Epileptic encephalopathy

− Pre-Specified Interim Analysis Shows Positive Safety and Efficacy Results; Mezagitamab Safe and Well Tolerated − Takeda Intends to Initiate a Global Phase 3 Trial of Mezagitamab in Patients with Primary Immune Thrombocytopenia in Fiscal Year 2024 − Late-Stage Pipeline Continues to Gain Momentum With Five New Molecular Entities in Phase 3 Development in Fiscal Year 2024 OSAKA, Japan & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Takeda (TSE:4502/NYSE:TAK) today announced positive topline results from a Phase 2, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability and efficacy of mezagitamab (TAK-079) in patients with persistent or chronic primary immune thrombocytopenia (ITP). Mezagitamab is a fully human immunoglobulin IgG1 monoclonal antibody (mAb) with high affinity for CD38 expressing cells (including plasmablasts, plasma cells, natural killer cells) resulting in their depletion. The TAK-079-1004 trial (NCT04278924) evaluated three different doses of subcutaneous mezagitamab vs placebo, given once weekly for eight weeks in patients with chronic (more than one year in duration) or persistent (3-12 months in duration) primary ITP. An interim analysis of the ongoing Phase 2 study demonstrated positive safety and efficacy results. Mezagitamab has been generally safe and well tolerated across all three cohorts. All mezagitamab doses tested demonstrated a higher platelet response rate than placebo. The increases in platelet count were dose-dependent with the greatest platelet response observed at the highest dose tested. Platelet response in mezagitamab treated patients occurred rapidly and was maintained post-therapy. Based on these positive results, and following consultation with global health authorities, Takeda plans to initiate a global Phase 3 trial of mezagitamab in ITP in fiscal year 2024. When mezagitamab advances to Phase 3 in ITP Takeda will have five new molecular entities in Phase 3 development in fiscal year 2024 including TAK-279 for the treatment of psoriasis and psoriatic arthritis, TAK-861 for the treatment of narcolepsy type 1, soticlestat for the treatment of Lennox-Gastaut syndrome and Dravet syndrome, and fazirsiran for the treatment of α1-antitrypsin associated liver disease. ITP is a rare, IgG mediated autoimmune disease caused, in part, by the development of autoantibodies to platelets (and/or megakaryocytes), which are blood cells responsible for preventing or stopping bleeding. ITP is characterized by the accelerated destruction of platelets (with or without impaired production), resulting in a decreased platelet count and an increased risk of bleeding, which can be debilitating (including fatigue and impaired quality of life), and in severe cases may be life-threatening. The precedent for approval of new drugs in this indication requires that platelet counts be maintained at 50,000/uL or more for a sustained period. Approximately 20 percent of patients with ITP do not achieve a platelet count above 50,000/uL following treatment with available first- and second-line therapies creating significant patient burden and unmet need for a disease modifying treatment that is also tolerable.1,2 “These Phase 2 results demonstrate mezagitamab’s compelling disease modifying mechanism of action, which has the potential to achieve disease remission for people with ITP. There remains considerable unmet need among ITP patients who may not respond or have inadequate response to prior treatment. In addition, some patients who do respond to available therapies struggle to manage side effects or relapse despite treatment,” said Chinwe Ukomadu, Head of the Gastrointestinal & Inflammation Therapeutic Area Unit at Takeda. “We look forward to initiating the Phase 3 trial and presenting these data at an upcoming scientific congress.” Therapy with mezagitamab is designed to deliver rapid and sustained improvement in platelet response and generally rapidly restores platelet counts to functional levels. Mezagitamab previously received Orphan Drug Designation for the treatment of ITP from the U.S. Food and Drug Administration and the program recently received Fast Track Designation. Results from the Phase 2 trial have no impact on the full year consolidated reported forecast for the fiscal year ending March 31, 2024 (Fiscal Year 2023). About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience, and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit . 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Takeda does not undertake to update any of the forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule. Past performance is not an indicator of future results and the results or statements of Takeda in this press release may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda’s future results. Medical Information This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. References Provan D, Donald A, et al. Blood Advances. 2019;26;3(22):3780-3817. Rodeghiero F. International Journal of Hematology. 2023;117:316–33.

