On May 5, 2022 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 first quarter ended March 31, 2022 and provided an update on the Company’s operations (Press release, BridgeBio, MAY 5, 2022, View Source [SID1234613613]).
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!
"Building on our positive Phase 2 data in LGMD2i, we are excited for a summer of ongoing focused execution where we have the opportunity to deliver meaningful data in two additional large conditions with great unmet need: ADH1 and achondroplasia," said Neil Kumar, Ph.D., founder and CEO of BridgeBio.
BridgeBio’s key programs:
Acoramidis (AG10) – Transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM): The Company released updated 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 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. Topline data from the Month 30 primary endpoint of the ongoing Phase 3 trial of acoramidis in ATTR-CM (ATTRibute-CM), a hierarchical composite including all-cause mortality and cardiovascular hospitalizations, are expected in mid-2023.
Encaleret – Calcium-sensing receptor (CaSR) inhibitor for autosomal dominant hypocalcemia type 1 (ADH1): Data from BridgeBio’s Phase 2b study of encaleret in ADH1 to be presented at the Endocrine Society’s 2022 ENDO conference in Atlanta from June 11-14, 2022. The planned presentation will include the profile of encaleret on clinically relevant mineral homeostasis parameters over 24 weeks of outpatient evaluation. Achieving simultaneous blood and urine calcium normalization is a challenge for patients with ADH1 due to the limitations of the current standard of care. 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. The Company intends to initiate a Phase 3 registrational trial of encaleret in patients with ADH1 in 2022 and anticipates Phase 3 topline data in 2023. Issued and filed patents are expected to provide market protection for encaleret in ADH1 to 2041.
Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia and hypochondroplasia: Initial data from the ongoing Phase 2 dose-escalation and expansion study is anticipated in mid-2022. The Company also plans to share multiple presentations at the Endocrine Society’s 2022 ENDO conference in Atlanta from June 11-14, 2022, including preclinical data for low-dose infigratinib in a mouse model of hypochondroplasia (an FGFR3-driven skeletal dysplasia), new analyses of natural history data in achondroplasia, and the results of a qualitative research study conducted to identify concepts and quality-of-life questionnaires relevant for the achondroplasia community. Achondroplasia is the most common form of genetic short stature and one of the most common genetic diseases, with a prevalence of over 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 development for achondroplasia.
BBP-631 – AAV5 gene therapy candidate for congenital adrenal hyperplasia (CAH): Dosed first patient in Phase 1/2 gene therapy trial in January 2022. Initial Phase 1/2 data readout anticipated in second half of 2022. CAH is one of the most prevalent genetic diseases potentially addressable with adeno-associated virus (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 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.
BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2i (LGMD2i): Announced positive Phase 2 data at the Muscular Dystrophy Association 2022 Annual Meeting on March 14, 2022. BridgeBio plans to engage with regulatory health bodies in 2022 to discuss potential paths to approval and subsequently intends to initiate a Phase 3 clinical trial. If successful, BBP-418 could be the first approved therapy for patients with LGMD2i. BridgeBio believes its initial Phase 2 results indicate the potential for BBP-418 to increase glycosylation of αDG and drive functional improvements for patients, as well as reduce CK, a key marker of muscle breakdown. Furthermore, the 90- and 180-day data show improvements on walk tests from baseline, which the Company believes suggests a potential impact on clinical function and on the rate of disease progression.
RAS cancer portfolio: BridgeBio expects to select a RAS development candidate in 2022. It previously 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.
Recent corporate updates
Sale to Sentynl Therapeutics, Inc., of NULIBRY (Fosdenopterin) for Injection: Sentynl has acquired global rights to NULIBRY and will be responsible for the ongoing development and commercialization of NULIBRY in the United States and developing, manufacturing and commercializing fosdenopterin globally. BridgeBio will share development responsibilities for fosdenopterin through approval of the marketing authorization application already under accelerated assessment with the European Medicines Agency and through approval of its regulatory submission with the Israeli Ministry of Health. Sentynl will provide cash payments upon the achievement of certain regulatory milestones. BridgeBio will be eligible to receive commercial milestone payments as well as tiered royalties on adjusted net sales of NULIBRY. NULIBRY is approved by the U.S. Food and Drug Administration (FDA) to reduce the risk of mortality in patients with molybdenum cofactor deficiency Type A, an ultra-rare, life-threatening pediatric genetic disorder.
