SUZHOU and SHANGHAI China, Dec 26, 2024—Suzhou Forlong Biotechnology Co., Ltd. (“Forlong”), a clinical-stage biotech specializing in innovative cytokine drug discovery and development through synthetic immunology announced a clinical trial collaboration and supply agreement with Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that researches, develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major diseases. The collaboration will evaluate the combination therapy of FL115, an IL-15 super agonist, with Innovent’s TYVYT® (sintilimab injection), the market-leading anti-PD-1 inhibitor in China.

Under the collaboration agreement, Innovent will provide sintilimab injection free of charge for the combination treatment clinical trial, while Forlong will lead Phase 1/2 clinical studies in China to evaluate the safety, tolerability and efficacy of sintilimab injection combined with FL115 in patients with solid tumor. This partnership leverages the complementary strengths and expertise of both companies—Innovent's extensive experience with sintilimab in the field of anti-cancer treatment and Forlong's research and development advantages in immune agonists. Together, the companies aim to advance novel immune combination therapies to benefit more cancer patients.

IL-15 possesses the ability to activate NK cells and T cells, and its mechanism of action is highly synergistic with PD-1 antibodies. The clinical potential of such combination therapy has been demonstrated. At the 2024 WCLC, data from the Phase 2 QUILT 3.055 trial[i] showed that IL-15 plus CPI therapy in 2nd line or greater NSCLC demonstrated long-term median OS, independent of PDL1 status, and independent of prior lines of therapy in patients with acquired resistance to CPI. These findings support the novel mechanism of action of IL-15 to rescue CPI activity through the activation of NK and T cells, driving long-term memory, with median OS ongoing survival of 33% and 30% at 18 and 21 months respectively, exceeding the standard of care.

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 was approved and included in the National Reimbursement Drug List (NRDL) for seven indications in China, including lung, liver, gastric, and esophageal cancers, with an eighth indication recently approved. Innovent is continuously exploring sintilimab’s clinical value potential through combination therapies with ADCs, oncolytic viruses, cytokines, and more in various clinical studies.

FL115 is a long-acting IL-15/IL-15Rα monomeric Fc fusion protein independently developed by Forlong with global patents, boasting antibody-like yields. Ongoing Phase 1 clinical studies in China and the United States indicate that FL115 possesses promising development prospects.

Mr. En Ji, Co-founder & Chairman of Forlong, stated: “Tumors continue to evolve during treatment, and combination therapy is regarded as the development trend in clinical cancer treatment. We are pleased to collaborate with Innovent Biologics to jointly explore the broad prospects of combination therapy. IL-15 has an activating effect on NK cells and T cells[ii], thus PD-1 and IL-15 combination therapy is expected to enhance treatment efficacy and bring more clinical benefits to patients. This collaboration marks another significant milestone for Forlong in advancing innovative therapies for cancer.”

Dr. Hui Zhou, Senior Vice President of Innovent, stated: “We are delighted to embark on a clinical collaboration with Forlong. Sintilimab, as a cornerstone immunotherapy for cancer treatment, continues to strengthen its leading position while delivering significant clinical value. We anticipate that the synergistic effects of cytokine drugs and PD-1 immunotherapy could provide innovative treatment solutions for a wide range of cancer patients.”  

About FL115

FL115 is a new-generation, long-acting IL-15 super agonist independently developed by Forlong Biotechnology. It can expand and activate NK cells and T cells. Currently, three Phase 1 clinical studies of FL115 are ongoing in both China and the United States, demonstrate promising development prospects.

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[iii].

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.

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 Forlong

Forlong Biotechnology is an innovative research and development company driven by synthetic immunology, focusing on the development of protein drugs such as cytokines. The company is supported by internationally renowned laboratories for protein drug discovery. The company boasts proprietary platforms such as the Fbody® long-acting technology platform and the Syntokine® artificial cytokine platform. FL115, the IL-15 agonist based on these technology platforms, is currently undergoing Phase I clinical trials in both China and the United States, showcasing promising development prospects.

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 13 products in the market. It has 4 new drug applications under regulatory review, 34 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.

Statement:

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

（2）Ramucirumab (Cyramza) and Selpercatinib (Retsevmo) and Pirtobrutinib (Jaypirca) were developed by Eli Lilly and Company.

References

i https://cattendee.abstractsonline.com/meeting/20598/presentation/2571

Ii Robinson T O, et al.The potential and promise of IL-15 in immuno-oncogenic therapies[J].Immunology Letters, 2017:159-168.DOI:10.1016/j.imlet.2017.08.010.

iii Wang J, et al. Durable blockade of PD-1 signaling links preclinical efficacy of sintilimab to its clinical benefit. mAbs 2019;11(8): 1443-1451. DOI: 10.1080/19420862.2019.1654303.