Henry Ford Health System

国产B7H3 ADC管线正在狂奔。3月中，宜联生物的B7H3 ADC管线YL201登上了《Nature Medicine》杂志并公布了其在小细胞肺癌的临床一期临床结果，在72名广泛期小细胞肺癌（ES-SCLC）患者中客观缓解率（ORR）为63.9%、疾病控制率（DCR）为86.6%，展现出了显著的抗肿瘤活性，并且YL201在去年10月启动三期临床。4月17日，翰森制药的B7H3 ADC管线HS-20093治疗局部晚期或转移性非鳞状非小细胞肺癌获得第三项突破性疗法认定，预计将在近期启动三期临床，过去HS-20093已经启动了二线广泛期小细胞肺癌和三线滑膜肉瘤的三期临床。随着映恩生物的IPO和全球领头羊第一三共在全球启动了其B7H3 ADC（I-DXd）的四项全球临床（小细胞肺癌、食管鳞癌和转移去势抵抗性前列腺癌），全球B7H3 ADC的研发竞争正进入一个加速期。 同样可以期待的是，随着HER2、TROP2热门靶点ADC获批之后，未来国内乃至全球将不日迎来又一重磅炸弹B7H3 ADC的面市。 01B7H3 ADC潜力和I-DXd的打头B7H3靶点属于B7配体家族成员，具备共刺激或共抑制T细胞的作用，帮助或介导肿瘤的免疫逃逸，同时，B7H3抑制NK细胞介导的细胞裂解，可赋予肿瘤细胞更具攻击性的表型。此外，B7H3 有促进迁移和侵袭、血管生成、化疗耐药、内皮细胞向间充质细胞转化以及影响肿瘤细胞代谢等作用。B7H3在在正常细胞表达较少，而在肺癌、头颈癌、食管癌、前列腺癌、子宫内膜癌和乳腺癌等中过度表达，广谱性的表达推动其成为研发的热门靶点。据弗若沙利文预计，首款B7H3 ADC可能将于2027年获批，2027年全球B7-H3 ADC市场规模预估为3亿美元，并在2032年将增至55亿美元，2027-2032年的CARG为74.2% 。2023年以来，全球B7H3 ADC达成BD交易超过5笔，其中最大的一笔交易莫过于第一三共与默沙东关于I-DXd与其他两款ADC的打包交易（总对价220亿美元），国内首付款价值最高的为翰森制药与GSK的交易（1.85亿美元+累计不超过17.1亿美元里程碑付款+销售分成），另外还有映恩生物和宜联生物与BioNTech的合作、百奥赛图与IDEAYA Biosciences的合作，这无一不彰显B7H3 ADC的价值与潜力。目前，全球进度最快的B7H3 ADC管线莫过于第一三共/MSD的I-DXd，其首项临床三期IDeate-2研究在2024年初已经启动，针对复发性小细胞肺癌，主要终点为ORR和总生存期（OS）。从I-DXd已有早期数据看，其在小细胞肺癌领域展现出了相当不俗的潜力，也算是对B7H3 ADC先行潜力的验证。据I-DXd在2024 WCLC大会公布的治疗ES-SCLC的IDeate-Lung01二期研究数据显示，8mg/kg、12mg/kg剂量组的中位PFS为4.2个月、5.5个月，DCR分别为80.4%、90.5%，mOS分别为9.4个月、11.8个月。值得注意的是，该研究入组患者复发性转移性ES-SCLC患者，曾接受过至少一线铂类化疗和最多三线全身治疗。安全性方面，12mg/kg组16.7%患者在治疗期间不良事件（TEAE），主要TEAE恶心、食欲下降和贫血等，另外间质性肺病/肺炎的发生率为11.9%，8mg/kg组有1例死亡与此TEAE有关。过去复发性小细胞肺癌化疗耐药患者治疗方案包括拓扑替康、伊立替康和铂类再治疗，可提供约20-40%的ORR和约6个月的OS，I-DXd的出现给这类患者提供了全新的治疗方案。02国产两大三期分子的进击与选择I-DXd之后，更好的两大领头国产分子正在为B7H3 ADC赛道开疆扩土。宜联生物YL201公布在《Nature Medicine》临床1b期数据纳入了312例患者，其中涵盖了ES-SCLC、鼻咽癌、NSCLC、食管鳞状细胞癌等，入组的均为标准治疗失败后的晚期患者，且大多数患者既往接受过至少两种治疗方案。YL201在1b期临床的疗效表现亮眼，在总的287名可评估患者中，ORR达40.8%、DCR高达83.6%、mPFS为5.9个月。在分瘤种的亚组数据中，YL201在ES-SCLC中的数据疗效突出，ORR高达63.9%、DCR为91.7%和mPFS为6.3个月，相比目前二线标准治疗有非常大的提升，以及在ORR、mPFS这一关键指标上非头对头比较有优于I-DXd的潜力。另外，鼻咽癌和肺淋巴上皮瘤样癌适应症中也分别录得48.6%、54.2%的ORR。安全性层面，97.1%出现了治疗相关不良事件（TRAEs），其中≥3级的TRAEs发生率为54.5%，最常见为中性粒细胞减少症，而市场关注的间质性肺病（ILD）、输液反应发生率分别只有1.3%、0.3%，证明药物的安全性可控。目前，YL201的小细胞肺癌、鼻咽癌的三期已经启动。翰森制药HS-20093的潜力，则是同样是在肺癌（ES-SCLC、NSCLC）适应症，以及更小众的滑膜肉瘤获得早期数据验证。2024 WCLC大会公布的Ia/Ib期数据显示，HS-20093的8.0mg/kg和10.0 mg/kg剂量组在ES-SCLC患者中分别取得61.3%、50.0%的ORR，DCR分别为80.6%和95.5%，mPFS分别为5.9和7.3个月。安全性方面，HS-20093安全性良好，≥3级的最常见不良事件为血液毒性。在治疗复发/难治性骨肉瘤二期临床ARTEMIS-002研究中，在38例可评估疗效患者，12.0mg/kg组患者的ORR为17.4%，8mg/kg组和12.0mg/kg组患者的DCR分别为66.7%和87.0%。值得注意的是，该研究入组患者的中位治疗线数为3，同时其展现出的疗效已经优于现有标准治疗方法，展现了一定的突破性。从宜联生物、翰森制药的两大分子的早期临床探索的适应症分析，除了通行的SCLC适应症探索之外，两家都分别通过诸如鼻咽癌、骨肉瘤等一些小适应症加速打开局面，打造不同的差异化竞争优势，这也直接展现了B7H3 ADC管线的可延展性和泛癌种开发的潜力。03紧随二梯队分子的差异化尽管第一梯队的管线有进度上的优势，但二梯队的分子差异化优势可能来的更加猛烈，其中最有力的竞争者莫过于映恩生物的DB-1311。DB-1311在2024 ESMO Asia最新公布I/IIa期临床数据显示，该临床入组277例实体瘤患者（欧美人群约占47%、中位治疗线数为3），肿瘤类型包括但不限于SCLC、NSCLC、CRPC以及HNSCC，总体uORR为32.4%，DCR为82.4%。其中，73位SCLC患者的uORR为56.2%，DCR为89.0%；在9mg/kg最高剂量水平下，既往接受过免疫治疗、但未接受过拓扑异构酶I抑制剂治疗的SCLC患者中，uORR为70.4%。更值得注意的是，映恩生物的DB-1311是继I-DXd之后率先读出CRPC早期数据的国产B7H3 ADC分子，32位可评估患者的uORR为28.0%，DCR为92.0%，rPFS尚未成熟，中位rPFS为7.2个月，6个月rPFS率为94.7%。过去，第一三共曾于2023 ESMO公布I-DXd治疗末线mCRPC数据：在接受中位6线治疗后，59例患者ORR为25.4%，mPFS为5.3个月，mOS为13.0个月。目前，I-DXd已经启动了mCRPC全球多中心临床，计划入组1440例，足以见到默沙东/第一三共对于I-DXd在该领域的信心。不难看出，映恩生物DB-1311在CRPC适应症不仅是B7H3 ADC赛道上前三的领先进度，同时存在Me-better或者潜在Best in class的潜力。数据之外，更多额外的竞争力可能在于“IO+ADC”的想象力。DB-1311海外合作伙伴BioNTech在2025年3月已经启动了DB-1311与BNT327/PM8002（PD-L1/VEGF-A双抗）的联合治疗晚期肺癌（SCLC和NSCLC）的Ib/II期临床。值得注意的是，这也是全球首个B7H3 ADC联合PDL1/VEGF双抗的临床研究。PD-1单抗联合ADC已经突破了部分实体瘤的一线治疗，而PD-L1/VEGF双抗作为未来有望在多项头对头战胜PD-1的迭代药物，可以展望其未来与多款热门靶点ADC进军多项一线实体瘤治疗，市场空间广阔。结语：随着国内HER2、TROP2靶点重磅ADC的首个商业化产品获批落下帷幕，下一个备受市场关注的B7H3靶点之争也走到舞台中央，面对这一至少10亿美元的市场机会，从中突围而出的药企必定饱含丰富的价值投资机会。识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

NEW YORK, Feb. 25, 2025 /PRNewswire/ -- Novita Pharmaceuticals, Inc. ("Novita"), a privately held, clinical-stage pharmaceutical company dedicated to developing novel cancer drugs through its proprietary fascin inhibitor technology, today announced additional results from its Phase 2 study (NCT05023486) evaluating NP-G2-044 in combination with SOC anti-PD-1 therapy in patients with advanced solid tumors resistant to prior anti-PD-1 therapy at the American Association for Cancer Research Immuno-oncology (AACR IO) Annual Meeting. The data was presented in a poster presentation titled "Phase 2 Study of NP-G2-044, a Novel Fascin Inhibitor, in Combination with Anti-PD-1 Therapy in Patients with Solid Tumors Resistant to Prior Anti-PD-1 Therapy." Findings indicate that NP-G2-044 provides a novel therapeutic opportunity when combined with ICIs. "We are very pleased with the findings generated to date in our Phase 2 trial of NP-G2-044 both as a monotherapy and in combination with anti-PD-1 immune checkpoint inhibitors (ICIs) in ICI-resistant patients with advanced and metastatic solid tumors," said Jillian Zhang, Ph.D., President & Chief Scientific Officer of Novita. "The strong safety and durable efficacy we have observed with our first-in-class fascin inhibitor further support the simultaneous inhibition of metastasis and enhancement of cancer immunotherapy as a promising and innovative approach in cancer treatment with broad applications for many solid tumors. We look forward to sharing additional data from the Phase 2 expansion cohort of NP-G2-044 in combination with ICI in the second half of 2025." Among the 45 patients treated with NP-G2-044 as of the last data cutoff (Oct. 2024), 80% had progressed on prior anti-PD-(L)1 therapies. The anti-PD-1 Combination RP2D for NP-G2-044 was 1600 mg QD with 4-week cycles. The primary endpoint was objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), metastasis-free interval (MFI), overall survival (OS), safety, and tolerability. Key highlights include: A Disease Control Rate of 76% (includes patients with Stable Disease and Objective Responses) An ORR of 21% (95% CL 9-38.9%) including 4 patients with Partial Response (PR) and 3 patients with Complete Responses (CR) including Pathologic Complete Response Results indicate durable responses and tumor control in a significant proportion of patients across at least seven cancer types, including cases converted from ICI-non-responsive to ICI-responsive. Long lasting objective responses have been observed. Notable outcomes include a CR in a cervical cancer patient, target lesion CR in an endometrial cancer patient, pathological CRs in a pancreatic cancer patient and a patient with gastroesophageal junction adenocarcinoma and PRs in cutaneous squamous cell carcinoma, non-small cell lung cancer, and cholangiocarcinoma. Seven patients are still on treatments, with the longest duration of 18+ months in an endometrial cancer patient and a patient with pancreatic cancer. An amendment to the study is underway to open additional cohorts. These new cohorts aim to further evaluate the combination of NP-G2-044 with anti-PD-1 therapy across patient populations and solid tumor subtypes, providing a broader understanding of its therapeutic potential. Future analysis will also explore biomarkers for response prediction and mechanisms of resistance, guiding personalized approaches in treatment-resistant cancer. Novita is on track to begin enrollment in its pivotal Phase 3 study of NP-G2-044 + PLD in platinum resistant ovarian cancer in the third quarter of 2025. About Novita's Pioneering Research in Fascin Inhibition Cancer metastasis is the primary cause of over 90% of cancer-related deaths, yet there is currently no drug on the market specifically targeting metastasis. Furthermore, while Immuno-Oncology (IO) therapies, particularly immune checkpoint inhibitors, have made significant strides in cancer treatment, a large proportion of patients do not respond to existing IO treatments. Novita aims to address both of these critical medical needs by developing fascin inhibitors, which target a key protein involved in tumor cell motility and highly expressed in tumor cells and antigen-presenting cells within tumor tissues. The Company's lead asset, NP-G2-044, is a small-molecule fascin inhibitor that has demonstrated the ability to block metastasis in both preclinical and clinical studies. Additionally, when combined with immune checkpoint inhibitors, NP-G2-044 has shown potential to reinvigorate anti-tumor immune responses. Novita's multicenter Phase 2 clinical trial, titled "NP-G2-044 as Monotherapy and Combination Therapy in Patients with Advanced or Metastatic Solid Tumor Malignancies," is currently ongoing. About Novita Pharmaceuticals, Inc. Novita Pharmaceuticals, Inc. is a privately held, clinical-stage biopharmaceutical company focused on developing groundbreaking therapies using its proprietary fascin inhibitor technology to prevent and treat cancer metastasis while simultaneously enhancing anti-cancer immune responses. For more information, visit Cautionary Note Regarding Forward-Looking Statements This press release contains certain forward-looking statements. Such statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in the forward-looking statements. These statements are based on a number of assumptions and estimates that are inherently subject to significant uncertainties and contingencies, many of which are beyond the Company's control, and respect future business decisions, which are subject to change. Among those factors that could cause actual results to differ materially from those described in the forward-looking statements are the risks associated with the Company's being a development stage company with uncertain revenue streams; uncertain results or outcomes during clinical trials; failure to raise necessary capital in the future; the loss of key personnel; competition from other larger, better-capitalized peers; the Company's reliance on incorrect assumptions regarding the market for its products, the costs of developing, manufacturing and marketing the Company's products, and the timing and receipt of regulatory approval for the Company's products; adverse economic conditions; and other risks. In light of the significant uncertainties inherent in the forward-looking statements, the inclusion of any such statement should not be regarded as a representation by Novita or any other person that the Company's objectives or plans will be achieved. Media Contact: Argot Partners (media) David Rosen 212.600.1902 [email protected] Investor Contact: Argot Partners (investors) Noor Pahlavi 212.600.1902 [email protected] SOURCE Novita Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

