SAN FRANCISCO and SUZHOU, China, Sept. 17, 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, cardiovascular and metabolic, ophthalmology and other major diseases, announces that clinical data of IBI363 (first-in-class PD-1/IL-2^α-bias bispecific antibody fusion protein) combined with bevacizumab in advanced colorectal cancer is presented at the 2024 ESMO Congress. Currently, Innovent is conducting Phase 1/2 clinical trials in China, the United States, and Australia to evaluate the safety, tolerability and efficacy of IBI363 in subjects with advanced solid tumors.

First-in-class PD-1/IL-2 ^α-bias bispecific antibody fusion protein IBI363 combined with bevacizumab in patients with advanced colorectal cancer: Results from Phase 1 study

This Phase 1 study was conducted to evaluate the safety, tolerability and preliminary efficacy of IBI363 combined with bevacizumab in subjects with advanced colorectal cancer.

A total of 35 subjects received treatment of IBI363 combined with bevacizumab, demonstrating promising anti-tumor efficacy with good tolerability and safety

• As of the data cutoff date (Aug 30, 2024), a total of 35 subjects with advanced colorectal cancer received combination treatment at 3 different dose levels (0.6 mg/kg IBI363 combined with 5 mg/kg bevacizumab Q2W, 1 mg/kg IBI363 combined with 5 mg/kg bevacizumab Q2W, and 1.5 mg/kg IBI363 combined with 7.5 mg/kg bevacizumab Q3W). Among them, 91.4% of the subjects had advanced colorectal cancer with microsatellite stable (MSS) or proficient mismatch repair (pMMR), and the MSI/MMR status was unknown in 8.6% subjects. 91.4% of the subjects had previously received 2 or more lines of systemic anti-tumor treatment. 51.4% of the subjects had liver metastases. 25.7% of the subjects had received prior immunotherapy. 40% of the subjects had KRAS/NRAS exon 2/3/4 mutations.
• The most common treatment related adverse events (TRAEs) were arthralgia, thyroid disorders, and rash. The total incidence of TRAEs ≥ grade 3 was 22.9%. Immune related adverse events (irAEs) ≥ grade 3 occurred in 5.7% of subjects. The safety profile of the combination regimen was similar to that of IBI363 monotherapy, and no new safety signals were identified.

Promising anti-tumor activity in subjects with MSS/pMMR colorectal cancer ; durable responses with a trend towards long-term benefit

• As of the cutoff date, 32 subjects were efficacy evaluable having underwent at least one post-baseline tumor assessment. The ORR was 21.9% (confirmed ORR was 15.6%), and DCR was 65.6%. The median DoR was 8.1 months (95% CI: 1.5~8.2). The median PFS follow-up time was 7.6 months (95% CI: 4.0~9.4), and the median PFS was 4.1 months (95% CI: 1.7~8.1). The median OS was not reached.

Promising efficacy signals in colorectal cancer with and without baseline liver metastases

• Among the 17 subjects with baseline liver metastases who underwent at least one post-baseline tumor assessment, ORR was 11.8% and DCR was 58.8%.
• Among the 15 subjects without baseline liver metastases who underwent at least one post-baseline tumor assessment,ORR was 33.3% and DCR was 73.3%.

Promising efficacy signals in both IO-treated and IO-naïve colorectal cancer

• Among the 8 subjects who had received prior  immunotherapy and underwent at least one post-baseline tumor assessment, ORR was 25.0% and DCR was 62.5%.
• Among the 24 IO -naïve subjects who underwent at least one post-baseline tumor assessment, ORR was 20.8% and DCR was 66.7%.

Promising efficacy signals in colorectal cancer with and without KRAS/NRAS exon 2/3/4 mutations

• Among the 14 subjects with RAS exon 2/3/4 mutations and who had undergone at least one post-baseline tumor assessment, ORR was 21.4% and DCR was 57.1%.
• Among the 10 subjects without RAS exon 2/3/4 mutations who had undergone at least one post-baseline tumor assessment, ORR was 30.0% and DCR was 90.0%.

In addition, data from a Phase 1 clinical study of IBI363 monotherapy in a colorectal cancer cohort, presented at ASCO 2024, showed promising efficacy and good tolerability. Ongoing studies are now exploring IBI363 in other malignancies, including NSCLC, melanoma and other solid tumors, as well as in combination regimens for MSS/pMMR advanced colorectal cancer. Updates on relevant data and analysis will be shared at upcoming academic conferences and in journals.

Professor Tao Zhang, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, stated: "Colorectal cancer is the third most common cancer type globally and ranks fourth in cancer-related mortality^[1]. Despite recent advancements in colorectal cancer treatment, challenges such as chemotherapy toxicity and resistance continue to affect patients and clinicians. While immunotherapy offers new hope for advanced colorectal cancer patients, it is currently only approved for those with MSI-H/dMMR tumors. Research indicates that immunotherapy has limited efficacy in non-MSI-H/dMMR advanced colorectal cancer^[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. The PD-1/IL-2^α-bias bispecific molecule IBI363, when combined with bevacizumab, has shown promising anti-tumor activity in patients with non-MSI-H/dMMR advanced colorectal cancer. This combination has shown clinical benefits in both ORR and PFS, and maintains a manageable safety profile. Additionally, the combination regimen has proven effective in colorectal cancer patients with or without liver metastasis, prior immunotherapy, and RAS exon 2/3/4 mutations. IBI363 combined with bevacizumab elicited encouraging objective response rates and disease control rates, with durable responses and a trend towards long-term benefits, without introducing new safety risks in a colorectal cancer population that has previously shown very little response to immunotherapy. Overall, current clinical data suggest that IBI363 combined with bevacizumab holds significant promise for colorectal cancer and deserves further exploration."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "On top of the preliminary data reported at ASCO, we are presenting more updated data at the ESMO Congress. In non-MSI-H/dMMR advanced colorectal cancer, the combination of IBI363 with bevacizumab has demonstrated strong anti-tumor effects, with durable responses and a trend towards long-term benefits. These promising results in a relatively 'cold' tumor suggest significant potential for IBI363 in this disease area. We are confident in the broad development prospects of IBI363 and look forward to seeing more mature data from higher doses and extended follow-up, which will help us advance to the next stage of clinical development."

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

IBI363 is a first-in-class PD-1/IL-2^α-bias bispecific antibody fusion protein independently developed by Innovent Biologics. It functions by both blocking the PD-1/PD-L1 pathway and activating the IL-2 pathway. The IL-2 arm of IBI363 is designed to maintain its affinity for IL-2Rα while reducing binding to IL-2Rβ and IL-2Rγ, thereby minimizing toxicity. The PD-1 binding arm not only blocks PD-1 but also selectively delivers IL-2. This approach targets and activates tumor-specific T cells that express both PD-1 and IL-2α, leading to more precise and effective activation of this T cell subpopulation. IBI363 has demonstrated robust antitumor activity in various tumor-bearing pharmacological models, but also showed outstanding efficacy in PD-1 resistance and metastasis models. In response to urgent clinical needs, Innovent is conducting clinical studies in China, the United States and Australia to further explore the efficacy and safety of IBI363 in advanced tumors.

About 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 has launched 11 products in the market. It has 3 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.

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.

Forward-Looking Statements

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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. 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.

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