Plasma Cell Neoplasms

Results from the dose-escalation portion of the Phase 1 clinical study of ISB 2001 in patients with heavily pretreated multiple myeloma to be presented at the 2025 ASCO Annual Meeting NEW YORK, May 5, 2025 /PRNewswire/ -- IGI, a global, fully integrated clinical-stage biotechnology company focused on developing multispecifics™ in oncology, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for ISB 2001. This important designation was granted for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least three prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. ISB 2001 is an investigational trispecific antibody therapeutic that targets BCMA and CD38 on myeloma cells and CD3 on T cells. ISB 2001 is currently being evaluated in a Phase 1 dose-expansion study. "A growing number of patients with multiple myeloma have been heavily pretreated, have exhausted currently approved therapies, and continue to face disease progression," said Cyril Konto, M.D., President and CEO of IGI. "At IGI, we have long recognized the urgent need for novel treatment options – particularly for patients who have already received first-generation bispecifics or CAR T-cell therapies. Our trispecific candidate is designed to enhance tumor targeting while reducing on-target, off-tumor toxicity. We are honored to receive this Fast Track designation and look forward to working closely with the FDA to advance our Multispecific™ T-cell engager, with the goal of delivering a first-in-class therapy for patients with relapsed or refractory multiple myeloma." IGI recently completed the dose-escalation portion of its Phase 1 clinical study in patients with heavily pretreated multiple myeloma. Initial study results, presented in an oral session at the American Society of Hematology (ASH) Annual Meeting in December 2024, demonstrated a high overall response rate (ORR) with durable responses and a favorable safety profile. Complete results from the dose-escalation portion will be presented in a rapid oral session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting on Monday, June 2, 2025. The FDA's Fast Track designation is designed to enable the development and expedite the review of drugs that treat serious conditions and address unmet medical needs, with the ultimate goal of getting important new drugs to patients earlier. A drug that receives Fast Track designation may be eligible for more frequent meetings and communications with the FDA and rolling review of any application for marketing approval. A drug receiving Fast Track designation also may be eligible for Priority Review if relevant criteria are met. ISB 2001 was previously granted Orphan Drug Designation by the FDA in July 2023. ASCO Rapid Oral Presentation Details: Session title: Phase 1, first-in-human study of ISB 2001: A BCMAxCD38xCD3-targeting trispecific antibody for patients with relapsed/refractory multiple myeloma (RRMM)—Dose escalation results. (Abstract # 7514) Session Name: Hematologic Malignancies—Plasma Cell Dyscrasia Date & Time: June 2, 2025, 8 AM – 9:30 AM CDT About ISB 2001 and Relapsed/Refractory Multiple Myeloma