GV20 Therapeutics announced promising Phase 1 clinical data for GV20-0251, a first-in-class monoclonal antibody targeting the novel immune checkpoint IGSF8, at the European Society for Medical Oncology (ESMO) Congress 2024. The results represent a significant milestone as the first clinical data for an AI-designed antibody against an AI-predicted target in oncology.
Safety Profile Demonstrates Tolerability Across Dose Range
The Phase 1/2 dose escalation study (NCT05669430) enrolled 38 heavily pre-treated patients with advanced solid tumors across six dose levels ranging from 0.5 to 20 mg/kg and two dosing schedules. The patient population had a median age of 62 years and a median of four prior lines of treatment, representing a challenging cohort with limited therapeutic options.
GV20-0251 demonstrated a favorable safety profile with no dose-limiting toxicities observed across all tested dose levels. Most treatment-related adverse events were grade 1 or 2, with only one case of grade 3 pneumonitis reported throughout the study. This safety profile supports continued development and potential combination strategies.
Preliminary Efficacy Signals in Melanoma Patients
Among 12 efficacy-evaluable patients with metastatic cutaneous melanoma, two confirmed partial responses were observed, indicating meaningful anti-tumor activity in this heavily pre-treated population. Additionally, 14 of 29 efficacy-evaluable patients across all tumor types demonstrated stable disease, with four patients showing tumor shrinkage.
"We are excited by these encouraging results for GV20-0251, which represent a significant milestone as the first clinical data for an AI-designed antibody against an AI-predicted target," said Dr. Shirley Liu, Co-founder and Chief Executive Officer of GV20 Therapeutics. "The favorable safety profile and preliminary efficacy signals, particularly in melanoma patients, support the potential of IGSF8 as a novel immune checkpoint target."
Pharmacokinetic Profile Supports Clinical Development
The study revealed dose-proportional pharmacokinetics with a half-life of approximately 25.6 days, consistent with typical monoclonal antibody profiles. Full target occupancy on circulating T cells was achieved at doses of 3 mg/kg and above, providing important guidance for optimal dosing in future studies.
Novel Mechanism Targets Immune Resistance
GV20-0251 is designed to enhance natural killer (NK) cell killing of malignant cells, upregulate dendritic cell antigen presentation, and increase T cell signaling. This multi-faceted mechanism of action may be particularly relevant for patients with antigen presentation-deficient tumors, which often demonstrate resistance to current immune checkpoint inhibitors targeting PD-1 or PD-L1.
The IGSF8 target represents a novel approach to immune checkpoint inhibition, potentially addressing limitations of existing therapies in certain patient populations. The AI-driven discovery and design process that identified both the target and therapeutic antibody demonstrates the potential for artificial intelligence to accelerate drug development in oncology.
Combination Strategy Under Investigation
GV20 Therapeutics is currently recruiting patients with anti-PD-1-relapsed and refractory cancers for combination treatment with GV20-0251 and pembrolizumab. This combination approach aims to further evaluate drug safety, pharmacokinetics, pharmacodynamics, and efficacy in patients who have failed standard checkpoint inhibitor therapy.
The combination strategy reflects the company's hypothesis that IGSF8 inhibition may restore immune function in tumors that have become resistant to PD-1 blockade, potentially expanding treatment options for patients with limited alternatives.
