Semorinemab

Takeda has signed a worldwide licensing agreement with Swiss biotech AC Immune to develop and commercialize ACI-24.060, an immunotherapy aimed at treating Alzheimer's disease by targeting amyloid beta plaques. Under the terms of the agreement, AC Immune will receive an upfront payment of $100 million upon the closing of the deal. Additionally, the company is eligible for an option exercise fee, along with potential milestones that could total approximately $2.1 billion if all targets are met. Upon commercialization, AC Immune will also receive tiered double-digit royalties on worldwide net sales. ACI-24.060 is currently under investigation in the ABATE phase 1b/2 trial, which is a randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, immunogenicity, and pharmacodynamic effects of the immunotherapy in individuals with prodromal Alzheimer's disease and adults with Down syndrome. The partnership aims to leverage Takeda’s global presence and experience in drug development and commercialization while AC Immune continues to oversee the ongoing phase 1b/2 trial. Takeda will take responsibility for further clinical development, global regulatory activities, and worldwide commercialization upon exercise of the option. AC Immune has faced significant setbacks in its pursuit of an effective Alzheimer’s treatment. In 2019, Roche and AC discontinued a phase 3 trial of crenezumab, an early Alzheimer’s treatment, after it was found ineffective. Despite the setback to the hypothesis that blocking amyloid plaques could slow cognitive decline, Roche decided to continue a study of crenezumab on healthy individuals with a genetic predisposition to Alzheimer’s. Then in 2020, Roche and AC Immune faced another setback when their experimental Alzheimer's treatment, semorinemab, failed to enhance cognitive function in a phase 2 trial with early-stage patients. Unlike many treatments that target amyloid beta peptides, semorinemab aimed at "tau" proteins but did not prove more effective.

Net cash used in operating and investing activities was $73.2 million in the first quarter of 2024; quarter-end cash and restricted cash position was $548.7 million Advanced potential best-in-class Alzheimer’s disease portfolio: 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; Phase 2 clinical trial initiated in patients with early Alzheimer’s disease for BMS-986446 (formerly PRX005) 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 birtamimab mechanism of action and pharmacological characteristics in Leukemia & Lymphoma in April 2024 Daniel G. Welch appointed to Prothena Board of Directors as an independent director and Chair Designate 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 first quarter of 2024 and provided business highlights. “We continued to meaningfully advance our wholly-owned and partnered programs across our protein dysregulation portfolio, highlighted by our ongoing clinical programs, as we continue to move closer to becoming a fully integrated commercial company. We look forward to multiple upcoming clinical milestones and program updates over the next 15 months from our wholly-owned programs, including topline data from the confirmatory Phase 3 AFFIRM-AL clinical trial for birtamimab, Phase 1 data on PRX012, and an update on timing of the Phase 1 program for PRX123,” said Gene Kinney, Ph.D., President and Chief Executive Officer, Prothena. “Our partnership with Bristol Myers Squibb achieved an important milestone in 2024, as BMS-986446, an anti-tau monoclonal antibody, began recruiting patients with early Alzheimer’s disease into a Phase 2 clinical trial. Partner Roche presented important four-year data at AD/PD 2024 from the Phase 2 PASADENA open label extension trial of prasinezumab which impressively continues to show reduced motor and functional progression compared to real-world data from the Michael J. Fox Foundation. In addition, we expect topline readouts from our partners Roche, with Phase 2b PADOVA data on prasinezumab expected in the second half of 2024, and Novo Nordisk, with Phase 2 data on NNC6019 expected in the first half of 2025.” First Quarter, Recent Business Highlights and Upcoming Milestones Alzheimer’s Disease PRX012, a wholly-owned potential best-in-class, next-generation antibody delivered subcutaneously 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. Initial Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) data supports once-monthly subcutaneous administration and ongoing evaluation in MAD cohorts 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. Bristol Myers Squibb has initiated a Phase 2 clinical trial in approximately 475 patients with early Alzheimer’s disease for BMS-986446 (NCT06268886) Bristol Myers Squibb is responsible for all development, manufacturing, and commercialization of BMS-986446 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. The FDA cleared the investigational new drug (IND) application and granted Fast Track designation for PRX123 for the treatment of Alzheimer’s disease. 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 Data from partner Roche from Phase 2 PASADENA clinical trial presented at AD/PD 2024 showed patients with early Parkinson’s disease taking prasinezumab after four years continued to show reduced motor and functional progression compared to real-world data Data from partner Roche on motor progression in four pre-specified subpopulations from the Phase 2 PASADENA clinical trial published in Nature Medicine Topline results from Phase 2b PADOVA clinical trial in patients with early Parkinson’s disease, which has completed enrollment, expected in 2H 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. Phase 1 clinical trial timeline update expected in 2024 Rare Peripheral Amyloid Diseases Portfolio AL Amyloidosis Birtamimab, a wholly-owned potential best-in-class anti-amyloid 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). Birtamimab mechanism of action and pharmacological characteristics published in Leukemia & Lymphoma in April 2024 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 completed enrollment with topline data expected in 1H 2025 (NCT05442047) Corporate Highlights Following a comprehensive search process in connection with Prothena’s regular Board of Directors succession planning, the Company appointed Daniel G. Welch to the Board of Directors as an independent director and Chair Designate Prothena announced the appointment of David Ford to a newly created position of Chief People Officer in March 2024. In this role, Mr. Ford is responsible for people, culture, and human resources strategy to drive the company’s vision and overall growth strategy. First Quarter of 2024 Financial Results For the first quarter of 2024, Prothena reported a net loss of $72.2 million, as compared to a net loss of $46.9 million for the first quarter of 2023, respectively. Net loss per share was $1.34 for the first quarter of 2024, as compared to net loss per share of $0.89 for the first quarter of 2023, respectively. Prothena reported total revenue of $0.1 million for the first quarter of 2024, as compared to total revenue of $2.2 million for the first quarter of 2023. Total revenue for the first quarter of 2024 was from license fees recognized under a License Agreement with F. Hoffmann-La Roche Ltd. and total revenue for the first quarter of 2023 was primarily from collaboration revenue from Bristol Myers Squibb. Research and development (R&D) expenses totaled $64.1 million for the first quarter of 2024, as compared to $44.8 million for the first quarter of 2023. The increase in R&D expenses for the first quarter of 2024 compared to the same period in the prior year was primarily due to higher clinical trial expenses, higher personnel related expenses and higher manufacturing expenses. R&D expenses included non-cash share-based compensation expense of $5.5 million for the first quarter of 2024, as compared to $4.4 million for the first quarter of 2023. General and administrative (G&A) expenses totaled $17.5 million for the first quarter of 2024, as compared to $13.7 million for the first quarter of 2023. The increase in G&A expenses for the first quarter of 2024 compared to the same period 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 $6.9 million for the first quarter of 2024, as compared to $4.4 million for the first quarter of 2023. Total non-cash share-based compensation expense was $12.4 million for the first quarter of 2024, as compared to $8.8 million for the first quarter of 2023. As of March 31, 2024, Prothena had $548.7 million in cash, cash equivalents and restricted cash, and no debt. As of May 1, 2024, Prothena had approximately 53.8 million ordinary shares outstanding. 2024 Financial Guidance The Company continues to expect 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. 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, PRX019, 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; our anticipated net cash used 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 May 8, 2024, and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC. 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 CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (unaudited - amounts in thousands except per share data) Three Months Ended March 31, 2024 2023 Collaboration revenue $ — $ 2,119 Revenue from license and intellectual property 50 50 Total revenue 50 2,169 Operating expenses: Research and development 64,114 44,756 General and administrative 17,464 13,738 Total operating expenses 81,578 58,494 Loss from operations (81,528 ) (56,325 ) Total other income, net 7,088 6,549 Loss before income taxes (74,440 ) (49,776 ) Benefit from income taxes (2,201 ) (2,912 ) Net loss $ (72,239 ) $ (46,864 ) Basic net income (loss) per ordinary share $ (1.34 ) $ (0.89 ) Diluted net income (loss) per ordinary share $ (1.34 ) $ (0.89 ) Shares used to compute basic net income (loss) per share 53,714 52,501 Shares used to compute diluted net income (loss) per share 53,714 52,501 PROTHENA CORPORATION PLC CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited - amounts in thousands) March 31, December 31, 2024 2023 Assets Cash and cash equivalents $ 546,512 $ 618,830 Restricted cash, current 1,352 1,352 Prepaid expenses and other current assets 18,004 19,100 Total current assets 565,868 639,282 Property and equipment, net 3,672 3,836 Operating lease right-of-use assets 12,510 12,162 Restricted cash, non-current 860 860 Other non-current assets 40,284 40,242 Total non-current assets 57,326 57,100 Total assets $ 623,194 $ 696,382 Liabilities and Shareholders’ Equity Accrued research and development 17,340 14,724 Lease liability, current 2,372 1,114 Other current liabilities 23,554 41,053 Total current liabilities 43,266 56,891 Deferred revenue, non-current 67,405 67,405 Lease liability, non-current 10,124 10,721 Total non-current liabilities 77,529 78,126 Total liabilities 120,795 135,017 Total shareholders’ equity 502,399 561,365 Total liabilities and shareholders’ equity $ 623,194 $ 696,382 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: