C1 Esterase Inhibitor (Human) (ViroPharma)

First patient dosed in open label extension (OLE) study with 25 mg daily dosing of nomlabofusp; interim data on track for Q4 2024 Positive top-line Phase 2 dose exploration study data demonstrated nomlabofusp was generally well-tolerated with dose-dependent increases in tissue frataxin levels, reinforcing therapeutic potentialBiologics License Application (“BLA”) submission targeted for 2H 2025; discussions initiated with Food and Drug Administration (“FDA”) on potential to pursue accelerated approval pathwaySuccessful $161.8 million financing strengthens cash, cash equivalents, and marketable securities to $239 million as of March 31, 2024, extending projected cash runway into 2026 BALA CYNWYD, Pa., May 09, 2024 (GLOBE NEWSWIRE) -- Larimar Therapeutics, Inc. (“Larimar”) (Nasdaq: LRMR), a clinical-stage biotechnology company focused on developing treatments for complex rare diseases, today reported its first quarter 2024 operating and financial results. “We have started 2024 off strong, achieving critical milestones that support late-stage advancement of our nomlabofusp clinical program. Positive Phase 2 dose exploration study data demonstrated that nomlabofusp appears to be generally well-tolerated, and observed dose dependent increases in tissue frataxin levels that have the potential to address the underlying frataxin deficiency that is the root cause of Friedreich’s ataxia (FA). In March, we dosed the first patient in our OLE study and continue to enroll patients and activate additional sites. We are on track to report interim data in the fourth quarter of the year which will inform on the long-term safety and tissue frataxin levels of nomlabofusp,” said Carole Ben-Maimon, MD, President, and Chief Executive Officer of Larimar. “Together, these datasets will help support our BLA submission which we are targeting for the second half of 2025. We are continuing our regulatory discussions with the FDA on the potential use of frataxin as a novel surrogate endpoint to support accelerated approval and are planning for a global double-blind placebo-controlled confirmatory study which we expect to initiate prior to BLA submission. With our recent capital infusion and runway extended through key registrational catalysts, we are well positioned to further advance the first potential therapy to increase frataxin levels in patients with FA.” Recent Highlights In February 2024, Larimar announced positive top-line data and successful completion of its four-week, placebo-controlled Phase 2 dose exploration study of nomlabofusp (CTI-1601) in patients with FA. Nomlabofusp was generally well-tolerated throughout the four-week treatment periods, had a predictable pharmacokinetic profile, and led to dose-dependent increases in frataxin in skin and buccal cells after daily dosing for 14 days followed by every other day dosing until day 28 in the 25 mg and 50 mg cohorts. Increases in frataxin levels in skin cells were seen in all treated patients, and in buccal cells for the majority of patients. At Day 14, all patients (with quantifiable levels at baseline and Day 14) treated with 50 mg of nomlabofusp achieved frataxin levels in skin cells greater than 33% of the average level observed in healthy volunteers, with 3 patients achieving levels greater than 50% of the average healthy volunteer level.In February 2024, Larimar announced the Company had initiated discussions with the FDA on use of tissue frataxin levels as a potential novel surrogate endpoint. Larimar received FDA acknowledgement that frataxin deficiency appears to be critical to the pathogenic mechanism of FA, and that there continues to be an unmet need for treatments that address the underlying disease pathophysiology. The Company intends to pursue an accelerated approval using FXN levels, supportive pharmacodynamics and clinical information, and safety data from the OLE study, along with additional nonclinical pharmacology information needed