Adrenal Hyperplasia, Congenital

来源：药渡撰文：五月     编辑：哦呼2023年对生物制药行业来说是艰难的一年，几家公司裁员和重组员工以维持生计。随着2023年下半年制药和生命科学行业的并购回升，并持续到2024 年，逐渐出现了复苏的迹象。但裁员仍在继续，3月份至少有18家公布了裁员计划，如下表所示[1]。3月药企裁员名单3月28日Xilio Therapeutics宣布将裁员15人，约占其现有员工总数的21%，作为“战略投资组合重新排序”的一部分。此次裁员与1.13亿美元的私募配售以及此前与吉利德科学公司达成协议有关，吉利德以4350万美元的预付款和高达6.04亿美元的里程碑付款引进Xilio的XTX301（一种肿瘤激活的IL-12蛋白）和XTX101（一种肿瘤激活的Fc增强CTLA-4抑制剂）。3月27日据Fierce Pharma报道，拜耳在一份警告通知中透露，它将在其位于新泽西州惠帕尼的美国总部裁员90人，自6月19日起生效。3月27日Avalo Therapeutics做出了一项重要的管线战略决策，收购了AlmataBio公司，并将重点放在该生物技术公司的前礼来化脓性扁桃体炎候选药物抗IL-1β抗体AVTX-009上，而不是其现有资产上，裁员其它管线员工。3月25日BMS在加利福尼亚州的一份警告通知中披露，该公司将于4月22日解雇位于圣地亚哥的前Mirati Therapeutics总部的252名员工。BMS于1月23日完成了对Mirati的48亿美元收购。3月22日Theratechnologies正在逐步淘汰临床前肿瘤学研究活动，以支持其用于晚期卵巢癌的肽药物偶联物sudocetaxel zendusortide (TH1902)的I期试验。该公司表示，作为重组的一部分，它将使用625,000美元的现金费用，以支付遣散费和相关费用，以及770,000美元的非现金费用。上个月，FDA拒绝审查Theratechnologies关于HIV疗法Trogarzo新配方的补充生物制品许可申请。3月21日根据前Bellus首席执行官Roberto Bellini的领英，GSK将于3月31日裁掉其大部分前Bellus Health员工。一年前，GSK以20亿美元的价格收购了Bellus，主要是为了收购后者的III期候选药物camlipixant，这是一种用于治疗慢性咳嗽的P2X3受体拮抗剂。去年12月，竞争对手Merck的P2X3候选药物gefapixant第二次未能获得FDA的批准。3月21日NextCure在一份监管文件中披露，该公司正在将其全职员工从目前的81人削减至51人，减少了37%。为了节省资金，该公司将专注于其用于卵巢癌和结直肠癌的NC410联合疗法以及靶向B7-H4的ADC药物LNCB74，该药物正在与LegoChem Biosciences合作开发。NextCure将暂停其其他资产的开发，因为该公司正在寻找合作伙伴或买家来推进这些资产。3月21日Catalent将在印第安纳州伯明顿的一个制造工厂裁员130人。据《先驱时报》报道，该制造商表示将裁员以“提高效率”和“降低成本”，但没有提供哪些职位将被削减的细节或进一步的解释。这不是Catalent第一次在其伯明顿工厂进行裁员，因为CDMO在2022年和2023年裁员了数百名员工。就在上个月，诺和诺德同意以165亿美元收购Catalent，伯明顿工厂将很快出售给诺和诺德，以提高GLP-1的制造能力。3月20日拜耳已将其高管团队从14人削减至8人，这是1月份宣布的重大运营改革的一部分。失业者包括全球营销主管Anne-Grethe Mortensen、放射科主任Gerd Krüger以及该公司消费者健康部门总裁Heiko Schipper。首席营销官迈克尔·德沃伊（Michael Devoy）将保留其职位，但将不再是领导团队的一员。3月18日药明康德于3月18日发布2023年财报，截至本报告期末，公司共拥有 41116名员工，其中12851名获得硕士或以上学位，1412名获得博士或同等学位。而2022年底药明康德拥有44,361名员工，与此相比，药明康德减少了3245名员工，尤其是亚洲地区裁员最多，为2962人。3月13日Spruce Biosciences在其2023年第四季度财务报告中宣布，作为一轮成本削减的一部分，该公司已裁员21%，其中包括关闭其CAHmelia-203临床试验。在另一份新闻稿中，Spruce透露，其口服CRF1拮抗剂tildacerfont在治疗成人经典先天性肾上腺皮质增生症方面的试验失败了。3月13日Coherus BioSciences在其2023年第四季度财务业绩和业务更新中宣布，作为重组的一部分，该公司将裁员30%，这将导致对肿瘤学的更多关注。该公司于3月1日完成了以1.7亿美元将其眼科业务出售给山德士的交易，尽管本轮裁员直到3月7日才开始。3月12日据Endpoints News援引奥地利报纸《Kronen Zeitung》报道，武田制药正在关闭位于奥地利多瑙河畔奥尔特的一家工厂的研发和制造业务，在此过程中削减了190个工作岗位。大约140人将留在现场进行质量控制，因为武田寻求出售该物业，该物业在2019年收购Shire时被收购。3月12日BioSpace首次报道，信达生物制药公司于2月底取消了其位于马里兰州罗克维尔的美国总部整个研究团队，并将在不久的将来关闭该设施。这家总部位于中国苏州的生物技术公司主要在华盛顿特区的实验室进行ADC研究。3月11日据剑桥出版物《商业周刊》报道，赛诺菲正在关闭位于英国剑桥的前Kymab研发设施。虽然这家大型制药公司表示将尝试为90名受影响的员工在公司其他地方寻找住所，但可能会裁员。赛诺菲于2021年以14亿美元的价格收购了 Kymab。3月7日作为公司重组的一部分，Kronos Bio正在裁员21%，该公司表示，该公司将把现金跑道延长到2026年底。据雅虎财经报道，目前拥有约100名员工的Kronos在去年12月宣布，一项关键试验在Ib期失败。3月5日住友制药宣布，将裁员约400人，以削减其北美业务，此前该公司的三款药物销售令人失望。在随后的公告中，住友商事详细介绍了其所谓的组织调整，包括解散其CNS销售部门以及其常务执行官和两名执行官的离职。现任副总裁 Yutaka Wakemi将于4月1日担任执行官一职。3月5日据FierceBiotech报道，由于资金短缺，Meissa Vaccines正在停止启动其MV-012-968鼻内RSV疫苗的II/III期临床研究的计划，导致裁员人数不详。首席执行官Frank Glavin表示，Meissa将根据这一资金问题“审查其战略选择”，这使公司的未来受到质疑。3月4日据路透社报道，化工集团和CDMO Evonik工业将在2026年之前从其全球劳动力中裁减多达2000个工作岗位。这占这家德国公司目前6200多名员工的32%。3月1日根据《普吉特海湾商业杂志》和GeekWire的报道，辉瑞公司将裁员120人，决定结束计划在华盛顿州埃弗雷特建造一座耗资3.5亿美元、占地27万平方英尺的制造工厂的一部分。据报道，辉瑞去年以430亿美元的价格收购了Seagen，该公司将把西雅图地区工厂计划的大部分生产转移到北卡罗来纳州桑福德的现有工厂。3月1日据Endpoints News报道，Arrakis Therapeutics正在裁员约20%。这家正在开发靶向RNA降解剂疗法的初创公司生物技术公司截至2023年8月拥有近100名员工。3月1日据Endpoints News报道，Moderna在其位于马萨诸塞州伯灵顿和诺伍德的工厂解雇了数量不详的制造和质量保证工人。这家mRNA疫苗制造商将裁员归因于之前宣布的对COVID-19疫苗的需求下降，尽管该公司上周表示，它已经完成了魁北克新mRNA生产设施的建设。参考文献1. https://www.biospace.com/article/biospace-layoff-tracker-2023-athenex-shutters-facility-cuts-staff/专栏作者五月药物化学硕博，国外博士后，现从事药物研发工作，热爱医药行业，愿与各位同行互相学习、进步，共同见证创新药的发展。*声明：本文仅是介绍医药疾病领域研究进展或简述研究概况或分享医药相关讯息，并非也不会进行治疗或诊断方案推荐，也不对相关投资构成任何建议。内容如有疏漏，欢迎沟通指出！Wegovy日本热卖，诺和诺德为何将亚洲首站设在此地？MNC巨资追逐核药创新，国内企业加速抢滩FDA九个月内批准的三种DMD治疗方法点击蓝字 | 关注我们

MENLO PARK, Calif., April 01, 2024 (GLOBE NEWSWIRE) -- Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of medications to treat severe endocrinologic, oncologic, metabolic and neurologic disorders by modulating the effects of the hormone cortisol, today announced completion of enrollment in GRADIENT, a Phase 3 trial of its proprietary selective cortisol modulator relacorilant in patients with Cushing’s syndrome (hypercortisolism) caused by an adrenal adenoma or adrenal hyperplasia. “Hypercortisolism with adrenal etiology affects many patients and is associated with serious cardiometabolic comorbidities, including hypertension and hyperglycemia, and increased risk of premature death,” said Bill Guyer, PharmD, Corcept’s Chief Development Officer. “GRADIENT is the first prospective placebo-controlled study to be conducted exclusively in these patients with Cushing’s syndrome. We expect data from GRADIENT in the fourth quarter of this year.” GRADIENT is a randomized, double-blind, placebo-controlled trial conducted at sites in the United States, Europe and Israel. One-hundred thirty-seven patients were randomized 1:1 to receive relacorilant or placebo for 22 weeks. Primary endpoints are improvement in glucose metabolism and hypertension. About Cushing’s Syndrome (Hypercortisolism)Cushing’s syndrome is caused by excessive activity of the hormone cortisol. Endogenous Cushing’s syndrome is an orphan disease that most often affects adults aged 20-50. Symptoms vary, but most patients experience one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper-body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Cushing’s syndrome can affect every organ system and can be lethal if not treated effectively. About RelacorilantRelacorilant is a selective cortisol modulator that binds to the glucocorticoid receptor (GR), but does not bind to the body's other hormone receptors. Corcept is studying relacorilant in a variety of serious disorders, including ovarian, adrenal and prostate cancer and Cushing’s syndrome. Relacorilant is proprietary to Corcept and is protected by composition of matter, method of use and other patents. Relacorilant has orphan drug designation in the United States and the European Union for the treatment of Cushing’s syndrome. About Corcept TherapeuticsFor over 25 years, Corcept’s focus on cortisol modulation and its potential to treat patients across a wide variety of serious disorders has led to the discovery of more than 1,000 proprietary selective cortisol modulators. Corcept’s advanced clinical trials are being conducted in patients with hypercortisolism, solid tumors, amyotrophic lateral sclerosis (ALS) and liver disease (NASH). In February 2012, the company introduced Korlym, the first medication approved by the U.S. Food and Drug Administration for the treatment of patients with Cushing’s syndrome. Corcept is headquartered in Menlo Park, California. For more information, visit Corcept.com. Forward-Looking StatementsStatements in this press release, other than statements of historical fact, are forward-looking statements based on our current plans and expectations that are subject to risks and uncertainties that might cause our actual results to differ materially from those such statements express or imply. These risks and uncertainties include, but are not limited to, our ability to operate our business; risks related to the study and development of Korlym as well as relacorilant, miricorilant, dazucorilant and our other product candidates, including their clinical attributes, regulatory approvals, mandates, oversight and other requirements; and the scope and protective power of our intellectual property. These and other risks are set forth in our SEC filings, which are available at our website and the SEC’s website. In this press release, forward-looking statements include those concerning the development of relacorilant as a treatment for Cushing’s syndrome, and design, timing and expectations regarding our GRADIENT trial. We disclaim any intention or duty to update forward-looking statements made in this press release. CONTACTInvestor inquiries:ir@corcept.comMedia inquiries:communications@corcept.com www.corcept.com

56% of Participants on Paltusotine Achieved IGF-1 ≤1.0 xULN vs. 5% on Placebo (p<0.0001) Paltusotine was Generally Well-tolerated with No Serious Adverse Events Positive Topline Results Support Planned NDA Submission to the FDA in 2H 2024 Management Will Host a Conference Call Today at 8:30 a.m. Eastern Time SAN DIEGO, March 19, 2024 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) a clinical stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors, today announced positive topline results from PATHFNDR-2, the second of two Phase 3 studies evaluating the efficacy and safety of oral, once-daily investigational paltusotine for the treatment of acromegaly. PATHFNDR-2 (NCT05192382) was a randomized, double-blind, placebo-controlled 24-week treatment period followed by an optional open-label extension study evaluating paltusotine in 111 participants with acromegaly who were not pharmacologically treated. The study met statistical significance (p<0.0001) on the primary endpoint, based on the proportion of participants taking paltusotine (56%) who achieved an insulin-like growth factor 1 (IGF-1) level ≤ 1.0 times the upper limit of normal (xULN) compared to those taking placebo (5%). All secondary endpoints also met statistical significance: Paltusotine (n=54) Placebo (n=57) p-value Primary Endpoint: Proportion of participants who achieved an IGF-1 level ≤ 1.0 xULN, % (n) 56% (30/54) 5% (3/57) <0.0001 Secondary Endpoints: Change from baseline in IGF-1 level (xULN) -0.82 0.09 <0.0001 Proportion of participants who achieved IGF-1 level of <1.3 xULN at EoR* 67% 14% <0.0001 Change from baseline in Acromegaly Symptoms Diary (ASD) total score -2.67 2.75 0.004 Proportion of participants who achieved growth hormone (GH) level of <1.0ng/mL at EoR 57% 18% <0.0001 *EoR: End of Randomized control phase “These positive topline results of PATHFNDR-2 are incredibly exciting for both patients with acromegaly and the healthcare providers who treat them,” stated Monica R. Gadelha, M.D., Ph.D., professor of endocrinology at the Medical School of the Universidade Federal do Rio de Janeiro and a principal investigator in the PATHFNDR program. “This study demonstrates that paltusotine can provide both symptom control as well as biochemical control in patients who are not currently on pharmacologic treatment. If approved, the prospect that paltusotine can offer an innovative, once-daily oral alternative represents a significant step forward in improving the treatment experience for patients.” In PATHFNDR-2, paltusotine was generally well-tolerated and no serious adverse events were reported in participants treated with paltusotine. The frequency of participants with at least one treatment emergent adverse event (TEAE) was comparable in the paltusotine treatment arm and placebo arm. The most commonly reported TEAEs in paltusotine-treated participants included: diarrhea, headache, arthralgia and abdominal pain. The frequency of adverse events considered related to acromegaly was notably lower in paltusotine treated participants compared to placebo treated participants. “Paltusotine continues to exceed expectations. Today, PATHFNDR-2 delivered statistically significant topline results across the board,” said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “Building upon the success of PATHFNDR-1, the totality of data underscores the potential of paltusotine to provide an important new treatment option for all people living with acromegaly, if approved. We intend to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration in the second half of 2024, and our team is actively preparing for a potential 2025 launch. We are deeply grateful to all the individuals who participated in this study, the skilled clinical staff who provided exceptional care, and the dedicated Crinetics team from around the globe. This collective endeavor has brought an important new potential acromegaly treatment option closer to becoming a reality.” Data Review Conference Call Crinetics will hold a conference call and live webcast on Tuesday, March 19 at 8:30 a.m. Eastern Time to discuss topline results from the PATHFNDR-2 Phase 3 study. To participate, please dial 1-888-886-7786 (domestic) or 1-416-764-8658 (international), or request a callback here and refer to conference ID 95442954. To access the webcast, click here. A presentation to accompany the webcast can be found here. Following the live event, a replay will be available on the Investors section of the Company’s website. About the PATHFNDR Program The PATHFNDR Program consists of two Phase 3 double-blind, placebo-controlled studies. PATHFNDR-1 (NCT04837040) enrolled a total of 58 adults with acromegaly who entered with an IGF-1 level ≤ 1.0x ULN on octreotide or lanreotide depot monotherapy. The participants were randomized to receive once-daily, oral paltusotine for 36 weeks or placebo. PATHFNDR-2 (NCT05192382) enrolled 111 adults with acromegaly who had elevated IGF-1 levels but were medication naïve or were not being treated with pharmacotherapy (untreated patients). The primary endpoint for both studies is the proportion of patients achieving IGF-1 ≤1.0 xULN compared to placebo. Crinetics believes these studies could support registration of paltusotine in the United States and Europe for all acromegaly patients who require pharmacotherapy, including untreated patients and those switching from standard of care. About Acromegaly Acromegaly is a serious rare disease generally caused by a pituitary adenoma, a benign tumor in the pituitary that secretes growth hormone (GH). Excess GH secretion causes excess secretion of IGF-1 from the liver. Prolonged exposure to increased levels of IGF-1 and GH leads to progressive and serious systemic complications, often resulting in bone, joint, cardiovascular, metabolic, cerebrovascular, or respiratory disease. Acromegaly symptoms include headache, joint aches, fatigue, sleep apnea, severe sweating, hyperhidrosis/oily skin, bone and cartilage overgrowth, abnormal growth of hands and feet, enlargement of heart, liver, and other organs and alteration of facial features. Uncontrolled acromegaly results in increased mortality and has a debilitating impact on daily functioning and quality of life. Surgical removal of pituitary adenomas, if possible, is the preferred initial treatment for most acromegaly patients. Pharmacotherapy is used for patients who are not candidates for surgery, or when surgery is unsuccessful in achieving treatment goals. Approximately 50% of patients with acromegaly prove to be candidates for pharmacotherapy. Injectable depot somatostatin analogues are the most common initial pharmacologic treatment; however, these drugs require monthly depot injections with large gauge needles that are commonly associated with pain, injection site reactions, and an increased burden on the lives of patients. About Paltusotine Paltusotine is the first oral, once-daily selectively-targeted somatostatin receptor type 2 (SST2) agonist and is currently in investigational Phase 3 studies for acromegaly and a Phase 2 study for carcinoid syndrome. It was designed by the Crinetics’ discovery team to provide an efficacious and convenient once-daily option for people living with acromegaly and carcinoid syndrome. In Phase 2 studies and the recently completed PATHFNDR-1 Phase 3 study, paltusotine maintained IGF-1 levels in acromegaly patients who switched from monthly injectable medications to paltusotine. IGF-1 is the primary biomarker endocrinologists use to manage acromegaly