South San Francisco, Calif. – September 15, 2026 -- Apeximmune Therapeutics said a peer-reviewed study published in Nature independently validates PLA2G2D as a novel immune checkpoint capable of overcoming resistance to anti-PD-1 cancer therapies, with the company's lead antibody AI-306 targeting an IND filing in the second quarter of 2027.
Two independent research teams identified the same target through different methods
Apeximmune's computational screen of more than 9,000 primary tumor samples from The Cancer Genome Atlas ranked PLA2G2D as its top novel checkpoint candidate, ahead of PD-1 and CTLA-4 in the same analysis. Working separately and without knowledge of Apeximmune's program, researchers at Erasmus University Medical Center in Rotterdam used spatial proteogenomic analysis of melanoma patient samples with divergent outcomes and arrived at PLA2G2D as a top hit in dendritic cell and macrophage populations linked to poorer prognosis.
Apeximmune uncovered an enzyme-independent mechanism that eluded prior drug programs
Previous efforts targeting the broader sPLA2 enzyme family, including terminated late-stage small-molecule inflammation programs at major pharmaceutical companies, assumed enzymatic activity drove the biology. Apeximmune demonstrated that an enzyme-dead form of PLA2G2D retains full immunosuppressive activity, showing the checkpoint's role in tumor immune evasion operates independently of its enzymatic function.
Preclinical data show PLA2G2D blockade restores immunity and potentiates PD-1 response
The Nature findings report that PD-1 and PLA2G2D act through nonredundant, reciprocally regulated pathways. Blocking PLA2G2D restored anti-tumor immunity in preclinical models resistant to anti-PD-1 therapy and enhanced anti-PD-1 activity in tumor types otherwise unresponsive to checkpoint inhibition, pointing to potential use both as a standalone option for PD-1 failures and as a combination approach for treatment-resistant, immunologically "cold" tumors.
AI-306 advances through IND-enabling studies with a 2027 filing target
AI-306, Apeximmune's first-in-class monoclonal antibody, blocks both the enzymatic and non-enzymatic activity of PLA2G2D and is covered by patents spanning target antagonism, antibody constructs and combination therapies. Cell line development is underway, GLP toxicology studies are scheduled to begin in late 2026, and the company has built proprietary PLA2G2D knockout and humanized mouse models to support the program.
Response rates to anti-PD-1 remain in the single digits for some cancers
Anti-PD-1 therapies have transformed treatment for certain cancers, but most patients across indications fail to respond or eventually relapse, with response rates falling to single digits in gastrointestinal and other tumor types, according to the companies. Dan Ross, managing partner at BioPharma Capital and an Apeximmune advisor, said the Nature publication marks an inflection point for the AI-306 program and that the firm is actively engaging with partners to accelerate the therapy toward patients.