to support the novel surrogate endpoint approach, with a BLA submission targeted for the second half of 2025.In February 2024, Larimar raised net proceeds of approximately $161.8 million through a public offering of common stock.In March 2024, the first patient was dosed in the OLE study evaluating daily subcutaneous injections of 25 mg of nomlabofusp self-administered or administered by a caregiver. Participants who completed treatment in the Phase 2 dose exploration study, or who previously completed a prior clinical trial of nomlabofusp, are potentially eligible to screen for the OLE study. The OLE study will evaluate the safety and tolerability, pharmacokinetics, and frataxin levels in peripheral tissues as well as other exploratory pharmacodynamic markers (lipid profiles and gene expression data) following long-term subcutaneous administration of nomlabofusp. Dose escalation in the OLE study is contingent on the FDA’s review of data from the 50 mg cohort of the Phase 2 study and available data from the OLE study, due to the continued partial clinical hold. Interim data is expected in the fourth quarter of 2024. In addition, clinical assessments collected during the study will be compared to data from a matched control arm derived from participants in the Friedreich’s Ataxia Clinical Outcomes Measures Study (FACOMS) database.In March 2024, Larimar began to build its commercial team with the appointment of Frank Nazzario, RPh, as Vice President of Commercial. Mr. Nazzario brings nearly 30 years of leadership experience in drug launches for rare diseases. Most recently, he served as Senior Vice President of Sales at BioCryst Pharmaceuticals. Previously, he held commercial leadership roles at Spark Therapeutics where he led the commercialization of Luxturna®, the first FDA-approved gene therapy for an inherited retinal disorder, and at ViroPharma, Inc., where he led the launch of Cinryze®, the first approved biologic for Hereditary Angioedema. First Quarter 2024 Financial Results As of March 31, 2024, the Company had cash, cash equivalents and marketable securities totaling $239 million. In February 2024, we raised approximately $161.8 million in net proceeds through a public offering of common stock. The Company reported a net loss for the first quarter of 2024 of $14.7 million, or $0.27 per share, compared to a net loss of $6.5 million, or $0.15 per share, for the first quarter of 2023. Research and development expenses for the first quarter of 2024 were $12.9 million, compared to $4.6 million for the first quarter of 2023. The increase in research and development expenses was primarily driven by an increase of $5.7 million in nomlabofusp manufacturing costs, an increase of $1.0 million in clinical costs primarily associated with the initiation of the OLE study, an increase of $1.0 million in personnel expense driven by increasing headcount, an increase of $0.3 million in consulting fees and an increase of $0.2 million in stock compensation expense. General and administrative expenses were $3.8 million in the first quarter of 2024, compared to $3.1 million in the first quarter of 2023. The increase in general and administrative expenses was primarily driven by an increase of $0.2 million in personnel expense, an increase of $0.2 million in legal fees, and an increase of $0.1 million in stock compensation expense. About Larimar TherapeuticsLarimar Therapeutics, Inc. (Nasdaq: LRMR), is a clinical-stage biotechnology company focused on developing treatments for complex rare diseases. Larimar’s lead compound, nomlabofusp, is being developed as a potential treatment for Friedreich's ataxia. Larimar also plans to use its intracellular delivery platform to design other fusion proteins to target additional rare diseases characterized by deficiencies in intracellular bioactive compounds. For more information, please visit: https://larimartx.com. Forward-Looking StatementsThis press release contains forward-looking statements that are