# Novel α2-Antiplasmin Inactivation for Lysis of Intravascular Thrombi (NAIL-IT) Trial

> **NIH NIH R44** · TRANSLATIONAL SCIENCES, INC. · 2021 · $1,408,991

## Abstract

Each year venous thromboembolism affects up to 2 million Americans and 24 million people worldwide.
Patients with venous thromboembolism have blood clots in the legs (venous thrombosis) that may travel to the
lungs (pulmonary embolism). Pulmonary embolism (PE) is a leading cause of hospital deaths. Pulmonary
emboli may acutely obstruct blood flow, causing right heart failure, circulatory collapse and death within hours
or days. Over a longer period of time, persistent pulmonary emboli may cause serious, disabling complications
such as chronic thromboembolic pulmonary hypertension and right heart failure
 For more than 85 years, anticoagulation has been standard therapy for PE. Anticoagulation does not
dissolve thrombi and is an inadequate treatment for massive PE. However, treatment with a thrombus-
dissolving agent, such as recombinant tissue plasminogen activator (r-tPA), dissolves pulmonary emboli to
improve heart pressures, reduce clot burden, increase the ability of the lung tissue to oxygenate the blood and
decrease post-thrombotic symptoms better than standard anticoagulation therapy. Nevertheless, r-tPA-like
agents cause severe or fatal hemorrhage and the benefit of r-tPA therapy exceeds the risk of bleeding only in
patients that face imminent death from massive PE. For the vast majority of patients, r-tPA therapy is not safe,
even in those patients with intermediate-risk PE, which may have 30-day death rates as high as 10%.To save
lives, reduce recurrent thrombosis and decrease long term complications in patients with PE, Translational
Sciences (TSI) seeks to develop a therapeutic a2AP-inactivating monoclonal antibody (a2AP-I) as the first new
class of safe, thrombus-dissolving agents since plasminogen activator therapy was first used in humans > 60
years ago. This new therapy is targeted to neutralize a2AP, the major inhibitor of thrombus dissolution in vivo.
Extensive research from our lab and others has shown that a2AP deficiency, or an a2AP-I removes the brakes
on thrombus dissolution by activating endogenous fibrinolysis, causing venous thrombi and pulmonary emboli
to dissolve spontaneously without causing bleeding. Even in experimental stroke, where the ischemic brain is a
sensitive test of therapeutic risk, a2AP-I therapy enhances thrombus dissolution, reduces brain infarction,
decreases brain hemorrhage and saves lives by comparison to r-tPA. An a2AP-I has extraordinary potential for
improving the treatment of PE. On the basis of pre-clinical data, we project that by comparison to current
therapy, treatment with TS23 could significantly reduce right heart failure, improve survival, decrease recurrent
thrombosis and prevent long-term disability in patients with pulmonary embolism. TSI currently holds an IND
for Phase II trial of TS23 in PE and now brings together leading investigators for an efficient trial to assess the
safety and efficacy of TS23 in patients with intermediate-risk pulmonary embolism.

## Key facts

- **NIH application ID:** 10255174
- **Project number:** 1R44HL158376-01
- **Recipient organization:** TRANSLATIONAL SCIENCES, INC.
- **Principal Investigator:** Sun Yong Jeong
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,408,991
- **Award type:** 1
- **Project period:** 2021-07-05 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10255174

## Citation

> US National Institutes of Health, RePORTER application 10255174, Novel α2-Antiplasmin Inactivation for Lysis of Intravascular Thrombi (NAIL-IT) Trial (1R44HL158376-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10255174. Licensed CC0.

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