Pantothenate Kinase-Associated Neurodegeneration

– Project ‘NADER’ is intended to span multiple phases, starting from mapping rare diseases in the UAE and wider region through innovative risk assessment algorithms, and moving towards clinical trials with transformative medicines Burjeel Holdings, one of the largest healthcare providers in the MENA region, and BridgeBio Pharma, Inc., a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, have announced a new project to revolutionize the field of early diagnosis and treatment of rare diseases or disorders in the UAE and the region. The two entities signed a preliminary, non-binding Collaboration Agreement establishing a mutual intention to work together on project ‘NADER’ (Needs Assessment and Therapeutics Development for Rare Diseases – ‘nader’ meaning ‘rare’ in Arabic). Genetic in origin, these often life-threatening or chronically debilitating diseases affect a small percentage of the population and are present throughout the person's entire life, even if symptoms do not immediately appear. The partnership will launch operations in Abu Dhabi to conduct clinical trials and research, leveraging the Emirate’s advanced infrastructure for innovation and life science. Project ‘NADER’ aims to revolutionize the field of early diagnosis and treatment in order to potentially improve patient outcomes. The entities intend to collaborate on identifying patients with several rare diseases, including achondroplasia, hypochondroplasia, FGFR-driven craniosynostoses, autosomal dominant hypocalcemia type 1, limb girdle muscular dystrophy type 2i, congenital adrenal hyperplasia, Canavan disease, propionic acidemia, methylmalonic acidemia, pantothenate kinase-associated neurodegeneration, and others as mutually agreed. Even though these rare diseases affect a small percentage of the population and can present with nonspecific signs and symptoms, they are often misdiagnosed or only diagnosed later in the disease course after severe complications manifest. Accurate and early diagnosis are crucial to starting intervention promptly and avoiding disease progression. The project will also allow identification of patients who have already been diagnosed but do not currently have access to cutting edge therapies or clinical trial options. In the first phase of project ‘NADER’, the two entities intend to utilize innovative risk assessment algorithms that will be deployed through the healthcare provider’s secure internal data to identify patients at risk for specific rare diseases. Expectations for future phases of the project include analyses of vast amounts of data to identify patterns and markers associated with the diseases and generate personalized risk scores for patients, followed by genetic testing to confirm the diagnosis of identified potential patients. The project also aims to run awareness campaigns and education activities about such rare diseases, to further support the mapping activity and encourage local collaborations from other healthcare providers. Burjeel Holdings will deploy the project across its widespread hospitals and medical centers across the UAE as part of routine diagnostic care, with plans to expand the project through its growing healthcare infrastructure in the region. Local partnerships will also be sought to facilitate wider implementation. Speaking on the partnership’s potential to transform the way rare diseases are identified, Mr. John Sunil, CEO of Burjeel Holdings, said, “Project ‘NADER’ marks a significant milestone in our commitment to delivering the best possible care to our patients. It brings together Burjeel’s expertise in healthcare delivery and outreach and BridgeBio’s vast expertise in delivering breakthrough therapies for rare diseases. By combining our strengths, we seek to address the challenges faced in identification of rare diseases, which often go undiagnosed until symptoms become severe. The project will enable early interventions whether in the form of established treatments or novel therapies.” Commenting on the project launch, Dr. Asma Ibrahim Al Mannaei, Executive Director of the Research, and Innovation Center at the Department of Health – Abu Dhabi (DoH), said: “As part of our ongoing efforts to advance early diagnosis and treatment, the Department of Health – Abu Dhabi is proud to witness yet another leading partnership aimed at propelling transformative medicine to safeguard the health and well-being of community members. Reinforcing Abu Dhabi’s position as a leading destination for life science and innovation, we remain committed to empowering healthcare providers in the Emirate with the means to lead research studies and conduct clinical trials to map out a path towards discovery and breakthrough healthcare in the Emirate and beyond. Similar initiatives translate the Department’s vision in securing health for all while accelerating healthcare outcomes for the benefit of the global community.” The first phase will aim to set the roadmap to providing novel treatment options for identified patients through clinical trials. Dr. Khaled Musallam, Group Chief Research Officer of Burjeel Holdings and project lead said, “Many rare diseases are highly clustered in our region due to our unique genetic pool. These diseases are often ‘lost in the system’ or have very limited treatment options. Our ultimate goal from project ‘NADER’ is to link patients to evolving treatment options through clinical trials of small molecules and gene therapies. The first step to bringing such innovative solutions to our region is to identify disease burden and patients’ unmet needs.” “Building on our already established foundation of genetic disease patient care, we hope that BridgeBio can help bring more patients access to novel treatments, clinical trials, and capabilities alongside a strong partner like Burjeel, and so we are