BBP-812

- Patients on acoramidis, a near complete (≥90%) TTR stabilizer in clinical development, lived longer and better as shown in the ATTRibute-CM study. This is the only Phase 3 study of an ATTR-CM disease-modifying treatment to demonstrate improvement in hard clinical outcomes in the combined assessment of CVH and ACM to this degree, this quickly - BridgeBio’s late-stage pipeline continues to rapidly progress with three Phase 3 readouts expected in 2025. Program highlights from this quarter include: - CALIBRATE, the Phase 3 clinical trial of encaleret in ADH1, completed screening - FORTIFY, the Phase 3 clinical trial for LGMD2I/R9, completed enrollment - The FDA granted Breakthrough Therapy Designation to oral infigratinib for achondroplasia - Regenerative Medicine Advanced Therapy Designation awarded to BBP-812 for Canavan disease - Published a MIT Business School case study on BridgeBio’s pioneering business model in the 50th edition of the Journal of Portfolio Management celebrating the work of Harry Markowitz, the Nobel prize-winning inventor of Modern Portfolio Theory, outlining our efforts to build a new type of biopharmaceutical company - The Company ended the quarter with $406 million in cash, cash equivalents, and short-term restricted cash. It anticipates receiving a $500 million milestone payment under our royalty funding agreement upon FDA approval of acoramidis, as well as $105 million in aggregate regulatory milestone payments upon approval of acoramidis in European and Japanese territories PALO ALTO, Calif., Nov. 12, 2024 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio or the Company), a new type of biopharmaceutical company focused on genetic diseases, today reported its financial results for the third quarter ended September 30, 2024, and provided an update on the Company’s operations. “I’m grateful for the continued progress that we have seen across our late-stage pipeline, and I’m excited for the upcoming opportunity to serve patients with ATTR-CM in the commercial marketplace,” said Dr. Neil Kumar, Ph.D., CEO and Founder of BridgeBio. “Underpinning this headway is a corporate experiment we have been conducting for over 9 years now that posits a new type of biotech business model, and so I’m also proud to have released our first case study in The Journal of Portfolio Management, highlighting salient elements of that model.” Pipeline overview: ProgramStatusNext expected milestoneAcoramidis for ATTR-CMNDA filed with U.S. FDANovember 29, 2024 PDUFA dateEncaleret for ADH1Enrolling CALIBRATE, Phase 3 studyEnrollment completion in 2024BBP-418 (ribitol) for LGMD2I/R9 FORTIFY, Phase 3 study enrollment completed Interim analysis in 2025 Infigratinib for achondroplasiaEnrolling PROPEL 3, Phase 3 studyEnrollment completion in 2024Infigratinib for hypochondroplasiaEnrolling observational run-in for ACCEL 2, Phase 2 studyEnrollment completion date to be announcedBBP-812 for Canavan diseaseEnrolling at high dose in Phase 1/2 studyEnrollment completion date to be announced Late-stage investigational programs updates: Acoramidis – Near-complete transthyretin (TTR) stabilizer for transthyretin amyloid cardiomyopathy (ATTR-CM): Based on the positive results from ATTRibute-CM, BridgeBio filed a new drug application (NDA) to the FDA, which has been accepted with a PDUFA action date of November 29, 2024, and the late cycle meeting with the FDA has been completed.Outcomes data through 42 months from the ongoing long-term open-label extension (OLE) of ATTRibute-CM, the Company’s Phase 3 study of acoramidis in ATTR-CM, will be shared at the American Heart Association (AHA) Scientific Sessions on November 18th. During the European Society of Cardiology (ESC) 2024, a new analysis was shared in an oral presentation, showing: Increased serum TTR at Day 28 of ATTRibute-CM was correlated with reduced risk of ACM, cardiovascular mortality (CVM) and CVH in ATTR-CM.A mean of 3.0mg/dL increase in serum transthyretin (TTR) at Month 1 of the OLE (n=21) and mean of 3.4mg/dL increase in serum TTR at Month 6 of the OLE (n=18) in participants who switched from tafamidis and placebo to acoramidis in the ATTRibute-CM study. A post-hoc analysis of ATTRibute-CM evaluating the effect of acoramidis on the composite endpoint of ACM and recurrent CVH events was shared at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2024, which included the following data: A 42% reduction in composite ACM and recurrent CVH events at 30 months observed with acoramidis treatment compared to placebo by applying a negative binomial regression