Congenital Hyperinsulinism

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。4月3日，据外媒Endpoints News独家报道，一家名为Metsera Therapeutics的新减肥初创公司获得了顶级风投公司3.5亿美元（25.32亿元人民币）的投资，并由一位资深制药公司首席执行官领导，该公司一直在悄悄地制定计划，计划在未来两年内将多种药物投入临床。本次融资可能是2024年生物技术领域最大的一轮融资。根据外媒信息，Population Health和ARCH Venture Partners是该公司创始人，其他投资者包括GV、F-Prime Capital、Exor Ventures、Mubadala、Newpath Partners、软银、阿布扎比投资局和Americo。Metsera的首席执行官是the Medicines Company(2020年被诺华以97亿美元收购)的前任首席执行官Clive Meanwell。该公司于2022年由投资公司Population Health Partners注册成立，这是一家由Meanwell和辉瑞前首席执行官Ian Read于2020年创立的公司。Metsera以隐形模式运营，该公司已从一家韩国生物技术公司获得了6种肥胖候选药物的授权，并收购了一家伦敦生物技术公司，且计划在未来12至24个月内申请多达7项IND。Metsera已获得许可的候选肥胖药物来自韩国生物技术公司D&D Pharmatech。去年4月，两家公司宣布了一项关于三种产品的初始授权协议:一种口服GLP-1激动剂DD02S，一种口服GLP-1/GCG/GIP，称为“triple G”激动剂的DD03和MET06。今年3月18日，两家公司宣布了一项扩大协议，获得DD07和DD14的许可。DD07是一种口服胰肽受体激动剂，DD14是一种口服GLP-1/GIP受体双重激动剂。根据D&D制药公司在韩国的新闻稿，Metsera和D&D同时宣布了第二笔交易，授权一种名为DD15的注射用triple G候选药物，计划在2025年上半年进入临床试验，该新闻稿还提到了DD15治疗肝病MASH的潜力。两笔交易加在一起，对D&D的里程碑式支付价值可能超过1万亿韩元(7.39亿美元)。Metsera高级副总裁Stephen Bloom表示，我目前正在进一步研究利用肠道激素来控制体重，这是一种无副作用、方便的治疗方法。我加入Metsera是因为这家公司有能力和精神，能够成功地将这些急需的治疗方法实现。可见，减肥药赛道可谓是火爆。3月5日，派格生物递交招股书，准备在港交所主板上市，这是今年第一个减肥药IPO。派格生物是一家专注于慢性病创新疗法的企业，派格生物的产品管线全面覆盖了包括2型糖尿病、非酒精性脂肪肝病、肥胖、阿尔兹海默症、阿片类药物引起的便秘（OIC）及先天性高胰岛素血症等多个疾病治疗领域。发展至今，派格生物旗下共有6款在研药物，其中有4条管线与GLP-1类药物相关，适应症几乎都是针对肥胖、超重、糖尿病等领域。2月底，印度的太阳制药、Cipla、Dr Reddys  和Lupin都表示，他们已经开始研发自己的“Wegovy”，太阳制药正在开发自己的新型专利治疗肥胖症和2型糖尿病的药物，但还需要通过临床试验。Reddy’s和Cipla正在复制一种更像仿制药的创新药物。参考资料:www.endpts.com 活动推荐【4.12日上海】Focus抗体/XDC类系列见面会:生物偶联药物，早期研发专场-上海首站蓄势待发，精准聚焦ADC/XDC早期研发最新进展与难点案例，面对面学习头部领先经验，了解行业新兴项目最新数据与趋势，与行业专家共同探索更多市场空间，创造更多产业商机与价值！现场特设新兴项目路演及点评交流，更有大咖点评互动。席位有限，机不可失~

Pictured: A U.S. federal bankruptcy courthouse building/iStock, GussWilder Eiger BioPharmaceuticals on Monday announced that it has voluntarily filed for bankruptcy and has kicked off the process of selling its assets and winding down the company’s operations. The California-based biotech has filed for Chapter 11 protection with the Bankruptcy Court for the Northern District of Texas, and has also submitted customary “first day” motions. If granted, the motion will provide Eiger some relief allowing it to transition into bankruptcy while it meets the company’s commitments to its stakeholders without “material disruptions” to its ordinary operations, according to the announcement. Eiger will sell all its assets during the bankruptcy case as it prepares for “an orderly wind down” of its operations. As part of the process, the biotech has inked a “stalking horse” agreement with rare disease player Sentynl Therapeutics which has agreed to purchase Zokinvy (lonafarnib), a farnesyltransferase inhibitor approved to treat the rare and progressive genetic disease Hutchinson-Gilford progeria syndrome. Sentynl will pay up to $26 million for Zokinvy, with the final price subject to other adjustments including per diem reductions. Zokinvy is an oral small molecule drug that blocks the farnesyltransferase protein. It is also approved for use in processing-deficient progeroid laminopathies with specific genetic mutations. The companies expect to close the sale by April 24, 2024. As part of its bankruptcy filing, other bidders can also submit competing offers for Eiger’s assets through a court-supervised process. Eiger’s bankruptcy filing on Monday caps off a difficult year for the biotech. In September 2023, it announced that it was discontinuing the Phase III LIMT-2 study of its candidate peginterferon lambda for chronic hepatitis delta. A quarterly review by a Data Safety Monitoring Board (DSMB) found concerning safety signals associated with peginterferon lambda. Four patients who received the investigational therapy developed hepatobiliary events, which led to liver compensation, leading the DSMB to recommend the study’s discontinuation. In September 2022, the FDA also rejected Eiger’s application for an Emergency Use Authorization for peginterferon lambda, which the biotech was proposing for the treatment of mild-to-moderate COVID-19. Following this rejection, Eiger in June 2023 laid off 25% of its workers in a sweeping reprioritization and savings program. The initiative also included a pivot to its GLP-1 receptor antagonist avexitide, which at the time was being developed for post-bariatric hypoglycemia and congenital hyperinsulinism. Eiger expected the cost-cutting measures to support its operations through the fourth quarter of 2024. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

