China's First NDA for a KRAS G12C Inhibitor: Innovent Announces the National Medical Products Administration of China Has Accepted and Granted Priority Review Designation to the New Drug Application for IBI351

ROCKVILLE, Md. and SUZHOU, China, Nov. 23, 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, metabolic, autoimmune, ophthalmology and other major diseases, announces that the New Drug Application (NDA) for IBI351 (KRAS G12C inhibitor) has been accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China and granted Priority Review designation^[1], 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. It is China's first NDA for a KRAS G12C inhibitor and is anticipated to benefit more lung cancer patients harbouring KRAS G12C mutation after approval.

The NDA acceptance and Priority Review designation are based on the results from a single-arm registrational Phase 2 clinical study (NCT05005234) intended to evaluate the efficacy and safety of IBI351 monotherapy in advanced NSCLC patients harbouring KRAS G12C mutation who failed or were intolerant to the standard treatment in China. The results will be presented at the upcoming European Society for Medical Oncology (ESMO) Asia Congress 2023. 

Professor Yi-Long Wu from Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, stated: "KRAS mutation as the 'undruggable' target for decades has become one of the most popular direction for clinical development recently. Although FDA has approved KRAS G12C targeted drugs overseas, there's no drug approved in China. IBI351, as a novel, irreversible covalent inhibitor of KRAS G12C mutation, demonstrated favorable safety and promising efficacy in KRAS G12C mutated advanced NSCLC as monotherapy. We look forward to the NDA approval of this novel drug to benefit more NSCLC patients with KRAS G12C mutation soon."

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "Median survival is poor for advanced NSCLC patients with KRAS G12C mutation who failed or intolerant to standard of care treatment, highlighting the need for more effective options. We are glad about the NDA acceptance of IBI351 and it could potentially become the first approved KRAS G12C inhibitor in China, which could bring more treatment options to NSCLC patients. We are also advancing clinical development of IBI351 as monotherapy and combination therapy for more solid tumors such as colorectal cancer and lung cancer to look for opportunities to benefit more patients."

Previously, the results of IBI351 from a Phase 1 clinical trial in patients with solid tumors were updated in an oral presentation at the 2023 American Association for Cancer Research Annual Meeting (AACR 2023).

• As of February 10, 2023, of the 67 evaluable NSCLC patients, objective response rate (ORR) is 61.2% and disease control rate (DCR) is 92.5%.
• Among 30 patients with NSCLC treated at 600mg BID (the recommended phase 2 dose), better efficacy signal was observed, with ORR 66.7% (confirmed ORR 53.3%) and DCR 96.7%. The median duration of response (DoR) was not reached yet, the 6-month DoR rate was 75.4% (95% CI, 39.8-91.7). The median progression free survival (PFS) was 8.2m (PFS events 46.7%), the 6-month and 9-month PFS rate were 58.9% (95% CI, 39.0-74.3) and 47.3% (95% CI, 26.1-65.8), respectively, with a median follow-up of 8.1 months, and the data is immature.
• As of November 30 2022, IBI351 was well tolerated. No dose limiting toxicity (DLT) was reported and maximum tolerated dose (MTD) was not reached. Treatment-related adverse events (TRAEs) occurred in 94.0% (63/67) patients and the most common TRAEs were anemia, pruritus, transferase increased, asthenia, protein urine present and bilirubin increased. The majority of the TRAEs were grade 1-2 with 31.3% of patients reporting ?grade 3 TRAEs. There were no TRAEs led to treatment discontinuation or death.

Innovent is also exploring the potential of IBI351 in combination therapy for previously-untreated advanced NSCLC patients with KRAS G12C mutation. Two Phase 1b studies of IBI351, in combination with cetuximab (ERBITUX®, EGFR inhibitor) and sintilimab (TYVYT®, PD-1 inhibitor) respectively, are currently ongoing.

Besides, IBI351 monotherapy also demonstrated excellent efficacy and safety in previously-treated advanced colorectal carcinoma (CRC) patients with KRAS G12C mutation, of which the preliminary results were presented at the American Society of Clinical Oncology (ASCO) 2023. In May 2023, IBI351 became China's first KRAS G12C inhibitor to receive NMPA Breakthrough Therapy Designation as monotherapy for CRC patients with KRAS G12C mutation who have received at least two systemic therapies.

About KRAS G12C Mutated Non-small Cell Lung Cancer

Lung cancer is one of the malignancies with the highest incidence and mortality worldwide, among which non-small cell lung cancer (NSCLC) is the most common pathological type, accounting for about 85% of all lung cancers. KRAS mutations are common driver gene mutations in NSCLC, most of which occur in lung adenocarcinoma. KRAS mutations rarely co-exist with driver mutations such as EGFR and ALK, and patients with advanced NSCLC with KRAS G12C mutations are often unable to benefit from the multiple drugs already on the market that target these mutations or rearrangements. After the progress of first-line standard treatment in this population, there are limited second-line treatment options with low effective rate and poor prognosis.

About IBI351 (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.

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 (GenFleet R&D code: GFH925) 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 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 advanced CRC patients with KRAS G12C mutation who have received at least two systemic therapies. In November 2023, the CDE of NMPA accepted and granted Priority Review designation to the NDA for IBI351 for the treatment of advanced NSCLC patients harboring KRAS G12C mutation who have received at least one systemic therapy.

About Innovent

Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to discover and develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to discovering and developing, manufacturing and commercializing high-quality innovative medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, and ophthalmology diseases to enhance the quality of the patients' lives. Innovent has 10 products in the market, including TYVYT® (Sintilimab Injection), BYVASDA® (Bevacizumab Injection), SULINNO® (Adalimumab Injection), HALPRYZA® (Rituximab Injection), Pemazyre® (Pemigatinib Oral Inhibitor), olverembatinib, Cyramza® (Ramucirumab Injection), Retsevmo® (Selpercatinib Capsules ), FUCASO® (Equecabtagene  Autoleucel Injection) and SINTBILO® (Tafolecimab Injection). Additionally, we have 2 NDA under NMPA review, 5 assets in Phase III or pivotal clinical trials, and 19 more molecules in early clinical stage.

Innovent has also entered into 30 strategic collaborations with Eli Lilly, Roche, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. We strive to work with many collaborators to help advance the biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives.

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.

[1] Priority Review Designation accelerates the research and development of innovative drugs that have significant clinical advantages and fills urgent medical needs. According to the Provisions for Drug Registration (SAMR Order No. 27) and Working Procedures for Priority Review and Approval of Drug Marketing Authorization (Interim) (No. 82 of 2020) implemented on July 1, and July 7, 2020, respectively, the regulatory authority will prioritize the review process and evaluation resources for NDAs which helps accelerate the market access of these innovative drugs. Priority review designation is not an approval for marketing the drug.

SOURCE Innovent Biologics