CaSR

- In our study, encaleret restored physiologic mineral homeostasis in 13 participants with ADH1, specifically correcting hypocalcemia and reducing hypercalciuria - Rapid and sustained impact of encaleret on mineral homeostasis was observed, specifically in the normalization of blood calcium, urine calcium and parathyroid hormone (PTH) -No serious adverse events were reported with encaleret and no treatment discontinuations or study withdrawals occurred during the trial -The Phase 3 CALIBRATE trial of encaleret in patients with ADH1 is ongoing in six countries with topline data expected in the first half of 2024 - If approved, encaleret could be the first therapy specifically indicated for the treatment of ADH1 PALO ALTO, Calif., Oct. 10, 2023 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, announced that the proof-of-concept Phase 2b data evaluating the effects of orally-administered encaleret on mineral homeostasis in patients with ADH1 were published in the New England Journal of Medicine in partnership with the National Institutes of Health (NIH). “Conventional therapy for ADH1 includes raising the blood calcium levels with calcium supplements and activated vitamin D, taken in multiple doses throughout day. But this burdensome regimen may also increase urine calcium levels above normal, which can damage the kidney, leading to kidney failure in worst-case scenarios. People with ADH1 need better treatments, so they are not constantly walking on a tightrope. It’s been rewarding to observe the robust response in our study participants, some of whom I’ve known for almost 20 years, to this investigational medication that directly targets the underlying cause and appears to restore the calcium balance back towards normal,” said Rachel Gafni, M.D., the principal investigator of the study and a senior research physician in the National Institute of Dental and Craniofacial Research at the NIH. As part of the Phase 2b study, participants completed one or two 5-day inpatient dose-ranging periods, followed by a 24-week outpatient period. Encaleret was administered twice daily with doses adjusted to achieve normal albumin-corrected blood calcium levels and participants stopped taking calcium and vitamin D supplements, the standard of care for ADH1. The results showed that: Encaleret corrected hypocalcemia and reduced hypercalciuria within a few days of treatment initiation with sustained effect during the 24-week outpatient period As expected with elevated PTH levels, levels of bone turnover markers increased during the outpatient period, with levels in nine of 13 participants remaining normal. Long-term study will continue to assess skeletal effects Kidney function and preexisting renal calcifications did not worsen and will continue to be monitored in longer-term studies. No serious adverse events were reported with encaleret. Treatment-related adverse events were limited to infrequent mild, transient, asymptomatic hypophosphatemia, or hypercalcemia that resolved either spontaneously or with dose adjustment No treatment discontinuations or study withdrawals occurred “The profound impact we’ve seen on mineral homeostasis in the ADH1 participants to date is deeply encouraging. Encaleret appeared to restore physiologic mineral homeostasis in 13 participants with ADH1 within days of undergoing treatment and the results continue to be sustained 18 months out from the trial’s start date. We hope to see similar results in our Phase 3 trial and are excited about what this means for a patient population in need of targeted therapeutic options,” Scott Adler, M.D., chief medical officer of Calcilytix, a BridgeBio affiliate that is focused on developing encaleret for ADH1. BridgeBio recently shared data from 18 months of outpatient treatment in the long-term extension of its Phase 2b trial in an oral presentation at the Endocrine Society Meeting 2023. Additionally, the Company plans additional presentations related to the program at the upcoming American Society for Bone and Mineral Research (ASBMR) 2023 Annual Meeting. CALIBRATE, BridgeBio’s Phase 3 trial (NCT05680818) of encaleret for the treatment of ADH1 is ongoing in six countries with topline data expected in the first half of 2024. The design of the CALIBRATE study incorporates feedback from global regulatory authorities and patients, with a primary composite endpoint of blood and urine calcium concentrations within target ranges in participants treated with encaleret compared to standard of care and secondary endpoints evaluating other measures of mineral homeostasis, quality of life and kidney function. About Encaleret Encaleret is an investigational, orally administered small molecule that selectively antagonizes the calcium sensing receptor (CaSR), targeting ADH1 at its source. The current standard of care for patients with ADH1 includes oral calcium and/or active vitamin D supplements that are typically administered to manage signs and symptoms associated with hypocalcemia. Encaleret has received Fast Track Designation by the U.S. Food and Drug Administration (FDA) and Orphan Drug designation in the United States and the European Union. About Autosomal Dominant Hypocalcemia