Ocadusertib

业内传来一条重磅消息，礼来公司（Eli Lilly and Company）将以总额约32亿美元收购生物医药公司Morphic Holding，后者主打项目在研口服整合素疗法正在开发用以治疗炎症性肠病（IBD）。公开信息显示，这是礼来2024年披露的首笔生物技术公司收购，此次收购将扩展礼来的免疫学管线。这一新闻备受行业瞩目。 自身免疫疾病是以局部或全身性异常炎症免疫反应为特征的炎症免疫性疾病，全球患者人群和药物规模都在增加，是当前全球生物医药产业的热门研发领域之一。免疫学也是礼来公司布局的四大核心领域之一。本文将基于公开资料盘点下礼来公司的免疫学研发管线，以及这些管线在中国的研发进展。 根据礼来官网披露的管线信息，该公司在免疫学领域有诸多布局，靶点涉及JAK、IL-17和IL-23、PD-1、CD19、RIPK1等等。除了已获批上市的JAK1/2抑制剂巴瑞替尼、IL-17单抗依奇珠单抗、IL-23p19拮抗剂mirikizumab、IL-13特异性抗体lebrikizumab，还有10多款临床在研的免疫学研发管线，治疗领域涉及类风湿关节炎、斑秃、特应性皮炎、银屑病等。在中国，依奇珠单抗注射液和巴瑞替尼片也已经获批上市。 Mirikizumab：一款人源化IgG4单克隆抗体，可与IL-23的p19亚基结合，阻断IL-23介导的炎症反应。2023年10月，美国FDA批准该产品用于治疗中重度活动性溃疡性结肠炎（UC）成人患者。根据礼来此前新闻稿，这是首个用于治疗这一患者群体的IL-23p19拮抗剂。此外，今年5月，礼来宣布mirikizumab治疗中重度克罗恩病的关键3期研究取得积极结果，礼来已经向FDA递交该产品针对克罗恩病的新适应症上市申请。 在中国，mirikizumab注射液已经被NMPA纳入突破性治疗品种，拟开发用于治疗中重度活动性克罗恩病成人患者。其在中国已经完成了针对克罗恩病的3期临床研究患者招募工作。 Lebrikizumab：一款由Almirall公司和礼来联合开发的IL-13特异性抗体疗法，礼来拥有在欧洲以外全球其他地区的独家开发和商业化权利。Lebrikizumab于2023年11月在欧盟获得批准上市，用于青少年和成人中度至重度特应性皮炎患者。该产品已经展示出短期和长期的有效性和安全性，且维持剂量为每月一次。在中国，礼来已启动lebrikizumab注射液治疗中重度特应性皮炎的国际多中心（含中国）3期临床研究。 Peresolimab：一款PD-1激动剂抗体疗法，正在研究用于治疗类风湿性关节炎和其他自身免疫性疾病。该产品可与人类PD-1结合并作为其激动剂，抑制淋巴细胞的激活和扩增，从而恢复免疫调节，有望成为一种治疗自身免疫性疾病或自身炎症性疾病患者的新方法。2023年5月，该产品治疗难治性类风湿关节炎的2a期研究发表于《新英格兰医学杂志》（NEJM）。在中国，研究人员正在开展该产品治疗类风湿关节炎的国际多中心（含中国）2b期临床研究。 DC-806：礼来以约24亿美元收购DICE公司获得的一款口服银屑病（又称牛皮癣）疗法，为一款细胞因子白细胞介素（IL）-17A的小分子抑制剂。据悉，DICE公司专有的技术平台旨在开发能够影响蛋白-蛋白相互作用（PPI）的创新口服小分子药物，这类药物能够改变蛋白整体结构，且影响PPI的效果与抗体类药物相当。目前，公开信息尚未查阅到该药物在中国的注册进展。 LY3972406：一款离子通道蛋白Kv1.3的高选择性小分子抑制剂，目前正在研究用于治疗银屑病。2022年6月，礼来与D. E. Shaw Research公司达成合作，获得了后者在研的高选择性离子通道蛋白Kv1.3靶向治疗药物用于治疗免疫和炎症性疾病在全球的临床开发和商业化权利，并支付6000万美元的首付款及4.75亿美元后续里程碑付款。Kv1.3是一种参与效应记忆T（TEM）细胞激活和增殖的特殊离子通道，TEM细胞是许多自身免疫性疾病及某些罕见癌症的根源。目前，公开信息尚未查阅到该药物在中国的注册进展。 LY3541860：一款抑制B细胞活性的新型非耗竭CD19抗体，拟开发治疗多发性硬化。B细胞参与自身免疫性疾病的多个方面，B细胞靶向治疗已被证明对多种自身免疫性疾病有效。根据文献报道，研究表明LY3541860是一种高效的B细胞抑制剂，在治疗自身免疫性疾病时，可能比目前可用的B细胞靶向疗法疗效更佳，且不会导致B细胞耗竭。目前，公开信息尚未查阅到该药物在中国的注册进展。 Eltrekibart（LY3041658）：一款单抗疗法，可中和与CXCR1或CXCR2受体结合的趋化因子，目前正在研究用于治疗化脓性汗腺炎。据文献报道，CXCR1和CXCR2信号在中性粒细胞迁移、血管生成和肿瘤发生中起着关键作用。人体中共有7种趋化因子通过这些受体发出信号，组成了ELR+CXC趋化因子家族。为了充分拮抗CXCR1和CXCR2信号，有效的治疗方法应该阻断两种受体或全部七种配体。Eltrekibart正是一款可中和所有7种人和食蟹猴ELR+CXC趋化因子的单抗疗法。目前，公开信息尚未查阅到该药物在中国的注册进展。 Ocadusertib（LY3871801）：靶向RIPK1的小分子药物，正在研究用于治疗类风湿性关节炎。受体相互作用蛋白激酶1（RIPK1）是肿瘤坏死因子受体信号通路中的关键性信号蛋白，它能调节全身组织中的炎症和细胞死亡。目前，公开信息尚未查阅到该药物在中国的注册进展。 Ucenprubart（LY3454738）：一款免疫检查点受体蛋白激动剂，为一种靶向激活CD200R的单克隆抗体，正在被开发用于治疗特应性皮炎和其他自身免疫性疾病。CD200R在先天和适应性免疫细胞表面表达，激活这一受体可以降低细胞因子的释放和减少细胞增生。根据中国药物临床试验登记与信息公示平台官网，礼来已经在中国启动了该产品的国际多中心2期研究，评估其针对中重度特应性皮炎成人患者的疗效和安全性。 除了以上产品，礼来还有几款免疫领域产品处于1期研究阶段，已披露的产品包括了DC853（小分子新药）、GITR拮抗剂、衣康酸盐类似物（Itaconate Mimetic）等。 参考资料： [1] Lilly to Acquire Morphic to Improve Outcomes for Patients with Inflammatory Bowel Disease. Retrieved July 8, 2024 from https://www.prnewswire.com/news-releases/lilly-to-acquire-morphic-to-improve-outcomes-for-patients-with-inflammatory-bowel-disease-302190489.html [2]礼来官网管线信息. From https://www.lilly.com/discovery/clinical-development-pipeline# [3]中国药物临床试验登记与信息公示平台官网. From http://www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml 内容来源于网络，如有侵权，请联系删除。

First quarter 2023 Total Revenue of $26.1 million which includes TAVALISSE® net product sales of $22.3 million and REZLIDHIA® net product sales of $1.5 million Global expansion of TAVALISSE in ITP with Japanese launch by partner Kissei Conference call and webcast scheduled today at 4:30 p.m. Eastern Time SOUTH SAN FRANCISCO, Calif., May 2, 2023 /PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today reported financial results for the first quarter ended March 31, 2023, including sales of TAVALISSE® (fostamatinib disodium hexahydrate) tablets for the treatment of adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment and sales of REZLIDHIA® (olutasidenib) capsules for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. "We are thrilled with our strong first quarter net product sales performance, a 47% increase from Q1 2022. This reflects our ability to advance our launch of REZLIDHIA in mIDH1 R/R AML while driving continued growth in TAVALISSE ITP sales," said Raul Rodriguez, Rigel's president and CEO. "For the remainder of 2023, we have established a strong foundation for our hematology-oncology business to successfully deliver growth in both TAVALISSE and REZLIDHIA, and to advance our development programs." Business Update In the first quarter of 2023, a total of 2,281 bottles of TAVALISSE were sold in the U.S., 2,256 of which were shipped directly to patients and clinics, representing the highest number of bottles shipped to patients and clinics in a quarter since launch. During the first full quarter of launch, a total of 113 bottles of REZLIDHIA were sold in the U.S., 109 of which were shipped directly to patients and clinics. REZLIDHIA was added by the National Comprehensive Cancer Network® (NCCN®) to the latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for AML in January 2023. REZLIDHIA is included as a recommended targeted therapy for adult patients with R/R AML with IDH1 mutation. Rigel announced a peer-reviewed publication of data in Blood Advances in February 2023, which summarized clinical results from the Phase 2 registration trial of REZLIDHIA in patients with mIDH1 R/R AML. The published data demonstrate that REZLIDHIA induced durable remissions and transfusion independence with a well-characterized safety profile. In April, Rigel's partner Kissei announced the launch of TAVALISSE in Japan for the treatment of chronic ITP. Rigel continues to advance the open-label, Phase 1b clinical trial of R2891, an investigational, potent, and selective IRAK1/4 inhibitor, in patients with lower-risk myeloid dysplastic syndrome (LR-MDS) who are refractory/resistant to prior therapies. Rigel has completed enrollment of the first cohort of the trial and enrollment of the second cohort is underway. R552, an investigational, potent, and selective RIPK1 inhibitor, is being advanced by Rigel's partner Eli Lilly (Lilly). The initial Phase 2a trial in approximately 100 patients with moderately to severely active rheumatoid arthritis (RA) is anticipated to begin in the second quarter of 2023 and will involve global recruitment. The Phase 2a trial analysis is expected by the end of 2024. Financial Update For the first quarter of 2023, Rigel reported a net loss of $13.5 million, or $0.08 per basic and diluted share, compared to a net loss of $27.4 million, or $0.16 per basic and diluted share, for the same period of 2022. For the first quarter of 2023, total revenues were $26.1 million, consisting of $22.3 million in TAVALISSE net product sales, $1.5 million in REZLIDHIA net product sales, and $2.3 million in contract revenues from collaborations. TAVALISSE net product sales of $22.3 million increased by 38% from $16.2 million for the same period of 2022. Contract revenues from collaborations for the first quarter of 2023 consisted primarily of revenue from Grifols S.A., with $1.6 million related to the delivery of drug supplies and a royalty of $0.7 million. For the first quarter of 2023, total costs and expenses were $38.8 million, compared to $43.0 million for the same period of 2022. The decrease in costs and expenses was primarily due to decreased research and development costs related to the Phase 3 clinical trial of fostamatinib for wAIHA, the Phase 3 clinical trial of fostamatinib in high-risk hospitalized patients with COVID-19, and the IRAK 1/4 inhibitor program. As of March 31, 2023, Rigel had cash, cash equivalents and short-term investments of $58.7 million, compared to $58.2 million as of December 31, 2022. In March 2023, Rigel accessed an additional $20.0 million term loan through its credit facility with MidCap Financial Trust. Conference Call and Webcast with Slides Today at 4:30pm Eastern Time Rigel will hold a live conference call and webcast today at 4:30pm Eastern Time (1:30pm Pacific Time). Participants can access the live conference call by dialing (877) 407-3088 (domestic) or (201) 389-0927 (international). The conference call will also be webcast live and can be accessed from the Investor Relations section of the company's website at . The webcast will be archived and available for replay after the call via the Rigel website. About ITP In patients with ITP (immune thrombocytopenia), the immune system attacks and destroys the body's own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs), and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP. About AML Acute myeloid leukemia (AML) is a rapidly progressing cancer of the blood and bone marrow that affects myeloid cells, which normally develop into various types of mature blood cells. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that in the United States alone, there will be about 20,380 new cases, most in adults, in 2023.2 Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.3 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.4 Quality of life declines for patients with each successive line of treatment for AML, and well-tolerated treatments in relapsed or refractory disease remain an unmet need. About TAVALISSE® Indication TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Important Safety Information Warnings and Precautions Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required. Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to ≥3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation. Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE. Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation. TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose. Drug Interactions Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose. It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406. Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug. Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug. Adverse Reactions Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%). Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia. Please see for full Prescribing Information. To report side effects of prescription drugs to the FDA, visit or call 1-800-FDA-1088 (800-332-1088). TAVALISSE and TAVLESSE are registered trademarks of Rigel Pharmaceuticals, Inc. About REZLIDHIA® INDICATION REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Differentiation Syndrome REZLIDHIA can cause differentiation syndrome. In the clinical trial of REZLIDHIA in patients with relapsed or refractory AML, differentiation syndrome occurred in 16% of patients, with grade 3 or 4 differentiation syndrome occurring in 8% of patients treated, and fatalities in 1% of patients. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal. Symptoms of differentiation syndrome in patients treated with REZLIDHIA included leukocytosis, dyspnea, pulmonary infiltrates/pleuropericardial effusion, kidney injury, fever, edema, pyrexia, and weight gain. Of the 25 patients who experienced differentiation syndrome, 19 (76%) recovered after treatment or after dose interruption of REZLIDHIA. Differentiation syndrome occurred as early as 1 day and up to 18 months after REZLIDHIA initiation and has been observed with or without concomitant leukocytosis. If differentiation syndrome is suspected, temporarily withhold REZLIDHIA and initiate systemic corticosteroids (e.g., dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and until resolution of signs and symptoms. If concomitant leukocytosis is observed, initiate treatment with hydroxyurea, as clinically indicated. Taper corticosteroids and hydroxyurea after resolution of symptoms. Differentiation syndrome may recur with premature discontinuation of corticosteroids and/or hydroxyurea treatment. Institute supportive measures and hemodynamic monitoring until improvement; withhold dose of REZLIDHIA and consider dose reduction based on recurrence. Hepatotoxicity REZLIDHIA can cause hepatotoxicity, presenting as increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased blood alkaline phosphatase, and/or elevated bilirubin. Of 153 patients with relapsed or refractory AML who received REZLIDHIA, hepatotoxicity occurred in 23% of patients; 13% experienced grade 3 or 4 hepatotoxicity. One patient treated with REZLIDHIA in combination with azacitidine in the clinical trial, a combination for which REZLIDHIA is not indicated, died from complications of drug-induced liver injury. The median time to onset of hepatotoxicity in patients with relapsed or refractory AML treated with REZLIDHIA was 1.2 months (range: 1 day to 17.5 months) after REZLIDHIA initiation, and the median time to resolution was 12 days (range: 1 day to 17 months). The most common hepatotoxicities were elevations of ALT, AST, blood alkaline phosphatase, and blood bilirubin. Monitor patients frequently for clinical symptoms of hepatic dysfunction such as fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice. Obtain baseline liver function tests prior to initiation of REZLIDHIA, at least once weekly for the first two months, once every other week for the third month, once in the fourth month, and once every other month for the duration of therapy. If hepatic dysfunction occurs, withhold, reduce, or permanently discontinue REZLIDHIA based on recurrence/severity. ADVERSE REACTIONS The most common (≥20%) adverse reactions, including laboratory abnormalities, were aspartate aminotransferase increased, alanine aminotransferase increased, potassium decreased, sodium decreased, alkaline phosphatase increased, nausea, creatinine increased, fatigue/malaise, arthralgia, constipation, lymphocytes increased, bilirubin increased, leukocytosis, uric acid increased, dyspnea, pyrexia, rash, lipase increased, mucositis, diarrhea and transaminitis. DRUG INTERACTIONS Avoid concomitant use of REZLIDHIA with strong or moderate CYP3A inducers. Avoid concomitant use of REZLIDHIA with sensitive CYP3A substrates unless otherwise instructed in the substrates prescribing information. If concomitant use is unavoidable, monitor patients for loss of therapeutic effect of these drugs. LACTATION Advise women not to breastfeed during treatment with REZLIDHIA and for 2 weeks after the last dose. GERIATRIC USE No overall differences in effectiveness were observed between patients 65 years and older and younger patients. Compared to patients younger than 65 years of age, an increase in incidence of hepatotoxicity and hypertension was observed in patients ≥65 years of age. HEPATIC IMPAIRMENT In patients with mild or moderate hepatic impairment, closely monitor for increased probability of differentiation syndrome. Click here for Full Prescribing Information, including