Sairopa B.V.

关注并星标CPHI制药在线 8月16日，科望（苏州）生物医药科技有限公司1类新药「ES004注射液」的临床试验申请获CDE受理。据公开资料，ES004是科望医药开发的一种具有“同类最 佳”潜质的SIRPα阻断性抗体，与不同的人SIRPα变体均有纳摩尔级高亲和力。       研究发现，ES004拥有独特的抗原结合表位，可有效阻断CD47-SIRPα相互作用以及CD47 介导的SIRPα胞内段对SHP-1磷酸酶的募集。通过阻断CD47介导的“抗吞噬”信号，ES004可以大大增强巨噬细胞针对肿瘤抗原特异性抗体调理后的肿瘤细胞的吞噬。ES004和肿瘤抗原特异性抗体联合使用在小鼠肿瘤模型中显著抑制肿瘤生长。虽然ES004识别T细胞表面表达的SIRPγ，但它不会对T细胞功能活化有负面影响。食蟹猴对于高剂量ES004具有良好的耐受性。       关于SIRPα及其靶向药研究进展       信号调节蛋白（SIRP）主要表达在髓系造血细胞如巨噬细胞、单核细胞、树突状细胞和粒细胞表面，包括α、β、γ三类。其中SIRPα是SIRP家族的一个典型的抑制性受体，与CD47亲和力高。CD47是一种各类细胞广泛表达的类Ig膜蛋白，可以与多种细胞表面受体相互作用，在癌细胞上经常过度表达。       SIRPα与配体CD47结合产生“别吃我”信号，从而阻止巨噬细胞吞噬健康细胞，癌细胞也可以借此逃过免疫系统监视。研究发现：抑制癌细胞中CD47-SIRPα信号通路可以促进巨噬细胞对肿瘤细胞的吞噬，最终限制肿瘤生长。       因此，CD47/SIRPα成为抗肿瘤药研发的新方向,且被认为是继PD-1/PD-L1后最 具前景的肿瘤免疫治疗靶点之一。然而，目前针对CD47/SIRPα靶点还未有药物获批上市。       据药渡数据库，全球CD47在研管线较SIRPα在研管线多，且进展较快。但由于CD47在正常细胞上广泛表达，尤其是红细胞，使用抗CD47抗体作为抗癌治疗存在潜在的脱靶效应，可能会误杀红细胞，导致严重的血液不良反应，CD47靶向药的进展并不顺利，Arch Oncdogy 的 Ti-061、新基的CC-90002 和 Surface Oncology 的SFR231都因发生严重溶血反应导致临床失败。       目前，全球药企针对SIRPα靶向也已研发出多款药物，详见下表。在研SIRPα靶向药适应症涉及血液肿瘤和实体瘤，而且其药物类型多样，涉及单抗、双抗、融合蛋白。       具体品种上，IBC0966是一种潜在同类首 创PD-L1/SIRPα双靶点疗法，也是全球首 个进入临床的PD-L1/SIRPα双靶点mAb-Trap抗体融合蛋白，可同时刺激先天性和适应性免疫，从而产生强大的协同效应和持久的肿瘤特异性免疫反应。       值得一提的是，IBC0966是盛禾生物于2019年10月从宜明昂科引进，拥有该药在中国内地、中国香港、中国澳门和中国台湾（“授权区域”）的所有权利和利益。       DS-1103a是第一三共开发的一种靶向SIRPα的单克隆抗体，今年3月其联合德曲妥珠单抗（T-DXd）治疗晚期实体瘤的1期临床试验启动。已公布的一项体外研究显示：与T-DXd单药治疗相比，DS-1103a联合疗法明显增强了ADCP。       JMT601 (CPO107)是全球首个进入临床阶段的具有协同靶向结合效应的双特异性SIRPα融合蛋白，是一种基于已批准的抗CD20抗体奥法木单抗并透过加入CD47结合片段SIRPα而合理设计的新型双特异性融合蛋白，可有效结合肿瘤细胞表面的CD20，以诱发抗体依赖性细胞介导的细胞毒作用(ADCC)及补体依赖的细胞毒作用(CDC)。       与传统的CD20靶向抗体相比，多项人类B细胞淋巴瘤模型显示JMT601 (CPO107)的疗效更为明显。已进行的非临床毒理学研究显示JMT601 (CPO107)对CD20阴性的细胞无明显结合，100mpk 剂量下未见红细胞、血小板等CD47强阳性细胞显著受累，安全状况理想并可支持其临床研究。2022年1月，JMT601被FDA授予快速通道资格，用于治疗成人复发或难治性弥漫大B细胞淋巴瘤。       LM-101是一款SIRPα靶向单抗，拟开发用于治疗肾细胞癌、结直肠癌、非霍奇金淋巴瘤等。2022年8月和11月，该药先后在美国和国内获批临床。       BR105是博锐生物自主开发的靶向SIRPα的人源化单克隆抗体，能够识别SIRPα的常见基因型，并阻断SIRPα与其配体CD47的相互作用，解除“别吃我”信号，激活巨噬细胞发挥肿瘤吞噬作用，实现抗肿瘤免疫治疗。2022年1月，该药在国内获批临床，用于治疗晚期肿瘤。       通过靶向SIRPα抑制CD47/SIRPα信号通路，BR105可避免靶向CD47带来的血液毒 性，具有更优的安全性。靶向SIRPα可通过激活髓系细胞激活先天免疫反应，而且可桥接先天免疫与适应性免疫。因此BR105具有与抗PD-1抗体、抗PD-L1抗体等T细胞免疫检查点抑制剂联用的潜力，有望解决临床上PD-1/PD-L1抑制剂面临的耐药和不响应问题；另一方面，BR105可与靶向肿瘤相关抗原(TAA)抗体发挥协同作用，进一步增强TAA抗体介导的免疫细胞对肿瘤的杀伤作用。       在临床前的研究中，BR105能与SIRPα的不同变体结合，并阻断CD47和SIRPα的相互作用，体内外药效表明BR105能有效解除CD47/SIRPα介导的吞噬抑制信号，促进抗肿瘤免疫反应。而且BR105不影响SIRPγ参与的T细胞激活信号。同时在毒理学研究中，BR105不会引起血液学毒 性，表现出优良的安全性。       BYON4228是一种针对SIRPα的抗体，可识别人类SIRPα的两种常见等位基因变体，这使其在广泛人群中的潜在临床应用很广泛。BYON4228与SIRPα的N-末端部分结合，其表位与CD47结合位点重叠。因此，BYON4228阻止CD47与SIRPα的结合，从而阻断通过CD47-SIRPα轴的抑制性信号传导。       功能研究表明，BYON4228在存在多种不同的肿瘤靶向抗体（如曲妥珠单抗、利妥昔单抗、达雷木单抗和西妥昔单克隆抗体）的情况下，在体外增强巨噬细胞和中性粒细胞介导的血液和实体癌症细胞的清除，这说明BYON428具有广泛的潜在临床效益和应用。雄性和雌性食蟹猴单次静脉输注高达100 mg/kg BYON4228耐受性良好，没有引起任何不良反应。       ADU-1805是一种单克隆抗体，针对SIRPα以阻断SIRPα-CD47检查点。ADU-1805能够阻断肿瘤微环境中重要的免疫抑制成分SIRPα，有望提高免疫系统攻击肿瘤的能力。       2022年11月，Exelixis和Sairopa B.V.就ADU-1805达成独家临床开发和选择协议。据协议，Exelixis将向Sairopa B.V.预付4000万美元，并在近期里程碑中额外支付7000万美元，以获得开发和商业化ADU-1805和其他抗SIRPα抗体的独家全球许可，以及Sairopa B.V.在选择期内进行ADU-1805的预先指定的1期临床研究所产生的某些费用。       IBI397是一款具有独特双机理的SIRPα抑制剂，其并非直接阻断SIRPα与CD47 的结合，而是通过刺激巨噬细胞上的SIRPα内吞和降解来降低CD47-SIRPα通路信号，解除免疫抑制。此外，IBI397 的Fc端可以结合激活型的 Fc gamma 受体来进一步提高肿瘤免疫反应，达到抑制肿瘤目的。       在临床前的人源化小鼠肿瘤模型中，数据显示IBI397可抑制肿瘤生长、增强M1型巨噬细胞活性。与其它靶向SIRPα的抗体相比，IBI397可以结合所有常见基因型的SIRPα蛋白，在肿瘤细胞吞噬作用方面具有同类最 佳的效能，并且在临床前研究中未出现红细胞或血小板的清除等副作用。      IBI397由Alector研发。2020年3月，信达生物与 Alector达成合作，获得IBI397在中国区（包括中国港澳台地区）的开发和商业化权益。       BI 765063是SIRPα/CD47“别吃我”信号通路中的靶向SIRPα的抑制剂。