Type 1 (ADH1) ADH1 is caused by gain-of-function variants of the CASR gene encoding the CaSR. The calcium-sensing receptor regulates the extracellular calcium concentration in the body primarily through its activity in the parathyroid glands and the kidney. Due to increased sensitivity of the variant CaSR to extracellular calcium, patients with ADH1 have low blood calcium (hypocalcemia), inappropriately low parathyroid hormone levels, and excess excretion of calcium in the urine (hypercalciuria). Hypocalcemia can cause neuromuscular symptoms, which can include severe muscle cramping and seizures, while hypercalciuria can lead to kidney calcifications and impaired kidney function. Studies estimate that there are 25,000 carriers of gain-of-function variants of the calcium-sensing receptor (CaSR) gene, the underlying cause of ADH1, in the US and EU. This estimate is based on analyses of independent general population genetic datasets, including Geisinger Health System, UK Biobank, gnomAD, and TopMed.1,2 About BridgeBio 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 Forward-Looking Statements This press release contains forward-looking statements. Statements BridgeBio makes 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. BridgeBio intends 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 expectations, plans and prospects regarding the preclinical and clinical development plans, clinical trial designs, clinical and therapeutic potential, and strategy of our product candidates, including, but not limited to, the continuation of the Phase 3 CALIBRATE trial of encaleret in patients with ADH1 in six countries; the timeline of expected topline data of the Phase 3 CALIBRATE trial; the statement regarding the expectation of data from the Phase 3 trial in Dr. Adler’s quote; the timing and success of our interactions with regulatory health authorities, including the FDA, in connection with Phase 3 CALIBRATE trial; and the timing of these events, reflect our current views about our plans, intentions, expectations, strategies and prospects, which are based on the information currently available to us and on assumptions we have made. Although BridgeBio believes that its plans, intentions, expectations, strategies and prospects as reflected in or suggested by those forward-looking statements are reasonable, BridgeBio 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, BridgeBio’s ability to continue and complete its ongoing and planned clinical trials of Phase 3 CALIBRATE trial of encaleret in patients with ADH1, the design and success of BridgeBio’s ongoing and planned clinical trials, difficulties with enrollment in BridgeBio’s clinical trials, adverse events that may be encountered in BridgeBio’s clinical trials, the FDA or other regulatory agencies not agreeing with BridgeBio’s regulatory approval strategies, components of BridgeBio’s filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted, as well as those risks set forth in the Risk Factors section of BridgeBio’s Annual Report on Form 10-K for the year ended December 31, 2022, and BridgeBio’s other SEC filings. Moreover, BridgeBio operates 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 BridgeBio’s 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. References Dershem et al., Am. J. Hum. Genet., 2020. Data obtained from the gnomAD, TopMed, and UK Biobank databases as of 2022. BridgeBio Media Contact: Vikram Bali contact@bridgebio.com (650)-789-8220

- Announced consistently positive results from the Phase 3 ATTRibute-CM study of acoramidis in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), including a highly statistically significant result observed on the primary endpoint with a Win Ratio of 1.8 (p<0.0001) and clinically meaningful and consistent separation observed on measures of mortality, morbidity, function, and quality of life; the Company intends to New Drug Application (NDA) for acoramidis with the U.S. Food and Drug Administration (FDA) by the end of 2023 - Presented updated six-month results from Cohort 5 of PROPEL2, a Phase 2 trial of infigratinib in children with achondroplasia, at the Endocrine Society 2023 Annual Conference (ENDO 2023), demonstrating a continued potentially best-in-class efficacy and well-tolerated safety profile, and a mean increase in annualized height velocity (AHV) of 3.38cm/year with no treatment-related adverse events - Dosed the first participant in FORTIFY, a global Phase 3 study of BBP-418 in patients with limb girdle muscular dystrophy type 2I/R9 (LGMD2I/R9) and met with the FDA to discuss the use of glycosylated alpha-dystroglycan (αDG) levels as a surrogate endpoint; based on this meeting, the Company believes there is potential to pursue Accelerated Approval in the U.S. for BBP-418 - Shared 18-month data from the long-term extension of the Phase 2 study of encaleret in patients with autosomal dominant hypocalcemia type 1 (ADH1) at ENDO 2023, including observation of a rapid and sustained treatment effect; Phase 3 CALIBRATE registrational trial remains ongoing, with topline results expected to be announced in the first half of 2024 - Phase 1/2 trial of BBP-631 for treatment of congenital adrenal