6月 13, 2023
  • Chinook Therapeutics是一家专注于临床阶段的生物制药公司,拥有治疗IgA肾病(即IgAN,一种罕见的进展性慢性肾病)的两项临床开发后期高价值药物
  • 收购的资产将包括阿曲生坦(atrasentan,一种口服内皮素A受体拮抗剂,已进入IgAN3期开发)和Zigakibart(一种抗APRIL单克隆抗体,已进入IgAN 3期研究)
  • 该项交易金额高达35亿美元(包括每股40美元的现金,以及每股最高4美元的或有价值权),已获诺华和Chinook董事会批准,在符合惯例成交条件下,预计将于2023年下半年完成

诺华日前宣布已经达成一项协议,将收购一家专注于临床阶段的生物制药公司Chinook Therapeutics。总部位于华盛顿州西雅图的Chinook Therapeutics拥有两款正在开发的、治疗罕见的严重慢性肾病的临床开发后期的高价值药物。该交易须符合惯例成交条件,与诺华专注于创新药物的战略完全契合,将显著扩展诺华在肾脏疾病领域的产品组合,并补充现有的研发管线。

诺华集团首席执行官万思瀚 (Vas Narasimhan) 表示:“IgA肾病是一种进展性疾病,主要影响年轻人,并可能导致透析或肾移植。诺华致力于解决社会最具挑战性的医疗问题,此次收购将为我们创造一个独特的机会,有望为患者带来更多急需的治疗选择。我们期待最终达成这一交易,也希望Chinook员工顺利过渡,加入诺华大家庭”。

Chinook的管线包括两款处于临床开发阶段的药物,用于治疗IgA肾病(IgAN)。IgAN是一种进展性的、罕见的肾脏疾病,主要影响年轻人,目前缺乏针对性的治疗方案。多达十分之三的患者在10年内会进展为肾衰竭及透析治疗1,2

阿曲生坦是一种口服内皮素A受体拮抗剂(ERA),目前正处于IgAN的3期开发阶段,预计将在2023年第四季度获得关键临床数据,目前的研究已显示其可显著减少蛋白尿。针对其它罕见肾脏疾病,阿曲生坦也处于早期开发阶段。

Zigakibart(BION-1301)是一种皮下给药的抗APRIL单克隆抗体,预计将于2023年第三季度开启3期临床试验。

Chinook在肾脏疾病建模和疾病研究方面拥有丰富的专业知识,并拥有治疗多种严重肾脏疾病的早期管线。

交易细节
根据双方公司董事会一致批准的协议,诺华将以最高达35亿美元的金额收购Chinook,并将其与新成立的一家诺华子公司合并。根据此协议的条款,Chinook普通股持有人将在结算时获得32亿美元(每股40美元)的现金,以及高达3000万美元(每股4美元)的或有价值权,这一权利将在达到特定监管里程碑时以现金支付。预计交易将于2023年下半年完成,但须符合惯例成交条件,包括经Chinook股东和监管机构的批准。在交易结束之前,Chinook将继续作为一家独立的公司运营。

关于IgAN
IgAN是一种进行性的、罕见肾脏疾病,主要影响年轻人,目前缺乏针对性的治疗选择。在IgAN中,对异常形式IgA的自身免疫反应导致形成免疫复合物在肾脏沉积。这些免疫复合物触发炎症和肾损伤,导致肾功能进行性丧失3

在美国,IgAN的年发病率达21/100万4-6,亚洲人群中的发病率更高。IgAN是高加索年轻成人肾衰竭的最常见原因7。随着肾脏损害加重,可能会出现蛋白尿和血尿8,9。尿蛋白水平较高(≥ 1g/天)的IgAN患者发生疾病进展的风险较高,约30%患者在10年内进展为肾衰竭1,2。不同疾病通路的创新靶向疗法正在改变IgAN患者的治疗前景,并为IgAN患者提供了不进展至终末期肾脏病的希望10

关于Atrasentan和Zigakibart
一项2期研究表明,与基线相比,阿曲生坦可显著降低蛋白尿,且耐受性良好,包括肝脏安全性特征。Zigakibart是一种靶向性生物疗法,有可能从发病机制上靶向治疗IgAN,即针对异常半乳糖缺陷型的IgA产生,从而保护肾功能。1期及2期中期数据显示蛋白尿较基线显著减少。作为一种靶向治疗, 预期Zigakibart的耐受性会优于广谱淋巴细胞耗竭疗法。

参考文献

[1]Nam, K.H., Kie, J.H., Lee, M.J., Chang, T.I., Kang, E.W., Kim, D.W., Lim, B.J., Park, J.T., Kwon, Y.E., Kim, Y.L. and Park, K.S., 2014. Optimal proteinuria target for renoprotection in patients with IgA nephropathy.PLoS One, 9(7), p.e101935.

[2]Sevillano, A.M., Gutiérrez, E., Yuste, C., Cavero, T., Mérida, E., Rodríguez, P., García, A., Morales, E., Fernández, C., Martínez, M.A. and Moreno, J.A., 2017. Remission of hematuria improves renal survival in IgA nephropathy. Journal of the American Society of Nephrology, 28(10), pp.3089-3099.

[3]Lai KN, et al. Nat Rev Dis Primers 2016;2:16001

[4]Fischer EJ, et al. 2009; Clin Nephrol;72:163‒169

[5]Swaminathan S. Clin J Am Soc Nephrol 2006;1:483–487

[6]Sim JJ et al. Am J Kidney Dis 2016;68:533‒544; 6. Zaza G. Am J Nephrol 2013;37:255–263

[7]Nair R, Walker PD. Kidney Int 2006;69:1455-83.

[8]Nolin, L. and Courteau, M., 1999. Management of IgA nephropathy: evidence-based ecommendations. Kidney International, 55, pp.S56-S62.doi: 10.1046/j.1523-1755.1999.07008.x. PMID: 10369196.

[9]National Institute of Diabetes and Digestive and Kidney Diseases. IgA nephropathy. Available at: https://www.niddk.nih.gov/health-information/kidney-disease/iga-nephrop… [Accessed August 2021]

[10]Haresh Selvaskandan, Guillermo Gonzalez-Martin, Jonathan Barratt & Chee Kay Cheung (2022) IgA nephropathy: an overview of drug treatments in clinical trials, Expert Opinion on Investigational Drugs, 31:12, 1321-1338

Disclaimer

This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “look forward,” “investigational,” “pipeline,” “to acquire,” “development,” “to include,” “progress,” “expected,” “continue,” “opportunity,” “to address,” “commitment,” or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for atresentan or zigakibart, the acquisition of Chinook Therapeutics, or regarding potential future revenues from atresentan or zigakibart. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that atresentan or zigakibart will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Neither can there be any guarantee expected benefits or synergies from this transaction will be achieved in the expected timeframe, or at all, nor can there be any guarantee that atresentan or zigakibart will be commercially successful in the future. In particular, our expectations regarding atresentan or zigakibart or the transaction described in this press release could be affected by, among other things, expected revenues, cost savings, synergies and other benefits from the proposed transaction might not be realized within the expected time frames or at all and costs or difficulties relating to integration matters, including but not limited to employee retention, might be greater than expected; the requisite regulatory approvals and clearances for the proposed transaction may be delayed or may not be obtained (or may result in the imposition of conditions that could adversely affect the combined company or the expected benefits of the proposed transaction); the requisite approval of Chinook’s stockholders may be delayed or may not be obtained, the other closing conditions to the proposed transaction may be delayed or may not be obtained, or the merger agreement may be terminated; business disruption may occur following or in connection with the proposed merger; Novartis or Chinook’s businesses may experience disruptions due to transaction-related uncertainty or other factors making it more difficult to maintain relationships with employees, other business partners or governmental entities; the possibility that the proposed transaction is more expensive to complete than anticipated, including as a result of unexpected factors or events; diversion of management’s attention from ongoing business operations and opportunities as a result of the proposed merger or otherwise; the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.