Nintedanib esylate

勃林格殷格翰 勃林格殷格翰2月24日宣布，其在研肺纤维化疗法口服磷酸二酯酶4B（PDE4B）抑制剂nerandomilast的上市申请（NDA）已获得中国国家药品监督管理局（NMPA）药品审评中心（CDE）的受理，用于治疗成人特发性肺纤维化（IPF）。此前，该疗法已被CDE纳入优先审评审批程序，以加速其在中国获批上市的步伐。 本次上市申请递交是基于nerandomilast关键性III期临床试验FIBRONEER™-IPF的积极结果。勃林格殷格翰在公告中称“这是十年来首个达到主要终点的IPF III期临床试验。IPF治疗领域有望迎来下一代突破性疗法。” 尽管目前已有多款特发性肺纤维化First-In-Class新疗法进入到临床试验晚期阶段，而勃林格殷格翰的nerandomilast却率先突围成功。 延伸阅读：IPF也疯狂：新药开发“三剑客”突围 值得一提的是，2月10日，nerandomilast在治疗进展性肺纤维化III期研究达到主要终点。 勃林格殷格翰首先在中国提交nerandomilast上市申请，而非在欧美等发达市场，可能主要是基于市场竞争原因。 首先，勃林格殷格翰的同适应症药物Ofev（尼达尼布）在中国已失去专利保护，多款仿制药获批上市，面临激烈的市场竞争。而该药物在国欧美仍处于专利保护期内，如在美国的专利保护/市场独占权保护最长至2029年。 其次，PDE4B抑制剂同样面临着国内follow者的压力。如海思科的HSK-44459今年1月进入到II期临床试验中；石药集团2月10日宣布其开发的SYH2059已在美国和中国获批准开展临床试验。 此外，勃林格殷格翰在特发性肺纤维化领域还有多款早期管线布局。就在近期，该公司管线中又添加了一款抗纤维化新药。 延伸阅读：勃林格殷格翰一口气在特发性肺纤维化布局4款不同机制新药，国内follow者恒瑞、海思科...... 本文由「新药前沿」微信公众号根据公开资料整理编辑，欢迎个人转发至朋友圈。媒体或机构转载授权请在「新药前沿」微信公众号留言公众号名称，审核通过后开通白名单获取转载授权，转载请标识来源。 免责声明：本文仅作信息交流之目的，非投资建议或者治疗方案推荐，「新药前沿」微信公众号不对任何主体因使用本文内容而导致的任何损失承担责任。 限于作者水平和专业知识所限，如有谬误，欢迎指正！

2024 revenues of $286M , +43% v. 2023; 4Q 2024 revenues of $77M , +31% v. 4Q 2023 2024 net income of $28M ; Non-GAAP net income of $68M 4Q 2024 net income of $7M ; Non-GAAP net income of $23M Reduced debt principal by $236M ; remaining convertible debt of $36M Year-end 2024 cash, cash equivalents and investments of $203M Advanced pipeline: Reported primary endpoint of INHALE-1 for Afrezza in pediatrics Progressed MNKD-101 to Global Phase 3 Completed Phase 1 of MNKD-201 Reported primary endpoint of INHALE-1 for Afrezza in pediatrics Progressed MNKD-101 to Global Phase 3 Completed Phase 1 of MNKD-201 DANBURY, Conn. and WESTLAKE VILLAGE, Calif. , Feb. 26, 2025 (GLOBE NEWSWIRE) -- MannKind Corporation (Nasdaq: MNKD) today reported financial results for the quarter and year ended December 31, 2024 , and provided a business update. “Throughout 2024, we accomplished the milestones we outlined at the beginning of the year, including delivering robust revenues as we exited the year with an annual run rate of $300 million ,” said Michael Castagna , PharmD, Chief Executive Officer of MannKind Corporation . “We are thrilled to have welcomed Dominic Marasco as President, Endocrine Business Unit, positioning Afrezza for further growth, including a planned submission this summer to seek approval in the pediatric population. In our orphan lung clinical programs, nintedanib DPI is progressing to the next phase of development and our Phase 3 trial of clofazimine inhalation suspension in NTM lung disease is expected to meet the interim enrollment target by the end of 2025.” 4Q 2024 Business Update and Upcoming Milestones Afrezza® INHALE-1 Pediatric Phase 3 clinical trial Six-month safety and efficacy results announced Requested meeting with the U.S. Food and Drug Administration ("FDA") in 1H 2025 to discuss data submission for potential approval of Afrezza in the pediatric population Expect twelve-month data set with safety extension in 1H 2025 Anticipate supplemental new drug application filing in 1H 2025 pending FDA feedback Clofazimine Inhalation Suspension Phase 3 (ICON-1) global clinical trial (MNKD-101) Approximately 70% of anticipated sites have been activated in four countries ( U.S. , Japan , Australia , South Korea ) Patients randomized in two countries ( U.S. and Australia ) Expect to meet the interim enrollment target by YE 2025 Nintedanib DPI Phase 1 clinical trial (MNKD-201) Successfully completed Phase 1 trial, demonstrating nintedanib DPI was well tolerated with no serious adverse events or study drug discontinuation reported Expect to meet with the FDA in 1H 2025 to advance MNKD-201 into next phase of development Commercial – Endocrine Business Unit Announced the appointment of Dominic Marasco as President, Endocrine Business Unit Afrezza INHALE-3 Phase 4 clinical trial 17-week data published in Diabetes Care; 30-week data manuscripts expected to be published in 1H 2025 Inhaled insulin recognized as comparable to injectable insulin in the American Diabetes Association ® Standards of Care in Diabetes – 2025 Label application to update initial Afrezza conversion dose submitted to FDA Afrezza approved in India for adults; expect to ship in 4Q 2025 once Cipla obtains registration certificate and import license; earned $1.1M regulatory milestone Corporate and Financial: Strong Balance Sheet Cash, cash equivalents and investments as of December 31, 2024 totaled $203 million Eliminated principal of $236 million across three debt instruments during 2024 resulting in: Remaining outstanding debt balance of $36 million in 2.5% senior convertible notes due 2026 Utilized a combination of cash and stock to avoid potential dilution of 12 million shares of common stock Interest expense savings of $9 million through the respective maturity dates Remaining outstanding debt