hyperplasia (CAH) continuing to progress with an update planned by the end of 2023 - Three lead KRAS programs are advancing, with an Investigational New Drug (IND) application planned for first-in-class direct KRASG12C (ON) inhibitor BBO-8520 in 2023 as well as a recent selection of a clinical candidate for PI3Kα:RAS breaker with the intention to IND application in 2024 - Ended the quarter with $353 million in cash, cash equivalents, marketable securities, and short-term restricted cash, and $50 million of investments in equity securities, providing runway into 2H 2024 PALO ALTO, Calif., Aug. 03, 2023 (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, 2023 and provided an update on the Company’s operations. “We’ll remain ever grateful for the support of the physicians and patients in the ATTR-CM community, which helped bring the ATTRibute-CM study to its final readout,” said Neil Kumar, Ph.D., founder and CEO of BridgeBio. “With these data in hand, coupled with a pipeline that could produce an additional three pivotal readouts in the next 24 months, we feel we have the ingredients to build a sustainable engine for the patients that we serve in large and small markets alike.” BridgeBio’s key programs: Acoramidis (AG10) – Transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM): In July 2023, the Company released topline results from ATTRibute-CM, its Phase 3 trial of acoramidis for patients with ATTR-CM. The primary endpoint analysis was highly statistically significant with a Win Ratio of 1.8 (p<0.0001). A clinically meaningful and consistent treatment effect was observed across all measures of mortality, morbidity, function, and quality of life. An on-treatment survival rate of 81% was observed, versus a placebo survival rate of 74% (absolute risk reduction of 6.43%; relative risk reduction of 25%). A highly statistically significant relative risk reduction of 50% (p<0.0001) was observed on frequency of cardiovascular-related hospitalization. In comparative exploratory post hoc analyses enabled by tafamidis drop-in, albeit at low patient numbers, acoramidis showed a 42% greater increase in serum TTR levels and a 92% improvement in median NT-proBNP relative to placebo + tafamidis. Acoramidis was well-tolerated with no safety signals of potential clinical concern identified. BridgeBio intends to NDA for acoramidis with the FDA by end of 2023 and marketing authorization applications with additional regulatory authorities globally in 2024. The details of the topline results of the ATTRibute-CM trial will be presented at the annual meeting of the European Society of Cardiology, one of the premier global cardiology congresses, in Amsterdam at the end of August 2023. Low-dose infigratinib – FGFR1-3 inhibitor for achondroplasia and hypochondroplasia: In June 2023, the Company presented updated six-month results from Cohort 5 of PROPEL2, its Phase 2 trial of infigratinib for children with achondroplasia, at ENDO 2023; the data demonstrated a significant and robust increase in annualized height velocity (AHV) with a mean change from baseline of +3.38 cm/year for 12 children. 83% of children in Cohort 5 responded to infigratinib, as defined by an increase from baseline AHV of at least 25%. The mean change from baseline in AHV of responders was +4.08 cm/year. Early but promising trends towards improvement in proportionality were observed, as measured by the upper and lower body segment ratio. At six months, infigratinib was well-tolerated as a single daily oral therapy with no adverse events assessed as treatment-related in all patients in Cohort 5. The Company has started to enroll children in the run-in for a registrational Phase 3 trial. If approved, BridgeBio believes that infigratinib has the potential to capture a significant share of the market based on blinded market research. BBP-418 – Glycosylation substrate for limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9): The Company met with the FDA to discuss the use of glycosylated αDG levels as a surrogate endpoint. Based on this meeting, the Company believes there is potential to pursue Accelerated Approval in the U.S. for BBP-418. The Company has dosed the first participant in FORTIFY, its global Phase 3 study of BBP-418 in patients with LGMD2I/R9. FORTIFY includes an interim analysis at 12 months focused on change in glycosylated αDG levels; topline data from this analysis is expected in late 2024/early 2025. Deficiency of glycosylated αDG is the causal molecular driver of LGMD2I/R9. In the ongoing Phase 2 study, patients treated with BBP-418 had a rapid and sustained increase of glycosylated αDG levels, concurrent with sustained decreases in creatine kinase and improvements from baseline in ambulatory and clinical function measures. BBP-418 has a potentially addressable population of 7,000 patients in the United States and European Union. There are currently no disease-modifying treatments available for LGMD2I/R9. Encaleret – Calcium-sensing receptor (CaSR) inhibitor for autosomal dominant hypocalcemia type 1 (ADH1): The Company presented 18-month data from the long-term extension of its Phase 2 study of encaleret in patients with ADH1 at ENDO 2023, including