2021年ESMO大会上公布的BI 765063联合PD-1单抗BI 754091 (ezabenlimab) 治疗晚期实体瘤的1期剂量递增数据表明，BI 765063单药或联合BI 754091治疗大量预处理晚期实体肿瘤患者具有良好的耐受性和活性。       SG404是尚健生物自主开发的重组人SIRPα-Fc融合蛋白，通过亲和力及结构优化，可有效阻断CD47-SIPRα“别吃我”信号通路，且不引起红细胞凝集，临床前研究显示出显著优于同类分子的安全性和有效性。中生尚健拥有SG404项目在中国（包含台湾、香港、澳门）的开发权，尚健生物拥有除中国以外的全球开发权益。       BSI-082是同类最优、高度差异化的全人源抗SIRPα拮抗性单克隆抗体。对huSIRPα蛋白变体V1/V2/V8都具有强大的结合活性。BSI-082特异性结合SIRPα，不结合SIRPβ和SIRPγ，能有效地阻断SIRPα与CD47的相互作用。阻断SIRPα可使肿瘤相关的巨噬细胞和树突状细胞恢复吞噬活性并破坏肿瘤。博奥信拥有BSI-082的全球开发和商业化权益。       总结       鉴于CD47/SIRPα信号能够使恶性细胞逃避巨噬细胞介导的吞噬作用，抑制CD47/SIRPα信号轴是一种很有前途的癌症治疗策略。然而，目前无论是CD47靶点，还是SIRPα靶点均未有药物获批。对比来看，SIRPα靶向药进展较慢，但较CD47靶向药安全性更好。我国药企也积极布局SIRPα靶点，多款在研药企进入临床试验阶段。而且，围绕SIRPα靶向药，药企间达成数项合作。期待在药企不懈的努力下，CD47/SIRPα信号通路可以早日迎来首款药物。智药研习社近期课程报名来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

Blaine Templeman will support the team’s mission to develop more precise and effective cancer immunotherapies for patients SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Cartography Biosciences, an immuno-oncology company creating biologic therapies against novel targets guided by the first-ever comprehensive antigen atlas, today announced the appointment of Blaine Templeman as Chief Administrative and Legal Officer. “With nearly three decades of experience supporting immuno-oncology and vaccine companies, Blaine brings a lifetime of experience to the operations of Cartography,” said Kevin Parker, Ph.D., co-founder and CEO of Cartography Biosciences. “We’re excited to tap into Blaine’s broad experience in the industry and have him play an integral role in our strategy and growth as our team translates our novel immuno-oncology targets to therapeutic programs.” Mr. Templeman continues at Cartography after serving as the company’s interim Chief Operating Officer. In his new role, Mr. Templeman will oversee Cartography’s administrative operations, including managing the company’s worldwide legal affairs, compliance, facilities, finance, human resources, risk management, and other administrative functions. “I am inspired by Cartography’s mission and innovative team – working tirelessly to find the safest, most effective targets for oncology patients in need,” said Mr. Templeman. “I look forward to guiding and growing the company’s operations and supporting the development of a smarter and more efficient path for precision therapeutics.” Having represented many biotechnology companies in various roles, Mr. Templeman most recently provided strategic support to companies such as Sairopa BV and Shiru, Inc. prior to joining Cartography. Previously, Mr. Templeman was the Chief Administrative and Legal Officer at Aduro Biotech and a corporate and intellectual property transactions partner at Arnold & Porter LLP, the managing partner of the New York office of Sheppard Mullin LLP and partner at Heller Ehrman LLC. He holds a Juris Doctor from New York University School of Law, studied at Princeton Seminary, and received a B.A. from Oral Roberts University. About Cartography Biosciences Cartography Biosciences is focused on developing tumor-selective therapeutics that are based on a unique genomics and computational platform. Cartography’s platform integrates data from proprietary sample sourcing relationships, an industry-leading comprehensive reference atlas, and our target identification algorithms to identify the cells of interest and the single or pairs of targets that are most specific to the intended target cells. Cartography is unlocking the full potential of immunotherapy by discovering and developing therapeutics as precise as their targets. To learn more about Cartography and our mission to treat every patient with cancer, visit cartography.bio and follow us on LinkedIn and Twitter @cartographybio. View source version on businesswire.com: Contacts Media: MacDougall Advisors Karen Sharma ksharma@macdougall.bio 781-235-3060 Source: Cartography Biosciences View this news release online at:

