SBIR-STTR Award

MT-125 for the Therapeutic Treatment of Glioblastoma
Award last edited on: 1/31/2024

Sponsored Program
SBIR
Awarding Agency
NIH : NCI
Total Award Amount
$1,545,093
Award Phase
2
Solicitation Topic Code
395
Principal Investigator
Steven S Rosenfeld

Company Information

Myosin Therapeutics Inc

130 Scripps Way
Jupiter, FL 33458
   (844) 696-7469
   contact@myosintx.com
   www.myosintherapeutics.com
Location: Single
Congr. District: 18
County: Palm Beach

Phase I

Contract Number: 1R42CA278293-01A1
Start Date: 4/1/2023    Completed: 12/31/2023
Phase I year
2023
Phase I Amount
$406,500
An area of significant unmet need is the treatment of glioblastoma (GBM), an aggressive, fast-growingand lethal brain cancer that represents 48% of all malignant brain tumors. Untreated, GBM is fatal within threemonths, and due to its high rate of recurrence and invasive nature, the current standard of care, consisting ofsafe maximal tumor resection, radiation therapy and chemotherapy, only extends survival following initialdiagnosis to one year. Invasion and proliferation, also known as Go and Grow, are defining phenotypes of GBM,and GBM cells do only one or the other. However, blocking invasion stimulates proliferation and vice versa,implying that an ideal therapeutic needs to block both Go and Grow simultaneously. Extensive geneticinterventions have shown that simultaneous disruption of two non-muscle myosin II (NMII) molecular motors(NMIIA and IIB) meet these criteria. However, the translational potential of this research has been limited by thelack of a clinically safe, CNS-penetrant NMII small molecule inhibitor. Following extensive medicinal chemistryefforts to optimize selectivity for safety and tolerability, MT-125 was identified. MT-125 is a well-tolerated, dualsmall molecule inhibitor of NMIIA and IIB with a high degree of brain penetrance, a requirement for an effectiveGBM therapeutic. Preclinical in vitro and in vivo studies show that MT-125 blocks the Go and Grow phenotypesand extends survival. Due to its unique mode of action, MT-125 also synergizes with existing FDA-approvedtreatments, presenting a path to a potentially curative treatment. The overarching goal of the current proposalis to ready MT-125 for rapid entry into IND-enabling studies. This will be achieved through several activities.Phase I will focus on confirmation of preclinical efficacy with a clinically viable route of administration, in vitrostudies of synergy between MT-125 and additional existing FDA-approved treatments, and in vitro safetyprofiling, pre-formulation studies and demo batch scale-up of MT-125. Quantitative milestones for transition toPhase II are detailed in the application. In Phase II, in vivo efficacy testing will be performed on the mostpromising synergy combinations identified in Phase I, as well as a non-GLP dosing safety study, GLP synthesis,and formulations development with polymorph screening. The Commercialization Plan details the GBM market,as well as Myosin Therapeutics' clinical and regulatory strategy for rapid advancement of MT-125 to the clinic.

Public Health Relevance Statement:
PROJECT NARRATIVE Glioblastoma is an aggressive, fast-growing brain cancer that represents nearly half of all malignant brain tumors. Due to the high rate of recurrence, current treatment options only extend survival following initial diagnosis to one year. Building on years of basic research into the biology of glioblastoma identifying nonmuscle myosin II as a potential therapeutic target, an interdisciplinary team has been brought together with the necessary expertise in glioblastoma and myosin biology, drug development and the clinical treatment of glioblastoma to advance a small molecule inhibitor for glioblastoma therapy.

Project Terms:

Phase II

Contract Number: 4R42CA278293-02
Start Date: 4/1/2023    Completed: 12/31/2025
Phase II year
2024
Phase II Amount
$1,138,593
An area of significant unmet need is the treatment of glioblastoma (GBM), an aggressive, fast-growingand lethal brain cancer that represents 48% of all malignant brain tumors. Untreated, GBM is fatal within threemonths, and due to its high rate of recurrence and invasive nature, the current standard of care, consisting ofsafe maximal tumor resection, radiation therapy and chemotherapy, only extends survival following initialdiagnosis to one year. Invasion and proliferation, also known as Go and Grow, are defining phenotypes of GBM,and GBM cells do only one or the other. However, blocking invasion stimulates proliferation and vice versa,implying that an ideal therapeutic needs to block both Go and Grow simultaneously. Extensive geneticinterventions have shown that simultaneous disruption of two non-muscle myosin II (NMII) molecular motors(NMIIA and IIB) meet these criteria. However, the translational potential of this research has been limited by thelack of a clinically safe, CNS-penetrant NMII small molecule inhibitor. Following extensive medicinal chemistryefforts to optimize selectivity for safety and tolerability, MT-125 was identified. MT-125 is a well-tolerated, dualsmall molecule inhibitor of NMIIA and IIB with a high degree of brain penetrance, a requirement for an effectiveGBM therapeutic. Preclinical in vitro and in vivo studies show that MT-125 blocks the Go and Grow phenotypesand extends survival. Due to its unique mode of action, MT-125 also synergizes with existing FDA-approvedtreatments, presenting a path to a potentially curative treatment. The overarching goal of the current proposalis to ready MT-125 for rapid entry into IND-enabling studies. This will be achieved through several activities.Phase I will focus on confirmation of preclinical efficacy with a clinically viable route of administration, in vitrostudies of synergy between MT-125 and additional existing FDA-approved treatments, and in vitro safetyprofiling, pre-formulation studies and demo batch scale-up of MT-125. Quantitative milestones for transition toPhase II are detailed in the application. In Phase II, in vivo efficacy testing will be performed on the mostpromising synergy combinations identified in Phase I, as well as a non-GLP dosing safety study, GLP synthesis,and formulations development with polymorph screening. The Commercialization Plan details the GBM market,as well as Myosin Therapeutics' clinical and regulatory strategy for rapid advancement of MT-125 to the clinic.

Public Health Relevance Statement:
PROJECT NARRATIVE Glioblastoma is an aggressive, fast-growing brain cancer that represents nearly half of all malignant brain tumors. Due to the high rate of recurrence, current treatment options only extend survival following initial diagnosis to one year. Building on years of basic research into the biology of glioblastoma identifying nonmuscle myosin II as a potential therapeutic target, an interdisciplinary team has been brought together with the necessary expertise in glioblastoma and myosin biology, drug development and the clinical treatment of glioblastoma to advance a small molecule inhibitor for glioblastoma therapy.

Project Terms:
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