observations of a rapid and sustained treatment effect. Additionally, the Company shared initial findings from its genetic testing program, highlighting that ADH1 may be the most common presentation of nonsurgical hypoparathyroidism. Population genetics analyses estimate approximately 25,000 carriers of gain-of-function variants of the CaSR, the underlying cause of ADH1, in the United States and European Union. The Company anticipates sharing topline data from CALIBRATE, a Phase 3 registrational trial of encaleret for ADH1, in the first half of 2024. If approved, encaleret could be the first therapy specifically indicated for the treatment of ADH1. BBP-631 – AAV5 gene therapy candidate for congenital adrenal hyperplasia (CAH): The Phase 1/2 gene therapy trial of BBP-631 for CAH continued to progress, and the Company plans to provide an update by the end of 2023. 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. RAS cancer portfolio: BridgeBio is continuing to develop the three main programs of its RAS franchise: BBO-8520, an investigational, next-generation small molecule direct KRASG12C(ON) inhibitor candidate that is designed to directly bind and inhibit KRASG12C in both its ON (GTP-bound) and OFF (GDP-bound) conformations, which remains on track to IND application and enter the clinic in 2023. A PI3Kα:RAS breaker program, investigational small molecules that are designed to block RAS-driven PI3Kα activation with a novel and potentially broad mechanism of action to target not only PI3Kα mutant tumors and RAS mutant tumors, but potentially other tumors driven by RTK activation of RAS signaling. The Company has selected a development candidate and expects to IND application in 2024 as the second investigational RAS cancer therapy from the BridgeBio portfolio. The Company’s pan-KRAS program, which targets multiple KRAS mutants including KRASG12D and KRASG12V, which are present in a large percentage of colorectal, pancreatic, and non-small cell lung cancer tumors. Development candidate selection for this program is planned for late 2023 or early 2024. Recent Corporate Updates: Partnership with Burjeel Holdings on project ‘NADER’ (Needs Assessment and Therapeutics Development for Rare Diseases – ‘nader’ meaning ‘rare’ in Arabic): Signed a preliminary, non-binding Collaboration Agreement establishing a mutual intention to revolutionize the field of early diagnosis and treatment of rare diseases in the United Arab Emirates and the region. Updated encouraging clinical and biomarker data shared for the Company’s Canavan disease gene therapy program: Presented promising positive data from six participants dosed in CANaspire, the Company’s Phase 1/2 clinical trial of BBP-812, an investigational intravenous (IV) adeno-associated virus serotype 9 (AAV9) gene therapy for the treatment of Canavan disease. Following treatment, the N-acetylaspartate (NAA) levels of CANaspire participants were consistent with levels seen in individuals with milder Canavan disease based on findings from the Company’s natural history study and reports in the scientific literature. Sustained reductions in NAA were measured in the urine, cerebrospinal fluid (CSF), and brain of all participants and have been observed for over one year in the earliest dosed participants. Second Quarter 2023 Financial Results: Cash, Cash Equivalents, Marketable Securities and Short-Term Restricted Cash Cash, cash equivalents, marketable securities and short-term restricted cash, totaled $353.2 million as of June 30, 2023, compared to $466.2 million as of December 31, 2022. The net decrease of $113.0 million in cash, cash equivalents, marketable securities and short-term restricted cash is primarily attributable to net cash used in operating activities of $257.7 million, offset by net proceeds received of $144.0 million from the Follow-on public offering during the six months ended June 30, 2023. Revenue Revenue for the three and six months ended June 30, 2023 was $1.6 million and $3.5 million, respectively, as compared to $73.7 million and $75.4 million for the same periods in the prior year. Revenue for the three and six months ended June 30, 2023 primarily consisted of $1.5 million and $3.2 million, respectively, of services revenue under the Navire-BMS License Agreement. Revenue for the three and six months ended June 30, 2022 primarily consisted of $70.2 million of license revenue and $3.2 million of services revenue under the Navire-BMS License Agreement. Operating Costs and Expenses Operating costs and expenses for the three and six months ended June 30, 2023 were $147.7 million and $275.7 million, respectively, compared to $153.9 million and $329.3 million for the same periods in the prior year. The overall decrease in operating costs and expenses for the three and six months ended June 30, 2023 compared to the comparative periods was due mainly to the decreases in research, development and other (R&D) expenses resulting from the Company's reprioritization of its R&D programs; selling, general and administrative expenses resulting from its company-wide streamlining of costs; and restructuring, impairment and related charges since the majority of the restructuring initiatives