SEATTLE, May 09, 2023 (GLOBE NEWSWIRE) -- Chinook Therapeutics, Inc. (Nasdaq: KDNY), a biopharmaceutical company focused on the discovery, development and commercialization of precision medicines for kidney diseases, today reported financial results for the first quarter ended March 31, 2023 and provided corporate updates. “During the first quarter of 2023, we continued to advance our pipeline of clinical and preclinical programs for rare, severe chronic kidney diseases. We recently completed full enrollment of the phase 3 ALIGN clinical trial, are on track to initiate the phase 3 BION-1301 IgAN clinical trial mid-year and expect to report topline ALIGN results in the fourth quarter of this year,” said Eric Dobmeier, president and chief executive officer of Chinook Therapeutics. “We also look forward to the upcoming 60th European Renal Association (ERA) Congress being held June 15th - 18th, where we will present clinical data from the phase 1/2 trial of BION-1301 as well as the phase 1 trial of CHK-336 in healthy volunteers.” Recent Accomplishments and Updates AtrasentanAtrasentan is a potent and selective endothelin A (ETA) receptor antagonist that has potential therapeutic benefit in multiple chronic kidney diseases by reducing proteinuria and having direct anti-inflammatory and anti-fibrotic effects to preserve kidney function. The phase 3 ALIGN trial is evaluating atrasentan in patients with IgAN and the phase 2 AFFINITY basket trial is evaluating atrasentan in patients with proteinuric glomerular diseases. Chinook has completed enrollment of the phase 3 ALIGN trial, including 320 patients in the main stratum and 64 patients in the SGLT2 inhibitor (SGLT2i) combination stratum. Following a Type D meeting with the U.S. Food and Drug Administration (FDA), Chinook has agreed to change the primary proteinuria endpoint in the ALIGN study to be evaluated at 36 weeks, and plans to report topline data from this endpoint in the fourth quarter of 2023 to potentially support an application for accelerated approval with the FDA.Chinook has completed enrollment of the first four cohorts of the AFFINITY trial, including patients with IgAN, focal segmental glomerulosclerosis (FSGS), Alport syndrome and diabetic kidney disease in combination with SGLT2 inhibitors, and is continuing to enroll the fifth cohort of FSGS patients at a 1.5 mg dose of atrasentan. Chinook plans to present data from one or more additional cohorts of the AFFINITY trial in the second half of 2023.Chinook is preparing to initiate the phase 2 ASSIST trial evaluating atrasentan in patients with IgAN on stable doses of a renin-angiotensin system inhibitor (RASi) and an SGLT2i. The goal of the ASSIST trial is to generate proteinuria data with the combination that will be available at the time of atrasentan’s launch. More details of the ASSIST trial design will be presented in June at the ERA Congress in Milan. BION-1301 (Zigakibart)BION-1301 