Bexicaserin (LP352) Phase 1b/2a PACIFIC Study positive topline data in participants with Developmental and Epileptic Encephalopathies (DEEs) was reported in January Announcing an update to the primary efficacy endpoint data previously reported in January, which show further improvement in seizure reductions and no change in the reported safety results – bexicaserin achieved a median seizure reduction of 59.8% in countable motor seizures compared to 17.4% in the placebo group across the DEE study population. A median seizure reduction of 74.6% in Dravet Syndrome (DS), 50.8% in Lennox-Gastaut Syndrome (LGS) and 65.5% in DEE Other was achieved PACIFIC data to be presented at medical meetings in Q2 2024 Preparing for End of Phase 2 Meeting with regulators and conducting start-up activities for bexicaserin’s global Phase 3 program; expect to initiate the Phase 3 program by YE 2024 LP659 first-in-human Phase 1 single-ascending dose (SAD) study topline data expected Q2 2024 Completed public offering of common stock with gross proceeds of $241.5 million LA JOLLA, Calif.--(BUSINESS WIRE)-- Longboard Pharmaceuticals, Inc. (Nasdaq: LBPH), a clinical-stage biopharmaceutical company focused on developing novel, transformative medicines for neurological diseases, today provided a corporate update and reported full year 2023 financial results. “I am extremely proud of what our team has accomplished starting with the immense effort that went into the PACIFIC Study in participants with DEEs. We are impressed with the data in this study showing evidence of a potentially clinically meaningful benefit for both overall median seizure reduction and seizure reduction across all subgroups for Dravet, LGS and DEE Other. We are motivated by the enthusiasm and anticipation from the DEE community for our Phase 3 program and look forward to providing additional details later in the year. With the completion of our recent financing, we believe we are well positioned to deliver on key milestones later this year, including presenting additional topline and open-label extension data from PACIFIC, conducting our End of Phase 2 Meeting with the FDA, and initiating our global Phase 3 program. We appreciate the tremendous support from our existing and new shareholders who play an integral part in the continued success of Longboard. “We also look forward to Phase 1 topline SAD data next quarter from our second clinical-stage asset, LP659, an oral, centrally acting, highly selective S1P receptor modulator,” stated Kevin R. Lind, Longboard’s President and Chief Executive Officer. PACIFIC STUDY UPDATE In January 2024, we announced positive topline data from the Phase 1b/2a PACIFIC Study evaluating bexicaserin (LP352) in 52 participants with a broad range of DEEs, including DS (4), LGS (29) and other DEEs (19). Of the 52 participants enrolled in the study, 43 participants were randomized to bexicaserin (DS=4, LGS=24, DEE Other=15) and 9 to placebo (DS=0, LGS=5, DEE Other=4). Of note, results were on top of current standard of care; participants were typically on 3-4 other anti-seizure medications. Following our review of the full data set, we are announcing an update to the previously reported primary efficacy endpoint data. The updated data, which show even further improvements in seizure reductions and do not change the reported safety results, reflect corrections made by the study’s contract research organization to their statistical programming errors. The following table outlines the revisions: Revised Previously Reported Median percent change from baseline in countable motor seizure frequency: Bexicaserin Placebo Delta Bexicaserin Placebo Delta Overall 59.8% 17.4% 42.4% 53.3% 20.8% 32.5% DS 74.6% N/A N/A 72.1% N/A N/A LGS 50.8% 17.4% 33.4% 48.1% 20.8% 27.3% DEE Other 65.5% 32.2% 33.3% 61.2% 32.6% 28.6% UPCOMING MILESTONES: Bexicaserin (LP352), an oral, centrally acting, 5-HT2C superagonist in development for the potential treatment of seizures associated with DEEs PACIFIC data to be presented at medical meetings in Q2 2024 PACIFIC open-label extension (OLE) data expected in H2 2024 100% of PACIFIC completers entered into the OLE study Preparing for our End of Phase 2 Meeting with U.S. Food and Drug Administration (FDA) and aligning with other regulatory agencies Planning for Phase 3 initiation before YE 2024 LP659, an oral, centrally acting, S1P receptor subtypes 1 and 5 (S1P1,5) modulator in development for rare neuroinflammatory conditions Phase 1 SAD topline data expected in Q2 2024 FULL YEAR 2023 FINANCIAL RESULTS: Balance Sheet Highlights At December 31, 2023, Longboard’s cash, cash equivalents and short-term investments were approximately $48.5 million. On January 8, 2024, we completed a public offering of 11,500,000 shares of common stock and received gross proceeds of $241.5 million before deducting underwriting discounts and commissions of $14.5 million and offering expenses of $0.5 million. As of January 31, 2024, Longboard’s cash, cash equivalents and short-term investments were approximately $272.4 million. Operating Results Research and development expenses were $43.8 million for the year ended December 31, 2023, an increase of $9.2 million or 26.3%, compared to $34.6 million for the year ended December 31, 2022. The net increase of $9.2 million is primarily related to increases of $6.0 million in preclinical and clinical trial expenses related to bexicaserin, $2.7 million in personnel-related expenses, $0.5 million in other preclinical programs and early stage research expenses and $0.2 million of other miscellaneous expenses, offset by a decrease of $0.3 million in preclinical