commenced in the first quarter of 2022. The effects of the Company's restructuring initiative which commenced in the first quarter of 2022, continue to be realized due to the Company's reductions in operating costs and expenses. Restructuring, impairment and related charges for the three and six months ended June 30, 2023, amounted to $3.5 million and $6.9 million, respectively. These charges primarily consisted of winding down, exit costs, and severance and employee-related costs. Restructuring, impairment and related charges for the same periods in the prior year were $8.4 million and $31.1 million, respectively. These charges primarily consisted of impairments and write-offs of long-lived assets, severance and employee-related costs, and exit and other related costs. The Company remains committed to evaluating various restructuring alternatives aimed at driving operational changes in business processes. These alternatives includes enhancing commercialization efforts, improving efficiencies, and achieving cost savings. Stock-based compensation expenses included in operating costs and expenses for the three months ended June 30, 2023 were $27.2 million, of which $13.2 million is included in research, development and other (R&D) expenses, $14.0 million is included in selling, general and administrative expenses. Stock-based compensation expenses included in operating costs and expenses for the three months ended June 30, 2022 were $28.3 million, of which $14.3 million is included in research, development and other (R&D) expenses, and $14.0 million is included in selling, general and administrative expenses. Stock-based compensation expenses included in operating costs and expenses for the six months ended June 30, 2023 were $50.7 million, of which $25.0 million is included in research, development and other (R&D) expenses, $25.7 million is included in selling, general and administrative expenses. Stock-based compensation expenses included in operating costs and expenses for the six months ended June 30, 2022 were $52.6 million, of which $22.9 million is included in research, development and other (R&D) expenses, $28.5 million is included in selling, general and administrative expenses, and $1.2 million is included in restructuring, impairment and related charges. “Following the recent announcement and strength of our Phase 3 ATTRibute-CM data, we will continue to explore multiple options to fully resource the acoramidis launch while optimizing cost of capital, including partnerships, royalty transactions, and equity financing,” said Brian Stephenson, Ph.D., CFA, Chief Financial Officer of BridgeBio. “We anticipate $300-$350 million of investment will support acoramidis from here through the first 12 months of commercial launch. This coupled with our slate of pivotal readouts over the next 24 months offers the opportunity for meaningful value creation for both patients and investors.” 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, 2023 2022 2023 2022 (Unaudited) (Unaudited) Revenue $ 1,641 $ 73,746 $ 3,467 $ 75,440 Operating costs and expenses: Research, development and others 108,087 109,100 201,599 218,097 Selling, general and administrative 36,122 36,426 67,230 80,139 Restructuring, impairment and related charges 3,531 8,396 6,900 31,058 Total operating costs and expenses 147,740 153,922 275,729 329,294 Loss from operations (146,099 ) (80,176 ) (272,262 ) (253,854 ) Other income (expense), net: Interest income 4,514 766 8,667 1,033 Interest expense (20,594 ) (20,279 ) (40,715 ) (40,623 ) Gain from sale of priority review voucher, net — 107,946 — 107,946 Other income (expense), net 1,476 (10,816 ) 875 (18,391 ) Total other income (expense), net (14,604 ) 77,617 (31,173 ) 49,965 Net loss (160,703 ) (2,559 ) (303,435 ) (203,889 ) Net loss (income) attributable to redeemable convertible noncontrolling interests and noncontrolling interests 2,804 (7,297 ) 5,380 (2,364 ) Net loss attributable to common stockholders of BridgeBio $ (157,899 ) $ (9,856 ) $ (298,055 ) $ (206,253 ) Net loss per share, basic and diluted $ (0.98 ) $ (0.07 ) $ (1.90 ) $ (1.41 ) Weighted-average shares used in computing net loss per share, basic and diluted 160,535,435 146,684,804 156,645,838 146,285,694 Three Months Ended June 30, Six Months Ended June 30, Stock-based Compensation 2023 2022 2023 2022 (Unaudited) (Unaudited) Research, development and others $ 13,229 $ 14,352 $ 25,008 $ 22,909 Selling, general and administrative 13,947 13,953 25,645 28,505 Restructuring, impairment and related charges — — — 1,172 Total stock-based compensation $ 27,176 $ 28,305 $ 50,653 $ 52,586 BRIDGEBIO PHARMA, INC. Condensed Consolidated Balance Sheets (In thousands) June 30, December 31, 2023 2022 Assets (Unaudited) (1) Cash and cash equivalents and marketable securities $ 333,307 $ 428,269 Investment in equity securities 50,487 43,653 Receivable from licensing and collaboration agreements 8,614 17,079 Short-term restricted cash 19,930 37,930 Prepaid expenses and other current assets 20,546 21,922 Property and equipment, net 13,047 14,569 Operating lease right-of-use assets 9,814 10,678 Intangible assets, net 27,515 28,712 Other assets 20,401 20,224 Total