Leveraging our multi specific antibody platform to target and modulate the tumor microenvironment to enhance or re-activate anti-tumor immune response.
A bispecific antibody targeting PD-L1-positive tumors stimulates T cell via 4-1BB
QL301 activates 4-1BB only when concurrently engaged to PD-L1, an immune checkpoint mediator elevated in the immuno-suppressive tumor microenvironment. Unwanted toxicity associated with non-specific activation of 4-1BB is therefore minimized. QL301 blocks the interaction of PD-1 with PD-L1 independent of 4-1BB binding. The combination of 4-1BB activation and PD-L1 blockade promotes a robust and lasting anti-tumor immune response. QL301 was well tolerated in a toxicology study. A phase 1 clinical trial is ongoing.
Selective CD47 targeting to improve therapeutic windows
The ubiquitous expression of CD47 on normal cells, including red blood cells, presents a therapeutic challenge. Systemic targeting of CD47, by either anti-CD47 monoclonal antibodies or SIRPα-Fc fusion proteins, yielded only moderate clinical benefit due to severe adverse side effects, mainly anemia. QLSF has developed a tumor targeted CD47 bispecific antibody with reduced binding to red blood cells while retaining potent phagocytosis of tumor cells in vitro and delayed tumor growth in vivo. QL401 also blocked the PD-L1/PD-1 checkpoint, providing a secondary mechanism of immune reactivation. QL401 was well tolerated in a toxicology study without anemia. A phase 1 clinical trial is expected to start late Q4 2021.
A tumor targeted cytokine fusion with an improved therapeutic window
Cytokines are potent stimulators of the immune system and have long been investigated and used as therapeutics to treat cancer. However, free cytokines have short half-life and the lack tumor targeting often resulted in systemic toxicity. IL-15 is a stimulatory cytokine that shares the common beta and gamma receptors with IL-2. In contrast to IL-2, IL-15 is more selective for NK and effector memory T cells, with less proliferative effect on Tregs, making it a more preferred therapeutic candidate. QL415 is a PD-L1 x IL-15 fusion protein that was designed to enhance tumor accumulation and prolong blood circulation, thereby widening the therapeutic window. QL415 was highly effective in suppressing tumor growth in vivo, in contrast to PD-L1 monoclonal antibody or a non-targeted IL-15 fusion molecule. The follow up tumor rechallenge study showed lasting protective memory. QL415 was tolerated in a toxicology study well above the therapeutic efficacious dose. A phase 1 clinical trial is ongoing.
A novel T cell engager targeting CLEC12A-positive AML
QL325 is a T cell engager targeting CLEC12A on AML blasts. In healthy individuals, CLEC12A expression is limited to monocytes and CD34+CD38- progenitor cells. In vitro, QL325 activated T cells in a CLEC12A-dependent manner and redirected T cells to kill CLEC12A-positive AML cancer cells. QL325 suppressed the growth of AML tumors in multiple xenograft models, including ones that are resistant to venetoclax. A phase 1 clinical trial is ongoing to evaluate the safety and early efficacy of QL325 in patients with refractory or relapsed AML.
A novel T cell engager with enhanced safety profile targeting MSS colorectal cancer
QL335 targets the LY6G6D antigen on colorectal cancer cells. LY6G6D is a GPI-anchored membrane protein that is highly specific to the microsatellite stable (MSS) subtype of colorectal cancer (CRC), representing the majority of all CRC cases. QL335 demonstrated highly potent and specific killing of LY6G6D-positive cancer cells in vitro and in vivo. QL335 is being evaluated in a phase 1 clinical trial for safety and early efficacy.