Atirmociclib

– On track to report topline data from Phase 3 VERITAC-2 trial in 4Q24 or 1Q25 – – Initial clinical data from Phase 1/2 TACTIVE-U sub-study of abemaciclib in combination with vepdegestrant to be presented at San Antonio Breast Cancer Symposium in December 2024 – – Recently presented new preclinical data for the PROTAC LRRK2 degrader ARV-102 demonstrating that LRRK2 degradation affects biomarkers in the CSF – - $1.1 billion in cash, cash equivalents and marketable securities as of Sept. 30, 2024 - – Company to host conference call today at 8:00 a.m. ET – NEW HAVEN, Conn., Oct. 30, 2024 (GLOBE NEWSWIRE) -- Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, today reported financial results for the third quarter ended September 30, 2024, and provided a corporate update. “We maintained strong momentum across our portfolio in the third quarter and remain on track to report topline data from VERITAC-2, our Phase 3 clinical trial in metastatic breast cancer, in the fourth quarter of 2024 or the first quarter of 2025,” said John Houston, Ph.D., Chairperson, Chief Executive Officer and President at Arvinas. “In partnership with our colleagues at Pfizer, we are excited by the possibility of changing the treatment paradigm for ER+/HER2- breast cancer and look forward to sharing results from VERITAC-2 in the coming months.” “Our path to reaching our goal of becoming a multi-product, commercial-stage organization with a robust pipeline across several indications is clearly defined, and our novel PROTAC platform technology has the potential to enable opportunities across multiple therapeutic areas,” continued Dr. Houston. “We look forward to completing the multiple ascending dose portion of our Phase 1 clinical trial with ARV-102, our first PROTAC degrader with the potential to treat neurodegenerative diseases, and sharing data in 2025. We are also encouraged by the preclinical profile of ARV-393, our BCL6 PROTAC degrader currently being evaluated in a first-in-human Phase 1 clinical trial in patients with B-cell lymphomas. We look forward to sharing more about these programs in the coming months.” 3Q 2024 Business Highlights and Recent Developments Vepdegestrant Continued enrollment globally in multiple clinical studies of vepdegestrant in ER+/HER2- metastatic breast cancer. VERITAC-2: Phase 3 monotherapy clinical trial in patients with metastatic breast cancer (ClinicalTrials.gov Identifier: NCT05654623)TACTIVE-U: Phase 1b/2 combination umbrella trial evaluating combinations of vepdegestrant with abemaciclib, ribociclib, or samuraciclib (ClinicalTrials.gov Identifiers: NCT05548127, NCT05573555, and NCT06125522).TACTIVE-K: Phase 1/2 clinical trial with vepdegestrant plus Pfizer’s novel CDK4 inhibitor atirmociclib (ClinicalTrials.gov Identifier: NCT06206837) ARV-102: Oral PROTAC LRRK2 degrader In October, presented preclinical data at the 2024 Michael J. Fox Foundation Parkinson’s Disease Conference further supporting the potential of PROTAC-induced leucine-rich repeat kinase 2 (LRRK2) degradation as a potential treatment for patients with neurodegenerative diseases. New findings presented included data demonstrating: Orally delivered ARV-102 crosses the blood-brain barriers and degrades LRRK2 in the cerebrospinal fluid (CSF) of non-human primates (NHPs).Degradation of LRRK2 by ARV-102 induces changes in pathway (lysosomal and inflammation) biomarkers in the CSF of NHPs, which has not previously been demonstrated by kinase inhibitors of LRRK2.In murine tauopathy models, oral PROTAC LRRK2 degrader treatment led to ~50% pathologic tau reduction. Initiated the multiple ascending dose portion of the ongoing Phase 1 clinical trial in healthy volunteers. ARV-393: Oral PROTAC BCL6 degrader Continued recruiting patients in the first-in-human Phase 1 clinical trial in patients with B-cell lymphomas. Anticipated Upcoming Milestones and Expectations Vepdegestrant As part of Arvinas global collaboration with Pfizer, the companies plan to: Complete enrollment (4Q24) and announce topline data (4Q24/1Q25) for the VERITAC-2 Phase 3 monotherapy clinical trial in patients with metastatic breast cancer.Present initial safety and pharmacokinetic data from the TACTIVE-U sub-study (NCT05548127) of abemaciclib in combination with vepdegestrant at the San Antonio Breast Cancer Symposium (SABCS) in December 2024.Present data from the Phase 1 healthy volunteer pharmacokinetic trial of vepdegestrant in combination with midazolam to assess potential for drug-drug interaction at SABCS in December 2024 (NCT06256510).Continue enrollment of the ongoing Phase 1b/2 combination umbrella trial evaluating combinations of vepdegestrant with abemaciclib, ribociclib, or samuraciclib (TACTIVE-U; ClinicalTrials.gov Identifiers: NCT05548127, NCT05573555, and NCT06125522).Evaluate data from the study lead-in of the VERITAC-3 Phase 3 trial (NCT05909397) in patients with ER+/HER2- locally advanced or metastatic breast cancer (2H24).Continue enrollment and evaluate preliminary data from the ongoing clinical trial with vepdegestrant plus Pfizer’s novel CDK4 inhibitor atirmociclib (TACTIVE-K).Start Phase 3 combination trials in the first- and second-line settings (anticipated in 2025; pending emerging data and regulatory feedback). First-line setting with vepdegestrant plus atirmociclib or palbociclib.Second-line setting with vepdegestrant plus palbociclib and/or another CDK4/6 inhibitor. ARV-102: Oral PROTAC LRRK2 degrader Complete enrollment in the ongoing multiple ascending dose portion of a Phase 1 trial evaluating ARV-102 in healthy volunteersPresent data from the Phase 1 trial in 2025. ARV-393: Oral PROTAC BCL6 degrader Continue recruiting patients in the first-in-human Phase 1 clinical trial evaluating ARV-393 in patients with B-cell lymphomas. Novel PROTAC KRAS G12D degrader File an Investigational New Drug (IND) application in 2025. Financial GuidanceBased on its current operating plan, Arvinas believes its cash, cash equivalents, and marketable securities as of September 30, 2024, is sufficient to fund planned operating expenses and capital expenditure requirements into 2027. Third Quarter Financial Results Cash, Cash Equivalents, and Marketable Securities Position: As of September 30, 2024, cash, cash equivalents and marketable securities were $1,121.6 million as compared with cash, cash equivalents, restricted cash and marketable securities of $1,266.5 million as of December 31, 2023. The decrease in cash, cash equivalents and marketable securities of $144.9 million for the nine months ended September 30, 2024 was primarily related to cash used in operations of $158.1 million (net of $150.0 million received from the Novartis agreements), inclusive of a one-time cash termination fee in the amount of $41.5 million related to the termination of our laboratory and office space lease with 101 College Street LLC in August 2024 and the purchase of lab equipment and leasehold improvements of $1.5 million, partially offset by proceeds from the exercise of stock options of $7.7 million and unrealized gains on marketable securities of $7.2 million. Research and Development Expenses: Research and development expenses were $86.9 million for the quarter ended September 30, 2024, as compared with $85.9 million for the quarter ended September 30, 2023. The increase in research and development expenses of $1.0 million for the quarter was primarily due to an increase in compensation and related personnel expenses of $2.8 million, which are not allocated by program, partially offset by a decrease in external expenses of $2.2 million. External expenses include program-specific expenses, which decreased by $1.1 million, primarily driven by decreases in our ARV-766 and ARV-110 programs of $3.8 million and $1.6 million, respectively, partially offset by increases in our ARV-102 and ARV-393 programs of $2.5 million and $1.4 million, respectively, and our non-program specific expenses, which decreased by $1.1 million. General and Administrative Expenses: General and administrative expenses were $75.8 million for the quarter ended September 30, 2024, as compared with $22.6 million for the quarter ended September 30, 2023. The increase in general and administrative expenses of $53.2 million for the quarter was primarily due to a loss on the termination of our laboratory and office space lease with 101 College Street LLC of $43.4 million as well as increases in personnel and infrastructure related costs of $5.0 million, professional fees of $3.4 million and in developing our commercial operations of $1.2 million. Revenue: Revenue was $102.4 million for the quarter ended September 30, 2024 as compared with $34.6 million for the quarter ended September 30, 2023. Revenue for the quarter is related to the license agreement with Novartis, the Vepdegestrant (ARV-471) Collaboration Agreement with Pfizer, the collaboration and license agreement with Bayer and the collaboration and license agreement with Pfizer. The increase in revenue of $67.8 million was primarily due to revenue from the Novartis license agreement of $76.7 million, offset by a decrease in revenue from the Vepdegestrant (ARV-471) Collaboration Agreement with Pfizer of $7.6 million related to timing differences in clinical trials and program expenses and a decrease in revenue from Bayer of $1.1 million related to the termination of the Bayer Collaboration Agreement in August 2024. Investor Call & Webcast Details Arvinas will host a conference call and webcast today, October 30, 2024, at 8:00 a.m. ET to review its third quarter 2024 financial results and discuss recent corporate updates. Participants are invited to listen by going to the Events and Presentation section under the Investors page on the Arvinas website at www.arvinas.com. A replay of the webcast will be available on the Arvinas website following the completion of the event and will be archived for up to 30 days. About VepdegestrantVepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive (ER+)/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits. The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy. About ArvinasArvinas (Nasdaq: ARVN) is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases. Through its PROTAC® (PROteolysis Targeting Chimera) protein degrader platform, the Company is pioneering the development of protein degradation therapies designed to harness the body’s natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. Arvinas is currently progressing multiple investigational drugs through clinical development programs, including vepdegestrant, targeting the estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin Lymphoma; and ARV-102, targeting LRRK2 for neurodegenerative disorders. Arvinas is headquartered in New Haven, Connecticut. For more information about Arvinas, visit www.arvinas.com and connect on LinkedIn and X. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the expected timing in connection with the completion of enrollment and reporting of topline data from the VERITAC-2 clinical trial; the potential to change the treatment paradigm for ER+/HER2- breast cancer; the goal of becoming a multi-product, commercial-stage organization with a robust pipeline across several indications; novel PROTAC platform technology having the potential to enable opportunities across multiple therapeutic areas; plans to present initial safety and pharmacokinetic data from the TACTIVE-U sub-study of abemaciclib in combination with vepdegestrant at SABCS; plans to present data from the Phase 1 healthy volunteer pharmacokinetic trial of vepdegestrant in combination with midazolam at SABCS; plans to continue enrollment in the TACTIVE-U study and evaluate data from the study lead-in of the VERITAC-3 Phase 3 clinical trial; plans to continue enrollment and evaluate preliminary data from the TACTIVE-K clinical trial; the expected timing of initiation of Phase 3 vepdegestrant combination trials in the first- and second-line settings, pending emerging data and regulatory feedback; expected timing of filing an investigational new drug application for a KRAS G12D degrader; plans to compete enrollment in the multiple ascending dose portion of the ARV-102 Phase 1 clinical trial, the timing of the presentation of data from such clinical trial, and the timing of sharing additional information about the program; plans to continue recruiting patients in the Phase 1 ARV-393 clinical trial and timing of sharing additional information about the program; and statements regarding Arvinas’ cash, cash equivalents and marketable securities. All statements, other than statements of historical fact, contained in this press release, including statements regarding Arvinas’ strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “goal,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Arvinas may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on such forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements Arvinas makes as a result of various risks and uncertainties, including but not limited to: Arvinas’ and Pfizer’s performance of the respective obligations with respect to Arvinas’ collaboration with Pfizer; whether Arvinas and Pfizer will be able to successfully conduct and complete clinical development for vepdegestrant; whether Arvinas will be able to successfully conduct and complete development for its other product candidates, including whether Arvinas initiates and completes clinical trials for its product candidates and receives results from its clinical trials and preclinical studies on its expected timelines or at all; whether Arvinas and Pfizer, as appropriate, will be able to obtain marketing approval for and commercialize vepdegestrant and other product candidates on current timelines or at all; Arvinas’ ability to protect its intellectual property portfolio; whether Arvinas’ cash and cash equivalent resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements, and other