DAAO

Company Today Also Provided Updates on R&D Portfolio and Strategy at Investor Event Crinecerfont New Drug Application Submission Planned in 2024 NBI-'770, an Oral NMDA NR2B Negative Allosteric Modulator, Entering Phase 2 for the Treatment of Major Depressive Disorder Advancing Largest Portfolio of Muscarinic Compounds in Clinical Development Top-Line Phase 2 Data Readouts for Five Programs Anticipated in 2024 Including NBI-'568, an M4 Agonist, for the Treatment of Schizophrenia SAN DIEGO, Dec. 5, 2023 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced it received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for crinecerfont in congenital adrenal hyperplasia. The Company also provided updates on its R&D portfolio and strategy at its Analyst Day, held in New York. "We are very pleased that the FDA granted Breakthrough Therapy designation for crinecerfont, thus recognizing both the seriousness of congenital adrenal hyperplasia and the significant unmet need currently faced by patients and families living with this condition," said Eiry W. Roberts, Chief Medical Officer, Neurocrine Biosciences. "The outstanding safety and efficacy results from the Phase 3 CAHtalyst™ studies in pediatric and adult patients suggest that crinecerfont has the potential to represent a substantial improvement over current standard of care in CAH by controlling androgen levels and allowing for reduced steroid doses. We remain on track to submit the new drug application in 2024." 2023 Analyst Day R&D Portfolio and Strategy Updates At today's Analyst Day, Neurocrine Biosciences provided an update on its R&D portfolio and strategy, including the Company's focus on building breadth and depth across therapeutic areas and modalities with key focus areas in VMAT2 inhibition, CRF antagonism, muscarinic agonism to antagonism, and gene therapy. With a diversified early-stage portfolio spanning a range of modalities including small molecules and biologics, and a growing pre-clinical and development candidate portfolio, Neurocrine is uniquely positioned to advance a steady flow of innovative clinical candidates to patients across its neuroscience-focused therapeutic areas of interest. The Company remains on-track to advance two gene therapies into the clinic in 2025, and anticipates at least 20 development candidates by 2027. Other key portfolio and pipeline updates include: Valbenazine Ongoing Phase 3 study of valbenazine in adjunctive treatment of schizophrenia (ATS) will inform potential advancement of NBI-'890, a next-generation, long-acting VMAT2 inhibitor, which we anticipate will enter the clinic in 2024 No additional Phase 3 studies of valbenazine in ATS planned NBI-'770 (Oral, NMDA NR2B Negative Allosteric Modulator) Represents a potential first-in-class opportunity on a clinically validated target Program entering Phase 2 for treatment of major depressive disorder Muscarinic Compounds Validated and differentiated mechanisms of action Five programs represent largest number of muscarinic assets in human studies, including lead molecule, NBI-'568, in Phase 2 study for the treatment of schizophrenia 2024 portfolio will include four Phase 1 programs: NBI-'570 (dual M1/M4 agonist) NBI-'567 (M1-preferring agonist) NBI-'569 (M4-preferring agonist) NBI-'986 (M4 antagonist, internally discovered at Neurocrine Biosciences) Phase 2 Top-Line Clinical Data Expected in 2024 NBI-'568 (M4 agonist) for the treatment of schizophrenia Luvadaxistat (DAAO inhibitor) for cognitive impairment associated with schizophrenia NBI-'845 (AMPA potentiator) for inadequate response to treatment in major depressive disorder Efmody (long-acting glucocorticoid) for adrenal insufficiency Efmody for congenital adrenal hyperplasia About Breakthrough Therapy Designation Breakthrough Therapy designation is a process developed by the FDA to expedite development and review of drugs that are intended to treat a serious condition and where clinical evidence indicates that the potential drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s). To learn more about Breakthrough Therapy designation, click here. About Classic Congenital Adrenal Hyperplasia Congenital adrenal hyperplasia (CAH) refers to a group of genetic conditions that result in an enzyme deficiency that alters the production of adrenal hormones which are essential for life. Approximately 95% of CAH cases are caused by a mutation that leads to deficiency of the enzyme 21-hydroxylase (21-OHD). In classic CAH, severe deficiency of this enzyme leads to an inability of the adrenal glands to produce cortisol and, in approximately 75% of cases, aldosterone. If left untreated, classic CAH can result in salt wasting, dehydration, and even death. There are currently no non-glucocorticoid treatments approved by the U.S. Food and Drug Administration (FDA) for classic CAH. Glucocorticoids (GCs), the current standard of care, are used not only to correct the endogenous cortisol deficiency but typically used at greater than physiologic (supraphysiologic) doses to try to suppress the high levels of corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH) that result in androgen excess. However, glucocorticoid treatment at supraphysiologic doses has been associated with serious and significant complications of steroid excess, including metabolic issues such as weight gain and diabetes, cardiovascular disease, and osteoporosis. Additionally, long-term treatment with supraphysiologic GC doses may have psychological and cognitive impact such as changes in mood and memory. Androgen excess has been associated with abnormal bone growth and development in pediatric patients, female health problems such as acne, excess hair growth and menstrual irregularities, testicular rest tumors in males, and fertility issues in both sexes. To learn more about CAH, click here. About Corticotropin Releasing Factor (CRF) Corticotropin releasing factor (CRF) regulates the secretion of adrenocorticotropic hormone (ACTH) by the pituitary gland. The neuropeptide was discovered, isolated and identified by the late Wylie W. Vale, PhD., a founder of Neurocrine Biosciences who led the Clayton Foundation Laboratories for Peptide Biology and was the Helen McLoraine Chair in Molecular Neurobiology at the Salk Institute. Dr. Vale mapped the key role CRF played in the regulation of the stress response. In the 95% of classic CAH cases caused by a mutation in the 21-hydroxylase