assets $ 503,661 $ 623,036 Liabilities, Redeemable Convertible Noncontrolling Interests and Stockholders’ Deficit Accounts payable $ 3,874 $ 11,558 Accrued and other liabilities 102,470 106,195 Operating lease liabilities 14,692 15,949 2029 Notes 735,940 734,988 2027 Notes 542,501 541,634 Term loan 440,496 430,993 Other long-term liabilities 13,326 26,643 Redeemable convertible noncontrolling interests 333 (1,589 ) Total BridgeBio stockholders' deficit (1,362,023 ) (1,254,617 ) Noncontrolling interests 12,052 11,282 Total liabilities, redeemable convertible noncontrolling interests and stockholders’ deficit $ 503,661 $ 623,036 (1 ) The condensed consolidated financial statements as of and for the year ended December 31, 2022 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, 2023 2022 Operating activities: Net loss $ (303,435 ) $ (203,889 ) Adjustments to reconcile net loss to net cash used in operating activities: Stock-based compensation 49,085 52,409 Depreciation and amortization 3,270 3,466 Noncash lease expense 2,024 2,889 Accrual of payment-in-kind interest on term loan 6,742 — Loss on deconsolidation of PellePharm 1,241 — (Gain) loss from investment in equity securities, net (2,399 ) 23,228 Fair value of shares issued under a license agreement — 4,567 Accretion of debt 4,580 4,383 Fair value adjustment of warrants (222 ) 1,390 Loss on sale of certain assets — 6,261 Impairment of long-lived assets — 12,653 Gain from sale of priority review voucher, excluding transaction costs — (110,000 ) Gain from recognition of receivable from licensing and collaboration agreement — (12,500 ) Other noncash adjustments (328 ) 853 Changes in operating assets and liabilities: Receivable from licensing and collaboration agreements 8,466 2,993 Prepaid expenses and other current assets 1,057 (3,021 ) Other assets 32 8,691 Accounts payable (4,098 ) (3,090 ) Accrued compensation and benefits (11,071 ) (9,402 ) Accrued research and development liabilities (11,322 ) 5,953 Operating lease liabilities (2,443 ) (3,348 ) Deferred revenue (3,184 ) 16,641 Accrued professional and other liabilities 4,330 7,785 Net cash used in operating activities (257,675 ) (191,088 ) Investing activities: Purchases of marketable securities (19,754 ) (119,611 ) Maturities of marketable securities 41,550 293,919 Purchases of investment in equity securities (71,504 ) (10,930 ) Sales of investment in equity securities 67,068 9,708 Decrease in cash and cash equivalents resulting from deconsolidation of PellePharm (503 ) — Payment for an intangible asset — (1,500 ) Proceeds from sale of priority review voucher — 110,000 Proceeds from sale of certain assets — 10,000 Purchases of property and equipment (440 ) (3,261 ) Net cash provided by investing activities 16,417 288,325 Financing activities: Proceeds from issuance of common stock through Follow-on offering, net 144,049 — Repayment of term loan — (20,486 ) Proceeds from BridgeBio common stock issuances under ESPP 1,809 966 Repurchase of shares to satisfy tax withholding (1,715 ) (476 ) Issuance costs associated with term loan — (1,120 ) Proceeds from stock option exercises, net of repurchases 312 160 Other financing activities 4,563 — Net cash provided by (used in) financing activities 149,018 (20,956 ) Net (decrease) increase in cash, cash equivalents and restricted cash (92,240 ) 76,281 Cash, cash equivalents and restricted cash at beginning of period 416,884 396,365 Cash, cash equivalents and restricted cash at end of period $ 324,644 $ 472,646 Six Months Ended June 30, 2023 2022 Supplemental Disclosures of Cash Flow Information: Cash paid for interest $ 28,738 $ 25,435 Supplemental Disclosures of Noncash Investing and Financing Information: Payment-in-kind interest added to principal of term loan $ — $ 5,075 Unpaid property and equipment $ 131 $ 73 Transfers (to) from noncontrolling interests $ (5,940 ) $ 1,456 Reconciliation of Cash, Cash Equivalents and Restricted Cash: Cash and cash equivalents $ 302,438 $ 470,098 Short-term restricted cash 19,930 — Restricted cash — Included in “Prepaid expenses and other current assets” — 140 Restricted cash — Included in “Other assets” 2,276 2,408 Total cash, cash equivalents and restricted cash at end of period shown in the condensed consolidated statements of cash flows $ 324,644 $ 472,646 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,” “on track”, “remains” 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, market potential of our programs and product candidates, including the statement in Dr. Kumar’s quote regarding our data, pipeline and potential product launches; the timing and success of our clinical development programs, including the progress of our ongoing and planned clinical trials of acoramidis for patients with ATTR-CM, our plans to new NDA for acoramidis with the FDA by end of year 2023, our planned marketing authorization applications with additional regulatory authorities in 2024, the planned presentation of the details of the topline results of ATTRibute-CM trial at the annual meeting of the European Society of Cardiology, and the availability of data from our clinical trials of acoramidis; the availability of data from our clinical trials