Origin Biosciences, Inc.

CGT产业何去何从？8月底，北京！九大论坛将直面产业创新与监管挑战。国药集团中国生物副总裁孙京林老师将在本次会议讲解“创新生物药的分段生产管理”。武汉科技大学生命科学与健康学院院长，波睿达生物董事长张同存教授将与会报告“CAR-T细胞治疗现状和展望”。 跨行做药的创业者不乏其人，但开创了一个行业新范式的，美籍华裔经济学家罗闻全（Andrew Wen-Chuan Lo）大概是少有的案例。 基于所长，罗闻全提出“巨型资金”概念，并设立了BridgeBio Pharma加以实践。4年后，公司凭借年度“最大生物科技IPO”一战成名，资本和关注蜂拥而来。“巨型资金”模型也为不少Biotech和风投机构提供了新的思路。 但这种以“专注高效”“灵活募资”“分散风险”为特点的“中心聚合”模式，确实如人们所期待的那样运转吗？对于BridgeBio，长期命运有因此得到加成吗？ 至少目前看，BridgeBio远没有同样贯彻这一模式的Roivant和它的“vant王国”过得舒适。成立近十年，BridgeBio旗下仅有的2款商业化产品，一款被撤市，一款营收惨淡。 今年以来，BridgeBio已两次分拆出新的子公司，以专注不同的研究领域。可以看出，BridgeBio仍然贯彻着“中心聚合”的发展模式。来自资本的支持，预示着这家Biotech还没被资本市场抛弃，哪怕走势波折。 眼下，BridgeBio被绑定在其在研心脏药物acoramidis上，股价随产品进展大涨大跌。这款产品备受期待，市场巨大且仅有辉瑞一个竞品。 1 “巨型资金” 成立于2015年的BridgeBio，致力于从源头上针对病因明确的遗传性疾病开发和推进具有革命性的药物。2019年6月，BridgeBio成功登陆美国纳斯达克，IPO当日股价涨逾62%，市值达到33亿美元，夺得当年度“最大生物科技IPO”桂冠。 不同于其他初创制药公司“科学家”或“职业经理人”的标配初始团队，罗闻全出身金融，并在原本的领域颇有建树。 这位美籍华裔经济学家30岁时，获得麻省理工终身教职，拥有“金融工程学界领袖”“对冲基金研究泰斗”“生物金融学创始人”“华人金融学家第一人”等众多金融界的重磅头衔。 罗闻全，图源：湛庐阅读 罗闻全之所以涉足制药行业，跟其母亲的患病遭遇有关。很不幸的是，本可以成为救人希望当在研产品，因为资金问题没能得到后续研究，最终母亲也离世。 通过对生物制药发展的观察，罗闻全认为，资本的逐利性是市场竞争和资源分配的底层逻辑，投资人的风险偏好很难被改变，但只要能使投向生物制药研发的资本风险更低，或预期收益率更高，自然会赢得资本的关注。 很早之前，罗闻全就提出过“适应性市场假说”，后来也被人们称为“生物金融学”。其中一点是：人们具有抽象思维，特别是前瞻性分析的能力；有基于过去经验对未来做出预测的能力；有对未来环境的改变做出准备的能力，这是以思维速度的进化，它与生物进化相关却又不同。 于是，结合一系列金融学的理论和技术，罗闻全提出一种名为“巨型基金”（Megafund）的新型运营模式。 这个理论的底层逻辑是一种“中心聚合”（Hub-and-spoke）的模式，通过成立一个基金运作实体，同时支持大量独立的候选药物研发项目。利用多种投资组合，基金公司将期望收益标准差降低，达到远低于投资单个项目的风险。 因为投资回报率可观，可以通过更广泛的融资渠道筹集，如发行股票、长期债券和其他金融衍生工具，甚至由政府背书成立一个“巨型基金”。 图源：药融圈 罗闻全对于这个模式的落地，就是成立BridgeBio Pharma。 不同于很多Biotech的成长起点——聚焦某一类型的细分赛道，BridgeBio以“母公司”的角色存在，同时对单个新药项目成立子公司，它们各自享有半自治运营权。母公司可为子公司在成立初期提供专业技术、研发资源和临床运营等支持，助其快速灵活的创造价值。 同样利用这种模式运营的代表性企业，典型的还有Roivant和他的“vant王国”——这些名字带有“vant”尾缀的公司涵盖了多个治疗领域，比如特应性皮炎、溃疡性结肠炎、系统性红斑狼疮等；多个技术路线，比如小分子疗法、基因疗法、RNA疗法…… Cullinan Oncology也是采用类似模式的公司。