MORAb-028 / Eisai, Amgen - LARVOL DELTA

Development of clinically viable non-muscle myosin II small molecule inhibitors. (PubMed, Cell) - "MT-228 and MT-110 have excellent properties, including high brain penetration and efficacy in preclinical models of methamphetamine use disorder (MUD), which has no current FDA-approved therapies. The structure of MT-228 bound to myosin II provides insight into its selectivity for NMII over CMII. The broad therapeutic windows of these NMII inhibitors provide valuable tools for the scientific community and a promising clinical candidate for the treatment of MUD."

Journal • Oncology

Development of Clinically Viable Non-Muscle Myosin II Small Molecule Inhibitors with Broad Therapeutic Potential. (PubMed, bioRxiv) - "Research suggests numerous indications, from axon regeneration and cancer, would benefit from a small molecule inhibitor of non-muscle myosin II, a molecular motor that regulates the actin cytoskeleton. Current chemical probe options are very limited and lack sufficient safety for in vivo studies, which we show is primarily due to potent inhibition of cardiac myosin II.Rational design that focused on improving target selectivity over the pan-myosin II inhibitor, blebbistatin, led to the identification of MT-228, a small molecule inhibitor with a wide therapeutic window.High-resolution structure of MT-228 bound to myosin II reveals that selectivity results from a different positioning compared to blebbistatin and an important sequence difference between cardiac and non-muscle myosin II in the inhibitor binding pocket.A single administration of MT-228 shows long-lasting efficacy in animal models of stimulant use disorder, a current unmet and rapidly escalating need with no..."

Journal • Oncology

Safety Study of Human IgM (MORAb-028) to Treat Metastatic Melanoma (clinicaltrials.gov) - P1; N=18; Terminated; Sponsor: Morphotek; Suspended -> Terminated

Trial termination • Biosimilar • Melanoma • Oncology