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汉腾生物与韩国IMBiologics达成战略合作

汉腾生物与韩国IMBiologics达成战略合作中国融媒产业网2023年10月25日 16:09:00 来自北京市0人参与0评论2023 年 10 月 23 日,汉腾生物宣布与韩国IMBiologics签署战略合作协议。双方将在lgM分子开发与表达平台方面展开战略合作,包括但不限于联合营销/联合业务开发、CDMO项目、Licenses in/out等。本次合作基于汉腾生物高产量、高纯度和高效价的lgMax®平台技术与IMBiologics的ePENDY®平台技术。汉腾生物将与IMBiologics携手,共同为推动中韩两国及全球生物医药的高质量发展贡献力量。IMBiologics 创始人/CEO Dr. HA GYONGSIK(左)与 汉腾生物创始人/CEO沈潇博士(右)作为双方代表签订合作协议汉腾生物CEO 沈潇 博士“很高兴能有机会与IMBiologics合作。‘ePENDY’是一项创新的技术,在免疫调节的创新药物开发上有着独到的优势。汉腾将利用自身的lgMax®平台技术协助‘ePENDY’平台分子的CMC开发,实现规模化生产,同时,期待双方能在IgM领域共同协作,在不久的将来利用新型抗体平台技术造福全球患者。”IMBiologics CEODr. HA GYONGSIK“我们很高兴能与汉腾生物合作。这次合作是我们公司‘ePENDY’平台技术的首次全球合作,也代表着市场对‘ePENDY’平台技术卓越性的认可。通过这一合作,许多中国的公司将能够使用IMBiologics的‘ePENDY’开发新的药物。我们将这次合作视为进入中国和全球市场的第一步,期待未来能与更多公司建立合作关系。”关于lgMax®平台lgMax®平台是汉腾生物自主研发的IgM相关表达及开发平台,其具备了高产量、高纯度和高效价的特点,技术转移路线清晰,可满足大规模生产的需求。该平台已成功助力客户lgM抗体开发项目获批IND。高表达lgM载体通过特殊设计的载体系统,细胞株产量可达8 g/L ,并且lgM构型均一,五聚体比例接近100%,无六聚体产生,从源头避免后续六聚体难去除风险lgM工艺开发能力下游纯化包含亲和层析和非亲和层析两种纯化路线,均可达到97%以上纯度,回收率达到>55%,让工艺成本及效益达到较理想的状态lgM理化分析能力汉腾生物已完成了五聚体和六聚体超大型蛋白分子的全面质量分析和表征工作。成功完成lgM聚集体构型、轻链重链J链完整性、98对二硫键、2个游离巯基,51个N-糖位点和各N-糖位点优势糖型等全面属性揭示,大大加快了lgM在生物制药领域的应用进度lgM生化分析能力汉腾生物可通过ELISA结合、假病毒体外中和试验和SPR技术等方法评估lgM活性及综合效力lgM制剂开发能力汉腾生物的制剂平台可以为IgM抗体提供稳定的可长期保存的液体或冻干制剂开发关于ePENDY®平台IMBiologics作为韩国唯一的IgM抗体研发公司,开发了下一代的IgM分子构型(已获专利授权):ePENDY®平台与全球领先的IGM bioscience的IgM平台对比,具有 :-更高的生物活性-更长的半衰期-更简单的下游工艺-显著改善的疗效-更小的副作用适应症可扩展范围广-扩展了开发免疫疗法各种激动剂和拮抗剂候选药物的可能性-适应症可以扩展到眼科疾病、传染病和粘膜免疫相关疾病市场价值-全球大型制药公司高度感兴趣:赛诺菲和IGM Bioscience签订了价值60亿美元的合同(2022.03)关于韩国IMBiologicsIMBiologics 是一家成立于2020年8月的生物技术公司,致力于研究基于免疫调节的创新药物。IMBiologics在2021年1月以4亿韩元的种子基金启动了研发旅程,并于2021年8月进行了13亿韩元的A轮融资,及在2023年7月成功进行了20亿韩元的B轮融资。B轮融资将用于确保IMB-101的全球临床试验结果,扩展其他适应症,并利用下一代IgM平台技术ePENDY开发肿瘤免疫产品线。IMB-101所靶向的OX40/OX40L抑制信号最近在自身免疫性疾病中引起了新的关注,而ePENDY的亲和力和靶蛋白聚集效应比IgG抗体更高。IMBiologics解释说,他们目前正在寻找潜在的合作伙伴来推广IMB-101,并通过与多家全球制药公司进行商务会议来努力建立合作关系。关于汉腾生物广州汉腾生物科技有限公司(简称“汉腾生物”)自2016年成立以来,专注于大分子生物药CDMSO领域,包括抗体优化、细胞株构建及开发、上下游工艺开发、分析方法开发、制剂工艺开发、技术及质检方法转移、中试及商业化生产、临床生物分析,临床供应服务,以及国际一流的质量保障体系等,面向全球生物医药企业提供符合国际监管标准、覆盖从早期发现到商业化的一站式服务。创新是企业发展的核心竞争力。注重研发投入,提升自主研发的能力是汉腾生物多年来坚持的目标。汉腾生物擅长于研究难以表达的蛋白质,包括双抗特异性抗体(BsAb)和重组蛋白;在细胞系的驯化,优化和开发方面,拥有行业领先的知识、专利技术储备以及丰富的项目技术经验,尤其是自主开发的高表达CHO细胞株构建平台,抗体表达滴度高,工艺稳定,包括了CHOzen®细胞系平台和GLYCOEXPRESS® (GEX®)细胞系平台等。经过多年科研技术的转化,汉腾生物发展欣欣向荣,规模已从广州总部扩大至全球六大研发及生产基地,科学家团队约300余人,研发人员中硕博士占比达60%以上;技术服务方面,目前拥有符合中、美、欧GMP标准的12+4条独立生产线,具备50-2500L(批次、流加、灌流、环轨)的原液及商业化制剂灌装生产能力。