model (post-hoc) (p=0.0005). A 42% reduction in the total number of ACM and recurrent CVH events per patient observed over 30 months with acoramidis treatment compared to placebo. A 30.5% hazard reduction in ACM and recurrent CVH events at 30 months observed with acoramidis treatment compared to placebo by applying the Andersen-Gill model (post-hoc) (p=0.0008). BridgeBio announced the initiation of a scientific collaboration with the CarDS Lab, led by cardiologist-data scientist, Rohan Khera, M.D., M.S. at the Yale School of Medicine, for the launch of the TRACE-AI Network, a novel paradigm of large-scale federated AI screening for ATTR-CM. Upon FDA approval of acoramidis, it is our intent to honor the courage of our U.S. clinical trial patients by providing them acoramidis free for life. Encaleret – Calcium-sensing receptor (CaSR) antagonist for autosomal dominant hypocalcemia type 1 (ADH1): CALIBRATE, the Phase 3 clinical trial of encaleret in ADH1, completed screening; the Company anticipates completing enrollment of the CALIBRATE study in 2024.Proof-of-principle data of encaleret, an oral option for post-surgical hypoparathyroidism, were presented at the American Society for Bone Mineral Research meeting demonstrating a concomitant normalization of blood and urine calcium in 86% of participants within 5 days. BBP-418 (ribitol) – Glycosylation substrate for limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9): BridgeBio completed enrollment of FORTIFY, the Company’s Phase 3 registrational study of BBP-418 in individuals with LGMD2I/R9, with topline data readout from the interim analysis expected in 2025. BridgeBio believes there is an opportunity to pursue Accelerated Approval in the U.S. for BBP-418 in LGMD2I/R9 based on a potential biomarker surrogate endpoint of glycosylated alpha-dystroglycan (αDG) at time of the interim analysis. The FDA has granted Rare Pediatric Disease Designation for BBP-418 in the treatment of LGMD2I/R9. If BBP-418 is approved, BridgeBio may qualify for a Priority Review Voucher, which can be applied to another therapy in the Company’s pipeline for a shorter timeline during the review process of a New Drug Application or can be sold and transferred to another company looking to receive priority review for one of its applications. Infigratinib – FGFR1-3 inhibitor for achondroplasia and hypochondroplasia: The FDA granted Breakthrough Therapy Designation to infigratinib for demonstrating substantial improvement in efficacy over available therapies on clinically significant endpoint(s). The PROPEL 3 global Phase 3 registrational study of infigratinib in achondroplasia continues to enroll; study completion anticipated by the end of the year. PROPEL, BridgeBio’s observational lead-in study in achondroplasia for PROPEL 3, has completed enrollment. The initial phase of MyAchonJourney, a new online resource to support individuals and families living with achondroplasia, was launched. ACCEL 2/3 will be a global Phase 2/3 multicenter, single-dose study, to evaluate the efficacy and safety of 0.25mg/kg/day of infigratinib in children living with hypochondroplasia. ACCEL, BridgeBio’s observational lead-in study for hypochondroplasia, continues to enroll. BBP-812 – Adeno-associated virus (AAV) 9 gene therapy for Canavan disease: The Canavan disease program received RMAT Designation based on preliminary clinical evidence from the CANaspire Phase 1/2 clinical trial.BridgeBio will leverage the benefits of RMAT designation, including early and more frequent interactions with the FDA, to establish an Accelerated Approval pathway for BBP-812. New positive data from the high-dose cohort includes: Progressive and continued post-dose improvement in gross motor function (measured by Gross Motor Function Measure (GMFM)-88) and achievement of motor milestones (measured by Hammersmith Infant Neurological Examination (HINE)-2).In the low-dose cohort, these strikingly divergent trajectories resulted in statistically significant improvements in achieved motor function and milestones at 12-months after treatment with BBP-812, compared to what is observed in and predicted by the natural history of the disease seen in BridgeBio’s study, CANinform; data from the high dose cohort are not yet available. Third Quarter 2024 Financial Results: “We are prepared to launch acoramidis in the U.S., upon approval by the FDA, at the end of 2024 as well as to read out our three ongoing Phase 3 studies in 2025,” said Brian Stephenson, Ph.D., CFA, Chief Financial Officer of BridgeBio. “As we continue to move our late-stage