patients. Results from the Phase 2 study in carcinoid syndrome further support paltusotine’s potential use beyond acromegaly. About Crinetics Pharmaceuticals Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors. Paltusotine, an investigational, first-in-class, oral somatostatin receptor type 2 (SST2) agonist, is in Phase 3 clinical development for acromegaly and in Phase 2 clinical development for carcinoid syndrome associated with neuroendocrine tumors. Crinetics has demonstrated pharmacologic proof-of-concept in a Phase 1 clinical study for CRN04894, an investigational, first-in-class, oral ACTH antagonist, that is currently in Phase 2 clinical studies for the treatment of congenital adrenal hyperplasia and Cushing’s disease. All of the company’s drug candidates are orally delivered, small molecule new chemical entities resulting from in-house drug discovery efforts, including additional discovery programs addressing a variety of endocrine conditions such as hyperparathyroidism, polycystic kidney disease, Graves’ disease, thyroid eye disease, diabetes and obesity. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the plans and timelines for the clinical development of paltusotine and CRN04894, including the therapeutic potential and clinical benefits or safety pro plans to submit data from the ongoing Phase 3 clinical studies of paltusotine in acromegaly to regulators in support of applications seeking approval for the use of paltusotine in acromegaly patients and the expected timing of an NDA submission for paltusotine for the treatment for all acromegaly patients who require pharmacotherapy;our expected plans and timing for commercialization of paltusotine and other product candidates pending regulatory approval; the ability for paltusotine to effectively provide symptom control and biochemical control in acromegaly patients; and the commercialization of paltusotine as the first once-daily, oral SRL for the treatment of acromegaly; the commercial acceptance of paltusotine as a new medical treatment for acromegaly with improvements in treatment experience and access to care for patients and medical providers; the potential for our discovery program for endocrine diseases including hyperparathyroidism, polycystic kidney disease, Graves’ disease, thyroid eye disease, diabetes and obesity to progress to drug candidates and show safety or efficacy; and our plans to identify and create new drug candidates for additional diseases. These forward-looking statements speak only as of the date of this press release and are subject to a number of known and unknown risks, uncertainties and assumptions, including, without limitation, topline results that we report may change following a more comprehensive review of the data related to the clinical studies and such data may not accurately reflect the complete results of a clinical study, the possibility of unfavorable new clinical data and further analyses of existing clinical data, and the FDA and other regulatory authorities may not agree with our interpretation of such results; and the other risks and uncertainties described in the company’s periodic filings with the Securities and Exchange Commission (SEC). The events and circumstances reflected in the company’s forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Additional information on risks facing Crinetics can be found under the heading “Risk Factors” in Crinetics’ periodic filings with the SEC, including its annual report on Form 10-K for the year ended December 31, 2023. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by applicable law, Crinetics does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contact: Corey Davis LifeSci Advisors cdavis@lifesciadvisors.com (212) 915-2577 Media: Natalie Badillo Head of Corporate Communications nbadillo@crinetics.com (858) 345-6075