2023-10-31

金斯瑞蓬勃生物祝贺IMBiologics双抗项目IMB-101获FDA临床试验批准

做更好的财经信息平台下载金斯瑞蓬勃生物祝贺IMBiologics双抗项目IMB-101获FDA临床试验批准蓝鲸财经 09-12 15:31一键收听（预计播放4分30秒）金斯瑞生物科技+3.15%近期，金斯瑞蓬勃生物的合作伙伴IMBiologics宣布其创新双特异性抗体药物项目（IMB-101）获得FDA 的临床试验批准。在此项目中，金斯瑞蓬勃生物负责CMC开发，并提供IND申报资料的撰写和支持。金斯瑞蓬勃生物对此项目的重要里程碑达成表示热烈祝贺。IMB-101是一种靶向OX40L和TNF的双特异性抗体，调节参与炎症细胞因子和获得性免疫的免疫细胞，开发该药物用于治疗自身免疫性疾病。金斯瑞蓬勃生物成功解决了该项目中技术转移的挑战，建立了一个稳健的细胞培养和纯化工艺体系。该工艺仅经过一次试验就成功地扩大到200升和500升的规模，展示了其可靠性。此外，达到的产量比原先的工艺显著提高了33%。在猴模型试验中，与"Humira"相比，IMB-101剂量较低时在抑制关节炎方面显示出相当或更好的疗效，并在猴模型的13周重复给药毒性试验中确认了药物的安全性。IMB-101可以成为对抗TNF药物治疗无反应患者的有效的新型治疗选择。FDA临床试验批准后，IMBiologics将从2023年下半年开始在美国进行IMB-101的一期临床试验。一期临床试验将使用安慰剂作为对照，评估健康受试者和类风湿性关节炎患者在单次和多次剂量下IMB-101的安全性、耐受性并进行药代动力学和药效学研究。IMBiologics的开发部门负责人Park Chi-hye,表示："这种免疫调节抗体候选药物可以克服现有治疗的低反应率的问题，这是类风湿性关节炎患者急需解决的重要医疗需求。在临床前研究中，IMB-101的优异疗效和安全性为其提供了宽广的安全边界。FDA的临床试验批准以及与金斯瑞蓬勃生物的专业团队的合作，我们对推进IMB-101的全球临床发展充满信心。"金斯瑞蓬勃生物董事长兼代理首席执行官柳振宇博士表示："我们对IMBiologics的创新双特异性抗体药物项目IMB-101获得FDA批准临床试验感到非常高兴。该项目的获批证明了我们卓越的工艺开发能力，我相信这款产品将在未来造福类风湿性关节炎患者，我们将继续与IMBiologics团队紧密合作推进临床试验。"关于IMBiologics IMBiologics 是一家成立于2020年8月的生物技术公司，致力于研究基于免疫调节的创新药物。IMBiologics在2021年1月以4亿韩元的种子基金启动了研发旅程，并于2021年8月进行了13亿韩元的A轮融资，及在2023年7月成功进行了20亿韩元的B轮融资。B轮融资将用于确保IMB-101的全球临床试验结果，扩展其他适应症，并利用下一代IgM平台技术ePENDY开发肿瘤免疫产品线。IMB-101所靶向的OX40/OX40L抑制信号最近在自身免疫性疾病中引起了新的关注，而ePENDY的亲和力和靶蛋白聚集效应比igg抗体更高。IMBiologics解释说，他们目前正在寻找潜在的合作伙伴来推广IMB-101，并通过与多家全球制药公司进行商务会议来努力建立合作关系。

