Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, announces that the New Drug Application (NDA) for ipilimumab injection (anti-CTLA-4 monoclonal antibody; R&D Code: IBI310) has been accepted by the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) and granted Priority Review designation[1] in combination with sintilimab as neoadjuvant treatment for resectable microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colon cancer.

This is China's first NDA for a domestic CTLA-4 inhibitor and another milestone strengthening sintilimab's leadership position in cancer immunotherapy. Immune checkpoint blockade (ICB) therapy targeting PD-1 and CTLA-4 has transformed oncology treatment, ipilimumab with sintilimab as a neoadjuvant treatment could increase R0 resection rate, achieve pathological complete response, and relieve the majority of patients from adjuvant chemotherapy burdens. This novel treatment is also expected to reduce recurrence rate and improve long-term prognosis, anticipated to benefit MSI-H/dMMR colon cancer patients upon NDA approval.

The NDA acceptance and Priority Review designation are based on results from a randomized, controlled, multicenter, pivotal Phase 3 clinical trial (NeoShot, NCT05890742) which evaluated the safety and efficacy of ipilimumab  combined with sintilimab as neoadjuvant therapy and as compared with direct radical surgery for MSI-H/dMMR colon cancer. The primary endpoints are pathologic complete response (pCR) rate and event-free survival (EFS). Interim analysis by the Independent Data Monitoring Committee (IDMC) showed that the NeoShot trial has met its primary endpoint. Detailed results will be presented at future academic conferences or published in academic journals.

Previously, the results of a randomized controlled Phase 1b trial evaluating ipilimumab in combination with sintilimab as neoadjuvant treatment for MSI-H/dMMR colon cancer were presented orally at the 2024 American Society of Clinical Oncology (ASCO) Annual Meetingⁱ. Based on promising Phase 1b results, the CDE has granted Breakthrough Therapy Designation (BTD) for ipilimumab.

• As of February 4, 2024, 101 patients were enrolled and randomized to receive ipilimumab plus sintilimab (n=52) or sintilimab alone (n=49).
• In the per-protocol population, the pCR rate in the ipilimumab-plus-sintilimab arm was significantly higher than in the sintilimab-alone arm（80.0% vs 47.7%, p=0.0007）.
• All patients in both treatment arms had R0 resection. With median follow-up of 5.65 months, no patient had disease recurrence.
• At postoperative pathological evaluation, 3.9% of patients with ipilimumab plus sintilimab and 15.9% of patients with sintilimab alone were stage N+. The majority of patients could be relieved from adjuvant treatment according to clinical guidelines.
• Ipilimumab -plus-sintilimab increased neither safety risk compared to sintilimab alone nor risk for subsequent surgery delay or cancellation.

The Principal Investigator of the NeoShot study, Prof. Ruihua Xu from Sun Yat-sen University Cancer Center, stated: "At present, R0 resection for certain locally advanced colon cancer patients remains a significant challenge, along with risks of extensive trauma and poor prognosis. The results of the FOxTROT study suggested that neoadjuvant chemotherapy is not effective in MSI-H/dMMR colon cancer, and the pCR rate is only around 5%ⁱⁱ. The NeoShot trial is the first randomized, controlled, Phase 3 clinical trial to show promising efficacy of dual checkpoint inhibition as neoadjuvant therapy in MSI-H/dMMR colon cancer. Results from the phase 1b study suggest that ipilimumab with sintilimab as short-term neoadjuvant treatment could increase R0 resection rate, achieve pathological complete response, and relieve patients from adjuvant chemotherapy burdens. This novel treatment is also expected to lower recurrence rate and improve long-term prognosis ⁱ.As this dual immunotherapy regimen has the potential to change clinical practice, we look forward to the NDA approval of this novel drug to benefit more MSI-H/dMMR colon cancer patients soon. "

Dr. Hui Zhou, Senior Vice President of Innovent, stated: "There is a huge unmet clinical need for neoadjuvant therapy of resectable MSI-H/dMMR colon cancer in China. Interim analysis showed that the NeoShot trial has met its primary endpoint. With Innovent's highly efficient and high-quality clinical development, ipilimumab has become China's first domestic CTLA-4 inhibitor to submit an NDA. We will actively cooperate with regulatory authorities to accelerate approval, and provide a new treatment option for patients with resectable MSI-H/dMMR colon cancer in China."

About Ipilimumab

Ipilimumab (R&D code: IBI310) is a fully human monoclonal antibody injection independently developed by Innovent. Ipilimumab can specifically bind cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), thereby blocking CTLA-4 mediated T cell inhibition, promoting T cell activation and proliferation, improving tumor immune response, and achieving anti-tumor effects. ⁱⁱⁱ

The NDA for ipilimumab in combination with sintilimab as neoadjuvant treatment for resectable microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colon cancer is under the NMPA review and has been granted Priority Review designation.