- 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
- 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
- Reported operating expense for Q3 2022 at
- Ended quarter with $558.3 million in cash, cash equivalents and marketable securities, providing financial runway into 2024
“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
“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
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 profile to 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
- 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 Statesalone.
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 Statesand European Union, Canavan disease is an ultra-rare, disabling and fatal disease with no approved therapy.
- Approvals in
Israeland 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 Healthapproved 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 Israelin 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
SHP2inhibitor BBP-398 with Amgen’s LUMAKRAS: First lung cancer patient was dosed in a Phase 1/2 trial of BridgeBio’s SHP2inhibitor 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 Chinaand 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 Statesand European Unioncollectively.
Third Quarter 2022 Financial Results:
Cash, cash equivalents and marketable securities, excluding restricted cash, totaled
Cash, cash equivalents and marketable securities, excluding restricted cash, decreased by
Operating Costs and Expenses
Operating costs and expenses for the three and nine months ended
“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
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.
Condensed Consolidated Statements of Operations
(in thousands, except shares and per share amounts)
|Three Months Ended
||Nine Months Ended
|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:|
|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 attributable to redeemable convertible noncontrolling interests and noncontrolling interests||2,854||5,081||490||18,810|
|Net loss attributable to common stockholders
|Net loss per share, basic and diluted||$||(0.93||)||$||(1.06||)||$||(2.34||)||$||(2.88||)|
|Weighted-average shares used in computing net
loss per share, basic and diluted
|Three Months Ended
||Nine Months Ended
|Research, development and others||$||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||$||83,061|
Condensed Consolidated Balance Sheets
|Cash and cash equivalents and marketable securities||$||558,315||$||787,515|
|Investment in equity securities||33,662||49,148|
|Receivable from licensing and collaboration agreements||24,581||19,749|
|Prepaid expenses and other current assets||25,661||32,446|
|Property and equipment, net||15,603||30,066|
|Operating lease right-of-use assets||11,738||15,907|
|Intangible assets, net||29,310||44,934|
|Liabilities, Redeemable Convertible Noncontrolling Interests and Stockholders’ Deficit|
|Accrued and other liabilities||104,992||118,247|
|Operating lease liabilities||17,044||22,366|
|Other long-term liabilities||28,226||22,069|
|Redeemable convertible noncontrolling interests||(2,388||)||1,423|
|Total BridgeBio stockholders' deficit||(1,138,417||)||(870,414||)|
|Total liabilities, redeemable convertible noncontrolling interests and stockholders’ deficit||$||728,740||$||1,012,792|
|(1||)||The condensed consolidated financial statements as of and for the year ended
Condensed Consolidated Statements of Cash Flows
|Nine Months Ended
|Adjustments to reconcile net loss to net cash used in operating activities:|
|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||)|
|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||)|
|Other accrued and other long-term liabilities||3,797||(1,629||)|
|Net cash used in operating activities||(326,251||)||(364,039||)|
|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||)|
|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||$||183,079|
|Nine Months Ended
|Supplemental Disclosures of Cash Flow Information:|
|Cash paid for interest||$||47,575||$||28,239|
|Supplemental Disclosures of Noncash Investing and Financing Information:|
|Payment-in-kind interest added to principal of term loan||$||8,503||$||—|
|Net noncash portion of repurchase of Eidos noncontrolling interests||$||—||$||38,167|
|Direct transaction costs in the repurchase of Eidos recorded in “Additional paid-in capital”
previously classified in “Prepaid expenses and other current assets”
|Noncash contribution by a noncontrolling interest||$||—||$||21,600|
|Recognized intangible asset recorded in “Accrued research and development liabilities”||$||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
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
Source: BridgeBio Pharma, Inc.