A Dose-escalation, Single-arm, Open-Label, Phase 1 Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of EU103 in an Advanced or Metastatic Solid Tumors Who Have Failed Standard Therapy

Phase 1 (dose escalation) of this study will evaluate:
The safety and tolerability of EU103 treatment are evaluated for patients with advanced or metastatic solid tumors who have failed standard therapy to determine the maximum tolerated dose and recommended Phase 2 dose.
And preliminary efficacy (tumor response), The pharmacokinetic characteristics are evaluated, and changes are investigated.

开始日期2023-08-08

申办/合作机构

Eutilex Co., Ltd.

100 项与 EU-103 相关的临床结果

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100 项与 EU-103 相关的转化医学

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100 项与 EU-103 相关的专利（医药）

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项与 EU-103 相关的文献（医药）

2015-02-01·Immunobiology4区 · 医学

Monitoring liver macrophages using nanobodies targeting Vsig4: Concanavalin A induced acute hepatitis as paradigm

4区 · 医学

Article

作者: Sparkes, Amanda ; Lahoutte, Tony ; Zheng, Fang ; Abels, Chloé ; De Baetselier, Patrick ; Stijlemans, Benoit ; Raes, Geert ; Muyldermans, Serge ; Schoonooghe, Steve ; Beschin, Alain ; Morias, Yannick ; Devoogdt, Nick

Kupffer cells (KCs) are liver resident macrophages which are important for tissue homeostasis and have been implicated in immunogenic, tolerogenic and pathogenic immune reactions depending on the insult. These cells and the biomarkers they express thus represent interesting in vivo sensors for monitoring liver inflammation. In the current study, we explored whether KCs can be monitored non-invasively using single-photon-emission computed tomography (SPECT) with (99m)Tc labeled nanobodies (Nbs) targeting selected biomarkers. Nbs targeting V-set and immunoglobulin domain-containing 4 (Vsig4) or macrophage mannose receptor (MMR) accumulated in the liver of untreated mice. The liver targeting of anti-Vsig4 Nbs, but not anti-MMR Nbs, was blunted upon depletion of macrophages, highlighting specificity of anti-Vsig4 Nbs for liver macrophage imaging. Ex vivo flow cytometry and immunohistochemistry analysis confirmed that anti-Vsig4 Nbs specifically targeted KCs but no other cell types in the liver. Upon induction of acute hepatitis using concanavalin A (ConA), down-regulation of the in vivo imaging signal obtained using anti-Vsig4 Nbs reflected reduction in KC numbers and transient modulation of Vsig4 expression on KCs. Overall, these results indicate that Nbs targeting Vsig4 as molecular imaging biomarker enable non-invasive monitoring of KCs during hepatic inflammation.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Antibodies Targeting Human or Mouse VSIG4 Repolarize Tumor-Associated Macrophages Providing the Potential of Potent and Specific Clinical Anti-Tumor Response Induced across Multiple Cancer Types

Article

作者: Klebanov, Boris ; Manfra, Denise ; Ritter, Jessica ; Novobrantseva, Tatiana ; Sazinsky, Stephen ; Kauffman, Kevin J. ; Zafari, Mohammad ; Nguyen, Phuong A. ; Wahle, Joe ; Feldman, Igor ; Razlog, Maja ; Phennicie, Ryan T.

V-set immunoglobulin domain-containing 4 (VSIG4) is a B7 family protein with known roles as a C3 fragment complement receptor involved in pathogen clearance and a negative regulator of T cell activation by an undetermined mechanism. VSIG4 expression is specific for tumor-associated and select tissue-resident macrophages. Increased expression of VSIG4 has been associated with worse survival in multiple cancer indications. Based upon computational analysis of transcript data across thousands of tumor and normal tissue samples, we hypothesized that VSIG4 has an important role in promoting M2-like immune suppressive macrophages and that targeting VSIG4 could relieve VSIG4-mediated macrophage suppression by repolarizing tumor-associated macrophages (TAMs) to an inflammatory phenotype. We have also observed a cancer-specific pattern of VSIG4 isoform distribution, implying a change in the functional regulation in cancer. Through a series of in vitro, in vivo, and ex vivo assays we demonstrate that anti-VSIG4 antibodies repolarize M2 macrophages and induce an immune response culminating in T cell activation. Anti-VSIG4 antibodies induce pro-inflammatory cytokines in M-CSF plus IL-10-driven human monocyte-derived M2c macrophages. Across patient-derived tumor samples from multiple tumor types, anti-VSIG4 treatment resulted in the upregulation of cytokines associated with TAM repolarization and T cell activation and chemokines involved in immune cell recruitment. VSIG4 blockade is also efficacious in a syngeneic mouse model as monotherapy as it enhances efficacy in combination with anti-PD-1, and the effect is dependent on the systemic availability of CD8+ T cells. Thus, VSIG4 represents a promising new target capable of triggering an anti-cancer response via multiple key immune mechanisms.

项与 EU-103 相关的新闻（医药）

2023-03-20

·药明康德

肿瘤细胞量降低超90%的新疗法；登上《自然》的靶向疗法... | 一周盘点

▎药明康德内容团队编辑本期看点1. 用于治疗携带NPM1突变或KMT2A重排的复发/难治性急性白血病（AML）的选择性小分子menin抑制剂revumenib登上《自然》杂志，53%的受试者对治疗有反应，12名患者争取到了接受干细胞或骨髓移植的机会。2. 新型合成微管不稳定药物AB8939在1例难治性AML患者中展现积极疗效，仅连续给药3天，接受治疗28天后就观察到白血病细胞的急剧减少，从55%降低到5%，降幅超过90%。3. Kiora Pharmaceuticals公司公布三项罕见眼科疾病的创新小分子疗法的积极数据。药明康德内容团队整理Revumenib：公布1/2期临床试验数据Syndax Pharmaceuticals公司公布了其选择性小分子menin抑制剂revumenib用于治疗携带NPM1突变或KMT2A重排的复发/难治性AML患者的积极结果，并发表在了权威学术期刊《自然》上。AML是成人中最常见的白血病之一，约占所有病例的三分之一。MLL基因重排和NPM1突变发生在大约40%的AML患者身上，这两种基因变异都需要menin蛋白质的参与来驱动癌症发生。Revumenib是一种有效的选择性小分子抑制剂，旨在抑制menin-MLL结合的相互作用以治疗白血病。研究共招募了68名AML患者。此次公布的数据显示，53%的患者对revumenib治疗有反应，30%实现了完全缓解或伴有部分血液学恢复的完全缓解。在获得缓解的患者中，超过78%患者的可测量残留病灶为阴性，表明即使通过最灵敏的方法，也无法检测到白血病。所有患者的整体中位缓解时间为9.1个月，中位总生存期为7个月（含对治疗无反应的患者）。12名原本无法进行移植手术的患者在出现病情缓解后进行了异体干细胞移植。总的来说，试验中观察到的副作用并不严重，没有患者因副作用而退出试验。AB8939：公布1/2期临床试验的初步数据AB Science公司公布了其针对血液恶性肿瘤开发的新型合成微管不稳定药物AB8939在1/2期临床试验中的积极初步结果。临床前数据表明，AB8939具有广泛的抗肿瘤活性，与靶向微管的标准化疗相比具有显著的优势，能够克服P-糖蛋白（Pgp）和髓过氧化物酶（MPO）介导的耐药性。此前，AB8939已被美国FDA授予AML的孤儿药资格。在这项研究中，一位未能事先接受阿扎胞苷治疗，并出现MECOM基因重排（一种对标准化疗耐药的生物标志物，与疾病进展的高风险和较差的预后相关）的AML患者在第一个治疗周期（即连续三天的AB8939治疗）一个月后，骨髓原始细胞（即白血病细胞）的水平从治疗前的55%急剧减少到5%。值得注意的是，这种反应是在AB8939的剂量非常低的情况下实现的，也就是1期剂量增量研究的第2个剂量（一共设计了13个待研究的剂量）。患者对AB8939的耐受性良好，没有出现治疗相关的毒性反应。在该低剂量下，第二个治疗周期后一个月时，患者的白血病细胞水平保持在10%（相当于相对于基线减少5倍）。考虑到迄今为止的总体研究，没有出现中度或严重毒性反应的迹象，大约50%的患者在第一个治疗周期和第28天的评估后请求继续接受AB8939的治疗。KIO-101：公布1期临床试验的新数据KIO-101是Kiora Pharmaceuticals公司的一种靶向二氢乳清酸脱氢酶（DHODH）的下一代非甾体类免疫调节小分子抑制剂，旨在克服市售的DHODH抑制剂的相关脱靶副作用和安全问题。该疗法的给药方式为玻璃体内注射，正在12名患有自身免疫性后部葡萄膜炎（posterior uveitis）的患者中接受评估。此次公布的结果显示，玻璃体内注射KIO-101是安全且可耐受的，具有治疗自身免疫性后部葡萄膜炎和黄斑囊样水肿（CME）患者的潜力。患者的视力呈剂量依赖性增加，前房细胞和玻璃体混浊的综合炎症评分在第2周下降了53.0%，并在第4周保持低水平。接受0.6 µg或1.2 µg治疗的5名患者中有3名（66.7%）的CME消退。在整个研究期间，所有组的眼压、视野和视网膜电图（ERG）都保持稳定，没有观察到不良事件。KIO-201：公布早期临床试验结果KIO-201是Kiora Pharmaceuticals公司的一种交联的、化学修饰的透明质酸，用于患有持续性角膜上皮缺损（PCED）的患者。该公司于近日报告了KIO-201在8名患者中的临床研究结果。数据显示，KIO-201是PCED的一种潜在的治疗方法。8只眼睛在治疗至少3周后通过重复荧光素染色进行评估，在治疗开始后4周，KIO-201使缺损的尺寸缩小>90.0%。8名患者中有5名（62.5%）在4周内达到了主要的愈合终点。该药物的安全性和耐受性良好，8名患者中有2名（25.0%）报告了6起非严重不良事件。研究人员报告的所有不良事件均与研究药物无关。KIO-301：公布首次人体试验数据KIO-301是Kiora Pharmaceuticals公司的一种小分子光控开关（Photoswitch），旨在治疗视网膜色素变性。该公司于近日公布了KIO-301的首次人体试验的初步数据。该试验作为正在进行的、更大规模临床试验的一部分，将初步评估KIO-301在晚期视网膜色素变性患者中的安全性、耐受性和疗效。试验的初始人群患有晚期色素性视网膜炎，伴有最低限度的光感或无光感。患者报告的结果表明，在注射KIO-301后，其感知光的能力、描绘明暗对比的能力以及整体视觉功能都有所改善。在研究过程中没有报告不良事件，包括眼部不良事件。CM24：公布1期临床试验的初步数据Purple Biotech公司公布了其靶向CEACAM1的单克隆抗体CM24用于治疗晚期实体肿瘤患者的初步临床数据。CEACAM1是一种免疫检查点蛋白，可通过多种途径支持肿瘤免疫逃逸和存活。NET是一种网状DNA结构，覆盖着由活化的中性粒细胞释放的致癌蛋白，已被证明可包裹肿瘤并促进免疫逃避、肿瘤进展和转移。当CEACAM1与NET结合时，它将成为癌症细胞粘附的重要位点，因此被认为是预防肿瘤转移进展和免疫逃逸的潜在治疗靶点。在临床前研究中，CM24已被证明可直接与NET结合，并抑制NET诱导的癌症细胞迁移。此次研究招募了14名晚期癌症患者，包括11名胰腺癌（PDAC）患者、两名结直肠腺癌患者和一名乳头状甲状腺癌患者。在八名可评估的PDAC患者中进行的分析表明，CM24联用纳武利尤单抗首次给药后和15天后，血清髓过氧化物酶（myeloperoxidase，一种NET的生物标志物）出现了具有临床意义的持续降低。此外，对来自可评估PDAC患者的肿瘤样本的分析表明，患者存活可能与肿瘤微环境中较高水平的CEACAM1+肿瘤浸润淋巴细胞呈正相关。Povetacicept（ALPN-303）：公布1期临床试验的初步数据Alpine Immune Sciences公司公布了其BAFF（B细胞激活因子）和APRIL（一种增殖诱导配体）的双重拮抗剂povetacicept（ALPN-303）在健康受试者中的初步临床数据。这些细胞因子在B细胞，特别是抗体分泌细胞的活化和存活中起着关键作用。Povetacicept正在被开发用于多种B细胞和/或自身抗体相关疾病。此次公布的研究结果表明，povetacicept在960 mg的剂量下耐受性良好，具有剂量依赖性的药代动力学特征，以及剂量依赖性的循环免疫球蛋白和抗体分泌细胞的减少。该结果支持在后续研究中使用每4周一次的剂量方案。EU103：IND申请获得韩国食品药品安全部许可EU103是Eutilex公司开发的靶向肿瘤相关巨噬细胞（TAM）表面的VSIG4的候选抗体药物，用于治疗标准治疗失败的晚期或转移性实体肿瘤。EU103旨在激活T细胞，并将诱导肿瘤生长的M2巨噬细胞转化为抑制肿瘤生长的M1巨噬细胞。近日，韩国食品药品安全部已经批准了EU103的IND申请，将在30例实体肿瘤患者中对该候选疗法的安全性和耐受性进行评估。ST316：IND申请获得FDA许可ST316是Sapience Therapeutics公司开发的潜在“first-in-class”的β-连环蛋白（β-catenin）拮抗剂，能够抑制β-连环蛋白与其共激活因子BCL9之间的相互作用。β-连环蛋白是Wnt信号通路的效应蛋白，该通路是最重要的致癌通路之一。BCL9是一种在多种癌症中驱动致癌基因表达的复合物，在这些癌症常常中观察到异常的Wnt/β-连环蛋白通路信号传导。β-连环蛋白和BCL9之间的相互作用以前被认为是一个“不可成药”的靶点，因为小分子无法抑制复合物的形成，而抗体无法进入细胞质或细胞核以破坏相互作用。ST316包含了允许进入细胞内的细胞穿透部分和设计用于结合β-连环蛋白第一个armadillo重复结构域的结构域，该位点仅与BCL9发生相互作用。ST316能将β-连环蛋白的生理活性和致癌活性分开，从而能够治疗Wnt驱动的肿瘤，同时保持正常的β-catenin功能完好无损。该研究的第1阶段剂量递增部分将在2023年上半年开展，招募可能患有Wnt/β-连环蛋白信号通路异常的肿瘤患者。TRE-515：公布1期临床试验数据Trethera Corporation公司公布了其口服潜在“first-in-class”的脱氧胞苷激酶（dCK）抑制剂TRE-515用于治疗高危、先前接受过多线治疗的恶性实体肿瘤患者的积极早期临床数据。TRE-515旨在抑制核苷补救通路中的关键酶dCK。实体恶性肿瘤中的肿瘤细胞和自身免疫性疾病中的病理免疫细胞的一个共同特征是需要升高的核苷酸水平来支持异常和加速的细胞分裂。而大多数健康成人细胞并不需要dCK活性。因此，由限速酶dCK介导的核苷补救通路有望在限制癌细胞和异常活化的淋巴细胞的快速增殖方面发挥关键作用。此次公布的临床结果显示，TRE-515的耐受性良好，不良事件有限、短暂且可控。其在40 mg至320 mg剂量范围内的暴露量几乎与剂量成正比，显示出良好的药代动力学特征，其特点是吸收快速（Tmax＜2小时）和超过6小时的血浆半衰期，支持每日一次口服给药。在研究的所有剂量水平中，根据RECIST v1.1标准报告了5例（n=5）达到疾病稳定（SD）的病例。这些患者中的大多数已经接受过至少5线的治疗，并伴有广泛的转移。血浆核苷浓度，即dCK的底物，提供了令人信服的靶标参与的证据（p<0.0001）。BSG005：公布1期临床试验数据Biosergen公司公布了其用于治疗毛霉菌病的候选药物BSG005的积极1期临床试验结果。毛霉菌病，也称为黑真菌病，是一种持续性且难以治疗的全身性真菌感染，死亡率高，因此迫切需要新的有效和安全的抗真菌疗法。BSG005是一种抗真菌化合物，此前已在毒理学研究中证明了安全性。此次双盲、安慰剂对照的1期临床试验结果显示，BSG005的安全性和耐受性良好，没有报告严重的不良事件，也没有关于肾脏和肝脏的负面安全信号。CT1812：IND申请获得FDA许可CT1812是Cognition Therapeutics公司开发的一种旨在穿透血脑屏障和血视网膜屏障的口服小分子，能够选择性地结合σ-2受体复合物，有望治疗干性年龄相关性黄斑变性（AMD）引起的地图样萎缩（GA）。σ-2受体复合物参与了一些关键的细胞过程，例如膜运输和自噬的调节，这些过程会因与可溶性β淀粉样蛋白（Aβ）低聚物、氧化应激和其他应激源的毒性相互作用而受损。在干性AMD中，这些细胞过程的受损会导致视力下降，最终导致视力丧失。CT1812的早期概念验证研究表明，σ-2受体调节剂能在拯救敏感的视网膜色素上皮细胞（RPE）免受致病蛋白和氧化应激等应激源的损害中发挥作用，从而保护黄斑中的这一重要组成部分。GRC 54276：IND申请获得FDA许可GRC 54276是Glenmark Specialty公司开发的一种口服小分子造血祖细胞激酶1（HPK1）抑制剂。HPK1调节的功能几乎参与癌症免疫循环的每一步，使其成为免疫肿瘤学的一个有吸引力的靶点。通过抑制HPK1，GRC 54276旨在潜在地增强患者自身的免疫系统以对抗癌症。GRC 54276正在一项1/2期临床试验中作为单一疗法或与抗PD-（L）1疗法联用治疗患有晚期实体肿瘤和淋巴瘤的成人患者。迄今为止，已有16名患有各种类型晚期癌症的患者参加了这项在印度进行的研究，该公司计划在接下来的几个月中在印度以外展开研究。大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看）[1] Karolinska Development’s portfolio company Biosergen presents positive results from phase 1 study of drug candidate to treat systemic fungal infection. Retrieved March 17, 2023, from https://www.globenewswire.com/news-release/2023/03/13/2625991/0/en/Karolinska-Development-s-portfolio-company-Biosergen-presents-positive-results-from-phase-1-study-of-drug-candidate-to-treat-systemic-fungal-infection.html[2] 유틸렉스, 'VSIG4 항체' 고형암 1상 "국내 IND 승인". Retrieved March 17, 2023, from http://biospectator.com/view/news_view.php?varAtcId=18492[3] 13/03/2023 – AB Science today announces a case report from the initial stage of its Phase I/II study (AB18001) evaluating AB8939, a microtubule destabilizer, in patients with refractory and relapsed acute myeloid leukemia (AML). Retrieved March 17, 2023, from https://www.ab-science.com/ab-science-reports-a-first-complete-bone-marrow-response-in-a-relapsed-refractory-acute-myeloid-leukemia-patient-from-the-very-low-dose-arm-of-its-ab8939-phase-i-ii-clinical-trial-ab18001/[4] ALX Oncology and Quantum Leap Healthcare Collaborative™ Announce First Patient Dosed in the I-SPY-P1 TRIAL in Breast Cancer. Retrieved March 17, 2023, from https://ir.alxoncology.com/news-releases/news-release-details/alx-oncology-and-quantum-leap-healthcare-collaborativetm-0[5] Sapience Therapeutics Receives IND Clearance from FDA to Proceed with Phase 1-2 Study of ST316 in Patients with Solid Tumors. Retrieved March 17, 2023, from https://www.prnewswire.com/news-releases/sapience-therapeutics-receives-ind-clearance-from-fda-to-proceed-with-phase-1-2-study-of-st316-in-patients-with-solid-tumors-301771021.html[6] TScan Therapeutics Announces First Patient Dosed in Phase 1 Umbrella Clinical Trial Evaluating TSC-100 and TS-101 for the Treatment of Hematologic Malignancies. Retrieved March 17, 2023, from https://ir.tscan.com/news-releases/news-release-details/tscan-therapeutics-announces-first-patient-dosed-phase-1[7] Albumedix and Heartseed announce Recombumin® as a critical excipient in the manufacture of Heartseed's HS-001 investigational cell therapy as its first in-human trial commences. Retrieved March 17, 2023, from https://www.prnewswire.com/news-releases/albumedix-and-heartseed-announce-recombumin-as-a-critical-excipient-in-the-manufacture-of-heartseeds-hs-001-investigational-cell-therapy-as-its-first-in-human-trial-commences-301769974.html[8] ITM, Helmholtz Munich and University Hospital Münster Announce Start of Phase I Clinical Trial with Radiotherapeutic ITM-31 for Glioblastoma. Retrieved March 17, 2023, from https://www.itm-radiopharma.com/news/press-releases/press-releases-detail/ITM,_Helmholtz_Munich_and_University_Hospital_M%C3%BCnster_Announce_Start_of_Phase_I_Clinical_Trial_with_Radiotherapeutic_ITM-31_for_Glioblastoma-605/[9] Kiora Pharmaceuticals Announces the Acceptance of Three Abstracts at the 2023 ARVO Annual Meeting. Retrieved March 17, 2023, from https://www.newsfilecorp.com/release/157917[10] Dose Escalation Portion of Phase 1 Solid Tumors Trial Produces Favorable Results in Heavily Pretreated Solid Tumor Patients. Retrieved March 17, 2023, from https://www.globenewswire.com/news-release/2023/03/15/2627997/0/en/Dose-Escalation-Portion-of-Phase-1-Solid-Tumors-Trial-Produces-Favorable-Results-in-Heavily-Pretreated-Solid-Tumor-Patients.html[11] Syndax Pharmaceuticals Announces Two Publications in Nature of Data from the Phase 1 Portion of AUGMENT-101 in Acute Leukemia Patients. Retrieved March 17, 2023, from https://www.prnewswire.com/news-releases/syndax-pharmaceuticals-announces-two-publications-in-nature-of-data-from-the-phase-1-portion-of-augment-101-in-acute-leukemia-patients-301773322.html[12] ReCode Therapeutics Announces First Participants Dosed in a Phase 1 Healthy Volunteer Clinical Trial of Novel Disease-Modifying Genetic Medicine, RCT1100 for the Treatment of Primary Ciliary Dyskinesia. Retrieved March 17, 2023, from https://www.businesswire.com/news/home/20230315005163/en/[13] Cognition Therapeutics Announces Development Plans for Oral CT1812 in Geographic Atrophy Secondary to Dry AMD. Retrieved March 17, 2023, from https://ir.cogrx.com/news-releases/news-release-details/cognition-therapeutics-announces-development-plans-oral-ct1812[14] ORYZON announces First Patient In in FRIDA, a Phase Ib trial with iadademstat in relapsed/refractory FLT3-mutant acute myeloid leukemia patients. Retrieved March 17, 2023, from https://www.oryzon.com/en/news-events/news/oryzon-announces-first-patient-frida-phase-ib-trial-iadademstat-relapsedrefractory[15] Glenmark receives acceptance from U.S. FDA on its IND application for GRC 54276 to proceed with a Phase 1/2, first-in-human clinical study of the molecule for the treatment of patients with advanced solid tumors and lymphomas. Retrieved March 17, 2023, from https://www.prnewswire.com/news-releases/glenmark-receives-acceptance-from-us-fda-on-its-ind-application-for-grc-54276-to-proceed-with-a-phase-12-first-in-human-clinical-study-of-the-molecule-for-the-treatment-of-patients-with-advanced-solid-tumors-and-lymphomas-301774105.html[16] Clearmind Medicine Submits IND Application to FDA for its Proprietary CMND-100 Treating Alcohol Use Disorder. Retrieved March 17, 2023, from https://www.globenewswire.com/news-release/2023/03/16/2628683/0/en/Clearmind-Medicine-Submits-IND-Application-to-FDA-for-its-Proprietary-CMND-100-Treating-Alcohol-Use-Disorder.html[17] Purple Biotech Reports Biomarker Data from CM24 Phase 1 Dose Escalation Study. Retrieved March 17, 2023, from https://www.globenewswire.com/news-release/2023/03/16/2628495/0/en/Purple-Biotech-Reports-Biomarker-Data-from-CM24-Phase-1-Dose-Escalation-Study.html[18] Arbutus Doses First Subject in Phase 1 Clinical Trial with its Oral RNA Destabilizer, AB-161. Retrieved March 17, 2023, from https://investor.arbutusbio.com/news-releases/news-release-details/arbutus-doses-first-subject-phase-1-clinical-trial-its-oral-rna[19] Pyxis Oncology Announces Dosing of First Subject in Phase 1 Trial of PYX-201, a Novel ADC for Solid Tumors. Retrieved March 17, 2023, from https://ir.pyxisoncology.com/news-releases/news-release-details/pyxis-oncology-announces-dosing-first-subject-phase-1-trial-pyx[20] Matrivax Initiates Phase 1 Clinical Development of MVX01, a Novel Pneumococcal Vaccine Candidate. Retrieved March 17, 2023, from https://www.businesswire.com/news/home/20230316005723/en[21] Anaveon announces first patient dosed with ANV419 in a Phase I/II Study of ANV419 in patients with multiple myeloma. Retrieved March 17, 2023, from https://anaveon.com/anaveon-announces-first-patient-dosed-with-anv419-in-a-phase-i-ii-study-of-anv419-in-patients-with-multiple-myeloma/[22] Alpine Immune Sciences to Present Povetacicept (ALPN-303) Phase 1 (RUBY-1) Study Data at the 2023 American Academy of Dermatology Annual Meeting. Retrieved March 17, 2023, from https://www.businesswire.com/news/home/20230316005751/en/免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

孤儿药临床结果快速通道

2022-11-10

·PipelineReview

Sensei Biotherapeutics Presents Preclinical Data at the 37th Society for Immunotherapy of Cancer (SITC) Annual Meeting

免疫疗法AACR会议临床研究

2022-11-10

·BioSpace

Sensei Biotherapeutics Presents Preclinical Data at the 37th Society for Immunotherapy of Cancer (SITC) Annual Meeting

- SNS-101, a highly pH-selective antibody to VISTA, demonstrated anti-tumor effects and promising pharmacokinetic properties in preclinical studies - - Characterization of endogenous expression patterns, and identification of novel T-cell receptors, of VSIG4 enables advancement of SNS-102 program - BOSTON, Nov. 10, 2022 (GLOBE NEWSWIRE) -- Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients, today presented preclinical data for SNS-101, a conditionally active VISTA-blocking antibody, as well as characterization of VSIG4, an immune checkpoint targeted by Sensei’s discovery-stage SNS-102 program, at the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting. “The data presented at SITC add to the growing body of evidence that our TMAb™ platform is a potentially powerful approach for unlocking previously undruggable immune targets. With the advancement of SNS-101, we have a highly pH-selective antibody to VISTA, which is designed to be conditionally active within the tumor microenvironment,” said Robert Pierce, M.D., Chief R&D Officer at Sensei. “We have also made exciting progress in our SNS-102 program, with the functional characterization and identification of novel T-cell receptors that may play a role in VSIG4-mediated immunosuppression. We look forward to advancing both programs with an upcoming IND filing for SNS-101 and identification of a lead anti-VSIG4 antibody in 2023.” Presentation Highlights: Poster presentation titled, “SNS-101, a highly pH-selective VISTA:PSGL-1 inhibitory antibody, potentiates anti-PD-1 sensitivity, expands memory T-cells and enhances tumor infiltration of CD8 T-cells" Summary: Sensei has developed SNS-101, a conditionally active, human monoclonal IgG1 antibody specific for the protonated, active form of VISTA, which in preclinical studies has demonstrated the ability to disrupt the immunosuppressive VISTA:PSGL-1 interaction, avoid target-mediated drug disposition (TMDD) and mitigate potential cytokine release syndrome (CRS). SNS-101 did not bind to human or non-human primates (NHP) VISTA+ monocytes, neutrophils and natural killer cells in blood or other normal tissue compartments. SNS-101 induced significant expansion of naïve CD8 T-cells and memory CD4 and CD8 T-cells in vivo without activation or depletion of monocytes. SNS-101 exhibited linear elimination kinetics in non-human primates, overcoming TMDD-induced pharmacokinetic limitations observed with other anti-VISTA antibodies. In an MC-38 syngeneic tumor model, SNS-101 demonstrated significant enhancement of anti-tumor effects in combination with anti-PD-1 antibodies and a dose-dependent increase in CD8+ T-cells. IND filing for SNS-101 is anticipated in the first half of 2023. Poster presentation titled, “Functional characterization of the inhibitory activity and identification of novel T-cell receptors for the tumor-associated macrophage receptor VSIG4” Summary: Sensei characterized endogenous expression patterns of VSIG4 in polarized macrophage populations and showed a robust VSIG4-mediated suppression of primary human T-cells. Additionally, a ligand receptor capture-trifunctional chemoproteomic (LRC-TriCEPS)-based proteomics strategy identified receptors on primary human T-cells that interact with recombinant VSIG4 protein. Primary monocytes were purified from peripheral blood mononuclear cells and differentiated into macrophages. Multiplexed droplet digital PCR analysis revealed a robust induction of gene expression of VSIG4 following multiple immunosuppressive stimulations. Development of multiple functional assays demonstrated VSIG4-mediated suppression of primary human CD4 T-cells. Through the LRC-TriCEPS proteomics screen, a