Why RNA?

Overlooked for Drug Discovery

For many decades, RNA was simply viewed as a facilitator, transcribing DNA into proteins.  It was also difficult to work with as a drug itself or as a drug target: too unstable; flexible, dynamic structure; poor drug-like properties; and inability to deliver adequate doses into cells.

RNA has become an attractive area for drug discovery, because of its key role in regulation and advantages over DNA or protein targets.

Issues & Opportunity for Oncology Drug Discovery


  • Earliest anti-cancer drugs interfered with DNA replication
  • Drugs are systemic toxins, not specific for tumor
  • Poorly tolerated
  • Relapse is common


  • Most approved drugs today target proteins
  • Specific geometry of drug binding site enables design of selective drugs that may be safer than general cytotoxics
  • However, tumors can mutate around the drug-targeted protein, resulting in relapse


  • Dysregulation of a single RNA pathway can activate many oncogenic pathways and their protein targets
  • Drugging RNA itself is technically challenging; few approved RNA drugs
  • However, some RNAs are regulated by proteins

Our Design Ethos

We Design Therapeutics to Proteins that Modulate RNA

Rather than attempt to drug RNA directly, we build on the extensive tradition of drugging proteins.  We carefully select those proteins that bind regulatory RNAs to achieve:

  • Simultaneous suppression of multiple oncogenic pathways
  • A wide safety margin by working on RNA-binding proteins that are upregulated or re-expressed in cancer, but are absent or limited in healthy cells

Rebalancing LIN28 & let-7

Restoring a Key Control Mechanism Hijacked by Cancer

Our lead target is LIN28, a highly evolutionarily conserved RNA-binding protein involved in determining cell fate during embryogenesis of many organisms, including humans.  As shown below, LIN28 is largely absent in healthy individuals, but is re-expressed in certain cancers and re-activates multiple oncogenes by reducing the level of let-7, a microRNA.

Normal Cell

Normal Cell

In a normal healthy person, let-7 levels are high, and it suppresses oncogenes, such as RAS, MYC, and HMGA2, by binding to their 3’ UTRs to prevent translation.

Let-7 is high in a healthy person, because LIN28 is absent.  Without LIN28, let-7 can be generated from its precursor, pre-let-7.

Cancer Cell

Cancer Cell

In some cancers, LIN28 is re-expressed, binds to pre-let-7, and targets it for degradation, thereby decreasing let-7. Oncogenes, such as MYC, KRAS, and HMGA2, are coordinately re-expressed.

Analysis of clinical samples from multiple tumor types shows a strong correlation between high LIN28 and/or low let-7 and decreased survival.

Not surprisingly, restoring high let-7 levels reverses tumor growth in vitro and in vivo.

Clinical and Pre-clinical Support

Analysis of clinical samples from multiple tumor types shows a correlation between high LIN28 (or low let-7) and decreased survival. Not surprisingly, inhibition of the pathway reverts cancer cells in preclinical models.

Read more about our foundational science.

Closing Cancer’s Paths


Tumor cells regress; tissues and cells regain normal phenotype

Building a Comprehensive Therapy

Nearly two decades of research has shown that the LIN28 pathway centrally controls many oncogenic pathways via its dysregulation of let-7, a key tumor suppressor.  By restoring beneficial levels of let-7, our programs have the potential to inhibit many cancer pathways simultaneously1, a scientifically stronger approach than the single target agents deployed to date.

1 Balzeau et al, Front Genet, 2017

LIN28 / let-7 Beyond Cancer

The LIN28 / let-7 pathway is also dysregulated in other serious non-oncology diseases with high unmet need, such as

  • Metabolic diseases
  • Auto-immune diseases
  • Cardiovascular diseases

While our corporate focus is on oncology, we seek partners to explore these other therapeutic areas.

Pipeline & Partnering

Our goal is to become the leader in the therapeutic regulation of RNA.  Beyond the LIN28 pathway, we are developing compounds to other novel RNA-binding proteins.

We welcome the opportunity to:

  • Partner our compounds in non-oncology settings
  • Explore new technologies and therapeutics for RNA applications