grateful to be working with them to expand our efforts in the MENA region. The BridgeBio vision is to serve patients around the world, and this is an important step in that direction,” said Neil Kumar, Ph.D., BridgeBio founder and CEO. As the collaboration unfolds, both Burjeel Holdings and BridgeBio anticipate significant progress in the field of rare diseases in the region. The project could also provide patients in the region with increased access to BridgeBio’s state-of-the-art pharmacologic and gene therapies that are currently in development. About Burjeel Holdings Founded in 2007, Burjeel Holdings is one of the leading private healthcare services providers in the MENA region. With a network of 62 assets, including 16 hospitals and 24 medical centers, as well as pharmacies and other allied services, the group provides the highest standard of patient care in the region. Burjeel Medical City, the flagship facility of Burjeel Holdings, is a 400-bed multi-specialty hospital and quaternary care center located in Abu Dhabi, UAE. It offers high-quality specialized treatment and complex care in over 40 adult and pediatric specialties, aided by state-of-the-art medical technology and an international team of experts. Find more information at www.burjeelmedicalcity.com, www.burjeelholdings.com. 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. The content above comes from the network. if any infringement, please contact us to modify.

- Initial data readout for patients with PA and MMA expected in the first half of 2023 - Interim data from healthy individuals, reported earlier this year, showed that BBP-671 was detected in plasma and cerebrospinal fluid (CSF) at concentrations above predicted therapeutic thresholds, suggesting the compound has the potential to impact key systemic and neurological complications of PA and MMA - BridgeBio is in active discussions with regulators and expects to launch a pivotal Phase 2/3 clinical study of BBP-671 in pantothenate kinase-associated neurodegeneration (PKAN) in 2023 - If successful, BBP-671 has potential to be a best-in-class therapy for PA, MMA, and PKAN patients, as well as the first approved oral therapy for the treatment of systemic complications caused by CoA deficiencies PALO ALTO, Calif., Aug. 18, 2022 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, today announced that the first patient has been dosed in its Phase 1 clinical trial of BBP-671, an investigational oral therapy being developed for the potential treatment of conditions caused by coenzyme A (CoA) deficiencies. BBP-671 is an investigational oral therapy intended to increase CoA levels by allosterically modulating pantothenate kinases, key enzymes in the CoA biosynthesis pathway. It is being developed as a potential therapy for diseases in which CoA metabolism is deficient, including propionic acidemia (PA), methylmalonic acidemia (MMA), and pantothenate kinase-associated neurodegeneration (PKAN). PA, MMA, and PKAN affect an estimated 7,000 patients in the United States and European Union collectively, with PA and MMA typically diagnosed in early infancy. BBP-671 is based on breakthrough scientific developments from St. Jude Children’s Research Hospital in Memphis, Tennessee. The first-in-human Phase 1 study of BBP-671 is a single- and multiple-ascending dose study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of BBP-671. The first part of the study evaluated BBP-671 in healthy individuals and the second part of the study is evaluating BBP-671 in PA and MMA patients. Positive interim data from healthy individuals were reported earlier this year. The first patient dosed in the second part of the trial has PA. In this part of the study, up to eight PA patients and eight MMA patients will receive BBP-671. Safety and tolerability will be assessed, as well as the PK and PD of BBP-671 using validated bioanalytical assays. A wide range of disease-related biomarkers with potential clinical relevance will be monitored during the study and compared to baseline values. The potential use of biomarkers for PA and MMA as surrogate endpoints in clinical trials for metabolic diseases is a subject of active discussion among key opinion leaders in the field.1 “We are eager to advance the trial of BBP-671 in the hope that it will provide a positive improvement for patients, valuable data, and ultimately lead to a meaningful therapy for patients who currently have no approved treatment options,” said Zineb Ammous, M.D., clinical geneticist and Medical Director of The Community Health Clinic in Topeka, Indiana, which specializes in rare genetic conditions. PA and MMA are rare metabolic disorders caused by mutations in genes that impact the development of enzymes that participate in amino acid metabolism, leading to life-threatening metabolic decompensations, as well as long-term complications involving multiple organ systems, including the heart, pancreas, kidney, liver, and brain. The current standard of care includes dietary restrictions, supplementation, and sometimes liver and/or kidney transplantation but unmet need remains high due to the long-term and life-threatening impact of these diseases. “Currently, the majority of individuals with PA and MMA are being diagnosed through newborn screening and are on a strict diet and regimen of supplements and medications. PA and MMA patients experience life-threatening metabolic decompensations, as well as many other serious complications as a result of their disease. We are hopeful that by creating a therapy designed to target the disease by modulating fundamental metabolic pathways, we may be able to treat a condition that impacts young people so early in their lives.,” said Jerry Vockley, M.D., Ph.D., Chief of Genetic and Genomic Medicine and Director of the Center for Rare Disease Therapy at the University of Pittsburg Medical Center (UPMC) Children's Hospital of Pittsburgh, Pennsylvania. Initial data from the second part of this clinical trial are expected in the first half of 2023. The company also plans to initiate a pivotal Phase 2/3 clinical study in PKAN in 2023. “We are excited by biomarker changes observed with BBP-671 in a preclinical study using a mouse model for PA, which were associated with improved survival. Individuals diagnosed with PA and MMA and their families currently have no treatment options beyond dietary management and liver and/or kidney transplant, and we hope that BBP-671 may represent a novel therapeutic strategy for these diseases.” said Uma Sinha, Ph.D., Chief Scientific Officer of BridgeBio. More information about the ongoing Phase 1 clinical trial of BBP-671 (study number NCT04836494) can be found here on the ClinicalTrials.gov website. References 1 Longo, N. et al. Journal of Inherited Metabolic Disease. 2022;45:2. 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. BridgeBio Pharma, Inc. Forward-Looking Statements This press release contains forward-looking statements. Statements we make in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), which are usually identified by the use of words such as “anticipates,” “believes,” “estimates,” “expects,” “intends,” “may,” “plans,” “projects,” “seeks,” “should,” “will,” and variations of such words or similar expressions.  We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions.  These forward-looking statements, including statements relating to the timing and prospects of success for the development of BBP-671, including plans for an initial data readout from the second part of the Phase 1 clinical study for patients with PA and MA in the first half of 2023, the expected initiation of a pivotal Phase 2/3 clinical study in PKAN in 2023, and the potential for BBP-671, if successful, to be a best-in-class therapy for PA, MMA, and PKAN patients, as well as the first approved oral therapy for the treatment of systemic complications caused by CoA deficiencies, reflect our current views about our plans, intentions, expectations, strategies and prospects, and are based on the information currently available to us and on assumptions we have made and are not forecasts, promises nor guarantees. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by these forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved.  Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to, the success of our product candidates to treat genetically driven diseases and cancers with clear genetic drivers, our anticipated cash runway and our being fully funded through the completion of the BBP-671 and our ability to access additional funding upon achievement of portfolio milestones, as well as those risks set forth in the Risk Factors section of our most recent Annual Report on Form 10-K and BridgeBio Pharma’s other SEC filings. Moreover, we operate in a very competitive and rapidly changing environment in which new risks emerge from time to time. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. BridgeBio Contact: Grace Rauh Grace.rauh@bridgebio.com (917) 232-5478

- Reported positive interim Phase 2 data for infigratinib in achondroplasia demonstrating a mean increase in annualized height velocity (AHV) of 1.52 cm/year among all Cohort 4 children 5 years of age and older, and announced addition of a 5th cohort to the trial - Reported positive Phase 2 data for encaleret in autosomal dominant hypocalcemia type 1 (ADH1) and announced design of the Phase 3 pivotal study, which is expected to begin later this year - Selected a next-generation KRAS G12C dual inhibitor development candidate and plans to be in the clinic in mid-2023 - Presented updated results from the open-label extension of the Phase 2 study of acoramidis in transthyretin amyloid cardiomyopathy (ATTR-CM), which continue to suggest long-term tolerability of acoramidis and stabilization of disease progression in ATTR-CM - Reported positive data for five early-to-mid-stage genetic disease programs in pipeline, including primary hyperoxaluria type 1 (PH1) and recurrent kidney stone formation; Canavan disease; pantothenate kinase-associated neurodegeneration (PKAN) and organic acidemias; recessive dystrophic epidermolysis bullosa (RDEB); and venous, lymphatic and mixed venolymphatic malformations (VM, LM and VLM) - Received positive opinion from the Committee for Medicinal Products for Human Use (CHMP) recommending approval in the European Union (EU) for NULIBRY® (fosdenopterin) for the treatment of molybdenum cofactor deficiency (MoCD) Type A - Entered into exclusive license agreement with Bristol Myers Squibb for BBP-398, a potentially best-in-class SHP2 inhibitor, in oncology; BridgeBio is eligible to receive up to $905 million, including an upfront payment of $90 million received during the quarter and up to $815 million in additional milestone payments and royalties - Announced sale of Priority Review Voucher (PRV) for $110 million - Secured a two-year deferral for first principal payment on the Company’s senior debt - Ended quarter with $688.6million in cash, cash equivalents and marketable securities, providing financial runway into 2024 PALO ALTO, Calif., Aug. 04, 2022 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio or the Company), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, today reported its financial results for the second quarter ended June 30, 2022, and provided an update on the Company’s operations.  “Focused execution is our top priority, and we are delivering with positive proof-of-concept data in three of our key programs so far this year – achondroplasia, ADH1 and LGMD2i. At the same time, we’ve reported positive data for five additional early-to-mid-stage pipeline programs designed to target a range of genetic diseases with high unmet need. Our productive pipeline is bolstered by new value-creating partnerships, which we believe allow us to keep our attention fixed on driving forward the strongest science for patients,” said Neil Kumar, Ph.D., founder and CEO of BridgeBio. BridgeBio’s Key Programs Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia and hypochondroplasia Positive interim results from Phase 2 trial of infigratinib demonstrated a mean increase in annualized height velocity (AHV) of 1.52 cm/year among all children 5 years of age and older enrolled in Cohort 4 (dose: 0.128 mg/kg once daily) (p=0.02, n=11), the highest dose level evaluated to date based on longest available follow-up at time of data cut The responder rate was 64% (7 of 11 children) in children 5 years and older enrolled in Cohort 4 (dose: 0.128 mg/kg once daily), with response defined as ≥25% increase in AHV from baseline For the avoidance of doubt, the 1.52 cm/year AHV was calculated based on all participants 5 years and older in Cohort 4 and not just the responders Given infigratinib’s pro date, and after discussions with regulators, BridgeBio has added a 5th cohort to the trial and has begun dosing children in Cohort 5 (dose: 0.25 mg/kg once daily), with an expected readout of full data at a medical conference in the first half of 2023 Infigratinib was well-tolerated with no serious adverse events (SAE), no treatment-related ocular adverse events (AE) and no discontinuations due to AEs including in Cohort 5 (dose: 0.25 mg/kg once daily) participants dosed to date, with a median duration of follow-up of 48.1 weeks across all participants in the study; only a limited number of AEs were assessed as related to study drug and all were Grade 1, the lowest level There were no dose or exposure-dependent serum phosphorus elevations; a single case of mild hyperphosphatemia (Grade 1, <10% above upper limit of normal) led to a dose reduction in a participant in Cohort 3 (dose: 0.064 mg/kg once daily), the only dose adjustment made to date in the study, and the participant continues at the lower dose without issue As predicted based on preclinical data, BridgeBio began to see efficacy in Cohort 4; also consistent with preclinical data, the Company expects to see efficacy increase further in Cohort 5 as a result of the higher dose Baseline AHV for Cohort 4 was 4.01 cm/year, which aligns with expectations for natural history, and responder rates were consistent irrespective of baseline AHV Infigratinib is the only known oral product candidate currently under clinical investigation for achondroplasia, with issued patents and filed patent applications expected to provide market protection as late as 2041 With more than 55,000 cases estimated in the United States (US) and Europe, achondroplasia is the most common form of genetic short stature and one of the most common genetic conditions BridgeBio expects to evaluate development of infigratinib in other FGFR-driven skeletal dysplasias, which affect more than 50,000 people in the US and Europe, building on the positive interim Phase 2 data in achondroplasia as well as preclinical data in hypochondroplasia presented at the Endocrine Society’s 2022 annual meeting earlier this year The Company expects to initiate its pivotal Phase 3 trial in the first half of 2023 Encaleret – Calcium-sensing receptor (CaSR) inhibitor for autosomal dominant hypocalcemia type 1 (ADH1) The Company intends to initiate a Phase 3 pivotal study of encaleret in patients with ADH1 by the end of 2022 and expects to release topline data by year-end 2023 Positive data from BridgeBio’s Phase 2b study of encaleret in ADH1 were shared in an oral presentation at the Endocrine Society’s 2022 annual meeting The Phase 2b study demonstrated that treatment with encaleret resulted in rapid and sustained restoration of normal mineral homeostasis by day 5 of therapy which sustained at 24 weeks, and encaleret was well-tolerated without any reported SAEs If approved, encaleret could be the first therapy indicated for the treatment of ADH1, a condition caused by gain-of-function variants of the CASR gene estimated to be carried by 12,000 individuals in the US alone Issued patents and filed patent applications are expected to provide market protection for encaleret in ADH1 into 2041 BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2i (LGMD2i) BridgeBio engaged with regulatory health bodies to align on a Phase 3 trial design and intends to initiate a Phase 3 clinical trial in the first half of 2023 Positive Phase 2 data were shared in a poster presentation at the Muscular Dystrophy Association (MDA) 2022 Annual Meeting in March and in an oral presentation at the International Congress on Neuromuscular Diseases (ICNMD) in July If proven to be successful, BBP-418 could be the first approved therapy for patients with LGMD2i Initial Phase 2 results indicate the potential for BBP-418 to increase glycosylation of alpha-dystroglycan (αDG), which is directly linked to the underlying disease mechanism, and to drive consistent improvements of muscle function in patients through the reduction of creatine kinase, a key marker of muscle breakdown 90- and 180-day data show improvements on walk tests from baseline, which BridgeBio believes suggests a potential impact on clinical function and on the rate of disease progression Acoramidis (AG10) – Transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM) Topline data from the Month 30 primary endpoint, a hierarchical composite including all-cause mortality and cardiovascular hospitalizations, of the ongoing Phase 3 ATTRibute-CM trial of acoramidis in ATTR-CM are expected in mid-2023 In an oral presentation at the American College of Cardiology (ACC) Annual Scientific Session & Expo, BridgeBio shared updates on its data from its ongoing Phase 2 open-label extension (OLE) study of acoramidis in patients with ATTR-CM, which demonstrated that acoramidis