is a novel anti-APRIL monoclonal antibody currently in phase 2 development for patients with IgAN. BION-1301’s potentially disease-modifying approach to treating IgAN by reducing circulating levels of galactose-deficient IgA1 (Gd-IgA1) has been demonstrated clinically in both healthy volunteers and patients with IgAN. Chinook has finalized trial design and is completing site and country feasibility and global regulatory interactions to enable initiation of the phase 3 BEYOND trial of BION-1301 in mid-2023. More details of the BEYOND trial design will be presented in June at the ERA Congress in Milan.Chinook has completed enrollment of 30 patients in Cohort 2 of Part 3 of the ongoing phase 1/2 trial of BION-1301. Patients in Cohort 2 receive a subcutaneous (SC) dose of 600 mg of BION-1301 every two weeks. Chinook plans to report additional data from Cohorts 1 and 2 in June at the ERA Congress in Milan as well as in the second half of 2023. CHK-336CHK-336 is an oral small molecule lactate dehydrogenase A (LDHA) inhibitor with liver-targeted tissue distribution that Chinook is developing for the treatment of patients with primary hyperoxaluria (PH) and other kidney stone disorders driven by endogenous overproduction of oxalate. In April 2022 Chinook initiated a phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) clinical trial in healthy volunteers evaluating the safety, tolerability and pharmacokinetic profile of CHK-336. Initial data from this trial will be presented in June at the ERA Congress in Milan.In April 2023 Chinook voluntarily paused dosing in the phase 1 clinical trial of CHK-336 in healthy volunteers to allow for a thorough investigation of a serious adverse event that occurred in a single subject following the first dose in the 125 mg MAD group. Based on information available thus far, we believe the subject may have had a hypersensitivity reaction shortly after receiving their first dose of 125 mg of CHK-336. Comprehensive follow-up of this subject is ongoing, and Chinook is determining next steps for the program. Corporate Chinook recently announced the appointment of Robert W. Azelby to its Board of Directors. Mr. Azelby brings more than 20 years of executive leadership and commercial experience in the biopharmaceutical industry to Chinook, including chief executive officer roles at Eliem Therapeutics and Alder Biopharmaceuticals, as well as chief commercial officer at Juno Therapeutics and commercial positions across Amgen’s nephrology and oncology business units.In November 2022, Sairopa B.V., in which Chinook owns approximately a 36 percent equity interest, entered into an exclusive license and option agreement with Exelixis, Inc. for the development of ADU-1805, a monoclonal antibody targeting SIRPα. Under this agreement, Sairopa received an upfront payment of $40.0 million and an additional $35.0 million milestone payment when the FDA cleared Sairopa's Investigational New Drug (IND) Application for a phase 1 trial of ADU-1805 in adults with advanced solid tumors in the first quarter of 2023. First Quarter 2023 Financial Results Cash Position – Cash, cash equivalents and marketable securities totaled $357.4 million at March 31, 2023, compared to $385.3 million at December 31, 2022.Revenue – Revenue for the quarter ended March 31, 2023 was $1.8 million compared to $2.7 million for the same period in 2022. The decrease was primarily due to revenue recognized