On November 4, 2021 BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio or the Company), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported its financial results for the third quarter ended September 30, 2021 and provided an update on the Company’s operations (Press release, BridgeBio, NOV 4, 2021, View Source [SID1234594564]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

BridgeBio has more than 30 programs in its pipeline for patients living with genetic diseases and cancers and 20 ongoing clinical trials underway across more than 450 sites around the world. Earlier this year BridgeBio received its first two U.S. Food and Drug Administration (FDA) drug approvals and has successfully filed 15 Investigational New Drug (IND) applications since the Company’s founding in 2015.

BridgeBio’s four core value drivers:

Acoramidis (AG10) – Transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM): Topline results from Part A of the Phase 3 ATTRibute-CM trial are expected in late 2021 and from Part B in 2023. The primary endpoint at Part A is the change from baseline in a 6-minute walk distance (6MWD) in trial participants receiving acoramidis or placebo after 12 months. If the change from baseline in 6MWD in Part A is highly statistically significant, BridgeBio expects to submit an application for regulatory approval of acoramidis in 2022 to the FDA. The study enrolled more than 600 subjects with either wild-type or variant TTR across more than 80 sites in 18 countries. ATTR-CM is a rare heart condition with a progressive and debilitating impact on quality of life likely affecting more than 400,000 patients worldwide.
Encaleret – Calcium-sensing receptor (CaSR) inhibitor for autosomal dominant hypocalcemia type 1 (ADH1): BridgeBio presented updated Phase 2b data for encaleret in an oral presentation at the American Society of Bone and Mineral Research (ASBMR) 2021 Annual Meeting in October. Within five days of individualized dose titration in 13 participants, encaleret normalized mean blood calcium levels and 24-hour urine calcium excretion. Achieving simultaneous blood and urine calcium normalization is a challenge for patients with ADH1 due to the limitations of current standard-of-care. If approved, encaleret could be the first therapy on the market for ADH1, a condition caused by gain of function variants in the calcium-sensing receptor (CASR) gene estimated to be carried by 12,000 individuals in the United States alone. BridgeBio plans to initiate a Phase 3 registrational trial of encaleret in patients with ADH1 in 2022.
Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia: Initial data from the ongoing Phase 2 dose ranging study are expected in the first half of 2022. Achondroplasia is the most common form of genetic short stature and one of the most common genetic diseases, with a prevalence of greater than 55,000 cases in the United States and European Union. Low-dose infigratinib is the only known product candidate in clinical development for achondroplasia that is designed to target the disease at its genetic source and the only orally administered product candidate in clinical-stage development.
BBP-631 – AAV5 gene therapy candidate for congenital adrenal hyperplasia (CAH): Received Fast Track designation from the FDA in May 2021. IND cleared by the FDA and site activation for initiation of a first-in-human Phase 1/2 study is ongoing, with initial data anticipated in mid-2022. CAH is one of the most prevalent genetic diseases potentially addressable with AAV gene therapy, with more than 75,000 cases estimated in the United States and European Union. The disease is caused by deleterious mutations in the gene encoding an enzyme called 21-hydroxylase, leading to lack of endogenous cortisol production. BridgeBio’s AAV5 gene therapy candidate is designed to provide a functional copy of the 21-hydroxylase-encoding gene (CYP21A2) and potentially address many aspects of the disease course.
Recent pipeline progress and corporate updates:

Stock repurchases: BridgeBio repurchased $148.4 million in BridgeBio common stock under its 2021 Share Repurchase Program, demonstrating the Company’s confidence in the long-term prospects of its pipeline.
LianBio IPO and partnership: China-based partner LianBio raised $325 million in its initial public offering on November 1. BridgeBio is estimated to own approximately 4.7% post-IPO. BridgeBio and LianBio announced in August that the first patient was treated in a Phase 2a trial of infigratinib in patients with gastric cancer and other advanced solid tumors. LianBio in-licensed rights from BridgeBio for infigratinib for development and commercialization in Mainland China, Hong Kong and Macau.
RAS cancer portfolio: BridgeBio announced the discovery of its next-generation KRAS G12C dual inhibitors, the first-known compounds that directly bind and inhibit KRAS in both its active (GTP bound) and inactive (GDP bound) conformations, and 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. BridgeBio expects to select a RAS development candidate in 2022.
BBP-812 – AAV9 gene therapy candidate for Canavan disease: BridgeBio announced that the first patient was dosed in its Phase 1/2 trial of BBP-812 for Canavan disease. If successful, BridgeBio’s gene therapy could be the first approved therapeutic option for children born with Canavan disease, a devastating and life-threatening condition. An initial Phase 1/2 data readout is expected in 2022.
BBP-818 – AAV gene therapy candidate for classic galactosemia (severe GALT deficiency): BridgeBio announced a new gene therapy program for classic galactosemia, which is caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT), affecting approximately 7,000 patients in the United States and the European Union. Preclinical studies in a mouse model of classic galactosemia have shown that BridgeBio’s BBP-818 therapy restored up to 72% of wild-type levels of GALT enzyme in the brain following a single dose.
BBP-398 – SHP2 inhibitor: First publication of preclinical data for BridgeBio’s potentially best-in-class SHP2 inhibitor designed for the treatment of resistant cancer. Data demonstrated activity in non-small cell lung cancer (NSCLC) driven by RAS or other MAPK-pathway activating mutations. The results were featured in a poster presentation shared at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in October.
BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2i (LGMD2i): Fast Track designation granted by the FDA. The Phase 2 trial was initiated in patients with LGMD2i in the first quarter of 2021. If successful, BBP-418 could be the first approved therapy for patients with LGMD2i. With approximately 7,000 patients with potentially treatable mutations, LGMD2i is an inherited recessive muscular dystrophy caused by mutation of fukutin-related protein. A Phase 2 data readout is expected in 2022.
BBP-711 – Glycolate oxidase (GO) inhibitor for hyperoxaluria: BridgeBio announced preliminary Phase 1 data in which BBP-711 was well-tolerated and resulted in maximal increases in plasma glycolate exceeding those achieved by any GO-targeting agents reported in healthy adult volunteers. BBP-711 is being developed for the treatment of primary hyperoxaluria type 1 (PH1) and hyperoxaluria caused by hepatic overproduction of oxalate in recurrent kidney stone formers. A full readout of Phase 1 data in healthy adult volunteers is expected in 2022, to be followed by initiation of a Phase 2/3 trial in PH1 and a Phase 2 proof-of-concept trial in recurrent kidney stone formers.
TRUSELTIQ (infigratinib): Health Canada approved TRUSELTIQ (infigratinib), a small molecule kinase inhibitor that targets fibroblast growth factor receptor (FGFR), under the Notice of Compliance with Conditions (NOC/c) policy, for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma (CCA) with a FGFR2 fusion or other rearrangement. BridgeBio’s partner Helsinn Group has exclusive commercial rights for TRUSELTIQ in Canada with BridgeBio eligible for tiered royalties as a percentage of net sales as part of the global collaboration and license agreement entered into between the two companies in March 2021.
BridgeBio Pharma R&D Day: Held a virtual R&D Day on October 12, 2021. Presentation replay can be found on BridgeBio’s investor website here.
Four new independent directors added to BridgeBio’s board:
Hannah Valantine, M.D., a leader in organ transplant genomics and workforce diversity who is a professor of medicine at Stanford University School of Medicine
Fred Hassan, a pharmaceutical and financial industry leader who is the former CEO of Schering-Plough and former chairman of Bausch & Lomb
Andrea Ellis, a consumer technology innovator and the chief financial officer of Lime
Douglas Dachille, an investment management veteran and the former chief investment officer of American International Group, Inc. (AIG)
Third Quarter 2021 Financial Results:

Cash, Cash Equivalents and Marketable Securities

Cash, cash equivalents and marketable securities, excluding restricted cash, totaled $599.6 million as of September 30, 2021, compared to $607.1 million as of December 31, 2020. Over the past three quarters, the Company repurchased $148.4 million in BridgeBio common stock under its 2021 Share Repurchase Program and $50.0 million in BridgeBio common stock in conjunction with its issuance of the 2029 convertible notes, paid $61.3 million for capped call options related to the issuance of its 2029 convertible notes and $35.0 million of regulatory-related milestone payments in connection with its approved products. Earlier during the year, BridgeBio paid $21.3 million to Eidos shareholders who elected for cash settlement in exchange for their Eidos shares and $63.8 million of direct transaction costs arising from the merger with Eidos. These were offset by cash receipts of $731.4 million in net proceeds from the issuance of BridgeBio’s 2029 convertible notes, $65.1 million from collaboration partner, Helsinn Group, and $25.0 million in net proceeds from Hercules Capital, Inc. under an amended loan agreement. The remaining change primarily related to payments of interest and operating costs and expenses.

Cash, cash equivalents and marketable securities, excluding restricted cash decreased by $298.8 million when compared to balance as of June 30, 2021, which was $898.4 million. During the quarter, the Company repurchased $143.1 million of BridgeBio common stock and paid $35.0 million of regulatory-related milestone payments in connection with its approved products.

Operating Costs and Expenses

Operating costs and expenses for the quarter increased by $23.7 million to $151.8 million in the current quarter as compared to $128.1 million for the same period in the prior year. The increase in operating costs and expenses was due to an increase in personnel and external costs to support the progression in BridgeBio’s research and development programs and staged buildout of its commercial organization as part of commercial launch readiness activities. This increase in personnel and external costs was offset by $12.2 million in reimbursement of expenses from the cost sharing arrangement recognized under BridgeBio’s License and Collaboration Agreement with Helsinn Group. Stock-based compensation for the quarter was $16.1 million as compared to $17.7 million for the same period in the prior year.

The Company’s research and development 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 in this unprecedented time to enable alternative site, telehealth and home visits, 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.