of for BBP-418 in LGMD2I/R9, the potential and the opportunity to pursue Accelerated Approval Pathway for BBP-418 in LGMD2I/R9 in the U.S., and the potentially-addressable population of BBP-418 in the United States and European Union; the potential of infigratinib for achondroplasia to have a potential of best-in-class efficacy with well-tolerated safety pro to capture a significant share of the market based on blinded market research, if approved; the Company’s finding that ADH1 may be the most common presentation of nonsurgical hypoparathyroidism, the timing and status of Phase 3 CALIBRATE registrational trial of encaleret for ADH1, the timing of announcement of topline data from CALIBRATE in the first half of 2024, and the success of encaleret (if approved), including its potential to be the first therapy specifically indicated for the treatment of ADH1; the continuation and progress of our ongoing Phase 1/2 trial of BBP-631 for CAH, with a planned update by the end of 2023; the continued development, the timing, progression and success of the RAS franchise, including an IND application planned for first-in-class direct KRASG12C (ON) inhibitor BBO-8520 in 2023, the intention to IND for a selected development candidate for PI3Kα:RAS breaker in 2024 as the second RAS cancer therapy from the BridgeBio portfolio, and the planned development candidate selection for the pan-KRAS program, for late 2023 or early 2024; our anticipated cash runway; the anticipated amounts needed to support our planned operations, including the potential commercial launch of acoramidis, and potential sources and availability of additional capital, 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 obtain additional funding under our credit facility or through potential partnerships, royalty transactions and equity financings, potential volatility in our share price, uncertainty regarding any impacts due to COVID-19, such as delays in regulatory review, manufacturing and supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy, the impacts of current macroeconomic and geopolitical events, including changing conditions from hostilities in Ukraine, increasing rates of inflation and rising interest rates, on business operations and expectations, 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, 2022 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

New in vitro data from Europe show that simufilam can reverse altered filamin A protein (FLNA) in pituitary tumor cells, leading to improved cell signaling. Data suggest FLNA is a central factor influencing pituitary tumor cell behavior. Data to be presented at the European Society of Endocrinology, May 13-16th. AUSTIN, Texas, May 08, 2023 (GLOBE NEWSWIRE) -- Cassava Sciences Inc. (Nasdaq: SAVA), a clinical-stage biotechnology company, today announced new data from European researchers that highlight the bioactivity of simufilam on the filamin A (FLNA) protein. Prior research has shown that FLNA is altered in pituitary tumor cells, leading to impaired cell signaling. New in vitro data now show that simufilam can reverse this FLNA alteration in pituitary tumor cells, leading to improved cell signaling. The data also suggest that improved cell signaling may enhance the clinical efficacy of an FDA-approved drug used to manage a type of pituitary tumor. “These findings take filamin A research to the next level,” said Remi Barbier, President & CEO. “They show an in vitro drug effect for simufilam in a pathway outside of neurodegeneration. This bioactivity is thematically consistent with the proposed mechanism of action of simufilam in Alzheimer’s disease, namely, simufilam reverses a filamin A alteration. To be clear, we’re inspired by this promising research, but that’s as far as it goes. We have no immediate plans to initiate by ourselves a clinical program in cancer.” Prior research publications have demonstrated the essential role of the filamin A (FLNA) protein in signaling of numerous receptors, including dopamine receptors, calcium-sensing receptors, calcitonin receptors, insulin receptors, acetylcholine receptors and somatostatin receptors. Today’s new data by researchers in Europe shows a functional interaction between simufilam, FLNA and somatostatin receptors. Specifically, the researchers show simufilam treatment significantly reduced levels of phosphorylation (minus 28% ± 13% after 10 min, p<0.01 vs basal) at a site on FLNA in human pituitary tumor cells. The reduced FLNA phosphorylation was accompanied by improved cell signaling of somatostatin receptors. The authors also show that cells co-treated with simufilam plus an FDA-approved drug used to manage a type of pituitary tumor significantly increased cell death (+37% ± 9%, p<0.01 vs basal, p<0.05 vs. either drug alone) in a rat pituitary tumor cell line. These in vitro data suggest FLNA is a central factor influencing pituitary tumor cell behavior. The data also suggest co-treatment with simufilam may enhance somatostatin analogs, a class of FDA-approved drugs used to manage a type of pituitary tumor; however, there is not enough information from which scientific conclusions can be drawn regarding a relationship between simufilam and