Boxed WARNING. To report side effects of prescription drugs to the FDA, visit or call 1-800-FDA-1088 (800-332-1088). REZLIDHIA is a registered trademark of Rigel Pharmaceuticals, Inc. About Rigel Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve the lives of patients with hematologic disorders and cancer. Founded in 1996, Rigel is based in South San Francisco, California. For more information on Rigel, the Company's marketed products and pipeline of potential products, visit . R289 is an investigational compound not approved by the FDA The American Cancer Society. Key Statistics for Acute Myeloid Leukemia (AML). Revised January 12, 2023. Accessed Feb. 15, 2023: Leukaemia Care. Relapse in Acute Myeloid Leukaemia (AML). Version 3. Reviewed October 2021. Accessed Feb 15, 2023: Thol F, Schlenk RF, Heuser M, Ganser A. How I treat refractory and early relapsed acute myeloid leukemia. Blood (2015) 126 (3): 319-27. doi: Forward Looking Statements This press release contains forward-looking statements relating to, among other things, the potential and market opportunity of olutasidenib as therapeutics for R/R AML and other conditions, the commercialization of fostamatinib in the U.S. and international markets including Japan, and Rigel's ability to further develop its clinical stage and early-stage product candidates and Rigel's partnering effort, including the progress of Phase 1b clinical trial of R289 for the treatment of lower-risk myeloid dysplastic syndrome, and the advancement of Phase 2a clinical trial of R552 for the treatment of rheumatoid arthritis. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Forward-looking statements can be identified by words such as "plan", "potential", "may", "expects", "will" and similar expressions in reference to future periods. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on Rigel's current beliefs, expectations, and assumptions and hence they inherently involve significant risks, uncertainties and changes in circumstances that are difficult to predict and many of which are outside of our control. Therefore, you should not rely on any of these forward-looking statements. Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties, which include, without limitation, risks and uncertainties associated with the commercialization and marketing of TAVALISSE or REZLIDHIA; risks that the FDA, European Medicines Agency, PMDA or other regulatory authorities may make adverse decisions regarding fostamatinib or olutasidenib; risks that clinical trials may not be predictive of real-world results or of results in subsequent clinical trials; risks that fostamatinib or olutasidenib may have unintended side effects, adverse reactions or incidents of misuses; the availability of resources to develop Rigel's product candidates; market competition; as well as other risks detailed from time to time in Rigel's reports filed with the Securities and Exchange Commission, including its Annual Report on Form 10-K for the year ended December 31, 2022 and subsequent filings. Any forward-looking statement made by us in this press release is based only on information currently available to us and speaks only as of the date on which it is made. Rigel does not undertake any obligation to update forward-looking statements, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise, and expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein, except as required by law. Contact for Investors & Media: Investors: Rigel Pharmaceuticals, Inc. 650.624.1232 [email protected] Media: David Rosen Argot Partners 212.600.1902 [email protected] SOURCE Rigel Pharmaceuticals, Inc.