and clinical trial expenses related to LP659. General and administrative expenses were $13.0 million for the year ended December 31, 2023, an increase of $2.8 million or 28.0%, compared to $10.2 million for the year ended December 31, 2022. The net increase of $2.8 million is primarily related to increases of $1.7 million in personnel-related costs, $1.2 million of professional services and consulting expenses, and $0.4 million of other miscellaneous expenses, offset by a decrease of $0.5 million in insurance expense. ABOUT LONGBOARD PHARMACEUTICALS Longboard Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on developing novel, transformative medicines for neurological diseases. Longboard is working to advance a portfolio of centrally acting product candidates designed to be highly selective for specific G protein-coupled receptors (GPCRs). Longboard’s small molecule product candidates are based on more than 20 years of GPCR research. Longboard plans to advance bexicaserin (LP352), an oral, centrally acting 5-hydroxytryptamine 2C (5-HT2C) receptor superagonist, with no observed impact on 5-HT2B and 5-HT2A receptor subtypes, into a global Phase 3 program. Longboard recently reported positive topline data from a Phase 1b/2a clinical trial (the PACIFIC Study) evaluating bexicaserin in participants ages 12 to 65 years old with Developmental and Epileptic Encephalopathies (DEEs), including Lennox-Gastaut syndrome, Dravet syndrome and other DEEs. Longboard is also evaluating LP659, an oral, centrally acting, sphingosine-1-phosphate (S1P) receptor subtypes 1 and 5 modulator, which is in development for the potential treatment of rare neuroinflammatory conditions. Longboard is conducting a Phase 1 single-ascending dose (SAD) clinical trial for LP659 in healthy volunteers, with topline data expected in the second quarter of 2024. FORWARD-LOOKING STATEMENTS Certain statements in this press release are forward-looking statements that involve a number of risks and uncertainties. In some cases, you can identify forward-looking statements by words such as “to be”, “expect”, “focused on”, “anticipation”, “look forward”, “well positioned”, “plan”, “working to”, “designed to”, the negative, plural or other tenses of these words, references to specific future dates or time periods, or other comparable language, and they may include, without limitation, statements about the following: Longboard’s clinical and preclinical product candidates and programs, including their advancement (including plans for an End of Phase 2 Meeting and for alignment with other regulatory agencies and plans for a global Phase 3 program for bexicaserin), timing of study initiation (including for a global Phase 3 program for bexicaserin), timing of topline data (including for the PACIFIC OLE study for bexicaserin and the Phase 1 SAD study for LP659), their potential (including to be transformative, best-in-class, clinically meaningful or highly selective, the number and type of conditions they may address and their commercial opportunity), and their design and characteristics; upcoming presentations (including of additional PACIFIC topline data); Longboard’s cash position, expenses and runway to support operations; and Longboard’s focus and work. For such statements, Longboard claims the protection of the Private Securities Litigation Reform Act of 1995. Actual events or results may differ materially from Longboard’s expectations. Factors that could cause actual results to differ materially from those stated or implied by Longboard’s forward-looking statements include, but are not limited to, the following: risks related to Longboard’s limited operating history, financial position and need for additional capital; Longboard will need additional managerial and financial resources to advance all of its programs, and you and others may not agree with the manner Longboard allocates its resources; risks related to the development and commercialization of Longboard’s product candidates; Longboard’s product candidates are in the early phase of a lengthy research and development process, the timing, manner and outcome of research, development and regulatory review is uncertain, and Longboard’s product candidates may not advance in research or development or be approved for marketing; enrolling participants in Longboard’s ongoing and intended clinical trials is competitive and challenging; PACIFIC Study participants’ diagnoses are as of time of screening and are subject to change; risks related to unexpected or unfavorable new data; nonclinical and clinical data is voluminous and detailed, and regulatory agencies may interpret or weigh the importance of data differently and reach different conclusions than Longboard or others, request additional information, have additional recommendations or change their guidance or requirements before or after approval; results of clinical trials and other studies are subject to different interpretations and may not be predictive of future results; topline data may not accurately reflect the complete results of a particular study or trial; risks related to relying on licenses or collaborative arrangements; other risks related to Longboard’s dependence on third parties; competition; product liability or other litigation or disagreements with others; government and third-party payor actions, including relating to reimbursement and pricing; risks related to regulatory compliance; and risks related to Longboard’s and third parties’ intellectual property rights. Additional factors that could cause actual results to differ materially from those stated or implied by Longboard’s