continued to be well-tolerated and to potently stabilize TTR NT-proBNP, a biomarker of cardiac failure and independent predictor of mortality in ATTR-CM patients, was stable or improving throughout the study and serum TTR levels were sustainably increased from baseline at Month 30 BBP-631 – AAV5 gene therapy candidate for congenital adrenal hyperplasia (CAH) Initial Phase 1/2 data readout is anticipated by year-end 2022 With more than 75,000 patients estimated in the US and EU, CAH is one of the most prevalent genetic diseases potentially addressable with adeno-associated virus (AAV) gene therapy The disease is caused by deleterious mutations in the gene encoding an enzyme called 21-hydroxylase, leading to a lack of endogenous cortisol production BBP-631 is designed to provide a functional copy of the 21-hydroxylase-encoding gene (CYP21A2) and potentially address many aspects of the disease course If successful, BridgeBio’s investigational gene therapy would be the first therapy for CAH to restore the body’s hormone and steroid balance by enabling people with CAH to make their own cortisol and aldosterone RAS cancer portfolio BridgeBio has selected a next-generation KRAS G12C dual inhibitor development candidate and plans to be in the clinic in mid-2023. The Company's development candidate is the first-known small molecule that directly binds and inhibits KRAS G12C in both its active (GTP bound) and inactive (GDP bound) conformations. BridgeBio believes this will lead to differentiated activity in cancer patients with KRAS G12C driven disease as all other clinical stage direct KRAS G12C inhibitors do not inhibit the active oncogenic form of the protein (GTP-bound KRAS G12C) BridgeBio is also pursuing PI3Ka:RAS breakers, small molecules that block RAS driven PI3Ka activation – a novel approach with the potential to inhibit oncogenic PI3Ka signaling without adverse effects on glucose metabolism 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 Recent Corporate Updates Exclusive license agreement of up to $905 million with Bristol Myers Squibb to develop and commercialize BBP-398, a potentially best-in-class SHP2 inhibitor, in oncology: Under the terms of the agreement, BridgeBio received an upfront payment of $90 million from Bristol Myers Squibb and is eligible to receive up to $815 million in development, regulatory and sales milestone payments, and tiered royalties in the low- to mid-teens. BridgeBio will retain the option to acquire higher royalties in the US in connection with funding a portion of development costs upon the initiation of registrational studies. Based on the terms of the agreement, BridgeBio continues to lead its ongoing Phase 1 monotherapy and combination therapy trials. Bristol Myers Squibb will lead and fund all other development and commercial activities. Sale of PRV for $110 million: Entered into a definitive agreement with an undisclosed purchaser to sell its PRV for $110 million. The Company received the voucher in February 2021 through the U.S. Food and Drug Administration (FDA) approval of NULIBRY (fosdenopterin) for injection as the first therapy to reduce the risk of mortality in patients with MoCD Type A. Two-year extension for principal payment on senior debt: Executed an amendment to the Company’s existing senior secured credit facility. Amendment extended the interest-only period by two years and principal repayment to November 17, 2026. BridgeBio retains access to up to $100 million in delayed debt draws through year-end 2022, subject to certain conditions. The amendment was approved unanimously by existing lenders in the syndicate without adjusting pricing and without imposing financial covenants. Positive Phase 1 data and Phase 2/3 trial design for GO inhibitor for patients with primary hyperoxaluria type 1 (PH1) and recurrent kidney stone formers: Positive data in a feature oral presentation at the European Society for Pediatric Nephrology (ESPN 2022) showed that 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 formations. Overproduction of oxalate in hyperoxaluria, including PH1 and recurrent kidney stone formation with elevated oxalate, can lead to kidney stone formation, nephrocalcinosis and renal impairment. PH1 affects an estimated 5,000 patients in the US and EU, while recurrent stone formers are much more common, affecting an estimated 1.5 million individuals in the US and EU. 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. Positive early data for investigational AAV9 gene therapy in Canavan disease: Promising pharmacodynamic data from the first two participants dosed in the Phase 1/2 clinical trial of BBP-812 for the treatment of Canavan disease. Results showed unprecedented decreases in N-acetylaspartate (NAA) in the brain and urine, suggesting the therapy is producing functional ASPA enzyme. Affecting approximately 1,000 children in the US and EU, Canavan disease is an ultra-rare, disabling and fatal disease with no approved therapy. Positive data in healthy volunteers to support BBP-671 for pantothenate kinase-associated neurodegeneration (PKAN) and organic acidemias: Positive interim Phase 1 data from healthy volunteers was shared in a scientific poster session in support of the development of BBP-671 for PKAN and organic acidemias at the Pan American Parkinson and Movement Disorders (PAS) Congress. Results showed that BBP-671 was detected in healthy volunteer plasma and cerebrospinal fluid, suggesting that BBP-671 is entering the brain, a location critical to target neurological complications of PKAN and organic acidemias at their source. BBP-671 also increased whole blood acetyl-coenzyme-A (CoA) levels in healthy volunteers, a signal supporting proof of mechanism of the therapy. These data represent, to the best of the Company’s knowledge, the first time acetyl-CoA has been directly increased by a pharmacological intervention in humans. 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. Positive data from PTR-01 in patients with recessive dystrophic epidermolysis bullosa (RDEB): Shared updates on positive Phase 2 data in a poster at the Society for Investigative Dermatology (SID) Annual Meeting 2022. Treatment with PTR-01 led to rapid, consistent, and durable wound healing as observed in reduction of wound surface area and clinician-reported assessments. All patients that completed the study reported a decrease in pain over the course of treatment with PTR-01. Positive preliminary data in patients with venous, lymphatic and mixed venolymphatic malformations (VM, LM and VLM): Positive Phase 1b data for VM, LM and VLM was shared in a virtual presentation at the International Society for the Study of Vascular Anomalies (ISSVA). Data showed that the investigational drug was well-tolerated and showed a reduction of pS6 in lesions from baseline to day 28. Positive opinion from CHMP for NULIBRY (fosdenopterin): The CHMP of the European Medicines Agency (EMA) issued a positive opinion recommending approval of NULIBRY in the EU for the treatment of patients with MoCD Type A. Opinion is based on the efficacy and safety data collected to date compared to data from a natural history study. Under an accelerated assessment pathway, a decision by the European Commission (EC), which authorizes marketing approval in the EU, is expected later this year. If approved by the EC, NULIBRY would be the first and only approved therapy in the EU to treat patients with MoCD type A, an ultra-rare, life-threatening genetic disorder that often progresses rapidly in infants with a median overall survival age of about four years. NULIBRY was BridgeBio’s first FDA-approved therapeutic. Sentynl Therapeutics, Inc. acquired global rights to NULIBRY in March 2022. Academic research collaborations: Initiated an academic partnership with Baylor School of Medicine, and a founding affiliation with Bakar Labs, the incubator at UC Berkeley’s Bakar BioEnginuity Hub. Second Quarter 2022 Financial Results: Cash, Cash Equivalents and Marketable Securities Cash, cash equivalents and marketable securities, excluding restricted cash, totaled $688.6 million as of June 30, 2022, compared to $787.5 million as of December 31, 2021. The net decrease of $98.9 million is primarily attributable to net cash used in operating activities of $191.1 million. The net cash used in operating activities was partially offset by a $90.0 million in upfront payment received under the License, Development and Commercialization Agreement between the Company, its affiliate, Navire Pharma, Inc., and Bristol Myers Squibb (the “Navire-BMS License Agreement”). During the six months ended June 30, 2022, the Company also received upfront payments of $110.0 million from the sale of its priority review voucher and $10.0 million upon closing of an asset purchase agreement between its affiliate, Origin Biosciences, Inc., and Sentynl Therapeutics, Inc. The Company also made a $20.5 million mandatory prepayment of a portion of its term loan obligations under its Amended Loan and Security Agreement in connection with the upfront payment received from BMS. Cash, cash equivalents and marketable securities, excluding restricted cash, increased by $55.1 million when compared to the balance as of March 31, 2022 of $633.5 million. Net cash used in operating activities, which was partially offset by a $90.0 million in upfront payment received from BMS, was $30.5 million for the three months ended June 30, 2022. Net cash used in operating activities was $160.6 million for the three months ended March 31, 2022. Operating Costs and Expenses Operating costs and expenses for the three and six months ended June 30, 2022 were $153.9 million and $329.3 million, respectively, as compared to $148.0 million and $316.0 million for the same periods in the prior year. The overall increase in operating costs and expenses for the three and six months ended June 30, 2022 compared to the comparative periods was due mainly to costs incurred related to the restructuring initiative that was started in the first quarter of 2022. Restructuring, impairment and related charges for the three and six months ended June 30, 2022 of $8.4 million and $31.1 million, respectively, were primarily comprised of impairments and write-offs of long-lived assets, severance and employee-related expenses, and exit costs. The Company continues to evaluate restructuring alternatives to drive operational changes in business processes, efficiencies, and cost savings. “We expect that operating expenses and cash burn will continue to decline meaningfully in the third and fourth quarters as restructuring charges decline and anticipated additional business development activity allows us to further decrease from this baseline. Cash on hand provides us with runway into 2024,” said Brian Stephenson, Ph.D., CFA, BridgeBio’s Chief Financial Officer. The Company’s research and development and other expenses have not been significantly impacted by the global COVID-19 pandemic for the periods presented. While BridgeBio experienced some delays in certain of its clinical enrollment and trial commencement activities, it continues to adapt with alternative site, telehealth and home visits, and at-home drug delivery, as well as mitigation strategies with its contract manufacturing organizations. The longer-term impact, if any, of COVID-19 on BridgeBio’s operating costs and expenses is currently unknown. BRIDGEBIO PHARMA, INC. Condensed Consolidated Statements of Operations (in thousands, except shares and per share amounts) Three Months Ended June 30, Six Months Ended June 30, 2022 2021 2022 2021 (Unaudited) (Unaudited) Revenue $ 73,746 $ 54,024 $ 75,440 $ 54,486 Operating costs and expenses: Research, development and others 109,100 102,069 218,097 224,628 