Young onset Parkinson disease

Driving clinical, regulatory, and operational excellence across five innovative platforms focused on immunology, neuroscience, and oncology: Portfolio targeting large indications including obesity, epilepsy, bipolar disorder, depression, obsessive-compulsive disorder (OCD), migraine, pain, Alzheimer's disease, Parkinson's disease, multiple sclerosis, rheumatoid arthritis, and cancer. Also advancing potential novel treatments for rare autoimmune and inflammatory diseases, including myasthenia gravis, cardiomyopathy, spinal muscular atrophy (SMA) and IgA nephropathy. Pivotal clinical data milestones expected across three distinct programs: First-in-human Phase 1 study with BHV-1300 initiated in 1Q 2024. Preliminary immunoglobulin G (IgG) lowering data from the single ascending dose (SAD) portion of the study expected in late 1Q 2024/early 2Q 2024. The MAD portion of the study is being planned in a relevant patient population with the possibility of benefit from BHV-1300. Phase 3 database lock for interim efficacy analysis with troriluzole in OCD remains on schedule for 1Q 2024, with results expected in 2Q 2024. Phase 3 topline data in ongoing fully enrolled SMA study with taldefgrobep expected 2H 2024. Multiple trial initiations and Investigational New Drug (IND) filings projected over next three years present potential for continued growth and value creation. NEW HAVEN, Conn., Feb. 29, 2024 /PRNewswire/ -- Biohaven Ltd. (NYSE: BHVN) (Biohaven or the Company), a global clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of life-changing therapies to treat a broad range of rare and common diseases, today reported financial results for the fourth quarter and full year ended December 31, 2023, and provided a review of recent accomplishments and anticipated upcoming developments. Vlad Coric, M.D., Chairman and Chief Executive Officer of Biohaven, commented, "We embarked on a bold execution plan after completing our spin-off, re-emerging as a separate entity focused on immunology, neuroscience, and oncology. In just over a year's time, we made tremendous strides in progressing our programs, providing impressive and supportive pre-clinical and clinical outcomes for our key stakeholders, including patients, who may gain access to differentiated drugs for difficult to treat medical conditions. Today we are focused on delivering outcomes across five platforms spanning inflammation and immunology, ion channel modulation, myostatin inhibition, glutamate modulation, and oncology. In the year ahead, we expect to deliver potentially groundbreaking data across three distinct programs. In the near-term, we expect to report first-in-human Phase 1 IgG lowering data with our pan-IgG degrader, BHV-1300, with broad potential application. Given the profoundly deep and rapid reduction in IgG levels observed in non-human primate studies, unique ability to co-administer with Fc-containing biologics, ease of self-administration, and favorable toxicology profile observed to date, we are eagerly awaiting the proof-of-concept human data. We also plan to report OCD Phase 3 topline data in the second quarter of 2024 from an interim analysis with our glutamate modulating agent, troriluzole. There has been little to no innovation in advancing treatments for this disorder in decades and a win in this Phase 3 trial would be a substantial clinical success for the three million patients across the OCD community, many of whom are plagued by debilitating intrusive thoughts and compulsions. And finally, we're expecting Phase 3 topline data in the second half of the year with our anti-myostatin compound, taldefgrobep alfa, for patients with SMA. Dr. Coric continued, "Beyond data expectations, we are excited with the progress made across the balance of our portfolio, starting with our Kv7 ion channel activation program, where we have operationalized over 110 clinical trial sites in our focal epilepsy trials and are advancing development programs in generalized epilepsy, bipolar disorder, and major depressive disorder. Excitement is also mounting for the potential of taldefgrobep alfa in weight loss, a compound that we believe will maintain and grow muscle mass as a means of helping to address the global obesity crisis. We also expect to deliver additional trial initiations across our broad IgG degrader program targeting both large indications and rare autoimmune/inflammatory diseases, TYK2/JAK1 inhibition in neuroinflammatory disorders, TRPM3 antagonism initially in migraine and neuropathic pain, and with our antibody drug conjugates program in an array of oncology indications. We are passionate about helping patients in need, and excited about our portfolio, the skilled drug development team we have in place, and the vast opportunity in the year ahead." Full Year and Recent Business Highlights Ion Channel Platform - Milestones and Next Steps: Kv7 Ion Channel Activation: Epilepsy & Neuropsychiatric Indications BHV-7000, the lead asset from the Kv7 platform, is a selective activator of Kv7.2/Kv7.3, a key ion channel involved in regulation of neuronal signaling and hyperexcitability. Reported BHV-7000 Phase 1 study results: In December 2023, the Company reported full results from the BHV-7000 Phase 1 SAD and multiple ascending dose (MAD) studies examining doses up to 120mg daily, demonstrating BHV-7000 was well-tolerated at all doses studied without the typical central nervous system (CNS) adverse effects associated with other anti-seizure medications (ASMs), such as somnolence and cognitive/mood disturbances. Results were consistent with previously reported preclinical data demonstrating BHV-7000's lack of GABAA receptor activation and lack of adverse impacts on neurobehavior in preclinical testing. Demonstrated CNS target engagement: In December 2023, the Company reported additional data from a Phase 1 electroencephalogram (EEG) biomarker study, where BHV-7000 demonstrated