BMCC-2022-P03

The Second Generation of αIIbβ3 Antagonist Prevent Thrombosis without the Risk of Bleeding

BMCC

The Second Generation of αIIbβ3 Antagonist Prevent Thrombosis without the Risk of Bleeding

未定中標題
BMCC Targeted indication

Acute Myocardial Infarction and Thrombotic Stroke

BMCC Status

Pre-clinical studies

BMCC Key features
  • High anti-platelet and anti-thrombotic efficacy
  • Highly stable αIIbβ3 antagonist with a stable pharmacokinetic profile
  • Favorable safety profile with no thrombocytopenia and bleeding side effects
BMCC Market

Use of antithrombotic therapy, including antiplatelet and anticoagulant agents, is a vital element in reducing the overall morbidity and mortality in patients with cardiovascular disease. Importantly, RR with very high safety profile can potentially help resolve the issue that clinical anti-thrombotics (i.e., abciximab, eptifibatide, and tirofiban) have significant bleeding risk. Furthermore, RR exhibiting stable pharmacokinetic profile given by intramuscular injection offers greater convenience to patients and reduces overall healthcare costs compared to standard IV infusion.

MODE OF ACTION

RR is selective inhibitor of aIIbb3 that can prevents thrombosis and minimizes hemorrhage.

Current αIIbβ3 antagonists are effective anti-thrombotics but have significant bleeding risk. Disintegrin TMV-7 and its derivative RR prevent thrombosis by selectively inhibiting integrin outside-in signaling without affecting processes of hemostasis (i.e., platelet adhesion and clot retraction) in human thrombin-activated platelets, thus they do not increase bleeding risk and have a greater safety profile than the current aIIbb3 antagonists (i.e., Eptifibatide).

EXPERIMENTAL RESULTS

in vitro efficacy

TMV-7, and TMV-7 mutant RR inhibit agonist-induced human platelet aggregation through αIIbβ3 receptor blockade, especially RR exhibits higher potency in inhibiting platelet aggregation and its safety index is raised to 260-time higher than eptifibatide in human platelet suspension.

in vivo efficacy

The anti-platelet and thrombotic efficacy of RR has been proven in mouse and pig models; RR neither prolonged the bleeding time nor reduced in platelet counts in the bleeding tendency in both animal models.

Safety pharmacology and general toxicology
  • At doses up to 20 times the clinical dose of RR, no prolonging tail-bleeding time and thrombocytopenia are observed in FcgRIIa transgenic mice in vivo.
  • At doses up to 3 times the clinical dose of RR, no defected hemostatic function and toxicological findings are observed in pigs in vivo.

RR does not impair the appropriate balance between potent antithrombotic effects and physiological hemostasis as revealed by in vivo thrombosis model and bleeding time test.

Pharmaceutical development
  • Drug product as a solution for injection is stable for minimum 40 hours.
  • A new PEGylated RR provides enhancing pharmaceutical advantages and pharmacokinetic characterization.
  • The optimal small-molecules mimetics are being developed with NMR studies and computer modeling.

INTELLECTUAL PROPERTY

Applications of Taiwan and PCT patents

SELECTED PUBLICATIONS

Kuo et al., 2017. J Thromb Haemost. doi: 10.1111/jth.13803
Kuo et al., 2017. ISTH Conference. Abstract A-859-0079-00721
Hung et al., 2017. Eur J Pharmacol. 813:24-32 Huang et al., 2016. Thromb J. 14(Suppl 1):18

BUSINESS OPPORTUNITY

License and/or Collaboration and Sponsored Research

CONTACT

service@biip-dcc.org

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