Birtamimab

DUBLIN--(BUSINESS WIRE)-- Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, today announced the publication related to the mechanism of action, pharmacological characteristics, and clinical utility of birtamimab, a potential best-in-class anti-amyloid treatment for AL amyloidosis. The publication can be found in the latest issue of Leukemia & Lymphoma, an international peer-reviewed journal that publishes research on all aspects of hematological malignancies. AL amyloidosis is an idiopathic, rare, progressive and often fatal disease characterized by amyloid deposits that build up in vital organs leading to damage, dysfunction and failure. The risk of early mortality is especially high in patients with significant cardiac involvement as there are no current treatment options that target existing amyloid deposits in these patients. Birtamimab binds to a highly conserved cryptic epitope which is only exposed in misfolded kappa and lambda light chain (LC) protein. Birtamimab binds and neutralizes soluble, toxic LC aggregates and binds and clears insoluble AL amyloid deposits, without affecting normally folded LC proteins. This mechanism of action is complementary to the current standard of care therapy for AL amyloidosis which does not target the existing toxic LC aggregates and amyloid deposits. “Birtamimab was designed to clear deposited amyloid from vital organs and is the only treatment that has shown a significant survival benefit in patients with Mayo Stage IV AL amyloidosis, which was demonstrated in a post hoc analysis of the Phase 3 VITAL placebo-controlled clinical trial,” said Hideki Garren, M.D., Ph.D., Chief Medical Officer, Prothena. “Birtamimab is being evaluated in patients with Mayo Stage IV AL amyloidosis, who are at high risk of early mortality, in the ongoing confirmatory Phase 3 AFFIRM-AL clinical trial.” A copy of the peer-reviewed article can be found here in Leukemia & Lymphoma: About Birtamimab Birtamimab is an investigational, humanized monoclonal antibody designed to specifically and selectively target and clear the amyloid that accumulates and causes organ dysfunction and failure in patients with AL amyloidosis. Birtamimab specifically binds to a defined epitope on kappa and lambda AL protein involved in the disease process. Birtamimab is the only investigational drug that has shown a significant survival benefit in patients with Mayo Stage IV AL amyloidosis post-hoc in a placebo-controlled clinical trial. Birtamimab has been granted orphan drug designation for AL amyloidosis by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency and has been granted Fast Track designation by the FDA. A Special Protocol Assessment (SPA) was agreed to between Prothena and the FDA for the AFFIRM-AL clinical trial which represents FDA’s agreement that the design and planned analysis for the primary endpoint of time to all-cause mortality adequately address the objectives necessary to support a regulatory submission. Results from confirmatory Phase 3 AFFIRM-AL clinical trial are expected between 4Q 2024 and 2Q 2025 (NCT04973137). Final marketing approval is predicated upon FDA’s complete review of the entire application. About Prothena Prothena Corporation plc is a late-stage clinical biotechnology company with expertise in protein dysregulation and a pipeline of investigational therapeutics with the potential to change the course of devastating neurodegenerative and rare peripheral amyloid diseases. Fueled by its deep scientific expertise built over decades of research, Prothena is advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which its ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. Prothena’s pipeline includes both wholly-owned and partnered programs being developed for the potential treatment of diseases including AL amyloidosis, ATTR amyloidosis, Alzheimer’s disease, Parkinson’s disease and a number of other neurodegenerative diseases. For more information, please visit the Company’s website at and follow the Company on Twitter @ProthenaCorp. View source version on businesswire.com: Contacts Media Michael Bachner, Senior Director, Corporate Communications 609-664-7308, michael.bachner@prothena.com Investors Mark Johnson, CFA, Vice President, Investor Relations 650-417-1974, mark.johnson@prothena.com Source: Prothena Corporation plc View this news release online at:

Net cash used in operating and investing activities was $52.6 million in the fourth quarter and $136.7 million for the full year of 2023; quarter-end cash and restricted cash position was $621.0 million The company expects cash guidance for the full year 2024 net cash used in operating and investing activities to be $208 to $225 million and expects to end the year with approximately $405 million in cash (midpoint) Advanced potential best-in-class Alzheimer’s disease portfolio in 2023: initial data supportive of ongoing Phase 1 clinical trial for PRX012, an anti-amyloid beta antibody; received FDA clearance for IND application and Fast Track designation for PRX123, a dual amyloid beta/tau vaccine; reported Phase 1 data for BMS-986446 (formerly PRX005), an anti-tau antibody, data supports moving into a Phase 2 clinical trial by partner Bristol Myers Squibb Strengthened leadership position in the amyloidosis community with ongoing enrollment of the confirmatory Phase 3 AFFIRM-AL clinical trial of birtamimab in patients with Mayo Stage IV AL amyloidosis; published Phase 3 VITAL clinical trial data in Blood, the peer-reviewed journal of ASH Received $55 million milestone payment from Bristol Myers Squibb in July 2023 for exclusive worldwide license to BMS-986446 (formerly PRX005) DUBLIN--(BUSINESS WIRE)-- Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, today reported financial results for the fourth quarter and full year 2023. In addition, the Company provided 2024 financial guidance and business highlights. “2023 was a year of strong progress for Prothena as we advanced our protein dysregulation portfolio and moved closer to becoming a fully integrated commercial company. The next 12 to 18 months have the potential to transform Prothena with multiple upcoming clinical readouts across our robust portfolio,” said Gene Kinney, Ph.D., President and Chief Executive Officer, Prothena. “We continue to advance our confirmatory Phase 3 AFFIRM-AL clinical trial for birtamimab and for PRX012 are evaluating multiple dose level cohorts in our ongoing Phase 1 clinical trial. In addition, we ended the year with IND clearances by the FDA for both PRX123 and PRX019, including Fast Track designation for PRX123. As we continue to grow our leadership at Prothena, we also appointed the founding, former Director of the FDA CDER Office of Neuroscience, Dr. Billy Dunn, to our board of directors. Dr. Dunn brings immeasurable regulatory and clinical development expertise, combined with a passion for helping patients, which will greatly benefit the millions of people affected by diseases caused by protein dysregulation. Lastly, Prothena remains well financed with sufficient capital to ensure funding of activities beyond the completion of ongoing clinical trials.” 2023 Business Highlights and Upcoming Milestones Neurodegenerative Diseases Portfolio Alzheimer’s Disease PRX012, a wholly-owned potential best-in-class, next-generation subcutaneous antibody for the treatment of Alzheimer’s disease that targets a key epitope at the N-terminus of amyloid beta (Aβ) with high binding potency. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for PRX012 for the treatment of Alzheimer’s disease. Presented two preclinical studies at AD/PD in March 2023 and AAIC in July 2023 showing superior binding characteristics of PRX012 Partnered with Walgreens in April 2023 to accelerate patient identification and recruitment for ongoing ASCENT-2 clinical trial Initial Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) data supports once-monthly subcutaneous administration and ongoing evaluation in MAD cohorts Ongoing Phase 1 clinical trial continues as planned and expect to update in 2024 BMS-986446 (formerly PRX005), a potential best-in-class antibody for the treatment of Alzheimer’s disease that specifically targets a key epitope within the microtubule binding region (MTBR) of tau, a protein implicated in the causal pathophysiology of Alzheimer’s disease. BMS-986446 is part of a Global Neuroscience Research and Development Collaboration with Bristol Myers Squibb. Presented Phase 1 clinical trial SAD results in a poster presentation at AAIC in July 2023 showing that all three tested dose levels (low, medium, high) of PRX005 were considered generally safe and well tolerated, meeting the primary objective of this part of the clinical trial and supporting evaluation of doses in the ongoing MAD portion of this two-part clinical trial Bristol Myers Squibb paid $55 million for exclusive worldwide rights for PRX005 in July 2023 under the Global Neuroscience Research and Development Collaboration Bristol Myers Squibb will be responsible for future development, manufacturing, and commercialization of BMS-986446 Bristol Myers Squibb reported that Phase 1 data supports moving BMS-986446 into a Phase 2 clinical trial in 1H 2024 PRX123, a wholly-owned potential first-in-class dual Aβ/tau vaccine designed for the treatment and prevention of Alzheimer’s disease, is a dual-target vaccine targeting key epitopes within the N-terminus of Aβ and MTBR-tau designed to promote amyloid clearance and block the transmission of