dose-dependent target engagement in the brain as shown by dose-dependent effects on EEG spectral power across all frequency bands. While changes in spectral power were observed across all frequency bands with BHV-7000, the minimal impact on slower frequencies (i.e., delta) is consistent with the low incidence of CNS adverse events observed in the BHV-7000 Phase 1 SAD/MAD studies. EEG delta activity is associated with somnolence, an undesirable CNS adverse event commonly reported with other ASMs. Developed once-daily formulation: In September 2023, the Company announced it had formulated an extended release, once-a-day tablet designed to achieve target therapeutic concentrations (25mg, 50mg and 75mg). This dosing approach with a Kv7 activator will allow for assessment of distinct target concentrations over a wide range, above and below projected efficacious EC50 drug concentrations, not previously feasible with drugs in this class. Sites operationalized: In January 2024, the Company completed its End-of-Phase 2 meeting with FDA to advance to Phase 3 trials and announced that more than 110 global clinical sites have been selected in the ongoing focal epilepsy trial, with enrollment planned for 1Q 2024. Upcoming trial initiations: The Company expects to initiate Phase 2/3 programs in focal epilepsy in 1Q 2024 and in generalized epilepsy in 2Q 2024; the Company also expects to initiate a Phase 2 study in major depressive disorder and a Phase 2/3 study in bipolar disorder in 1H 2024. TRPM3 Ion Channel Antagonism: Migraine & Neuropathic Pain BHV-2100 is an oral, selective TRPM3 antagonist offering a novel, non-addictive treatment for migraine and neuropathic pain. Phase 1 study data supports evaluation in acute migraine: In January 2024, the Company detailed preliminary pharmacokinetic (PK) and safety data from an ongoing Phase 1 study; in the study, BHV-2100 was rapidly absorbed, achieved 90% inhibitory concentrations within one hour, and was well tolerated at projected therapeutic concentrations Upcoming trial initiations: The Company expects to initiate a BHV-2100 Phase 2 study in acute migraine in 2H 2024 and conduct a POC study for neuropathic pain in 2H 2024. Inflammation and Immunology Platform - Milestones and Next Steps: Targeted Extracellular Protein Degradation: Molecular Degraders of Extracellular Proteins (MoDEs™) uniquely harness the hepatic ASGPR receptor for efficient and safe removal of circulating pathogenic targets; BHV-1300, is an IgG degrader. Reported on progress with BHV-1300: The Company has demonstrated the effect of a single dose of BHV-1300 in lowering IgG in nonhuman primates (NHPs), previously reporting over 75-80% reduction of IgG levels from baseline in three days. These data compare favorably to other IgG targeting agents, such as the FcRn inhibitor efgartigimod, where reduction of IgG levels, following a single dose, was shown to be approximately 50% in 5-7 days. In September 2023, the Company announced positive multiple dose, pharmacodynamic (PD) data from a NHP study with BHV-1300 demonstrating dose-dependent reductions of over 90% in IgG levels from baseline, suggesting the potential for achieving greater efficacy with finely calibrated, deeper IgG reductions as compared with existing standard of care FcRn targeting treatments. Demonstrated potential for same-day, co-administration with Fc-containing biologics: In January 2024, the Company presented new NHP data demonstrating that Biohaven's IgG degrader technology allows for co-administration with Fc-containing biologics; PK of Humira® was unaltered after being dosed 12 hours after BHV-1300 administration. Reported preclinical pharmacodynamic data with single dose of BHV-1310: In January 2024, the Company showed that a next generation and optimized IgG degrader, BHV-1310, allowed for much deeper 90% reductions in IgG after a single dose. Given the deep and rapid reductions observed, the Company believes BHV-1310 may have potential application in acute settings. Unveiled plans for BHV-1600: next-generation, selective degrader targeting β1-AR autoantibodies: In January 2024, the Company reported preclinical data demonstrating degradation of anti-β-1AR antibody in mice. The Company expects to file an IND application and initiate a first-in-human Phase 1 study in 2H 2024. BHV-1600 will initially be evaluated in patients with dilated cardiomyopathy. Near-term data expected: The Phase 1 SAD study examining BHV-1300 in healthy subjects was initiated in 1Q 2024 and the Company expects preliminary results in late 1Q 2024/early 2Q 2024. The FDA indicated that the MAD assessment of BHV-1300 should be performed in a relevant patient population. Upon completion of the SAD study, Biohaven is planning the MAD portion of the study in a relevant patient population with the possibility of benefit from BHV-1300. Upcoming trial initiations: A total of 4 INDs are expected for the degrader program in 2024. TYK2/JAK1 Inhibition: BHV-8000 is an oral, brain-penetrant, selective TYK2/JAK1 inhibitor with broad potential for neuroinflammatory and neurodegenerative disorders. Successfully completed single ascending dose cohorts; advanced multiple ascending dose cohorts in ongoing Phase 1 study of TYK2/JAK1 inhibitor, BHV-8000: In January 2024, the Company provided a program update for the ongoing Phase 1 study designed to evaluate the safety, tolerability, PK and PD of single and multiple ascending doses of BHV-8000 in healthy volunteers. The SAD cohorts have now completed dosing (10, 20 and 30 mg); in the MAD cohorts, the Company completed up to the 20 mg dose. Based on the preliminary data available, projected therapeutic concentrations of BHV-8000 were achieved and BHV-8000 was well tolerated with only mild adverse events reported. Upcoming trial initiations: The Company expects to initiate a Phase 2 study in multiple sclerosis in 2H 2024, a Phase 2a study in prevention of amyloid therapy induced ARIA in 2H 2024, and Phase 2/3 studies in early Parkinson's disease and early Alzheimer's disease in 2H 2024. Myostatin Platform - Milestones and Next Steps: Taldefgrobep alfa is a novel myostatin inhibitor optimized to target myostatin and associated signaling pathways of muscle growth. Taldefgrobep alpha also has promise as a potential treatment for obesity and, in preclinical models as well as preliminary healthy human studies, has demonstrated meaningful reductions in fat mass, the primary pathogenic tissue in obesity, while increasing lean mass. Biohaven is also studying taldefgrobep in a global Phase 3 study in Spinal Muscular Atrophy to enhance muscle mass and function in patients treated with standard-of-care gene therapy treatments. Preclinical data demonstrated taldefgrobep alfa reduces fat and improves lean mass: In October 2023, the Company presented preclinical data demonstrating the ability of taldefgrobep alfa to significantly reduce fat mass while increasing lean mass in an obese mouse model at The Obesity Society's annual ObesityWeek conference. Completed enrollment in pivotal Phase 3 study in SMA: In September 2023, the Company announced that it had completed enrollment in RESILIENT, a pivotal Phase 3 study designed to evaluate the efficacy and safety of taldefgrobep as adjunctive therapy to enhance muscle mass and function in SMA patients treated with standard-of-care treatments. In July 2023, the Company announced that taldefgrobep received orphan drug designation (ODD) from the European Commission for the treatment of SMA. Taldefgrobep previously received Fast-Track and ODD from the FDA. Topline data expected: The Company expects to announce Phase 3 topline data from the ongoing SMA study in 2H 2024. Upcoming trial initiation: The Company expects to initiate a Phase 2 study in patients with obesity in 2Q 2024. Glutamate Modulation Platform - Milestones and Next Steps: Troriluzole is a novel glutamate modulator currently being evaluated in Phase 3 trials for obsessive-compulsive disorder as an adjunctive therapy in patients with an inadequate response to existing standard-of-care treatment. Topline data from interim analysis in OCD expected in 2Q 2024: In January 2024, the Company shared an update on the ongoing Phase 3 trial in OCD. The Company remains on schedule for a database lock in 1Q 2024, with an interim efficacy analysis expected in 2Q 2024. Biohaven has also continued to have constructive dialogue with the FDA regarding its SCA development program and potential future data analyses to address regulatory concerns in the previously issued refuse-to-file decision on its NDA application for SCA3. Biohaven will provide further updates on the SCA development program as warranted by any continued positive progress from the outcome of future regulatory interactions on this topic. Next-Generation ADC Platform - Milestones and Next Steps: Biohaven's antibody drug conjugate (ADC) technology is focused on novel conjugation chemistry with the potential to be superior to the current industry standard maleimide and lipophilic click chemistry. BHV-1510 is a TROP2 directed ADC, with a highly differentiated efficacy and safety profile providing an opportunity to broaden therapeutic margin, increase time on treatment, and improve efficacy; BHV-1500 demonstrated superior efficacy to Adcetris® (brentuximab vedotin) and improved survival in a mouse xenograft model. Upcoming trial initiations: The Company completed its regulatory interactions to begin first-in-human studies with BHV-1510 (TROP2 directed ADC) and expects to initiate a Phase 1 trial in 2Q 2024. The company also expects to submit an IND for BHV-1500 (next-generation brentuximab ADC) in 2H 2024. Corporate Updates: Public offering: On October 5, 2023, the Company closed its previously announced underwritten public offering of 11,761,363 of its common shares, which included the full exercise of the underwriters' option to purchase 1,534,090 additional shares, at the public offering price of $22.00 per share. The net proceeds raised in the offering, after deducting underwriting discounts and estimated expenses of the offering payable by the Company, were approximately $242.4 million. As of February 26, 2024, we had 81,579,914 common shares outstanding. Expected Upcoming Milestones: We believe Biohaven is well positioned to achieve significant, value-creating milestones in 2024 across numerous programs: Selective Kv7 Activator: Initiate BHV-7000 Phase 2/3 program in focal epilepsy in 1Q 2024 Initiate BHV-7000 Phase 2/3 study in generalized epilepsy in 2Q 2024 Initiate BHV-7000 Phase 2/3 study in bipolar disorder in 1H 2024 Initiate BHV-7000 Phase 2 study in major depressive disorder in 1H 2024 Troriluzole: Database lock in 1Q 2024 and report troriluzole Phase 3 interim efficacy analysis topline results in OCD in 2Q 2024 Taldefgrobep alfa: Initiate taldefgrobep Phase 2 study in obesity in 2Q 2024 Report taldefgrobep Phase 3 topline results in SMA in 2H 2024 First-in-class TRPM3 Antagonist: Initiate BHV-2100 Phase 2 study in acute migraine in 2H 2024 Conduct BHV-2100 POC study for neuropathic pain in 2H 2024 TYK2/JAK1 Inhibitor: Initiate BHV-8000 Phase 2 study in Multiple Sclerosis in 2H 2024 Initiate BHV-8000 Phase 2a study in prevention of amyloid therapy induced ARIA in 2H 2024 Initiate BHV-8000 Phase 2/3 study in early Parkinson's disease in 2H 2024 Initiate BHV-8000 Phase 2/3 study in early Alzheimer's disease in 2H 2024 Extracellular protein degradation platform BHV-1300 first-in-human clinical data demonstrating IgG lowering expected late 1Q 2024/early 2Q 2024 A total of 4 INDs are expected for the degrader program in 2024 Next Generation ADC Platform: Initiate Phase 1 trial of BHV-1510 (TROP2 directed ADC) in 2Q 2024 File IND for BHV-1500 (next generation brentuximab ADC) in 2H 2024 Capital Position: Cash, cash equivalents and marketable securities as of December 31, 2023 was $385.5 million, which includes $3.7 million of restricted cash. Fourth Quarter 2023 Financial Highlights: Research and Development (R&D) Expenses: R&D expenses, including non-cash share-based compensation costs, were $134.8 million for the three months ended December 31, 2023, compared to $137.0 million for the three months ended December 31, 2022. The decrease of $2.2 million was primarily due to decreased non-cash share-based compensation expense during the three months ended December 31, 2023, and $5.2 million of one-time employee costs related to the Pfizer acquisition of Biohaven Pharmaceutical Holding Company Ltd. (the Former Parent) in the fourth quarter of 2022. This was partially offset by increased costs related to advancing additional clinical development program activities, including late Phase 2/3 studies and preclinical research programs, and recognition of one-time expenses of a $10.0 million cash payment and a $21.8 million non-cash issuance of common shares to acquire rights related to our agreement with Highlightll in the three months ended December 31, 2023, as compared to the same period in the prior year. Non-cash share-based compensation expense was $9.1 million for the three months ended December 31, 2023, a decrease of $60.3 million as compared to the same period in 2022. The decrease was primarily due to $61.7 million of expense allocated from the Former Parent recognized in connection with the settlement of outstanding Former Parent stock options and restricted stock units (RSUs) upon the effectiveness of the Former Parent's distribution to holders of all outstanding common shares of Biohaven and the spin-off of Biohaven from the Former Parent (the Separation) in the fourth quarter of 2022. General and Administrative (G&A) Expenses: General and administrative expenses were $18.9 million for the three months ended December 31, 2023, compared to $76.4 million for the three months ended December 31, 2022. The decrease of $57.5 million was primarily due to decreased non-cash share-based compensation expense during the three months ended December 31, 2023, and $8.2 million of transaction-related expenses and $8.9 million of one-time employee costs related to the Pfizer acquisition of the Former Parent in the fourth quarter of 2022. Non-cash share-based compensation expense was $6.8 million for the three months ended December 31, 2023, a decrease of $39.5 million as compared to the same period in 2022. The decrease was primarily due to $39.7 million of expense allocated from the Former Parent recognized in connection with the settlement of outstanding Former Parent stock options and RSUs upon the effectiveness of the Separation in the fourth quarter of 2022. Other Income (Expense), Net: Other income (expense), net was a net income of $7.7 million for the three months ended December 31, 2023, compared to a net expense of $1.8 million for the three months ended December 31, 2022. The increase of $9.6 million was primarily due to a $10.0 million impairment loss recognized during the fourth quarter of 2022 on our Artizan Series A-2 Preferred Stock Investment. Net Loss: Biohaven reported a net loss for the three months ended December 31, 2023, of $144.8 million, or $1.81 per share, compared to $201.1 million, or $3.32 per share, for the same period in 2022. Non-GAAP adjusted net loss for the three months ended December 31, 2023 was $128.9 million, or $1.61 per share, compared to $77.3 million, or $1.27 per share for the same period in 2022. These non-GAAP adjusted net loss and non-GAAP adjusted net loss per share measures, more fully described below under "Non-GAAP Financial Measures," exclude non-cash share-based compensation charges and transaction-related costs incurred relating to the Company's spin-off from Biohaven Pharmaceutical Holding Company Ltd. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the tables below. Full Year 2023 Financial Highlights Note: As described in our Annual Report on Form 10-K, full year results for the year ended December 31, 2022 include direct and allocated expenses on a carve-out basis of accounting for the period prior to October 3, 2022, when the Company became a standalone public company. R&D Expenses: R&D expenses, including non-cash share-based compensation, were $373.3 million for the year ended December 31, 2023, compared to $437.1 million for the year ended December 31, 2022. The decrease of $63.8 million was primarily due to a decrease of $91.5 million in personnel related costs primarily due to decreased non-cash share-based compensation expense, and reduced program spend for discontinued programs in 2023 compared to 2022. R&D expenses for the year ended December 31, 2022 also included a one-time $93.7 million expense for our Kv7 Platform acquisition, and a $25.0 million milestone relating to BHV-7000. The decrease was partially offset by increases in direct program spend for additional and advancing clinical trials, including late Phase 2/3 studies and preclinical research programs, and recognition of one-time expenses of a $10.0 million cash payment and a $21.8 million non-cash issuance of common shares to acquire rights related to our agreement with Highlightll, as compared to the same period in the prior year. Non-cash share-based compensation expense was $16.0 million for the year ended December 31, 2023, a decrease of $100.4 million as compared to the same period in 2022. Non-cash share-based compensation expense for the year ended December 31, 2022 included $108.7 million of expense allocated from the Former Parent, including $61.7 million of expense recognized in connection with the settlement of outstanding Former Parent stock options and RSUs upon the effectiveness of the Separation in the fourth quarter of 2022. G&A Expenses: G&A expenses, including non-cash share-based compensation costs, were $62.8 million for the year ended December 31, 2023, compared to $130.9 million for the year ended December 31, 2022. The