Ranok Therapeutics Announces Positive Interim Phase 1 Data Of Its KRAS G12D Inhibitor RNK08954 In Patients With KRAS G12D-Mutated Metastatic Non-Small Cell Lung Cancer Presented At ASCO 2026

• Clinically Meaningful Overall Antitumor Activity, with ORR of 42.6% and DCR of 95.7% across all evaluated dose levels in heavily pretreated patients.
• Enhanced Clinical Activity at the Recommended Phase 2 Dose (RP2D), with ORR of 50% in patients who were Taxane-Naïve.
• Differentiated safety profile; RNK08954 was well tolerated, with 1200 mg once daily established as the RP2D.

WALTHAM, Mass. and HANGZHOU, China, June 2, 2026 /PRNewswire/ -- Ranok Therapeutics, a clinical-stage biotechnology company developing innovative therapies, today announced positive interim Phase 1 clinical data for RNK08954, an investigational oral, selective KRAS G12D inhibitor. The results were featured in an Oral Presentation at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. The multicenter Phase 1 study (NCT06667544) evaluated RNK08954 in heavily pre-treated patients with KRAS G12D-mutated solid tumors in China.

Based on comprehensive assessment of safety, tolerability, pharmacokinetics, and anti-tumor activity, a dose of 1200 mg once daily (QD) was selected as the Recommended Phase 2 Dose (RP2D).

In the cohort of patients (N=47) with metastatic non-small cell lung cancer (NSCLC), RNK08954 demonstrated enhanced anti-tumor activity. In the overall evaluable NSCLC population across all tested doses (400–1200 mg, QD), the Objective Response Rate (ORR) was 42.6% (95% confidence interval (CI), 28.3%–57.8%), alongside a Disease Control Rate (DCR) of 95.7% (95% CI, 85.5%–99.5%).

Clinical activity was further enhanced at the RP2D of 1200 mg QD. Patients with only one prior line of therapy achieved an ORR of 45.0% (95% CI, 23.1%–68.5%), and DCR of 95.0% (95% CI, 75.1%–99.9%). Notably, patients who were taxane-naïve achieved the highest response rate in the study, with ORR of 50.0% (95% CI, 26.0%–74.0%) and DCR of 94.4% (95% CI, 72.7%–99.9%), demonstrating the potent antitumor activity of RNK08954. Longitudinal follow-up demonstrated durable clinical benefit. Progression-free survival (PFS) data for the optimized 1200 mg QD cohort remain immature and continue to mature. In the pooled lower-dose cohorts (400–1000 mg QD), RNK08954 achieved a median PFS of 7.6 months (95% CI, 2.8–NR). Robust molecular responses were evidenced by circulating tumor DNA (ctDNA) kinetics, corroborating the radiologic responses. Among the evaluable patients, 83.3% achieved a critical biological threshold of ≥50% variant allele frequency (VAF) clearance of the mutant KRAS G12D clone. Crucially, 44.4% of patients achieved complete molecular clearance of the driver mutation, providing strong biological validation of RNK08954 potent target engagement and mechanism of action.

Professor Zhengbo Song, MD, PhD, Lead Investigator, Zhejiang Cancer Hospital commented "These interim data are highly encouraging for patients with advanced KRAS G12D-mutated NSCLC who currently face limited treatment options. Achieving a 50.0% response rate specifically in taxane-naïve patients at the 1200 mg RP2D provides a strong scientific rationale for moving RNK08954 into earlier lines of therapy, before the introduction of traditional chemotherapy. Combined with a favorable, manageable safety profile, RNK08954 demonstrates the potential to significantly shift how we sequence treatments for these patients."

"The clinical activity and tolerability observed at the 1200 mg QD dose level confirm that RNK08954 is a highly competitive agent in the KRAS G12D landscape. The robust responses in taxane-naïve patients strongly support our strategy to explore RNK08954 in earlier treatment lines." said Iman El-Hariry, MD, PhD, Chief Medical Officer, Ranok Therapeutics. "Our immediate focus is on swift clinical execution to fully characterize this monotherapy profile in broader NSCLC populations while systematically exploring RNK08954's potential in rational combination regimens."

"The clinical results demonstrated by RNK08954 at ASCO represent a significant corporate milestone for Ranok Therapeutics, establishing a well-tolerated, active oral profile at the RP2D." commented Weiwen Ying, PhD, Chief Executive Officer, Ranok Therapeutics. "This strong data package provides us with excellent strategic flexibility as we evaluate corporate development opportunities to accelerate our clinical programs. These results also offer a powerful validation of our internal discovery platform, giving us high confidence as we advance our broader multi-asset KRAS franchise spanning G12D, G12C, and beyond."

About RNK08954

RNK08954 is a highly selective, oral KRAS G12D inhibitor with unique pharmacokinetic properties designed for deep, sustained target inhibition. It is currently being investigated as monotherapy and in combination with chemotherapy and/or other targeted agents in NSCLC, PDAC, and additional solid tumor indications.

About Ranok Therapeutics

Ranok Therapeutics is a clinical-stage biopharmaceutical company developing next-generation targeted oncology therapies. Its pipeline includes multiple programs against high-value oncogenic drivers, with a lead program in KRAS G12D (RNK08954).

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Ranok Therapeutics (Hangzhou) Co., Ltd.
bd@ranoktherapeutics.com | www.ranoktherapeutics.com

The study evaluated the safety, tolerability, and clinical activity of RNK08954 in patients harboring KRAS G12D mutation across multiple sites in China. The study enrolled patients with advanced solid tumors, primarily focusing on safety and the determination of the Recommended Dose for Expansion. A total of 36 patients were evaluable for clinical activity. The overall objective response rate (ORR) was 28%, with a disease control rate (DCR) of 86%. Notably, patients with non-small cell lung cancer (NSCLC) achieved an ORR of 58.33% and a DCR of 100%. RNK08954 was generally well tolerated, with treatment-related adverse events consisting predominantly of Grade 1-2 gastrointestinal adverse events and decreased appetite. No dose-limiting toxicities were observed during the dose-escalation phase. ^[1]

"I am grateful that the editors of Cancer Discovery selected our study for publication," said Professor Song Zhengbo, Director of Phase I Clinical Trial Unit at Zhejiang Cancer Hospital, and the study's Principal Investigator. "RNK08954 represents a critical step in advancing KRAS G12D-targeted therapy from concept to clinical validation. These findings not only accelerate the clinical translation of precision oncology but also lay a solid data foundation for subsequent pivotal clinical studies."

"The publication of these data underscores the potential for RNK08954 to provide a meaningful option for KRAS G12D-mutant cancers," commented Dr. Iman Elhariry, Chief Medical Officer at Ranok Therapeutics and co-author of the article. "Seeing a 58.33% objective response rate in the NSCLC cohort is particularly encouraging as it validates our approach of targeting the Switch II pocket with high selectivity. Based on these strong signals of clinical activity and the clean safety profile, we have already initiated our Phase 1b expansion study to further explore the drug's potential as a monotherapy and in combination regimens across NSCLC, pancreatic and other indications."

Dr. Weiwen, Founder and CEO of Ranok Therapeutics, added: "The significant progress in KRAS inhibitors has been made possible by over a decade of accumulated knowledge in structural biology and medicinal chemistry. These clinical research achievements will inspire our team to further explore the clinical potential of RNK08954, fully unlocking its value for patients who currently lack effective targeted therapies."

About RNK08954 and KRAS G12D

KRAS G12D is one of the most prevalent oncogenic drivers in solid tumors, including pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and non-small cell lung cancer (NSCLC). For decades, this mutation was considered "undruggable". RNK08954 is designed to bind directly to the Switch II pocket of the KRAS G12D protein in its active and inactive states, effectively blocking downstream signaling pathways that drive tumor growth.

About Ranok Therapeutics

Ranok Therapeutics is a clinical stage biopharmaceutical company committed to discovering and developing breakthrough therapies for cancer patients. By leveraging deep expertise in protein regulation and medicinal chemistry, Ranok aims to address significant unmet medical needs in oncology. For more information, please visit www.ranoktherapeutics.com

For business development or media inquiries, please contact bd@ranoktherapeutics.com

Cautionary Statement Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act. These statements are based on current expectations and involve risks and uncertainties. Actual results may differ materially from those expressed or implied due to various risks and uncertainties, including clinical development risks, regulatory approval uncertainties, and competitive factors. The investigational new drug referenced herein (IND 172260) has been authorized by the U.S. Food and Drug Administration (FDA) for clinical study purposes only; it has not been approved by the FDA for commercial marketing or sale. No representation is made that the product is safe or effective for any use not authorized under applicable law. These statements speak only as of the date hereof, and we undertake no obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.