Cobomarsen

来源：药渡撰文：雨巷少年    编辑：丸子众所周知，癌症是一个无法攻克的挑战，目前还没有特效药可以完全治愈。近年来，随着生物制药领域的发展，癌症治疗的研究方向逐渐转向RNA疗法，包括寡核苷酸药物和mRNA疫苗等。通常，常规治疗只会产生短暂的治疗效果，因为它们针对的是蛋白质而不是致病根源，而RNA疗法直接作用于致病靶基因或者靶mRNA，在基因水平上发挥治疗疾病的作用。RNA疗法具有治疗效率高、药物毒性小、特异性强和应用领域广等优点，在医学、生命科学等领域表现出巨大的前景。1RNA疗法及其研发现状目前，癌症治疗在世界范围内仍然是一个挑战。虽然通过手术切除肿瘤组织、化疗和放疗可以提高患者的总体生存期，但癌症的复发和转移是无法避免的。此外，化疗具有严重的不良反应，如全身毒性和多重耐药，这就需要开发新型有效的治疗药物。近年来，靶向肿瘤细胞内或细胞外蛋白质的小分子药物和抗体因其强大的抗肿瘤作用而越来越受欢迎。然而，它们针对转录因子和“不可成药”癌蛋白等靶点却显得束手无策，如RAS等。理论上，RNA疗法可以特异性靶向和沉默任何基因靶点。因此，在针对“不可成药”靶点无药可用的问题方面具有巨大优势。随着RNA技术的不断发展和改进，许多寡核苷酸药物和大分子RNA药物，如反义寡核苷酸(ASOs)、小干扰RNA (siRNAs)和mRNA疫苗已被批准上市(图1)。此外，越来越多的寡核苷酸药物(如ASOs、siRNAs和miRNAs)和mRNA药物正在全球范围内进入临床试验。目前RNA疗法已成为癌症治疗的潜在候选工具。图1.已上市的核酸药物2RNA疗法潜力赛道：寡核苷酸疗法寡核苷酸是由10-50个核苷酸组成的药物，包括ASOs、siRNA和microRNAs (miRNAs)。寡核苷酸可以通过与特定的DNA或RNA序列或蛋白质结合并干扰靶基因表达来治疗疾病。它们可以调节转录后水平，并有望靶向难以直接靶向的特殊靶点。因此，寡核苷酸被认为是继小分子药物和抗体之后的第三大类型药物。目前，ASOs、siRNAs和miRNAs是研究最广泛的治疗恶性肿瘤的寡核苷酸药物。1反义寡核苷酸（ASO）ASOs是通过化学合成的寡核苷酸，通常长度为1-30个核苷酸，遵循沃森-克里克碱基配对规则与RNA结合。ASOs的长度允许它们只能与一个靶RNA结合。因此，ASOs具有高度特异性和专一性。尽管前两种上市的ASO药物Fomivirsen和Mipomersen已经停产，但市场上仍有7种被批准用于医疗用途的ASO药物，用于治疗杜氏肌营养不良症(DMD)、脊髓性肌萎缩、家族性淀粉样蛋白多神经病、家族性乳糜少血症综合征等疾病（图1））。在过去数十年来，大量制药大厂布局ASO药物。目前，ASO在合成和配方以及分布和安全性方面取得了令人满意的进展已有多种ASOs药物开展临床试验（图2）。  图2.开展临床试验的ASO药物接下来介绍一些重点ASO药物：2.1.1 Oblimersen sodium (Genasense™, G3139)Oblimersen钠(Genasense™，G3139)是一种反义寡核苷酸，与Bcl-2 mRNA开放阅读框的前六个密码子杂交，导致Bcl-2 mRNA降解并诱导细胞凋亡。oblimersen联合化疗药物如卡铂、紫杉醇、多西他赛、伊立替康等治疗实体肿瘤已开展了较多临床试验。在I/II期试验中，转移性结直肠癌患者对oblimersen和前药伊立替康的联合耐受性良好；其中，1例患者出现部分缓解，另外10例患者病情稳定，持续2.5-10个月(NCT00004870)。此外，临床试验的安全性数据进一步支持oblimersen联合细胞毒性药物临床开发的可行性。2.1.2 BP1001BP1001是一种脂质体结合的反义寡核苷酸，旨在抑制生长因子受体结合蛋白-2 (Grb-2)的表达，Grb-2是癌细胞信号传导中的一种必要的癌蛋白。在I期临床研究(NCT01159028)中，BP1001作为单药治疗和与低剂量ala - c (LDAC)联合使用都具有良好的耐受性。2.1.3 OGX-011 (custirsen)OGX-011 (custirsen)是第二代反义聚集蛋白抑制剂。为了确定OGX-011的临床活性，一项随机II期研究多西他赛/强的松联合用药用于治疗转移性去势抵抗性前列腺癌患者。研究结果表明OGX-011和多西他赛治疗耐受性良好，且与生存率提高有关，因为OGX011可以通过增加肿瘤细胞对多西他赛的敏感性来增强肿瘤杀伤能力。因此，OGX-011也可能是去势抵抗性前列腺癌(CRPC)患者的一种新的治疗策略。2.1.4 OGX-427OGX-427 (Apatoren)是一种2 ' -甲氧基修饰的ASO，可抑制Hsp27的表达。热休克蛋白27 (Hsp27)是一种应激诱导的多功能伴侣，通过其增殖和抗凋亡功能促进癌症的发展。Hsp27参与内质网(ER)稳态，使用OGX-427敲除Hsp27可诱导内质网应激。在I期临床试验中，OGX-427在晚期癌症患者中的安全性显示，OGX-427在最高剂量(1000 mg)下耐受(NCT00487786)。2.1.5 AZD9150 (Danvatirsen, ISIS 481464)AZD9150 (danvatersen, ISIS 481464)， 2.5代ASO，是STAT3的特异性抑制剂。与2.0代和以前的ASOs相比，2.5代ASOs具有更高的亲和性和更强的内在效力。AZD9150可以特异性抑制STAT3并诱导多种白血病细胞系凋亡。此外，AZD9150还通过抑制内源性STAT3和STAT3靶基因，降低成神经细胞瘤细胞的致瘤性，增加细胞的化学敏感性。在两项I期临床研究(NCT01563302和NCT01839604)中，AZD9150单药治疗诱导了免疫介导的抗肿瘤反应，表明AZD9150联合免疫检查点抑制剂治疗有望增强抗肿瘤免疫效能。2.1.6 EZN-2968缺氧诱导因子-1 (HIF-1)是一种转录因子，在血管生成、存活、转移、耐药和葡萄糖代谢中起关键作用。研究表明，HIF-1高水平与实体瘤患者预后差、耐药有关。因此，HIF-1是癌症治疗的一个有吸引力的靶点。EZN-2968(RO7070179)是第三代ASO，专门针对HIF-1的一个亚基HIF-1α。EZN-2968在临床前模型中与HIF-1α 的mRNA杂交并阻断HIF-1α蛋白表达。EZN-2968在描述剂量和时间下耐受性良好，且大多数报告的毒性为1或2级，无意外毒性。2小干扰RNA（SiRNA）自RNA干扰技术(RNAi)的发现及其随后在哺乳动物细胞中基因敲除的应用以来，siRNA治疗取得了显著的进展，已成为治疗各种疾病的有力工具。作为一种非编码双链RNA (dsRNA)分子，siRNAs的长度只有18-25个碱基对。siRNA在转录后通过mRNA降解干扰具有互补核苷酸序列的特定基因的表达。迄今为止，已有四种siRNA药物(patisiran、givosiran、lumasiran和inclisiran)被批准上市，用于治疗TTR、急性肝性卟啉症、原发性高草酸尿症1型、高胆固醇血症。相较于传统药物，siRNA疗法具有以下几大优势：1、siRNA可以敲除直接或间接导致癌细胞异常增殖的基因。2、大量siRNA文库的可用，可以快速筛选和优化出对靶点具有高度选择性和特异性的SiRNA先导化合物。3、siRNA药物的合成和生产成本与抗体相比相对较低。4、优化的siRNA药物可以提供更方便的给药方案。这些优势有力地支持了siRNA作为治疗癌症关键的治疗工具之一的观点，推动更多siRNA药物进入临床试验（图3）。 图3.已进入临床阶段的SiRNA接下来介绍一些重点siRNA药物：2.2.1 CALAA-01CALAA-01是一种基于聚合物的纳米颗粒，含有靶向核糖核酸还原酶(RRM2) M2亚基的siRNA，是Calando制药公司于2008年筛选的第一种基于RNAi技术的实体肿瘤药物。I期临床试验表明，CALAA-01在静脉注射给药后很快在血液中被清除，并且清除与体重有关。2.2.2 Atu027另一种siRNA药物是Atu027，它被包裹在脂质纳米颗粒(LNP)中， 可以特异性靶向致癌靶点PKN3。临床试验结果表明，Atu027在晚期或转移性胰腺腺癌患者联合标准化疗药物吉西他滨(NCT00938574)时具有良好的安全性和活性。2.2.3 siG12D LODERsiG12D LODER是一种局部长效SiRNA递送系统，用于针对突变型的KRAS蛋白。一项I期研究显示siG12D LODE在胰腺癌患者中的良好的耐受性、安全性和有效性，并且无明显毒性。目前，siG12D LODER正在进行II期临床试验。这种siRNA药物为抑制KRAS在胰腺癌中的表达提供了另一种方法。2.2.4 DCR-MYCMYC癌基因家族，由C-MYC、MYCN和MYCL组成，其产物调控至少15%的全基因组转录，并参与许多实体肿瘤恶性肿瘤的生长。siRNA药物DCR-MYC由DiceRNA Pharma设计，是一种新型合成的稳定脂质颗粒悬浮液dsRNA，可靶向肝癌、实体瘤和多发性骨髓瘤中的MYC。I期研究表明，DCR-MYC可有效抑制实体瘤患者的肿瘤生长(NCT02110563)。2.2.5 NU-0129由于很多药物不能有效透过血脑屏障BBB，因此胶质母细胞瘤(GBM)一度被认为是最难治疗的癌症之一。NU-0129基于球形核酸类型，是一种靶向GBM癌基因Bcl2L12的siRNA药物，可穿越血脑屏障，可能是治疗GBM的新策略。在早期I期试验中，静脉注射NU-0129后，肿瘤组织中的Bcl2L12蛋白水平显著降低。3miRNA药物miRNA是内源性基因编码的一类小的非编码RNA，大小约为19-25个核苷酸，参与转录后基因表达的调控。通常情况下，一旦miRNAs与RISC结合形成基因沉默复合物miRISC，相对基因表达就会通过基于RISC的机制通过阻断翻译或切割mRNA，这与siRNA机制相类似。值得注意的是，虽然siRNA和miRNA都是非编码RNA，在基因沉默和调控方面的作用相似，但siRNA在特定位置与单个基因完全互补，而一个miRNA通常具有多个靶点，可以调节数百或数千个基因的表达。并且，一个基因可以被几种不同的miRNA调控。尽管大量资本涌入miRNA赛道，但由于安全性问题，许多miRNA药物大多被终止，没有候选药物进入III期临床试验（图4）。因此，解决miRNA药物的特异性问题可以提高miRNA在临床中应用价值。 图4.已进入临床试验的miRNA在过去的二十年中，miRNA与各种癌症之间的关系得到了广泛的研究。目前，基于miRNA的疗法有两种策略:miRNA模拟物和miRNA抑制剂，这取决于是否应该替换或下调miRNA以控制细胞中靶mRNA的数量。miRNA mimics是人工合成的双链寡核苷酸，可以过表达相应的内源性miRNA序列，模拟靶miRNA的功能，导致癌细胞增殖下调，从而促进mRNA抑制。与miRNA模拟物不同，miRNA抑制剂（Anti-miRNAs）为基于ASOs生成的互补单链RNA类似物，以靶向内源性miRNA。Anti-miRNAs可以特异性阻断与癌症发展相关的miRNAs的上调表达。2.3.1MRX34作为一种潜在的肿瘤抑制miRNA, miR-34a在干细胞和晚期肿瘤中表达匮乏。MRX34是一种可以与miR-34a模拟物结合的脂质纳米颗粒LNP。MRX34可以通过抑制非小细胞肺癌(NSCLC)小鼠模型中的DNA修复功能来增强放疗的效果。2.3.2  Cobomarsen (MRG-106)研究表明，miR-155血液系统恶性肿瘤中是一种被广泛研究的miRNA，它主要与淋巴瘤和白血病的不良预后相关。Cobomarsen (MRG-106)是一种miR-155的抑制剂，目前正在进行临床试验，研究发现Cobomarsen在体外可以抑制miR-155的下游靶点及其介导的信号通路，包括JAK/STAT、MAPK/ ERK和PI3K/AKT等。2.3.3 Remlarsen (MRG-201)Remlarsen (MRG-201)是一种 miR-29模拟物，目前正在对其进行研究，以确定它是否可以抑制瘢痕疙瘩中纤维性瘢痕组织的形成。一项研究发现miR-29高表达可调控STAT3信号通路，抑制子宫平滑肌瘤的增殖、侵袭和转移;因此，miR-29可能是治疗子宫平滑肌瘤的一个新靶点。3RNA疗法的递送策略目前，递送问题是RNA疗法的最大问题之一。特别是如何安全、高效和有针对性地递送RNA药物仍然是一个重大挑战。核酸药物稳定性差（核酸酶降解）、透膜性差（核酸药物高度负电性）。因此，合适的递送系统可以保护RNA结构不被降解，提高靶向能力，减少毒副作用。目前，RNA疗法主要有三种病毒递送载体:腺病毒(AdV)、腺相关病毒(AAV)和慢病毒。然而，病毒载体具有毒性问题，并且由于其炎症和免疫原性作用而对人类不安全，这限制了它们的临床转化。与病毒载体相比，非病毒载体具有更广泛的应用范围，并克服了成本高、免疫原性和毒性等问题。因此，相对安全的非病毒载体，如基于脂质的递送系统、基于聚合物的纳米颗粒和无机纳米颗粒正在迅速发展（图5）。 图5.已报道的核酸药物递送系统1脂质递送系统脂质递送系统，如胶束、脂质体和LNP。其中，LNPs是寡核苷酸药物和mRNA疫苗最广泛使用的非病毒传递系统之一，其优点包括易于生产，可生物降解，保护嵌入的RNA免受核酸酶RNAse的降解和肾脏清除，促进细胞摄取和内体逃逸。近年来LNP作为mRNA疫苗的递送载体受到了全球的关注，在有效保护mRNA并将其转运到细胞中发挥着关键作用。2聚合物递送系统聚合物是继脂类递送系统之后的第二大核酸递送载体。阳离子聚合物可与阴离子核酸形成稳定的复合物，为高效的核酸递送提供了一个多功能、可扩展和易于适应的平台，同时最大限度地减少免疫反应和细胞毒性。这些递送体系可以增加RNA进入细胞的效率，并提高药物稳定性。3无机纳米递送系统无机纳米载体因其稳定性高、生物相容性好、免疫原性低、量产性好等特点，为核酸药物有效递送肿瘤细胞提供了独特的平台，如金纳米颗粒、二氧化硅纳米颗粒、碳纳米管等。总的来说，病毒载体比非病毒传递系统更有效，但更具有免疫原性。非病毒基因载体是通用的、简单的、具有成本效益的和潜在的更安全的替代品，但可能缺乏足够的临床效果。因此，在选择RNA药物的递送载体时，需要考虑多方面的因素，选择最合适的给药载体，以达到最大的疗效和最小的副作用。4小结近年来，由于寡核苷酸药物和mRNA疫苗的成功商业化，在医药圈掀起了一波核酸药物的研发热潮。目前的RNA疗法在疾病诊断和治疗方面都发挥着重要作用。尽管RNA疗法取得了巨大的进展，但临床应用方面仍然面临多种挑战:药物靶点的确定、核酸药物的稳定性和递送问题。通常，靶点和给药途径的选择可以提高药物的疗效，同时减少正常组织的副作用，增加药物的安全性。随着研究人员对多种类型RNA功能的深入了解，有望诞生出具有更高稳定性和药物活性的RNA药物以及更好的核酸递送载体。我们相信，RNA疗法有望改变人类癌症治疗的格局，使更多癌症患者获益。参考文献1、Cancer statistics, 2021[J]. CA: Cancer J Clin. 2021;71(1):7.2、Research progress on non-protein-targeted drugs for cancer therapy. https://doi.org/10.1186/s13046-023-02635-y3、RNA-based drugs and vaccines[J]. Expert Rev Vaccines. 2015;14(2):253–63.4、Deliver the promise: RNAs as a new class of  molecular entities for therapy and vaccination[J]. Pharmacol Ther. 2022;230:107967.5、Current advances in RNA therapeutics for human diseases[J]. Int J Mol Sci. 2022;23(5):2736封面图来源：123rf2023年1月1日至今，~17笔中国新药出海交易横空出世，总金额高达上百亿美元！一时间，喜讯频传，令行业、企业和每一位同药振奋！曾经提出“百靶竞技，百炼创新，百家上市，百药争先”的药时代团队再一次真切感受到：中国新药研发正当时！中国新药出海正当时！中国新药BD正当时！在这个BD如火如荼的好时代里，企业对于BD的要求不断提高，如何与时俱进，学习最新BD知识，掌握最新BD技能，成为摆在每一位BD同药面前的一个实际而迫切的问题。为了帮助企业培养优秀的BD高级人才，为了帮助BD人才成长进步，药时代学苑全力打造创新药BD高级研讨会，致力于成为中国制药界ZUI有实力和活力的学习平台。药时代BD高阶研讨会火热报名中！

DUBLIN--( BUSINESS WIRE )--The "Cutaneous T-Cell Lymphoma - Pipeline Insight, 2022" clinical trials has been added to ResearchAndMarkets.com's offering. This "Cutaneous T-Cell Lymphoma - Pipeline Insight, 2022" report provides comprehensive insights about 25+ companies and 27+ pipeline drugs in Cutaneous T-Cell Lymphoma pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space. Geography Covered Global coverage Cutaneous T-Cell Lymphoma Understanding Cutaneous T-Cell Lymphoma: Overview Cutaneous T-cell lymphoma (CTCL) is a rare type of blood cancer. It begins in a type of white blood cell called the T-lymphocyte (T-cell). T-cells help prevent infections and other diseases. As odd as it sounds, most T-cells are found in our skin. That's because our skin is the first line of defense against disease. The surface of an adult's skin contains about 20 billion T-cells. That's nearly twice as many T-cells as found in other parts of the body. There are many types of CTCL. More than half the people who develop CTCL will have one of the following types: Mycosis fungoides or Sezary syndrome. Mycosis fungoides is the most common type of CTCL. This type tends to worsen very slowly. It can stay in its earliest stage, which often looks like rash, for years. In this stage, the cancer is often difficult to diagnose because it tends to looks like eczema or psoriasis. These conditions are much more common than CTCL. Sezary syndrome is more aggressive. It can also look like eczema. Some people develop red and swollen skin over much of their body. Their skin may feel hot, sore, and extremely itchy. Because CTCL is rare and often looks like eczema or another common skin disease, it can take time to get the diagnosis. Some people who have CTCL are referred to a dermatologist because it's thought that they have a stubborn case of eczema or psoriasis. This report outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the Cutaneous T-Cell Lymphoma pipeline landscape is provided which includes the disease overview and Cutaneous T-Cell Lymphoma treatment guidelines. The assessment part of the report embraces, in depth Cutaneous T-Cell Lymphoma commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Cutaneous T-Cell Lymphoma collaborations, licensing, mergers and acquisition, funding, designations and other product related details. Cutaneous T-Cell Lymphoma Emerging Drugs Chapters This segment of the Cutaneous T-Cell Lymphoma report encloses its detailed analysis of various drugs in different stages of clinical development, including phase II, I, preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases. Cutaneous T-Cell Lymphoma Emerging Drugs SGX301: Soligenix SGX301 is a novel first-in-class photodynamic therapy utilizing safe, visible light for activation. The active ingredient in SGX301 is synthetic hypericin, a potent photosensitizer that is topically applied to skin lesions, is taken up by the malignant T-cells, and then activated by fluorescent light 16 to 24 hours later. HyBryte (synthetic hypericin or SGX301) may provide a safer, more convenient alternative. It is a topical ointment which is applied to the lesions and then activated by safe visible fluorescent light. HyBryte is being tested as a photodynamic light therapy with an enhanced safety profile and a treatment regimen that may be completed in as little as 6 weeks. Its pivotal Phase III clinical study (the "FLASH" study) for CTCL has completed enrollment showing a statistically significant outcome after 6 weeks treatment (p=0.04) with continued improvement to 40% response rate after 12 weeks treatment (p< 0.0001). Lacutamab : Innate Pharma Lacutamab (IPH4102) is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody, which is currently in clinical trials for treatment of cutaneous T-cell lymphoma (CTCL), an orphan disease. This group of rare cutaneous lymphomas of T lymphocytes has a poor prognosis with few efficacious and safe therapeutic options at advanced stages. KIR3DL2 is an inhibitory receptor of the KIR family, expressed by approximately 65% of patients across all CTCL subtypes and expressed by up to 90% of patients with certain aggressive CTCL subtypes, in particular, Sezary syndrome. It is currently being evaluated in Phase II stage of development. BNZ-1: Bioniz BNZ-1 is a selective inhibitor of three members of the IL-2 family: IL-2, IL-9, and IL-15. The profile of BNZ-1 is promising as a long-term therapy capable of transforming the standard of care in CTCL as data implicates the dysregulation of IL-2/IL-9/IL-15 as responsible for disease pathology. Bioniz conducted a Phase I/II study in CTCL, in which BNZ-1 exhibited a substantial improvement in safety and efficacy relative to standard of care. BNZ-1 has orphan drug designation in US and EU. In February 2022, Equillium, Inc. announced that it has acquired Bioniz Therapeutics, Inc., a privately held clinical-stage biotechnology company. Bioniz developed its novel structured-domain peptides, including BNZ-1 and BNZ-2, entirely in-house from its proprietary product discovery platform. BNZ-1 is Phase II/III ready in CTCL with open U.S. INDs for each indication and has orphan designation for CTCL in the U.S. and Europe. Cutaneous T-Cell Lymphoma: Therapeutic Assessment This segment of the report provides insights about the different Cutaneous T-Cell Lymphoma drugs segregated based on following parameters that define the scope of the report, such as: Major Players in Cutaneous T-Cell Lymphoma There are approx. 