decrease of $68.1 million was primarily due to decreased non-cash share-based compensation costs. Non-cash share-based compensation expense was $12.8 million for the year ended December 31, 2023, a decrease of $64.4 million as compared to the same period in 2022. Non-cash share-based compensation expense for the year ended December 31, 2022 included $70.6 million of expense allocated from the Former Parent, including $39.7 million of expense recognized in connection with the settlement of each outstanding Former Parent stock option and RSU upon the effectiveness of the Separation in the fourth quarter of 2022. Other Income (Expense), Net: Other income (expense), net was a net income of $26.5 million for the year ended December 31, 2023, compared to a net expense of $1.9 million for the three months ended December 31, 2022. The increase of $28.4 million was primarily due to increased net investment income of $14.5 million and increased service revenue from the Transition Service Agreement we entered into with the Former Parent of $5.2 million in 2023, as compared to the same period in the prior year, as well as a $10.0 million impairment loss recognized during the fourth quarter of 2022 on our Artizan Series A-2 Preferred Stock Investment. Net Loss: The Company reported a net loss attributable to common shareholders for the year ended December 31, 2023 of $408.2 million, or $5.73 per share, compared to $570.3 million, or $12.75 per share for the same period in 2022. Non-GAAP adjusted net loss for the year ended December 31, 2023 was $379.4 million, or $5.33 per share, compared to $362.7 million, or $8.11 per share for the same period in 2022. These non-GAAP adjusted net loss and non-GAAP adjusted net loss per share measures, more fully described below under "Non-GAAP Financial Measures," exclude non-cash share-based compensation charges and transaction-related costs incurred relating to the Company's spin-off from Biohaven Pharmaceutical Holding Company Ltd. A reconciliation of the GAAP financial results to non-GAAP financial results is included in the tables below. Non-GAAP Financial Measures This press release includes financial results prepared in accordance with accounting principles generally accepted in the United States (GAAP), and also certain non-GAAP financial measures. In particular, Biohaven has provided non-GAAP adjusted net loss and adjusted net loss per share, which are adjusted to exclude non-cash share-based compensation, which is substantially dependent on changes in the market price of common shares, and transaction-related costs incurred relating to the Company's spin-off from Biohaven Pharmaceutical Holding Company Ltd., which are limited to a specific period of time and related to Biohaven Ltd. being established as a standalone public company. Non-GAAP financial measures are not an alternative for financial measures prepared in accordance with GAAP. However, Biohaven believes the presentation of non-GAAP adjusted net loss and adjusted net loss per share, when viewed in conjunction with GAAP results, provides investors with a more meaningful understanding of ongoing operating performance and can assist investors in comparing Biohaven's performance between periods. In addition, these non-GAAP financial measures are among those indicators Biohaven uses as a basis for evaluating performance, and planning and forecasting future periods. These non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between these non-GAAP measures and the most directly comparable GAAP measures is provided later in this news release. About Biohaven Biohaven is a biopharmaceutical company focused on the discovery, development, and commercialization of life-changing treatments in key therapeutic areas, including immunology, neuroscience, and oncology. The company is advancing its innovative portfolio of therapeutics, leveraging its proven drug development experience and multiple proprietary drug development platforms. Biohaven's extensive clinical and preclinical programs include Kv7 ion channel modulation for epilepsy and mood disorders; extracellular protein degradation for immunological diseases; TRPM3 antagonism for migraine and neuropathic pain; TYK2/JAK1 inhibition for neuroinflammatory disorders; glutamate modulation for OCD and SCA; myostatin inhibition for neuromuscular and metabolic diseases, including SMA and obesity; and antibody recruiting, bispecific molecules and antibody drug conjugates for cancer. Forward-looking Statements This news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The use of certain words, including "continue", "plan", "will", "believe", "may", "expect", "anticipate" and similar expressions, is intended to identify forward-looking statements. Investors are cautioned that any forward-looking statements, including statements regarding the future development, timing and potential marketing approval and commercialization of development candidates, are not guarantees of future performance or results and involve substantial risks and uncertainties. Actual results, developments and events may differ materially from those in the forward-looking statements as a result of various factors including: the expected timing, commencement and outcomes of Biohaven's planned and ongoing clinical trials; the timing of planned interactions and filings with the FDA; the timing and outcome of expected regulatory filings; complying with applicable U.S. regulatory requirements; the potential commercialization of Biohaven's product candidates; the potential for Biohaven's product candidates to be first in class therapies; and the effectiveness and safety of Biohaven's product candidates. Additional important factors to be considered in connection with forward-looking statements are described in Biohaven's filings with the Securities and Exchange Commission, including within the sections titled "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations". The forward-looking statements are made as of the date of this news release, and Biohaven does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law. MoDEs is a trademark of Biohaven Therapeutics Ltd. Investor Contact: Jennifer Porcelli Vice President, Investor Relations [email protected] +1 (201) 248-0741 Media Contact: Mike Beyer Sam Brown Inc. [email protected] +1 (312) 961-2502 SOURCE Biohaven Ltd.