2023-10-31

IMBiologics, ‘Bispecific Antibody’ approved for phase 1 in the US, entering the second half of the year.

For more information, please visit : IMBiologics News (full article available in Korean)

2023-08-01

IMBiologics successfully closes series B financing round with 20B KRW

For more information, please visit : IMBiologics News (full article available in Korean)

2023-07-26

IMBiologics, 'OX40LxTNF' biospecific antibody " US FDA IND submission"

For more information, please visit : IMBiologics News (full article available in Korean)

2023-07-26

Nature magazine publicity release of IMB-101 project supported by KDDF

nature  biopharma dealmakers  advertisement feature  articleADVERTISEMENT FEATURE Advertiser retains sole responsibility for the content of this articleKDDF: bringing next-generation immunotherapies to global marketsAs a government funder, the Korea Drug Development Fund (KDDF) invests in promising selected compounds by taking them through assessment and translating them into cutting-edge science for patient benefits and market opportunities.Korea Drug Development FundProduced by Twitter Facebook EmailThe Korea Drug Development Fund (KDDF), a national consortium of three government ministries, is the largest public funder of drug research and development (R&D) in Korea. With a $1.5 billion 10-year budget, KDDF invests more than $150 million a year in over 100 promising projects from academia, biotech, and pharmaceutical companies, spanning the whole R&D process from discovery to clinical trials.KDDF actively seeks opportunities for co-development and other partnerships with global pharma companies on behalf of Korean biopharma companies to maximize the potential of their assets, and presents three companies with innovative drugs in the immunotherapeutics space working towards these goals.KDDF’s therapeutic pipeline as of December 2022.IMBiologicsIMBiologics develops innovative new drugs based on immunomodulation and platform technologies. The company concentrates research resources on a two-track strategy: one involves IMB-101, a first-in-class bispecific antibody against tumor necrosis factor-α (TNF-α) and the OX40 receptor ligand (OX40L) that is being developed for the treatment of autoimmune diseases including RA; and the other is a fully proprietary next-generation immunoglobulin M (IgM) platform technology, Enhanced & Engineered Pentamer Body (ePendy).IMB-101 reduces inflammatory cytokines through inhibition of TNF-α and also normalizes over-active effector immune cells by blocking OX40L to manage chronic inflammation and restore immune balance. IMB-101 has shown superior efficacy compared with TNF-α or OX40L monoclonal antibodies in a collagen-induced arthritis monkey model, even at a quarter molar dose of Humira (adalimumab), and shows robust efficacy without paradoxical reactions that exacerbate inflammation, which are sometimes seen with other biologics. Additionally, IMB-101 reduces osteoclastogenesis, autoantibodies and systemic exposure to TNF antibodies because of localization at the inflammation site.

