On October 20, 2025 Upthera (CEO Si-Woo Choi), a company specializing in the development of innovative new drugs based on Targeted Protein Degradation (TPD) technology, reported that it has received approval from the U.S. Food and Drug Administration (FDA) for its Investigational New Drug (IND) application for a Phase 1/2a clinical trial of its PLK1-targeted protein degradation-based (TPD) drug candidate ‘UP1002’ for small cell lung cancer (SCLC).

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This approval marks the first global entry into clinical trials for a new TPD-class drug targeting PLK1, and is considered an achievement that demonstrates Upthera’s proprietary protein degradation technology and global competitiveness. Next year, we plan to proceed with the IND approval process in Korea as well to expand the global clinical trials of ‘UP1002’ in earnest.

The clinical trial approved this time is a Phase 1/2a combined design that proceeds to confirm safety and tolerability through initial dose escalation, followed by evaluating efficacy indicators through an expansion cohort. Uptera aims to administer the drug to the first patient starting next year, involving 30 to 60 patients in the U.S., and plans to consider expanding to other solid tumor indications depending on future results.

Small cell lung cancer (SCLC) has been known for decades as a cancer where new drug development is significantly more difficult compared to other types of cancer, and even recently approved drugs have limited anticancer efficacy, such as extending survival.

In addition, it is an intractable cancer with a very low 5-year survival rate of less than 7% due to the rapid rate of tumor metastasis and high recurrence rate. While the development of numerous targeted anticancer drugs based on reliable biomarkers is underway for non-small cell lung cancer, the development of targeted anticancer drugs for small cell lung cancer is difficult due to the lack of accurate biomarkers.

To overcome these limitations, Upthera is developing ‘UP1002,’ a novel drug candidate that directly degrades PLK1 (Polo-like kinase 1), a key protein regulating cell division, by utilizing TPD technology. PLK1 is an essential protein (kinase) that regulates cell division during the cell cycle (G2/M phase) and is overexpressed in rapidly proliferating cells, such as cancer cells. While numerous global pharmaceutical companies, including Boehringer Ingelheim and Takeda, have developed PLK1 inhibitors (small molecule inhibitors), most have been discontinued during clinical trials due to dose-limiting toxicity (DLT). To date, there are no approved drugs with a mechanism that selectively inhibits or degrades PLK1.

UP1002 is characterized by inducing an anticancer effect even at lower concentrations than existing inhibitors by directly degrading the PLK1 protein, and by fundamentally overcoming the problem of dose-limiting toxicity (DLT). This mechanism is a novel approach that induces apoptosis by halting the cell cycle of cancer cells, and is expected to lead a paradigm shift in treatment for cancers with rapid cell proliferation, such as small cell lung cancer.

Upthera’s UP1002 (PLK1) was recognized for its innovation and technological capabilities and was selected as a project under the Korea Drug Development Fund (KDDF) ​​in 2022, receiving support. Based on the Global RA support program within the KDDF, Upthera has established a global clinical development strategy in collaboration with global clinical research institutions such as QubeST Bio and KCRN Research.

UP1002 is recognized as the first-in-class anticancer drug that degrades PLK1 and the first clinical pipeline in the TPD industry to target cell cycle-related proteins, which are difficult to develop. In addition, Upthera has filed 82 domestic and international patents related to UP1002, 19 of which have been registered. The company plans to continuously strengthen its patent portfolio and build patent barriers to effectively block the entry of latecomers in the PLK1 degradation field and solidify its position as a first mover.

"This FDA IND approval is an achievement that officially recognizes Upthera’s proprietary protein degradation technology and global development capabilities," said Choi Si-woo, CEO of Upthera. "We will present new treatment options to patients with small cell lung cancer through clinical results and strengthen our global competitiveness in the TPD field."

(Press release, Uppthera, OCT 20, 2025, View Source [SID1234664781])