Selling, general and administrative 36,426 45,970 80,139 91,377 Restructuring, impairment and related charges 8,396 — 31,058 — Total operating costs and expenses 153,922 148,039 329,294 316,005 Loss from operations (80,176 ) (94,015 ) (253,854 ) (261,519 ) Other income (expense), net: Interest income 766 323 1,033 717 Interest expense (20,279 ) (10,839 ) (40,623 ) (20,577 ) Gain from sale of priority review voucher, net 107,946 — 107,946 — Other income (10,816 ) 2,457 (18,391 ) 8,223 Total other income (expense), net 77,617 (8,059 ) 49,965 (11,637 ) Net loss (2,559 ) (102,074 ) (203,889 ) (273,156 ) Net loss (income) attributable to redeemable convertible noncontrolling interests and noncontrolling interests (7,297 ) 5,726 (2,364 ) 13,729 Net loss attributable to common stockholders of BridgeBio $ (9,856 ) $ (96,348 ) $ (206,253 ) $ (259,427 ) Net loss per share, basic and diluted $ (0.07 ) $ (0.66 ) $ (1.41 ) $ (1.82 ) Weighted-average shares used in computing net loss per share, basic and diluted 146,684,804 146,754,299 146,285,694 142,713,463 (1) Amounts include stock-based compensation expense as follows: Three Months Ended June 30, Six Months Ended June 30, 2022 2021 2022 2021 (Unaudited) (Unaudited) Research, development and others $ 14,352 $ 19,284 $ 22,909 $ 41,733 Selling, general and administrative 13,953 12,751 28,505 25,198 Restructuring, impairment and related charges — — 1,172 — Total stock-based compensation expense $ 28,305 $ 32,035 $ 52,586 $ 66,931 BRIDGEBIO PHARMA, INC. Condensed Consolidated Balance Sheets (In thousands) June 30, December 31, 2022 2021 Assets (Unaudited) (1) Cash and cash equivalents and marketable securities $ 688,564 $ 787,515 Investment in equity securities 27,141 49,148 Receivable from licensing and collaboration agreements 22,821 19,749 Prepaid expenses and other current assets 32,754 32,446 Property and equipment, net 16,873 30,066 Operating lease right-of-use assets 12,850 15,907 Intangible assets, net 29,908 44,934 Other assets 31,322 33,027 Total assets $ 862,233 $ 1,012,792 Liabilities, Redeemable Convertible Noncontrolling Interests and Stockholders’ Deficit Accounts payable $ 8,793 $ 11,884 Accrued and other liabilities 128,057 118,247 Operating lease liabilities 18,586 22,366 2029 Notes 734,047 733,119 2027 Notes 540,779 539,934 Term loans 418,353 430,752 Other long-term liabilities 28,631 22,069 Redeemable convertible noncontrolling interests (1,499 ) 1,423 Total BridgeBio stockholders' deficit (1,025,532 ) (870,414 ) Noncontrolling interests 12,018 3,412 Total liabilities, redeemable convertible noncontrolling interests and stockholders’ deficit $ 862,233 $ 1,012,792 (1 ) The condensed consolidated financial statements as of December 31, 2021 are derived from the audited consolidated financial statements as of that date. BRIDGEBIO PHARMA, INC. Condensed Consolidated Statements of Cash Flows (in thousands) Six Months Ended June 30, 2022 2021 (Unaudited) Operating activities: Net loss $ (203,889 ) $ (273,156 ) Adjustments to reconcile net loss to net cash used in operating activities: Stock-based compensation 52,409 63,689 Depreciation and amortization 3,466 4,052 Net loss from investment in equity securities 23,228 — Gain from sale of priority review voucher, excluding transaction costs (110,000 ) — Gain from recognition of receivable from licensing and collaboration agreement (12,500 ) — Fair value of shares issued under a license agreement 4,567 — Accretion of debt 4,383 2,653 Fair value adjustment of warrants 1,390 — Loss on sale of certain assets 6,261 — Impairment of long-lived assets 12,653 3,300 LEO call option income — (5,550 ) Other noncash adjustments 3,742 3,906 Changes in operating assets and liabilities: Accounts receivable — (1,040 ) Receivable from licensing and collaboration agreements 2,993 (35,363 ) Receivable from a related party — (8,962 ) Prepaid expenses and other current assets (3,021 ) 1,400 Other assets 8,691 (5,723 ) Accounts payable (3,090 ) 13,025 Accrued compensation and benefits (9,402 ) (8,494 ) Accrued research and development liabilities 5,953 2,463 Accrued professional services (602 ) 1,499 Operating lease liabilities (3,348 ) (2,776 ) Deferred revenue 16,641 — Other accrued and other long-term liabilities 8,387 2,599 Net cash used in operating activities (191,088 ) (242,478 ) Investing activities: Purchases of marketable securities (119,611 ) (509,934 ) Maturities of marketable securities 293,919 238,934 Purchases of investment in equity securities (10,930 ) (20,000 ) Sales of investment in equity securities 9,708 — Increase in cash and cash equivalents from consolidation of PellePharm — 13,654 Proceeds from sale of priority review voucher 110,000 — Proceeds from sale of certain assets 10,000 — Payment for an intangible asset (1,500 ) — Purchases of property and equipment (3,261 ) (4,248 ) Net cash provided by (used in) investing activities 288,325 (281,594 ) Financing activities: Proceeds from issuance of 2029 Notes — 747,500 Issuance costs and discounts associated with issuance of 2029 Notes — (16,064 ) Issuance costs associated with term loan (1,120 ) — Purchase of capped calls — (61,295 ) Repurchases of common stock — (55,308 ) Transactions with noncontrolling interests — 70 Repurchase of Eidos noncontrolling interest, including direct transaction costs — (84,840 ) Proceeds from term loan — 25,000 Repayment of term loan (20,486 ) (18,108 ) Proceeds from BridgeBio common stock issuances under ESPP 966 1,652 Repurchase of shares to satisfy tax withholding (476 ) (3,302 ) Proceeds from stock option exercises, net of repurchases 160 11,216 Net cash provided by (used in) financing activities (20,956 ) 546,521 Net increase in cash, cash equivalents and restricted cash 76,281 22,449 Cash, cash equivalents and restricted cash at beginning of period 396,365 358,679 Cash, cash equivalents and restricted cash at end of