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-2^α-bias bispecific antibody fusion protein) in advanced solid tumors are presented at the 2024 ESMO Virtual Plenary (ClinicalTrials.gov, NCT04085185).

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. 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. 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."

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

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

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

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

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

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

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

–         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%.

–         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). 11 of 13 responders are free of disease progression.

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

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

–         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.

–         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%.

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.

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. 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]. 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-2^α-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. At the same time, the safety is manageable, without new safety signals at high dose level, which gives us more confidence."

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. As a novel PD-1/IL-2^α-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. 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."

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, 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.

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 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.

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

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

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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