pipeline forward, we are excited to also take an initial step in explaining the thesis and underlying logic of our decision making with the recent release of our case study in The Journal of Portfolio Management.” Cash, Cash Equivalents, and Short-term Restricted Cash Cash, cash equivalents and short-term restricted cash, totaled $405.7 million as of September 30, 2024, compared to $392.6 million of cash, cash equivalents and short-term restricted cash as of December 31, 2023. The $13.1 million net increase in cash, cash equivalents and short-term restricted cash was primarily attributable to net proceeds received from the term loan under the credit facility with Blue Owl of $434.0 million, net proceeds received from various equity financings of $314.7 million, proceeds from the sale of investments in equity securities of $63.2 million, and special cash dividends received from investments in equity securities of $25.7 million. These increases in cash, cash equivalents and short-term restricted cash were primarily offset by the impacts of refinancing the Company’s previous senior secured credit term loan, inclusive of prepayment fees and exit-related costs in aggregate of $473.4 million, net cash used in operating activities of $325.4 million, purchases of equity securities of $20.3 million, and repurchase of shares to satisfy tax withholdings of $6.1 million during the nine months ended September 30, 2024. Revenue Revenue for the three and nine months ended September 30, 2024 were $2.7 million and $216.0 million, respectively, as compared to $4.1 million and $7.6 million for the same periods in the prior year. The decrease of $1.4 million in revenue for the three months ended September 30, 2024, compared to the same period in the prior year, was primarily due to the recognition of services revenue under the exclusive license and collaboration agreements with Bayer and Kyowa Kirin. Revenue for the three months ended September 30, 2023 primarily consists of the recognition of services revenue under the Navire-BMS License Agreement, which terminated effective June 2024. The increase of $208.4 million in revenue for the nine months ended September 30, 2024, compared to the same period in the prior year, was primarily due to $205.3 million from recognition of non-refundable upfront payments and service revenue under the Bayer and the Kyowa Kirin exclusive license and collaboration agreements. Operating Costs and Expenses Operating costs and expenses for the three and nine months ended September 30, 2024 were $194.5 million and $583.0 million, respectively, compared to $161.8 million and $437.5 million for the same periods in the prior year. The overall increase of $32.7 million in operating costs and expenses for the three months ended September 30, 2024, compared to the same period in the prior year, was primarily due to an increase of $33.0 million in selling, general and administrative (SG&A) expenses mainly to support commercialization readiness efforts which included costs incurred for marketing, advertising and buildup of salesforce, an increase of $4.3 million in restructuring, impairment and related charges, offset by a decrease of $4.6 million in research and development and other expenses (R&D) mainly due to the deconsolidation of certain subsidiaries. The overall increase of $145.5 million in operating costs and expenses for the nine months ended September 30, 2024, compared to the same period in the prior year, was primarily due to an increase of $91.1 million in SG&A expenses mainly to support commercialization readiness efforts which included costs incurred for marketing, advertising and buildup of salesforce, an increase of $50.6 million in R&D expenses to advance the Company’s pipeline of research and development programs, and an increase of $3.8 million in restructuring, impairment and related charges. Operating costs and expenses for the nine months ended September 30, 2024, include $25.0 million of nonrecurring deal-related costs for transactions that were completed during the nine months ended September 30, 2024. Restructuring, impairment and related charges for the three and nine months ended September 30, 2024 amounted to $4.6 million and $10.9 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. Restructuring, impairment and related charges for the same periods in the prior year were $0.3 million and $7.2 million, respectively. These charges primarily consisted of winding down, exit costs, and severance and employee-related costs. Stock-based compensation expenses included in operating costs