BERWYN, Pa., Dec. 05, 2023 (GLOBE NEWSWIRE) -- Annovis Bio, Inc. (NYSE: ANVS), a clinical-stage drug platform company developing novel therapies for neurodegenerative diseases today announced last patient last visit in the phase III study of its lead candidate buntanetap in patients with early Parkinson’s disease (PD). Topline data results are expected in January 2024. "We are pleased to share the completion of our Parkinson's study which marks a significant step forward in our ongoing mission to bring new therapies for those affected by this challenging neurodegenerative disease," said Maria Maccecchini, Ph.D., Founder, President, and CEO of Annovis. “The study saw a substantial level of participation, with patients enrolling at a record pace." "We extend our appreciation to all participants and collaborators whose contributions enabled efficient and timely completion of the study," said Melissa Gaines, Senior Vice President, Clinical Operations. “Our team now shifts its focus to diligently cleaning and analyzing the data to meet our goal of sharing the topline results early next year." About the Phase III TrialThis study is a phase III, randomized, double-blind, placebo-controlled trial investigating the efficacy, safety, and tolerability of buntanetap for early PD patients on top of their standard of care. Patients were treated with buntanetap (10 mg or 20 mg) or placebo for 6 months. The study was initiated in August 2022 with a record pace of full enrollment in just nine months and a total of 616 screened, 523 randomized and 471 completed patients across 67 sites (43 in the United States and 24 in the European Union). Screen failure (15%) and drop out (9.9%) rates were below projections. About Buntanetap Buntanetap (formerly known as Posiphen or ANVS401) attacks neurodegeneration by reducing multiple neurotoxic proteins, thereby improving synaptic transmission and axonal transport, which is the information highway of the nerve cell. Dysfunction of synaptic transmission and axonal transport has been shown to be the cause of nerve cell degeneration and ultimately death. Unlike other PD drugs in development which attempt to remove only one toxic protein, buntanetap inhibits several toxic proteins before they can form, thereby preventing the formation of all the major neurotoxic proteins responsible for PD and AD. About Annovis Bio, Inc.Headquartered in Berwyn, Pennsylvania, Annovis Bio, Inc. is a clinical-stage, drug platform company addressing neurodegeneration, such as Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and other chronic neurodegenerative diseases. It is believed to be the only company developing a drug for both AD and PD designed to inhibit more than one neurotoxic protein to restore axonal and synaptic activity. By improving brain function, the company’s goal is to treat memory loss and dementia associated with AD as well as body and brain dysfunction associated with PD. For more information on Annovis Bio, please visit the Company's website www.annovisbio.com and follow us on LinkedIn and Twitter. Forward-Looking StatementsThis press release contains "forward-looking" statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The Company advises caution in reliance on forward-looking statements. Forward-looking statements include, without limitation, the Company's plans related to clinical trials. These statements involve known and unknown risks, uncertainties and other factors that may cause actual results to differ materially from those implied by forward-looking statements, including regarding patient enrollment, the effectiveness of Buntanetap and the timing, effectiveness, and anticipated results of the Company's clinical trials evaluating the efficacy, safety and tolerability of buntanetap. See also additional risk factors set forth in the Company's periodic filings with the SEC, including, but not limited to, those risks and uncertainties listed in the section entitled "Risk Factors," in the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the SEC. All forward-looking statements in this press release are based on information available to the Company as of the date of this filing. The Company expressly disclaims any obligation to update or alter its forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable law. Investor Contacts:Maria Maccecchini, Ph.D.maccecchini@annovisbio.com

BERWYN, Pa., Nov. 08, 2023 (GLOBE NEWSWIRE) -- Annovis Bio, Inc. (NYSE: ANVS), a late-stage clinical drug platform company developing transformative therapies to treat neurodegenerative diseases, including Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) announced third quarter financial results for the period ended September 30, 2023, and reviewed recent accomplishments. Third Quarter 2023 Highlights and New Developments Clinical Updates AD phase II/III study Status of Phase II/III Alzheimer's Study Sept. 30Nov. 8Sites activated5054Patients enrolled210305Patients completed44115Expected full enrollmentNovember 22 This is a dose ranging trial of buntanetap (formerly known as posiphen or ANV401) in patients with mild to moderate Alzheimer’s Disease with a dosing treatment period of 12 weeks. 