NMPA Accepts NDA and Grants Priority Review Designation to Innovent's Ipilimumab Injection, China's First Domestic CTLA-4 Inhibitor, in Combination with Sintilimab as Neoadjuvant Treatment for Colon C

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.

About Sintilimab

Sintilimab, marketed as TYVYT® (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells.iv

In China, sintilimab has been approved and included in the updated NRDL for seven indications. The updated NRDL reimbursement scope for TYVYT® (sintilimab injection) includes:

● For the treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy;

● For the first-line treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;

● For the treatment of patients with EGFR-mutated locally advanced or metastatic non-squamous non-small cell lung cancer who progressed after EGFR-TKI therapy;

● For the first-line treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;

● For the first-line treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;

● For the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;

● For the first-line treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.

Furthermore, sintilimab's eighth indication, in combination with fruquintinib for the treatment of patients with advanced endometrial cancer with pMMR tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation, was conditional approved by the NMPA in December 2024. And the NDA for sintilimab in combination with ipilimumab as neoadjuvant treatment for resectable MSI-H/dMMR colon cancer is under the NMPA review and has been granted Priority Review designation.

In addition, two clinical studies of sintilimab have met their primary endpoints:

● Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;

● Phase 3 study of sintilimab monotherapy as second-line treatment for squamous non-small cell lung cancer with disease progression following platinum-based chemotherapy.

About Innovent

Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 14 products in the market. It has 4 new drug applications under regulatory review, 2 assets in Phase III or pivotal clinical trials and 17 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Eli Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center.

Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.