Delving into the Latest Updates on RM-008 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

KRAS G13C

Mechanism

KRAS G13C inhibitors(GTPase KRas G13C inhibitors)

Therapeutic Areas

Neoplasms

Active Indication

Neoplasms

Inactive Indication-

Originator Organization

Revolution Medicines, Inc.

Active Organization

Revolution Medicines, Inc.

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Chimeric antigen receptor (CAR)-T cell therapy is a groundbreaking immunotherapy for cancer. However, the intricate and costly manufacturing process remains a hurdle. Improving the transduction rate is a potential avenue to cut down costs and boost therapeutic efficiency. Peptide nanofibrils (PNFs) serve as one such class of transduction enhancers. PNFs bind to negatively charged virions, facilitating their active engagement by cellular protrusions, which enhances virion attachment to cells, leading to increased cellular entry and gene transfer rates. While first-generation PNFs had issues with aggregate formation and potential immunogenicity, our study utilized in silico screening to identify short, endogenous, and non-immunogenic peptides capable of enhancing transduction. This led to the discovery of an 8-mer peptide, RM-8, which forms PNFs that effectively boost T cell transduction rates by various retroviral vectors. A subsequent structure-activity relationship (SAR) analysis refined RM-8, resulting in the D4 derivative. D4 peptide is stable and assembles into smaller PNFs, avoiding large aggregate formation, and demonstrates superior transduction rates in primary T and NK cells. In essence, D4 PNFs present an economical and straightforward nanotechnological tool, ideal for refining ex vivo gene transfer in CAR-T cell production and potentially other advanced therapeutic applications.

100 Deals associated with RM-008

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