HUTCHMED and Innovent Announce NDA Acceptance

HUTCHMED and Innovent Jointly Announce NDA Acceptance in China for Fruquintinib Combination with Sintilimab for the Treatment of Advanced Renal Cell Carcinoma

Hong Kong, Shanghai & Florham Park, NJ - Thursday, June 5, 2025: HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) and Innovent Biologics, Inc. ("Innovent") (HKEX: 01801) today jointly announce that the New Drug Application ("NDA") for the combination of fruquintinib and sintilimab for the treatment of patients with locally advanced or metastatic renal cell carcinoma who have failed prior treatment with one tyrosine kinase inhibitor ("TKI") has been accepted for review by the China National Medical Products Administration ("NMPA").

The NDA is supported by data from FRUSICA-2, a randomized, open-label, active-controlled registration study evaluating the efficacy and safety of fruquintinib in combination with sintilimab versus axitinib or everolimus monotherapy for the second-line treatment of advanced renal cell carcinoma. The study has met its primary endpoint of progression free survival ("PFS"), as assessed by blinded independent central review (BICR) according to RECIST 1.1 criteria. The combination also demonstrated improvements in secondary endpoints including objective response rate ("ORR") and duration of response ("DoR"). The safety profile was tolerable and no new safety signals were observed. Data from FRUSICA-2 will be submitted for presentation at an upcoming scientific conference. Additional details may be found at clinicaltrials.gov, using identifier NCT05522231.

"Kidney cancer continues to pose significant challenges in China, with limited treatment options for patients who fail first-line therapies. Submitting this NDA for the fruquintinib and sintilimab combination for advanced renal cell carcinoma marks an important step in our efforts to address this unmet need," said Dr Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED. "We are dedicated to making this combination therapy available to patients with renal cell carcinoma. At the same time, through ongoing research, we remain focused on exploring the full potential of this combination, as well as advancing our broader pipeline across multiple cancer types, to provide more patients with new and effective treatment options."

"The NDA acceptance of sintilimab and fruquintinib combination represents a significant step toward providing a more effective second line treatment option for patients with advanced renal cell carcinoma in China," said Dr Hui Zhou, Senior Vice President of Innovent. "Our PD-1 inhibitor, sintilimab (TYVYT®), has solidified its position as a cornerstone of immuno-oncology (IO) therapy with this NDA as its 10th indication, marking a meaningful milestone in lifecycle management and clinical value optimization."

In December 2024, the combination of fruquintinib and sintilimab received conditional approval from the China NMPA for the treatment of patients with advanced mismatch repair proficient ("pMMR") endometrial cancer who have failed prior systemic therapy and are not candidates for curative surgery or radiation, based on data from the FRUSICA-1 study (NCT03903705).

About Kidney Cancer and Renal Cell Carcinoma

It is estimated that approximately 435,000 new patients were diagnosed with kidney cancer worldwide in 2022.[1] In China, an estimated 74,000 new patients were diagnosed with kidney cancer in 2022.[2] Approximately 90% of kidney tumors are renal cell carcinoma.

About Fruquintinib

Fruquintinib is a selective oral inhibitor of all three vascular endothelial growth factor receptors ("VEGFR") -1, -2 and -3. VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy.[3]

About Fruquintinib Approvals

Fruquintinib is co-developed and co-commercialized in China by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE®. It is approved for the treatment of patients with metastatic colorectal cancer who have previously received fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy, and those who have previously received or are not suitable to receive anti-VEGF therapy or anti-epidermal growth factor receptor (EGFR) therapy (RAS wild-type) in China. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. Since its launch in China, over 100,000 patients with colorectal cancer have been treated with fruquintinib.

The combination of ELUNATE® (fruquintinib) and TYVYT® (sintilimab injection) has conditional approval in China for the treatment of patients with advanced pMMR endometrial cancer who have failed prior systemic therapy and are not candidates for curative surgery or radiation.

Takeda holds the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside mainland China, Hong Kong and Macau, marketing it under the brand name FRUZAQLA®. Fruquintinib received approval for the treatment of previously treated metastatic colorectal cancer in the US, Europe, Japan and many other countries around the world.

The safety and efficacy of fruquintinib for the following investigational uses have not been established and there is no guarantee that it will receive health authority approval or become commercially available in any country for the uses being investigated:

About Fruquintinib for Second-line Treatment of Renal Cell Carcinoma

Single-agent targeted therapy continues to be one of the primary choices for first-line treatment of advanced renal cell carcinoma in China. Notably, advanced renal cell carcinoma patients who have experienced failure with single-agent targeted therapy previously still indicate an unmet medical need.

Results from a proof-of-concept Phase Ib/II study of fruquintinib plus sintilimab were published in Targeted Oncology in January 2025. The combination showed promising efficacy and a tolerable safety profile in this setting. At the data cutoff of October 9, 2024, all 20 enrolled previously treated patients were evaluable for efficacy, with a median follow-up duration of 45.7 months. The confirmed ORR was 60.0% and DCR was 85.0%. Median DoR was 13.9 months and median PFS was 15.9 months. Overall survival ("OS") was not reached, and the 36-month OS rate was 58.3%.[4]

About Sintilimab

Sintilimab, marketed as TYVYT® (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed and co-commercialized by Innovent and Eli Lilly and Company, 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. [5]

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:

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.

Two NDAs for sintilimab are currently under the NMPA review, including:

• 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 combination with fruquintinib for the treatment of patients with locally advanced or metastatic renal cell carcinoma who failed prior treatment with a TKI.

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;

Statement: Innovent does not recommend the use of any unapproved drug(s)/indication(s).

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 15 products in the market. It has 3 new drug applications under regulatory review, 4 assets in Phase III or pivotal clinical trials and 15 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Lilly, Sanofi, Incyte, LG Chem and MD Anderson Cancer Center.

Statement:

• Innovent does not recommend the use of any unapproved drug (s)/indication(s).
• Ramucirumab (Cyramza®) and Selpercatinib (Retsevmo®) and Pirtobrutinib (Jaypirca®) were developed by Eli Lilly and Company.

Medical Information

[4] Xu H, et al. Fruquintinib Plus Sintilimab in Patients with Treatment‑Naïve and Previously Treated Advanced Renal Cell Carcinoma: Results from a Phase Ib/II Clinical Trial. Targeted Oncology. 2025; 20:113-125. doi.org/10.1007/s11523-024-01120-6.