enzyme, the severe enzyme deficiency results in little or no production of the stress hormone cortisol, which can lead to adrenal crisis. The lack of cortisol production also causes a break in the feedback loop that would normally regulate the body's secretion of CRF, and as a result ACTH, which maintains adrenal androgen production within normal ranges. About Crinecerfont Crinecerfont is an investigational, oral, selective corticotropin-releasing factor type 1 receptor (CRF1) antagonist being developed to reduce and control excess adrenal androgens through a steroid-independent mechanism for the treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). The compound was identified by Dimitri Grigoriadis, Ph.D., Chief Research Officer at Neurocrine Biosciences who conducted post-graduate research with Dr. Wylie Vale at the Salk Institute. Antagonism of CRF1 receptors in the pituitary has been shown to decrease adrenocorticotropic hormone (ACTH) levels, which in turn decreases the production of adrenal androgens and potentially the symptoms associated with classic CAH. Our data demonstrates that lowering androgen levels enables lower, more physiologic dosing of glucocorticoids and thus could potentially reduce the complications associated with exposure to greater than normal glucocorticoid doses in patients with classic CAH. Prior to receiving Breakthrough Therapy designation from the FDA, crinecerfont also received Fast Track and Rare Pediatric Disease designations in congenital adrenal hyperplasia. To learn more about crinecerfont, click here. About the CAHtalyst Phase 3 Studies The CAHtalyst Phase 3 Pediatric and Adult global registrational studies were designed to evaluate the safety, efficacy, and tolerability of crinecerfont in children and adolescents (2–17 years of age) and adults (18 years of age and older) with classic congenital adrenal hyperplasia (CAH) due to 21-OHD, respectively. The CAHtalyst Phase 3 Pediatric and Adult clinical studies met their primary and secondary endpoints. The CAHtalyst Pediatric study demonstrated a statistically significant decrease in serum androstenedione from baseline with crinecerfont at Week 4 over baseline, while both studies showed crinecerfont treatment led to statistically significant reductions in daily glucocorticoid from baseline while maintaining androgen control at Week 28 and Week 24, respectively. Crinecerfont was generally well tolerated in the CAHtalyst Phase 3 studies. The most common adverse events in the CAHtalyst Pediatric study were headache, fever, vomiting, upper respiratory tract infection, and nasopharyngitis, while the most common adverse events in the CAHtalyst Adult study were fatigue, headache, and coronavirus infection. Few serious adverse events were seen in either study, with none assessed as related to crinecerfont. Both studies achieved a >95% completion rate. Details about the Phase 3 data from the CAHtalyst Pediatric Study were reported in October 2023 and can be found here. For more information about the CAHtalyst Pediatric Phase 3 study, please visit ClinicalTrialsPediatric.gov. Details about the Phase 3 data from the CAHtalyst Adult Study were reported in September 2023 and can be found here. For more information about the CAHtalyst Phase 3 study in adults, please visit ClinicalTrialsAdult.gov. About Neurocrine Biosciences, Inc. Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, Parkinson's disease, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, Twitter, and Facebook. (*in collaboration with AbbVie) NEUROCRINE BIOSCIENCES and NEUROCRINE are registered trademark of Neurocrine Biosciences, Inc. CAHtalyst and the Neurocrine logo are trademarks of Neurocrine Biosciences, Inc. Forward-Looking Statement In addition to historical facts, this press release contains forward-looking statements that involve a number of risks and uncertainties. These statements include, but are not limited to, statements regarding the potential benefits to be derived from certain of our product candidates and our future development plans. Among the factors that could cause actual results to differ materially from those indicated in the forward-looking statements include: our future financial and operating performance; the risk that our products and/or product candidates will not be found to be safe and/or effective or may not prove to be beneficial to patients; that development activities for our products and/or product candidates may not be completed on time or at all; risks that clinical development activities may be delayed for regulatory or other reasons, may not be successful or replicate previous and/or interim clinical trial results, or may not be predictive of real-world results or of results in subsequent clinical trials; risks that regulatory submissions for our products and/or product candidates may not occur or be submitted in a timely manner; risks that our products and/or product candidates may not obtain regulatory approvals; or that the U.S. Food and Drug Administration or regulatory authorities outside the U.S. may make adverse decisions regarding our products and/or product candidates; risks and uncertainties relating to competitive products and technological changes that may limit demand for our products; risks associated with our dependence on third parties for development and manufacturing activities related to our products and our product candidates, and our ability to manage these third parties; and other risks described in the Company's periodic reports filed with the Securities and Exchange Commission, including without limitation the Company's quarterly report on Form 10-Q for the quarter ended September 30, 2023. Neurocrine Biosciences disclaims any obligation to update the statements contained in this press release after the date hereof. SOURCE Neurocrine Biosciences, Inc.

一手靠庞大的仿制药军团贡献营收，一手用创新药来拉动增长、实现市场突围。继梯瓦之后，不安分的仿制药巨头晖致，又在资本寒冬中出手收购了创新药企。而中国的仿制药企在尚未成长为全球仿制药巨头之前，也已纷纷聚力创新，未来国内药企谁会实现创新与仿创相结合的国际化突围，值得期待。继梯瓦之后，又一仿制药巨头加码创新。2020年底才正式横空出世的仿制药巨头晖致（Viatris）在努力改头换面，添加创新成色。近日，晖致瞄准了眼科赛道，为市场贡献了一个关于仿制药巨头收购2015后商业化阶段生物制药公司的经典案例。01晖致开始收割创新药企11月7日，仿制药巨头晖致传出重磅消息，该公司同意将以每股11美元的现金价格购买Oyster Point 的所有已发行股票，总价约2.95亿美元。并且，如果Oyster Point在2022财年达到规定的业绩目标，晖致还将向现有Oyster Point普通股东支付每股高达2美元的潜在现金支付，根据2683万股已发行股票，这笔交易的价值约为3.49亿美元。该交易完成后眼科业务将在晖致作为独立部门运营。据了解，Oyster Point成立于2015年6月，已经是一家处于商业化阶段的生物制药公司，致力于发现、开发和商业化治疗眼科疾病的药物疗法。今年上半年Oyster Point营收为739.7万美元，净利润为-9783.4万美元。