set of potentially novel T cell receptor candidates that interact with VSIG4 were identified. A Cas9/CRISPR-based target gene knockdown methodology will be implemented for validation of VSIG4-interacting T-cell receptor candidates. An initial set of pH-selective anti-VSIG4 antibodies have been identified and further optimization is ongoing to identify a lead antibody. A copy of the presentation materials will be added to the “Events & Presentations” section of the Company’s Investor Relations website at . About Sensei Biotherapeutics Sensei Biotherapeutics (NASDAQ: SNSE) is an immuno-oncology company focused on the discovery and development of next-generation therapeutics for cancer patients. Through its TMAb™ (Tumor Microenvironment Activated biologics) platform, Sensei develops conditionally active therapeutics designed to disable checkpoints and other immunosuppressive signals selectively in the tumor microenvironment to unleash T cells against tumors. Sensei’s lead investigational candidate is SNS-101, a conditionally active antibody designed to block the V-domain Ig suppressor of T cell activation (VISTA) checkpoint selectively within the low pH tumor microenvironment, where VISTA acts as a suppressor of T cells by binding the receptor PSGL-1. The company is also developing SNS-102, a conditional binding monoclonal antibody targeting V-Set and Immunoglobulin Domain Containing 4 (VSIG-4), as well as SNS-103, also a conditionally active monoclonal antibody targeting ecto-nucleoside triphosphate diphosphohydrolase-1 (ENTPDase1), also known as CD39. For more information, please visit , and follow the company on Twitter @SenseiBio and LinkedIn. Cautionary Note Regarding Forward-Looking Statements Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as “believe”, “designed to,” “expect”, “may”, “plan”, “potential”, “will”, and similar expressions, and are based on Sensei’s current beliefs and expectations. These forward-looking statements include expectations regarding the development of Sensei’s product candidates and platforms; the potential safety pro Sensei’s product candidates; the potential benefits of Sensei’s product candidates; the timing of selection of lead product candidates; and the timing of an IND submission to the FDA. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the development of therapeutic product candidates, such as the risk that any one or more of Sensei’s product candidates will not be successfully developed or commercialized; the risk of delay or cessation of any planned clinical trials of Sensei’s product candidates; the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies, including the preclinical studies described in this press release, will not be replicated or will not continue in ongoing or future studies or clinical trials involving Sensei’s product candidates; the risk that Sensei’s product candidates or procedures in connection with the administration thereof will not have the safety or efficacy pro we anticipate; risks associated with Sensei’s dependence on third-party suppliers and manufacturers, including sole source suppliers, over which we may not always have full control; risks regarding the accuracy of our estimates of expenses, capital requirements and needs for additional financing; and other risks and uncertainties that are described in Sensei’s Annual Report on Form 10-Q filed with the U.S. Securities and Exchange Commission (SEC) on November 8, 2022 and Sensei’s other Periodic Reports filed with the SEC. Any forward-looking statements speak only as of the date of this press release and are based on information available to Sensei as of the date of this release, and Sensei assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise. Investor Contact: Michael Biega Senior Director, Investor Relations Sensei Biotherapeutics mbiega@senseibio.com Media Contact: Chris Railey Ten Bridge Communications chris@tenbridgecommunications.com

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