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"The search to discover PTP-1B inhibitors as a therapeutic target for thetreatment of obesity and type 2 diabetes has long been a goal of drugdevelopment but achieving the selectivity necessary to demonstrate safety hasbeen a significant hurdle. The new information on the mechanism by whichMSI-1436 inhibits PTP-1B supports its first-in-class status," stated JackArmstrong, President and Chief Executive Officer of Genaera. "MSI-1436 is theonly reversible, noncompetitive inhibitor of PTP-1B in clinical stagedevelopment. It is the allosteric nature of MSI-1436 and its ability toreversibly inhibit PTP-1B that is believed to be the key to the safety we haveobserved in Phase 1. We anticipate this will be attractive to both potentialpartners and clinicians as we obtain further evidence of the efficacy andsafety of MSI-1436 in future studies."
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Inhibition of PTP-1B, a non-receptor isoform of the protein tyrosinephosphatase family, by MSI-1436 has been shown to reduce food intake, induceweight loss, and increase insulin sensitivity in diet induced and geneticallyobese animal models. The poster described the inhibition of PTP-1B byMSI-1436 as fully reversible and characterized by a classic noncompetitive,dose-dependent mechanism which exhibited greatest potency for the full-lengthform of the enzyme. Cellular studies demonstrating that phosphataseinhibition by MSI-1436 in the presence of insulin pretreatment providedfurther support for the inhibition of PTP-1B and a greater understanding ofthe role of enhanced insulin signaling associated with weight loss and glucosecontrol observed during treatment in preclinical models of obesity anddiabetes with MSI-1436.
To date, MSI-1436 has been shown to have few adverse events and to bewell-tolerated in the over 50 subjects who participated in the Phase 1clinical program of MSI-1436. Genaera plans to conduct an ascendingmultiple-dose study later this year.
About Trodusquemine (MSI-1436)
Trodusquemine is a centrally and peripherally-acting appetite suppressantand the first highly selective inhibitor of protein tyrosine phosphatase 1B(PTP-1B). PTP-1B is central to controlling the function of both the leptinand insulin pathways. By inhibiting PTP-1B, MSI-1436 is expected to decreaseappetite and normalize blood sugar. Trodusquemine has produced consistent,sustainable weight loss in a variety of animal models and appears to overcomemetabolic readjustment, which often limits sustained weight loss duringcaloric restriction. In addition, trodusquemine has shown the ability toreverse co-morbidities associated with obesity such as abnormal glucosemetabolism and cholesterol elevation.
About Genaera
Genaera Corporation is focused on advancing the science and treatment ofmetabolic diseases. The Company has significant market opportunities with afirst-in-class molecule, trodusquemine (MSI-1436), that has the potential toredefine the treatment paradigm for obesity and type 2 diabetes and ispresently in a phase 1 trial in obesity. In addition, Genaera has avalue-driven, fully out-licensed partnership with MedImmune, Inc. for a secondcore program that is presently undergoing phase 2 clinical testing in asthma.Genaera is committ