2022-12-05

IMBiologics, MOU with Dong-A ST to discover drugs for ‘IgM platform’

For more information, please visit : IMBiologics News (full article available in Korean)

2022-12-05

(August 30, 2022) IMBiologics unveils next-generation IgM platform aiming new concept of immune cell engager

IMBiologics unveils next-generation IgM platform aiming new concept of immune cell engagerby Sungmin KimDevelopment strategy and positioning of ‘OX40LxTNF-α bispecific antibody.’..What are the 5 differentiating points of the ‘IgM platform’ and it's applications in anti-cancer?▲GyongSik Ha, CEO of IMBiologicsIMBiologics is seeking a change different from the past as it unveils an IgM-based antibody platform after two years of establishment. Most antibody platforms are based on IgG, and even in the global market, platform development using IgM antibodies is not common. An IgG antibody has two antigen-binding sites, whereas an IgM antibody has about 10 ~ 12. Globally, only IGM Biosciences, which entered a partnership deal with Sanofi in March this year, is known as a company with an IgM antibody platform.In the midst of this, in April of this year, IMBiologics completed a patent application for 'ePENDY' technology, a long-acting multivalent antibody platform that overcomes the limitations of existing IgM antibodies in terms of new drug development, and appeared in the industry. It is throwing a fresh keyword of the next-generation IgM multi-antibody platform to the domestic industry.Until now, IMBiologics has been known only as a company established when HK inno.N (formerly CJ Healthcare) introduced the OX40LxTNF-α bispecific antibody ‘IMB-101’, which is an autoimmune disease target. But now, it is showing an upgraded aspect. IMBiologics is a company that researchers, who have been leading the preclinical development process from the idea of autoimmune disease bispecific antibody asset since the old CJ Healthcare days, started with a willingness to continue clinical development.IMBiologics was established in August 2020 and started in earnest three months later when it licensed the global development and exclusive license of IMB-101 from HK inno.N. It is an independent form without capital participation of HK inno.N.GyongSik Ha, CEO of IMBiologics, said, "At the time of establishment, we thought that one asset alone would not have the possibility of sustainable growth of the company, so we needed an asset that we develop ourselves. We needed to study the platform related to antibodies, and we thought it would be advantageous to build a platform with IgM antibodies while thinking about vaccines." "We have implemented a platform that has been only an idea for the past two years and have finally completed a patent application for ePENDY technology this year."The clinical start of IMB-101, the lead program next year, is also expected. After introducing the OX40LxTNF-α bispecific antibody ‘IMB-101’, IMBiologics is finishing the study (IND-enabling study) for the submission of the clinical trial protocol. In the first half of next year, IMB-101 is planned to be submitted an IND to the US Food and Drug Administration (FDA). As the platform and tasks have been sophisticated, the R&D manpower of the company, which was established with five researchers from CJ Healthcare, increased to 23.The headquarters and research center of IMBiologics is located in Gwanggyo, Gyeonggi-do, and since its establishment, it has secured a total investment of 17 billion won, including seed investment (4 billion won) and Series A (13 billion won). The lead program, IMB-101 dual antibody, was selected as a project for the Korea Drug Development Fund (KDDF) in March this year and will receive a total project cost of KRW 2 billion (KRW 1.5 billion from the project group) until approval for phase 1 clinical trials.What is the positioning of the OX40LxTNF-α bispecific antibody strategy?OX40 is a co-stimulatory immune checkpoint molecule that activates immunity as one of the tumor necrosis factor (TNF) receptor family. During the boom in immuno-oncology, OX40/OX40L signaling was developed focusing on immune activation factors, but no clear efficacy results were obtained. Rather, drugs that inhibit it are a target that has recently been highlighted as it has produced positive results in autoimmune diseases.Large deals followed in the last year alone. In January last year, Sanofi acquired Kymab for $1.45 billion, including upfront fee of $1.1 billion, to secure 'KY1005 (SAR445229)', an OX40 ligand (OX40L) antibody which is developed as an autoimmune disease treatment under a phase 2 clinical stage. In June, Amgen also followed Sanofi and entered the OX40/OX40L competition. Amgen purchased the OX40 antibody 'Rocatinlimab (KHK4080)' from its long-time partner, Japan's Kyowa Kirin, for a total of $1.25 billion, including upfront fee of $400 million, and is leading the way in phase 3 clinical trials. The remaining clinical development asset is Ichnos Sciences' OX40 antibody 'Telazorlimab (ISB 830; GBR 830)' of the US.