SAN FRANCISCO and SUZHOU, China, June 13, 2024 /PRNewswire/ -- Innovent Biologics, Inc. ('Innovent') (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, announced that clinical data of IBI363 (first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein) in advanced solid tumors are presented at the 2024 ESMO Virtual Plenary (ClinicalTrials.gov, NCT04085185)..

旧金山和中国苏州，2024年6月13日/PRNewswire/--Innovent Biologics，Inc.（“Innovent”）（香港交易所：01801），一家世界级的生物制药公司，开发，制造和商业化用于治疗肿瘤，自身免疫，代谢，眼科和其他主要疾病的高质量药物，宣布IBI363（一流的PD-1/IL-2α-偏倚双特异性抗体融合蛋白）在晚期实体瘤中的临床数据将在2024年ESMO虚拟全体会议（ClinicalTrials.gov，NCT04085185）上公布。。

Dr. Hui Zhou, Senior Vice President of Innovent, stated: 'IBI363, as a first-in-class molecule, represents Innovent's continuous innovation and advancement in the immunotherapy field. Starting from molecular design, the unique approach of α bias with β and γ attenuated were creatively adopted, which greatly improved the therapeutic window of IL-2.

Innovent高级副总裁周辉博士表示：“IBI363作为一流分子，代表了Innovent在免疫治疗领域的不断创新和进步。从分子设计开始，创造性地采用了α偏倚与β和γ减毒的独特方法，极大地改善了IL-2的治疗窗口。

Meanwhile, through the specific traction of PD-1, tumor-specific T cells expressing both PD-1 and CD25 can be selectively stimulated and amplified, thus exerting anti-tumor effects. IBI363 has demonstrated excellent druggability with antibody-like pharmacokinetics (IgG-like PK) and low immunogenicity.

同时，通过PD-1的特异性牵引，可以选择性地刺激和扩增表达PD-1和CD25的肿瘤特异性T细胞，从而发挥抗肿瘤作用。IBI363已显示出优异的可药物性，具有抗体样药代动力学（IgG样PK）和低免疫原性。

On top of the preliminary data reported at ASCO, we presented more informative data at the ESMO virtual plenary. Especially in the IO-treated squamous NSCLC, IBI363 has demonstrated strong anti-tumor effects, which could potentially be the next breakthrough in this area. Moreover, a promising efficacy signal was shown in IO-naïve mucosal melanoma, a relatively 'cold' tumor, which brings us great confidence in the next step to expand the IO-naïve population, and also indicates the broad application potential of IBI363.'.

在ASCO报告的初步数据之上，我们在ESMO虚拟全体会议上提供了更多信息。特别是在IO治疗的鳞状NSCLC中，IBI363表现出强大的抗肿瘤作用，这可能是该领域的下一个突破。此外，在IO幼稚粘膜黑色素瘤（一种相对“冷”的肿瘤）中显示出有希望的疗效信号，这为我们下一步扩大IO幼稚人群带来了极大的信心，也表明了IBI363的广泛应用潜力。

First-in-class PD-1/IL-2α-bias bispecific antibody fusion protein IBI363 in patients with advanced solid tumors: Results from Phase 1 study

晚期实体瘤患者中一流的PD-1/IL-2α偏倚双特异性抗体融合蛋白IBI363：第一阶段研究的结果

This Phase 1a/1b Study was conducted to evaluate the safety, tolerability and preliminary efficacy of IBI363 in subjects with advanced solid tumors.

这项1a/1b期研究旨在评估IBI363在晚期实体瘤患者中的安全性，耐受性和初步疗效。

Over 300 subjects received IBI363 monotherapy treatment, unprecedented dosing level compared with traditional IL-2 therapy, with good tolerability and safety

超过300名受试者接受了IBI363单药治疗，与传统的IL-2治疗相比，剂量水平前所未有，具有良好的耐受性和安全性

As of the data cutoff date (Apr 16, 2024), 347 subjects with advanced solid tumors received IBI363 monotherapy (0.2μg/kg QW~3mg/kg Q3W). The tumor types included NSCLC (N=100), melanoma (N=89), colorectal cancer (N=102) and others (N=56). 81.8% of subjects had 2 or more lines of prior systemic therapy.

截至数据截止日期（2024年4月16日），347名患有晚期实体瘤的受试者接受了IBI363单药治疗（0.2μg/kg QW〜3mg/kg Q3W）。肿瘤类型包括NSCLC（N=100），黑色素瘤（N=89），结直肠癌（N=102）和其他（N=56）。81.8%的受试者之前有2行或更多行全身治疗。

In patients with solid tumors other than CRC (N=245), 84.1% received prior immunotherapy..

在CRC以外的实体瘤患者（N=245）中，84.1%接受过免疫治疗。。

As for safety, the most common treatment related adverse events (TRAEs) were arthralgia, anaemia, hyperthyroidism and hypothyroidism. The total incidence of TRAEs ≥ grade 3 was 23.9%. Immune related adverse events (irAEs) ≥ grade 3 occurred in 10.4% of subjects. In the 38 subjects of 3mg/kg Q3W dose group, 13.2% had TRAEs ≥ grade 3, the safety profile was similar to that of the total population, and no new safety signals were identified..

就安全性而言，最常见的治疗相关不良事件（TRAEs）是关节痛，贫血，甲状腺功能亢进和甲状腺功能减退。TRAEs≥3级的总发生率为23.9%。10.4%的受试者发生免疫相关不良事件（irAEs）≥3级。在3mg/kg Q3W剂量组的38名受试者中，13.2%的TRAEs≥3级，安全性与总人群相似，未发现新的安全信号。。

Broad anti-tumor activity and applicability across tumor types, dose-dependent efficacy observed as dose reached 3mg/kg

广泛的抗肿瘤活性和跨肿瘤类型的适用性，当剂量达到3mg/kg时观察到剂量依赖性功效

As for efficacy, 300 subjects received IBI363 ≥0.1mg/kg and had at least one post-baseline tumor assessment. 3 subjects achieved complete response (CR) and 49 subjects had partial response (PR). As of the data cutoff date, 38 responders are still free of disease progression (PD). The duration of response (DoR) was immature.

至于疗效，300名受试者接受IBI363≥0.1mg/kg，并至少进行了一次基线后肿瘤评估。3名受试者获得完全缓解（CR），49名受试者获得部分缓解（PR）。截至数据截止日期，38名应答者仍然没有疾病进展（PD）。反应持续时间（DoR）不成熟。

In 204 IO-treated subjects, the ORR was 17.6%..

在204名接受IO治疗的受试者中，ORR为17.6%。。

In 15 subjects who received IBI363 3mg/kg and had at least one post-baseline tumor assessment, the ORR was 46.7% and DCR was 80.0%.

在接受IBI363 3mg/kg且至少有一次基线后肿瘤评估的15名受试者中，ORR为46.7%，DCR为80.0%。

Promising efficacy signals in driver gene wild-type non-small cell lung cancer

驱动基因野生型非小细胞肺癌的有希望的疗效信号

-         70 subjects received IBI363 ≥0.3mg/kg and had at least one post-baseline tumor assessment. 77% of them had 2 or more lines of prior systemic therapy, and only 1 subject was IO-naïve. The overall ORR was 27.1%, and DCR was 72.9%.

-70名受试者接受IBI363≥0.3mg/kg，并至少进行了一次基线后肿瘤评估。其中77%的人有2行或更多的全身治疗，只有1名受试者是IO天真的。总体ORR为27.1%，DCR为72.9%。

-         In the 37 subjects with squamous cell carcinoma (36 received prior PD-(L)1 treatment, 1 received prior TCE treatment), 13 achieved PR. The ORR was 35.1%, and DCR was 75.7%. As of the data cutoff date, the median follow up time was 5.7 months and the median PFS was 5.5 months (95% CI, 3.2-6.9).

-在37例鳞状细胞癌患者中（36例接受PD-（L）1治疗，1例接受TCE治疗），13例达到PR。ORR为35.1%，DCR为75.7%。截至数据截止日期，中位随访时间为5.7个月，中位PFS为5.5个月（95%CI，3.2-6.9）。

11 of 13 responders are free of disease progression..

13名应答者中有11名没有疾病进展。。

-         A total of 9 NSCLC subjects (8 received prior PD-(L)1 treatment, 1 received prior TCE treatment) received IBI363 at 3mg/kg Q3W and had at least one post-baseline tumor assessment, including 6 squamous and 3 driver gene wild-type adeno NSCLC. All of the 6 patients with squamous NSCLC and 1 patient with adeno NSCLC achieved PR.

-共有9名NSCLC受试者（8名接受PD-（L）1治疗，1名接受TCE治疗）接受3mg/kg Q3W的IBI363治疗，并至少进行了一次基线后肿瘤评估，包括6例鳞状细胞癌和3例驱动基因野生型腺NSCLC。6例鳞状NSCLC患者和1例腺NSCLC患者均达到PR。

The ORR was 100% and 33.3%, respectively, and the DCR were both 100%..

ORR分别为100%和33.3%，DCR均为100%。。

Promising efficacy signals in IO-treated melanoma and IO-naïve mucosal melanoma

IO治疗的黑色素瘤和IO初治的粘膜黑色素瘤有希望的疗效信号

-         37 IO-treated melanoma subjects received IBI363 1mg/kg and had at least one post-baseline tumor assessment. There were 11 responders, including 1 CR and 10 PR. The ORR and DCR was 29.7% and 73.0%, respectively.

-37名IO治疗的黑色素瘤受试者接受IBI363 1mg/kg，并进行至少一次基线后肿瘤评估。有11名应答者，包括1名CR和10名PR。ORR和DCR分别为29.7%和73.0%。

-         In 8 IO-naïve mucosal melanoma subjects, 1 patient achieved CR and 5 patients had PR. The ORR was 75.0%, and DCR was 100%.

-在8名IO初治粘膜黑色素瘤受试者中，1名患者达到CR，5名患者达到PR。ORR为75.0%，DCR为100%。

As IBI363 has shown encouraging efficacy signals and good tolerability, this study is continuing to further explore the anti-tumor activity of IBI363 in NSCLC, melanoma and other tumors. Relevant data and analysis results will be updated in future academic conferences or journals.

由于IBI363显示出令人鼓舞的疗效信号和良好的耐受性，因此本研究正在继续进一步探索IBI363在NSCLC，黑色素瘤和其他肿瘤中的抗肿瘤活性。相关数据和分析结果将在未来的学术会议或期刊上更新。

Professor Xueli Bai, The First Affiliated Hospital, School of Medicine, Zhejiang University, stated: 'Lung cancer is the leading cause of cancer death worldwide, of which non-small cell lung cancer accounts for about 80%[1]. In recent years, PD-1/PD-L1 inhibitors have shown promising efficacy in non-small cell lung cancer.

浙江大学医学院第一附属医院白雪莉教授表示：“肺癌是全球癌症死亡的主要原因，其中非小细胞肺癌约占80%[1]。近年来，PD-1/PD-L1抑制剂在非小细胞肺癌中显示出有希望的疗效。

However, most patients developed primary or secondary resistance to immune checkpoint inhibitors after treatment. IO-failed patients with NSCLC always suffer from a lack of effective treatment, and chemotherapy such as docetaxel elicits an ORR of only about 10% and a median PFS of less than 4 months[2].

然而，大多数患者在治疗后对免疫检查点抑制剂产生了原发性或继发性耐药性。IO失败的NSCLC患者总是缺乏有效的治疗，多西紫杉醇等化疗引起的ORR仅为约10%，中位PFS小于4个月（2）。

As an important cytokine activating tumor-specific CD8+T cells, IL-2 is complementary to immune checkpoint inhibitors in MOA. The combination of PD-1 and IL-2 may reverse the exhaustion of tumor-specific CD8+ T cells, thereby overcoming immune resistance. As a PD-1/IL-2α-bias bispecific molecule, IBI363 showed promising antitumor activity in IO-resistant driver gene wild-type NSCLC, and clinical benefits were demonstrated by both ORR and PFS.

作为激活肿瘤特异性CD8+T细胞的重要细胞因子，IL-2与MOA中的免疫检查点抑制剂互补。PD-1和IL-2的组合可以逆转肿瘤特异性CD8+T细胞的耗竭，从而克服免疫抗性。作为PD-1/IL-2α偏向双特异性分子，IBI363在IO抗性驱动基因野生型NSCLC中显示出有希望的抗肿瘤活性，ORR和PFS均证明了临床益处。

At the same time, the safety is manageable, without new safety signals at high dose level, which gives us more confidence.'.

同时，安全性是可控的，在高剂量水平下没有新的安全信号，这给了我们更多的信心。”。

Professor Yu Chen, Fujian cancer hospital, stated: 'Melanoma is a rare tumor in China, and the majority of patients are acral or mucosal subtypes (about 60%-70%[3]), which are not sensitive to immunotherapy. IL-2, as an important cytokine that activates tumor-specific CD8+ T cells and mechanistically complementary to immune checkpoint inhibitors, has long become a well-established target in melanoma.

福建省肿瘤医院的余晨教授表示：“黑色素瘤在中国是一种罕见的肿瘤，大多数患者是肢端或粘膜亚型（约60%〜70%[3]），对免疫治疗不敏感。IL-2作为激活肿瘤特异性CD8+T细胞并与免疫检查点抑制剂机制互补的重要细胞因子，早已成为黑素瘤中公认的靶标。

As a novel PD-1/IL-2α-bias bispecific molecule, IBI363 demonstrates significantly higher response rate than the current standard of care in IO-failed melanoma, and the response is durable. Encouraging high ORR and DCR have been observed in mucosal melanoma, a subtype known to be insensitive to immunotherapy.

作为一种新型的PD-1/IL-2α偏向双特异性分子，IBI363在IO失败的黑色素瘤中表现出比当前标准治疗更高的反应率，并且反应持久。在粘膜黑色素瘤中观察到令人鼓舞的高ORR和DCR，粘膜黑色素瘤是一种已知对免疫疗法不敏感的亚型。

IBI363 is well tolerated, and the toxicity is manageable. The current safety profile is similar to that of previous anti-PD-1 monoclonal antibodies. The clinical data suggest that IBI363 has great development potential in melanoma population. Clinical trials are ongoing for further confirming the clinical benefits of IBI363 in melanoma population.'.

IBI363耐受性良好，毒性可控。目前的安全性与以前的抗PD-1单克隆抗体相似。临床数据表明，IBI363在黑色素瘤人群中具有巨大的发展潜力。正在进行临床试验，以进一步证实IBI363在黑色素瘤人群中的临床益处。”。

About IBI363 (First-in-class PD-1/IL-2α-bias bispecific antibody fusion protein)

关于IBI363（一流的PD-1/IL-2α偏向双特异性抗体融合蛋白）

IBI363 is a First-in-class PD-1/IL-2α-bias bispecific antibody fusion protein independently developed by Innovent Biologics, which has two functions: blocking the PD-1/PD-L1 pathway and activating the IL-2 pathway. The IL-2 arm of IBI363 was modified to retain its affinity for IL-2Rα, but weakened its binding ability to IL-2Rβ and IL-2Rγ, thereby reducing toxicity. The PD-1 binding arm can simultaneously block PD-1 and selectively deliver IL-2. Since the newly activated tumor specific T cells express both PD-1 and IL-2α, this differential strategy allows for more precise and effective targeting and activation of this T cell subpopulation. IBI363 not only showed good antitumor activity in a variety of tumor-bearing pharmacological models, but also showed outstanding efficacy in PD-1 resistance and metastasis models. Starting from the urgent clinical needs, Innovent Biologics is conducting clinical studies in China, the United States and Australia to explore the efficacy and safety of IBI363 in advanced tumors..

IBI363是Innovent Biologics独立开发的一流PD-1/IL-2α偏向双特异性抗体融合蛋白，具有阻断PD-1/PD-L1途径和激活IL-2途径两种功能。IBI363的IL-2臂被修饰以保留其对IL-2Rα的亲和力，但削弱了其对IL-2Rβ和IL-2Rγ的结合能力，从而降低了毒性。PD-1结合臂可以同时阻断PD-1并选择性递送IL-2。由于新激活的肿瘤特异性T细胞同时表达PD-1和IL-2α，因此这种差异策略可以更精确和有效地靶向和激活该T细胞亚群。IBI363不仅在各种荷瘤药理学模型中显示出良好的抗肿瘤活性，而且在PD-1抗性和转移模型中也显示出优异的功效。从迫切的临床需求出发，Innovent Biologics正在中国、美国和澳大利亚进行临床研究，以探索IBI363在晚期肿瘤中的有效性和安全性。。

About Innovent

关于Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases.

Innovent是一家领先的生物制药公司，成立于2011年，其使命是为全球患者提供负担得起的高质量生物制药。该公司发现、开发、制造和商业化针对一些最难治疾病的创新药物。它的开创性疗法治疗癌症，心血管和代谢，自身免疫和眼部疾病。

Innovent has launched 10 products in the market. It has 4 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center..

Innovent在市场上推出了10种产品。它有4个新药申请正在接受监管审查，4个资产在III期或关键临床试验中，还有18个分子在早期临床阶段。Innovent与30多家全球医疗保健公司合作，包括礼来、赛诺菲、Incyte、Adimab、LG Chem和MD安德森癌症中心。。

Guided by the motto, 'Start with Integrity, Succeed through Action,' Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn..

Innovent秉承“从诚信做起，通过行动取得成功”的座右铭，保持行业实践的最高标准，并合作推进生物制药行业，使一流的药物可以广泛使用。有关更多信息，请访问www.innoventbio.com，或在Facebook和LinkedIn上关注Innovent。。

Forward-Looking Statements

前瞻性声明

This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words 'anticipate', 'believe', 'estimate', 'expect', 'intend' and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements.

本新闻稿可能包含某些前瞻性声明，这些声明本质上具有重大风险和不确定性。与Innovent相关的“预期”、“相信”、“估计”、“预期”、“打算”等词语旨在识别某些此类前瞻性陈述。

Innovent does not intend to update these forward-looking statements regularly..

Innovent不打算定期更新这些前瞻性声明。。

These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict.

这些前瞻性陈述基于Innovent管理层在做出这些陈述时对未来事件的现有信念、假设、期望、估计、预测和理解。这些声明并不能保证未来的发展，并且受到风险、不确定性和其他因素的影响，其中一些因素超出了Innovent的控制范围，难以预测。

Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions..

因此，由于我们的业务、Innovent的竞争环境以及政治、经济、法律和社会条件的未来变化或发展，实际结果可能与前瞻性声明中包含的信息存在重大差异。。

Innovent, the Directors and the employees of Innovent assume (a) no obligation to correct or update the forward-looking statements contained in this site; and (b) no liability in the event that any of the forward-looking statements does not materialize or turn out to be incorrect.

Innovent，Innovent的董事和员工不承担（a）纠正或更新本网站中包含的前瞻性声明的义务；（b）如果任何前瞻性陈述没有实现或证明不正确，则不承担任何责任。

References

参考文献

[1] Sung H, Ferlay J, Siegel R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: a cancer journal for clinicians, 2021, 71(3): 209-249.

[1] Sung H，Ferlay J，Siegel R L，et al。2020年全球癌症统计：全球185个国家36种癌症发病率和死亡率的全球估计（J）。CA：临床医生癌症杂志，2021,71（3）：209-249。

[2] TROPION-Lung01 ESMO 2023

[2] TROPION-Lung01 ESMO 2023

[3] Clin Cancer Res 2020;26:4250–9. doi: 10.1158/1078-0432.CCR-19-3922; BMC Cancer (2023) 23:121. https://doi.org/10.1186/s12885-022-10473-y.

[3] 癌症临床研究2020；26:4250–9.doi:10.1158/1078-0432.CCR-19-3922；BMC癌症（2023）23:121。https://doi.org/10.1186/s12885-022-10473-y.

SOURCE Innovent Biologics

来源Innovent Biologics