Pamvatamig

氨基观察-创新药组原创出品 作者 | 黄凯 200亿美金市场风云再起。 11月18日，强生宣布口服IL-23R拮抗剂Icotrokinra(JNJ-2113)治疗斑块状银屑病(PsO)的III期ICONIC-LEAD研究获得了积极的关键结果。这是第一款成功完成III期研究的口服IL-23R靶向药物。 云顶新耀又有新进展。 11月19日，云顶新耀宣布，韩国食品药品安全部已完全批准该公司的布地奈德肠溶胶囊的新药上市许可申请，用于治疗罹患原发性免疫球蛋白A肾病变的成人患者。 在过去的一天里，国内外医药市场还有哪些热点值得关注？让氨基君带你一探究竟。 / 01 / 市场速递 1）橙帆医药Nectin4/TROP2双抗ADC达成海外授权 11月18日，橙帆医药宣布，与Avenzo Therapeutics达成一项全球战略合作协议。后者获得公司Nectin4/TROP2双特异性抗体偶联药物（ADC）全球范围内（不包括大中华区）权益，橙帆医药将获得高达5000万美元的首付款及近期里程碑付款。 2）博奥信生物两款药物授权出海 11月18日，博奥信生物宣布，与 Aclaris Therapeutics就TSLP单抗BSI-045B和TSLP/IL4R双抗BSI-502达成全球（除大中华区外）独家授权协议。博奥信将获得超过4000万美元的现金付款，但需要承担部分开发成本和药物产品材料费用。博奥信还将获得Aclaris Therapeutics 19.9%的股权。 / 02 / 资本信息 1）何氏眼科：股东先进制造基金计划减持公司股份不超过2% 11月19日，何氏眼科公告，股东先进制造基金计划自本公告披露之日起十五个交易日后的三个月内，减持公司股份合计不超过310.61万股，占公司剔除回购专用证券账户中股份数量后的总股本比例的2%。 / 03 / 医药动态 1）恒瑞医药注射用SHR-4394获临床许可 11月19日，据CDE官网，恒瑞医药注射用SHR-4394获临床许可，拟开展治疗前列腺癌的研究。 2）百济神州BGB-58067片获临床许可 11月19日，据CDE官网，百济神州BGB-58067片获临床许可，拟用于治疗晚期实体瘤患者。 3）贝达药业注射用MCLA-129获临床许可 11月19日，据CDE官网，贝达药业注射用MCLA-129获临床许可，拟用于治疗晚期实体瘤患者。 4）再鼎医药注射用ZL-1310获临床许可 11月19日，据CDE官网，再鼎医药注射用ZL-1310获临床许可，拟用于治疗小细胞肺癌患者。 5）三生国健递交IL-17A单抗上市申请 11月18日，三生国健宣布，该公司递交的重组抗IL-17A人源化单克隆抗体注射液（608）上市申请已获得CDE受理，用于治疗成人中重度斑块状银屑病。 6）云顶新耀耐赋康在韩国完全获批 11月19日，云顶新耀宣布，韩国食品药品安全部已完全批准该公司的布地奈德肠溶胶囊的新药上市许可申请，用于治疗罹患原发性免疫球蛋白A肾病变的成人患者。 / 04 / 器械跟踪 1）康膝生物胶原蛋白软骨再生载体终止注册 11月19日，据NMPA官网，康膝生物胶原蛋白软骨再生载体终止注册。 2）恒瑞迪生外周球囊扩张导管获注册许可 11月19日，据NMPA官网，恒瑞迪生外周球囊扩张导管获注册许可。 3）芸禾光电半导体激光治疗仪获注册许可 11月19日，据NMPA官网，芸禾光电半导体激光治疗仪获注册许可。 / 05 / 数字医疗日报 1）鹰瞳医疗糖尿病视网膜病变眼底图像辅助诊断软件获注册许可 11月19日，据NMPA官网，鹰瞳医疗糖尿病视网膜病变眼底图像辅助诊断软件获注册许可。 / 06 / 海外药闻 1）强生口服IL-23R拮抗剂两项III期研究获得积极关键结果 11月18日，强生宣布口服IL-23R拮抗剂Icotrokinra(JNJ-2113)治疗斑块状银屑病(PsO)的III期ICONIC-LEAD研究获得了积极的关键结果。这是第一款成功完成III期研究的口服IL-23R靶向药物。 2）诺华合作开发SSTR2放射性治疗药物 11月18日，Ratio Therapeutics宣布，已与诺华达成一项独家全球许可和合作协议。此次合作将利用Ratio在放射配体治疗（RLT）发现和开发方面的专业知识及其技术平台，共同开发针对生长抑素受体2（SSTR2）的放射性治疗药物。 PS：欢迎扫描下方二维码，添加氨基君微信号交流。

Phase 3 registrational trials evaluating petosemtamab in combination with pembrolizumab in 1L and petosemtamab monotherapy in 2/3L r/m HNSCC enrolling Petosemtamab in 2L+ r/m HNSCC interim clinical data accepted for rapid oral presentation at ESMO® Asia Congress 2024 Based on the Company’s current operating plan, existing cash, cash equivalents, and marketable securities expected to fund Merus’ operations into 2028 UTRECHT, The Netherlands and CAMBRIDGE, Mass., Oct. 31, 2024 (GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics® and Triclonics®), today announced financial results for the third quarter and provided a business update. “I'm encouraged by our continued operational effectiveness, with phase 3 trials accelerating for petosemtamab in both 1L and 2/3L recurrent/metastatic head and neck cancer. I believe petosemtamab has the potential to offer both a first and best in class chemo-free option for these patients,” said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. “We look forward to providing an update on petosemtamab’s monotherapy efficacy, duration and safety in 2L+ HNSCC this December at ESMO® Asia and, in the near future, providing more information on a number of important potential near term catalysts in 2025.” Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics®): Solid TumorsLiGeR-HN1 phase 3 trial in 1L head and neck squamous cell carcinoma (HNSCC) and LiGeR-HN2 phase 3 trial in 2/3L HNSCC enrolling; phase 2 trial in 2L metastatic colorectal cancer (mCRC) enrolling; clinical data update on 2L+ HNSCC planned for ESMO® Asia in December 2024 In the third quarter, Merus announced the first patient was dosed in LiGeR-HN1, a phase 3 trial evaluating the efficacy and safety of petosemtamab in combination with pembrolizumab in 1L HNSCC expressing PD-L1 (CPS≥1) compared to pembrolizumab. In this trial, patients will be randomized to petosemtamab plus pembrolizumab or pembrolizumab monotherapy. This was detailed in our press release, Merus Announces First Patient Dosed in LiGeR-HN1, a Phase 3 Trial Evaluating Petosemtamab in Combination with Pembrolizumab in 1L r/m HNSCC (September 30, 2024). Merus provided an interim clinical update on petosemtamab with pembrolizumab in 1L r/m HNSCC at the American Society of Clinical Oncology® (ASCO) Annual Meeting 2024, demonstrating a 67% response rate among 24 evaluable patients. The oral presentation was detailed in our press release, Merus’ Petosemtamab in Combination with Pembrolizumab Interim Data Demonstrates Robust Response Rate and Favorable Safety Profile in 1L r/m HNSCC (May 28, 2024). Merus also provided an interim clinical update on petosemtamab monotherapy in 2L+ HNSCC at the American Association of Cancer Research® (AACR®) Annual Meeting 2023, demonstrating a 37% response rate among 43 evaluable patients. The oral presentation was detailed in our press release (April 17, 2023). Merus plans to provide updated efficacy, durability and safety data of this cohort along with clinical data from the dose optimization cohort evaluating petosemtamab monotherapy 1500 or 1100 mg dose levels in 2L+HNSCC. This was detailed in our press release, Merus Announces Abstract Accepted for Presentation at the ESMO Asia Congress 2024 (September 17, 2024). Merus believes a randomized registration trial in HNSCC with an overall response rate endpoint could potentially support accelerated approval and the overall survival results from the same study could potentially verify its clinical benefit to support regular approval. In the third quarter, Merus announced the first patient was dosed in a phase 2 trial evaluating petosemtamab in combination with standard chemotherapy in 2L mCRC. This was detailed in our press release, Merus Announces First Patient Dosed in Phase 2 Trial of Petosemtamab in 2L CRC (July 8, 2024). Zenocutuzumab (Zeno or MCLA-128: HER2 x HER3 Biclonics®): NRG1 fusion-positive (NRG1+) lung, pancreatic and other solid tumorsZeno BLA for treatment of NRG1+ non-small cell lung cancer (NSCLC) and pancreatic cancer (PDAC) accepted for priority review by the FDA The FDA has accepted for priority review a Biologics License Application (BLA) for the bispecific antibody Zeno in patients with NRG1+ NSCLC and PDAC cancer. This acceptance was detailed in our press release Merus Announces U.S. FDA Acceptance and Priority Review of Biologics License Application for Zeno for the Treatment of NRG1+ NSCLC and PDAC (May 6, 2024). Merus believes that obtaining a commercialization partnership agreement is an important step in bringing Zeno to patients with NRG1+ cancer, if approved. MCLA-129 (EGFR x c-MET Biclonics®): Solid TumorsInvestigation of MCLA-129 is ongoing in METex14 NSCLC; phase 2 trial in combination with chemotherapy in 2L+ EGFR mutant (EGFRm) NSCLC enrolling In the third quarter, Merus announced the first patients were dosed in the phase 2 trial evaluating MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC, with a cohort receiving MCLA-129 and paclitaxel and carboplatin, and another cohort receiving MCLA-129 and docetaxel. We also remain interested in partnering MCLA-129 to sufficiently resource the development of MCLA-129 and the potential benefit it may have for patients. MCLA-129 is subject to a collaboration and license agreement with Betta Pharmaceuticals Co. Ltd. (Betta), which permits Betta to develop MCLA-129 and potentially commercialize exclusively in China, while Merus retains global rights outside of China. MCLA-145 (CD137 x PD-L1 Biclonics®): Solid Tumors Investigation continues of the phase 1 trial of MCLA-145 in combination with pembrolizumab Collaborations Incyte CorporationSince 2017, Merus has been working with Incyte Corporation (Incyte) under a global collaboration and license agreement focused on the research, discovery and development of bispecific antibodies utilizing Merus’ proprietary Biclonics® technology platform. For each program under