Updated strategic collaboration with Helsinn Group to develop, manufacture and commercialize infigratinib in oncology indications in the U.S.: Under the terms of the amended and restated agreement, Helsinn will gain an exclusive license to commercialize infigratinib in the United States and will be responsible for developing, manufacturing and commercializing infigratinib in oncology indications worldwide except for achondroplasia or any other skeletal dysplasias, and except in mainland China, Hong Kong and Macau. BridgeBio will be eligible to receive regulatory and commercial milestone payments as well as tiered royalties on adjusted net sales from Helsinn. BridgeBio will retain all rights to develop, manufacture and commercialize infigratinib in skeletal dysplasia, including achondroplasia. In 2021, Helsinn and BridgeBio obtained accelerated approval for TRUSELTIQ (infigratinib) from the FDA for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 fusion or other rearrangement as detected by an FDA-approved test.
Business development – Due to the need to conserve capital and prioritize focused execution, BridgeBio is engaged in partnering and out-licensing discussions for the following programs:
BBP-589 – Recombinant collagen 7 for dystrophic epidermolysis bullosa
Completed Phase 2 clinical trial evaluating safety and tolerability of BBP-589, as well as clinical proof-of-concept, and initiated a Phase 2 extension study
BBP-681 – Topical PI3KA inhibitor for venous and lymphatic malformations
Phase 1/2 clinical trial underway
BBP-561 – KLK 5/7 inhibitor for Netherton syndrome
Investigational New Drug application (IND) enabling studies underway
BBP-815 – AAV gene therapy for nonsyndromic hearing loss
Preclinical development
BBP-818 – AAV gene therapy for classic galactosemia
IND-enabling studies underway
BBP-472 – PI3KB inhibitor for PTEN autism
Preclinical development
First Quarter 2022 Financial Results:
Cash, Cash Equivalents and Marketable Securities
Cash, cash equivalents and marketable securities, excluding restricted cash, totaled $633.5 million as of March 31, 2022, compared to $787.5 million as of December 31, 2021. The net decrease of $154.0 million pertains primarily to payments for operating costs and expenses of $160.6 million, which includes $18.8 million in payments for debt-related interests, timing of payments of accrued compensation and benefits of $16.9 million and $3.9 million in payments related to the restructuring initiative that the Company implemented during the current quarter as described below. During the current quarter, the Company received an upfront payment of $10.0 million upon closing of the asset purchase agreement between its affiliate, Origin Biosciences, and Sentynl Therapeutics.
"We made significant progress in reducing our expenditures in the first quarter, highlighted by a combined reduction of over $100 million in 2022-2023 operating expenses through the Helsinn and Sentynl deals, but we are not yet done. Our priorities are focusing resources towards select internal programs while finding value-creating partnerships for others that we believe allow science to advance seamlessly towards patients. Our expectation is that operating expenses and cash burn will meaningfully decline in the second quarter as restructuring charges from the beginning of the year decline and anticipated additional business development activity allows us to decrease further from that baseline, establishing a reduced run rate for the rest of the year. We currently expect to have runway up to and beyond the readout of our ATTR catalyst in mid-2023 without requiring equity dilution. We reiterate our guidance of runway into 2024," said Brian Stephenson, Ph.D., CFA, BridgeBio’s Chief Financial Officer.
BridgeBio is engaged in partnering and out-licensing discussions for a select number of programs, which are listed on the Company’s website.
Operating Costs and Expenses
Operating costs and expenses increased by $7.4 million to $175.4 million for the first quarter of 2022 as compared to $168.0 million for the same period in the prior year. During the current quarter, the Company incurred $22.7 million in restructuring, impairment and related charges, as part of its restructuring initiative. In January 2022, the Company committed to a restructuring initiative designed to drive operational changes in its business processes, efficiencies and cost savings to advance corporate strategy and development programs. The restructuring initiative included, among other components, consolidation and rationalization of facilities, reprioritization of development programs and the reduction of our workforce. The Company has substantially completed the activities and has incurred most of the costs related to the restructuring initiative during the current quarter. The Company estimates to incur total charges in the range of approximately $23.0 million to $25.0 million for the fiscal year 2022, consisting primarily of impairments and write-offs of long-lived assets, severance and employee-related costs, and exit and other related costs. The estimate of the range of costs is subject to certain assumptions, such as the Company’s ability to sublease certain office spaces. Actual results may differ from those estimates or assumptions. The nonrecurring charges related to the restructuring initiative were partially offset by a $15.3 million decrease in the Company’s normal operating expenses compared to the same period in the prior year, primarily due to cost savings and impacts from such restructuring initiative.
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.