Platforms That Accelerate Drug Discovery
Our RNAi platform allows us to develop impactful new therapies to treat diseases with significant unmet needs.
The Arrowhead TRiM™ platform is a robust and versatile drug discovery and development platform. It has broad freedom to operate and utilizes a toolbox of RNAi delivery technologies, chemistries, structures and manufacturing techniques.
After more than a decade working on RNA interference (RNAi)-based therapies, this platform enables us to develop new therapies faster, more cost effectively, and with potentially lower risk relative to traditional approaches.
Regulates protein production
RNAi is a natural cellular mechanism whereby short oligonucleotide molecules called “RNAi triggers” silence gene expression and regulate the production of proteins.
RNAi offers the ability to target a broad range of genes, and to do so with high specificity. We target disease pathways that have proven difficult to address with traditional small molecule and biologic therapeutics.
A catalytic process
RNAi is a catalytic process, so each RNAi trigger can degrade mRNA hundreds of times, which results in a relatively long duration of effect for RNAi therapeutics.
Our Targeted RNAi Molecule (TRiM™) Platform
Arrowhead’s Targeted RNAi Molecule, or TRiM™, platform utilizes ligand-mediated delivery and is designed to enable tissue-specific targeting while being structurally simple.
Targeting has been core to Arrowhead’s development philosophy and the TRiM™ platform builds on more than a decade of work on actively targeted drug delivery vehicles. Arrowhead scientists have discovered ways to progressively “TRiM” away extraneous features and chemistries and retain optimal pharmacologic activity.
The TRiM™ platform comprises a highly potent RNA trigger with the following components optimized, as needed, for each drug candidate: a high affinity targeting ligand; various linker and chemistries; structures that enhance pharmacokinetics; and highly potent RNAi triggers with sequence specific stabilization chemistries.
What TRiM™ means for therapeutics
Therapeutics developed with the TRiM™ platform offer several advantages: simplified manufacturing and reduced costs, multiple routes of administration, and potential for improved safety.
At Arrowhead, we also believe that for RNAi to reach its true potential, it must target areas outside the liver. Arrowhead is leading this expansion with the TRiM™ platform which holds the promise of reaching multiple tissues, including liver, lung, and more.
Modifying RNA Chemistries
The structure and chemistries of the oligonucleotide molecules used to trigger the RNAi mechanism can be tailored for optimal activity. Arrowhead’s broad portfolio of RNA trigger structures and chemistries, including some proprietary structures, enable the company to optimize each drug candidate on a target-by-target basis and utilize the combination of structure and chemical modifications that yield the most potent RNAi trigger.
As a component of the TRiM™ platform, Arrowhead’s design philosophy on RNA chemical modifications is to start with a structurally simple molecule and only add selective modification and stabilization chemistries as necessary to achieve the desired level of target knockdown and duration of effect. The conceptual framework for the stabilization strategy starts with a more sophisticated RNAi trigger screening and selection process that identifies potent sequences rapidly in locations that others may miss.
We pursue chemical stabilization strategies with a target duration of effect of 30-90 days or more days.
Our intellectual property portfolio provides broad freedom to apply multiple RNAi delivery technologies, chemistries, structures and manufacturing techniques in the development of novel therapeutics. Access to a broad range of technologies allows us to choose the best approach for a wide range of gene targets and disease indications.
Collaboration can push our work to the next level. See our partners and approach.
Read about the latest discoveries coming from our labs.
Clinical trials are an essential part of our research. Discover the therapies we’re currently developing.