▲OX40 clinical asset development status, Source: BioSpectatorMeanwhile, IMBiologics is positioning it as a drug targeting rheumatoid arthritis (RA), based on the unique mechanism of the OX40LxTNF-α bispecific antibody.First of all, the IMB-101 task began by looking at the possibility of OX40L as a treatment target in autoimmune diseases. It has seen the possibilities in three main aspects. First, OX40/OX40L signal transmission may activate immunity in various aspects. Specifically, OX40 is not expressed in naive T-cells, but is a factor that stimulates them by expressing them as they are activated. At the same time, OX40L is expressed in antigen-presenting cells (APCs) such as B cells and dendritic cells (DCs) to stimulate them.Second, OX40L expressed by APC plays a role in balancing T cells and regulatory T cells (Treg). At that moment, unlike T cells, OX40L plays a role in inhibiting the activity of Treg, which inhibits excessive immunity in autoimmune diseases. It is observed that Treg has decreased in the lesions of patients with autoimmune diseases. Third, recent studies have shown that OX40L signaling activation is involved in autoantibody production.In addition, OX40/OX40L signaling overexpression is observed in several autoimmune diseases, and expression increases with disease progression in rheumatoid arthritis and systemic erythematous loops (SLE).On top of that, IMBiologics chose a strategy that inhibits OX40L while also inhibiting TNF-α at the same time. OX40/OX40L signaling is known to have a comprehensive effect on Th1, Th2, and Th17 in autoimmune diseases, and TNF-α is selected to enhance signal targets that can enhance Th1 and Th17 inhibitory efficacy.CEO Ha said, "Allergy diseases such as asthma and atopic dermatitis are mainly related to Th2, and based on the clinical results of oxelumab from asthma patient population, OX40/OX40L target was judged to be more suitable for autoimmune diseases involving Th1 or Th17. By adding TNF-α inhibitory ability, IMB-101 has set its target indication as rheumatoid arthritis, a typical Th1-related disease, and plans to expand its indications in the future.”Another advantage is expected. While inhibiting TNF-α, an innate inflammatory cytokine that has been proven effective in rheumatoid arthritis patients, it can regulate the overall immune response while inhibiting OX40L, which is important for the adaptive immune response. CEO Ha said, “Currently, most drugs targeting rheumatoid arthritis are focused on controlling specific cytokines, but there are 12 types of immune cells and 30 types of cytokines involved in autoimmune diseases.” “If both factors are targeted simultaneously using a bispecific antibody, the efficacy can be improved, and we expect that the impaired immune balance will be restored in the long term,” he added.IMB-101 is a '2+2' form in which two TNF-α inhibitory scFvs are bound to an antibody that inhibits OX40L. Each signal transduction is inhibited, and there is no antibody-dependent cytotoxicity (ADCC) function using an IgG4 antibody. The TNF-α binding site exhibits a similar level of inhibitory activity to that of Humira. When designing various types of bispecific antibodies, the most suitable form was determined in consideration of the inhibitory ability, physical properties, and half-life of each target.Differentiation is expected regarding the mechanism and efficacy of the OX40L inhibitory site. IMB-101 has a different mechanism of inhibiting OX40L compared to Kymab's KY1005. According to epitope mapping, IMB-101 inhibits the OX40/OX40L interaction, whereas KY1005 acts in a manner that prevents the formation of OX40L trimer. In addition, in the in vitro assay, IMB-101 had higher efficacy in inhibiting solubility and inhibiting its membrane OX40L compared to KY1005.In terms of safety, it is judged that there is an advantage over OX40 drug. CEO Ha said, “We judged that OX40 inhibitors inhibit T cells, which may cause long-term safety issues, so inhibiting OX40L seemed advantageous. On the other hand, OX40 manifests itself in both blood and tissues, affecting systemic immune control. At the same time, OX40L has the advantage of being able to specifically target lesions as it is mainly expressed high in inflammatory tissues.”The rheumatoid arthritis treatment market targeted