pathogenic tau Presented preclinical results in a late breaker poster presentation at AAIC in July 2023 showing a PRX123 vaccine surrogate elicited robust antibody responses that bound with high avidity to Aβ plaques in Alzheimer’s disease brain tissue ex vivo and significantly reduced Aβ brain plaques Investigational new drug (IND) application cleared by FDA Fast Track designation granted by FDA Phase 1 timeline update expected in 2024 Parkinson’s Disease Prasinezumab, a potential first-in-class antibody for the treatment of Parkinson’s disease that is designed to target key epitopes within the C-terminus of alpha-synuclein, and is the focus of a worldwide collaboration with Roche Roche completed enrollment for the Phase 2b PADOVA clinical trial in patients with early Parkinson’s disease in the first quarter of 2023 Poster and oral presentations at AD/PD in March/April 2023 highlighted aspects of the Phase 2 PASADENA clinical trial of prasinezumab for the treatment of Parkinson’s disease Roche presented data at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) from the open-label extension of the PASADENA clinical trial which shows that prasinezumab slowed the progression of motor deficits (MDS-UPDRS Part III OFF state score) in early-stage Parkinson’s disease Topline results from Phase 2b PADOVA clinical trial expected in 2024 (NCT04777331) Neurodegenerative Diseases PRX019, a potential treatment of neurodegenerative diseases with an undisclosed target, is part of a Global Neuroscience Research and Development Collaboration with Bristol Myers Squibb. IND application cleared by FDA in December 2023 Phase 1 clinical trial timeline update expected in 2024 Rare Peripheral Amyloid Diseases Portfolio AL Amyloidosis Birtamimab, a wholly-owned potential best-in-class amyloid depleter antibody for the treatment of AL amyloidosis designed to directly neutralize soluble toxic light chain aggregates and promote clearance of amyloid that causes organ dysfunction and failure. Among patients with AL amyloidosis, a rare, progressive, and fatal disease, newly diagnosed individuals with advanced disease (e.g., Mayo Stage IV) are at the highest risk for early death. Birtamimab has been granted Fast Track designation by the FDA for the treatment of patients with Mayo Stage IV AL amyloidosis to reduce the risk of mortality and has been granted Orphan Drug Designation by both the FDA and European Medicines Agency. A significant survival benefit was observed in the post hoc analysis of birtamimab-treated patients categorized as Mayo Stage IV at baseline in the previous Phase 3 VITAL clinical trial (Blood 2023). Published Phase 3 VITAL clinical trial data in June 2023 in Blood, the peer-reviewed journal of American Society of Hematology (ASH) The ongoing confirmatory Phase 3 AFFIRM-AL clinical trial in patients with Mayo Stage IV AL amyloidosis is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA with a primary endpoint of all-cause mortality (time-to-event) at a significance level of 0.10 Topline results from confirmatory AFFIRM-AL Phase 3 clinical trial expected between 4Q 2024 and 2Q 2025 (NCT04973137) ATTR Amyloidosis NNC6019 (formerly PRX004), a potential first-in-class amyloid depleter antibody for the treatment of ATTR cardiomyopathy designed to deplete the pathogenic, non-native forms of the transthyretin (TTR) protein and is being developed by Novo Nordisk as part of their up to $1.2 billion acquisition of Prothena’s ATTR amyloidosis business and pipeline Ongoing Phase 2 clinical trial in patients with ATTR cardiomyopathy is being conducted by Novo Nordisk The Phase 2 clinical trial has fully recruited patients with topline data expected in 1H 2025 (NCT05442047) 2023 Organizational and Corporate Highlights Announced the appointment of Billy Dunn, M.D., founding, former Director of the FDA CDER Office of Neuroscience, to its Board of Directors Fourth Quarter and Full Year of 2023 Financial Results For the fourth quarter and full year of 2023, Prothena reported a net loss of $67.5 million and $147.0 million, respectively, as compared to a net income of $6.3 million and a net loss of $116.9 million for the fourth quarter and full year of 2022, respectively. Net loss per share was $1.26 and $2.76 for the fourth quarter of 2023 and for the full year of 2023, respectively, as compared to net income per share on a diluted basis of $0.12 and net loss per share of $2.47 for the fourth quarter and full year of 2022, respectively. Prothena reported total revenue of $0.3 million and $91.4 million for the fourth quarter and full year of 2023, respectively, as compared to total revenue of $49.9 million and $53.9 million for the fourth quarter and full year of 2022, respectively. Total revenue for the fourth