On July 5, 2021 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, and Laekna Therapeutics Shanghai Co., Ltd. (Laekna), an emerging innovative pharma company based in China’s "Zhangjiang Pharma Valley" and New Jersey in the U.S., focusing on developing new ground-breaking innovative therapies to treat cancer and liver diseases, reported they have entered into a collaboration agreement to evaluate the combination of Innovent’s PD-1 inhibitor sintilimab and Laekna’s pan-AKT kinase inhibitor afuresertib (Press release, Innovent Biologics, JUL 5, 2021, View Source;agreement-to-co-develop-combination-therapy-of-sintilimab-and-afuresertib-in-clinical-studies-in-china-301325531.html [SID1234584596]).
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Under the agreement, the two companies will work together to conduct clinical studies assessing the combination of sintilimab and afuresertib (LAE002) in patients with multiple types of solid tumors that have been refractory – or failed to respond – to treatment with PD-1/PD-L1 inhibitors. The trials will evaluate the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the combination therapy. An investigational new drug (IND) application will soon be filed with the National Medical Products Administration (NMPA) in China.
Dr. Hui Zhou, Senior Vice President of Clinical Development of Innovent, said, "Since our inception in 2011, Innovent has built a robust pipeline of assets with five innovative drugs approved for marketing. Many unmet medical needs still exist for cancer patients around the world. To help address this, Innovent explores multiple indications and combinations of therapies when developing its existing and new drug candidates. At the same time, we seek to work together with additional collaborative partners as the Chinese biopharmaceutical industry continues to rapidly expand. Innovent is impressed with Laekna’s R&D pipeline and research team, and we look forward to our close collaboration and future possibilities produced by this clinical development agreement."
Dr. Yue Yong, Chief Medical Officer of Laekna, stated, "We hope our leading pipeline candidate afuresertib can potentially become a first-in-class targeted treatment in multiple types of cancer by demonstrating improved efficacy and acceptable safety in clinical trials. Notably, sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 inhibitor to be included in the list that year. In addition, sintilimab, in combination with pemetrexed and platinum chemotherapy, is currently being reviewed by the U.S. FDA for a potential BLA approval in the first-line treatment of nonsquamous non-small cell lung cancer. We now have the opportunity to explore the combination therapy of afuresertib and sintilimab in multiple types of solid tumors, with a particular focus on cancers that have commonly shown to be refractory to treatment with PD-1/PD-L1 inhibitors. We hope this combination therapy demonstrates results that can ultimately lead to it becoming a new treatment option for people with these difficult-to-treat cancers."
About Sintilimab
Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an 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. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.
In China, sintilimab has been approved for four indications, including:
The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma
Additionally, Innovent currently has a regulatory submission under review in China for sintilimab for the second-line treatment of squamous non-small cell lung cancer.
Innovent also has two clinical studies of sintilimab that have met their primary endpoints:
In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma
The second-line treatment of esophageal squamous cell carcinoma
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.
Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.
About Afuresertib (LAE002)
Afuresertib (LAE002) is an oral, small molecule pan-AKT kinase inhibitor. It has been investigated in over 10 Phase 1/2 clinical trials, including ovarian cancer, gastric cancer, multiple myeloma, and melanoma. These studies have demonstrated that afuresertib has strong anti-cancer activities and a tolerable safety profile in these studies.
In recent years, AKT (a serine/threonine-protein kinase) has emerged as an important mechanism in oncology, as it plays an important role in regulating various cell functions such as metabolism, survival, proliferation, tissue invasion, and chemotherapy resistance. PTEN deletion and AKT/PIK3CA alteration may lead to excessive activation of the AKT signaling pathways, which is one of the key drivers for cancer growth. The increased activation of the AKT signaling pathway is particularly common in recurrent ovarian cancer, breast cancer, and prostate cancer.
The global randomized, open-label, multi-center Phase 2 PROFECTA-II clinical trial of afuresertib is the world’s first registration-directed clinical study of a pan-AKT kinase inhibitor to treat platinum-resistant ovarian cancer. Laekna currently expects primary results of the endpoints will be available in 2022 and will discuss the data with regulatory authorities if the study outcome supports it.