based on Larimar’s management’s beliefs and assumptions and on information currently available to management. All statements contained in this release other than statements of historical fact are forward-looking statements, including but not limited to statements regarding Larimar’s ability to develop and commercialize nomlabofusp (also known as CTI-1601) and other planned product candidates, Larimar’s planned research and development efforts, including the timing of its nomlabofusp clinical trials, interactions with the FDA and overall development plan and other matters regarding Larimar’s business strategies, ability to raise capital, use of capital, results of operations and financial position, and plans and objectives for future operations. In some cases, you can identify forward-looking statements by the words “may,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “anticipate,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “ongoing” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. These statements involve risks, uncertainties and other factors that may cause actual results, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements. These risks, uncertainties and other factors include, among others, the success, cost and timing of Larimar’s product development activities, nonclinical studies and clinical trials, including nomlabofusp clinical milestones and continued interactions with the FDA; that preliminary clinical trial results may differ from final clinical trial results, that earlier non-clinical and clinical data and testing of nomlabofusp may not be predictive of the results or success of later clinical trials, and assessments; that the FDA may not ultimately agree with Larimar’s nomlabofusp development strategy; the potential impact of public health crises on Larimar’s future clinical trials, manufacturing, regulatory, nonclinical study timelines and operations, and general economic conditions; Larimar’s ability and the ability of third-party manufacturers Larimar engages, to optimize and scale nomlabofusp’s manufacturing process; Larimar’s ability to obtain regulatory approvals for nomlabofusp and future product candidates; Larimar’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators, and to successfully commercialize any approved product candidates; Larimar’s ability to raise the necessary capital to conduct its product development activities; and other risks described in the filings made by Larimar with the Securities and Exchange Commission (SEC), including but not limited to Larimar’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the SEC and available at www.sec.gov. These forward-looking statements are based on a combination of facts and factors currently known by Larimar and its projections of the future, about which it cannot be certain. As a result, the forward-looking statements may not prove to be accurate. The forward-looking statements in this press release represent Larimar’s management’s views only as of the date hereof. Larimar undertakes no obligation to update any forward-looking statements for any reason, except as required by law. Investor Contact:Joyce AllaireLifeSci Advisorsjallaire@lifesciadvisors.com(212) 915-2569 Company Contact:Michael CelanoChief Financial Officermcelano@larimartx.com(484) 414-2715 Larimar Therapeutics, Inc.Condensed Consolidated Balance Sheet(unaudited) March 31, December 31, 2024 2023 Assets Current assets: Cash and cash equivalents $110,125 $26,749 Short-term marketable securities 117,171 60,041 Prepaid expenses and other current assets 3,657 3,385 Total current assets 230,953 90,175 Long-term marketable securities 11,711 — Property and equipment, net 604 684 Operating lease right-of-use assets 2,920 3,078 Restricted cash 1,339 1,339 Other assets 678 659 Total assets $248,205 $95,935 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable $1,918 $1,283 Accrued expenses 10,098 7,386 Operating lease liabilities, current 825 837 Total current liabilities 