the treatment of any disease in humans. Oral Presentation Details When: May 15th, 2023 Where: 25th European Congress of Endocrinology, Istanbul, Turkey. Abstract Title:A Novel Filamin A-binding Molecule May Significantly Enhance Somatostatin Receptor Type 2 Antitumoral Actions in Growth Hormone-secreting PitNET Cells. Senior Authors: Prof. Erika Peverelli, PhD, and Prof. Giovanna Mantovani, PhD, Università di Milano, Italy and Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, U.O. di Endocrinologia, Milano, Italy. External Web Link to Abstract: Disclosures: Cassava Sciences provided simufilam drug to the Peverelli lab at no cost pursuant to a Material Transfer Agreement. Cassava Sciences did not fund Dr. Peverelli’s research. L. Burns, Ph.D., one of 15 co-authors of the abstract, is employed by Cassava Sciences as Senior VP of Neuroscience and holds equity in Cassava Sciences. Cassava Sciences owns intellectual property rights in the field of FLNA-binding compounds, including simufilam, and methods for inhibiting the growth of cancer cells. About Simufilam Simufilam is a novel drug candidate designed to treat and slow the progression of Alzheimer’s disease. Simufilam binds tightly to an altered conformation of the filamin A protein (FLNA) that is present in the brain of the Alzheimer’s patient and is critical to the toxicity of Aβ42. Simufilam is wholly owned by Cassava Sciences, without royalty or payment obligation to any third party. About Cassava Sciences, Inc. Cassava Sciences is a clinical-stage biotechnology company based in Austin, Texas. Our mission is to detect and treat neurodegenerative diseases, such as Alzheimer’s disease. Our novel science is based on stabilizing—but not removing—a critical protein in the brain. Our product candidates have not been approved by any regulatory authority, and their safety, efficacy or other desirable attributes have not been established. For more information, please visit our website: For More Information Contact: Eric Schoen, Chief Financial Officer (512) 501-2450 ESchoen@CassavaSciences.com Cautionary Note Regarding Forward-Looking Statements: This news release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, that may include but are not limited to: our strategy and plans; the treatment of Alzheimer’s disease dementia; the safety or efficacy of simufilam in patients; the release of evidential data by a third-party related to the biological activity of simufilam; verbal commentaries made by our employees; and potential benefits, if any, of the our product candidates. These statements may be identified by words such as “may,” “anticipate,” “believe,” “could,” “expect,” “forecast,” “intend,” “plan,” “possible,” “potential,” and other words and terms of similar meaning. Simufilam and SavaDx are investigational product candidates. They are not approved by any regulatory authority and their safety, efficacy or other desirable attributes have not been established in patients. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. You should not place undue reliance on any scientific data we or others present or publish. This press release may also contain science data and drug information based on the work of third-party researchers or other publicly available information. We have not independently verified the accuracy or completeness of the data and information obtained from these sources. Accordingly, we make no representations as to the accuracy or completeness of such research, data or information. You are cautioned not to give undue weight to such research, data or information. The content of this press release is solely our responsibility and does not represent the official views of any third-party researcher, university, clinical group practice or any country’s government agency. Such statements are based largely on our current expectations and projections about future events. Such statements speak only as of the date of this news release and are subject to a number of risks, uncertainties and assumptions, including, but not limited to, those risks relating to the ability of simufilam to enhance somatostatin analogs used to treat pituitary tumors; to demonstrate the specificity, safety, efficacy or potential health benefits of our product candidates; any unanticipated impacts of inflation on our business operations, and including those described in the section entitled “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2022, and future reports to be filed with the SEC. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from expectations in any forward-looking statement. In light of these risks, uncertainties and assumptions, the forward-looking statements and events discussed in this news release are inherently uncertain and may not occur, and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements as predictions of future events. Except as required by law, we disclaim any intention or responsibility for updating or revising any forward-looking statements contained in this news release. For further information regarding these and other risks related to our business, investors should consult our filings with the SEC, which are available on the SEC's website at .