Enzalutamide

DOR/ISL is the first non-INSTI, two-drug regimen to demonstrate non-inferiority and a similar safety pro Week 48 to BIC/FTC/TAF in adults living with HIV-1 who had not previously received antiretroviral treatment DOR/ISL maintained virologic suppression at Week 96 in adults with virologically suppressed HIV-1 who switched from other oral antiretroviral therapies, including BIC/FTC/TAF RAHWAY, N.J.--(BUSINESS WIRE)-- $MRK #MRK --Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the presentation of results from three pivotal Phase 3 trials evaluating the investigational, once-daily, oral, two-drug regimen of doravirine/islatravir [DOR/ISL (100 mg/0.25 mg), (MK-8591A)] in adults with HIV-1. The findings were shared in late-breaking presentations at the 33rd Conference on Retroviruses and Opportunistic Infections (CROI) being held in Denver. “We are proud to continue building on our 40-year history of HIV research with the presentation of compelling new data from our HIV pipeline at CROI this year,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “Islatravir blocks HIV-1 replication through multiple mechanisms, including reverse transcriptase translocation inhibition, and could serve as the anchor for a series of two-drug, non-INSTI, daily and weekly treatment regimens. If approved, DOR/ISL will be the first of these regimens in our portfolio and may provide an important new option to help meet the evolving treatment needs of people living with HIV.” The Phase 3, double-blind, clinical trial MK-8591A-053 evaluating DOR/ISL versus bictegravir/emtricitabine/tenofovir alafenamide i [(50 mg/200 mg/25 mg),(BIC/FTC/TAF)] in adults living with HIV-1 who had not previously received antiretroviral treatment (treatment-naïve), met its primary efficacy endpoint of percentage of participants achieving viral suppression (HIV-1 RNA 100,000 copies/mL). The primary efficacy endpoint was the percentage of participants with HIV-1 RNA 100,000 copies/mL, 10.3% had HIV-1 RNA >500,000 copies/mL and 17.2% had baseline CD4+ T-cell count 100,000 copies/mL (94.0% vs 87.6%, respectively) and >500,000 copies/mL (90.3% vs 84.4%, respectively). Drug-related AEs were reported in 14.1% of participants on DOR/ISL and 18.0% on BIC/FTC/TAF and discontinuations due to AEs (1.1% vs. 2.2%) were similar in both groups. Immune reconstitution was similar in DOR/ISL vs. comparator with no between-group differences in mean increases in CD4+ T-cell counts or total lymphocyte counts (TLC). About the Phase 3 data from MK-8591A-052 MK-8591A-052 is a Phase 3, randomized, active-controlled, double-blind, clinical trial to evaluate the efficacy and safety of a switch to investigational, once-daily DOR/ISL (100 mg/0.25 mg) in adults with HIV-1 infection that has been virologically suppressed on BIC/FTC/TAF (50 mg/200 mg/25 mg). In this trial, 513 adults with HIV-1 who had virologic suppression for three months or more on BIC/FTC/TAF, no history of treatment failure and no known resistance to DOR were randomized (2:1) and switched to DOR/ISL (n= 342) or continued treatment with BIC/FTC/TAF (n=171). The primary efficacy