12,841 9,506 Operating lease liabilities 4,520 4,709 Total liabilities 17,361 14,215 Commitments and contingencies (See Note 8) Stockholders’ equity: Preferred stock; $0.001 par value per share; 5,000,000 shares authorized as of March 31, 2024 and December 31, 2023; no shares issued and outstanding as of March 31, 2024 and December 31, 2023 — — Common stock, $0.001 par value per share; 115,000,000 shares authorized as of March 31, 2024 and December 31, 2023; 63,800,017 and 43,909,069 shares issued and outstanding as of March 31, 2024 and December 31, 2023, respectively 64 43 Additional paid-in capital 434,013 270,150 Accumulated deficit (203,208) (188,554)Accumulated other comprehensive gain (loss) (25) 81 Total stockholders’ equity 230,844 81,720 Total liabilities and stockholders’ equity $248,205 $95,935 Larimar Therapeutics, Inc.Condensed Consolidated Statements of Operations(In thousands, except share and per share data)(unaudited) Three Months Ended March 31, 2024 2023 Operating expenses: Research and development $12,939 $4,562 General and administrative 3,795 3,075 Total operating expenses 16,734 7,637 Loss from operations (16,734) (7,637)Other income, net 2,080 1,111 Net loss (14,654) (6,526)Net loss per share, basic and diluted $(0.27) $(0.15)Weighted average common shares outstanding, basic and diluted 53,553,707 43,897,603 Comprehensive loss: Net loss $(14,654) $(6,526)Other comprehensive gain (loss): Unrealized gain (loss) on marketable securities (106) 31 Total other comprehensive gain (loss) (106) 31 Total comprehensive loss $(14,760) $(6,495)

2023年12月30日，中国国家药监局药品审评中心（CDE）官网显示，阿斯利康旗下Alexion公司申报的C5补体抑制剂瑞利珠单抗注射液（ravulizumab，商品名Ultomiris）的上市申请申请获CDE受理。拟定的适应症为：用于预防进行体外心肺循环时慢性肾脏疾病患者的严重肾脏不良事件。 公开资料显示，瑞利珠单抗是Alexion公司开发的长效C5补体抑制剂，补体蛋白C5处于补体级联反应的末端，抑制C5的活性可以抑制免疫系统对自身的免疫攻击，从而缓解疾病症状。 瑞利珠单抗已获FDA批准治疗多种自身免疫性疾病，分别为：治疗阵发性睡眠性血红蛋白尿症（PNH）（2018年12月获批）；治疗非典型溶血性尿毒症综合征（aHUS）的成人及儿童（一个月以上）患者（2021年9月获批）；治疗成人全身型重症肌无力（gMG）（2022年4月获批）。 除了瑞利珠单抗外，Alexion公司还开发了C5补体抑制剂依库珠单抗（商品名Soliris），其通过抑制终端补体来抑制免疫系统的失控性激活。依库珠单抗于2007年获FDA批准上市，是全球获批的首款C5补体抑制剂，也成为了当时PNH唯一的治疗药物。依库珠单抗于2018年8月23日在国内获批上市，目前已批准多种超级罕见病，包括：PNH、aHUS、gMG、视神经脊髓炎谱系障碍（NMOSD）。 自上市以来，依库珠单抗的销售额常年未有下滑，成为阿斯利康的关键产品之一。以2019和2020年为例，其年销售额分别达到39.46亿美元、40.64亿美元。 瑞利珠单抗作为依库珠单抗的升级版，也被视为后者的接棒产品。与依库珠单抗相比，瑞利珠单抗具有更长的半衰期。在治疗PNH患者时，瑞利珠单抗只需每8周静脉给药一次就可以有效控制溶血的发生（依库珠单抗需每2周一次），并且具有良好的疗效和安全性。2022年，依库珠单抗和瑞利珠单抗全球销售额分别为37.62亿美元和19.65亿美元。EvaluatePharma预测，2024年，瑞利珠单抗销售额有望达到34.3亿美元。 可见补体抑制剂具有强烈的市场需求。也正因此，多家药企入局这一领域。那么什么是补体系统？目前进展如何？国内哪些药企在布局？ 补体系统是先天免疫系统的重要部分，由30种以上的蛋白质组成，可引起炎症和免疫攻击。通常情况下，由于机体的严密控制，不会出现自体损伤。但在一些疾病状态下，补体系统会过度激活或抑制，进而能在多种疾病的发病机制中发挥作用，其影响涵盖了从眼部疾病，牙周疾病等急性炎症，到癌症，自体免疫疾病，神经退行性疾病，肾脏疾病和慢性溶血性疾病等。 补体系统整个活化过程表现为一系列级联酶解反应。具体来说，补体系统的活化途径有三种：经典途径（Classical pathway）、旁路途径（Alternative pathway）和凝集素途径（Lectin pathway），这3条途径既相对独立又相互联系。它们下游会合于补体C3，通过C5最终活化产生攻膜复合物（MAC），进而发挥其吞噬、裂解细胞、介导炎症反应、调节免疫应答和清除免疫复合物等多种生物学效应。 自2007年，由Alexion研发的首款C5补体抑制剂依库珠单抗获批上市以来，至今，全球已有多款补体抑制剂获批，分别是C1抑制剂Berinert，Cinryze，Ruconest、Enjaymo，C3抑制剂Empaveli（即pegcetacoplan），以及C5抑制剂Soliris、Ultomiris、Tavneos、Veopoz。 在补体靶向药物研发领域，国内进展靠前的企业有科越医药、康景生物、天镜生物等。 科越医药是一家致力于研发新一代补体靶向药物来治疗补体介导疾病的全球临床阶段生物技术公司。其开发的KP104是一种潜在first-in-class双功能补体药物。能够同时选择性抑制补体旁路和末端途径，提供一种精准、强大的协同机制。 在今年的美国血液学协会（ASH）年会上，科越医药口头报告了KP104在未接受补体抑制剂治疗的PNH患者中的临床结果。中期分析显示，18例PNH患者完成了24/25周的三个递增剂量的治疗，并取得了积极的结果。患者的血红蛋白水平出现了快速和持续的改善，乳酸脱氢酶（LDH）水平迅速下降并持续控制。 目前，KP104正进入针对多个适应症的II期临床试验，包括PNH、IgA肾病、C3肾小球病和继发于系统性红斑狼疮的血栓性微血管病。 康景生物打造的补体系统相关药物研发平台以及药效研究平台应用前景广阔，利用该平台研发的全新靶点补体抑制剂将用于PNH的治疗，后续将继续利用该平台深入开展针对绝大多数自身免疫病（例如aHUS、gMG、NMOSD、系统性红斑狼疮、多种肾病、强直性脊柱炎等）的开发。 主要参考资料： 1、AstraZeneca's Ultomiris scores its 3rd FDA approval, setting up market clash with argenx. 2、Hill A, Platts P J, Smith A, et al. The incidence and prevalence of paroxysmal nocturnal hemoglobinuria (PNH) and survival of patients in yorkshire[J/OL]. Blood, 2006, 108(11): 985[2022-04-10]. 3、Avacopan for the Treatment of ANCA-Associated Vasculitis. (2021). New England Journal of Medicine, 384(21), e81. https://doi.org/10.1056/nejmc2104672. 内容来源于网络，如有侵权，请联系删除。