iStock, Sundry Photography The news comes on the heels of promising Phase I/Ib data, which point to the potential of casdatifan as a more effective alternative to Merck’s Welireg in renal cell carcinoma. Gilead will not move forward with Arcus Biosciences’ casdatifan, an investigational HIF-2a blocker that is being tested for kidney cancer. As per the California biotech’s Tuesday press announcement, Gilead’s window to exercise its exclusive option to obtain rights to casdatifan has “expired.” Arcus will retain full control over the asset and its development path forward. Arcus also announced that it will run a $150 million common stock offering—which Gilead will participate in—to help bankroll future studies of casdatifan. Arcus CEO Terry Rosen in a statement said that the biotech is “thrilled” to keep ownership of casdatifan, which he says “represents a transformational change for Arcus” and allows it to “address a significant unmet need for patients with an estimated $5 billion market opportunity.” Investors, however, are not as enthused: Arcus’ shares dipped 16% to $10.96 on Tuesday, a new 52-week low for the company, per SeekingAlpha . Analysts at Mizuho Securities, on the other hand, appeared optimistic about Arcus, writing in a Tuesday note that the stock offering “could allow [Arcus] to advance the casdatifan program independently” and provide freedom to assess the candidate as a monotherapy or as part of combination regimens. Tuesday’s news comes just days after Arcus presented promising Phase I/Ib data for casdatifan at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium. Results, disclosed over the weekend, showed that a 100-mg dose, given once a day, resulted in a 33% confirmed overall response rate (ORR) and a 52% stable disease rate in patients with metastatic clear cell renal cell carcinoma (RCC). Patients treated with this casdatifan dosage did not reach median progression-free survival (PFS) at the time of the readout, though a different dose level—50 mg twice-daily—had a median PFS of 9.7 months. Arcus is taking the 100-mg dose forward. According to Mizuho, these data suggest that casdatifan is “superior” to Merck’s Welireg (belzutifan), which is also a HIF-2a inhibitor that is FDA-approved for advanced RCC. In particular, the analysts zeroed in on casdatifan’s 9.7-month PFS in the 50-mg, once-daily dose arm, which they say compares favorably to Welireg’s 5.6-month PFS, as indicated in its label . Additionally, casdatifan’s 33% ORR is higher than Welireg’s 22%, as per Mizuho. Cross-study comparisons are inconclusive, however, in the absence of direct head-to-head trials. Arcus plans to ramp up investment to “position casdatifan as the HIF-2a inhibitor of choice,” Rosen said in a statement. The biotech will unveil more data for the therapy throughout 2025 and is preparing to launch another study, dubbed PEAK-1, which will test casdatifan with Cabometyx , Exelixis’s VEGF2 inhibitor, in metastatic clear cell RCC patients who had previously undergone immune-oncology treatments.