and expenses for the three months ended September 30, 2024 were $27.1 million, of which $12.1 million is included in R&D expenses, $15.0 million is included in SG&A expenses, and less than $0.1 million is included in restructuring, impairment and related charges. Stock-based compensation expenses included in operating costs and expenses for the same period in the prior year were $27.2 million, of which $14.1 million is included in R&D expenses, and $13.1 million is included in SG&A expenses. Stock-based compensation expenses included in operating costs and expenses for the nine months ended September 30, 2024 were $77.4 million, of which $29.8 million is included in R&D expenses, $47.5 million is included in SG&A expenses, and $0.1 million is included in restructuring, impairment and related charges. Stock-based compensation expenses included in operating costs and expenses for the same period in the prior year were $77.9 million, of which $39.2 million is included in R&D expenses, and $38.7 million is included in SG&A expenses. Total Other Income (Expense), net Total other income (expense), net for the three and nine months ended September 30, 2024 were $27.5 million and $91.0 million, respectively, compared to ($21.8) million and ($53.0) million for the same periods in the prior year. The increase in total other income (expense), net of $49.3 million for the three months ended September 30, 2024, compared to the same period in the prior year, was primarily due to the Company’s gain on deconsolidation of subsidiaries of $52.0 million and an increase in other income (expense), net of $7.1 million mainly due to mark to market fair value adjustments from the Company’s investments in equity securities. This was partially offset by a net loss from an equity method investment of $6.6 million and an increase in interest expense of $2.8 million. The increase in total other income (expense), net of $144.0 million for the nine months ended September 30, 2024, compared to the same period in the prior year, was primarily due to the Company’s gain on deconsolidation of subsidiaries of $178.3 million and an increase in other income (expense), net of $15.1 million mainly due to mark to market fair value adjustments from the Company’s investments in equity securities. These were partially offset by recognition of a loss on extinguishment of debt of $26.6 million, a net loss from equity method investments of $14.5 million and an increase in interest expense of $8.4 million. Net Loss Attributable to Common Stockholders of BridgeBio and Net Loss per Share For the three and nine months ended September 30, 2024, the Company recorded a net loss attributable to common stockholders of BridgeBio of $162.0 million and $270.7 million, respectively, compared to $177.0 million and $475.1 million, respectively for the three and nine months ended September 30, 2023. For the three and nine months ended September 30, 2024, the Company reported a net loss per share of $0.86 and $1.46, respectively compared to $1.08 and $2.99, respectively for the three and nine months ended September 30, 2023. BRIDGEBIO PHARMA, INC. Condensed Consolidated Statements of Operations (in thousands, except shares and per share amounts) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 (Unaudited) (Unaudited) Revenue $2,732 $4,091 $216,020 $7,558 Operating costs and expenses: Research, development and other expenses 121,042 125,734 377,905 327,333 Selling, general and administrative 68,819 35,777 194,149 103,007 Restructuring, impairment and related charges 4,621 272 10,912 7,172 Total operating costs and expenses 194,482 161,783 582,966 437,512 Loss from operations (191,750) (157,692) (366,946) (429,954)Other income (expense), net: Interest income 3,296 3,793 12,566 12,460 Interest expense (23,061) (20,306) (69,469) (61,021)Gain on deconsolidation of subsidiaries 52,027 — 178,321 — Loss on extinguishment of debt — — (26,590) — Net loss from equity method investments (6,563) — (14,488) — Other income (expense), net 1,797 (5,283) 10,648 (4,408)Total other income (expense), net 27,496 (21,796) 90,988 (52,969)Net loss (164,254) (179,488) (275,958) (482,923)Net loss attributable to redeemable convertible noncontrolling interests and noncontrolling interests 2,214 2,489 5,246 7,869 Net loss attributable to common stockholders of BridgeBio $(162,040) $(176,999) $(270,712) $(475,054)Net loss per share, basic and diluted $(0.86) $(1.08) $(1.46) $(2.99)Weighted-average shares used in computing net loss per share, basic and diluted 188,510,372 163,308,632 184,947,173 