endpoint, the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 (non-inferiority margin 4%), was met, demonstrating non-inferiority to BIC/FTC/TAF; 1.5% of participants who switched to DOR/ISL had a viral load of ≥50 copies/mL at Week 48, compared to 0.6% on BIC/FTC/TAF (treatment difference 0.9%, 95% CI -1.9, 2.9). Results at Week 48 were recently published in The Lancet . At Week 96, DOR/ISL continued to demonstrate similar efficacy compared to BIC/FTC/TAF; 1.5% of participants on DOR/ISL had a viral load of ≥50 copies/mL compared to 1.2% of participants on BIC/FTC/TAF (treatment difference 0.3%, 95% CI -2.8, 2.4); 88.9% of participants on DOR/ISL maintained virologic suppression (HIV-1 RNA <50 copies/mL) compared to 90.1% of participants continuing BIC/FTC/TAF (treatment difference -1.2%, 95% CI -6.5, 5.0). No hypothesis testing was performed for these secondary endpoints. The safety pro DOR/ISL at Week 96 continued to be similar to BIC/FTC/TAF with no new safety findings. No additional drug-related serious adverse events were reported in any group between Week 48 and Week 96. At Week 96, rates of discontinuation due to AEs were similar for both groups (3.2% vs. 2.9%). There were no differences between trial arms in CD4+ T-cell count or TLC changes through Week 96. About the Phase 3 data from MK-8591A-051 MK-8591A-051 is a Phase 3, open-label randomized, active-controlled, clinical trial to evaluate the efficacy and safety of a switch to investigational, once-daily DOR/ISL (100 mg/0.25 mg) in adults with HIV-1 infection that has been virologically suppressed using bART. In this trial, 551 adults with HIV-1 RNA <50 copies/mL for three months or more on oral 2- or 3-drug ART, with no history of treatment failure and no known virologic resistance to DOR, were randomized 2:1 and switched to DOR/ISL (n= 366) or continued bART (n=185), stratified by bART regimen. The primary efficacy endpoint, percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 (non-inferiority margin 4%), was met, demonstrating DOR/ISL to be non-inferior to bART; 1.4% of participants who received DOR/ISL had a viral load of ≥50 copies/mL at Week 48, compared to 4.9% on bART (treatment difference -3.6%, 95% CI -7.8, -0.8). After Week 48 of the comparative portion of the study, all participants received open-label DOR/ISL through Week 144. Results at Week 48 were recently published in The Lancet . At Week 96, 1.9% of participants who continued on DOR/ISL for 96 weeks had HIV-1 RNA ≥50 copies/mL and 1.1% of participants who switched from bART to DOR/ISL at Week 48. Additionally, 92.6% of participants who were on DOR/ISL through 96 weeks and 96.6% of participants who switched to DOR/ISL at Week 48 maintained virologic suppression (HIV-1 RNA <50 copies/mL) at Week 96. At Week 96, there were similar rates of drug-related AEs between those who continued on DOR/ISL (13.7%) for 96 weeks and for those who switched from bART to DOR/ISL at Week 48 (11.3%) and rates of discontinuations due to AEs for those on DOR/ISL for 96 weeks (1.1%) and for those who switched from bART to DOR/ISL at Week 48 (0.6%) were similar. The mean percent change in total lymphocyte and CD4 counts were similar