taminadenant (NIR178)

However, unlike blinatumomab, which tends to induce T cell exhaustion, we showed that the release of PBF-509 from NanoBiTE suppressed the A2AR pathway and substantially improved tumor cell killing induced by NanoBiTE. Moreover, NanoBiTE treatment led to substantially reduced tumor burden in vivo in a humanized mouse model. Our results demonstrate that NanoBiTE is a safe and potent bispecific therapy that can also reduce T cell exhaustion for cancer immunotherapy.

Furthermore, overexpression of PNP or using taminadenant, a A2aR-targeting inhibitor used in clinical trials, significantly enhances the EGFR-targeted therapeutic response in vitro, as well as in patient-derived organoids, cell-derived xenografts and mouse models bearing human EGFR-driven spontaneous lung tumor. Overall, our findings clarify the role of inosine metabolism in TKI resistance, highlighting a potential therapeutic strategy-targeting the inosine/A2aR axis-to counteract EGFR-TKI tolerance in LUAD treatment.

P1, N=40, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Sep 2025 --> Mar 2026 | Trial primary completion date: Sep 2025 --> Mar 2026

P1, N=40, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2025 --> Sep 2025 | Trial primary completion date: Feb 2025 --> Sep 2025

P1, N=40, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jul 2025 --> Feb 2025 | Trial primary completion date: Jul 2025 --> Feb 2025

P1, N=40, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=180 --> 40

P1, N=77, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business reasons

P1, N=77, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=145 --> 77

P1, N=145, Recruiting, Novartis Pharmaceuticals | Trial completion date: Feb 2025 --> Sep 2023 | Trial primary completion date: Feb 2025 --> Sep 2023

P1, N=145, Recruiting, Novartis Pharmaceuticals | Trial completion date: Aug 2024 --> Feb 2025 | Trial primary completion date: Aug 2024 --> Feb 2025

The study demonstrated the potential clinical utility of early AE-derived biomarkers in predicting positive and negative clinical outcomes. It could be TrAEs or combination of TrAEs and nonTrAEs from overall AEs, toxicity category AEs, to individual AEs with low-grade event leaning to encouraging effect and high-grade event to undesirable impact. Moreover, the methodology of the AE-derived biomarkers could change current AE analysis practice from a descriptive summary into modern informative statistics. It modernizes AE data analysis by helping clinicians discover novel AE biomarkers to predict clinical outcomes and facilitate the generation of vast clinically meaningful research hypotheses in a new AE content to fulfill the demands of precision medicine.

P2; Active, not recruiting --> Terminated; Sponsor decision