Qurient Study in Science Advances Shows Q901 Can Enhance TOP1-Targeting ADC Activity
Qurient Co., Ltd. (KRX: 115180), a clinical-stage biotechnology company focused on developing innovative cancer therapies, has announced the publication of a peer-reviewed study in Science Advances demonstrating the potential of its selective CDK7 inhibitor Q901 (mocaciclib) to enhance the antitumor activity of topoisomerase I inhibitor-based antibody-drug conjugates (TOP1i-ADCs).
The study, titled “Sensitizing tumor response to topoisomerase I antibody drug conjugate by selective CDK7 inhibition,” was conducted through a collaborative research effort involving scientists from Qurient, Pohang University of Science and Technology (POSTECH), the U.S. National Cancer Institute (NCI), and the University of Maryland. The findings provide a mechanistic explanation for how CDK7 inhibition can increase the vulnerability of cancer cells to TOP1-directed therapies and support Qurient’s strategy of developing combination treatments and next-generation ADCs with dual mechanisms of action.
TOP1 inhibitor-based ADCs have become an important therapeutic approach in oncology because they combine the tumor-targeting capabilities of antibodies with the DNA-damaging effects of topoisomerase I inhibitors. However, despite their clinical activity, there remains an opportunity to improve the depth and durability of tumor responses. Qurient’s newly published research suggests that selectively inhibiting CDK7 may create a temporary state of impaired homologous recombination repair (HRR), making cancer cells more susceptible to the DNA damage generated by TOP1 inhibitors.
Q901 Targets CDK7 to Increase Tumor Cell Sensitivity
Q901 is designed as a selective and sustained inhibitor of cyclin-dependent kinase 7 (CDK7), a protein kinase involved in transcriptional regulation and cell-cycle control. CDK7 has an important role in regulating RNA polymerase II (RNAPII), which is responsible for transcribing DNA into RNA.
According to the study, Q901 demonstrated strong selectivity for CDK7 across a kinome profiling panel. The compound also forms a covalent interaction with CDK7 at Cys312, supporting the sustained inhibition of the target.
The researchers found that CDK7 inhibition affects transcriptional programs driven by oncogenic factors such as MYC and E2F. These transcriptional networks regulate numerous genes involved in cancer-cell proliferation, DNA replication and the cellular response to DNA damage.
By suppressing these programs, Q901 reduced the expression of genes involved in homologous recombination repair, checkpoint control and DNA replication. The resulting changes in DNA repair capacity were central to the increased sensitivity of tumor cells to TOP1 inhibitors.
The findings point to a potentially complementary relationship between CDK7 inhibition and TOP1 inhibition. Rather than simply adding two independent mechanisms of action, the research indicates that CDK7 inhibition can alter the cellular environment in a way that allows TOP1-mediated DNA damage to persist for longer periods.
Prolonging TOP1-DNA Damage
A key finding of the study involves topoisomerase I-DNA protein crosslinks, commonly referred to as TOP1-DPCs.
TOP1 normally helps manage DNA topology during processes such as DNA replication and transcription. During the catalytic cycle of the enzyme, TOP1 can become temporarily attached to DNA. TOP1 inhibitors interfere with this process and stabilize TOP1-DNA complexes, producing DNA lesions that can ultimately become toxic to cancer cells.
Cells possess mechanisms for recognizing and removing these DNA-protein crosslinks. The efficiency with which cancer cells repair or eliminate this damage can influence their response to TOP1-targeting drugs.
Qurient’s research indicates that inhibiting CDK7 with Q901 interferes with transcriptional elongation by RNA polymerase II. This reduction in transcriptional activity decreases collisions between RNAPII and TOP1-DPCs. Under normal conditions, such collisions can promote mechanisms that facilitate proteasomal clearance of TOP1-DPCs.
When CDK7 is inhibited, the study found that TOP1-DPCs persist for a longer period. This prolonged persistence increases the accumulation of DNA damage and ultimately intensifies the cytotoxic effects of TOP1 inhibition.
The mechanism therefore provides a biological explanation for the enhanced activity observed when Q901 is combined with TOP1-targeting agents.
Creating a Transient HRR-Deficient State
Another important element of the research is the effect of Q901 on homologous recombination repair.
HRR is one of the cellular pathways responsible for repairing certain forms of DNA damage. Tumor cells that have compromised HRR mechanisms can become particularly vulnerable to therapies that generate DNA lesions.
The study suggests that Q901 can temporarily suppress the expression of genes associated with HRR, creating what Qurient describes as a transient HRR-deficient state. This condition can increase the impact of TOP1 inhibitor-mediated DNA damage without requiring permanent genetic alterations to the tumor.
The concept could have implications for the development of combination regimens. If CDK7 inhibition can temporarily reduce a tumor’s ability to repair DNA while a TOP1 inhibitor is delivering DNA damage, the two mechanisms may work together to produce a stronger antitumor response.
According to Qurient, this mechanism provides a scientific rationale for combining Q901 with existing TOP1i-ADCs.
