▎WuXiEdited by Kant Content Team

Today (June 11), the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration announced that Astellas（Astellas）The Phase 1 new drug ASP3082 Injection, developed by Astellas Pharma, Inc., has been approved for clinical trials and is proposed for development toCarryKRAS G12DPreviously Treated Locally Advanced (Unresectable) or Metastatic Solid Tumors with Mutations。Public information shows that this is a product with highly efficient selectivity.New TypeKRAS G12D Protein Degrader, is currently conducting Phase 1 clinical trials internationally.

Screenshot source: CDE official website

KRASIs a commonly mutated driver gene,KRAS G12DYesKRASThe predominant mutation subtype, occurring in approximately 34% ofPancreatic Ductal Adenocarcinoma, 12% of colorectal cancers, 4% of non-small cell lung cancers, and various other types of cancer can be detected.KRAS G12DPatients with mutations have a poor prognosis, and there are currently no targeted therapies approved for marketing, leaving the growing clinical needs unmet.

ASP3082 is aNovel small-molecule targeted protein degrader chimeraIt combines and selectively targets the KRAS G12D mutant protein, degrading it by recruiting E3 ubiquitin ligase proteins.Previously,The preclinical study results of ASP3082 were presented at the 2023 American Association for Cancer Research (AACR) Annual Meeting.

In preclinical studies, ASP3082 selectively degraded the KRAS G12D mutant protein, subsequently inhibiting downstream signaling pathways.Demonstrates growth inhibitory activity in KRAS G12D mutant cancer cells without affecting KRAS wild-type protein.ASP3082 can also inhibit extracellular signal-regulated kinase phosphorylation and its downstream genes, and induce caspase-3 cleavage.InKRAS G12DIn mice xenografted with mutated cancer cells, weekly intravenous administration of ASP3082 has been shown to have significant antitumor effects.There is also evidence that the target protein levels can be sustainably reduced.。

According to the introduction on Astellas' official website, the company has established a series ofTargeted Protein Degradation Development Pipeline, aiming to create the next generation of protein degraders for the treatment of cancer and other multiple indications. ASP3082 is one of the leading products in this series of pipelines, with the rest includingAnotherKRAS G12D Degrader ASP4396AndA product still in the preclinical stagePan-KRAS Degraderetc.

For several decades, scientists have believed that the KRAS protein is“Undruggable”. With the emergence of the first batch of KRAS G12C inhibitors in recent years, this "curse" of being undruggable has apparently been broken, giving rise to a group of treatments targeting different typesKRASInnovative Products for Mutational Cancers.

Among them, innovative therapies targeting KRAS G12D have gained industry recognition in recent years, leading to multiple licensing deals or related collaborations. For example:

• In February 2024, Jazz and Redx announced an $870 million agreement.AgreementJazz to Acquire Redx’s KRAS Inhibitor Development Program, IncludingIncluding KRAS G12D-specific inhibitorsAnd pan-KRAS molecules;
  

• In November 2023, AstraZeneca reached a deal exceeding $400 million with Yosen Jianheng.Cooperation, obtaining the latter's oneTargetedUA022 Project: Small Molecule Candidate Drug for KRAS G12D Mutation；

• In October 2023, Bristol-Myers Squibb announced a $4.8 billionAcquisitionMirati, obtaining the latter's multiple KRAS inhibitors, includingThe KRAS G12D inhibitor MRTX1133;

• In August 2023, Jifang Pharmaceuticals reached a collaboration worth over $600 million with Verastem Oncology. The latter obtained global development and commercialization rights outside of Greater China for three innovative RAS pathway-targeted therapies developed by Jifang Pharmaceuticals, includingKRAS G12D (ON/OFF) Inhibitor GFH375`, the preclinical study results of this product were also presented at this year's AACR annual meeting.`

The following lists some KRAS G12D inhibitors currently in the clinical stage for readers' reference.