158,891,152 Three Months Ended September 30, Nine Months Ended September 30, Stock-based Compensation 2024 2023 2024 2023 (Unaudited) (Unaudited) Research, development and other expenses $12,124 $14,144 $29,840 $39,152 Selling, general and administrative 14,969 13,086 47,511 38,731 Restructuring, impairment and related charges 38 — 81 — Total stock-based compensation $27,131 $27,230 $77,432 $77,883 BRIDGEBIO PHARMA, INC. Condensed Consolidated Balance Sheets (In thousands) September 30, December 31, 2024 2023 Assets (Unaudited) (1) Cash and cash equivalents $266,324 $375,935 Investments in equity securities — 58,949 Receivables from licensing and collaboration agreements 478 1,751 Short-term restricted cash 139,409 16,653 Prepaid expenses and other current assets 38,367 24,305 Investment in nonconsolidated entities 160,443 — Property and equipment, net 8,701 11,816 Operating lease right-of-use assets 6,439 8,027 Intangible assets, net 24,525 26,319 Other assets 20,291 22,625 Total assets $664,977 $546,380 Liabilities, Redeemable Convertible Noncontrolling Interests and Stockholders’ Deficit Accounts payable $13,363 $10,655 Accrued and other liabilities 109,482 122,965 Operating lease liabilities 10,433 13,109 Deferred revenue 30,398 9,823 2029 Notes, net 738,376 736,905 2027 Notes, net 544,719 543,379 Term loan, net 436,221 446,445 Other long-term liabilities 377 5,634 Redeemable convertible noncontrolling interests 645 478 Total BridgeBio stockholders' deficit (1,229,922) (1,354,257)Noncontrolling interests 10,885 11,244 Total liabilities, redeemable convertible noncontrolling interests and stockholders’ deficit $664,977 $546,380 (1)The condensed consolidated financial statements as of and for the year ended December 31, 2023 are derived from the audited consolidated financial statements as of that date. BRIDGEBIO PHARMA, INC. Condensed Consolidated Statements of Cash Flows (Unaudited) (In thousands) Nine Months Ended September 30, 2024 2023 Operating activities: Net loss $(275,958) $(482,923)Adjustments to reconcile net loss to net cash used in operating activities: Stock-based compensation 65,673 71,685 Loss on extinguishment of debt 26,590 — Accretion of debt 5,399 6,724 Depreciation and amortization 4,708 4,909 Noncash lease expense 3,119 3,024 Accrual of payment-in-kind interest on term loan — 6,742 Net loss from equity method investments 14,488 — Loss (gain) on deconsolidation of subsidiaries (178,321) 1,241 Loss (gain) from investment in equity securities, net (8,136) 2,951 Other noncash adjustments, net (2,059) (332)Changes in operating assets and liabilities: Receivables from licensing and collaboration agreements 1,273 11,909 Prepaid expenses and other current assets (17,543) (980)Other assets (428) 1,443 Accounts payable 5,257 (3,404)Accrued compensation and benefits 5,580 (4,156)Accrued research and development liabilities 15,454 (10,544)Operating lease liabilities (4,459) (3,671)Deferred revenue 20,575 (4,464)Accrued professional and other liabilities (6,612) (3,055)Net cash used in operating activities (325,400) (402,901)Investing activities: Purchases of marketable securities (93,811) (29,726)Maturities of marketable securities 95,000 82,550 Purchases of investments in equity securities (20,271) (78,314)Proceeds from sales of investments in equity securities 63,229 80,963 Proceeds from special cash dividends received from investments in equity securities 25,682 — Payment for an intangible asset (4,785) — Purchases of property and equipment (886) (871)Decrease in cash and cash equivalents resulting from deconsolidation of subsidiaries (140) (503)Net cash provided by investing activities 64,018 54,099 Financing activities: Proceeds from term loan under Financing Agreement 450,000 — Issuance costs and discounts associated with term loan under Financing Agreement (15,986) — Repayment of term loan under Loan and Security Agreement (473,417) — Proceeds from issuance of common stock through public offerings, net 314,741 450,264 Proceeds from BridgeBio common stock issuances under ESPP 4,502 3,397 Proceeds from stock option exercises, net of repurchases 808 5,222 Transactions with noncontrolling interests — 1,500 Repurchase of RSU shares to satisfy tax withholding (6,122) (4,325)Net cash provided by financing activities 274,526 456,058 Net increase in cash, cash equivalents and restricted cash 13,144 107,256 Cash, cash equivalents and restricted cash at beginning of period 394,732 416,884 Cash, cash equivalents and restricted cash at end of period $407,876 $524,140 Nine Months Ended September 30, 2024 2023 