LNL-005 Advanced Drug Monograph

LNL-005 Report

Name: LNL-005 Name (English): LNL-005

Drug Type: Bispecific antibody

Synonyms: BIS5, LB1410

Target: PD-1 x TIM3

Action: Inhibitor

Mechanism of Action: LNL-005 is a bispecific antibody that simultaneously targets Programmed cell death protein 1 (PD-1) and Hepatitis A virus cellular receptor 2 (TIM3). By blocking both PD-1 and TIM3 pathways, LNL-005 aims to enhance the immune response against cancer cells, particularly in patients resistant or refractory to PD-1/PD-L1 inhibitor treatments. This dual blockade can improve T cell activation and function, as well as modulate the activity of other immune cells like NK cells and dendritic cells.

Therapeutic Areas:

• Neoplasms (Cancer)
• Immune System Diseases
• Digestive System Disorders

Active Indication:

• Metastatic Solid Tumor
• Advanced cancer
• Advanced Malignant Solid Neoplasm

Inactive Indication: Not specified.

Highest Phase of Development: Phase I

Countries/Locations of Clinical Trials:

• China
• United States

Mechanism of Action Details: LNL-005 is engineered with two distinct antigen-binding fragments (Fabs), one for PD-1 and one for TIM3. This allows it to simultaneously bind to both targets on immune cells and tumor cells. By doing so, it disrupts the immunosuppressive signals mediated by these checkpoint proteins, leading to increased anti-tumor immunity.

Clinical Trial Information: A Phase I, multicenter, open-label study (NCT05357651) is ongoing in patients with advanced and/or metastatic solid tumors in China to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of LNL-005.

Preliminary Efficacy: Preclinical studies in tumor models resistant to PD-1 antibodies have shown that LNL-005 can inhibit tumor growth and improve survival rates. Early data from the Phase I trial have shown some stable disease in heavily pre-treated patients with Non-Small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC).

Safety and Tolerability: In the ongoing Phase I study, no dose-limiting toxicities have been observed up to the evaluated doses. The most common treatment-related adverse event with an incidence of ≥10% was anemia (Grade 1-2).

Potential Side Effects: As an immune checkpoint inhibitor, LNL-005 may have the potential to cause immune-related adverse events (irAEs) due to the activation of the immune system. These can affect various organs and may include, but are not limited to:

• Fatigue
• Rash
• Diarrhea
• Colitis
• Hepatitis
• Endocrine disorders (e.g., hypothyroidism, adrenal insufficiency, type 1 diabetes)
• Kidney injury
• Myocarditis
• Infusion reactions

Note: This report is based on currently available information and is subject to change as more data from ongoing clinical trials become available.