for participants who continued on DOR/ISL and switched from bART to DOR/ISL. No participants discontinued treatment due to decreased CD4+ T-cell count or TLC. About Islatravir (MK-8591) and Merck’s HIV Research Islatravir (MK-8591) is Merck’s investigational nucleoside analog that blocks HIV-1 replication by multiple mechanisms including inhibition of reverse transcriptase translocation, resulting in immediate chain termination and induction of structural changes in the viral DNA. Islatravir is under evaluation in multiple ongoing early and late-stage clinical trials in combination with other antiretrovirals for potential daily and once-weekly treatments for HIV-1, with islatravir serving as the anchor medicine in these two-drug regimens. Islatravir in combination with Gilead’s lenacapavir is in Phase 3 development as a novel oral once-weekly treatment for HIV-1 [ISLEND-1 ( NCT06630286 ) and ISLEND-2 ( NCT06630299 )], and islatravir in combination with our company’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) ulonivirine (MK-8507) is in Phase 2b development (MK-8591B-060, NCT06891066 and MK-8591B-062, NCT07266831 ) as an oral once-weekly treatment. MK-8527 is the company’s investigational, novel, once-monthly, oral candidate for pre-exposure prophylaxis (PrEP) for HIV-1. The Phase 3 EXPrESSIVE-11 (MK-8527-011, NCT07044297 ) trial is evaluating the safety and efficacy of MK-8527 as PrEP to reduce the risk of sexually acquired HIV-1 infection among people likely to be exposed to HIV-1 in 16 countries. The Phase 3 EXPrESSIVE-10 (MK-8527-010, NCT07071623 ) trial is evaluating the safety and efficacy of MK-8527 as PrEP to reduce the risk of sexually acquired HIV-1 infection among women and adolescent girls in sub-Saharan Africa. Both trials are now enrolling. For an overview of Merck’s HIV treatment and prevention clinical development program, please click here . Indications and usage for PIFELTRO ® (doravirine) and DELSTRIGO ® (doravirine, lamivudine, and tenofovir disoproxil fumarate) in the U.S. PIFELTRO is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine. DELSTRIGO is indicated as a complete regimen for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of DELSTRIGO. Selected Safety Information Warning: Posttreatment Acute Exacerbation of Hepatitis B Virus (HBV) for DELSTRIGO All patients with HIV-1 should be tested for the presence of HBV before initiating ARV therapy. Severe acute exacerbations of HBV have been reported in people with concomitant HIV-1 and HBV who have discontinued products containing lamivudine or tenofovir disoproxil fumarate (TDF), which are components of DELSTRIGO. Patients coinfected with HIV-1 and HBV who discontinue DELSTRIGO should be monitored with both clinical and laboratory follow-up for at least several months after stopping DELSTRIGO. If appropriate, initiation of anti-HBV therapy may be warranted. Contraindications PIFELTRO and DELSTRIGO are contraindicated when coadministered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers (including the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the androgen receptor inhibitor enzalutamide; the antimycobacterials