Supplemental Disclosure of Cash Flow Information: Cash paid for interest $78,236 $50,826 Supplemental Disclosures of Noncash Investing and Financing Information: Unpaid public offering issuance costs $— $455 Unpaid property and equipment $274 $192 Transfers to noncontrolling interests $(4,719) $(8,313)Reconciliation of Cash, Cash Equivalents and Restricted Cash: Cash and cash equivalents $266,324 $505,213 Restricted cash 139,409 16,652 Restricted cash — Included in “Other assets” 2,143 2,275 Total cash, cash equivalents and restricted cash at end of period shown in the condensed consolidated statements of cash flows $407,876 $524,140 About BridgeBio Pharma, Inc.BridgeBio Pharma (BridgeBio) is a new type of biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases. 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, Twitter and Facebook.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,” “continues,” “estimates,” “expects,” “hopes,” “intends,” “may,” “plans,” “projects,” “remains,” “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 express and implied statements relating to the Company’s clinical trials, including the PDUFA approval date for acoramidis for the treatment of ATTR-CM; timing to share data from the long-term open-label extension of ATTRibute-CM; the potential to receive payments of $500 million and $105 million upon approval of acoramidis; providing U.S. clinical trial patients acoramidis free for life, upon approval; timing for completion of enrollment in PROPEL 3 and completion of the study; timing for sharing top-line results from FORTIFY for the interim analysis population; the potential to pursue Accelerated Approval in the U.S. for ribitol in LGMD2I/R9; the Company’s ability to qualify for a Priority Review Voucher with respect to ribitol; timing for completion of enrollment in CALIBRATE; and the expectation of early and more frequent interactions with the FDA relating to BBP-812 for the treatment of Canavan disease, among others, reflect the Company’s current views about the Company’s plans, intentions, expectations and strategies, which are based on the information currently available to us and on assumptions the Company has made. Although the Company believes that its plans, intentions, expectations and strategies as reflected in or suggested by those forward-looking statements are reasonable, the Company 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 the Company’s preclinical studies and clinical trials not being indicative of final data, the potential size of the target patient populations the Company’s 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 the Company’s product candidates, the FDA or such other regulatory agencies not agreeing with the Company’s regulatory approval strategies, components of the Company’s filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted, the continuing success of the Company’s collaborations, the Company’s ability to obtain additional funding, including through less dilutive sources of capital than equity financings, potential volatility in the Company’s share price, the impacts of current macroeconomic and geopolitical events, including changing conditions from hostilities in Ukraine and in Israel and the Gaza Strip, increasing rates of inflation and changing interest rates, on business operations and expectations, as well as those risks set forth in the Risk Factors section of the Company’s most recent Quarterly Report on Form 10-Q and Annual Report on Form 10-K and the Company’s other filings with the U.S. Securities and Exchange Commission. Moreover, the Company 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 the Company’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, BridgeBio assumes 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

▎药明康德内容团队编辑 近期，全球细胞和基因疗法（CGT）领域迎来系列进展。用于治疗法布里病的在研基因疗法isaralgagene civaparvovec有望提前3年在美国获批上市。REGENXBIO公司与艾伯维（AbbVie）联合开发的ABBV-RGX-314有望成为首个治疗慢性视网膜疾病的基因疗法，在一项2期临床试验中使78%接受治疗的湿性年龄相关性黄斑变性（AMD）患者在治疗9个月后仍无需补充注射抗血管内皮生长因子（VEGF）抗体。基因编辑疗法NTLA-2002治疗遗传性血管水肿（HAE）患者的1/2期临床试验结果亮眼，单次给药使患者平均每月HAE发作率与安慰剂相比减少达81%。本文将节选其中部分重要进展做简单介绍，仅供读者参阅。 图片来源：123RF ———✦研发进展✦——— ◇ Sangamo Therapeutics宣布已与美国FDA就其在研基因疗法isaralgagene civaparvovec（ST-920）用于治疗法布里病的加速批准监管途径达成共识。FDA同意正在进行的1/2期STAAR研究的数据可以作为该疗法获得加速批准的主要依据，并将所有患者52周的估算肾小球滤过率（eGFR）斜率作为中间临床终点。Sangamo预计，支持加速批准的完整数据集将在2025年上半年完成，并计划于2025年下半年提交生物制品许可申请（BLA）。如果获批，将会比预期的批准时间提前三年，且无需进行额外的注册性研究。Sangamo已开始为isaralgagene civaparvovec的上市申请进行准备工作。 Isaralgagene civaparvovec是一种以重组腺相关病毒2/6（AAV2/6）为载体的基因疗法，将表达α-半乳糖苷酶A的GLA基因递送到肝脏，旨在通过一次性治疗获得持久疗效，减轻法布里病的标准治疗酶替代疗法（ERT）的输注负担。