FL115 Introduction:

IL -15

Interleukin-15 (IL-15) is a rare cytokine that can selectively activate natural killer cells (NK cells) while also stimulating specific memory T cells. Existing tumor immunotherapy drugs, such as immune checkpoint inhibitors, primarily focus on activating T cells. IL-15 offers a new mechanism for tumor killing and plays a significant role in tumor immunotherapy.

 

In April 2024, the world's first IL-15 super agonist, Anktiva^®, was approved for marketing in the United States. Its combination therapy with PD-1 monoclonal antibodies has advanced to Phase 3 clinical trials. Meanwhile, companies such as Nektar Therapeutics, Sanofi, and BeiGene are also developing various types of IL-15 agonists, which are currently in Phase 1/2 clinical trials.

 

FL115

Clinical translation of of IL-15 faces significant challenges, such as its small molecular weight, short half-life, and functionality that depends on binding to receptors on different immune cells. Forlong Biotech has developed FL115, a fusion protein composed of IL-15, IL-15Rα, and Fbody, through its own platform technology, significantly expanding the therapeutic window. FL115 has demonstrated superior safety and tumor-killing ability to Anktiva^® in multiple preclinical models. Currently, multiple clinical trials of FL115 are ongoing in China and the United States. As a monotherapy, it has shown good safety and initial clinical efficacy in patients with advanced solid tumors. It is the only IL-15 super agonist to achieve partial response (PR) as a monotherapy and has the potential to be the best-in-class globally.

 

IL-15 has been hindered by its low molecular weight and short half-life. Leveraging proprietary FBody platform, Forlong Biotech engineered a single-arm IL-15 fusion protein that markedly extends half-life and widens the therapeutic window. FL115 is currently in multiple Phase I clinical studies in China and the United States, showing robust safety profile and initial clinical efficacy in patients with advanced solid tumors. It is the only IL-15 super agonist to achieve partial response (PR) as a monotherapy and has the potential to be the best-in-class globally, currently being advanced to combo therapy with PD-1 antibodies in clinic. FL115 monotherapy and BCG combo has shown robust safety profile and initial clinical efficacy in NMIBC, currently being advanced to Phase II.

FL116 Introduction:

IL-18

Interleukin-18 (IL-18) is a pro-inflammatory cytokine that activates effector T cells and NK cells, and induces the secretion of IFN-γ, thereby transforming "cold" tumors into "hot" tumors. Therefore, it is considered an ideal candidate molecule for cancer immunotherapy. However, the presence of IL-18 binding protein (IL-18BP) in the tumor microenvironment can antagonize the binding of IL-18 to its receptor, impeding its function. This has become a major bottleneck in the development of IL-18 agonists. Additionally, CMC issues limit the drug development of wild-type IL-18. Currently, the most advanced IL-18 agonist globally is in Phase I clinical trials.

Forlong IL-18 assets

Leveraging its Intelligent Biomolecular Discovery Platform and Syntokine^® Synthetic Cytokine Platform, Forlong Biotech has developed a portfolio of IL-18 mutants with different preference of IL-18 receptor affinities vs IL-18 binding protein, as well as better drug-like properties.These IL-18 mutant molecules can be combined with other proteins (such as monoclonal antibodies) to develop multiple product pipelines.

• FL116 is an anti-PD-1/lL-18 fusion protein that can significantly enhance binding to T cells through cis- action, activating effector T cell functions. It has demonstrated potent tumor-killing capability in preclinical studies of several tumor models that are resistant to immune checkpoint inhibitors (CPI).
• FL117 is a tumor cell-targeted IL-18 fusion protein that can selectively recruit and activate T cells in the tumor microenvironment, mediating potent anti-tumor killing ability.
• FL118 is a non-targeted IL-18 fusion protein that can systemically activate effector T cells, and hold promise when combined with other immunotherapies across multiple indications.

FL117 Introduction:

IL-18

Interleukin-18 (IL-18) is a pro-inflammatory cytokine that activates effector T cells and NK cells, and induces the secretion of IFN-γ, thereby transforming "cold" tumors into "hot" tumors. Therefore, it is considered an ideal candidate molecule for cancer immunotherapy. However, the presence of IL-18 binding protein (IL-18BP) in the tumor microenvironment can antagonize the binding of IL-18 to its receptor, impeding its function. This has become a major bottleneck in the development of IL-18 agonists. Additionally, CMC issues limit the drug development of wild-type IL-18. Currently, the most advanced IL-18 agonist globally is in Phase I clinical trials.

Forlong IL-18 assets

Leveraging its Intelligent Biomolecular Discovery Platform and Syntokine^® Synthetic Cytokine Platform, Forlong Biotech has developed a portfolio of IL-18 mutants with different preference of IL-18 receptor affinities vs IL-18 binding protein, as well as better drug-like properties.These IL-18 mutant molecules can be combined with other proteins (such as monoclonal antibodies) to develop multiple product pipelines.

• FL116 is an anti-PD-1/lL-18 fusion protein that can significantly enhance binding to T cells through cis- action, activating effector T cell functions. It has demonstrated potent tumor-killing capability in preclinical studies of several tumor models that are resistant to immune checkpoint inhibitors (CPI).
• FL117 is a tumor cell-targeted IL-18 fusion protein that can selectively recruit and activate T cells in the tumor microenvironment, mediating potent anti-tumor killing ability.
• FL118 is a non-targeted IL-18 fusion protein that can systemically activate effector T cells, and hold promise when combined with other immunotherapies across multiple indications.

FL118 Introduction:

IL-18

Interleukin-18 (IL-18) is a pro-inflammatory cytokine that activates effector T cells and NK cells, and induces the secretion of IFN-γ, thereby transforming "cold" tumors into "hot" tumors. Therefore, it is considered an ideal candidate molecule for cancer immunotherapy. However, the presence of IL-18 binding protein (IL-18BP) in the tumor microenvironment can antagonize the binding of IL-18 to its receptor, impeding its function. This has become a major bottleneck in the development of IL-18 agonists. Additionally, CMC issues limit the drug development of wild-type IL-18. Currently, the most advanced IL-18 agonist globally is in Phase I clinical trials.

Forlong IL-18 assets

Leveraging its Intelligent Biomolecular Discovery Platform and Syntokine^® Synthetic Cytokine Platform, Forlong Biotech has developed a portfolio of IL-18 mutants with different preference of IL-18 receptor affinities vs IL-18 binding protein, as well as better drug-like properties.These IL-18 mutant molecules can be combined with other proteins (such as monoclonal antibodies) to develop multiple product pipelines.

• FL116 is an anti-PD-1/lL-18 fusion protein that can significantly enhance binding to T cells through cis- action, activating effector T cell functions. It has demonstrated potent tumor-killing capability in preclinical studies of several tumor models that are resistant to immune checkpoint inhibitors (CPI).
• FL117 is a tumor cell-targeted IL-18 fusion protein that can selectively recruit and activate T cells in the tumor microenvironment, mediating potent anti-tumor killing ability.
• FL118 is a non-targeted IL-18 fusion protein that can systemically activate effector T cells, and hold promise when combined with other immunotherapies across multiple indications.