period $ 472,646 $ 381,128 Reconciliation of Cash, Cash Equivalents and Restricted Cash: Cash and cash equivalents – Included in “Cash and cash equivalents and marketable securities” $ 470,098 $ 378,420 Restricted cash — Included in “Prepaid expenses and other current assets” 140 176 Restricted cash — Included in “Other assets” 2,408 2,532 Total cash, cash equivalents and restricted cash at end of period shown in the condensed consolidated statements of cash flows $ 472,646 $ 381,128 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. BridgeBio Pharma, Inc. Forward-Looking Statements This press release contains forward-looking statements. Statements in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended (the Exchange Act), which are usually identified by the use of words such as “anticipates,” “believes,” “estimates,” “expects,” “intends,” “may,” “plans,” “projects,” “seeks,” “should,” “will,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act. These forward-looking statements, including statements relating to the clinical and therapeutic potential of our programs and product candidates, including the availability and success of complete data from our ongoing Phase 2 OLE of acoramidis in patients with symptomatic ATTR-CM, availability and success of topline results from Part B of our Phase 3 ATTRibute-CM trial of acoramidis, the availability and success of additional data from our ongoing Phase 2b study of encaleret for ADH1, the timing and success of additional trials of encaleret for ADH1, including the timing and announced design of a Phase 3 pivotal study of encaleret for ADH1, the availability and success of initial data from our ongoing Phase 2 study of low-dose infigratinib for achondroplasia and our ongoing Phase 1/2 study of BBP-631 for CAH, the timing and success of our RAS program, including the selection of a next-generation KRAS G12C dual inhibitor candidate and plans to be in the clinic in mid-2013, the availability and success of additional data from our ongoing Phase 2 study of BBP-418 for patients LGMD2i, the timing and success of regulatory discussions regarding potential paths to approval for BBP-418, the ability of BBP-418 to be the first approved therapy for patients with LGMD2i, the timing and success of a Phase 3 trial of BBP-418 in patients with LGMD2i, the timing, success and announced design of our Phase 2/3 trial for BBP-711 for PH1, the availability and success of additional data from our ongoing Phase 1/2 trial of BBP-812 for the treatment of Canavan disease, the availability and success of additional data from our ongoing Phase 1 study of BBP-671 for PKAN and organic acidemias, the availability and success of Phase 2 data for PTR-01 in patients with RDEB, the availability and success of Phase 1b data for VT30 topical gel (BBP-681) in patients with VM, LM and VLM, the success of our license agreement with Bristol Myers Squibb to develop and commercialize BBP-398, including our eligibility for development, regulatory and sales milestone payments and tiered royalties, the success of our asset purchase agreement with Sentynl Therapeutics, including our ability to achieve future milestone and royalty payments from Sentynl Therapeutics and the timing of these events and the timing and success of a potential decision by the EC on NULIBRY (fosdenopterin) for patients with MoCD type A based on a positive CHMP opinion for NULIBRY, the success of our academic partnership with Baylor School of Medicine and our founding affiliation with Bakar Labs, the success of our updated strategic collaboration with Helsinn Group, including our ability to achieve future milestone and royalty payments from Helsinn and the timing of these events, the timing and success of partnering and out-licensing discussions for certain programs in our pipeline, the timing and availability of delayed debt draws under our senior secured credit facility, the success of our reduction in operating expenses and our expectations for our operating expenses and cash burn for the second quarter, the success of our restructuring initiative and its savings being realized, as well as our anticipated cash runway, reflect our current views about our plans, intentions, expectations and strategies, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations and strategies as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to, initial and ongoing data from our preclinical studies and clinical trials not being indicative of final data, the potential size of the target patient populations our product candidates are designed to treat not being as large as anticipated, the design and success of ongoing and planned clinical trials, future regulatory filings, approvals and/or sales, despite having ongoing and future interactions with the FDA or other regulatory agencies to discuss potential paths to registration for our product candidates, the FDA or such other regulatory agencies not agreeing with our regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted, the continuing success of our collaborations, the Company’s ability to unlock additional funding under our credit facility, potential volatility in our share price, potential adverse impacts due to the global COVID-19 pandemic such as delays in regulatory review, manufacturing and supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy, as well as those risks set forth in the Risk Factors section of our Annual Report on Form 10-K for the year ended December 31, 2021 and our other filings with the U.S. Securities and Exchange Commission. Moreover, we operate in a very competitive and rapidly changing environment in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of our management as of the date of this press release, and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise. BridgeBio Contact: Grace Rauh Grace.rauh@bridgebio.com (917) 232-5478