-- Proceeds from financing and existing cash on-hand sufficient to fund planned operations into 2026 --BOSTON, April 01, 2024 (GLOBE NEWSWIRE) -- Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a commercial-stage biopharmaceutical company focused on transforming the lives of patients and their families living with rare neuroendocrine diseases, today announced that it has signed an investment agreement with current shareholders, led by Perceptive Advisors LLC and its Discovery Fund and a life-sciences focused institutional investor, for the sale of its series A convertible preferred stock (“Preferred Stock”) for gross proceeds of $150 million to the Company. The Company intends to use the proceeds from the offering to fund its clinical development programs and commercialization activities, for working capital, and for general corporate purposes. The transaction is expected to close on or about April 15, 2024, subject to the satisfaction of customary closing conditions. Based on its current operating plans, Rhythm expects the net proceeds from the sale of Preferred Stock, in addition to its cash, cash equivalents and short-term investments as of December 31, 2023, will be sufficient to fund its operating expenses and capital expenditure requirements into 2026. “We are pleased to announce this convertible preferred stock offering, led by Perceptive Advisors and its Discovery Fund, and we are pleased to receive continued support from a second, existing shareholder who chose to participate in this financing,” said David Meeker, M.D., Chairman, Chief Executive Officer and President of Rhythm. “This financing is expected to extend our cash runway well into 2026 and beyond multiple potentially value-creating milestones including the topline data readout from our phase 3 trial in hypothalamic obesity in the first half of 2025.” “Rhythm – with its lead asset IMCIVREE® (setmelanotide) approved and available in 14 countries, including the United States, to treat certain rare melanocortin-4 receptor diseases – has executed very well against its development, regulatory and commercial strategies on a global level,” said Konstantin Poukalov, Managing Director and Perceptive Discovery Co-Head. “We believe the Company has a clear and achievable global vision to address the unmet needs in additional rare MC4R pathway diseases, including hypothalamic obesity, with setmelanotide and its additional pipeline assets.” Following the expiration or termination of any applicable waiting period under the HSR Act, the Preferred Stock will be convertible into common stock at any time at an initial conversion rate of 20.8333 shares of common stock per $1,000 of liquidation preference, implying a conversion price of $48 per share, which is a 19% premium to the Company’s 10-day trailing volume weighted average price. The conversion rate is subject to customary adjustments, and adjustment in respect of certain dilutive issuances. The Company also can require conversion if the price of its common stock exceeds 250% of the implied conversion price for 20 trading days in a 30-trading day period, subject to certain requirements. The Company has the right to redeem all, but not less than all, of the Preferred Stock for the then applicable liquidation preference, which is initially par, on and after the five-year anniversary of its issuance. Holders of the Preferred Stock will be entitled to a 6% cumulative annual dividend, commencing on the second anniversary of closing. Dividends will be compounded quarterly, and payable in cash or in kind at the Company’s option. The Preferred Stock will vote with the common stock on an as-converted