the collaboration, Merus receives reimbursement for research activities and is eligible to receive potential development, regulatory and commercial milestones and sales royalties for any products, if approved. Eli Lilly and CompanyIn January 2021, Merus and Eli Lilly and Company (Lilly) announced a research collaboration and exclusive license agreement to develop up to three CD3-engaging T-cell re-directing bispecific antibody therapies utilizing Merus’ Biclonics® platform and proprietary CD3 panel along with the scientific and rational drug design expertise of Lilly. The collaboration is progressing well with three programs ongoing at various stages of preclinical development. Gilead SciencesIn March 2024, Merus and Gilead Sciences announced a collaboration to discover novel antibody based trispecific T-cell engagers using Merus’ patented Triclonics® platform. Under the terms of the agreement, Merus will lead early-stage research activities for two programs, with an option to pursue a third. Gilead will have the right to exclusively license programs developed under the collaboration after the completion of select research activities. If Gilead exercises its option to license any such program from the collaboration, Gilead will be responsible for additional research, development and commercialization activities for such program. Merus received an equity investment by Gilead of $25 million in Merus common shares and an upfront payment of $56 million. Ono PharmaceuticalIn 2018, the Company granted Ono Pharmaceutical Co., Ltd. (Ono) an exclusive, worldwide, royalty-bearing license, with the right to sublicense, research, test, make, use and market a limited number of bispecific antibody candidates based on Merus’ Biclonics® technology platform directed to an undisclosed target combination. During the third quarter of 2024, Merus achieved and received a milestone payment based on the filing of an Investigational New Drug (IND) application in Japan. Cash Runway, existing cash, cash equivalents and marketable securities expected to fund Merus’ operations into 2028 As of September 30, 2024, Merus had $782.9 million cash, cash equivalents and marketable securities. Based on the Company’s current operating plan, the existing cash, cash equivalents and marketable securities are expected to fund Merus’ operations into 2028. Third Quarter 2024 Financial Results Collaboration revenue for the three months ended September 30, 2024 increased by $0.8 million as compared to the three months ended September 30, 2023, primarily as a result of increases in amortization of upfront deferred revenue. The change in exchange rates did not significantly impact collaboration revenue. Research and development expense for the three months ended September 30, 2024 increased by $26.5 million as compared to the three months ended September 30, 2023, primarily as a result of increases in external clinical services and drug manufacturing expenses. General and administrative expense for the three months ended September 30, 2024 increased by $8.2 million as compared to the three months ended September 30, 2023, primarily as a result of increases in personnel related expenses, facilities, depreciation expense and consulting expenses. Collaboration revenue for the nine months ended September 30, 2024 decreased by $8.0 million as compared to the nine months ended September 30, 2023, primarily as a result of decreases in milestone revenue and amortization of deferred revenue. Research and development expense for the nine months ended September 30, 2024 increased by $51.0 million as compared to the nine months ended September 30, 2023, primarily as a result of increases in external clinical services and drug manufacturing expenses. General and administrative expense for the nine months ended September 30, 2024 increased by $15.5 million as compared to the nine months ended September 30, 2023, primarily as a result of increases in personnel related expenses and consulting expenses. Other income (loss), net consists of interest earned and fees paid on our cash and cash equivalents held on account, accretion of investment earnings and net foreign exchange (losses) gains on our foreign denominated cash, cash equivalents and marketable securities. Other gains or losses relate to the issuance and settlement of financial instruments. MERUS N.V. CONDENSED CONSOLIDATED BALANCE SHEETS (UNAUDITED) (Amounts in thousands, except share and per share data) September 30,2024 December 31,2023 ASSETS Current assets: Cash and cash equivalents $432,998 $204,246 Marketable securities 199,270 150,130 Accounts receivable 1,134 2,429 Prepaid expenses and other current assets 32,874 12,009 Total current assets 666,276 368,814 Marketable securities 150,620 57,312 Property and equipment, net 12,146 12,135 Operating lease right-of-use assets 10,312 11,362 Intangible assets, net 1,856 1,800 Deferred tax assets 838 1,199 Other assets 2,628 2,872 Total assets $844,676 $455,494 LIABILITIES AND SHAREHOLDERS’ EQUITY Current liabilities: Accounts payable $6,185 $4,602 Accrued expenses and other liabilities 36,279 38,482 Income taxes payable 4,876 1,646 Current portion of lease obligation 1,762 1,674 Current portion of deferred revenue 30,974 22,685 Total current liabilities 80,076 69,089 Lease obligation 9,284 10,488 Deferred revenue, net of current portion 52,055 19,574 Total liabilities 141,415 99,151 Commitments and contingencies - Note 6 Shareholders’ equity: Common shares, €0.09 par value; 105,000,000 shares authorized at September 30, 2024 and December 31, 2023; 68,426,779 and 57,825,879 shares issued and outstanding as at September 30, 2024 and December 31, 2023, respectively 6,919 5,883 Additional paid-in capital 1,640,930 1,126,054 Accumulated other comprehensive income (7,124) (22,533)Accumulated deficit (937,464) (753,061)Total shareholders’ equity 703,261 356,343 Total liabilities and shareholders’ equity $844,676 $455,494 MERUS N.V.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS(UNAUDITED)(Amounts in thousands, except share and per share data) Three Months EndedSeptember 30, Nine Months EndedSeptember 30, 2024 2023 2024 2023 Collaboration revenue $11,772 $11,033 $26,993 $35,008 Total revenue 11,772 11,033 26,993 35,008 Operating expenses: Research and development 63,239 36,810 150,942 99,973 General and administrative 20,765 12,591 59,466 44,040 Total operating expenses 84,004 49,401 210,408 144,013 Operating loss (72,232) (38,368) (183,415) (109,005)Other income, net: Interest income, net 10,254 4,522 22,301 9,312 Foreign exchange gains (loss) (34,950) 11,952 (16,897) 7,062 Total other income (loss), net (24,696) 16,474 5,404 16,374 Net loss before income taxes (96,928) (21,894) (178,011) (92,631)Income tax expense 2,977 1,118 6,392 2,155 Net loss $(99,905) $(23,012) $(184,403) $(94,786)Other comprehensive loss: Currency translation adjustment 31,775 (10,722) 15,409 (6,985)Comprehensive loss $(68,130) $(33,734) $(168,994) $(101,771)Net loss per share attributable to common stockholders: Basic and diluted $(1.46) $(0.43) $(2.94) $(1.91)Weighted-average common shares outstanding: Basic and diluted 68,254,120 53,869,762 62,750,425 49,532,722 About Merus N.V. Merus is a clinical-stage oncology company developing innovative full-length human bispecific and trispecific antibody therapeutics, referred to as Multiclonics®. Multiclonics® are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information, please visit Merus’ website, and LinkedIn. Forward-Looking StatementsThis 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 content and timing of clinical trials, data readouts and clinical, regulatory, strategy and development updates for our product candidates; our ability to successfully advance Zeno through