SBIR-STTR Award

Development of Novel Therapeutic Molecules for Treatment of Squamous Head and Neck Cancers
Profile last edited on: 1/25/2022

Program
STTR
Agency
NIH | NCI
Total Award Amount
$299,503
Award Phase
1
Principal Investigator
Christopher Emil Whitehead
Activity Indicator

Company Information

MEKanistic Therapeutics LLC

U-M Venture Accelerator 1600 Huron Parkway:Huron Parkway
Ann Arbor, MI 48109
Multiple Locations:   
Congressional District:   12
County:   Washtenaw

Phase I

Phase I year
2021
Phase I Amount
$299,503
Mekanistic Therapeutics seeks to design, discover, and develop anti-cancer agents that selectively inhibit multiple oncogenic pathways. Among Mekanistic’s portfolio are dual and highly selective inhibitors of EGFR and PI3 kinase, which were rationally designed to only target these two critical oncogenes. The PI3 kinase (PI3K)/AKT/mTOR pathway plays a central role in driving tumor cell survival and progression. Despite intensive efforts of the pharmaceutical industry, PI3K inhibitors, encompassing isoform selective as well as pan-PI3K inhibitors, have largely failed to produce single agent activity against solid tumors. EGFR is a major contributor to the adaptive signaling mechanisms that lead to PI3K inhibitor resistance. Squamous cell carcinomas, which comprise an area of high unmet medical need, exhibit a high incidence of genomic alterations in both EGFR and PI3K. A central goal of this project is to provide preclinical proof of concept to support monotherapy development of a lead EGFR/PI3K inhibitor that is ideally suited to treat squamous head and neck cancers. Our preliminary data generated in multiple head and neck squamous cancer models strongly support this line of investigation. Phase I aims are focused on evaluation of the pre-lead molecule MTX-531 for its antitumor activity against patient-derived head and neck cancer xenografts in parallel with pharmacokinetic profiling in rats and dogs to assess bioavailability.

Public Health Relevance Statement:
PROJECT NARRATIVE Public Health Impact: There is an urgent need to develop more effective therapies to improve the low survival rate for squamous cell carcinomas of the head and neck. The prognosis for these cancers is especially poor. This project is focused on evaluation of MTX-531, a novel agent that selectively targets EGFR and PI3 kinase, that are key signaling molecules implicated in the progression of squamous cell carcinomas of the head and neck.