important factors discussed in the “Risk Factors” section of Arvinas’ Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent other reports on file with the U.S. Securities and Exchange Commission. The forward-looking statements contained in this press release reflect Arvinas’ current views with respect to future events, and Arvinas assumes no obligation to update any forward-looking statements, except as required by applicable law. These forward-looking statements should not be relied upon as representing Arvinas’ views as of any date subsequent to the date of this release. ContactsInvestors:Jeff Boyle+1 (347) 247-5089Jeff.Boyle@arvinas.com Media:Kirsten Owens+1 (203) 584-0307Kirsten.Owens@arvinas.com Arvinas, Inc.Condensed Consolidated Balance Sheets (Unaudited) (dollars and shares in millions, except per share amounts)September 30, 2024December 31,2023Assets Current assets: Cash and cash equivalents$85.2 $311.7 Restricted cash — 5.5 Marketable securities 1,036.4 949.3 Accounts receivable 7.3 — Other receivables 7.5 7.2 Prepaid expenses and other current assets 13.1 6.5 Total current assets 1,149.5 1,280.2 Property, equipment and leasehold improvements, net 6.8 11.5 Operating lease right of use assets 1.0 2.5 Collaboration contract asset and other assets 9.8 10.4 Total assets$1,167.1 $1,304.6 Liabilities and stockholders' equity Current liabilities: Accounts payable and accrued liabilities$75.9 $92.2 Deferred revenue 199.2 163.0 Current portion of operating lease liabilities 0.8 1.9 Total current liabilities 275.9 257.1 Deferred revenue 304.5 386.2 Long-term debt 0.6 0.8 Operating lease liabilities 0.1 0.5 Total liabilities 581.1 644.6 Stockholders’ equity: Preferred stock, $0.001 par value, zero shares issued and outstanding as of September 30, 2024 and December 31, 2023, respectively — — Common stock, $0.001 par value; 68.7 and 68.0 shares issued and outstanding as of September 30, 2024 and December 31, 2023, respectively 0.1 0.1 Accumulated deficit (1,486.5) (1,332.7)Additional paid-in capital 2,068.3 1,995.7 Accumulated other comprehensive income (loss) 4.1 (3.1)Total stockholders’ equity 586.0 660.0 Total liabilities and stockholders’ equity$1,167.1 $1,304.6 Arvinas, Inc.Condensed Consolidated Statements of Operations (Unaudited) Three Months Ended September 30,Nine Months Ended September 30,(dollars and shares in millions, except per share amounts) 2024 2023 2024 2023 Revenue$102.4 $34.6 $204.2 $121.6 Operating expenses: Research and development 86.9 85.9 264.9 284.5 General and administrative 75.8 22.6 131.3 73.3 Total operating expenses 162.7 108.5 396.2 357.8 Loss from operations (60.3) (73.9) (192.0) (236.2)Interest and other income, net 11.7 10.0 39.2 25.5 Net loss before income taxes and loss from equity method investment (48.6) (63.9) (152.8) (210.7)Income tax (expense) benefit (0.6) — (1.0) 0.7 Loss from equity method investment — (0.1) — (2.5)Net loss$(49.2)$(64.0)$(153.8)$(212.5)Net loss per common share, basic and diluted$(0.68)$(1.18)$(2.14)$(3.97)Weighted average common shares outstanding, basic and diluted 72.1 54.1 71.9 53.6

此次医博会由同写意策划，以“发展新质生产力，共享健康新未来”为主题，用全新的视角瞄准国内外医药及大健康产业发展前沿。诚邀海内外医药及大健康各界嘉宾齐聚中国医药城，共赴时代之约。展位/报告火热征集中！ 国产创新药对外授权的纪录又被打破了。 之前，百利天恒将EGFR×HER3双抗ADC药物BL-B01D1授权给百时美施贵宝（BMS），获得8亿美元的预付款，刷新了国产创新药出海的预付款纪录。 如今，这一纪录再一次被刷新。9月30日，罗氏旗下基因泰克以8.5亿美元的预付款及其他潜在里程碑收购了锐格医药的下一代CDK抑制剂产品组合。 再回溯到去年11月，百济神州以超13亿美元交易总额引进了昂胜医药的CDK2抑制剂ETX-197。 上述种种，足见下一代CDK抑制剂的市场价值。特别是罗氏此番出手，其背后的市场洞察与战略意图值得深思。 1 补齐乳腺癌“拼图” 罗氏的算盘打得很响：这次大手笔收购，不仅是对CDK抑制剂的看好，更是其建设乳腺癌生态圈的战略棋局。 罗氏在乳腺癌领域的打法十分清晰，通过布局PD-L1、HER2、PI3K、CDK等多种靶点，覆盖了所有的乳腺癌人群（HER2+/HR+/三阴乳腺癌），尤其积极布局占所有乳腺癌病例高达65%-70%的HR阳性乳腺癌。 针对三阴性乳腺癌，罗氏的PD-L1单抗Atezolizumab（Tecentriq）在2019年获FDA加速批准用于联合化疗一线治疗无法切除的局部晚期或转移性PD-L1阳性的三阴性乳腺癌，成为首个获批三阴乳腺癌一线的肿瘤免疫疗法。 在HER2+乳腺癌治疗中，罗氏获批了多款HER2靶向药，包括曲妥珠单抗、帕妥珠单抗、Kadcyla（T-DM1）、Phesgo（帕妥珠曲妥珠单抗皮下注射），药物类型涵盖单抗、ADC和HER2复合物，适应症覆盖了乳腺癌的早期、晚期、辅助治疗和新辅助治疗等全病程管理。 另外，罗氏还布局了双抗和小分子药物，包括用于HER2阳性乳腺癌的HER2/CD3双抗、潜在“best-in-class”的PI3Kα小分子抑制剂Inavolisib（Itovebi，伊那利塞）、第三代口服雌激素受体降解剂（SERD）Giredestrant。 其中，Inavolisib在近日获FDA批准上市，与CDK4/6抑制剂Palbociclib（哌柏西利）和氟维司群联用，治疗肿瘤携带PIK3CA突变、内分泌治疗耐药、激素受体（HR）阳性、人类表皮生长因子受体2（HER2）阴性局部晚期或转移性乳腺癌成年患者。 Giredestrant正在开展联用CDK4/6抑制剂治疗ER阳性、HER2阴性晚期乳腺癌患者的III期临床试验。 在一项Ⅱ期临床试验coopERA中，Giredestrant与Palbociclib（哌柏西利）联用作为新辅助疗法，在治疗早期ER阳性、HER2阴性乳腺癌患者时，与活性对照组相比，可更有效地降低生物标志物Ki67的水平（Ki67的水平昭示了癌细胞的分裂速度）。 从各种小分子药物联用CDK4/6抑制剂，到补齐下一代CDK抑制剂这块不可或缺的“拼图”，这一层层递进的战略部署，使得罗氏在乳腺癌治疗的优势不断扩大。 2 巨头必争的百亿赛道 CDK抑制剂是巨头必争的大药赛道，市场规模超过百亿美元。 2023年，仅辉瑞的哌柏西利、礼来的阿贝西利、诺华的瑞波西利销售额就合计高达107亿美元。根据Nature Reviews Drug Discovery预计，到2029年，CDK4/6抑制剂的市场规模将达到200亿美元，占乳腺癌药物销售市场份额的42%。 市场空间如此广阔，怎能不让罗氏垂涎？ 前有辉瑞、礼来等制药巨头布局，后有中国实力药企卡位抢食。 作为国产首款CDK4/6抑制剂，恒瑞医药的达尔西利于2021年获批治疗HR阳性、HER2阴性的经内分泌治疗后进展的复发或转移性乳腺癌，之后又在去年6月拿下一线治疗。目前，达尔西利还在开展HR+/HER2-乳腺癌术后辅助治疗的Ⅲ期研究。 涵盖一线、二线、术后辅助，CDK4/6抑制剂不断渗透HR阳性HER2阴性乳腺癌全病程管理。然而，这还不是CDK抑制剂的终点。 因为CDK4/6抑制剂并非完美，存在耐药、副作用问题，比如中性粒细胞减少、骨髓抑制。当然，这些缺陷也给下一代CDK抑制剂留下了突围机会，同时也是罗氏进场的契机。 在CDK家族成员中，CDK4与CDK6共同参与细胞周期调控，但功效与毒性分工明确。其中，CDK4/6抑制剂的临床治疗功效主要由CDK4驱动，而CDK6被认为更多与治疗毒性相关。 此外，CDK2可能与CDK4/6的耐药机制有关，有助于解决CDK4/6抑制剂的耐药问题。由此，CDK2抑制剂、CDK4抑制剂、CDK2/4/6抑制剂等下一代CDK抑制剂应运而生。 现阶段，CDK抑制剂争夺战进入了白热化阶段：百济神州引进了昂胜医药的口服CDK2抑制剂ETX-197，罗氏选择大手笔收购锐格医药，将下一代CDK抑制剂产品组合纳入囊中（CDK2抑制剂QR-6401、CDK2/4/6抑制剂RGT-419B）。 另外，辉瑞研发了CDK2抑制剂PF-07104091和CDK4抑制剂Atirmociclib（PF-07220060），中国生物制药子公司正大天晴研发了CDK2/4/6抑制剂TQB3616，恒瑞和百济均布局了CDK4抑制剂：HRS-6209、BGB-43395。 显然，下一代CDK抑制剂新药研发又是一场属于强者的角逐，入局者皆实力不凡。那么，罗氏又将以何种卓越能力，在这场较量中占据一席之地？ 3 能否杀出一条血路？ 在强者如林的CDK抑制剂市场中抢食，罗氏确实要花费一番功夫。 辉瑞、礼来、诺华的CDK4/6抑制剂都是年销售额超过20亿美元的“重磅炸弹”。其中，辉瑞的哌柏西利受专利到期影响销售额已出现下滑，但阿贝西利、瑞波西利均处在快速放量的状态，2023年销售额同比分别增长达56%、69%。 可即便如此，辉瑞仍是罗氏的强劲对手。 为了延长哌柏西利的生命周期，辉瑞采取联合疗法策略，开展了许多联用哌柏西利的临床试验，比如哌柏西利+氟维司群、哌柏西利+Vepdegestrant（ARV-471）等。 其中，ARV-471是辉瑞和Arvinas联合开发的新型口服、靶向ER的蛋白降解剂（PROTAC），目前单药二线治疗ER+/HER2-晚期乳腺癌（VERITAC-2）以及联合哌柏西利对比标准治疗（来曲唑+哌柏西利）一线治疗ER+/HER2-局部晚期乳腺癌（VERITAC-3）均已处于III期阶段。 在下一代CDK抑制剂，辉瑞研发了CDK2抑制剂PF-07104091和CDK4抑制剂Atirmociclib。 其中，Atirmociclib是首创（first-in-class）CDK4抑制剂，目前处于III期临床，在2024 ESMO BC年会上披露的首次人体I/IIa期研究结果中，展现了治疗经CDK4/6抑制剂治疗进展的HR+/HER2-转移性乳腺癌的全新可能，且安全性和耐受性良好。 此外，全球还没有CDK2抑制剂获批上市，辉瑞PF-07104091进度最快，已处于II期临床。此前有临床研究结果表明，PF-07104091单药治疗具有良好耐受性，且针对CDK4/6抑制剂耐药后的HR+/HER2乳腺癌具有良好疗效。 全球也还未有CDK2/4/6抑制剂获批上市，其中正大天晴的库莫西利（TQB3616）展现出优异疗效，不仅有望克服CDK4/6抑制剂的耐药性问题，而且CDE已受理库莫西利联合氟维司群用于既往内分泌经治的HR+/HER2-局部晚期或转移性乳腺癌适应症的上市申请，未来两年还将递交用于HR+/HER2-乳腺癌一线治疗及辅助治疗的NDA。 在此背景下，罗氏使出了“连环招”：继前瞻性布局可与CDK4/6抑制剂联用的小分子药物后，再收购锐格医药的下一代CDK抑制剂产品组合（CDK2/4/6抑制剂RGT-419B、CDK2抑制剂QR-6401）。 其中，RGT-419B在对亚型4、6进行抑制的基础上，增加了CDK2亚型，目前正在开展两项针对HR+/HER2-乳腺癌的I期临床试验，探索解决CDK4/6耐药性问题及达到长期疗效。 去年12月，锐格医药宣布RGT-419B用于既往接受过CDK4/6抑制剂和内分泌治疗联合的HR+/HER2-晚期乳腺癌患者获得积极的安全性和单药疗效数据。另外，根据2024 AACR年会上的摘要显示，RGT-419B单药治疗复发难治性HR+/HER2-晚期乳腺癌患者，达到28.6%的部分缓解率和44%的临床获益率，未发现剂量限制性毒性。 当然，CDK抑制剂只是罗氏在乳腺癌领域的其中一块“拼图”。 尤其随着近日潜在BIC药物PI3Kα抑制剂Inavolisib获批上市，罗氏的乳腺癌产品组合再添一员“猛将”。罗氏的制药主管特蕾莎·格雷厄姆表示，Inavolisib的峰值销售额潜力将达到20亿瑞士法郎（约23亿美元）。 — 结语 — 罗氏以8.5亿美元预付款为引擎，强势收购下一代CDK抑制剂产品组合，这一举动既深度布局了乳腺癌生态圈战略，也明确释放出在CDK抑制剂市场杀出一条血路的强烈信号。 猛踩油门的背后，足见罗氏巩固乳腺癌药物市场领先地位的坚定决心。 参考文献： 1.各家公司的财报、公告、官微 2.《20240902-医药生物行业乳腺癌专题：治疗方式更新孕育投资机会》，国联证券 3.《创纪录的出海预付款，与乳腺癌新变局》，氨基观察 同写意媒体矩阵，欢迎关注↓↓↓