the regulatory, BLA review and potential commercialization processes; our ongoing LiGeR-HN1, LiGeR-HN2 and phase 2 mCRC trials for petosemtamab, our planned update at ESMO Asia in December on the HNSCC 2L+ dose cohort and patients previously reported at AACR 2023; our belief that petosemtamab has the potential to offer both a first and best in class chemo-free option for r/m HNSCC patients; our belief that a randomized registration trial in HNSCC with an overall response rate endpoint could potentially support accelerated approval and the overall survival results from the same study could potentially verify its clinical benefit to support regular approval; our belief that obtaining a commercialization partnership agreement is an important step in bringing Zeno to patients with NRG1+ cancer, if approved; statements regarding the sufficiency of our cash, cash equivalents and marketable securities, and expectation that it will fund the Company into 2028; the continued investigation of MCLA-145 in combination with pembrolizumab; the investigation of MCLA-129 in monotherapy in Met ex14 NSCLC, and enrolling of patients in the investigation of MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC; our interest in partnering MCLA-129 to sufficiently resource the development of MCLA-129 and the potential benefit it may have for patients; the benefits of the collaborations between Incyte and Merus, Lilly and Merus, Gilead and Merus, and license agreement between Ono and Merus; and the potential of those collaborations and license for future value generation, including whether and when Merus will receive any future payments, including milestones or royalties, and the amounts of such payments; whether any programs under the collaboration will be successful; and our collaboration and license agreement with Betta, which permits Betta to develop MCLA-129 and potentially commercialize exclusively in China, while Merus retains full ex-China rights, including any future clinical development by Betta of MCLA-129. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our need for additional funding, which may not be available and which may require us to restrict our operations or require us to relinquish rights to our technologies or antibody candidates; potential delays in regulatory approval, which would impact our ability to commercialize our product candidates and affect our ability to generate revenue; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; the unpredictable nature of our early stage development efforts for marketable drugs; potential delays in enrollment of patients, which could affect the receipt of necessary regulatory approvals; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; impacts of the volatility in the global economy, including global instability, including the ongoing conflicts in Europe and the Middle East; we may not identify suitable Biclonics® or bispecific antibody candidates under our collaborations or our collaborators may fail to perform adequately under our collaborations; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; protection of our proprietary technology; our patents may be found invalid, unenforceable, circumvented by competitors and our patent applications may be found not to comply with the rules and regulations of patentability; we may fail to prevail in potential lawsuits for infringement of third-party intellectual property; and our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks. These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the period ended September 30, 2024, filed with the Securities and Exchange Commission, or SEC, on October 31, 2024, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except as required under applicable law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Multiclonics®, Biclonics® and Triclonics® are registered trademarks of Merus N.V.