by IMBiologics uses chemically synthesized antirheumatic drugs (DMARDs) such as methotrexate (MTX) as the first treatment, and then prescribes biological antirheumatic drugs (bDMARDs) from the second treatment. At this time, the biopharmaceutical market is formed around TNF-α drugs such as Humira, and after that, other TNF-α drugs are prescribed to patients who do not comply. Recently, oral JAK inhibitors have been released as a target specific treatment (tsDMARDs) option, but side effects such as cardiovascular (CV) and carcinogenesis continue to be an issue.Still, the unmet needs of the rheumatoid arthritis treatment market lack effective treatment options for patients who fail or refuse to comply with TNF-α treatment. In patients with refractory rheumatoid arthritis, the response rate is limited and the response period is short such as two years. It is also a market where IMBiologics is looking for opportunities.When the research team first conducted a conceptual proof (PoC) experiment on a new mechanism of action, IMB-101 showed additional inhibitory effects compared to TNF-α or OX40L monoclonal antibodies in animal models.Next, the advantage was confirmed by targeting TNF-α and OX40L together in the rheumatoid arthritis model. In an in-vitro setting, IMB-101 effectively regulated several cytokines, including IL-2, IL-17 and IL-21 compared to monoclonal antibodies. In addition, ex-vivo experiments confirmed the equivalent or improved efficacy of Humira in synovial fluid mononuclear cells (SFMC), an immune cell extracted from the lesions of patients with rheumatoid arthritis. In particular, while the inflammatory signal worsened in the case of patients who did not respond to drugs during treatment with Humira, no such paradoxical effect was observed when IMB-101 was administered. This is why it is expected to be effective in TNF-α refractory patients.Key data is effective in the monkey rheumatoid arthritis model. IMB-101 showed a higher response rate than Humira at a quarter concentration of Humira, and also significantly lowered autoantibody levels. CEO Ha said, "Mouse has a low homology of OX40 and OX40L with humans, and there is a limitation in that data reproducibility is poor even if a humanized model is used. Therefore, we have been conducting experiments on monkey models since last year, and we have obtained encouraging efficacy data.”Furthermore, it also confirmed the effect of reducing bone damage. When the degree of bone damage was measured as an inflammatory response in the monkey rheumatoid arthritis model (by X-ray imaging), at a certain dose or more of IMB-101, it was confirmed that bone damage was reduced compared to Humira. In addition, as a result of the mechanism study, IMB-101 had a high efficacy in inhibiting osteoclastogenesis compared to Humira.IMBiologics confirmed that, in monkeys, IMB-101 had a pharmacokinetic (PK) profile similar to that of the existing antibody, and showed similar bioavailability (BA, 96.3%) to that of intravenous (IV) even with subcutaneous (SC) administration. It also confirmed the possibility of development as an SC formulation. IMBiologics is currently conducting a GLP toxicity test, and plans to submit an IND for phase 1 clinical trials in the US in the first half of next year.Next-generation IgM platform concept, 'versatility' as an immuno-oncology drugAnother axis that will lead IMBiologics in the future is the IgM-based multi-combination platform 'ePENDY'. IgM (immunoglobulin M) is the first type of antibody secreted when external infectious bacteria enter the innate immunity because it can recognize the glycolysis pattern. It has a multi-coupler structure and has 10 pentamers including J-chain or 12 hexamers without J-chain. The IgM has a lower affinity to an antigen than the IgG having two binding groups, and has a high total avidity because it has 10 or 12 arms. The resulting molecular weight ranges from 900 to 1050 kDa.IgM is structurally easy to induce clusters of target antigens, and is known to have complement-dependent cytotoxicity (CDC) activity by binding to C1q to form clusters. In addition, IgM antibodies are known to bind to receptors such as pIgR, Fcα/μR, and FcμR.CEO Ha said, "The final target is a therapeutic vaccine for an anti-cancer treatment. As TCR forms a cluster, peptide is recognized through MHC and cytokines are secreted. In this process, we noted that TCR or immunomodulatory targets have many characteristics of clusters. I thought it would be advantageous to have a lot of binding couplers in terms of avidity, so I focused on the characteristics of IgM antibodies." He said, "We expect it to have strong effects even at low drug