balance of $36 million in 2.5% senior convertible notes due 2026 Utilized a combination of cash and stock to avoid potential dilution of 12 million shares of common stock Interest expense savings of $9 million through the respective maturity dates Fourth Quarter and Full Year 2024 Financial Results Revenues Total revenues for the fourth quarter and full year 2024 rose due to increases in revenue from royalties, collaborations and services, and commercial sales. The rise in royalties was primarily due to higher patient demand for Tyvaso DPI. Collaborations and services revenue grew due to increased manufacturing of Tyvaso DPI for United Therapeutics Corporation ("UT"). Net revenues for Afrezza and V-Go increased primarily as a result of improved gross-to-net percentages and higher demand and, to a lesser extent, pricing for Afrezza, partially offset by a decrease in V-Go product demand. Operating Expenses and Other Financial Highlights Cost of revenue – collaborations and services was $14.8 million for the fourth quarter of 2024, compared to $12.0 million for the same period in 2023, an increase of 24%. For the full year 2024, cost of revenue – collaborations and services was $59.2 million , compared to $41.9 million , an increase of 41%. These increases are primarily the result of increased manufacturing volume of Tyvaso DPI. Research and development ("R&D") expenses were $11.1 million for the fourth quarter of 2024 compared to $9.2 million for the same period in 2023, an increase of 21%. For the full year 2024, R&D expenses were $45.9 million compared to $31.3 million , an increase of 47%. The increases were primarily attributable to development activities including the ICON-1 clinical study, a Phase 1 clinical study of MNKD-201, and personnel costs primarily due to increased headcount resulting from the Pulmatrix Transaction. Selling, general and administrative ("SG&A") expenses were $24.0 million for the fourth quarter of 2024 compared to $20.5 million for the same period in 2023, an increase of 17%. For the full year 2024, SG&A expenses remained consistent compared to the same period in 2023. This was primarily attributable to a loss of $1.4 million for estimated returns associated with sales of V-Go that pre-date MannKind's acquisition of the product and increases in personnel costs, professional fees and promotional activities, offset by a decrease in selling expenses related to sales force restructuring activities completed during the first quarter of 2024. For the fourth quarter of 2024, MannKind reported net income of $7.4 million , or $0.03 earnings per share – basic, compared to net income of $1.4 million , or $0.01 earnings per share – basic, for the same period in 2023. For the full year 2024, MannKind reported net income of $27.6 million , or $0.10 earnings per share – basic, compared to net loss of $11.9 million , or $0.04 loss per share – basic for the same period in 2023. For the fourth quarter of 2024, MannKind reported non-GAAP net income of $23.0 million , or $0.08 earnings per share – basic, compared to non-GAAP net income of $7.1 million , or $0.02 earnings per share – basic, for the same period in 2023. For the full year 2024, MannKind reported non-GAAP net income of $67.7 million , or $0.25 earnings per share – basic, compared to non-GAAP net income of $5.9 million , or $0.03 earnings per share – basic for the same period in 2023. For a reconciliation of GAAP reported net income (loss) and net income (loss) per share for basic weighted average shares to these non-GAAP measures, please see the end of this press release. Conference Call MannKind will host a conference call and presentation webcast to discuss these results today at 4:30 p.m. Eastern Time . The webcast will be accessible via a link on MannKind’s website. A replay will also be available in the same location within 24 hours after the call and accessible for approximately 90 days. About MannKind MannKind Corporation (Nasdaq: MNKD) focuses on the development and commercialization of innovative inhaled therapeutic products and devices to address serious unmet medical needs for those living with endocrine and orphan lung diseases. We are committed to using our formulation capabilities and device engineering prowess to lessen the burden of diseases such as diabetes, nontuberculous mycobacterial (NTM) lung disease, pulmonary fibrosis, and pulmonary hypertension. Our signature technologies – dry-powder formulations and inhalation devices – offer rapid and convenient delivery of medicines to the deep lung where they can exert an effect locally or enter the systemic circulation, depending on the target indication. With a passionate team of Mannitarians collaborating nationwide, we are on a mission to give people control of their health and the freedom to live