On June 26, 2024, the clinical trial application for the domestic first βγ-biased PD1/IL2 fusion protein - KY-0118 injection developed independently by Novatim Immune Therapeutics (Zhejiang) Co., Ltd. in combination with atezolizumab for the treatment of locally advanced or metastatic solid tumors was officially approved by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA), and the clinical trial is about to commence. It is reported that this is the first clinical trial approval for a PD1-IL2v fusion protein + anti-PD-L1 in China, and it is also the fourth innovative drug project of Novatim to enter the clinical stage.
As of now, the KY-0118 injection, when used as a monotherapy, has completed the clinical phase Ia trial for the treatment of various advanced solid tumors. A total of 25 evaluable patients were included. Based on the current data, it appears to be more beneficial for the long-term benefits of patients while also being safer.
Preliminary effectiveness
A low dose (12 μg/kg) has already shown efficacy. The best disease control rate (DCR) in each dose group was 2/3 (67%), the objective response rate (ORR) was 1/3 (33%), and the longest progression-free survival (PFS) was over 9 months.
From the perspective of specific indications, the disease control rate (DCR) for melanoma was 3/3 (100%), with the longest progression-free survival (PFS) being 9 months; for renal cancer, the longest PFS was over 9 months; for triple-negative breast cancer, the first case received a positive response (reduction of 56%) in the first clinical assessment. The efficacy and other indications are still under continuous observation and exploration.
Preliminary safety
All patients were included in the safety analysis. The rate of grade 3 or higher drug-related adverse events (TEAE) was 4% (1 case), and the rate of grade 3 or higher drug-related serious adverse events (SAE) was also 4% (the same case). No DLT was observed in any of the dose groups, and further exploration of higher doses is currently underway.
Dr. Wu Guoxiang, the chairman and CEO of Novatim, stated that the strong R&D capabilities are the core advantage of Novatim. The company independently developed innovative technology platforms and multiple FIC pipelines from scratch. Besides the KY-0118 injection which has entered the clinical stage, the company's KQ-2003 product has also demonstrated very good efficacy and safety data in clinical trials. The hematological therapeutic effect of rrMM (with extramedullary involvement) is 94.4% (CR 88.9%), with multiple cases achieving PFS of over 18 months or more, and the median PFS has not been reached;
The hematological therapeutic effect of rrMM (with extramedullary involvement) is 71.4% of sCR/CR, with the longest PFS of over 18 months or more, and the median PFS has not been reached. In terms of safety, no grade 3 or higher CRS occurred, and the incidence of grade 3 or higher ICANS was 4%. While ensuring long-term efficacy, it also has a safety advantage.
Regarding KY-0118
The KY-0118 injection is the first βγ biased PD1/IL2 fusion protein developed based on the dual-function antibody platform independently researched and designed by Novatim. It has a high affinity for binding and blocking PD-1, selectively delivering IL-2 to PD-1-positive T cells, thereby targeting and preferentially activating tumor-specific T cells, which is more conducive to long-term benefits for patients. The monotherapy clinical trial is in Phase Ib and is about to obtain the FDA's IND approval for monotherapy and the IND approval for combination with PD-L1 monoclonal antibody. After its market launch, it is expected to become an innovative drug with annual sales of over 10 billion yuan.
Regarding Novatim
Novatim Immune Therapeutics (Zhejiang) Co., Ltd. was established in 2018. It is a biopharmaceutical technology enterprise specializing in the research and clinical application of innovative drugs for tumor immunotherapy. Based on clinical needs and differentiation, it is committed to establishing three research platforms through efficient and breakthrough research and development: dual-function antibody platform, nano-bispecific ADC platform, and enhanced dual-target CAR-T platform. It independently developed over 10 novel and differentiated potential FIC/BIC pipelines from scratch.
Based on the dual-functional antibody platform, the company independently developed the first PD1/IL2 fusion protein with a βγ bias in China. Currently, it is in the clinical Phase Ib stage as a single drug. Based on the nano-bispecific ADC platform, the company independently developed the world's first nano-bispecific ADC, and is about to obtain the IND approval in China and the US. Based on the enhanced dual-target CAR-T platform, the company independently developed the world's first CAR-T specifically targeting rrMM (with extramedullary involvement) and POEMS syndrome, and is currently in the clinical Phase I/IIa stage.