2021年10月，Oyster Point首款创新药TYRVAYA（鼻腔喷雾剂0.03mg，OC-01，酒石酸伐尼克兰）获FDA批准上市，用于治疗干眼症的症状和体征，并且Oyster Point还在探索该产品在其他领域的潜在应用，包括神经营养性角膜病变、与隐形眼镜不耐受相关干眼症和屈光手术的眼表面准备等。2021年8月，国内箕星药业获得了该产品在大中华区开发和商业化权益。分析师认为，在市场动荡下，该公司股价已经从2020年初的16美元下跌了约80%，如今被收购对于Oyster Point 而言也是不错的选择。对晖致而言，这笔买卖也相当划算。耗资3亿美元，晖致除了获得TYRVAYA这款专利创新药以强化其眼科赛道之外，还能从中获得Oyster Point其他颇具潜力的眼部护理产品管线，还有经验丰富的团队，这一团队无论是对临床、监管还是商业角度都对眼科领域拥有广泛的了解。据了解，Oyster Point还正在开发浓缩泪膜（ETFTM）基因治疗平台以治疗特定眼表疾病OC-101（AAV-NGF）、OC-103（AAV-DAO）），并且还合作开发了一种使用噬菌体治疗眼科细菌感染的独特疗法。除了收购Oyster Point之外，晖致正在斥资4亿美元左右收购印度私营公司 Famy Life Sciences来补充相关眼科产品管线。据了解，在眼科领域，今年晖致的重磅仿制药——艾伯维的干眼症治疗剂Restasis获得批准。02步梯瓦后尘，也靠创新药驱动业绩？晖致此举真正引人关注的原因或许是，这家由迈兰和原辉瑞仿制药部门辉瑞普强合并而来的全球仿制药巨头选择了向创新转型。晖致表示，两笔交易的目的是为了让晖致掌握具有竞争力的眼科产品组合，并预测到 2028 年，这两笔收购将会带来额外的 10 亿美元销售额和 5 亿美元的营业利润。不过晖致的收购或许才刚刚开始。2022年半年报中，晖致提出，正在不断评估产品和公司的潜在收购，作为其未来增长的战略部分。并且，此前晖致还透露通过不断的剥离资产，在2023年底之前筹集高达90亿美元的收益。对于这笔资产，晖致曾表示，除了偿还债务和股息之外，便是扩大部分领域的投资，并将眼科、胃肠道疾病和皮肤病列为三个重点治疗领域。而此前靠不断收购、采取仿制药和创新药齐头并进策略，成长为全球仿制药巨头的就是梯瓦。数据显示，2012年梯瓦的专科药收入达80亿美元，2016年则增加到86亿美元，梯瓦的专科药收入甚至可以排进制药巨头前三十强。盈利方面，创新药部门是梯瓦的主要利润来源，2012-2017年间，平均每年贡献盈利达44.9亿美元，占公司总盈利的53.7%以上；相比之下，仿制药部门只有25.3亿美元，仅占公司总盈利的23.5%。多年以来，梯瓦的核心收入都依赖于其原研产品Copaxone，该药一度贡献了其专利药收入的一半左右。但是受专利到期影响，其销售额到2020年已锐减至13亿美元。2021年该产品在北美市场销售额为5.7亿美元，下降了35%，国际市场领域该产品收入为3700万美元，下降了29%。并且梯瓦未来的业绩仍是以创新药驱动，包括 Austedo（治疗亨廷顿舞蹈病和迟发性运动障碍）、Ajovy （治疗偏头痛）以及生物类似药。2022 年梯瓦预计Austedo的销售额将达到约10亿美元，而Ajoby现已是欧洲第二大偏头痛品牌。不仅如此，梯瓦在中国市场的布局，便选择了以特药为切口进入，且取得了一定成效。例如梯瓦原研的肿瘤用药存达（注射用盐酸苯达莫司汀），便是梯瓦在中国推出的第一个真正意义上的特药产品，并且在第五批集采中该原研产品以比国内仿制药品更低的价格成功中标。另外其Austedo也在2020年5月获批进入中国市场。纵观全球仿制药TOP10，有8家公司的销售额均较2020年有所增长。但是位列第一和第二的梯瓦和山德士两家公司的销售额均下降了3%。其中梯瓦延续了过去五年的下滑趋势，而山德士目前正在经历最艰难的转型。2021年山德士实现销售收入75亿美元，较上一年微跌2.6%，5年前山德士的销售额为90亿美元。为了扭转业绩颓势，2019年诺华曾计划将山德士美国的皮肤病业务和口服仿制固体制剂业务出售给阿拉宾度的交易，但事与愿违，该项并未在预期时间内获得监管部门批准。之后，诺华开始探索山德士从保留业务到分拆的所有选择。今年8月诺华全球官宣，计划将仿制药和生物类似药部门的山德士分拆成一家全新的独立上市公司。本次分拆预计将在2023下半年完成，分拆后山德士将是欧洲最大的仿制药企。山德士不仅拥有多款抗生素、呼吸、肿瘤、中枢神经等领域的多款仿制药，还包括阿达木单抗、利妥昔单抗、英夫利西单抗等8款生物类似药，今后预计还有15个生物仿制药管线的产品上市。而分拆后的山德士是否也会选择如梯瓦和晖致的同样的策略，值得期待。03中国仿制药企，创新赛道上见反观中国的仿制药企的路径似乎非常明确，一种是出海成长为全球仿制药巨头，另一种则是向创新转型。但是在成长为全球仿制药巨头，似乎仍是国内药企遥不可及的梦。2021年全球TOP10的仿制药企中有4家来自印度，仍旧没有中国药企，中国的仿制药大多仍没有走出中国市场。一位业内人士在接受E药经理人采访时表示，中国仿制药企成长为国际仿制药巨头似乎已经丧失了最佳发展时期。曾经中国的仿制药企热衷于赴美国申报ANDA，但是在该人士眼中，中国企业的真实目标并非是深耕美国市场，而是借助相关政策红利，挖掘国内市场。仿制药比拼的是价格优势、质量保障、服务优势，还有信誉优势。相较而言，中国药企的仿制药在美国市场的商业化方面落后印度仿制药企20-30年。长期以来，国内不少企业能够出海的品种较为单一，很难在美国大型分销商中建立一定的可信度。而印度的仿制药企已经有数十款甚至上百款获得FDA批准的药物，已经在分销商渠道中建立了信任。而不完全统计，国内药企在美ANDA的数量仅仅相当于某一家或两家TOP10仿制药企的量。该人士认为，中国仿制药要想在美获得实质性的发展，不能一味依靠政策风口，要踏踏实实、一步一个脚印来积淀经验。如果企业战略定位计划进入美国市场，这并非没有可能，但是过程会非常艰辛，比较可行的路径是，寻找理念一致的平台进行合作。但是，该人士强调，目前无论是中国药企、印度药企、还是美国药企在仿制药领域都面临巨大的竞争，如果想在这个行业中立足，就必须要做有特色的，技术壁垒比较高的改良型新药。同时，随着集采常态化的推行，国内仿制药企业一方面要面对原研产品的竞争压力，另外则需要警惕全球仿制药巨头，尤其是以梯瓦为代表的印度仿制药在国内仿制药领域的崛起。选择创新转型似乎成为仿制药企共同的选择。但是根据此前E药经理人研究院一项600人投票的调研数据显示，集采常态化下，仿制药企仿制药企依靠自身积累成功转型创新药企的概率，有412人投票给“低于50%”，占比超过68%。凭借既有销售强势领域叠加创新药产品，这似乎成为仿制药企业最理想的转型方式。如恒瑞、先声、正大天晴等企业均是如此。在资本寒冬下，不少人士提出，手握充分现金流的仿制药企是时候如晖致这般抄底了，但是业内人士认为走如梯瓦收购的路径很容易债台高筑，让企业陷入另一个泥潭中。整体上，仿制药企转型创新并非是通过收购就能一蹴而就的。一般情况下，仿制药企向创新转型，还需要经过改良型新药的洗礼，而非直接弯道超车一步到位。另外在企业运作方面仿制药研发和创新药研发往往是两种不同的研发思维，需要两个不同的团队运作。正如E药经理人撰稿人黑土地所言，创新药的研发成功，常常发生在过往已经在创新药研发有积累的科学家团队。仿制药企业想要转型创新药成功，准备好钱和时间后，应该从学会和这些有成功经验的科学家团队合作开始。推荐阅读全球TOP10仿制药企又无中国药企，印度4席南非1席！中国仿制药企们别再「啃老」了梯瓦（Teva）中国: 在华市场布局从特药开始猛虎、饿狼环伺，中国仿制药企如何摆脱困兽之争？未来在哪里？仿制药企转型创新，成功率低于50%？难在哪儿？买个融资遇困的港股“18A”可行否？扫描二维码，免费获取完整研报。或点击文末“阅读原文”免费获取。

The Health Brand's Digestive Products Help Process Histamine and Improve Natural DAO Production FORT LAUDERDALE, Fla., Aug. 29, 2022 /PRNewswire/ -- Histamine intolerance is a relatively new medical subject. One of its critical components, the Diamine Oxidase (or DAO) enzyme that helps break down histamine in the body, wasn't even discovered until 1929. Even then, the concept of histamine intolerance wasn't properly outlined until early in the 21st century. Since then, the condition has received a growing amount of attention. It's already estimated that 1-3% of the global population could be intolerant to the biogenic amine, with that number expected to rise as more research is completed. As with all intolerances, the inability of the body to break down histamine isn't as serious as a food allergy. However, it can lead to a variety of unpleasant symptoms, from headaches and fatigue to nasal congestion, digestive concerns, and abdominal cramping. Dutch health brand Intoleran has created a two-part response to the issue of histamine intolerance. The company's cozidase supplement includes a combination of key vitamins and minerals that help boost DAO production in the body. Together, copper and zinc as well as vitamins C and B6 work together to stimulate natural DAO production. In addition, the brand has created a pair of DAO-titled products. Its DAO mini purely contains the DAO enzyme. DAO plus comes with the enzyme as well as vitamin C and quercetin, which aid in lowering histamine levels in the body. In either case, when ingested orally before or while eating foods that are high in histamines, these can help break down the chemical in the digestive tract and avoid symptoms. Cozidase is imminently available in the U.S. (Intoleran is completing the process of entering the North American market) while the pair of DAO products will follow soon afterward. "We are learning more about histamine intolerance every day," says Intoleran owner Harmen Treep, "Our team of dietician specialists is working hard to ensure that our histamine products provide the same level of relief as any of our other intolerance-focused product lines. As with everything the Intoleran team does, the goal here is simple: we want everyone to enjoy food again without any of the nasty consequences of food intolerances." About Intoleran: Intoleran was founded in the Netherlands in 2008. The Dutch health brand specializes in creating enzyme-based supplements that address a variety of food intolerances, including lactose, fructose, fructans, galactans, and sucrose. Intoleran products assist the digestive system by helping to properly digest food and, consequently, avoid many of the unpleasant side effects that come from food intolerances. In order to preserve quality and effectiveness, Intoleran only uses ingredients necessary for the effect of the supplements and no unnecessary additives. This allows as many people as possible to use the products without unwanted side effects. Learn more at intoleran.com. Please direct inquiries to: Anderson Spaur (954) 613-7822 [email protected] SOURCE Intoleran