接受该疗法的患者不需要预处理。在STAAR研究中，在18名接受isaralgagene civaparvovec治疗并有超过一年随访数据的男女患者中，观察到平均和中位eGFR水平的显著改善，年化eGFR斜率呈现积极趋势。不仅如此，截至目前，所有18名患者均不再使用ERT。 ◇ REGENXBIO公司公布了其与艾伯维联合开发的在研基因疗法ABBV-RGX-314在双眼湿性年龄相关性黄斑变性患者中进行的2期研究的积极数据。数据显示，在接受ABBV-RGX-314治疗9个月后，患者的治疗负担减少了97%。100%的患者只需零次或一次补充抗VEGF抗体注射，78%的患者完全无需注射。根据公司网站，ABBV-RGX-314有望成为首个治疗慢性视网膜疾病的基因疗法。 ABBV-RGX-314使用AAV8载体携带表达抗VEGF抗体片段的转基因，在体内表达的蛋白通过阻断VEGF信号传导，抑制心血生成和视网膜液体聚集。在治疗湿性AMD之外，两家公司也在探索ABBV-RGX-314治疗糖尿病视网膜病变和其他慢性视网膜疾病的潜力。 ◇ Intellia Therapeutics公司公布了其在研体内CRISPR基因编辑疗法NTLA-2002用于治疗遗传性血管水肿患者的1/2期临床试验的2期部分积极数据。结果显示，在第5至16周期间，单次输注50 mg NTLA-2002可使患者平均每月HAE发作率与安慰剂相比减少达81%。目前该疗法的全球关键性3期HAELO研究正在进行中。 NTLA-2002通过脂质纳米颗粒（LNP）以mRNA形式递送CRISPR-Cas9基因编辑系统，靶向血浆前激肽释放酶（KLKB1）基因，使该蛋白失活以永久性降低血浆中激肽释放酶活性，从而防止遗传性血管水肿的发作。根据新闻稿，NTLA-2002有望成为首个针对HAE的一次性治疗方案。 ◇ Spur Therapeutics公司公布了其用于治疗1型戈谢病的候选基因疗法FLT201的1/2期GALILEO-1试验的最新积极数据。结果显示，单次输注FLT201治疗的患者体内葡萄糖基神经酰胺（lyso-Gb1，戈谢病临床缓解的最佳预测指标之一）和骨髓负担持续降低，血细胞计数和器官容积得到改善或维持。在这项研究中接受治疗的所有患者中，FLT201继续表现出良好的安全性和耐受性。 FLT201是一种AAV基因疗法，用于治疗1型戈谢病成年患者。该疗法旨在提供一次性治疗，以持续增加患者体内GCase表达并减少有害底物的积累，阻止疾病进展，让患者不必终生接受治疗。FLT201采用Freeline的AAVS3衣壳，将新型基因引入肝细胞，生产经过理性设计的GCase变体。临床前和临床数据显示，FLT201的表达稳健而持久，并且由于酶缺乏而导致的底物毒性积累显著减少。 ◇ BridgeBio Pharma公司公布了其用于治疗卡纳万病（Canavan disease）的在研AAV9基因疗法BBP-812在CANaspire1/2期临床试验中的初步阳性数据。与该公司正在进行的CANinform自然史比较研究中观察到的疾病进程相比，接受BBP-812治疗后12个月时，患者运动功能的持续、渐进改善和运动里程碑的实现代表了重要的、具有统计学意义的变化。所有接受低剂量治疗患者的尿液、脑脊液和大脑中的N-乙酰天冬氨酸（NAA）水平显著、持续降低，接受高剂量BBP-812治疗患者尿液中的NAA水平呈进一步下降趋势。 卡纳万病是一种由编码天冬氨酸酶的ASPA基因突变引起的超罕见、可致残或致命的疾病。BBP-812能够将ASPA基因的功能拷贝递送到全身并进入大脑，从而可能根治疾病。新闻稿指出，如果获得批准，BBP-812有望成为患有卡纳万病这种先天性致命神经发育障碍的患儿的首个治疗方案。 ◇ Interius BioTherapeutics公司宣布已在一项1期临床试验中为首例B细胞恶性肿瘤患者提供其在研基因疗法INT2104。INT2104是一种慢病毒载体基因疗法，设计靶向CD7阳性的T细胞和NK细胞，并递送嵌合抗原受体（CAR）转基因，以在体内生成效应CAR-T和CAR-NK细胞。这些CAR细胞靶向CD20阳性B细胞，用于治疗B细胞恶性肿瘤。与体外CAR-T疗法不同，INT2104是一种现货型的单剂量疗法，可通过静脉输注系统性给药，患者无需进行淋巴清除，治疗时不需要任何特殊设备或人员培训。根据行业媒体STAT报道，INT2104是首个进入人体临床试验的体内CAR-T疗法。 ◇ Precision BioSciences公司宣布，其主打在研体内基因编辑疗法PBGENE-HBV的临床试验申请（CTA）已获得摩尔多瓦（Moldova）的监管单位批准。PBGENE-HBV旨在通过消除乙型肝炎病毒（HBV）的共价闭合环状DNA（cccDNA），同时灭活整合在肝细胞中的HBV DNA，以达到功能性治愈慢性乙型肝炎的目的。该公司已启动1期临床项目，并准备进行患者给药。Precision公司预计向全球监管单位提交更多的CTA和IND申请。根据新闻稿，PBGENE-HBV是进入临床阶段的首个靶向HBV的体内基因编辑疗法。 ◇ 艾尔普再生医学宣布FDA批准了其自主研发的新一代细胞疗法“人诱导多能干细胞（iPSC）来源心肌细胞注射液”（HiCM-188）用于治疗终末期心力衰竭的IND申请。新闻稿指出，HiCM-188是首个在美国接受用于治疗终末期心力衰竭临床评估的iPSC衍生细胞创新药。该候选疗法此前已在中国获准临床试验，并取得安全性及有效性结果。 ◇ 中国国家药监局药品审评中心（CDE）官网公示，贝斯昂科生物1类新药NK510细胞注射液获批临床，拟开发用于经标准治疗失败的晚期恶性实体瘤。新闻稿指出，在产品研发过程中，NK510采用了零脱靶碱基编辑器AccuBase，对NK细胞中关键基因进行了精确修改，编辑效率超过90%。研究表明，NK510既能克服癌细胞的免疫逃逸，又能特异性地识别和杀伤癌细胞，在多项体外、体内实验中展现出强大的抗肿瘤能力。 ◇ CDE官网公示，原启生物自主研发的双靶点Claudin 18.2/MSLN自体CAR-T细胞疗法OriC613注射液获批临床，拟开发治疗晚期实体瘤。根据原启生物新闻稿介绍，OriC613采用“AND”逻辑门控设计，通过拆分二代CAR结构元件，使OriC613 CAR-T细胞表面并联表达针对MSLN和Claudin 18.2的嵌合抗原受体，且仅对同时表达两个抗原的肿瘤细胞产生应答，从而能在增加肿瘤靶向杀伤活性的同时降低非肿瘤靶向毒性（OTOT），提高临床安全性。 ———✦融资、合作、M&A✦——— 图片来源：123RF ◇ AvenCell Therapeutics公司宣布完成1.12亿美元的B轮融资，此次融资所获得的资金将用于继续验证AvenCell的专有可控通用CAR-T细胞疗法平台，该平台产生的CAR-T细胞即使在患者接受治疗后也可以快速“关闭”和“打开”。与传统细胞疗法相比，该通用平台旨在更安全、更有效地治疗多种血液系统恶性肿瘤。 目前，AvenCell的临床管线包括一种高度差异化的自体CAR-T细胞疗法AVC-101，和一种通过CRISPR改造的异体CAR-T细胞疗法AVC-201，这两种管线均靶向急性髓系白血病（AML）细胞上常见的CD123抗原。这两款候选疗法已在早期临床试验中显示出令人鼓舞的安全性和疗效。此外，AvenCell有多个管线候选药物将在未来两年进入临床阶段。 ◇ 致力于开发B细胞疗法的Be Biopharma公司宣布完成8200万美元的融资，获得的资金将用于实现其用于治疗血友病B的主打项目BE-101的临床概念验证，并推进其用于治疗低磷酸酶症（HPP）的候选药物BE-102的开发。这两个项目均基于该公司强大且高效的B细胞药物（BCM）平台，该平台利用基因编辑技术改造B细胞，使其能够持续产生治疗性蛋白质，最终开发出具有持久性、可滴定且可重复给药的候选药物，无需预处理，具有成为潜在“best-in-class”基因疗法的潜力。 ◇ March Biosciences公司宣布成功完成超额认购的2840万美元A轮融资，获得资金将用于支持其主打在研自体CAR-T细胞疗法MB-105的2期临床开发，并进一步优化生产工艺。MB-105旨在治疗复发性和难治性CD5阳性T细胞淋巴瘤。MB-105专门设计用于克服与T细胞靶向相关的主要障碍，在解决T细胞同类相杀问题同时，保持对CD5阳性肿瘤细胞的高效杀伤力。MB-105在贝勒医学院（Baylor College of Medicine）进行的一项针对复发性T细胞淋巴瘤患者的1期临床试验中显示出良好的安全性和持久的缓解效果。该公司计划于2025年初开始2期临床试验。 ◇ 士泽生物宣布完成逾亿元B1轮市场化融资，至此，该公司近2年内已完成逾3亿元A轮/A+轮/B1轮融资。新闻稿指出，本轮融资将用于士泽生物临床级iPS衍生细胞药治疗神经系统疾病管线的完善、进一步开展临床研究以及推进多项注册临床试验。 该公司自研设计并建立了底层技术平台，覆盖iPSC重编程与建库、基因编辑iPSC、iPSC分化为亚型特化的神经细胞及临床前疾病动物模型的构建及评价等关键技术平台，并与多家知名研究机构及医院开展技术研究及临床开发合作。目前，士泽生物的自研临床级iPS衍生细胞药已在渐冻症和帕金森病患者中取得进展。其中，用于治疗帕金森病的iPS衍生多巴胺能神经前体细胞在多个临床案例中显示出了良好的安全性和有效性，患者症状有显著改善趋势，且未出现细胞疗法相关不良事件。 ◇ 利用人工智能（AI）推动体内基因递送的生物技术公司Dyno Therapeutics宣布与罗氏（Roche）达成第二项研究合作，开发针对神经疾病的下一代AAV载体基因疗法。Dyno和罗氏此前于2020年10月宣布了一项针对神经疾病和肝脏定向疗法的研究合作与许可协议。 根据此次新合作协议，Dyno将负责设计和发现具有改进功能特性的全新AAV衣壳。罗氏则负责进行衣壳验证研究，并推进多个神经基因疗法候选产品的临床前、临床期及商业化活动，这些产品均利用了Dyno开发的创新衣壳。罗氏将向Dyno支付5000万美元的预付款，此外在研究阶段还会进行额外付款，并有望根据临床前、临床期和销售里程碑支付总计超过10亿美元的款项。 ◇ Lyell Immunopharma公司宣布，已达成收购ImmPACT Bio公司的最终协议。ImmPACT公司的主打项目IMPT-314是一种CD19/20靶向CAR－T细胞候选产品，Lyell公司将继续开发该产品用于治疗血液恶性肿瘤，包括大B细胞淋巴瘤。新闻稿指出，收购ImmPACT公司预计将大大加强Lyell公司处于临床阶段的下一代CAR－T细胞疗法产品线，并补充其专有技术套件，这些技术旨在生成更持久的功能性T细胞，为实体瘤和血液系统恶性肿瘤患者带来更持久的疗效。