Onconic Therapeutics' Nesuparib Suggests Potential for Small Cell Lung Cancer Treatment Through Multi-Modal Mechanism

Preclinical Research Results Presented at 'AACR 2026'

Simultaneous Regulation of c-Myc and YAP

Synergistic Effect Maximized in Combination with Irinotecan

Onconic Therapeutics' next-generation dual-target anticancer drug candidate, 'Nesuparib,' has demonstrated not only overwhelming cancer cell growth inhibition compared to existing treatments for small cell lung cancer (SCLC), but also confirmed a multi-modal mechanism that simultaneously blocks key pathways involved in tumor proliferation.

Oncogenic Therapeutics announced the preclinical research results of its anticancer drug candidate "Nesuparib," targeting the treatment of the intractable cancer type small cell lung cancer (SCLC), at the "2026 American Association for Cancer Research (AACR 2026)" held on the 19th (local time) in San Diego, USA. Oncogenic Therapeutics

On April 19 (local time), Onconic Therapeutics announced for the first time the preclinical research results of Nesuparib, its anticancer drug candidate targeting the treatment of the refractory cancer type small cell lung cancer, at the '2026 American Association for Cancer Research (AACR 2026)' held in San Diego, USA.

Small cell lung cancer is a representative refractory cancer characterized by a high proliferation rate and rapid recurrence. It is also marked by elevated expression of proliferation-related factors such as the c-Myc gene, which is involved in cell proliferation and apoptosis, and Ki-67, a marker of tumor cell proliferation. As current treatment options remain limited, there has been a continued need for more potent tumor suppression and novel mechanism-based approaches.

In this study, Nesuparib, when administered alone in small cell lung cancer cell line models (in vitro), exhibited up to 133 times stronger cancer cell growth inhibitory efficacy compared to the existing PARP inhibitor olaparib, and approximately 25 times stronger efficacy compared to irinotecan, an anticancer agent used in the treatment of SCLC. In the in vivo xenograft animal model experiments, Nesuparib showed a tumor inhibition rate of 66.5%, demonstrating superior antitumor efficacy to olaparib (36%) and irinotecan (42.9%).

Notably, the effect of Nesuparib was even more pronounced when used in combination with irinotecan. Even when the Nesuparib dose was reduced by 50% and 25% compared to monotherapy, the combination maintained high tumor inhibition rates of 71.9% and 66%, respectively, confirming that the synergistic effect persisted even at reduced doses.

Mechanistic analysis revealed that Nesuparib exerts broad inhibition of key tumor proliferation pathways through a multi-modal mechanism that simultaneously regulates Wnt/β-catenin and Hippo/YAP signaling. Consequently, the expression of c-Myc and Ki-67, which are characteristically highly expressed in small cell lung cancer, was significantly reduced. The company explained that these results suggest Nesuparib has the potential not only to suppress tumor growth, but also to directly modulate the core proliferation mechanisms of tumors.

The model used in this study was the SCLC-A subtype, which is a major molecular subtype of small cell lung cancer and accounts for up to approximately 70% of all patients.

A representative from Onconic Therapeutics stated, "We have confirmed that Nesuparib, based on Tankyrase inhibition, can compensate for the limitations of existing treatment approaches through a multi-modal mechanism that simultaneously regulates Wnt and Hippo signaling. In particular, since it can simultaneously inhibit core tumor-driving factors such as c-Myc and YAP proteins, we believe it could be developed as a therapeutic strategy applicable to various molecular subtypes of small cell lung cancer."

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