rifampin and rifapentine; the cytotoxic agent mitotane; and the herbal product St. John’s wort (Hypericum perforatum)), as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of DELSTRIGO and PIFELTRO. DELSTRIGO is contraindicated in patients with a previous hypersensitivity reaction to lamivudine. Warnings and Precautions Severe Skin Reactions Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during the postmarketing experience with doravirine-containing regimens. Discontinue PIFELTRO or DELSTRIGO, and other medications known to be associated with severe skin reactions, immediately if a painful rash with mucosal involvement or a progressive severe rash develops. Clinical status should be closely monitored, and appropriate therapy should be initiated. New or Worsening Renal Impairment Renal impairment, including cases of acute renal failure and Fanconi syndrome, have been reported with the use of TDF. DELSTRIGO should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple NSAIDs). Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in people living with HIV with risk factors for renal dysfunction who appeared stable on TDF. Prior to or when initiating DELSTRIGO, and during treatment, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue DELSTRIGO in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Discontinue DELSTRIGO if estimated creatinine clearance declines below 50 mL/min. Bone Loss and Mineralization Defects In clinical trials in adults living with HIV, TDF was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher. Cases of osteomalacia associated with proximal renal tubulopathy have been reported with the use of TDF. The effects of TDF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk in adults are unknown. Immune Reconstitution Syndrome Immune reconstitution syndrome can occur, including the occurrence of autoimmune disorders with variable time to onset, which may necessitate further evaluation and treatment. Drug Interactions Because DELSTRIGO is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. Coadministration of PIFELTRO with efavirenz, etravirine, or nevirapine is not recommended. If DELSTRIGO is coadministered with rifabutin, take one tablet of DELSTRIGO once daily, followed by one tablet of doravirine (PIFELTRO) approximately 12 hours after the dose of DELSTRIGO. If PIFELTRO is coadministered with rifabutin, increase PIFELTRO dosage to one tablet twice daily (approximately 12 hours apart). Consult the full Prescribing Information prior to and during treatment for more information on potential drug-drug interactions. Dosage and Administration/Specific Populations Renal Impairment Because DELSTRIGO is a fixed-dose combination tablet and the dosage of lamivudine and TDF cannot be adjusted, DELSTRIGO is not recommended in patients with estimated creatinine clearance less than 50 mL/min. Adverse Reactions The most common adverse reactions with DELSTRIGO (incidence ≥5%, all intensities) were dizziness (7%), nausea (5%), and abnormal dreams (5%). The most common adverse reactions with PIFELTRO (incidence ≥5%, all intensities) were nausea (7%), dizziness (7%), headache (6%), fatigue (6%), diarrhea (6%), abdominal pain (5%), and abnormal dreams (5%). By week 96 in DRIVE-FORWARD, 2% of adult participants in the PIFELTRO group and 3% in the darunavir+ritonavir (DRV+r) group had adverse events leading to discontinuation of study medication. By week 96 in DRIVE-AHEAD, 3% of adult participants in the DELSTRIGO group and 7% in the efavirenz (EFV)/emtricitabine (FTC)/TDF group had adverse events leading to discontinuation of study medication. In DRIVE-FORWARD, mean changes from baseline at week 48 in LDL-cholesterol (LDL-C) and non-HDL-cholesterol (non-HDL-C) were pre-specified. LDL-C: -4.6 mg/dL in the PIFELTRO group vs 9.5 mg/dL in the DRV+r group. Non-HDL-C: -5.4 mg/dL in the PIFELTRO group vs 13.7 mg/dL in the DRV+r group. The clinical benefits of these findings have not been demonstrated. In DRIVE-AHEAD, mean changes from baseline at week 48 in LDL-C and non-HDL-C were pre-specified. LDL-C: -2.1 mg/dL in the DELSTRIGO group vs 8.3 mg/dL in the EFV/FTC/TDF group. Non-HDL-C: -4.1 mg/dL in the DELSTRIGO group vs 12.7 mg/dL in the EFV/FTC/TDF group. The clinical benefits of these findings have not been demonstrated. In DRIVE-SHIFT, mean changes from baseline at week 24 in LDL-C and non-HDL-C were pre-specified. LDL-C: -16.3 mg/dL in the DELSTRIGO group vs -2.6 mg/dL in the PI + ritonavir group. Non-HDL-C: -24.8 mg/dL in the DELSTRIGO group vs -2.1 mg/dL in the PI + ritonavir group. The clinical benefits of these findings have not been demonstrated. In DRIVE-AHEAD, neuropsychiatric adverse events were reported in the three pre-specified categories of sleep disorders and disturbances, dizziness, and altered sensorium. Twelve percent of adult participants in the DELSTRIGO group and 26% in the EFV/FTC/TDF group reported neuropsychiatric adverse events of sleep disorders and disturbances; 9% in the DELSTRIGO group and 37% in the EFV/FTC/TDF group reported dizziness; and 4% in the DELSTRIGO group and 8% in the EFV/FTC/TDF group reported altered sensorium. The safety of DELSTRIGO in virologically suppressed adults was based on week 48 data from participants in the DRIVE-SHIFT trial. Overall, the safety pro virologically suppressed adult participants was similar to that in participants with no ARV treatment history. Serum ALT and AST Elevations: In the DRIVE-SHIFT trial, 22% and 16% of participants in the immediate switch group experienced ALT and AST elevations greater than 1.25 X ULN, respectively, through 48 weeks on DELSTRIGO. For these ALT and AST elevations, no apparent patterns with regard to time to onset relative to switch were observed. One percent of participants had ALT or AST elevations greater than 5 X ULN through 48 weeks on DELSTRIGO. The ALT and AST elevations were generally asymptomatic, and not associated with bilirubin elevations. In comparison, 4% and 4% of participants in the delayed switch group experienced ALT and AST elevations of greater than 1.25 X ULN through 24 weeks on their baseline regimen. Pregnancy/Breastfeeding There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to PIFELTRO or DELSTRIGO during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Inform individuals with HIV-1 