July 14, 2021
GigaGen Publishes Research Describing Novel Mechanism of Action and Therapeutic Potential of its anti-CTLA-4 Drug Candidate, GIGA-564
- Reduced checkpoint inhibitor activity of GIGA-564 versus current anti-CTLA-4 inhibitors results in superior anti-tumor activity and lower toxicity in murine models
- Data supports advancement of GIGA-564 into the clinic for cancer indications
South San Francisco, Calif., July 14, 2021 (GLOBE NEWSWIRE) -- GigaGen Inc., a biotechnology company advancing transformative antibody drugs for infectious diseases, transplant rejection and checkpoint resistant cancers, and a subsidiary of Grifols, announced today publication of research in BioRxiv entitled, “Lack of blocking activity in anti-CTLA-4 antibodies reduces toxicity, but not anti-tumor efficacy.” The publication describes the novel mechanism of action of its anti-CTLA-4 drug candidate, GIGA-564, selected due to its reduced checkpoint inhibition, which resulted in superior anti-tumor activity and lower toxicity in murine models compared to commercially available anti-CTLA-4 drugs.
“Our work suggests that new anti-CTLA-4 drugs should be optimized for depletion of intratumoral regulatory T cells (Tregs) versus strong blocking of CTLA-4 to its ligands, i.e. checkpoint inhibition. The latter has recently been associated with increased toxicities and dampening of the immune response to tumors by commercially available anti-CTLA-4 drugs, such as ipilimumab, due to preferential increase in proliferation of Tregs versus tumor-killing cytotoxic T cells,” said Erica Stone, vice president of Oncology at GigaGen. “We selected GIGA-564 due to its minimal checkpoint inhibition and its ability to deplete intratumoral Tregs in the tumor. The data presented in this study shows that GIGA-564 has increased anti-tumor efficacy and reduced toxicity in pre-clinical models compared to ipilimumab, demonstrating its potential to improve outcomes for cancer patients.”
David Johnson, Ph.D., MBA, founder and chief executive officer of GigaGen, added, “Current anti-CTLA-4s such as ipilimumab have shown promising results, but the majority of patients don’t see reduction of tumors and experience life-threatening toxicities. We are excited to continue our work to advance GIGA-564 into the clinic, which has the potential to offer improved efficacy and reduced toxicities compared to commercially available anti-CTLA-4 therapies. In the near future we expect to move GIGA-564 toward large-scale GMP manufacturing and regulatory approval for first-in-human studies in patients with life-threatening cancers.”
Key study highlights include:
- GIGA-564 has limited immune checkpoint inhibition activity and induced less proliferation of regulatory T cells compared to ipilimumab
- GIGA-564 showed increased anti-tumor efficacy but lower toxicity than ipilimumab in pre-clinical models
- GIGA-564’s minimal checkpoint inhibition activity led to reduced colon and skin inflammation than ipilimumab in pre-clinical models. Strong checkpoint inhibition is considered the major cause of colon and skin inflammation by ipilimumab.