basis, subject to satisfaction of certain antitrust-related conditions. Holders of the Preferred Stock are entitled to 175% of the liquidation preference upon certain corporate events, including a change of control or liquidation of the Company. The Company has agreed to grant the investors certain registration rights with respect to the common stock underlying the Preferred Stock. J. Wood Capital Advisors acted as financial advisor and Latham & Watkins LLP acted as legal counsel to the Company on the transaction. Ropes & Gray LLP acted as legal counsel to Perceptive Advisors. This press release shall not constitute an offer to sell or a solicitation of an offer to buy the Preferred Stock, nor shall there be any sale of the Preferred Stock in any state or jurisdiction in which such offer, solicitation or sale would be unlawful under the securities laws of any such state or jurisdiction. About Rhythm PharmaceuticalsRhythm is a commercial-stage biopharmaceutical company committed to transforming the lives of patients and their families living with rare neuroendocrine diseases. Rhythm’s lead asset, IMCIVREE® (setmelanotide), an MC4R agonist designed to treat hyperphagia and severe obesity, is approved by the U.S. Food and Drug Administration (FDA) for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) deficiency confirmed by genetic testing, or patients with a clinical diagnosis of Bardet-Biedl syndrome (BBS). Both the European Commission (EC) and the UK’s Medicines & Healthcare Products Regulatory Agency (MHRA) have authorized setmelanotide for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or genetically confirmed loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. Additionally, Rhythm is advancing a broad clinical development program for setmelanotide in other rare diseases, as well as investigational MC4R agonists LB54640 and RM-718, and a preclinical suite of small molecules for the treatment of congenital hyperinsulinism. Rhythm’s headquarters is in Boston, MA. Setmelanotide IndicationIn the United States, setmelanotide is indicated for chronic weight management in adult and pediatric patients 6 years of age and older with monogenic or syndromic obesity due to POMC, PCSK1 or LEPR deficiency as determined by an FDA-approved test demonstrating variants in POMC, PCSK1 or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS) or BBS. In the European Union, setmelanotide is indicated for the treatment of obesity and the control of hunger associated with genetically confirmed BBS or loss-of-function biallelic POMC, including PCSK1, deficiency or biallelic LEPR deficiency in adults and children 6 years of age and above. In Europe, setmelanotide should be prescribed and supervised by a physician with expertise in obesity with underlying genetic etiology. Limitations of UseSetmelanotide is not indicated for the treatment of patients with the following conditions as setmelanotide would not be expected to be effective: Obesity due to suspected POMC, PCSK1 or LEPR deficiency with POMC, PCSK1 or LEPR variants classified as benign or likely benignOther types of obesity not related to POMC, PCSK1 or LEPR deficiency, or BBS, including obesity associated with other genetic syndromes and general (polygenic) obesity. ContraindicationPrior serious hypersensitivity to setmelanotide or any of the excipients in IMCIVREE. Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. WARNINGS AND PRECAUTIONS Skin Pigmentation and Darkening of Pre-Existing Nevi: Generalized increased skin pigmentation and darkening of pre-existing nevi have occurred because of its pharmacologic effect. Full body skin examinations prior to initiation and periodically during treatment should be conducted to monitor pre-existing and new pigmentary lesions. Heart rate and blood pressure monitoring: In Europe, heart rate and blood pressure should be monitored as part of standard clinical practice at each medical visit (at least every 6 months) for patients treated with setmelanotide. Disturbance in Sexual Arousal: Spontaneous penile erections in males and sexual adverse reactions in females have occurred. Patients who have an erection lasting longer than 4 hours should seek emergency medical attention. Depression and Suicidal Ideation: Depression and suicidal ideation have occurred. Patients should be monitored for new onset or worsening depression or suicidal thoughts or behaviors. Consideration should be given to discontinuing setmelanotide if patients experience suicidal thoughts or behaviors, or clinically significant or persistent depression symptoms occur. Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., anaphylaxis) have been reported. If suspected, advise patients to promptly seek medical attention and discontinue setmelanotide. Pediatric Population: The prescribing physician should periodically assess response to setmelanotide therapy. In growing children, the impact of weight loss on growth and maturation should be evaluated. In Europe, the prescribing physician should monitor growth (height and weight) using age- and sex-appropriate growth curves. Risk of Serious Adverse Reactions Due to Benzyl Alcohol Preservative in Neonates and Low Birth Weight Infants: Setmelanotide is not approved for use in neonates or infants. Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with benzyl alcohol-preserved drugs. ADVERSE REACTIONS Most common adverse reactions (incidence ≥20%) included skin hyperpigmentation, injection site reactions, nausea, headache, diarrhea, abdominal pain, vomiting, depression, and spontaneous penile erection. USE IN SPECIFIC POPULATIONS Lactation: Not recommended when breastfeeding. To report SUSPECTED ADVERSE REACTIONS, contact Rhythm Pharmaceuticals at +1 (833) 789-6337 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. See section 4.8 of the Summary of Product Characteristics for information on reporting suspected adverse reactions in Europe. Please see the full Prescribing Information for additional Important Safety Information. Forward-looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the potential, safety, efficacy, and regulatory and clinical progress of, and our business strategy and plans for, our drug products, the anticipated benefits of and activities under the investment transaction with Perceptive, our use of proceeds from the transaction with Perceptive, the expected timing for closing of the transaction, our expectation that the transaction with Perceptive will provide us capital to execute our corporate strategy in 2024 and 2025; and the issuance of dividends, and the sufficiency of our cash, cash equivalents and short-term investments to fund our operations. Statements using word such as “expect”, “anticipate”, “believe”, “may”, “will” and similar terms are also forward-looking statements. Such statements are subject to numerous risks and uncertainties, including, but not limited to, whether the conditions for the closing of the investment transaction; our ability to enroll patients in clinical trials, the design and outcome of clinical trials, the impact of competition, the ability to achieve or obtain necessary regulatory approvals, risks associated with data analysis and reporting, our ability to successfully commercialize setmelanotide, our liquidity and expenses, our ability to retain our key employees and consultants, and to attract, retain and motivate qualified personnel, and general economic conditions, and the other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2023 and our other filings with the Securities and Exchange Commission. Except as required by law, we undertake no obligations to make any revisions to the forward-looking statements contained in this release or to update them to reflect events or circumstances occurring after the date of this release, whether as a result of new information, future developments or otherwise. Corporate Contact:David ConnollyHead of Investor Relations and Corporate CommunicationsRhythm Pharmaceuticals, Inc.857-264-4280dconnolly@rhythmtx.com Media Contact:Adam DaleyBerry & Company Public Relations212-253-8881adaley@berrypr.com