infection of the potential risks of breastfeeding, including: (1) HIV-1 transmission (in HIV-1–negative infants), (2) developing viral resistance (in HIV-1–positive infants), and (3) serious adverse reactions in a breastfed infant similar to those seen in adults. Merck’s Commitment to HIV For 40 years, Merck has been committed to scientific research and discovery in HIV leading to scientific breakthroughs that have helped change HIV treatment. Our work has been pioneering in the development of new options across multiple drug classes to help those impacted by HIV. Today, we are developing a series of antiviral options designed to help people manage HIV and protect people from HIV. We are researching for real life and want to ensure people are not defined by HIV. Our work focuses on transformational innovations, collaborations with others in the global HIV community, and access initiatives aimed at the goal of helping to end the HIV epidemic for everyone. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U. Contacts Media Contacts: Eilyn Segura (203) 940-6259 Deb Wambold (215) 779-2234 Investor Contacts: Peter Dannenbaum (732) 594-1579 Damini Chokshi (732) 594-1577 Read full story here

我们在过年，他们在办大事！ 2026.2.18报道，礼来以1亿美元首付款引进CSL的IL-6单抗clazakizumab，布局免疫炎症与心血管领域。CSL保留其在终末期肾病心血管适应症上的权益，礼来将拓展其他适应症。该药当前处于III期临床阶段。 2026年以来，礼来密集进行并购与合作，包括收购Orna进军CAR-T、自Ventyx获得NLRP3资产，以及布局基因编辑与自身免疫耐受疗法，显示其在免疫炎症与前沿疗法领域的战略加速扩张。 2026.2.19报道，诺华与Unnatural Products达成最高17亿美元合作，开发基于AI设计的大环多肽疗法，潜在应用于心血管疾病。该技术兼具生物药的复杂靶点结合能力与小分子的细胞穿透性，旨在突破“不可成药”靶点。 诺华将负责后续开发与商业化。此次合作符合其强化早期创新管线的战略，延续其在20亿美元以下规模交易中的积极布局，显示其在前沿药物平台技术领域的持续投入。 2026.2.23报道，吉利德以78亿美元收购CAR-T合作伙伴Arcellx，核心资产为靶向BCMA的anito-cel，用于治疗复发或难治性多发性骨髓瘤。该疗法II期数据显示ORR达97%，预计2026年底获得FDA审批。 此前双方已建立多年合作并累计投入数亿美元。本次收购体现吉利德对CAR-T战略的进一步加码，在潜在获批前完成整合，巩固其在细胞治疗领域的布局，并强化Kite在血液肿瘤市场的竞争地位。 2026.2.24报道，辉瑞与先为达生物达成最高4.95亿美元协议，获得GLP-1药物ecnoglutide在中国的独家商业化权。该药已在中国获批治疗2型糖尿病，并提交减重适应症申请，临床数据显示减重效果达15.1%。 此举是辉瑞全球代谢疾病战略的重要一步，使其在中国市场与诺和诺德和礼来正面竞争。继100亿美元收购Metsera后，辉瑞持续加码GLP-1赛道，完善肥胖产品管线，显示其打造全球慢性体重管理领导地位的战略决心。 2026.2.24报道，安斯泰来与Vir达成最高17亿美元合作，共同开发PSMA/CD3双特异性T细胞连接器VIR-5500。I期数据显示82%患者PSA下降≥50%，显示较强疗效潜力。安斯泰来支付3.35亿美元upfront并承担60%开发费用，Vir保留美国共推权。 该交易强化安斯泰来在前列腺癌领域布局，与其重磅产品Xtandi形成协同；Vir则获得资金与成熟商业平台支持。VIR-5500凭借“肿瘤掩蔽”技术，有望在PSMA赛道形成差异化竞争优势。 五大交易亮点分析 01 礼来 Eli Lilly 一、交易结构与核心条款 首付款：礼来支付1亿美元upfront，获得clazakizumab在部分适应症的开发权。 后续付款：包含临床、监管、商业化里程碑及销售分成（金额未披露）。 权益划分： 1）CSL保留：终末期肾病（ESKD）患者心血管事件预防适应症的全球开发及商业化权利。 2）礼来获得：除该适应症外的其他潜在适应症开发权。 这是典型的“适应症拆分授权”模式，既降低礼来的风险，又为CSL保留最成熟的核心资产领域。 二、资产本身的科学与临床价值 1、机制层面 Clazakizumab是抗IL-6单抗。IL-6是关键炎症细胞因子，参与：免疫系统调控、血管炎症、造血过程、慢性炎症级联反应。IL-6过表达与动脉粥样硬化、慢性肾病、自身免疫疾病、炎症性心血管事件相关。 这意味着其潜在市场不止一个适应症，而是炎症驱动型疾病的大平台资产。 2、临床进展与历史风险 当前：ESKD心血管事件预防III期进行中（高价值适应症）。 过去：在移植排斥III期因疗效不足失败。 这说明机制具有生物学合理性，但不同适应症间疗效差异明显，并非“全能型”IL-6产品。IL-6赛道历史上已有托珠单抗等产品，因此差异化能力是关键。 三、战略逻辑：礼来为什么买？ 1、强化“免疫炎症（I&I）+ 心血管”双主线 礼来近年来明显强化I&I战略：1）收购Ventyx（NLRP3）；2）合作推进耐受性自身免疫疗法；3）收购Orna进入CAR-T；4）基因编辑布局。 clazakizumab补强的是“炎症驱动的心血管疾病”这一交叉赛道。心血管+炎症是一个正在崛起的方向（参考CANTOS研究验证IL-1β路径对心血管事件的影响）。 礼来显然在押注“炎症调控“将成为心血管治疗的下一个增长引擎。 2、风险控制型布局 1亿美元首付并不算高（对礼来体量而言）。 说明：1）礼来视其为“期权型资产”；2）并未孤注一掷；3）若III期ESKD数据成功，可进一步扩展。 这是一种典型的“低成本锁定潜在爆发资产”的策略。 