此外，投资机构Bain Capital、ARCH也都有利用“巨型基金”的理念募集资金。 别具一格的创新总是备受期待，最具象的表现是，BridgeBio在登陆纳斯达克两年左右的时间里，巅峰市值超过百亿美元。 2 降低风险？ 无论是豪华的创始人团队，还是背靠的明星风投机构，或者是创新的运营模式，这些都只是一家start-up初期转瞬即逝的光环。在医药市场的后续发展里，永远是产品为王。药企发展常常因为产品的起落而经历过山车，BridgeBio也不例外。 今年年初，Evaluate Pharma对2024年即将获批的10款重磅疗法进行了预测，并将来自BridgeBio的acoramidis列入其中。 Acoramidis是一种口服、强效、高选择性小分子转甲状腺素蛋白（TTR）稳定剂，用于治疗转甲状腺素蛋白淀粉样变性心肌病（ATTR-CM）。虽然这款产品隶属于BridgeBio子公司Eidos Therapeutics，但每一个子公司的动静都最终以BridgeBio的形式呈现。 2021年12月，acoramidis治疗ATTR-CM的III期ATTribute-CM研究未能达到主要终点。消息宣布当天，BridgeBio股价暴跌72%，不但百亿美元体量成为幻影，在将近1年的时间里，其市值都只在10亿美元徘徊。 但同样地，当产品取得优秀疗效时，市场也不吝赞美。 2023年7月，BridgeBio宣布ATTRibute-CM试验获得了积极的顶线结果。在试验的30个月内，主动治疗组的整体生存率为81%，这与美国数据库中年龄相匹配的一般人口85%的生存率相似。当月，BridgeBio股价几乎翻倍。 在沉寂的一年半时间里，BridgeBio经历了大部分“失意”Biotech的剧本：多次裁员、削减管线，还出售了一张优先审评券维系运营。 另一款对BridgeBio影响较大的产品，来自子公司QED Therapeutics。 这款名为infigratinib的药物，是一款具有ATP竞争性的FGFR1-3选择性口服TKI，原本出自诺华，QED Therapeutics在2018年获得授权。在2021年5月，infigratinib获得FDA加速批准，用于治疗胆管癌。 2023年3月，Bridgebio公布infigratinib针对另一适应症——软骨发育不全（ACH）的积极临床数据，当天收盘涨幅近52%，几天后公司更是凭借此数据成功募资超1.5亿美元。 戏剧性的是，今年5月，infigratinib被FDA撤回胆管癌的加速批准。根据当时的公告，申办方因“开展所要求的确证性临床试验（一线治疗新适应证）招募患者有困难”，主动要求撤回此前加速批准的胆管癌二线治疗适应证。 次月，infigratinib在治疗ACH儿童患者的II期临床试验PROPEL 2中表现出潜在“best-in-class”的持续疗效和安全性，但BridgeBio当天股价却下跌超过6%。 Infigratinib转向的ACH适应症，目前仅有同行BioMarin的Vosoritide（Voxzogo）得到批准。自2021年上市以来，Vosoritide在2022年、2023年连续两年打破年初定下的销售指引。BioMarin曾表示，由于Vosoritide的需求大增，产能不足，有可能会影响未来的销售收入。 由此看来，虽然ACH存在巨大的未满足需求，但对于被撤回的infigratinib，市场显然还在观望。 其实，市场对infigratinib的不信任，早在BridgeBio从诺华引进时就已存在。这笔交易完成之初，有评论表示，这是“捡起被诺华‘丢弃的’原研抗癌药物”。而对于胆管癌确证性试验“招募不足”的理由，市场显然也不买账，质疑其疗效问题。 不过Bridgebio在2024年第一季度财报中称，它仍将继续infigratinib对软骨发育不全的III期试验，预计将于2025年完成。