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.

- Reported positive preclinical data for its next-generation KRASG12C GTP/GDP dual inhibitor development candidate, BBO-8520, and for its novel PI3Kα:RAS breaker mechanism in late lead optimization - Reported positive updated 12-month Phase 2 data for BBP-418 in Limb-Girdle Muscular Dystrophy Type 2i - Enrolled Cohort 5 of Phase 2 trial of infigratinib in achondroplasia, with no serious adverse events (SAEs), and no adverse events that required dose modifications reported to date - Reported dosing of first lung cancer patient in Phase 1/2 trial of SHP2 inhibitor BBP-398 in combination with Amgen’s Lumakras (sotorasib); also reported dosing of first patient in Phase 1 trial of BBP-671 in Propionic Acidemia (PA) and Methylmalonic Acidemia (MMA) - Reported updated positive data from its Phase 1/2 trial of BBP-812, an AAV9 gene therapy candidate for the treatment of Canavan disease - Received approval of NULIBRY (fosdenopterin) as a treatment for molybdenum cofactor deficiency (MoCD) Type A in Israel and the European Union (EU) - Reported operating expense for Q3 2022 at $129.5 million, a reduction of 26.2% from $175.4 million in Q1 2022 when restructuring efforts began, and a reduction of 15.9% from $153.9 million in Q2 2022. - Ended quarter with $558.3 million in cash, cash equivalents and marketable securities, providing financial runway into 2024 PALO ALTO, Calif., Nov. 03, 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 third quarter ended September 30, 2022 and provided an update on the Company’s operations. “We remain committed to focused execution across our pipeline, and have continued to deliver exciting data for patients, including in our LGMD2i and KRAS programs, while at the same time materially reducing our operating expenses and putting the Company on safe footing,” said Neil Kumar, Ph.D., founder and CEO of BridgeBio. “The compounds that we have developed in our RAS franchise after years of intensive work now allow us to clinically interrogate the promise of direct inhibition of active KRAS, as well as the potential of breaking PI3Kα:RAS binding,” added Frank McCormick, Ph.D., Chairman of Oncology and cofounder of BridgeBio. “RAS and PIK3CA are the two most common oncogenes in human tumors, and we hope that our programs are able to serve the vast unmet need of the patients that they impact.” BridgeBio’s Key Programs RAS cancer portfolio: BridgeBio has selected a next-generation KRASG12C dual inhibitor development candidate, BBO-8520, and plans to be in the clinic in 2023. The Company shared promising preclinical data on BBO-8520, as well as its novel PI3Kα:RAS breaker program in late lead optimization, at the Fourth RAS Initiative Symposium. BBO-8520 has shown significantly greater potency in KRAS models than first-generation KRASG12C GDP-only inhibitors as measured by its ability to bind and covalently modify KRASG12C, block KRASG12C binding to effector proteins such as RAF, and inhibit downstream signaling. BBO-8520 was shown to retain potency in the context of receptor tyrosine kinase drive, which renders KRASG12C GDP-only inhibitors inactive and is thought to be a major mechanism of non-response and resistance to first-generation agents. BBO-8520 showed strong activity in KRASG12C in vivo models including deep regressions and differentiated efficacy compared to a first-generation KRASG12C GDP-only inhibitor. BridgeBio scientists highlighted rationale and design of compounds targeting PI3Kα:RAS binding, which is a novel and potentially broad MoA to target PI3Kα mutant tumors, RAS mutant tumors and potentially other tumors driven by RTK activation of RAS signaling. Targeting PI3Kα activity in tumors through its interaction with RAS may spare glucose metabolism, potentially allowing for potent target coverage without displaying the dose-limiting hyperglycemia common to PI3Kα kinase inhibitors. RAS is the most common oncogenic driver with approximately 30% of all human cancers being driven by RAS mutations, including large proportions of lung, colorectal and pancreatic tumors. PIK3CA is the second most common oncogene in human tumors, being present in more than 30% of breast and endometrial carcinomas. Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia and hypochondroplasia: Earlier this year BridgeBio shared positive interim results from available data in Cohort 4 from a Phase 2 trial of low-dose infigratinib in patients with achondroplasia, which demonstrated an increase in annualized height velocity of 1.52 cm/year in children 5 years of age and older. Given infigratinib’s pro date, and after discussions with regulators, BridgeBio started dosing children in Cohort 5; that cohort is now enrolled with no serious adverse events (SAEs), and no adverse events that required dose modifications reported to date. The Company expects to report an update on Cohort 5 AHV in the first half of 2023, followed by the initiation of a pivotal Phase 3 trial. 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 also expects to evaluate development of infigratinib in other FGFR-driven skeletal dysplasias, which affect more than 50,000 people in the US and Europe. Encaleret – Calcium-sensing receptor (CaSR) inhibitor for autosomal dominant hypocalcemia type 1 (ADH1): BridgeBio 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 the Company’s Phase 2b study of encaleret in ADH1 were shared earlier this year in an oral presentation at the Endocrine Society’s 2022 ENDO Conference. 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 United States alone. BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2i (LGMD2i): The Company shared updated positive Phase 2 data in a presentation at the World Muscle Society (WMS) 27th International Hybrid Annual Congress 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 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 as measured by the reduction of creatine kinase, a key marker of muscle breakdown 12-month data show improvements from baseline on 10-meter walk test and North Star Assessment for Dysferlinopathy, which BridgeBio believes suggests a potential impact on clinical function and on the rate of disease progression If proven to be successful, BBP-418 could be the first approved therapy for patients with LGMD2i Acoramidis (AG10) – Transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM): The Phase 3 ATTRibute-CM trial is progressing with topline data from the Month 30 primary endpoint, a hierarchical composite including all-cause mortality and cardiovascular hospitalizations, expected in mid-2023 The Company presented updated results of the Phase 2 open-label extension of acoramidis in ATTR-CM, demonstrating near-complete TTR stabilization and stable or improving serum NT-proBNP levels at month 30 BBP-631 – AAV5 gene therapy candidate for congenital adrenal hyperplasia (CAH): The Phase 1/2 study is ongoing with an update anticipated late in 2022 or early in 2023. 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 Recent Corporate Updates Updated positive data for investigational AAV9 gene therapy in Canavan disease: Promising pharmacodynamic data from the first three 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 United States and European Union, Canavan disease is an ultra-rare, disabling and fatal disease with no approved therapy. Approvals in Israel and EU for NULIBRY (fosdenopterin): The European Commission (EC) granted marketing authorization for NULIBRY Powder for Solution for Injection as the first therapy for the treatment of patients with molybdenum cofactor deficiency (MoCD) Type A in Europe, and the State of Israel Ministry of Health approved NULIBRY for Injection as a treatment for MoCD Type A patients in Israel. These decisions are based on the efficacy and safety data collected compared to data from a natural history study. NULIBRY is the first and only approved therapy in either region 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 and EC-approved therapeutic. Medison Pharma acquired commercialization rights to NULIBRY in Israel in December 2019. Sentynl Therapeutics, Inc. acquired global rights to NULIBRY in March 2022. First patient dosed in Phase 1/2 combination trial of BridgeBio’s SHP2 inhibitor BBP-398 with Amgen’s LUMAKRAS: First lung cancer patient was dosed in a Phase 1/2 trial of BridgeBio’s SHP2 inhibitor BBP-398 in combination with Amgen’s LUMAKRAS (sotorasib) in advanced solid tumors with the KRASG12C mutation; additionally, FDA Fast Track Designation was obtained for BBP-398 in combination with LUMAKRAS for adult patients with previously treated, KRASG12C mutated, metastatic