Project Terms:
inhibitor/antagonist ; inhibitor ; Antineoplastic Agents ; Anti-Cancer Agents ; Antineoplastic Drugs ; Antineoplastics ; Cancer Drug ; Neoplastic Disease Chemotherapeutic Agents ; Tumor-Specific Treatment Agents ; anti-cancer drug ; anticancer agent ; anticancer drug ; Automobile Driving ; driving ; Binding Sites ; Combining Site ; Reactive Site ; Biological Availability ; Bioavailability ; Biologic Availability ; Physiologic Availability ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; Capital ; capsule ; Capsules ; Squamous cell carcinoma ; Epidermoid Carcinoma ; Planocellular Carcinoma ; Squamous Carcinoma ; Squamous Cell Epithelioma ; Cell Survival ; Cell Viability ; Chemistry ; Clinical Trials ; Combined Modality Therapy ; Multimodal Therapy ; Multimodal Treatment ; combination therapy ; combined modality treatment ; combined treatment ; multi-modal therapy ; multi-modal treatment ; Deglutition ; Swallowing ; Diagnosis ; Canis familiaris ; Canine Species ; Dogs ; Dogs Mammals ; canine ; domestic dog ; intravenous administration ; Drug Industry ; Pharmaceutic Industry ; Pharmaceutical Industry ; Exhibits ; Face ; faces ; facial ; Future ; Goals ; In Vitro ; Incidence ; Investments ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Mus ; Mice ; Mice Mammals ; Murine ; Mutation ; Genetic Alteration ; Genetic Change ; Genetic defect ; genome mutation ; Oncogenes ; Cancer Genes ; Cancer-Promoting Gene ; Transforming Genes ; Patients ; Drug Kinetics ; Pharmacokinetics ; Phosphotransferases ; Kinases ; Phosphotransferase Gene ; Transphosphorylases ; Play ; Program Development ; Public Health ; Rattus ; Common Rat Strains ; Rat ; Rats Mammals ; Epidermal Growth Factor Receptor ; EGF Receptor ; EGFR ; ERBB Protein ; Epidermal Growth Factor Receptor Kinase ; Epidermal Growth Factor Receptor Protein-Tyrosine Kinase ; Epidermal Growth Factor-Urogastrone Receptors ; HER1 ; TGF-alpha Receptor ; Transforming Growth Factor alpha Receptor ; Urogastrone Receptor ; c-erbB-1 ; c-erbB-1 Protein ; erbB-1 ; erbB-1 Proto-Oncogene Protein ; erbBl ; proto-oncogene protein c-erbB-1 ; Research Design ; Study Type ; study design ; Role ; social role ; Signal Transduction ; Cell Communication and Signaling ; Cell Signaling ; Intracellular Communication and Signaling ; Signal Transduction Systems ; Signaling ; biological signal transduction ; Solubility ; Survival Rate ; Toxicology ; Up-Regulation ; Upregulation ; 1-Phosphatidylinositol 3-Kinase ; PI-3 Kinase ; PI-3K ; PI3-Kinase ; Phosphatidylinositol 3-Kinase ; Phosphatidylinositol-3-OH Kinase ; Phosphoinositide 3-Hydroxykinase ; PtdIns 3-Kinase ; Type I Phosphatidylinositol Kinase ; Type III Phosphoinositide 3-Kinase ; Measures ; Assimilations ; Proto-Oncogene Proteins c-akt ; AKT ; Akt protein ; Protein Kinase B ; RAC-PK protein ; c-akt protein ; proto-oncogene protein RAC ; proto-oncogene protein akt ; rac protein kinase ; related to A and C-protein ; base ; improved ; Area ; Clinical ; Phase ; Medical ; Evaluation ; Patient Selection ; Funding ; Head and Neck Cancer ; Malignant Head and Neck Neoplasm ; head/neck cancer ; malignant head and neck tumor ; Solid Neoplasm ; Solid Tumor ; Therapeutic ; Metabolic ; Investigation ; Oral ; Head and Neck ; Head and neck structure ; Heterograft ; Heterologous Transplantation ; Xenograft ; Xenotransplantation ; xeno-transplant ; xeno-transplantation ; Xenograft procedure ; Tumor Cell ; neoplastic cell ; Isoforms ; Protein Isoforms ; success ; Structure ; novel ; MMAC1 ; Mutated in Multiple Advanced Cancers 1 ; PHTS gene ; PHTS protein ; PTEN ; PTEN Hamartoma Tumor Syndrome ; PTEN Hamartoma Tumor Syndrome With Granular Cell Tumor ; PTEN1 ; Phosphatase and Tensin Homolog ; Phosphatase and Tensin Homolog Deleted on Chromosome 10 ; PTEN gene ; Malignant Neck Neoplasm ; malignant neck tumor ; Neck Cancer ; Head Cancer ; Pharmacodynamics ; single molecule ; pill ; Anti-EGFR Monoclonal Antibody ; Anti-Epidermal Growth Factor Receptor Monoclonal Antibody ; Cetuximab ; Tarceva ; Erlotinib ; Molecular Interaction ; Binding ; HNSCC ; Head and Neck Carcinoma ; SCCHN ; head and neck squamous cell cancer ; Head and Neck Squamous Cell Carcinoma ; kinase inhibitor ; Pharmaceutical Agent ; Pharmaceuticals ; Pharmacological Substance ; Pharmacologic Substance ; small molecule ; PI3K-Alpha ; PIK3-Alpha ; PIK3CA ; Phosphatidylinositol 3-Kinase, Catalytic, 110-kD, Alpha ; Phosphatidylinositol 3-Kinase, Catalytic, Alpha ; p110-Alpha ; PIK3CA gene ; FK506 Binding Protein 12-Rapamycin Associated Protein 1 ; FKBP12 Rapamycin Complex Associated Protein 1 ; FRAP1 ; FRAP2 ; Mechanistic Target of Rapamycin ; RAFT1 ; mTOR ; mammalian target of rapamycin ; FRAP1 gene ; EGFR Blocker ; EGFR Inhibitor ; EGFR Tyrosine Kinase Inhibitor ; EGFR-TK Inhibitor ; Epidermal Growth Factor Receptor Inhibitor ; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor ; Dose ; DNA Alteration ; DNA mutation ; Genetic mutation ; Sequence Alteration ; genomic alteration ; DNA Sequence Alteration ; Data ; in vivo ; Cancer Model ; CancerModel ; Cancer Prognosis ; Phosphatidylinositide 3-Kinase Inhibitor ; PI3-Kinase Inhibitors ; Signaling Molecule ; Small Business Technology Transfer Research ; STTR ; Xenograft Model ; xenograft transplant model ; xenotransplant model ; Molecular ; resistance mechanism ; resistant mechanism ; Development ; developmental ; safety study ; Pathway interactions ; pathway ; pre-clinical ; preclinical ; design ; designing ; Outcome ; EGFR inhibition ; Resistance ; resistant ; Oncogenic ; novel therapeutics ; new drug treatments ; new drugs ; new therapeutics ; new therapy ; next generation therapeutics ; novel drug treatments ; novel drugs ; novel therapy ; therapy development ; develop therapy ; intervention development ; treatment development ; commercial application ; tumor ; overexpression ; overexpress ; FDA approved ; candidate marker ; candidate biomarker ; effective therapy ; effective treatment ; comparative efficacy ; compare efficacy ; liquid formulation ; phase 2 study ; phase II study ; targeted treatment ; targeted drug therapy ; targeted drug treatments ; targeted therapeutic ; targeted therapeutic agents ; targeted therapy ; oral HPV-positive head and neck cancers ; HPV(+) HNSCC ; HPV(+) head and neck squamous cell carcinoma ; HPV+ HNSCC ; HPV+ head and neck cancers ; HPV-associated head and neck squamous cell carcinoma ; HPV-positive HNSCC ; HPV-positive head and neck cancers ; HPV-related HNSCC ; HPV-related head and neck squamous cell carcinoma ; oral HPV-positive HNSCC ; Formulation ; nanomolar ; nano-molar ; mutational status ; mutation status ; clinical development ; Computer Models ; Computerized Models ; computational modeling ; computational models ; computer based models ; computerized modeling ; alpelisib ; PIQRAY ; patient derived xenograft model ; PDX model ; Patient derived xenograft ;

Phase II

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