Enhanced Activity Observed With Multiple ADCs
The preclinical research evaluated Q901 in combination with multiple TOP1 inhibitor-based ADCs. The company reported that Q901 significantly enhanced overall antitumor activity when combined with leading ADCs, including trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG).
These ADCs use antibodies to recognize specific tumor-associated targets and deliver cytotoxic payloads to cancer cells. Their payloads include topoisomerase I inhibitor-derived components designed to induce DNA damage after delivery into tumor cells.
The combination findings suggest that the mechanism associated with Q901 may extend beyond a single TOP1i-ADC. This is significant for Qurient’s broader development strategy because it indicates that CDK7 inhibition could potentially be applied across different ADC programs and tumor-targeting approaches.
The company’s findings remain preclinical and provide mechanistic and experimental support rather than clinical evidence of improved patient outcomes. Further clinical evaluation would be required to determine whether the enhanced antitumor activity observed in laboratory and preclinical models translates into improved efficacy and safety in patients.
Scientific Rationale for Qurient’s ADC Strategy
Kiyean Nam, Ph.D., Chief Executive Officer of Qurient and co-corresponding author of the study, said the emergence of TOP1 inhibitor-based ADCs as a major cancer treatment modality creates an opportunity to investigate strategies that could extend progression-free survival by temporarily impairing HRR.
Nam said the publication describes the complementary molecular relationship between CDK7 and TOP1 inhibition and provides a scientific basis for combining Q901 with existing TOP1i-ADCs.
The company is also exploring a second application of the research: incorporating both CDK7 and TOP1 inhibitor activities into a single ADC.
This approach could potentially result in a dual-payload ADC, in which two distinct therapeutic mechanisms are delivered through one targeted antibody-based platform. Instead of administering separate agents, such a strategy is intended to bring complementary payloads directly to cancer cells through the same targeting mechanism.
Qurient said it is applying the scientific framework described in the Science Advances publication to the development of dual-payload ADCs directed against multiple antibody targets.
Potential Expansion of Qurient’s Oncology Pipeline
The company views the research as part of a broader effort to establish a scalable ADC development platform. By combining its expertise in CDK7 inhibition with TOP1-targeting technology, Qurient aims to pursue both combination therapies involving Q901 and next-generation ADC candidates incorporating multiple payloads.
The dual-payload strategy could provide additional flexibility in designing therapies intended to overcome mechanisms of tumor resistance. However, the development of such candidates will require extensive evaluation of factors including payload compatibility, antibody targeting, drug-to-antibody ratios, pharmacokinetics, tumor distribution, efficacy and safety.
The publication nevertheless adds a mechanistic foundation to Qurient’s development strategy. The findings connect selective CDK7 inhibition with transcriptional regulation, DNA repair suppression and prolonged TOP1-DPC persistence, providing a sequence of biological events that may explain the enhanced activity observed in preclinical models.
The collaboration with POSTECH, NCI and the University of Maryland also highlights the multidisciplinary nature of the research, bringing together expertise in cancer biology, transcriptional regulation, DNA damage response and therapeutic development.
Supporting Future Combination and Dual-Payload Development
For Qurient, the Science Advances publication represents more than an individual preclinical finding. The research supports a development framework in which selective CDK7 inhibition can be used to increase the susceptibility of cancer cells to TOP1-mediated DNA damage.
The company is pursuing this framework through two related approaches. The first involves evaluating Q901 in combination with existing TOP1i-ADCs, potentially allowing established ADC technologies to be paired with a mechanism designed to compromise tumor-cell DNA repair and increase the persistence of TOP1-associated DNA lesions.
The second approach involves developing dual-payload ADCs that incorporate CDK7 and TOP1 inhibition within a single targeted therapeutic format. Qurient believes this strategy could provide a platform for generating multiple ADC candidates against different tumor-associated targets.
As oncology drug development increasingly focuses on targeted delivery and rational combinations, the ability to combine complementary mechanisms within an ADC may offer additional opportunities for therapeutic innovation. The clinical relevance of the Q901/TOP1 combination, however, will ultimately depend on future clinical studies demonstrating an appropriate balance between antitumor activity, tolerability and pharmacological exposure.
With the publication of its findings in Science Advances, Qurient has added peer-reviewed evidence supporting the biological rationale behind its CDK7 and ADC programs. The company is now using these findings to guide the continued development of combination therapies and next-generation dual-payload ADCs across multiple cancer targets.
About Qurient Co., Ltd.
Qurient Co., Ltd. (KRX: 115180) is a clinical-stage biotechnology company focused on the discovery and development of innovative therapeutics for cancer and infectious diseases. The company is advancing a robust pipeline of internally discovered small-molecule therapeutics and next-generation antibody-drug conjugates. This includes Q901 (mocaciclib), a selective CDK7 inhibitor, and QP101, a dual-payload ADC combining complementary cytotoxic mechanisms. Qurient is also pioneering a broader dual-payload ADC platform designed to seamlessly apply complementary payload combinations across a variety of antibody targets.