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FDA Clears IND for MRANK-106, First-in-Class Dual WEE1/YES1 Kinase Inhibitor for Advanced Solid Tumors

• MindRank's novel dual WEE1/YES1 kinase inhibitor MRANK-106 received FDA IND clearance for treatment of multiple advanced solid tumors, with Phase I trials set to begin in 2025.

• Preclinical studies demonstrate MRANK-106's superior efficacy and improved safety profile compared to single-target WEE1 inhibitors, with 10-120 fold preferential distribution in tumors over plasma.

• The AI-designed compound shows promising activity against pancreatic cancer, small cell lung cancer, ovarian cancer, breast cancer, and colorectal cancer, addressing significant unmet medical needs.

The U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for MRANK-106, a first-in-class dual inhibitor of WEE1 and YES1 kinases developed by MindRank. This milestone enables the initiation of Phase I clinical trials in 2025 for patients with advanced or metastatic solid tumors, including pancreatic cancer, small cell lung cancer, ovarian cancer, breast cancer, and colorectal cancer.
MRANK-106 represents a significant advancement in oncology therapeutics through its novel dual-targeting mechanism. Unlike other WEE1 inhibitors in development, this orally available compound simultaneously inhibits both WEE1 and YES1 kinases, creating synergistic anti-tumor effects that address limitations of single-target DNA damage repair inhibitors.

Differentiated Mechanism and Preclinical Profile

Extensive preclinical studies have demonstrated several key advantages of MRANK-106:
  • Superior efficacy as both a monotherapy and in combination regimens across multiple cancer models
  • Preferential distribution in tissues and tumors over plasma (10- to 120-fold selectivity)
  • Reduced WEE1-associated hematotoxicity compared to single-target inhibitors
  • Improved safety window while maintaining potent anti-tumor activity
Dr. Zhangming Niu, Founder and CEO of MindRank, emphasized the significance of this development: "The FDA IND clearance of MRANK-106 is a significant milestone for MindRank and validates the potential of our AI-driven approach to drug discovery. As the company's second clinical-stage pipeline following our GLP-1 program, MRANK-106 demonstrates the versatility and reproducibility of our Molecule Pro™ platform in designing innovative therapies for undruggable targets."

Addressing Critical Unmet Needs

The upcoming Phase I clinical trial will evaluate MRANK-106's safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity in patients with advanced solid tumors. The compound has shown particularly promising results in preclinical models of pancreatic cancer, small cell lung cancer, ovarian cancer, breast cancer, and colorectal cancer – malignancies that often have limited treatment options and poor prognoses.
"By simultaneously targeting WEE1 and YES1 kinases, MRANK-106 has demonstrated remarkable preclinical efficacy in multiple hard-to-treat cancers with limited treatment options. We look forward to evaluating its potential in patients," Dr. Niu added.

AI-Driven Drug Discovery

MRANK-106 represents a triumph of artificial intelligence in pharmaceutical development. MindRank leveraged its proprietary AI platforms – PharmKG™, Molecule Dance™, and Molecule Pro™ – to rapidly advance the compound from preclinical candidate confirmation to IND clearance.
As MindRank's first officially nominated First-in-Class candidate, MRANK-106 marks a significant milestone in the company's pursuit of breakthrough therapies. The company has previously demonstrated success with its GLP-1 receptor agonist program, with lead asset MDR-001 currently in Phase 2b clinical studies.

Mechanism of Action

MRANK-106 targets two key proteins involved in DNA damage response and cancer cell proliferation. WEE1 kinase plays a crucial role in cell cycle regulation and DNA damage repair, while YES1 kinase contributes to cancer cell survival and proliferation pathways. By inhibiting both targets simultaneously, MRANK-106 aims to overcome resistance mechanisms that can limit the efficacy of single-target approaches.
The compound's preferential distribution to tumor tissues may provide a critical advantage in maximizing anti-cancer effects while minimizing systemic toxicities – a persistent challenge in oncology drug development.

Looking Toward Clinical Development

With IND clearance secured, MindRank is preparing to launch the Phase I clinical trial in 2025. The study will provide crucial insights into MRANK-106's clinical profile and potential to address significant unmet needs in oncology.
If successful in clinical development, MRANK-106 could represent a new therapeutic option for patients with advanced solid tumors who have exhausted standard treatment options or face limited therapeutic choices.
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