quarter and full year of 2023 included BMS collaboration revenue of $0.3 million and $91.3 million, respectively. The full year includes the $55 million option payment from BMS related to their exercise of their option to acquire the exclusive worldwide rights for BMS-986446 (formerly PRX005). This compares to total revenue for the fourth quarter of 2022 and the full year of 2022 that included BMS collaboration revenue of $9.9 million and $13.9 million, respectively and a $40.0 million milestone payment from Novo Nordisk related to the continued advancement of NNC6019 (formerly PRX004) in a Phase 2 clinical trial for the treatment of ATTR cardiomyopathy in the fourth quarter of 2022 and the full year of 2022. Research and development (R&D) expenses totaled $61.9 million and $220.6 million for the fourth quarter and full year of 2023, respectively, as compared to $36.9 million and $135.6 million for the fourth quarter and full year of 2022, respectively. The increase in R&D expense for the fourth quarter and full year of 2023 compared to the same periods in the prior year was primarily due to higher clinical trial expenses, higher personnel related expenses, higher consulting and other R&D expenses. R&D expenses included non-cash share-based compensation expense of $5.0 million and $19.2 million for the fourth quarter and full year of 2023, respectively, as compared to $3.5 million and $14.8 million for the fourth quarter and full year of 2022, respectively. General and administrative (G&A) expenses totaled $16.9 million and $61.8 million for the fourth quarter and full year of 2023, respectively, as compared to $13.1 million and $49.9 million for the fourth quarter and full year of 2022, respectively. The increase in G&A expenses for the fourth quarter and full year of 2023 compared to the same periods in the prior year was primarily related to higher personnel related and consulting expenses. G&A expenses included non-cash share-based compensation expense of $6.0 million and $21.7 million for the fourth quarter and full year of 2023, respectively, as compared to $3.9 million and $16.5 million for the fourth quarter and full year of 2022, respectively. Total non-cash share-based compensation expense was $11.1 million and $40.9 million for the fourth quarter and full year of 2023, respectively, as compared to $7.4 million and $31.3 million for the fourth quarter and full year of 2022, respectively. As of December 31, 2023, Prothena had $621.0 million in cash, cash equivalents and restricted cash, and no debt. As of February 9, 2024, Prothena had approximately 53.7 million ordinary shares outstanding. 2024 Financial Guidance The Company expects the full year 2024 net cash used in operating and investing activities to be $208 to $225 million and expects to end the year with approximately $405 million in cash, cash equivalents and restricted cash (midpoint). The estimated full year 2024 net cash used in operating and investing activities is primarily driven by an estimated net loss of $229 to $255 million, which includes an estimated $51 million of non-cash share-based compensation expense. Conference Call Details Prothena management will discuss these results and its 2024 financial guidance during a live audio conference call today, Thursday, February 15, 2024, at 4:30 PM ET. The conference call will be made available on the Company's website at under the Investors tab in the Events and Presentations section. Following the live audio webcast, a replay will be available on the Company's website for at least 90 days. To access the call via dial-in, please dial +1 (800) 715-9871 (U.S. and Canada toll free) or +1 (646) 307-1963 (international) five minutes prior to the start time and refer to conference ID number 1706941. A replay of the call will be available until February 22, 2024, via dial-in at +1 (800) 770-2030 (U.S. and Canada toll free) or +1 (609) 800-9909 (international), Conference ID Number 1706941. About Prothena Prothena Corporation plc is a late-stage clinical biotechnology company with expertise in protein dysregulation and a pipeline of investigational therapeutics with the potential to change the course of devastating neurodegenerative and rare peripheral amyloid diseases. Fueled by its deep scientific expertise built over decades of research, Prothena is advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which its ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. Prothena’s pipeline includes both wholly-owned and partnered programs being developed for the potential treatment of diseases including AL amyloidosis, ATTR amyloidosis, Alzheimer’s disease, Parkinson’s disease and a number of other neurodegenerative diseases. For more information, please visit the Company’s