320 patients will be enrolled to receive either one of three doses of buntanetap or placebo. Its mechanism of action, favorable toxicology profile, and oral mode of administration distinguish buntanetap as superior to other AD drugs. Other drugs attempt to remove just one neurotoxic protein and, at best, have a minor effect. Buntanetap has been shown to normalize the synthesis of four neurotoxic proteins -Amyloid Beta, Tau, alpha Synuclein, and TDP43 - the culprits behind nerve cell degeneration and death. Buntanetap’s early trials have shown its ability to reverse the destructive effects that Alzheimer’s Disease has on thinking and memory. Annovis announced on October 12 the positive efficacy interim analysis and on October 30 the safety review by the Data and Safety Monitoring Board (DSMB). The efficacy and safety analysis reviewed by the DSMB recommended that Annovis continue the trial as originally designed. The feedback from the DSMB about the AD trial was: No drug-related SAEs (Serious Adverse Events)Each AE (Adverse Event): less than 5 percentVery low dropout rate: 4.7 percent PD phase III study Status of Phase III Parkinson's Study Sept. 30Nov. 8Sites activated6767Patients enrolled523523Patients completed283415Full enrollmentJune 7 On June 3, Annovis announced it had reached full enrollment in the trial in a record nine months. Since the first patient was dosed in late August 2022, over 640 patients were screened and a total of 523 patients enrolled with 67 sites (43 in the United States and 24 in the European Union). The phase III trial is a randomized, double-blind, placebo-controlled trial investigating the efficacy, safety, and tolerability of buntanetap for early PD patients on top of their standard of care. Patients are treated with 10 mg, 20 mg, or placebo for 6 months. By lowering levels of all the neurotoxic proteins, buntanetap improves axonal transport (the nerve cell’s information highway). Dysfunction of axonal transport has been shown to be the cause of nerve cell degeneration and, ultimately, death. The record enrollment and low drop-out rate in this trial are believed to be due to the drug’s benefits demonstrated in the phase I/II trial: Improvements in both body and motor functionImprovements the speed of movementsEasy administration as a once daily pillSafe and well-tolerated. The study is expected to conclude on December 1 with top-line assessment data at the end of January 2024. Annovis announced on June 20 the positive safety review by the Data and Safety Monitoring Board (DSMB) for its phase III trial of buntanetap for PD. The DSMB recommended that Annovis continue the trial as originally designed. The feedback from the DSMB included: No drug-related SAEs (serious adverse events) Each AE (adverse event) less than 2 percentDropout rate 6 percent – significantly below expectationsPatients enrolled well ahead of the expected timeline: 9 months to enroll 523 patients. With planned enrollment completed and the DSMB endorsement, Annovis expects topline results at the end of January 2024. Patents Annovis announced on June 27, 2023, the creation of a novel crystalline form of buntanetap (ANVS402) and the filing of a new composition of matter provisional patent with the U.S. Patent and Trademark Office (ANVS402 is covered by a composition of matter claim as well as multiple claims for chronic and acute neurodegenerative diseases and for neuropsychiatric indications). This novel composition of matter form, ANVS402, is essentially the same drug as the previous form but offers structural advantages, including better stability and higher purity. Annovis is in communication with the FDA about conducting a bridge study to allow further drug trial work to utilize the new, crystalline form, ANVS402. Approval of this patent will come with protection of ANVS402 and all its uses for a 20-year patent term. This significant time frame will enable Annovis to continue working on its robust pipeline, moving forward expeditiously toward developing novel drug therapies for many neurodegenerative diseases. Financial Results (for the quarter ending September 30, 2023) Cash and cash equivalents were $6.4 million. Research and development expenses for the third quarter were $13.8 million, compared to $4.1 million for the same period in 2022. The increase was primarily the result of an increase of $10.0 million in clinical expenses, as Annovis incurred costs related to its phase III study in early Parkinson’s Disease (PD) and its phase II/III Alzheimer's Disease (AD) study. General and administrative expenses for the third quarter were $1.0 million, compared to $2.3 million for the same period in 2022. The decrease was primarily the result of a decrease of $1.2 million in stock-based compensation expenses, and a decrease in administrative expenses of $0.1 million.\ Annovis reported a net loss of $14.7 million for the quarter, compared to a net loss of $6.4 million for the same period in 2022. Staff News Annovis was named one of the 20 PHL Inno 2023 Fire Awards Honorees. The awards recognize businesses, institutions and individuals driving the region’s innovation scene in the Philadelphia region forward. The honorees were featured in a special print edition of the Philadelphia Business Journal on August 11.Maria Maccecchini, Ph.D, Annovis founder, president, and CEO, has been named a 2023 Woman of Influence by the Philadelphia Business Journal. The award, which celebrates the impactful businesswomen shaping Greater Philadelphia, was awarded October 12, with a feature on the honorees the following day. Maria Maccecchini, Ph.D, Annovis founder, president, and CEO, presented at the ThinkEquity conference on October 20, 2023. Melissa Gaines has been promoted from vice president of clinical operations to senior vice president of clinical operations, responsible for leading all clinical project activities. Her extensive CNS experience spans from small phase I and II studies to large global phase III trials in Alzheimer’s disease, Parkinson’s disease, and other disorders. Gaines joined Annovis in 2022. Annovis scientists spoke at events featuring novel approaches in neurodegenerative diseases with other leaders in the life sciences and pharmaceutical industries: Annovis presented three posters at the Alzheimer’s Association International