 demonstrated the potential to have strong efficacy and showed differentiated activity in some PDX models driving tumor regressions. BridgeBio believes this could lead to differentiated activity in cancer patients with KRASG12C driven cancer and plans to enter the clinic with its KRASG12C dual inhibitor in 2023.

PI3Kα:RAS breaker

PI3Kα:RAS breaker for KRAS cancers

disease

KRAS+ cancers

genetic source

KRAS

estimated prevalence

>500,000

modality

small molecule

Program summary

BridgeBio is pursuing PI3Kα:RAS breakers, which are small molecules that block RAS driven PI3Kα activation. Currently, the only approved PI3Kα inhibitor blocks all kinase activity from the protein, which interferes with normal cell signaling and ultimately, may result in hyperglycemia and insulin-driven resistance. Through its novel protein-protein interaction inhibition, breaker molecules deliver tumor selectivity that spares normal glucose metabolism as it interferes with oncogenic signaling. In addition to treating patients currently served by PI3Kα inhibitors, we expect this approach to potentially have broad utility for many other patients with oncogene-driven tumors (including HER2/HER3 dependency, RAS mutant tumors, PI3Kα mutant tumors, and tumors driven by RTK activation of RAS signaling) as both a monotherapy and in combination with other agents. The development candidate selection will take place in 2023 with IND filing in 2024.

Pan-KRAS inhibitor

Pan-KRAS inhibitor for KRAS cancers

disease

KRAS+ cancers

genetic source

KRAS

estimated prevalence

>500,000

modality

small molecule

Program summary

BridgeBio’s pan-KRAS program targets KRASG12D and KRASG12V mutations present in a large percentage of colorectal, pancreatic and non-small cell lung cancer tumors. BridgeBio has achieved in vivo target engagement and has identified leads with promising oral bioavailability. Development candidate selection is planned for 2023.

BBP-954

GPX4 inhibitor for multiple tumors

disease

Multiple tumors

estimated prevalence

>500,000

modality

small molecule

Program summary

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.

Gene therapy aims to replace functional copies of single genes harboring loss-of-function mutations. Genetic material is delivered into cells via non-replicating virus particles, offering the potential for one-time, curative therapy.

Pre-clinical

Phase 1

Phase 2

Phase 3

Commercial

BBP-631

AAV5 gene therapy for congenital adrenal hyperplasia (CAH)

disease

CAH

genetic source

CYP21A2

estimated prevalence

>75,000

modality

gene therapy

Program summary

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 hormone and steroid balance by enabling people with CAH to make their own cortisol and aldosterone — something that is not possible with any treatment on the market or currently in clinical trials for CAH. BridgeBio believes a gene therapy has the potential to restore the delicate balance of hormone production that is dysregulated in this disease. The initial Phase 1/2 data readout is expected in the second half of 2023.

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BBP-812

AAV9 gene therapy for Canavan disease

disease

Canavan Disease

genetic source

ASPA

estimated prevalence

1,000

modality

gene therapy

Program summary

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, BridgeBio seeks to deliver functional copies of the ASPA gene throughout the body and into the brain, correcting the disease. To date, results have shown promising pharmacodynamic, tolerability and preliminary functional efficacy. A broader Phase 1/2 data readout, including safety and efficacy findings and updates on the pharmacodynamic data, is expected in the first half of 2023.

AAV gene therapy

Tuberous sclerosis (TSC) 1/2

disease

Tuberous sclerosis (TSC) 1/2

genetic source

TSC

estimated prevalence

100,000

modality

gene therapy

Program summary

Tuberous sclerosis complex (TSC) is a genetic disease caused by a mutation in either the TSC1 or TSC2 gene. TSC encompasses significant symptoms across multiple organs, including refractory seizures. BBP-821 and BBP-822 are investigational adeno-associated virus (AAV) gene therapies to treat TSC due to a mutation in the TSC1 gene or the TSC2 gene. The AAV gene therapy is designed to deliver, through systemic administration, a functional copy of the TSC1 or TSC2 gene, and has shown through multiple animal studies to result in efficient and persistent delivery to the brain. If successful, the goal is to restore a working copy of the aberrant gene to the central nervous system, enabling people with mutations in those genes to make functional proteins, something that is not possible with any treatment on the market or currently in clinical trials for TSC1 or TSC2. IND submission is expected in 2025.

AAV gene therapy

Cystinuria

disease

Cystinuria

genetic source

SLC3A1, SLC7A9

estimated prevalence

30,000

modality

gene therapy

Program summary

Cystinuria is a renal disease characterized by severe kidney stones and is caused by mutations in either of two solute carrier genes- SLC3A1 or SLC7A9. BridgeBio is developing an investigational adeno-associated virus (AAV) gene therapy to potentially deliver a functional copy of the SLC3A1 gene directly to the cells of the kidney involved in amino acid reabsorption via the transport complex. If successful, BridgeBio hopes to restore the kidney’s ability to form a functional amino acid transport system, thereby correcting the hyperexcretion of urinary cystine that causes stone formation in cystinuria. There are currently no approved therapies for cystinuria other than limiting sodium and protein intake.

* BridgeBio has licensed these therapies to partners with the hope of reaching as many people with unmet need as possible.

Visit publications for selected literature and presentations for recent data presented at medical meetings about each program.

our commitment to patients

BridgeBio ultimately exists to help patients. We are committed to discover, create, test and deliver breakthrough medicines for genetic diseases to patients as quickly and safely as possible.

Elliot, living with MoCD Type A Read More

Porter, living with cholangiocarcinoma Read More

Lesley, living with CAH Read More