website at and follow the Company on Twitter @ProthenaCorp. Forward-Looking Statements This press release contains forward-looking statements. These statements relate to, among other things, the sufficiency of our cash position to fund advancement of a broad pipeline and completion of our ongoing clinical trials; the continued advancement of our discovery, preclinical, and clinical pipeline, and expected milestones in 2024, 2025, and beyond; the treatment potential, designs, proposed mechanisms of action, and potential administration of PRX012, BMS-986446/PRX005, PRX123, prasinezumab, birtamimab, and NNC6019/PRX004; plans for ongoing and future clinical trials of PRX012, BMS-986446/PRX005, PRX123, prasinezumab, PRX019, birtamimab, and NNC6019/PRX004; the expected timing of reporting data from clinical trials, including any updates regarding our ongoing Phase 1 clinical trial evaluating PRX012 in 2024 and topline study results for our Phase 3 AFFIRM-AL clinical trial between 4Q 2024 and 2Q 2025; and our anticipated net cash burn from operating and investing activities for 2024 and expected cash balance at the end of 2024; and our estimated net loss and non-cash share-based compensation expense for 2024. These statements are based on estimates, projections and assumptions that may prove not to be accurate, and actual results could differ materially from those anticipated due to known and unknown risks, uncertainties and other factors, including but not limited to uncertainties related to the completion of operational and financial closing procedures, audit adjustments and other developments that may arise that would require adjustments to the preliminary financial results included in this press release, as well as those described in the “Risk Factors” sections of our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 2, 2023, discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC, and our Annual Report on Form 10-K to be filed with the SEC for our fiscal year 2023. We undertake no obligation to update publicly any forward-looking statements contained in this press release as a result of new information, future events, or changes in our expectations. PROTHENA CORPORATION PLC CONSOLIDATED STATEMENTS OF OPERATIONS (unaudited - amounts in thousands except per share data) Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Collaboration revenue $ 316 $ 9,923 $ 91,320 $ 13,855 Revenue from license and intellectual property — 40,000 50 40,050 Total revenue 316 49,923 91,370 53,905 Operating expenses: Research and development 61,891 36,871 220,571 135,562 General and administrative 16,940 13,124 61,835 49,900 Total operating expenses 78,831 49,995 282,406 185,462 Income (loss) from operations (78,515 ) (72 ) (191,036 ) (131,557 ) Other income (expense), net 7,897 3,417 30,556 5,952 Income (loss) before income taxes (70,618 ) 3,345 (160,480 ) (125,605 ) Provision for (benefit from) income taxes (3,142 ) (3,004 ) (13,452 ) (8,656 ) Net income (loss) $ (67,476 ) $ 6,349 $ (147,028 ) $ (116,949 ) Basic net income (loss) per ordinary share $ (1.26 ) $ 0.13 $ (2.76 ) $ (2.47 ) Diluted net income (loss) per ordinary share $ (1.26 ) $ 0.12 $ (2.76 ) $ (2.47 ) Shares used to compute basic net income (loss) per share 53,668 48,960 53,216 47,369 Shares used to compute diluted net income (loss) per share 53,668 53,979 53,216 47,369 PROTHENA CORPORATION PLC CONSOLIDATED BALANCE SHEETS (unaudited - amounts in thousands) December 31, 2023 2022 Assets Cash and cash equivalents $ 618,830 $ 710,406 Restricted cash, current 1,352 — Prepaid expenses and other current assets 19,100 8,692 Total current assets 639,282 719,098 Property and equipment, net 3,836 1,731 Operating lease right-of-use assets 12,162 6,277 Restricted cash, non-current 860 2,212 Other non-current assets 40,242 28,717 Total non-current assets 57,100 38,937 Total assets $ 696,382 $ 758,035 Liabilities and Shareholders’ Equity Accrued research and development 14,724 10,794 Deferred revenue, current — 11,442 Lease liability, current 1,114 6,473 Other current liabilities 41,053 21,438 Total current liabilities 56,891 50,147 Deferred revenue, non current 67,405 85,293 Lease liability, non-current 10,721 — Other non-current liabilities — 553 Total non-current liabilities 78,126 85,846 Total liabilities 135,017 135,993 Total shareholders’ equity 561,365 622,042 Total liabilities and shareholders’ equity $ 696,382 $ 758,035 View source version on businesswire.com: Contacts Investors Mark Johnson, CFA, Vice President, Investor Relations 650-417-1974, mark.johnson@prothena.com Media Michael Bachner, Senior Director, Corporate Communications 609-664-7308, michael.bachner@prothena.com Source: Prothena Corporation plc View this news release online at: