Innovent Enters into Clinical Trial Collaboration with Merck KGaA, Darmstadt, Germany Investigating Combination Therapy of IBI351 (KRASG12C Inhibitor) and Cetuximab (ERBITUX®)for KRASG12C-mutated NSCLC in China

ROCKVILLE, Md. and SUZHOU, China, June 1, 2023 /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, today announced that it has entered into a clinical trial collaboration and supply agreement with Merck KGaA, Darmstadt, Germany for the combination therapy of IBI351 (GFH925) with cetuximab (ERBITUX®) as a potential frontline treatment for NSCLC patients harboring KRAS^G12C mutation in a Phase 1b clinical trial in China.

Under the agreement, Innovent will conduct a Phase 1b study to evaluate the anti-tumor activity and safety of the combination therapy of IBI351(GFH925) with cetuximab in Chinese patients with advanced or metastatic NSCLC harboring KRAS^G12C mutation. Merck KGaA, Darmstadt, Germany will provide clinical drug supplies of cetuximab in this multi-center trial in China. Cetuximab as a monotherapy or as a combination therapy has not been approved in any country for patients with advanced NSCLC.

Currently, Innovent is conducting a single-arm registrational trial of IBI351(GFH925) monotherapy in previously-treated advanced non-small cell lung cancer patients with KRAS^G12C mutation in China, with expected NDA filing by the end of 2023. A Phase 1b study of IBI351(GFH925) in combination with sintilimab for previously untreated advanced NSCLC patients with KRAS^G12C mutation is also under exploration. Latest data of a Phase 1 study of IBI351(GFH925) monotherapy in 67 previously-treated NSCLC patients with KRAS^G12C mutation were presented at the 2023 American Association for Cancer Research(AACR) Annual Meeting [Link].

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "We are pleased to collaborate with Merck KGaA, Darmstadt, Germany to further explore the potential of IBI351 and cetuximab combination therapy in the early line setting for NSCLC patients harboring KRAS^G12C mutation, and shed light on next-step clinical development. The combination of a KRAS^G12C inhibitor and an EGFR inhibitor has shown efficacy in heavily pre-treated patients with metastatic colorectal cancer ^[1],[2],[3]. Preclinical studies of IBI351 and cetuximab combination therapy also demonstrated potential anti-tumour activity in NSCLC. Innovent has observed favorable safety and promising antitumor activity of IBI351 monotherapy in previously-treated advanced NSCLC harboring KRAS^G12C mutation, and we are actively expanding treatment lines, hoping to provide better treatment options for more cancer patients. "

About IBI351/GFH925 (KRAS^G12C Inhibitor)

RAS protein family can be divided into KRAS, HRAS and NRAS categories. KRAS mutation are detected in nearly 90% of pancreatic cancer, 30-40% of colon cancer, and 15-20% lung cancer patients. The occurrence of KRAS G12C mutation subset is more frequently observed than those with ALK, ROS1, RET and TRK 1/2/3 mutations combined.

Discovered by GenFleet Therapeutics, GFH925 (Innovent R&D code: IBI351) is a novel, orally active, potent KRAS^G12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by modifying the cysteine residue of KRAS^G12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of IBI351 towards G12C. Subsequently, IBI351 effectively inhibits the downstream signal pathway to induce tumor cells' apoptosis and cell cycle arrest.

In September 2021, Innovent and GenFleet Therapeutics entered into an exclusive license agreement for the development and commercialization of IBI351 in China (including mainland China, Hong Kong, Macau and Taiwan) with additional option-in rights for global development and commercialization.

In January 2023, the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for IBI351 for the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring KRAS^G12C mutation who have received at least one systemic therapy. In May 2023, the CDE of China's NMPA granted another BTD for IBI351 for the treatment of previously treated advanced colorectal carcinoma (CRC) patients with KRAS^G12C mutation.

About Cetuximab (ERBITUX®)

Cetixumab (ERBITUX®) is an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of cetuximab is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth. Based on in vitro evidence, cetuximab also targets cytotoxic immune effector cells towards EGFR-expressing tumor cells (antibody-dependent cell-mediated cytotoxicity [ADCC]).

ERBITUX® has already obtained market authorization in over 100 countries worldwide for the treatment of RAS wild-type metastatic colorectal cancer and for the treatment of squamous cell carcinoma of the head and neck. Merck licensed the right to market ERBITUX®, a registered trademark of ImClone LLC, outside the U.S. and Canada from ImClone LLC, a wholly owned subsidiary of Eli Lilly and Company, in 1998.

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 in the fields of oncology, metabolism, autoimmunity, ophthalmology 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 35 valuable assets in the fields of cancer, metabolic disorder, autoimmune disease and other major therapeutic areas, with 8 approved products on the market. These include:  TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) , Pemazyre® (pemigatinib oral inhibitor), olverembatinib (BCR-ABL TKI) , Cyramza® (ramucirumab) and Retsevmo® (selpercatinib). An additional 3 assets are under NMPA NDA review, 6 assets are in Phase 3 or pivotal clinical trials, and 18 more molecules are 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, Roche, Sanofi, Adimab, Incyte, MD Anderson Cancer Center 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.

CYRAMZA® (ramucirumab, Eli Lilly). CYRAMZA® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

Retsevmo® (Selpercatinib, Eli Lilly). Retsevmo® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.

Disclaimer: Innovent does not recommend any off-label usage.

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.

Reference

[1]Yaeger R, Weiss J, et al. Adagrasib with or without Cetuximab in Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Jan 5;388(1):44-54. doi: 10.1056/NEJMoa2212419. Epub 2022 Dec 21. PMID: 36546659; PMCID: PMC9908297.
[2]Kuboki Y et al. Sotorasib in combination with panitumumab in refractory KRAS G12C-mutated colorectal cancer: safety and efficacy for phase 1B full expansion cohort. ESMO Congress 2022, Abstract 315O.
[3]Sae-Won Han et al. Phase Ib study of GDC-6036 in combination with cetuximab in patients with colorectal cancer (CRC)  with KRAS G12C mutation. AACR Congress 2023.

View original content:https://www.prnewswire.com/news-releases/innovent-enters-into-clinical-trial-collaboration-with-merck-kgaa-darmstadt-germany-investigating-combination-therapy-of-ibi351-krasg12c-inhibitor-and-cetuximab-erbituxfor-krasg12c-mutated-nsclc-in-china-301839797.html

SOURCE Innovent Biologics