Laekna Therapeutics announced that the investigational new drug (IND) application of a combination therapy for the phase 1/2 clinical trial in patients with solid tumors who have been refractory to treatment with PD-1/PD-L1 inhibitors has been approved by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China. Laekna Therapeutics is an emerging innovative biopharmaceutical company focused on developing groundbreaking and innovative therapies to treat cancer and liver diseases. The IND approval marks a key milestone under the clinical research partnership Laekna and Innovent formed in July 2021.

The imminent phase 1/2 dose escalation study will evaluate the efficacy and safety of the combination of afuresertib (LAE002), sintilimab and chemotherapy in patients with specific types of solid tumors who have been refractory to treatment with PD-1/PD-L1 inhibitors. The Principal Investigator of the study is Professor Shen Lin, Vice President of Peking University Hospital and Cancer Institute and Director of the Department of Gastrointestinal Oncology. The combination therapy includes Laekna Therapeutics' pan-AKT kinase inhibitor afresertib, Innovent's sintilimab, and albumin-bound paclitaxel or docetaxel.

The phase 1 study aims to evaluate the safety of the three-drug combination, and determine the recommended phase 2 dose (RP2D). The phase 2 study will aim to evaluate the clinical efficacy and safety of the combination therapy in patients who have been refractory to treatment with PD-1/PD-L1 inhibitors (monotherapy or in combination with other oncology drugs) and who have suffered from one of the following five types of tumors:

• Non-small cell lung cancer (NSCLC)
• Gastric cancer/gastro-oesophageal junction cancer (GC/GEJC)
• Esophageal cancer (EsC)
• Cervical cancer (CC)
• Endometrial cancer (EC)

Professor Shen Lin explains, "As a serine/threonine kinase, AKT is a potential new target for cancer treatment. The results of multiple preclinical studies has showed that inhibiting AKT has the potential to restore the sensitivity of cancer cells to oncology therapies. Therapy resistance remains a common clinical problem and challenge for the further application of PD-1/PD-L1 blockade therapies despite their promising prospects. Statistics has showed that only some patients are estimated to have a positive response to PD-1/PD-L1 blockade therapies. In additional, for most patients with initial clinical response, acquired resistance remains a significant challenge. I have high expectations for this clinical trial involving an AKT inhibitor, and I hope it will provide a new treatment option for patients with specific solid tumors refractory to treatment with PD-1/PD-L1 inhibitors."

"After partnering with Innovent in July last year, we worked together closely to identify a development strategy and design the clinical study. With the support of our partners and Principal Investigator, we have succeeded in obtaining the IND approval from the CDE. For next step, our team will redouble our efforts to advance the clinical research," says Dr. Yue Yong, Chief Medical Officer of Laekna Therapeutics. "As immuno-oncology combination therapies have been approved for multiple types of early-stage cancers, patients' survival and quality of life have been significantly improved. But still, quite a few patients are refractory to immunotherapies. Through this clinical trial, we will work with Innovent to explore the potential of afuresertib, sintilimab, and chemotherapy in the treatment of patients with solid tumors who have been refractory to immunotherapies. The success of this study is expected to benefit more cancer patients resistant to immunotherapies."

Laekna Therapeutics Chairman and CEO Dr. Chris Lu commented, "A document recently released by the CDE, 'Guiding Principles for Clinical Research of Antitumor Pharmaceuticals Based on Clinical Value', specifically mentions that 'tumor resistance is a major challenge that cancer treatments and new medicines face during development'. These joint clinical trials conducted by Laekna Therapeutics and Innovent responds to the advice of those guiding principles, which state that 'attention should be given to the needs of patients with refractory conditions in order to find a new generation of breakthrough antitumor medicines to overcome the tumor resistance, or antitumor combination treatments that can overcome the refractory condition'. The team at Laekna Therapeutics will do everything we can to make rapid progress in advancing these clinical trials."

About Afuresertib
Afuresertib (LAE002) is a Class 1 new drug candidate in clinical development, for which Laekna Therapeutics has obtained the global exclusive licenses from Novartis. It is a potent next-generation small molecule pan-AKT kinase inhibitor.

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.

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 worldwide, 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 and included in the National Reimbursement Drug List (NRDL) 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 non-squamous 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 bevacizumab biosimilar for the first-line treatment of unresectable or advanced hepatocellular carcinoma.
• Additionally, sintilimab currently has three regulatory submissions accepted for review in NMPA, including:
• In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma;
• In combination with chemotherapy for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma;
• In combination with bevacizumab biosimilar and chemotherapy for EGFR-mutated non-squamous NSCLC following EGFR-TKI treatment.
• Additionally, two clinical studies of sintilimab have met their primary endpoints:
• Phase 2 study as second-line treatment of esophageal squamous cell carcinoma;
• Phase 3 study as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.

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 non-squamous non-small cell lung cancer