25+ key companies which are developing the therapies for Cutaneous T-Cell Lymphoma. The companies which have their Cutaneous T-Cell Lymphoma drug candidates in the most advanced stage, i.e. Phase III include, Soligenix Phases The report covers around 27+ products under different phases of clinical development like Late stage products (Phase III) Mid-stage products (Phase II) Early-stage product (Phase I) along with the details of Pre-clinical and Discovery stage candidates Discontinued & Inactive candidates Route of Administration Cutaneous T-Cell Lymphoma pipeline report provides the therapeutic assessment of the pipeline drugs by the Route of Administration. Products have been categorized under various ROAs such as Intra-articular Intraocular Intrathecal Intravenous Ophthalmic Oral Parenteral Subcutaneous Topical Transdermal Molecule Type Products have been categorized under various Molecule types such as Oligonucleotide Peptide Small molecule Product Type Drugs have been categorized under various product types like Mono, Combination and Mono/Combination. Cutaneous T-Cell Lymphoma: Pipeline Development Activities The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses Cutaneous T-Cell Lymphoma therapeutic drugs key players involved in developing key drugs. Pipeline Development Activities The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging Cutaneous T-Cell Lymphoma drugs. Cutaneous T-Cell Lymphoma Report Insights Cutaneous T-Cell Lymphoma Pipeline Analysis Therapeutic Assessment Unmet Needs Impact of Drugs Cutaneous T-Cell Lymphoma Report Assessment Pipeline Product Profiles Therapeutic Assessment Pipeline Assessment Inactive drugs assessment Unmet Needs Key Players Soligenix Elorac Innate Pharma Viridian Therapeutics Sorrento Therapeutics Bio-Path Holdings Legend Biotech Genzada Pharmaceuticals VidacPharma Bioniz Therapeutics Otsuka Pharmaceutical Hoffmann-La Roche BioInvent International AB Scopus BioPharma Codiak BioSciences Merck Sharp & Dohme LLC Otsuka Pharmaceutical Co., Ltd. Myeloid Therapeutics Jiangsu Simcere Pharmaceutical miRagen Therapeutics Kymera Therapeutics Citius Pharmaceuticals 4SC Equillium Key Products SGX301 BNZ-1 Lacutamab ExoIL-12 BP1002 MRG-106 BBI-3000 WP1220 Tucidinostat IPH4102 Resiquimod VDA-1102 Resminostat Pembrolizumab ASTX660 KT-333 MT-101 SIM1811-03 Cobomarsen LB1901 EQ101 For more information about this clinical trials report visit https://www.researchandmarkets.com/r/uspzvl About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.