Innovent Announces First Patient Dosing of Claudin18.2/CD3 Bispecific Antibody IBI389 in Phase 1a/1b Clinical Trial for Advanced Solid Tumor

Rhea-AI Summary

Innovent Biologics announced the first patient dosing of IBI389, a bispecific antibody targeting Claudin18.2 and CD3, in a Phase I clinical trial for advanced malignancies. This multicenter trial will assess the safety, tolerability, and efficacy of IBI389 alone or in combination therapy against advanced solid tumors. Preclinical results showed IBI389's promise in treating CLDN18.2-expressing cancers, particularly in patients with low expression levels. The company aims to leverage this innovative approach to enhance immune response and improve treatment outcomes for gastric and pancreatic cancers.

Positive

• IBI389 demonstrates significant antitumor effects in preclinical studies.
• Targets Claudin18.2, which is expressed in various cancers, offering a new treatment avenue.
• Potential to benefit patients with low to moderate CLDN18.2 expression.

Negative

• None.

SAN FRANCISCO and SUZHOU, China, March 28, 2022 /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, metabolic, autoimmune and other major diseases, today announced the first patient dosing for its proprietary recombinant bispecific antibody targeting Claudin18.2 and CD3 (R&D code: IBI389) in a Phase I clinical trial for the treatment of advanced malignancies.

The study (NCT05164458) is an open, multicenter Phase 1a/1b study evaluating the safety, tolerability and efficacy of IBI389 monotherapy or combination therapy in the treatment of advanced solid tumors.

CD3-targeted bispecific antibodies (CD3-BsAbs) or T Cell Engager (TCE) are emerging novel therapeutic modalities in cancer immunotherapy in recent years. TCE redirects T cells to tumor cells by simultaneously binding tumor-associated antigen (TAA) expressed on tumor cells and CD3 expressed on T cells, thus inducing T cell killing of tumor cells. Differentiated from conventional immunotherapies, CD3-BsAbs provoke a stronger immune response through CD3-activated T cells without the binding of the T cell receptor (TCR) to the major histocompatibility complex (MHC)-peptide complex, and also do not rely on T cell-activated co-stimulatory signals.IBI389 has the potential to efficiently and selectively kill CLDN18.2-expressing tumor cells, increasing lymphocytic tumor infiltration and enhancing tumor immune response, while possessing a low risk of CRS (cytokine release syndrome). Preclinical results showed that IBI389 exhibited significant antitumor effects and could bound to tumor cells even in cell lines with low CLDN18.2 expression, and is promising to treat patient populations with low to moderate CLDN18.2 expression where conventional antibodies are found limited response.

The principal investigator of the study, Professor Feng Bi, Director of the Department of Abdominal Oncology and Director of the Molecular Targeted Therapy Research Unit at West China Hospital of Sichuan University, pointed out: "In recent years, CLDN18.2 has become one of the most topical R&D areas in molecular biology, and preliminary efficacy results in some clinical studies demonstrated encouraging druggablity of this target. IBI389 bispecific antibody distinguishes itself from traditional monoclonal antibodies by encouraging T-cell infiltration and killing of tumors, thus enhancing the antitumor effect as a single agent. We are looking forward to the positive results of IBI389 in patients with CLDN18.2-expressing solid tumors."

Dr. Hui Zhou, Senior Vice President of Innovent, said: " IBI389 marks an exciting start for Innovent in the TCE field. The scientists of Innovent Academy has accomplished sophisticated research, screen and design work in drug discovery stage, and the results of preclinical studies show that IBI389 has a potent anti-tumor effect with a good safety profile. We believe that as a differentiated molecule targeting CLDN18.2, IBI389 will bring benefits to patients with advanced gastric cancer and pancreatic cancer even with low CLDN18.2 expression."

About IBI389

IBI389 is an anti-CLDN18.2/CD3 bispecific antibody discovered and developed by Innovent. It induces immune synapse formations by linking CD3 molecules in T-cell receptor complexes and CLDN18.2 antigens on the surfaces of tumor cells. Therefore IBI389 stimulates T-cell activation, resulting in cytolytic protein production, inflammatory cytokine release and further T-cell proliferation, which eventually leads to durable anti-tumor effects.

About Claudin 18.2

Claudin protein is a critical component of tight junction complex molecules which play an important role in the life activities of the human body. Claudin18.2 is a member of the Claudin protein family, which is a highly tissue-specific protein expressed only in differentiated epithelial cells on the gastric mucosa under normal physiological conditions. Previous studies have revealed that Claudin18.2 is highly expressed in multiple types of cancer such as gastric cancer, pancreatic cancer, esophageal adenocarcinoma, and colorectalcancer. The unique feature of limited expression in normal tissues and highly specific expression in cancer makes Claudin18.2 an ideal target for developing the immunotherapeutic for solid tumors. Globally, there are many candidate therapies in clinical development. The drug modalities under development include monoclonal antibodies, bispecific antibodies, antibody-conjugated drugs and CAR-T cell products. However, currently no drug targeting Claudin18.2 has been approved.

About Gastric and Pancreatic adenocarcinoma

Gastric and pancreatic cancer are both malignant tumors of the digestive system that seriously endanger human life and health. The latest global cancer statistics show that there will be about 1.089 million new cases of gastric cancer worldwide in 2020, accounting for 5.6% of the global cancer incidence, and about 768,000 deaths, accounting for 7.7% of the global cancer deaths. There are about 495,000 new cases of pancreatic cancer, accounting for 2.6% of the global cancer incidence, and about 466,000 deaths, accounting for 4.7% of the global cancer deaths. According to the national cancer statistics released by the National Cancer Center of China in 2019, the incidence of gastric cancer in China in 2015 was about 403,000, accounting for 10.26% of the total cancer incidence, second only to lung cancer at 20.03%, with an incidence rate of 29.31/100,000 people, and about 291,000 deaths, accounting for 12.45% of the total cancer deaths, behind lung and liver cancer, with a mortality rate of 21.16/100,000 people. In 2015, the number of cases and deaths of pancreatic cancer nationwide were 95,000 and 85,000 respectively, ranking the 10th and 6th in the incidence and mortality of malignant tumors. The mortality ratio of pancreatic cancer was 0.89, making it a true "King of Cancer". Despite the treatment progress in recent years, drug resistance, recurrence and metastasis are still inevitable. The 5-year survival rate of patients with advanced gastric cancer is about 5-20%, and the median survival rate is about 10 months. Pancreatic cancer has a worse prognosis, with a 5-year survival rate of only 6 to 8%.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune, metabolic and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.

Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 32 valuable assets in the fields of cancer, metabolic, autoimmune disease and other major therapeutic areas, with 7 products approved for marketing in China – TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) , Pemazyre® (pemigatinib oral inhibitor) , NAILIKE(olverembatinib) and Cyramza® (ramucirumab), 1 asset under NMPA NDA review, 5 assets in Phase 3 or pivotal clinical trials, and an additional 19 molecules in clinical studies.

Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Adimab, Incyte, MD Anderson Cancer Center, Hanmi and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.

Note:

TYVYT® (sintilimab injection) is not an approved product in the United States.

BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab biosimilar injection) are not approved products in the United States.

TYVYT® (sintilimab injection, Innovent)

BYVASDA® (bevacizumab biosimilar injection, Innovent)

HALPRYZA® (rituximab biosimilar injection, Innovent)

SULINNO® (adalimumab biosimilar injection, Innovent)

Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.

Disclaimer:

1. This indication is still under clinical study, which hasn't been approved in China.

2. Innovent does not recommend any off-label usage.

3. For medical and healthcare professionals only.

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.

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 materialise or turn out to be incorrect.

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SOURCE Innovent Biologics

FAQ

What is the purpose of the IBI389 Phase I clinical trial?

The trial aims to evaluate the safety, tolerability, and efficacy of IBI389 for treating advanced solid tumors.

What types of cancer does IBI389 target?

IBI389 targets Claudin18.2, primarily in gastric and pancreatic cancers.

When was the first patient dosed with IBI389?

The first patient was dosed on March 28, 2022.

What are the expected outcomes of the IBI389 trial?

The trial seeks to demonstrate improved safety and efficacy in cancer treatment, especially for patients with low CLDN18.2 expression.

How does IBI389 differ from traditional immunotherapies?

IBI389 activates T cells without requiring T cell receptor binding to MHC-peptide, aiming for a stronger immune response.