此外，该公司预计，将于今年启动该产品针对软骨发育不良的临床计划。 3 拆拆不休 兜兜转转，成立快十年的BridgeBio，目前的上市产品仅有fosdenopterin（Nulibry）一款。该产品由子公司Origin Biosciences研发，在2021年2月获得FDA批准，用于降低因A型钼辅因子缺乏（MoCD）导致的死亡风险，这也是FDA批准的首款治疗这类患者的创新疗法。 MoCD是一种非常罕见的疾病，其表现是进行性产后脑病、难治性癫痫以及肌无力等，患者很少存活超过4年，EVP预测Nulibry2026年的销售额为0.29亿美元。因目标人群过于小众等原因，这款产品的商业化情况并不乐观。 少数子公司的失败，并不会给母公司带来毁灭性打击。虽然中心辐射模式卖点之一的“低风险”似乎并没有在BridgeBio上得到很好的体现，但确实给了这家Biotech机会翻盘。 QED Therapeutics开发的infigratinib前途未卜，但它的“兄弟”公司Eidos Therapeutics和旗下acoramidis则未来可期。 由于优异的III期数据，FDA已经接受acoramidis用于治疗ATTR-CM的新药申请，PDUFA日期为2024年11月29日。1月，acoramidis也已在欧洲申报上市，拜耳拥有这款产品在欧洲的独家商业化权益。 Acoramidis同样赢得了阿斯利康的青睐，后者子公司Alexion Pharmaceuticals在五年前获得该产品在日本的权益。同样是今年1月，BridgeBio还转让了acoramidis的5%特许权使用费，换来5亿美元的现金。 目前，市场上针对ATTR-CM的药物只有来自辉瑞的Vyndamax（tafamidis），在2019年5月被FDA批准上市，成为首个被批准用于该适应症的治疗药物。辉瑞年报透露，2022年Vyndamax的营收为24.47亿美元，2023年的销售为33.21亿美元。 根据美国市场研究与咨询公司Grand View Research的报告，从2022年到2030年，ATTR治疗药物的全球市场规模将以7.6%的复合年增长率增长，预计将于2030年达到91.7亿美元。 或许是acoramidis给了BridgeBio大大的信心，这家公司在今年加快了分拆聚合的速度，资本也依旧买账。 5月，BridgeBio分拆了其以KRAS为重点的癌症投资组合，并以2亿美元的初始资金首次推出BridgeBio Oncology Therapeutics。 8月，BridgeBio再次分拆出GondolaBio，后者获得了包括红杉资本在内多家机构支持的3亿美元股权投资。GondolaBio将针对罕见病红细胞生成原卟啉症、α-1抗胰蛋白酶缺乏症和结节性硬化症进行研究。 BridgeBio在研管线，图源：官网 截至2024年第二季度，BridgeBio拥有5.87亿美元的现金、现金等价物、有价证券和短期限制性现金。 无论BridgeBio的“实操”如何，不可否认的是，将创新要素重新组合安排，能够实现更大程度上的公司利润和患者需求的共赢；公司也无需头疼是“自己成为Big pharma”还是“卖身Big pharma”的问题。 同样地，推动一系列创新发生的前提，需要更加宽容耐心的资本市场，足够多样且具有流动性的人才环境，灵活高效的监管条件...... 参考文献： 1、BridgeBio官网 2、BridgeBio Launches GondolaBio With $300M, Transfers Programs to Joint Venture；Biospace 3、从艰难维生到股价暴增，BridgeBio逆袭启示录；药渡Daily 4、一场24亿美金的逆袭：临床试验会遇阻，但创新探索精神不会；氨基观察 同写意媒体矩阵，欢迎关注↓↓↓

- 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

- 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