# Novel Targeted Nanomedicine Delivering MicroRNA-30-5p ReplacementTherapy for Multi-drug Resistant Cancer Treatment

> **NIH NIH U44** · MIRECULE, INC. · 2021 · $1,000,000

## Abstract

Abstract:
In this phase 2 SBIR application, miRecule proposes to develop a microRNA-based therapeutic mimic of miR-
30-5p (miRecule candidate MC-30) for the treatment of multi-drug resistant (MDR) cancers. Head and Neck
Squamous Cell Carcinoma (HNSCC) is the 6th most common form of cancer. Greater than half of patients
present with late stage III or IV disease, with an average 5-year survival rate of ~40%. HNSCC tumors have high
levels of genetic mutations leading to high tumor heterogeneity and drug resistance. miR-30-5p expression is
widely repressed in tumor tissues and MIR30 gene deletion is observed in ~30% of HNSCCs. Loss of miR-30-
5p expression correlates with poor survival outcome in 100% of Oropharyngeal HNSCC patients (OPSCC),
which represents our initial clinical population. miR-based therapeutics offer a disruptive approach for
treatment of MDR cancer by targeting both primary oncogenic pathways and mechanisms of intrinsic or
acquired resistance. EGFR targeted therapy is often compensated for by overexpression of growth factor
receptors (GFRs) MET and IGF1R. However, we have discovered that miR-30-5p simultaneously targets and
repress all three of these GFRs. The rationale for miR-30-5p replacement therapy is that it will be superior in its
ability to treat heterogeneous late-stage HNSCC due to its ability to regulate not only EGFR, but also MET, IGF-
1R, and over two dozen other mRNAs confirmed to be deregulated in tumor tissue and associated with
proliferation, adhesion, migration, extracellular matrix remodeling, and differentiation. In phase 1 of our SBIR,
we developed a chemically-modified mimic of miR-30-5p with >1000x improved nuclease stability and 5X activity
in HNSCC models compared to the natural microRNA. We also demonstrated simultaneous inhibition of a dozen
critical oncogenes in HNSCC with evidence that our mimic to can overcome cisplatin and EGFR-related drug
resistance. We also demonstrated that of our clinically validated LNP formulation, which targets solid tumors via
an scFv against the transferrin receptor (TfR), overcomes the challenge of delivery to cancer cells by having
activity at a low dose of 1 mg/kg in vivo. This was demonstrated in both biodistribution studies and four
different in vivo models of HNSCC that all showed strong sensitivity to MC-30. In this Phase II SBIR study,
we propose to: 1) Characterized PK/PD and non-GLP Tox studies of MC-30. 2) Create a compelling data
package that demonstrates dose-dependent efficacy of MC-30 in syngeneic and PDX models. 3) Demonstrate
the competitive advantage of MC-30 over approved cisplatin, cetuximab, and anti-PD-1 therapies with potential
for combination use. 4) Validate our proposed clinical population of OPSCC patients in a mini ex vivo clinical
trial. 5) Optimize scale-up, manufacturing, and CMC release tests for MC-30. The sum of these studies will
support filing an orphan drug application, enable our pre-IND meeting, guide our clinical development, and
val...

## Key facts

- **NIH application ID:** 10203869
- **Project number:** 5U44CA221567-03
- **Recipient organization:** MIRECULE, INC.
- **Principal Investigator:** Anthony D Saleh
- **Activity code:** U44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,000,000
- **Award type:** 5
- **Project period:** 2017-09-22 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10203869

## Citation

> US National Institutes of Health, RePORTER application 10203869, Novel Targeted Nanomedicine Delivering MicroRNA-30-5p ReplacementTherapy for Multi-drug Resistant Cancer Treatment (5U44CA221567-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10203869. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*