四、CSL的策略意义 CSL保留ESKD心血管适应症，原因可能包括：1）该适应症最成熟，已进入III期；2）数据掌握最完整；3）心血管事件在ESKD人群中高发，市场明确；4）若成功，将成为重磅产品。 同时将其他适应症外授权给礼来：1）分散开发成本；2）引入大药企资源；3）保留核心价值资产。 这是典型的双赢结构。 五、风险因素 1、历史III期失败阴影（移植排斥） 2、IL-6赛道竞争激烈 3、心血管炎症机制转化难度高 4、若ESKD III期失败，资产估值会显著下降 但若成功，将成为“炎症-心血管交叉”领域重要里程碑。 六、对礼来2026年整体资本动作的意义 2026年礼来明显呈现三大战略方向： 1、炎症免疫平台化：IL-6，NLRP3，自身免疫耐受疗法。 2、细胞治疗与精准免疫：Orna CAR-T 3、基因编辑：Seamless合作 这不是零散交易，而是围绕“免疫调控”构建多层次技术平台矩阵，说明礼来正从传统制药公司向免疫与炎症驱动疾病的系统性平台公司转型。 七、投资视角总结 核心判断逻辑： 1、1亿美元买入的是“IL-6炎症平台期权” 2、适应症拆分降低风险 3、炎症+心血管是未来十年潜在爆发赛道 4、礼来正在系统性加码I&I赛道 如果ESKD III期成功，资产估值将大幅提升，礼来可能进一步深化合作甚至并购。 如果失败，损失可控，不影响整体战略方向。 这不是一笔简单的license交易，而是礼来在“炎症驱动型心血管与自身免疫大平台”战略中的关键拼图之一，用较低成本锁定一个具有跨适应症潜力的生物学核心通路资产。 02 诺华 Novartis 一、交易结构：典型“平台型早期押注” 首付款：1亿美元 里程碑：最高17亿美元 销售分成：上市后支付 特征：1）upfront较低；2）里程碑占比极高；3）明显属于早期技术平台合作。 说明诺华在以有限前期资本锁定一个潜在突破性平台。 二、核心技术：宏环多肽（Macrocyclic Peptides） 1、宏环分子的特点 宏环分子兼具： 生物药 小分子 可结合复杂靶点 可穿透细胞膜 高选择性 口服潜力 传统问题是：1）生物药不能进入细胞；2）小分子难以作用大面积蛋白-蛋白相互作用。 宏环肽理论上解决“不可成药靶点”（Undruggable Targets） 2、UNP的差异化优势 UNP核心在于：1）AI驱动设计；2）合成多肽模拟天然宏环；3）优化稳定性与穿膜能力。 这意味着不只是多肽，而是可工程化的药物设计引擎。 三、为何聚焦心血管？ 1、心血管仍存在大量未满足需求：1）炎症驱动动脉粥样硬化；2）心衰分子通路复杂；3）蛋白互作网络难以干预。 2、小分子与抗体均存在局限：1）抗体难进入细胞；2）小分子无法调控复杂蛋白界面；3）宏环分子正好处在两者之间。 四、行业趋势：宏环技术成为新热点 UNP此前合作：默沙东（2.2亿美元）；argenx（15亿美元） 说明多家大药企认为宏环分子是“下一代药物形态”。 当前行业趋势：1）分子胶；2）PROTAC；3）宏环多肽；4）AI驱动设计 诺华不愿在技术浪潮中落后。 五、与诺华整体战略的契合 CEO明确提出：“加强早期管线建设”“优先2B美元以下交易”。 近期动作：1）Monte Rosa（分子胶）；2）SciNeuro（早期阿尔茨海默）；3）UNP（宏环多肽） 可以看出一个清晰逻辑：1）布局前沿平台技术，而非单一产品。2）这是一种“去风险化、多平台分散押注、未来10年储备创新源头”的战略思维。 六、风险分析 1、技术仍属早期 2、未披露具体靶点 3、宏环分子临床成功案例有限 4、心血管领域临床试验成本极高 但由于首付款仅1亿美元，财务风险可控。 七、投资逻辑拆解 1、对诺华：1）抢占下一代药物技术高地；2）扩大早期创新来源；3）在心血管领域寻找差异化突破 2、对UNP：1）获得资本支持；2）获得全球开发能力背书；3）平台获得大药企认证 八、战略层面的深层含义 诺华正在完成转型：从“传统重磅产品驱动型制药公司“转向”多技术平台驱动的创新药企“。 这类交易不是为了短期收入，而是为了2030年后的产品储备。 九、关键判断 成功与否取决于：1）宏环分子是否真正实现细胞内复杂靶点调控；2）是否具备良好的药代与安全性；3）能否形成可扩展产品管线。 如果技术兑现，宏环多肽可能成为继抗体、小分子之后的“第三代主流分子形态”。 这不是一次心血管产品交易，而是诺华对“下一代可穿膜大分子技术”的战略布局，用小额首付款锁定一个可能改变药物设计边界的平台。 03 吉利德 Gilead 一、交易本质：从合作到彻底控股的“时间窗口型收购” 总对价78亿美元。每股115美元，较30日均价溢价68%。外加每股5美元CVR（商业里程碑触发）。 这说明吉利德希望在FDA审批结果公布前完成收购，以高溢价换取确定性，避免获批后估值暴涨。 这是一种典型的“审批前收购套利策略”。 二、核心资产：anito-cel的临床竞争力 1、机制 靶点：BCMA 类型：自体CAR-T 适应症：复发/难治性多发性骨髓瘤（R/R MM） BCMA是目前多发性骨髓瘤CAR-T的成熟靶点。 2、II期数据解读（iMMagine-1） ORR：97% CR/sCR：68% 6个月PFS：91.9% 6个月OS：96.6% 这是非常强劲的数据。对比市场已有BCMA CAR-T（如Abecma、Carvykti）：1）ORR处于行业顶级区间；2）CR率具竞争力；3）生存数据尚需长期随访。 如果后续安全性可控，anito-cel有潜力成为下一代BCMA CAR-T主力产品。 三、为何此时必须收购？ 1、吉利德的CAR-T战略背景 吉利德通过Kite拥有：Yescarta，Tecartus。 但问题在于血液肿瘤竞争加剧，多发性骨髓瘤市场被BMS和强生占据。 anito-cel可帮助吉利德正面进入MM核心赛道。 2、防御性收购逻辑 如果anito-cel获批：1）Arcellx市值将显著上升；2）竞争对手可能发起竞购；3）吉利德将失去完全控制权。 因此提前收购是防止资产外流+ 保持利润最大化。 四、III期试验的重要性 iMMagine-3：450名患者、对比标准疗法、2028年完成。 关键意义：若成功，将支持前线或更早线治疗扩展，市场规模可能倍增。 多发性骨髓瘤CAR-T市场规模当前已超百亿美元潜力，若前移治疗线，规模更大。 五、资本布局轨迹 吉利德并非突然行动。 2022年：2.25亿美元upfront + 1亿美元股权；最高39亿美元里程碑。 2023年：追加投资2.85亿美元 2026年：直接收购78亿美元 这是典型的：先小额绑定→ 逐步加深→ 最终吞并 说明吉利德长期跟踪资产进展，对数据趋势已有充分内部判断。 六、战略层面：吉利德的细胞治疗再加码 近期动作：1）Pregene（中国细胞治疗）；2）OncoNano合作；3）收购Arcellx 可以看出吉利德将细胞治疗视为未来增长核心引擎，尤其在HIV收入增速放缓背景下，肿瘤板块必须提供长期增长曲线。 七、风险因素 1、BCMA赛道已拥挤 2、CAR-T制造成本高 3、安全性风险（CRS、神经毒性） 4、长期缓解持续性仍需观察 如果疗效无法超越Carvykti，市场份额可能受限。 八、投资视角核心判断 这笔交易体现三层逻辑： 1、时间套利：审批前收购锁定价值。 2、平台升级：强化Kite在血液肿瘤的统治力。 3、战略聚焦：从广泛管线转向“高价值细胞疗法核心资产”。 九、关键战略问题 这笔交易真正的赌注在于：anito-cel能否在BCMA赛道中实现差异化。 若疗效、安全性、生产效率优于竞品：78亿美元可能是便宜的。 若不能形成代际优势：回报周期将拉长。 