under Chinook’s license agreement with SanReno.Expenses – Research and development expenses for the quarter ended March 31, 2023 were $50.9 million compared to $26.3 million for the same period in 2022. The increase was primarily due to higher licensing, contract research and manufacturing costs, employee-related costs, including stock-based compensation expense, as well as spending for consulting, outside services and other costs. These higher costs primarily resulted from completing enrollment of the phase 3 ALIGN trial, startup activities for additional atrasentan and BION-1301 clinical trials and an increase in hiring to support our clinical programs. General and administrative expenses for the quarter ended March 31, 2023 were $11.4 million compared to $7.9 million for the same period in 2022. The increase was primarily due to higher employee-related costs, including stock-based compensation expense, and higher consulting and outside services costs.The change in fair value of contingent consideration and contingent value rights liabilities for the quarter ended March 31, 2023 was an expense of $0.5 million compared to a benefit of $1.0 million for the same period in 2022. The increase in this non-cash expense primarily resulted from a change in estimate of the potential future proceeds derived from the Merck collaboration. Net Loss – Net loss for the first quarter of 2023 was $60.2 million, or $0.85 per basic share, compared to a net loss of $31.7 million, or $0.54 per share for the same period in 2022. About Chinook Therapeutics, Inc.Chinook Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing precision medicines for kidney diseases. Chinook’s product candidates are being investigated in rare, severe chronic kidney disorders with opportunities for well-defined clinical pathways. Chinook’s lead program is atrasentan, a phase 3 endothelin receptor antagonist for the treatment of IgA nephropathy and other proteinuric glomerular diseases. BION-1301, an anti-APRIL monoclonal antibody, is being evaluated in a phase 1/2 trial for IgA nephropathy. CHK-336, an oral small molecule LDHA inhibitor for the treatment of hyperoxalurias, is in phase 1 development. In addition, Chinook's research and discovery efforts are focused on building a pipeline of precision medicines for rare, severe chronic kidney diseases with defined genetic and molecular drivers. Chinook is leveraging insights from kidney single cell RNA sequencing and large CKD patient cohorts that have been comprehensively panomically phenotyped, with retained biosamples and prospective clinical follow-up, to discover and develop therapeutic candidates with mechanisms of action targeted against key kidney disease pathways. To learn more, visit www.chinooktx.com. Cautionary Note on Forward-Looking Statements Certain of the statements made in this press release are forward looking, including those relating to Chinook’s business, future operations, advancement of its product candidates and product pipeline, clinical development of its product candidates, including expectations regarding cash forecasts and timing of initiation and results of clinical trials, and regulatory submissions, including the timing of the results of our phase 3 ALIGN trial and phase 2 AFFINITY trial of atrasentan, phase 3 clinical trial of BION-1301, phase 1/2 trial of BION-1301, phase 1 clinical trial of CHK-336, and submission for potential accelerated