concentrations."However, attempts to develop new drugs using IgM antibodies have been slow. Clinical trials have been conducted based on the fact that IgM antibodies can recognize lipopolysaccharides, glycoproteins, and glycans. Safety was confirmed in clinical trials, but there were no clear results. Then, as IGM Biosciences, which was established in 2010, recently promoted clinical development of CD3 target T cell engager applied with IgM, the concept of IgM antibody-based platform began to draw attention in the global industry.IGM's new approach to IgM antibody platform also led to a agonist agent drug discovery deal with Sanofi in March this year targeting autoimmune, inflammatory and cancer diseases. However, the lead program CD20xCD3 "IGM-2323 (10+1 structure)" had lower-than-expected efficacy in phase 1 clinical trials for lymphoma, and there are still areas to be studied, such as the strongest drug response rate (ORR 60%) in the lowest dose (100mg).IMBiologics decided that IgM had to overcome its existing shortcomings in order to be applied to the development of new drugs and developed the next-generation IgM platform "ePENDY" technology that overcame these limitations. There are mainly five limitations of IgM analyzed by the company, and each is implemented to supplement.First, a hinge was introduced to increase biological activity/binding affinity. CEO Ha said, "IgG has the advantage of high flexibility because it has a hinge in structure," adding, "IgM is known that the CH2 domain acts as a hinge, but it is unclear whether it can actually act as a hinge." "It is known that there are only a few binding sites that can be bound in the body due to structural steric hindrance," he explained. With the introduction of hinges, ePENDY's avidity has increased several tens of times compared to existing IgM.Second, its half-life is increased. In literature, the half-life of IgM is 5 days, but in practice it is less than 1 day. IMBiologics introduced an FcRn binding group to increase the half-life to a level similar to that of an IgG antibody. Third, ADCC activity was introduced. IgM does not have ADCC activity, but IMBiologics introduced a CD16a binding site capable of activating NK cells. Accordingly, in an in vitro assay, it was confirmed that ePENDY has tens to thousands of times ADCC activity than IgG. Fourth, in consideration of safety, affinity to FcμR was eliminated. CEO Ha said, “Since no drug has been marketed as an IgM antibody, drug safety cannot be predicted. Therefore, we engineered it to have properties similar to those of an IgG antibody.”Finally, it improved the yield of production. "The biggest issue in terms of IgM CMC is that it is difficult to purify because there is no part that binds to protein A," CEO Ha said. "We expect high productivity by adding protein A binding part to ePENDY to facilitate the purification process."What is expected in the future is the versatility of the ePENDY platform. IMBiologics expects to be able to apply ▲ antibody (scFv, Fab) ▲ protein ligand (soluble ligand, extracellular membrane domain) ▲ HLA (human leukocyte antigen) to the ePENDY platform built in this way.IMBiologics focuses on two major directions in the field of immuno-oncology drugs. First is a therapeutic cancer vaccine platform, “STAM.ePENDY (or STAM.eP; specific T cell activating modulator)" in the form of HLA-A/peptide loaded with a peptide targeting cancer cells in HLA-A interacting with T-cell receptor (TCR).Based on HLA, it has the advantage of minimizing toxic side effects by activating cancer cell-specific CD8+ T cells and targeting internal proteins in cancer cells through HLA. In addition, it is possible to bind co-stimulating factors such as CD28. In conclusion, the concept is to replace the role of dendritic cells (DCs) used in the development of anticancer vaccines. In a study conducted with "IMB-401 (undisclosed)" applying STAM.ep, CD8+ T cells for cancer antigens were activated, and conceptual verification data were secured.In another direction, it is researching an engager platform that can activate both NK cells and T cells, and there is an IMB-402 (undisclosed) project to which it is applied. As a part that attracts T cells to the ePENDY platform, it is a ‘1+10’ type T cell engager in which one domain that specifically attracts CD8+ T cells and 10 domains that target cancer cells are hung. In addition, it is possible to activate NK cells through the ADCC action of the antibody. It is expected to mainly target naive T cells that have not yet encountered cancer cells.HLA-G immuno-oncology and anemia diseaseIMBiologics does not limit the project to autoimmune diseases or