Conference (AAIC) 2023 annual meeting held in Amsterdam, Netherlands, from July 16-20. Dr. Fang presented two posters: “Do Mouse Data Lie? For Buntanetap, They Totally Predict Human Outcome,” and “Interim Analysis Results of Buntanetap in Phase III Clinical Studies in Alzheimer’s and Parkinson’s Disease.”A third poster was presented by Don Elbert, Ph.D., associate professor of neurology, University of Washington School of Medicine, in collaboration with Annovis through the ongoing national Alzheimer’s Disease Cooperative Study (ADCS), titled “Stable Isotope Labelling Kinetics: Models and Methods to Evaluate APP Production Rates with Posiphen Treatment in the DISCOVER Clinical Trial.”The posters’ combined findings tell the story of an exceptionally promising treatment for neurodegenerative diseases such as AD and PD. First, in a mouse model of AD, buntanetap inhibits toxic proteins in the brain, improves axonal transport, lowers inflammation, and protects nerve cells from dying, all of which is associated with improved movement and cognition. Second, these findings are also replicated in all the human AD and PD phase I and II trials to date.Third, in both mice and humans, there is also evidence of a dose-response relationship between the drug dose administered and the inhibition of the neurotoxic proteins - important in determining the optimal dosage in future phase II and III trials. Message from Dr. Maria It is tremendously rewarding and important that our drug is safe, well-tolerated, and easily administered as a once-a-day pill. The only two FDA-approved drugs for Alzheimer’s Disease require I.V. infusions and repeated brain imaging, and have well-documented, serious side effects that manifest as brain swelling or brain bleeding. As buntanetap continues to show significant progress through clinical trials, we remain on course and anticipate having topline data with good news to share on our PD study around the end of January 2024, and on our AD study in Q1 of 2024. The positive momentum we’re building with this drug is reflected in the more than 800% annual growth rate of our company over the last two years. The crystalline form of buntanetap will allow us to have a new 20-year patent protection for Annovis Bio to continue to move forward. There’s growing interest and excitement in the scientific and investment communities about our drug’s very real potential to not just alleviate devastating neurodegenerative disease symptoms but ultimately change the course of the diseases themselves. –Maria L. Maccecchini, Ph.D., Annovis Founder, President, and CEO About BuntanetapBuntanetap (previously known as ANVS401 or posiphen) is an oral translational inhibitor of neurotoxic aggregating proteins (TINAPs), whose mode of action leads to a lower level of neurotoxic proteins and consequently less toxicity in the brain. In a phase I/II clinical trial in AD and PD patients, buntanetap was shown to be well-tolerated and its pharmacokinetics were found to be in line with levels measured earlier in humans, meeting both the primary and secondary endpoints. Additionally, exploratory endpoints were also met, as treatment with buntanetap resulted in statistically significant improvement in motor function in PD patients and cognition in AD patients. Presently buntanetap is being studied in a phase III study in early PD patients with study results expected in one to two months and in a phase II/III study in mild to moderate AD patients with study results expected in Q1 2024. About Annovis Bio, Inc.Headquartered in Berwyn, Pennsylvania, Annovis Bio, Inc. is a clinical-stage, drug platform company addressing neurodegeneration, such as Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and other chronic neurodegenerative diseases. It is believed to be the only company developing a drug for both AD and PD designed to inhibit more than one neurotoxic protein to restore axonal and synaptic activity. By improving brain function, the company’s goal is to treat memory loss and dementia associated with AD as well as body and brain dysfunction associated with PD. Annovis conducted two phase I/II studies: one in AD patients and one in both AD and PD patients. In the AD/PD study buntanetap showed improvements in cognition in AD as well as movement and function in PD patients. Annovis is nearing completion of their phase III PD study and phase II/III study in AD, with study results expected in the next one and three months, respectively. For more information on Annovis Bio, please visit the Company's website www.annovisbio.com and follow us on LinkedIn, Facebook, Twitter and Threads Forward-Looking StatementsThis press release contains "forward-looking" statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The Company advises caution in reliance on forward-looking statements. Forward-looking statements include, without limitation, the Company's plans related to clinical trials. These statements involve known and unknown risks, uncertainties and other factors that may cause actual results to differ materially from those implied by forward-looking statements, including regarding patient enrollment, the effectiveness of buntanetap and the timing, effectiveness, and anticipated results of the Company's clinical trials evaluating the efficacy, safety, and tolerability of buntanetap. See also additional risk factors set forth in the Company's periodic filings with the SEC, including, but not limited to, those risks and uncertainties listed in the section entitled "Risk Factors," in the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the SEC. All forward-looking statements in this press release are based on information available to the Company as of the date of this filing. The Company expressly disclaims any obligation to update or alter its forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable law. Investor Contact:Maria L. Maccecchini, Ph. D.maccecchini@annovisbio.com SOURCE: Annovis Bio