approval for atrasentan. In some cases, you can identify these statements by forward-looking words such as “may,” “will,” “continue,” “anticipate,” “intend,” “could,” “project,” “expect” or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, including initiation of clinical trials of our existing product candidates or those developed as part of the Evotec collaboration or other strategic collaborations, whether results of early clinical trials or preclinical studies will be indicative of the results of future trials, including our phase 3 ALIGN trial, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that may be more advanced or have greater resources than we do, our ability to obtain and adequately protect intellectual property rights for our product candidates, and the effects of macroeconomic conditions on our business operations, including rising interest rates and inflation. Many of these risks are described in greater detail in our filings with the SEC. Any forward-looking statements in this press release speak only as of the date of this press release. Chinook assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. CHINOOK THERAPEUTICS, INC.Condensed Consolidated Statements of Operations(In thousands, except per share amounts)(Unaudited) Three Months Ended March 31, 2023 2022 Collaboration and license revenue $1,828 $2,697 Operating expenses: Research and development 50,883 26,252 General and administrative 11,404 7,868 Change in fair value of contingent consideration and contingent value rights liabilities 526 (1,038)Amortization of intangible assets 433 429 Total operating expenses 63,246 33,511 Loss from operations (61,418) (30,814)Investment and other income (expense), net 3,102 (95)Loss before income taxes and equity method investment loss (58,316) (30,909)Equity method investment loss (1,861) (775)Net loss $(60,177) $(31,684)Net loss per share attributable to common stockholders, basic and diluted $(0.85) $(0.54)Weighted-average shares used in computing net loss per share attributable to common stockholders, basic and diluted 70,703 58,340 CHINOOK THERAPEUTICS, INC.Condensed Consolidated Balance Sheets(In thousands)(Unaudited) March 31, December 31, 2023 2022 Assets Current assets: Cash and cash equivalents $118,495 $115,438 Marketable securities 231,881 262,887 Accounts receivable 2,444 1,091 Prepaid expenses and other current assets 5,824 6,176 Total current assets 358,644 385,592 Marketable securities 7,002 6,989 Property and equipment, net 16,974 16,908 Restricted cash 2,074 2,074 Operating lease right-of-use assets 47,345 48,970 Investment in equity securities 41,200 41,200 Equity method investment 2,653 4,071 Intangible assets, net 23,854 24,287 In-process research & development 36,550 36,550 Goodwill 117 117 Other assets 7,462 7,326 Total assets $543,875 $574,084 Liabilities and Stockholders’ Equity Current liabilities: Accounts payable 9,774 9,751 Accrued and other current liabilities 33,605 33,636 Operating lease liabilities 5,085 4,948 Contingent value rights liability 2,500 2,500 Total current liabilities 50,964 50,835 Contingent value rights liability - non-current 37,794 37,318 Contingent consideration liability 4,470 4,420 Deferred tax liabilities 5,076 5,076 Operating lease liabilities, net of current maturities 33,178 34,494 Total liabilities 131,482 132,143 Stockholders’ equity 412,393 441,941 Total liabilities and stockholders’ equity $543,875 $574,084