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Next Generation Fusion Inhibitor Program – TRI-1144 (TR-0291144)
Our next generation fusion inhibitor, TRI-1144, has been developed with the specific goal of achieving durable suppression of HIV by increasing the potency and raising the genetic barrier to the development of resistance. Also, key to the development program was improving patient convenience via more patient-friendly administration with less frequent dosing and reduction of the injection site reactions associated with FUZEON. TRI-1144 (TR-0291144) is currently under investigation in a Phase I clinical trial.
TRI-1144 is a 38 amino acid peptide derived from the HIV gp41 sequence shown to be the most potent in inhibiting viral fusion; its sequence partially overlaps that of enfuvirtide. Through Discovery efforts undertaken at Trimeris, the nascent gp41 sequence was intentionally altered allowing the peptide to exist as a stable alpha helix of three peptide molecules known as a trimer. The key contact residues required for viral fusion were maintained or conservatively changed – the result of all of the modifications is TRI-1144. These alterations are believed to give TRI 1144 its unique properties of high genetic barrier to resistance, enhanced pharmacokinetic properties and excellent physical chemical properties.
In preclinical studies, TRI-1144 has proven to be as or more potent than enfuvirtide, have a much higher genetic barrier to resistance and have approximately a ten-fold longer half-life in cynomolgus monkeys than enfuvirtide. The potency, improved genetic barrier and pharmacokinetic properties suggest that TRI-1144 will be administered less frequently than FUZEON and possibly at a lower dose. In the appropriate sustained release formulations, it is envisaged that TRI-1144 could have a once weekly dosing profile.
No safety issues were identified in a full battery of IND supporting toxicology studies. The physical chemical properties of TRI-1144 indicate that a stable solution formulation should be achievable removing the requirement for the onerous reconstitution needed for FUZEON for a patient-friendly once daily administration from an auto-injector such as a pre-filled pen device.
An IND was filed in January 2008 for the clinical study of TRI-1144. Currently, one clinical protocol is in progress (TRI 1144-101). TRI 1144-101 is a single dose escalation study in healthy volunteers that is investigating the safety, including injection site reactions, tolerability and pharmacokinetics of TRI-1144. Results are expected in the third quarter of 2008.
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| Trimeris was founded by leading HIV research scientists, and continues to focus on drug discovery and design. |
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| We're motivated by the science. But we're passionate about improving life. |
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