ISB 2001 is a first-in-class trispecific T-cell engager that targets BCMA and CD38 on myeloma cells and CD3 on T cells. Developed using IGI's proprietary BEAT® protein platform, ISB 2001 was engineered with two distinct binders against myeloma-associated antigens to enhance avidity, even at low target expression levels, while aiming to improve safety over first-generation bispecific antibodies. The dose-expansion portion of the ongoing Phase 1 trial in patients with RRMM (NCT05862012) is currently enrolling patients across 9 sites in the United States and Australia. Nearly all patients with relapsed or refractory multiple myeloma (RRMM) ultimately experience disease progression. With no cure currently available and limited treatment options once approved therapies are exhausted, there remains a significant unmet need. IGI is developing ISB 2001 to address this gap, specifically for patients who have previously received T-cell–directed therapies, including CAR T-cell treatments and bispecific antibodies. About IGI IGI is a global, fully integrated clinical-stage biotechnology company focused on developing innovative biologics in oncology. Headquartered in New York, NY, IGI is advancing a robust pipeline of novel, first-in-class multispecifics™ aimed at addressing complex diseases and treating patients holistically. Powered by its proprietary BEAT technology platform, IGI is committed to delivering breakthrough, curative therapies to improve and extend the lives of patients battling hematological malignancies and solid tumors. For more information, visit . SOURCE Ichnos Glenmark Innovation WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

作者｜大道至简2025年3月默沙东宣布，帕博利珠单抗（可瑞达®，Keytruda®， K药）皮下注射版预计于今年10月获批。这是继去年年底，2024年12月百时美施贵宝的皮下型纳武利尤单抗（欧狄沃®，Opdivo Qvantig®，O药）后，全球第二款上市的PD-1单抗皮下注射剂。通过皮下给药的方式，单抗的单次治疗时间从数小时压缩至几分钟，患者治疗时间缩短90%以上。然而，皮下注射面临严苛的“不可能三角”：高浓度（保证药效）、低体积（≤2mL）、低刺激性（耐受性良好），三者难以同时满足。本文将从这一技术困局展开探讨，剖析行业突破路径，解读其面临的未来挑战。  01  技术瓶颈皮下单抗的“先天枷锁”静脉注射单抗的局限性长期困扰着医患双方。以PD-1抑制剂为例，单次静脉输注平均给药时间约0.5-2小时，患者每月需多次往返医院，输液过程中护士需全程监控输液反应，占用大量医疗资源。此外，与静脉注射相关的不良反应（如静脉炎、过敏反应）等，降低了患者依从性；部分患者需植入输液港，治疗体验差且易引发感染。因此，如何缩短治疗时间、优化资源分配，改善患者体验成为当务之急。1.1 大分子与皮下组织限制大分子单抗体积大，由于皮下细胞外基质（ECM）的3D网状结构，难以穿透皮肤组织，药物扩散受到限制。而且传统生物制剂在皮下的注射体积需控制在2ml以内，若超过这个范围会出现疼痛、鼓包等现象。1.2 剂量与体积的“生死博弈”单抗药物的治疗剂量通常在数百毫克级别，而皮下注射的体积在2mL以内。以纳武利尤单抗为例，常规静脉制剂的规格为10mg/mL，每两周用量为480mg，若直接改为皮下注射，要达到同样用量，2ml的皮下制剂的规格至少要提升至240mg/mL，是静脉给药的24倍。1.3 高浓度制剂的“陷阱”高浓度的制剂粘度高，注射时可能产生注射疼痛和组织损伤。此外，药物浓度过高会导致聚集、降低疗效，并引发免疫原性。  02  破局之道从配方优化到递送革命2.1 透明质酸酶——突破皮肤“防线”的钥匙重组人透明质酸酶（rHuPH20）成为突破皮下屏障的"破壁者"。它作为一种糖苷内切酶，可暂时降解透明质酸，通过局部皮下注射，改变皮下组织通透性，使药物能够快速扩散至血液循环系统，避免传统皮下注射的体积限制，提升注射容积上限，而且这种降解是暂时性的，通常在24-48小时内恢复，不影响皮下原有结构和功能。目前，这项Enhanze®给药技术的所有者——Halozyme公司，已将其授权给罗氏、强生、辉瑞等，产品开发涵盖肿瘤、罕见病、传染性疾病等多个领域。临床研究显示，罗氏使用该技术将皮下注射型曲妥珠单抗注射液（Herceptin Hylecta®）注射时间从1小时缩短至2至5分钟，药代动力学特征和静脉注射相似。强生的达雷妥尤单抗（Darzalex Faspro®）皮下注射剂2020年上市后，美国市场静脉注射向皮下制剂的转换率高达85%，而且近几年销售快速增长。根据强生最新2024年的财报，达雷妥尤单抗年销售额首次突破百亿美元，达到116.7亿美元。2.2 多抗复方制剂：剂量分摊的“巧思”在赫赛汀®皮下制剂成功的基础上，2020年罗氏又推出了多抗复方制剂——Phesgo®（赫捷康®），将帕妥珠单抗（Perjeta）与曲妥珠单抗（Herceptin）复配，通过共享rHuPH20载体，实现两种单抗同步皮下注射。一项关键临床III期研究（FeDerIca）数据显示，Phesgo®在疗效和安全性方面与静脉注射帕妥珠单抗和曲妥珠单抗相当。此外，由于缩短了给药时间，在患者偏好调查中，85%的患者更喜欢使用Phesgo®。2.3 抗体工程的“精准改造”罗氏靶向IL-6的萨特利珠单抗(satralizumab，Enspryng®，安适平)采用“再循环抗体技术”，通过改造Fc段增强与新生儿Fc受体（FcRn）结合，使抗体在细胞内循环利用，减少靶点介导的清除，提升血药浓度稳定性。该药于2020年首次上市，规格为1ml:120 mg，以皮下注射的方式给药，用于治疗视神经脊髓炎谱系疾病（NMOSD）。2021年11月，全球首个皮下注射的PD-L1“纳米抗体”——恩沃利单抗（Envafolimab，恩维达®）获得我国国家药品监督管理局（NMPA）批准上市，用于治疗不可切除或转移性的微卫星高度不稳定（MSI-H）或错配修复基因缺陷型（dMMR）的成人晚期实体瘤患者。这款由康宁杰瑞自主研发的PD-L1单抗，采用单域抗体（sdAb）融合人可结晶片段（Fc）的结构设计，具有分子量小、免疫原性低、毒性低的特点，而且组织穿透力和稳定性高；采用皮下注射方式，在30秒内完成给药，提高了患者依从性和便利性。2.4 递送设备创新：让注射更“无感”随着皮下预充注射笔、微针贴片、可穿戴设备等的出现，让患者可以在家中、社区，乃至其他任何环境中，灵活、便捷地自行治疗，进一步缩短注射时间、降低疼痛程度，实现无痛注射给药。2021年8月，信达生物的皮下注射产品阿达木单抗注射液（苏立信®）在中国获批上市，其为预充针剂型，采用BD Hypak™针头技术和组氨酸缓冲体系减轻注射疼痛，用于类风湿关节炎、强直性脊柱炎、银屑病等治疗。2022年，赛诺菲与Enable Injection合作，采用其enFuse可穿戴药物递送系统开发CD38抗体Isatuximab（Sarclisa®）的皮下注射剂型，以改善多发性骨髓瘤患者的治疗体验，目前尚处在临床研究早期阶段。接下来，我们对全球代表性的皮下单抗产品做一个简单梳理，如下表。（*：暂未批准，此为默沙东预计时间。）从表中可以看出，从罗氏Herceptin Hylecta®到近期默沙东Keytruda SC®，皮下单抗技术经历了从"依赖外源辅助"到"自主结构优化"演进，同时注射时间从分钟级迈入秒级时代，最终实现"浓度-体积-耐受性"三角平衡的技术跃迁。  03  未来挑战从技术到生态不容忽视的风险3.1 免疫原性：皮下注射的“隐形地雷”皮下单次和重复给药后可能增加产生抗药抗体（ADA）的风险，ADA可加速药物清除、降低血药浓度，影响治疗蛋白的药代动力学和药效学，从而削弱疗效。例如，阿达木单抗皮下给药后28%患者产生ADA，而曲妥珠单抗皮下制剂的ADA发生率（16%）也高于静脉制剂。3.2 稳定性：高浓度药物的难题高浓度单抗制剂最突出的挑战是在制造、运输和储存过程中的稳定性问题，可能导致聚集、降解和变性。因此，如何保持制剂的长期稳定性，并确保其在不同条件下的有效性是一个关键问题。3.3 成本与高定价的矛盾皮下注射单抗涉及复杂制剂工艺，与常规静脉制剂相比研发、生产成本高15%-20%。尽管可以通过纳入医保提升可及性，但皮下制剂的高定价在一定程度上会限制基层推广。  写在最后  从“静脉”到“皮下”，这场分秒必争的革命，我们看到皮下单抗的“不可能三角”正被逐一击破。当皮下注射技术将癌症治疗，从医院逐步向家庭与社区延伸，我们看到的不仅是给药方式的革新，更是医疗本质的回归——让技术服务于人。然而，医药开发者需始终牢记：任何技术创新都不能以牺牲安全性为代价。唯有在浓度、体积与耐受性间找到最佳平衡点，才能真正实现“患者获益最大化”的终极目标。参考资料1. Opdivo Qvantig®.BMS.2024年12月.2.ENHANZE®drug delivery technology.halozyme.com.3.Phesgo®.Roche.2020年6月.4.Enspryng®.Roche.2020年8月.5.恩沃利单抗（恩维达®）.康宁杰瑞.6.官网或其他公开资料.共建Biomedical创新生态圈！如何加入BiG会员？

The first shards of human data on in vivo CAR-T cell therapy look promising, based on recent separate reports from two biotech companies’ academic-led studies in China. Last week, a Chinese startup called Genocury became the second company to share initial clinical data on a CAR-T treatment that doesn’t require a patient’s cells to be extracted from their body. Genocury said that an advanced large B cell lymphoma patient went into complete remission after one month of in vivo CAR-T therapy, and has remained in remission for over three months. Notably, the in vivo CAR-T therapy does not require lymphodepletion, a course of chemotherapy that conventional CAR-T therapies require before treatment and that comes with toxicities. “This is good news for the field and demonstrates the increasing momentum around in vivo CAR-T approaches,” said University of Pennsylvania CAR-T pioneer Bruce Levine, who isn’t involved in Genocury’s studies but is a scientific founder of another in vivo CAR-T company called Capstan. Last week’s results follow Belgian startup EsoBiotec’s announcement in January that a multiple myeloma patient who received the lowest dose of its in vivo CAR-T therapy had no detectable cancer cells in their bone marrow at one month, without any significant adverse events during treatment. That patient also did not receive prior lymphodepletion. The data from both companies come from investigator-initiated