platforms. While developing the IMB-101 project and ePENDY platform, the monoclonal antibody immuno-oncology drug and agonist antibody ‘IMB-301 (undisclosed)’ project targeting anemia diseases are also underway.The target that IMBiologics is paying attention to in the field of immuno-oncology is the HLA protein. Proteins in HLA belong to MHC class I, and are broadly divided into two categories. First, there are HLA-A, B, and C belonging to HLA class Ia, of which polymorphism is large. These proteins induce antigen-specific T cell activation by interacting with the TCR. The others are HLA-E, F, G, and H belonging to HLA class Ib that have the opposite action. It is relatively low on polymorphism and interacts with immunosuppressive receptors to induce an immune avoidance mechanism.IMBiologics is working on a project for HLA-G antibody ‘IMB-201’ and Trap fusion protein ‘IMB-202 (undisclosed)’ with different characteristics.HLA-G is known as an immune tolerance molecule that prevents the fetus from being attacked by maternal immunity, and it has recently been found that HLA-G expressed in cancer cells interacts with ILT2 expressed by immune cells to induce an immune avoidance mechanism. Accordingly, IMBiologics has a concept of increasing immune activity by inhibiting HLA-G with antibodies.IMB-201 is on an antibody optimization step, and research is also underway to apply it to the ePENDY platform. CEO Ha said, "The most important thing in drug development targeting HLA proteins is selectivity. These proteins have the complete opposite effect of immune activation or inhibition depending on the class. In particular, HLA-A, B, and C play a key role in innate and adaptive immunity, and drug development is difficult due to their high polymorphism. We found drug candidates that have high specificity for HLA-G and do not bind to HLA-A, B, and C."The related deal is also active. Gilead Sciences acquired ‘TTX-080’, an HLA-G antibody, from Tizona Therapeutics in 2020, which is about to undergo a phase 1 clinical trial. Also last year, Sanofi acquired the ILT-2 antibody ‘BND-22’ from Biond Biologics, which is preparing for a phase 1 clinical trial.LeadershipWhen CEO Ha founded IMBiologics, he had the will to start the bispecific antibody project and lead it to the end of clinical development.CEO Ha previously gained experience in clinical teams and marketing PMs for anticancer drugs at CJ healthcare, and as CJ closed its bio business, he conducted business development and research at antibody biotech. Then, in 2011, CJ began researching proteins, antibodies, and biosimilars again and he joined. Since then, he has been a senior researcher at CJ CheilJedang and head of the BIO Research Center at HK inno.N.After that, HK inno.N (formerly CJ Healthcare), which was acquired by Kolmar Korea in 2018 and after discussion with the company, IMBiologics was established by licensing in the IMB-101 project. At that time, Dr. Chungmin Lee, who was in charge of the new biopharmaceutical group including this project, served as the CTO of the IMBiologics Research Center, and 4 researchers including Dr. Hong Jai Lee, who conducted the platform research, also joined. Dr. Chihye Park, who previously served as the head of the clinical medicine center at HK inno.N, also joined last year as the head of the clinical development division (CDO).In addition, Dr. Insoo Jung, who was in charge of national project planning/technical evaluation in the Korea Institute of Industrial Technology Evaluation and Planning previously, is the chief business development and COO of the company, and Eunsung Kang, who has 18 years of CMC research experience at Dong-A ST, joined as the chief of CMC Center.The company's motto, which CEO Ha thinks, is a " excellent performance company” centered on working-level staff with development capabilities in the industry. The development timeline established at the beginning of its establishment is also going as planned. "We are setting feasible goals when starting a company and positioning it as a company that keeps its promises," he said. "I think Biotech's way is to set clear goals to go, execute invested funds, and maintain a cycle of data." "We will also maximize shareholder value through L/O," he said.▲Leadership of IMBiologicsby Sungmin Kim press@bios.co.kr

2022-10-12

(May 10, 2022) ‘OX40LxTNFα’ bispecific antibody project of IMBiologics funded by KDDF

For more information, please visit :  IMBiologics News (full article available in Korean)

2022-08-30

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  • President(CEO) : Gyongsik Ha
  • 260, Changnyong-daero, Yeongtong-gu, Suwon-si, Gyeonggi-do, Republic of Korea