non-small-cell lung cancer (NSCLC). BridgeBio has a non-exclusive clinical collaboration with Amgen to evaluate the combination of BBP-398 with LUMAKRAS in patients with advanced solid tumors with the KRASG12C mutation. BridgeBio is party to an exclusive license agreement with Bristol Myers Squibb (BMS) to develop and commercialize BBP-398 in oncology worldwide, except for in mainland China and other Asian markets, which are part of BridgeBio’s strategic collaboration with LianBio. BridgeBio and BMS are also investigating the combination of BBP-398 with OPDIVO® (nivolumab) in patients with advanced solid tumors with KRAS mutations. First patient dosed in Phase 1 trial of BBP-671 for propionic acidemia (PA) and methylmalonic acidemia (MMA): An initial data readout of patients with PA and MMA is expected in mid-2023. BridgeBio is also in active discussions with regulators and expects to launch a pivotal Phase 2/3 study of BBP-671 in pantothenate kinase-associated neurodegeneration (PKAN) in 2024. 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. PA, MMA, and PKAN affect an estimated 7,000 patients in the United States and European Union collectively. Third Quarter 2022 Financial Results: Cash, Cash Equivalents and Marketable Securities Cash, cash equivalents and marketable securities, excluding restricted cash, totaled $558.3 million as of September 30, 2022, compared to $787.5 million as of December 31, 2021. The net decrease of $229.2 million in cash, cash equivalents and marketable securities, excluding restricted cash is primarily attributable to net cash used in operating activities of $326.3 million. The net cash used in operating activities for the nine months ended September 30, 2022 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 nine months ended September 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 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, decreased by $130.3 million when compared to the balance as of June 30, 2022 of $688.6 million. Net cash used in operating activities, was $135.2 million for the three months ended September 30, 2022. Net cash used in operating activities was $191.1 million for the six months ended June 30, 2022. Operating Costs and Expenses Operating costs and expenses for the three and nine months ended September 30, 2022 were $129.5 million and $458.7 million, respectively, as compared to $151.8 million and $467.8 million for the same periods in the prior year. The overall decrease in operating costs and expenses for the three and nine months ended September 30, 2022 compared to the comparative periods was mainly due to overall decreases in selling, general and administrative expenses and research, development and other (R&D) expenses resulting from the Company's reprioritization of its R&D programs and streamlining of costs. The effects of the Company's restructuring initiative that was started in the first quarter of 2022 are now being realized due to reductions of its operating costs and expenses. Restructuring, impairment and related charges for the three and nine months ended September 30, 2022 of $5.0 million and $36.1 million, respectively, were primarily comprised of winding down costs, exit and other related costs, impairments and write-offs of long-lived assets, and severance and employee-related costs. The Company continues to evaluate restructuring alternatives to drive operational changes in business processes, efficiencies, and cost savings. “We continue to take action to protect the Company, shore up our balance sheet, and preserve capital to read out our upcoming key catalysts,” said Brian Stephenson, Ph.D., CFA, Chief Financial Officer of BridgeBio. “We expect that cash burn will continue to decline in the fourth quarter as a result of ongoing potential business development and restructuring activities. Cash on hand provides us with runway into 2024, and we will continue to look for ways to extend runway via potential royalty monetizations, partnerships, and burn reduction.” 