life. Please visit mannkindcorp.com to learn more, and follow us on LinkedIn, Facebook, X or Instagram. Forward-Looking Statements Statements in this press release that are not statements of historical fact are forward-looking statements that involve risks and uncertainties. These statements include, without limitation, statements regarding MannKind's expectations about the development of Afrezza for the pediatric population, MNKD-101 and MNKD-201, including the expected timing for data readouts, regulatory filings, meetings with the FDA and patient enrollment timelines; expectations regarding the commercialization of Afrezza in India , including the estimated timing for the shipment of product; and MannKind being positioned for further growth. Words such as “believes,” “anticipates,” “plans,” “expects,” “intend,” “will,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon MannKind’s current expectations. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks associated with developing product candidates; risks and uncertainties related to unforeseen delays that may impact the timing of clinical trials and reporting data; risks associated with safety and other complications of our products and product candidates; risks associated with the regulatory review process; risks associated with competition; and other risks detailed in MannKind’s filings with the Securities and Exchange Commission (“SEC”), including under the “Risk Factors” heading of its Annual Report on Form 10-K for the year ended December 31, 2024 , being filed with the SEC later today, and subsequent periodic reports on Form 10- Q. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. All forward-looking statements are qualified in their entirety by this cautionary statement, and MannKind undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this press release. Tyvaso DPI is a trademark of United Therapeutics Corporation. AFREZZA, MANNKIND , and V-GO are registered trademarks of MannKind Corporation . _________________(1) Diluted weighted average shares ("DWAS") differs from basic weighted average shares due to the weighted average number of shares that would be outstanding upon exercise or vesting of outstanding share-based payments to employees and conversion of convertible notes. For the year ended December 31, 2024 , DWAS included 9,429 shares issuable upon exercise or vesting of outstanding share-based payments. 6,967 shares issuable upon conversion of our senior convertible notes were excluded as their effect would be antidilutive. Non-GAAP Measures To supplement our consolidated financial statements presented under GAAP, we are presenting non-GAAP net income (loss) and non-GAAP net income (loss) per share - basic, which are non-GAAP financial measures. We are providing these non-GAAP financial measures to disclose additional information to facilitate the comparison of past and present operations, and they are among the indicators management uses as a basis for evaluating our financial performance. We believe that these non-GAAP financial measures, when considered together with our GAAP financial results, provide management and investors with an additional understanding of our business operating results, including underlying trends. These non-GAAP financial measures are not meant to be considered in isolation or as a substitute for comparable GAAP measures; should be read in conjunction with our consolidated financial statements prepared in accordance with GAAP; have no standardized meaning prescribed by GAAP; and are not prepared under any comprehensive set of accounting rules or principles. In addition, from time to time in the future there may be other items that we may exclude for purposes of our non-GAAP financial measures; and we may in the future cease to exclude items that we have historically excluded for purposes of our non-GAAP financial measures. Likewise, we may determine to modify the nature of its adjustments to arrive at our non-GAAP financial measures. Because of the non-standardized definitions of non-GAAP financial measures, the non-GAAP financial measures as used by us in this report have limits in their usefulness to investors and may be calculated differently from, and therefore may not be directly comparable to, similarly titled measures used by other companies. The following table reconciles our financial measures for net income (loss) and net income (loss) per share ("EPS") for basic weighted average shares as reported in our consolidated statement of operations to a non-GAAP presentation: _________________(1) Represents the non-cash portion of the 1% royalty on net sales of Tyvaso DPI which is remitted to the royalty purchaser and recognized as royalties from collaborations in our consolidated statements of operations. Source: MannKind