# A reversible aptamer based therapeutic to treat stroke

> **NIH NIH R44** · BASKING BIOSCIENCES · 2020 · $575,406

## Abstract

PROJECT SUMMARY/ABSTRACT
Occlusive arterial thrombosis leading to stroke and myocardial infarction contribute to ~13 million deaths
around the world every year. Over the past two decades, recombinant tissue plasminogen activator (rTPA) has
remained the only drug approved to treat acute ischemic stroke. Unfortunately, patients who receive rTPA
have a significant increase in symptomatic hemorrhage with a conversion rate of 6.4%. Moreover, rTPA only
achieves an average of ~30% recanalization in arterial thrombi, which are commonly platelet rich and are
notoriously resistant to rTPA. Evidence for this was seen in a recent study in patients who presented with
large vessel occlusion (LVO) stroke and received rTPA, demonstrated vessel recanalization only 10% of the
time. The limitations of rTPA therapy result in only ~5% of patients actually receive the drug. Therefore, a
critical need exists to develop anti-thrombotic agents that: 1) prevent occlusive thrombus formation, 2)
recanalize acute arterial occlusions and 3) prevent restenosis, all with a superior safety profile than that of
rTPA.
Von Willebrand Factor (VWF) is an optimal target for anti-thrombotic therapy. Under high shear seen in
thrombosis, VWF binds to glycoprotein Ib (GPIb) of the platelet receptor complex GPIb-IX-V (GPIb-IX-V) as
well as to GPIIb-IIIa, resulting in platelet activation and aggregation. VWF also self-associates, extending into
the vessel lumen where it serves not only as a scaffold for platelets but also red blood cells. These central
processes ultimately result in arterial thrombosis as seen in ischemic stroke.
Aptamers are an innovative class of drug molecules that consist of oligonucleotides that specifically and
efficiently bind to and inhibit target proteins. Basking Biosciences Inc has developed an RNA aptamer that
inhibits VWF, named DTRI-031. It has also designed a reversal oligonucleotide, named DTRI-025 that
rapidly neutralizes DTRI-031 within minutes. DTRI-031 prevents thrombus formation, lyses fully formed
arterial occlusions and reduces the radiographic burden of ischemia better than rTPA in small and large animal
models of arterial thrombosis and stroke. It is currently in the final series of IND enabling studies. DTRI-025
rapidly reverses DTRI-031 activity in vitro and in vivo in small animal models. The overall goal of this proposal
is to define the optimum dose of DTRI-025 to neutralize DTRI-031 in a large animal model and to develop a
bioassay to perform GLP safety pharmacology and toxicity studies with GMP manufactured DTRI-025. The
Aims of this proposal will allow Basking Biosciences to submit a Pre-IND application to FDA and ultimately lead
to First In Human (FIH) trials in conjunction with DTRI-031.

## Key facts

- **NIH application ID:** 10011052
- **Project number:** 1R44HL152869-01
- **Recipient organization:** BASKING BIOSCIENCES
- **Principal Investigator:** Shahid Nimjee
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $575,406
- **Award type:** 1
- **Project period:** 2020-06-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011052

## Citation

> US National Institutes of Health, RePORTER application 10011052, A reversible aptamer based therapeutic to treat stroke (1R44HL152869-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10011052. Licensed CC0.

---

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