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 September 30, Nine Months Ended September 30, 2022 2021 2022 2021 (Unaudited) (Unaudited) Revenue $ 338 $ 2,344 $ 75,778 $ 56,830 Operating costs and expenses: Research, development and others 93,250 105,759 311,347 330,387 Selling, general and administrative 31,188 46,084 111,327 137,461 Restructuring, impairment and related charges 5,016 — 36,074 — Total operating costs and expenses 129,454 151,843 458,748 467,848 Loss from operations (129,116 ) (149,499 ) (382,970 ) (411,018 ) Other income (expense), net: Interest income 2,417 234 3,450 951 Interest expense (19,825 ) (11,067 ) (60,448 ) (31,644 ) Gain from sale of priority review voucher, net — — 107,946 — Other income (expense), net 6,331 (684 ) (12,060 ) 7,539 Total other income (expense), net (11,077 ) (11,517 ) 38,888 (23,154 ) Net loss (140,193 ) (161,016 ) (344,082 ) (434,172 ) Net loss attributable to redeemable convertible noncontrolling interests and noncontrolling interests 2,854 5,081 490 18,810 Net loss attributable to common stockholders of BridgeBio $ (137,339 ) $ (155,935 ) $ (343,592 ) $ (415,362 ) Net loss per share, basic and diluted $ (0.93 ) $ (1.06 ) $ (2.34 ) $ (2.88 ) Weighted-average shares used in computing net loss per share, basic and diluted 147,937,817 146,662,756 146,842,453 144,044,360 Three Months Ended September 30, Nine Months Ended September 30, 2022 2021 2022 2021 (Unaudited) (Unaudited) Research, development and others $ 6,137 $ 4,808 $ 29,046 $ 46,541 Selling, general and administrative 12,521 11,322 41,026 36,520 Restructuring, impairment and related charges — — 1,172 — Total stock-based compensation $ 18,658 $ 16,130 $ 71,244 $ 83,061 BRIDGEBIO PHARMA, INC. Condensed Consolidated Balance Sheets (In thousands) September 30, December 31, 2022 2021 Assets (Unaudited) (1) Cash and cash equivalents and marketable securities $ 558,315 $ 787,515 Investment in equity securities 33,662 49,148 Receivable from licensing and collaboration agreements 24,581 19,749 Prepaid expenses and other current assets 25,661 32,446 Property and equipment, net 15,603 30,066 Operating lease right-of-use assets 11,738 15,907 Intangible assets, net 29,310 44,934 Other assets 29,870 33,027 Total assets $ 728,740 $ 1,012,792 Liabilities, Redeemable Convertible Noncontrolling Interests and Stockholders’ Deficit Accounts payable $ 10,158 $ 11,884 Accrued and other liabilities 104,992 118,247 Operating lease liabilities 17,044 22,366 2029 Notes 734,516 733,119 2027 Notes 541,205 539,934 Term loans 422,972 430,752 Other long-term liabilities 28,226 22,069 Redeemable convertible noncontrolling interests (2,388 ) 1,423 Total BridgeBio stockholders' deficit (1,138,417 ) (870,414 ) Noncontrolling interests 10,432 3,412 Total liabilities, redeemable convertible noncontrolling interests and stockholders’ deficit $ 728,740 $ 1,012,792 (1 ) The condensed consolidated financial statements as of and for the year ended 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) Nine Months Ended September 30, 2022 2021 (Unaudited) Operating activities: Net loss $ (344,082 ) $ (434,172 ) Adjustments to reconcile net loss to net cash used in operating activities: Stock-based compensation 69,770 79,731 Depreciation and amortization 5,111 4,317 Net loss from investment in equity securities 12,969 1,510 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 6,469 4,043 Fair value adjustment of warrants 1,446 459 Loss on sale of certain assets 6,261 — Impairment of long-lived assets 12,720 3,300 LEO call option income — (5,550 ) Other noncash adjustments 4,687 7,322 Changes in operating assets and liabilities: Receivable from licensing and collaboration agreements (832 ) (7,710 ) Receivable from a related party — (462 ) Prepaid expenses and other current assets 4,072 (3,743 ) Other assets 10,095 (8,930 ) Accounts payable (1,725 ) 1,360 Accrued compensation and benefits (9,122 ) (4,443 ) Accrued research and development liabilities 452 4,686 Accrued professional services (2,556 ) 346 Operating lease liabilities (4,819 ) (4,474 ) Deferred revenue 16,969 — Other accrued and other long-term liabilities 3,797 (1,629 ) Net cash used in operating activities (326,251 ) (364,039 ) Investing activities: Purchases of marketable securities (134,635 ) (575,478 ) Maturities of marketable securities 452,819 305,200 Sales of marketable securities — 98,925 Purchases of investment in equity securities (26,312 ) (23,960 ) Sales of investment in equity securities 28,830 4,743 Increase in cash and cash equivalents from consolidation of PellePharm — 13,654 Acquisition and payment of an intangible asset (1,500 ) (35,000 ) Proceeds from sale of priority review voucher 110,000 — Proceeds from sale of certain assets 10,000 — Purchases of property and equipment (4,020 ) (10,710 ) Net cash provided by (used in) investing activities 435,182 (222,626 ) 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 — (198,458 ) Transactions with noncontrolling interests — 3,500 Repurchase of Eidos noncontrolling interest, including direct transaction costs — (85,090 ) Proceeds from term loan — 25,000 Repayment of term loan (20,486 ) (18,108 ) Proceeds from BridgeBio common stock issuances under ESPP 2,558 3,821 Repurchase of shares to satisfy tax withholding (1,072 ) (4,035 ) Proceeds from stock option exercises, net of repurchases 609 14,294 Net cash provided by (used in) financing activities (19,511 ) 411,065 Net increase in cash, cash equivalents and restricted cash 89,420 (175,600 ) Cash, cash equivalents and restricted cash at beginning of period 396,365 358,679 Cash, cash equivalents and restricted cash at end of period $ 485,785 $ 183,079 Nine Months Ended September 30, 2022 2021 Supplemental Disclosures of Cash Flow Information: Cash paid for interest $ 47,575 $ 28,239 Supplemental Disclosures of Noncash Investing and Financing Information: Payment-in-kind interest added to principal of term loan $ 8,503 $ — Net noncash portion of repurchase of Eidos noncontrolling interests $ — $ 38,167 Direct transaction costs in the repurchase of Eidos recorded in “Additional paid-in capital” previously classified in “Prepaid expenses and other current assets” $ — $ 8,749 Noncash contribution by a noncontrolling interest $ — $ 21,600 Recognized intangible asset recorded in “Accrued research and development liabilities” $ 11,000 $ 12,500 Leasehold improvements paid by landlord $ — $ 2,449 Repurchase of common stock recorded in Accounts payable $ — $ 1,542 Transfers from noncontrolling interests $ 1,153 $ (221 ) Reconciliation of Cash, Cash Equivalents and Restricted Cash: Cash and cash equivalents $ 483,235 $ 180,347 Restricted cash — Included in “Prepaid expenses and other current assets” 140 176 Restricted cash — Included in “Other assets” 2,410 2,556 Total cash, cash equivalents and restricted cash at end of period shown in the condensed consolidated statements of cash flows $ 485,785 $ 183,079 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 timing and success of our RAS program, including preclinical data for our next-generation KRASG12C GTP/GDP dual inhibitor development candidate, BBO-8520 and plans to be in the clinic in mid-2023, updated data from our 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 intended to be initiated in the first half of 2023, the availability and success of data from our ongoing Phase 1/2 trial of SHP2 inhibitor BBP-398 in combination with Amgen’s Lumakras (sotorasib), 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 approval of NULIBRY (fosdenopterin) for treatment of MoCD Type A in Israel and the EU, the availability and success of initial data from our ongoing Phase 2 study of low-dose infigratinib for achondroplasia, including plans to deliver an update on Cohort 5 in the first half of 2023, followed by the initiation of a pivotal Phase 3 trial, the evaluation of the development of infigratinib in other FGFR-driven skeletal dysplasias, 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 timing and success of our planned Phase 3 pivotal study of encaleret in patients with ADH1, the availability and success of topline results from the Part B Month 30 endpoint of our Phase 3 ATTRibute-CM trial of acoramidis, expected in mid-2023, the availability and success of data from our ongoing Phase 1/2 study of BBP-631 for CAH, with an update anticipated in late 2023 or early 2023, the timing, availability and success of an initial data readout from our Phase 1 trial of BBP-671 in patients with PA and MMA expected in mid-2023, the timing and success of discussions with regulators and the expected launch of a pivotal Phase 2/3 study of BBP-671 in PKAN in 2024, the potential of BBP-671 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, if successful, 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, 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: Vikram Bali contact@bridgebio.com (650)-789-8220

- 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