forward-looking statements are disclosed in Longboard’s filings with the Securities and Exchange Commission (SEC). These forward-looking statements represent Longboard’s judgment as of the time of this release. Longboard disclaims any intent or obligation to update these forward-looking statements, other than as may be required under applicable law. LONGBOARD PHARMACEUTICALS, INC. BALANCE SHEETS December 31, December 31, (in thousands, except share and per share data) 2023 2022 ASSETS Current assets: Cash and cash equivalents $ 14,331 $ 10,775 Short-term investments 34,167 56,814 Prepaid expenses and other current assets 1,723 2,249 Total current assets 50,221 69,838 Right-of-use assets 472 736 Property and equipment 4 9 Other long-term assets — 33 Total assets $ 50,697 $ 70,616 LIABILITIES AND EQUITY Current liabilities: Accounts payable $ 1,001 $ 1,310 Accrued research and development expenses 4,556 4,168 Accrued compensation and related expenses 3,374 2,438 Accrued other expenses 368 490 Right-of-use liabilities, current portion 475 358 Total current liabilities 9,774 8,764 Right-of-use liabilities, net of current portion — 382 Commitments and contingencies Stockholders' equity: Preferred stock, $0.0001 par value; authorized shares - 10,000,000 at December 31, 2023 and 2022, respectively; issued and outstanding shares - none at December 31, 2023 and 2022 — — Voting common stock, $0.0001 par value; authorized shares - 300,000,000 at December 31, 2023 and 2022, respectively; issued and outstanding shares - 22,096,494 and 13,585,950 at December 31, 2023 and 2022, respectively 2 1 Non-voting common stock, $0.0001 par value; authorized shares - 10,000,000 at December 31, 2023 and 2022, respectively; issued and outstanding shares - 2,420,755 and 3,629,400 at December 31, 2023 and 2022, respectively — — Additional paid-in capital 181,563 148,303 Accumulated other comprehensive loss (78 ) (692 ) Accumulated deficit (140,564 ) (86,142 ) Total stockholders' equity 40,923 61,470 Total liabilities and stockholders' equity $ 50,697 $ 70,616 LONGBOARD PHARMACEUTICALS, INC. STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS Year Ended December 31, (in thousands, except share and per share data) 2023 2022 Operating expenses: Research and development $ 43,752 $ 34,638 General and administrative 13,007 10,160 Total operating expenses 56,759 44,798 Loss from operations (56,759 ) (44,798 ) Interest income, net 2,405 837 Other income (expense) (68 ) 16 Net loss $ (54,422 ) $ (43,945 ) Net loss per share, basic and diluted $ (2.39 ) $ (2.56 ) Weighted-average shares outstanding, basic and diluted 22,726,325 17,150,907 Comprehensive loss: Net loss $ (54,422 ) $ (43,945 ) Unrealized gain (loss) on short-term investments 614 (528 ) Comprehensive loss $ (53,808 ) $ (44,473 )

Daiichi Sankyo’s quizartinib is indicated for use as a first-line treatment in adults with acute myeloid leukaemia. Credit: Nemes Laszlo / Shutterstock.com. The UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation to Daiichi Sankyo for quizartinib (Vanflyta) for use as a first-line treatment in adults with acute myeloid leukaemia (AML) with a FLT3-ITD mutation. The decision allows for the oral administration of quizartinib in combination with chemotherapy – a significant development in the treatment of AML. Taken once daily, quizartinib targets tyrosine kinases to hinder the growth of abnormal bone marrow cells. The treatment duration and dosage are determined by the prescribing physician and may continue post-chemotherapy. The approval is backed by a double-blind, randomised, placebo-controlled Phase III clinical trial in 539 adult subjects aged between 18 and 75 years with newly diagnosed FLT3-ITD positive AML. See Also: MHRA approves Marinus’ ganaxolone for CDKL5 deficiency disorder Innovent’s ROS1 TKI is one step closer to winning the Chinese NSCLC market The study demonstrated a statistically significant improvement in overall survival (time from randomisation to death from any cause) for patients who received quizartinib. Patients receiving quizartinib had a median overall survival of 31.9 months compared to 15.1 months for those receiving a placebo. Abnormal liver enzymes, low blood platelet and white blood cell levels, anaemia, diarrhoea, nausea, stomach pain and headache were the most common side effects linked to the trial. MHRA Healthcare Quality and Access interim executive director Julian Beach stated: “ Our key priorities are keeping patients safe and enabling their access to high quality, safe and effective medical products. “We’re assured that the appropriate regulatory standards for the approval of this medicine have been met. As with all medicines, we will keep its safety under close review.” In another development, the MHRA also gave marketing authorisation to Pfizer for etrasimod (Velsipity) for the treatment of moderately to severely active ulcerative colitis. Etrasimod is prescribed as a long-term treatment and should be initiated only under a doctor’s supervision. The approval is supported by two clinical studies, ELEVATE UC 52 and ELEVATE UC 12, indicating its efficacy for patients where standard treatments were inadequate. The UK National Institute for Health and Care Excellence (NICE) has also published a final guidance recommending etrasimod for ulcerative colitis. With the NICE recommendation, more than 25,000 people in England will be eligible to receive the treatment. The latest development comes after the MHRA approved Marinus Pharmaceuticals ’ ganaxolone, marketed as Ztalmy, an anti-seizure medication for cyclin-dependent kinase-like 5 (CDLK5) deficiency disorder .