studies in China, which biotech startups have been leveraging more frequently to quickly generate early clinical data on their experimental treatments. EsoBiotec is working with Pregene Biopharma which, like Genocury, is based in Shenzhen. In March, AstraZeneca announced plans to acquire EsoBiotec for $425 million, plus additional payments. At least five groups have begun clinical trials for in vivo CAR cell therapies. Aside from EsoBiotec and Genocury, Myeloid Therapeutics, Interius BioTherapeutics and Umoja Biopharma are all studying experimental in vivo cell therapies in patients. In conventional CAR-T therapy, a patient’s cells are extracted, engineered, and then reinfused — a complex, expensive process that can take weeks to months. The therapy, while transformative for certain blood cancers, comes with safety risks from the lymphodepletion before treatment and immune overreaction (cytokine release syndrome and ICANS) afterwards. And so far, comparatively less complex “off-the-shelf” treatments using donor cells have yet to take off. Makers of in vivo cell therapy hope that their treatments can become a different kind of “off-the-shelf” option. Their therapies deliver genetic material to turn the patient’s immune cells into cancer-fighting ones directly in the body. The companies are using different technologies to deliver their treatments and are also going after a range of diseases. The delivery technologies fall into two camps: viral and non-viral. Researchers have more concerns around the potential risks of a virus-based therapy, including of secondary cancer, but it’s an older and more proven approach. Non-viral delivery is newer and more challenging, and fewer companies have reached clinical studies. It is unclear based on Genocury’s disclosures whether it is using a viral or non-viral approach. A photo on its website mentions both viral and non-viral methods, and the company could not be reached for comment. EsoBiotec is developing a lentiviral-based cell therapy that goes after BCMA, a well-known target for multiple myeloma. Interius, which expects to report clinical data later this year, and Umoja are likewise studying lentiviral-based therapies. Umoja, like Genocury, is developing a CD19-targeted CAR-T therapy for blood cancer, and it plans to study the treatment in autoimmune disease as well. AbbVie has an option to license that therapy, and in January the startup raised $100 million to jumpstart its clinical studies. Interius’ therapy targets another immune cell protein called CD20, and it’s studying its B cell cancer therapy in both Australia and Germany. The Philadelphia biotech’s therapy is meant to make both ​​CAR-T and NK cells directly in the body. On the other hand, Sid Mukherjee’s startup Myeloid is using mRNA delivered non-virally. It uses fatty acid envelopes called lipid nanoparticles — similar to what’s used in the Covid vaccines. However, as its name suggests, it’s targeting a type of immune cell called myeloid cells. It has two programs in the clinic going after solid tumors — an area of cancer that conventional CAR-T therapies have yet to crack.