这是一笔“审批前高溢价锁定未来现金流”的战略收购——吉利德在CAR-T领域选择加码而非分散，通过完全控股anito-cel，争夺多发性骨髓瘤CAR-T市场的核心席位。 04 辉瑞 Pfizer 一、交易本质：辉瑞全球GLP-1战略的中国落子 获得ecnoglutide在中国的独家商业化权 总金额最高4.95亿美元（首付款+里程碑） 资产状态：1）已在中国获批治疗2型糖尿病；2）减重适应症上市申请已被受理。 这是一个“后期资产+已上市产品”型交易，风险明显低于早期研发资产。 二、产品质量与临床竞争力 1、机制：ecnoglutide为GLP-1受体激动剂（注射剂）。 2、临床数据 减重：15.1% placebo-adjusted；93%患者达到“有临床意义的减重” 这个数据明显优于早期GLP-1产品，接近或略低于部分高端多靶点产品，在单靶GLP-1中具有竞争力。 相比辉瑞自己的PF’3944（12.3% at 28周）：ecnoglutide在减重幅度上更优；且已获批上市，商业化更快。 三、辉瑞为何仍然“持续加码”？ 辉瑞在GLP-1赛道经历了三步走： 第一阶段：自研失败，Danuglipron因安全问题终止 第二阶段：巨额并购，100亿美元收购Metsera，获得PF’3944 III期资产 第三阶段：全球组合式布局：Sciwind（中国成熟资产）；YaoPharma（中国早期资产） 这说明辉瑞的逻辑是不再押注单一产品，而是构建“GLP-1组合矩阵”。 四、中国市场的战略意义 中国是全球最大糖尿病市场，增长最快的肥胖市场，GLP-1渗透率仍低。 辉瑞此举具有三层意义： 1、直接对抗诺和诺德和礼来：Wegovy已进入中国，Zepbound已进入中国，辉瑞必须在中国建立存在感，否则将被边缘化。 2、本土合作降低政策风险：通过与中国公司合作降低准入壁垒、优化医保谈判策略、加强渠道适配。 3、获取真实世界数据：中国人群减重数据对全球注册战略具有参考价值。 五、竞争格局：GLP-1进入“军备竞赛” 当前GLP-1格局： 诺和诺德：Wegovy（强势先发） 礼来：Zepbound（高效双靶） 辉瑞：通过并购+授权追赶 辉瑞的特点是：进入较晚，但资本弹药充足，采用“买时间”策略。 100亿美元买Metsera，本质上是用资本弥补研发时间差，再通过中国资产补强商业覆盖面。 六、风险因素 1、GLP-1市场可能价格内卷 2、中国医保控费压力 3、15%减重虽优秀，但未形成代际差距 4、长期安全性与依从性仍待观察 此外，辉瑞此前GLP-1失败记录仍是投资者心理阴影。 七、资本运作逻辑分析 辉瑞目前的代谢布局呈现“三层结构”： 层级 资产 作用 已上市 ecnoglutide 现金流与市场卡位 后期 PF’3944 核心重磅候选 早期 YaoPharma项目 未来储备 这是典型的“梯度式管线构建”，说明辉瑞已将肥胖视为长期核心增长引擎，而非短期机会。 八、核心投资结论 这笔交易的真正意义不在于4.95亿美元本身，而在于：1）辉瑞确认肥胖为公司级战略方向；2）中国成为全球GLP-1主战场；3）通过多资产组合降低单品风险；4）从“研发驱动”转向“资本+全球布局驱动”。 辉瑞正在尝试完成一次战略转型：从COVID时代收入高峰后的下滑压力中，转向慢病长期增长曲线。 这不是一笔区域授权交易，而是辉瑞构建全球GLP-1帝国拼图中的关键一块——在中国市场建立桥头堡，同时为其肥胖战略提供商业化落地与时间窗口。 05 安斯泰来 Astellas 一、交易结构：高风险高潜力的分阶段押注 1、近期确定投入：3.35亿美元（2.4亿美元现金，7500万美元股权投资，2000万美元近期付款） 2、潜在里程碑：13.7亿美元 3、海外销售双位数分成 总对价最高约17亿美元。这是典型的“中等规模upfront + 高里程碑对赌”结构。 说明资产仍处早期（I期），安斯泰来控制早期风险，若成功，Vir回报巨大。 二、资产核心：VIR-5500的技术含金量 1、机制：PSMA × CD3 双特异TCE 靶点1：PSMA（前列腺癌高度表达） 靶点2：CD3（T细胞活化核心分子） 作用机制：1）将T细胞“拉”到肿瘤细胞旁；2）激活免疫杀伤 这属于当前肿瘤免疫领域热门的T cell engager（TCE）技术路线。 2、差异化技术：PRO-XTEN“掩蔽技术” 这是交易真正的亮点。 该技术特点：1）药物在体内“非活化”；2）仅在肿瘤微环境中被激活；3）理论上降低全身毒性；4）支持更高剂量给药。 TCE的核心问题是：1）CRS（细胞因子风暴）；2）靶外毒性 如果PRO-XTEN能显著改善安全性，那么它可能成为下一代可高剂量给药的TCE平台。这是结构性差异化，而不是简单me-too。 三、临床数据解读 I期数据：1）82% PSA下降≥50%；2）53% PSA下降≥90%；3）呈剂量依赖性。 在前列腺癌领域：PSA下降50%通常被视为有效信号。 Truist称其为“robust competitor”，说明数据在同类PSMA-TCE中具有可比优势；安全性可能优于传统TCE。 不过要注意：仍为I期；尚无OS/PFS数据；PSA只是替代终点。 四、对安斯泰来的战略意义 1、现有支柱：Xtandi Xtandi前9个月销售额：47.2亿美元 但问题是：1)专利周期有限；2）前列腺癌竞争加剧；3）新一代疗法不断出现 VIR-5500的意义在于：为Xtandi之后的前列腺癌版图提前卡位 2、产品线升级路径 当前安斯泰来前列腺癌布局： 类型 产品 激素通路 Xtandi 小分子 Abiraterone decanoate 免疫TCE VIR-5500 这是从“激素驱动→ 精准小分子→ 免疫杀伤”的升级路线。 安斯泰来正在避免被新一代免疫疗法边缘化。 五、Vir的战略获益 对Vir来说：1）获得现金支持，缓解研发现金压力；2）获得成熟商业平台。 安斯泰来在前列腺癌市场拥有：1）强大的泌尿肿瘤销售网络；2）Xtandi多年市场积累；3）KOL资源。 这对未来商业化至关重要。 六、竞争格局判断 PSMA赛道当前存在：1）ADC；2）放射性配体疗法（如Pluvicto）；3）TCE 未来竞争将围绕：1）疗效深度；2）毒性管理；3）给药便利性。 如果PRO-XTEN技术成立，VIR-5500可能在安全性上形成结构优势。 七、风险因素 1、早期临床阶段风险高 2、PSA替代终点不能代表长期生存获益 3、TCE赛道拥挤 4、高剂量是否真正安全仍待验证 八、投资视角总结 1、对安斯泰来：1）用较合理的upfront 锁定下一代前列腺癌免疫平台；2）为Xtandi后时代布局；3）构建免疫肿瘤能力 2、对Vir：1）获得资金+ 商业通路；2）技术平台获得外部验证 九、关键战略判断 这不是简单的一款新药授权，而是安斯泰来从“激素疗法公司”向“肿瘤免疫综合玩家”的升级尝试。 如果成功，VIR-5500可能成为PSMA-TCE中领先产品，PRO-XTEN平台估值将显著提升。 如果失败，upfront可控，不会动摇安斯泰来核心业务。 这是一次围绕PSMA免疫杀伤赛道的“前瞻性技术押注”，安斯泰来用可控风险换取下一代前列腺癌免疫平台的潜在主导权。 欲深入了解更多行业洞察，请扫以下二维码加入社群： 公司已完成项目 星际微光已完成的项目（截至2023.9，仍在继续......）  圆满中秋 | 星际微光七年完成100个咨询项目 咨询、调研、PR、投资、融资、营销、技术转化项目需求请扫码联系我们： 点击“阅读原文”，看看：火星梦消逝了