LigaChem Biosciences’ antibody-drug conjugate (ADC) platform technology has shown promising results. Their new drug candidate IKS014 (LCB14) achieved a 50% objective response rate (ORR) in HER2-positive breast cancer patients previously treated with Enhertu.
LigaChem Biosciences announced that its partner, Iksuda Therapeutics, will present interim results from IKS014’s Phase 1 clinical trial at the San Antonio Breast Cancer Symposium (SABCS) in Texas, December 8-11.
IKS014 is a HER2-targeted ADC using LigaChem Biosciences’s proprietary ConjuAll platform. It’s designed for improved blood stability and selective release in cancer cells, using site-specific conjugation and a unique linker platform.
Notably, IKS014 carries an Monomethyl auristatin F (MMAF) payload, differing from Enhertu’s mechanism. It aims to offer a new option for patients resistant to topoisomerase 1 inhibitor (TOP1i) ADCs like Enhertu.
In the trial, 5 out of 10 evaluable HER2-positive breast cancer patients with prior Enhertu treatment showed partial responses (PR). The 50% ORR included some patients maintaining response for over 18 months.
These heavily pre-treated patients had a median of six prior therapies. Remarkably, responses were seen even in patients whose disease progressed on Enhertu, suggesting potential to overcome existing drug resistance.
Enhertu, co-developed by AstraZeneca and Daiichi Sankyo, is a HER2-targeted ADC combining an antibody with a TOP1i class cytotoxic drug.
HER2, a protein overexpressed in some breast cancers, characterizes about 15-20% of all breast cancer cases.
ADC technology combines cytotoxic drugs with antibodies targeting specific cancer cells, leveraging both antibody specificity and chemotherapy effects.
LigaChem Biosciences states these results show a high response rate among HER2-positive breast cancer patients previously treated with Enhertu, compared to existing therapies.
This outcome is considered significant. A recent MD Anderson Cancer Center study found no responses in 21 patients receiving Kadcyla after Enhertu, with a median progression-free survival of just 2.2 months.
Safety results were also favorable. Among 105 Phase 1 patients, only 15.2% experienced grade 3 treatment-related adverse events. No grade 5 or serious treatment-related adverse events were reported.
Iksuda noted the absence of high-grade pneumonia, interstitial lung disease (ILD), neutropenia, anemia, and gastrointestinal toxicity.
LigaChem Biosciences has licensed IKS014 rights in Greater China to Fosun Pharma and global rights (excluding Greater China and Korea) to Iksuda. Fosun Pharma is conducting a Phase 3 trial in China comparing IKS014 to Kadcyla in HER2-positive breast cancer patients.
These results are based on April’s data analysis. Iksuda plans to present updated results, including additional patients, at the December conference.
LigaChem Biosciences Chief Executive Officer (CEO) Park Se-jin stated that IKS014 is the most advanced ADC platform technology program. Its design, with a payload mechanism different from Enhertu’s, has shown meaningful responses even in post-Enhertu patients, demonstrating potential to overcome payload resistance in clinical settings.