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料（可上下滑动查看） [1] Sangamo Therapeutics Announces Alignment With FDA on Accelerated Approval Pathway for ST-920 in Fabry Disease With BLA Submission Expected in 2025. Retrieved October 23, 2024, from https://investor.sangamo.com/news-releases/news-release-details/sangamo-therapeutics-announces-alignment-fda-accelerated [2] REGENXBIO Presents Positive Data from the Phase II Study of Subretinal ABBV-RGX-314 in Patients with Bilateral Wet AMD at AAO 2024. Retrieved October 21, 2024, from https://ir.regenxbio.com/news-releases/news-release-details/regenxbio-presents-positive-data-phase-ii-study-subretinal-abbv [3] 世界首款碱基编辑NK细胞产品临床试验申请获得受理. Retrieved July 30, 2024, from https://mp.weixin.qq.com/s/_jnzmCZrRSi7pbSDHlUWSA [4] Spur Therapeutics Showcases Positive New Data from Phase 1/2 GALILEO-1 Trial of FLT201, Its Novel Gene Therapy Candidate for Gaucher Disease, in Oral Presentation at ESGCT 31st Annual Congress. Retrieved October 25, 2024, from https://www.globenewswire.com/news-release/2024/10/23/2967469/0/en/Spur-Therapeutics-Showcases-Positive-New-Data-from-Phase-1-2-GALILEO-1-Trial-of-FLT201-Its-Novel-Gene-Therapy-Candidate-for-Gaucher-Disease-in-Oral-Presentation-at-ESGCT-31st-Annua.html [5] Interius BioTherapeutics Doses First Patient with in vivo Chimeric Antigen Receptor (CAR) Gene Therapy for B-cell Malignancies. Retrieved October 25, 2024, from https://interiusbio.com/2024/10/interius-biotherapeutics-doses-first-patient-with-in-vivo-chimeric-antigen-receptor-car-gene-therapy-for-b-cell-malignancies/ [6] 重大突破！艾尔普再生医学新一代细胞创新药临床IND获美国FDA批准. Retrieved October 25, 2024, from https://mp.weixin.qq.com/s/sNs5TT0emP4ns_CysiWNQw [7] 原启生物宣布双靶点MSLN/Claudin 18.2 OriC613注射液新药临床试验（IND）申请获中国NMPA批准. Retrieved October 17, 2024, from https://www.oricell.com/newsdetail/id/40.html [8] AvenCell Raises $112 Million in Series B; Funding Led by Novo Holdings. Retrieved October 22, 2024 from https://avencell.com/avencell-raises-112-million-in-series-b-funding-led-by-novo-holdings/ [9] Be Bio Announces $82 Million Financing and Transition to Clinical Stage Company. Retrieved October 22, 2024, from https://www.businesswire.com/news/home/20241022283327/en [10] March Biosciences Closes Oversubscribed $28.4 Million Series A Financing. Retrieved October 23, 2024, from https://www.globenewswire.com/news-release/2024/10/23/2967726/0/en/March-Biosciences-Closes-Oversubscribed-28-4-Million-Series-A-Financing.html [11] 士泽生物完成超亿元B1轮融资，推进临床级iPS衍生细胞药治疗神经系统疾病管线. Retrieved October 25, 2024, from https://mp.weixin.qq.com/s/R4wXpGtrxhwkVnRDbwV4ZA [12] BridgeBio Shares Positive Data from High Dose Cohort of Phase 1/2 CANaspire Study of Gene Therapy BBP-812 for Canavan Disease at ESGCT 2024. Retrieved October 25, 2024, from https://www.globenewswire.com/news-release/2024/10/24/2968601/0/en/BridgeBio-Shares-Positive-Data-from-High-Dose-Cohort-of-Phase-1-2-CANaspire-Study-of-Gene-Therapy-BBP-812-for-Canavan-Disease-at-ESGCT-2024.html [13] Precision BioSciences Receives First Approval of Clinical Trial Application to Initiate PBGENE-HBV First-In-Human Study for the Treatment of Chronic Hepatitis B. Retrieved October 24, 2024, from https://investor.precisionbiosciences.com/news-releases/news-release-details/precision-biosciences-receives-first-approval-clinical-trial [14] Intellia Presents Positive Results from the Phase 2 Study of NTLA-2002, an Investigational In Vivo CRISPR Gene Editing Treatment for Hereditary Angioedema (HAE). Retrieved October 24, 2024 from https://ir.intelliatx.com/news-releases/news-release-details/intellia-presents-positive-results-phase-2-study-ntla-2002 [15] Dyno Therapeutics Forms New Strategic Partnership With Roche To Advance AAV Gene Therapy Vectors For Neurological Diseases. Retrieved October 24, 2024, from https://www.dynotx.com/dyno-therapeutics-forms-new-strategic-partnership-with-roche-to-advance-aav-gene-therapy-vectors-for-neurological-diseases/ [16] Lyell Immunopharma to Acquire ImmPACT Bio and Prioritizes its Pipeline to Focus on Next-Generation CAR T-cell Therapies. Retrieved October 24, 2024, from https://www.globenewswire.com/news-release/2024/10/24/2969054/0/en/Lyell-Immunopharma-to-Acquire-ImmPACT-Bio-and-Prioritizes-its-Pipeline-to-Focus-on-Next-Generation-CAR-T-cell-Therapies.html a-Therapeutics-and-Factor-Bioscience-Announce-Exclusive-License-and-Collaboration-Agreement-to-Accelerate-Cell-Therapy-Development-for-Oncology-Autoimmune-and-Rare-Diseases.html [12] 因诺惟康IVB103注射液获得CDE临床许可. Retrieved October 18, 2024, from https://mp.weixin.qq.com/s/OU_bxfT9u4a_-Cs6WreoDQ 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新