Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, today announced that the preclinical result of IBI319 was published in Nature Communications. The publication entitled, "Cancer immune therapy with PD-1-dependent CD137 co-stimulation provides localized tumour killing without systemic toxicity" is co-authored by Dr. Wei Xu and Dr. Xuan Wang, Vice President and Senior Manager of Innovent.

• The pre-clinical results show that IBI319 enhances the antitumor efficacy of PD-1 blockade without causing hepatotoxicity: In CT26 and MC38 tumor models, compared with PD-1 mAb or CD137 mAb, IBI319 generates synergistic antitumor efficacy by blocking PD-1 and activating CD137 simultaneously. It enhances tumor infiltration of T and NK cells in the absence of signs of hepatotoxicity.

• A non-human primate GLP toxicology study suggests that IBI319 is a well-tolerated molecule with a good safety profile; however, further evaluation in clinical studies is needed.

IBI319 is a next-generation bispecific antibody targeting both PD-1 and CD137. In addition to the synergistic effect of PD-1 immune checkpoint inhibitors and CD137 agonists, IBI319 has the following two features: first, the binding of PD-1 end of IBI319 is much stronger than that of the CD137 end, leading to an enrichment of antibody molecules in PD-1-highly expressing tumor-infiltrating T/NK cells, avoiding a systemic circulation of antibodies. Secondly, the trimerization of CD137 and downstream signal activation are completely dependent on the anchoring of its PD-1 arm, thus limiting systemic exposure and reducing toxic effects. IBI319 is a novel next-generation IO drug with proven mechanism and promising tumor suppression effects.

The corresponding author, Dr. Wei Xu, Vice President of Innovent, stated, "Our pre-clinical results suggest that IBI319 enhances the activity of PD-1 blockade without causing liver toxicity. As a new generation of bispecific IO drug, IBI319 has the potential of enhancing PD-1 response rate and efficacy in various types of tumors. IBI319 is currently in Phase I development in China and we look forward to evaluating the molecule in further development." 

The leading PI of the IBI319 Phase I study (CIBI319A101), Professor Yilong Wu, Tenured Professor of Guangdong Provincial People's Hospital and Director of Guangdong Lung Cancer Research Institute, stated, "While immune checkpoint inhibitors targeting PD-1/L1 have shown efficacy in treating a variety of tumor types, we still face challenges of primary and secondary drug resistance. The development of next-generation bispecific antibodies allows us to explore possible clinical gains of dual targeting PD-1/L1 and CD137, a key co-stimulatory immune checkpoint molecule, which plays a role in maintaining immune homeostasis and enhancing anti-tumor immune memory. We are pleased to see the preclinical research results of IBI319 and look forward to evaluating at the clinical study stage."

About CD137（4-1BB, TNFRS9）

CD137 is a member of the tumor necrosis factor (TNF) receptor family. CD137 is expressed by activated T cells and plays an important role in maintaining the immune response, resisting apoptosis of immune cells, reducing clearance of antigen-specific immune cells, and enhancing immunological memory. CD137 is also expressed on activated NK cells, monocytes, dendritic cells, neutrophils, eosinophils and mast cells, etc. On activated NK cells, CD137 pathway can increase antibody-dependent cell-mediated cytotoxicity (ADCC).

CD137 has emerged as a next generation antibody drug target, yet previous decades of clinical development of CD137 agonists have been hampered by the balance of toxicity and limited efficacy. The issue of how to develop a CD137 agonistic antibody that strikes a balance between enhancing antitumor efficacy while ensuring safety needs to be addressed.

About IBI319

IBI319 was discovered through a collaboration between Innovent and Eli Lilly and Company and has been developed in China by Innovent. The IND for IBI319 has been approved by the NMPA in China, and clinical trials in China are being conducted.

About the Phase 1 Study of IBI319 (CIBI319A101)

The Phase 1a/1b study (CIBI319A101) conducted by Innovent in China will assess the efficacy and safety of IBI319 in patients with advanced malignant tumors. Phase 1a of the study will evaluate dosing escalation and Phase 1b will further explore the safety and preliminary efficacy of IBI319 in a variety of solid and hematological tumors (ClinicalTrials.gov, NCT04708210).

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 diseases, and other major therapeutic areas. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong, S.A.R., China 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. By leveraging this platform, the company has built a robust pipeline of 26 valuable assets in major therapeutic areas, with 5 products - TYVYT? (sintilimab injection), BYVASDA? (bevacizumab biosimilar injection), SULINNO? (adalimumab biosimilar injection) , HALPRYZA? (rituximab biosimilar injection), and Pemazyre? (pemigatinib oral inhibitor) – officially approved for marketing, 1 asset's NDA under NMPA review, sintilimab's Biologics License Application (BLA) acceptance in the U.S., 5 assets in Phase 3 or pivotal clinical trials, and an additional 15 molecules in clinical studies.

Innovent has built an international team of advanced talented professionals in high-end biopharmaceutical development and commercialization, including many overseas 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 all relevant parties to help advance China's biopharmaceutical industry, improve drug availability to ordinary people and enhance the quality of the patients' lives.  For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.

Note:

Sintilimab is not an approved product in the United States.

BYVASDA? (bevacizumab biosimilar injection), HALPRYZA? (rituximab biosimilar injection), and SULINNO? (adalimumab 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, S.A.R., China, Macau, S.A.R., China and Taiwan, China.

Disclaimer:

1. This indication hasn't been approved in China.

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

3. For medical and healthcare professionals only.

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Source: Innovent Biologics