TEZCAT Laboratories LLC is an early-stage, Austin-based biotechnology company developing novel biologics with a unique mechanism of action to treat the most recalcitrant cancers, such as mutant KRas pancreatic cancer. As an alternative to targeting mutant KRas itself, much attention has been paid to targeting cellular events that are a result of mutant KRas. New efforts are underway to exploit previously unrecognized vulnerabilities. We have observed that mutant KRas pancreatic cancer cells display high levels of a protein scavenging process. Harnessing this metabolic adaptation, we have created protein-drug conjugates that carry an FDA-approved cytotoxic payload. In vitro and in vivo assays demonstrate that the protein-drug conjugates show selectivity for mutant KRas cancer cells and maintain potency in the low nanomolar range. The protein-drug conjugates display relatively fast systemic clearance but maintain beneficial characteristics of biologics such as decreased systemic toxicities and tumor accumulation. Thus, we hypothesize that our novel conjugates will reduce on-target and off-target effects often seen with traditional antibody-drug conjugates and fill a void of therapeutic options for patients with mutant KRas pancreatic cancer. We propose a Phase I STTR program for investigators at TEZCAT Laboratories and New York University Langone Health to advance this lead through Specific Aims that evaluate the lead drug candidates in controlling human cancer cell growth in a clinically-relevant mouse model of pancreatic cancer. TEZCAT Laboratories is working with NYU to facilitate licensing the underlying intellectual property covering the technology being developed. The commercialization strategy will be based on establishing initial efficacy and nontoxicity of the lead compound in relation to mutant KRas status in Phase I STTR studies, further development towards IND status in Phase II SBIR studies, and then first-in-human clinical trials. Thus, we expect Phase I STTR to provide the basis for pursuit of additional data in Phase II aimed at GMP protocols and further non-GLP and GLP safety and toxicity studies.
Public Health Relevance Statement: Project narrative: TEZCAT Laboratories LLC is an early-stage biotechnology company focused on developing innovative therapeutics to treat mutant Ras cancers. In this Phase I STTR, TEZCAT Laboratories is developing a proprietary monobody-drug conjugate that has tumor-cell specificity in pancreatic cancer.
Project Terms: Attention ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biologic Characteristic ; Biological Characteristics ; Biotechnology ; Biotech ; Blood Vessels ; vascular ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; Cell Line ; CellLine ; Strains Cell Lines ; cultured cell line ; Clinical Trials ; Dendritic Cells ; Veiled Cells ; Disease ; Disorder ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Endothelium ; Fibronectins ; Cold-Insoluble Globulins ; FN1 ; Fibronectin 1 ; LETS Proteins ; Large External Transformation-Sensitive Protein ; Opsonic Glycoprotein ; Opsonic alpha(2)SB Glycoprotein ; alpha 2-Surface Binding Glycoprotein ; Future ; Government ; Health ; Equus caballus ; Domestic Horse ; Equine ; Equine Species ; Equus przewalskii ; Horses ; Human ; Modern Man ; In Vitro ; Incidence ; Laboratories ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; Liposomes ; Liposomal ; Lung ; Lung Respiratory System ; pulmonary ; macrophage ; MÏ ; Morbidity - disease rate ; Morbidity ; mortality ; Persons ; Neoplasm Metastasis ; Metastasis ; Metastasize ; Metastatic Lesion ; Metastatic Mass ; Metastatic Neoplasm ; Metastatic Tumor ; Secondary Neoplasm ; Secondary Tumor ; cancer metastasis ; tumor cell metastasis ; neutrophil ; Blood Neutrophil ; Blood Polymorphonuclear Neutrophil ; Marrow Neutrophil ; Neutrophilic Granulocyte ; Neutrophilic Leukocyte ; Polymorphonuclear Cell ; Polymorphonuclear Leukocytes ; Polymorphonuclear Neutrophils ; New York ; Oncogenes ; Cancer Genes ; Cancer-Promoting Gene ; Transforming Genes ; Patients ; Proteins ; Research Personnel ; Investigators ; Researchers ; Resources ; Research Resources ; Safety ; Solubility ; Specificity ; Technology ; Tissues ; Body Tissues ; Universities ; Drug Delivery Systems ; Drug Delivery ; irinotecan ; Campto ; camptosar ; Paclitaxel ; Anzatax ; Asotax ; Bristaxol ; Paclitaxel (Taxol) ; Praxel ; Taxol ; Taxol A ; Taxol Konzentrat ; Apoptosis ; Apoptosis Pathway ; Programmed Cell Death ; base ; tumor progression ; cancer progression ; neoplasm progression ; neoplastic progression ; improved ; Penetration ; Phase ; Biological ; Evaluation ; Lesion ; Serum ; Blood Serum ; liver function ; Renal function ; kidney function ; Licensing ; Intellectual Property ; Therapeutic ; fluid ; liquid ; Liquid substance ; Metabolic ; Malignant Cell ; cancer cell ; Malignant Pancreatic Neoplasm ; Pancreas Cancer ; Pancreatic Cancer ; pancreatic malignancy ; Malignant neoplasm of pancreas ; Nature ; Knowledge ; programs ; Event ; Clinic ; Protocol ; Protocols documentation ; Hepatic Neoplasm Secondary ; Hepatic metastasis ; Liver secondaries ; Liver secondary cancer ; Metastatic Tumor to the Liver ; Metastatic malignant neoplasm to liver ; liver metastases ; malignant liver neoplasm, specified as secondary ; metastasis in the liver ; metastasis to the liver ; metastasize to the liver ; metastatic cancer to liver ; metastatic liver ; metastatic liver neoplasm ; secondary liver malignancy ; secondary malignant liver neoplasm ; Metastatic Neoplasm to the Liver ; Heterograft ; Heterologous Transplantation ; Xenograft ; Xenotransplantation ; xeno-transplant ; xeno-transplantation ; Xenograft procedure ; experience ; mutant ; Tumor Cell ; neoplastic cell ; synthetic protein ; cellular targeting ; Toxicities ; Toxic effect ; austin ; expectation ; novel ; validation studies ; Maximal Tolerated Dose ; Maximally Tolerated Dose ; Maximum Tolerated Dose ; Normal Cell ; Extracellular Protein ; Pancreas Ductal Adenocarcinoma ; Pancreatic Ductal Adenocarcinoma ; Address ; Dose ; cytotoxic ; Data ; pre-clinical testing ; Preclinical Testing ; precancerous ; premalignant ; in vivo ; in vivo Model ; Cancer Cell Growth ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Small Business Technology Transfer Research ; STTR ; Characteristics ; Process ; Development ; developmental ; nanoparticle ; nano particle ; nano-sized particle ; nanosized particle ; Cancer cell line ; cancer type ; innovation ; innovate ; innovative ; clinically relevant ; clinical relevance ; novel therapeutics ; new drug treatments ; new drugs ; new therapeutics ; new therapy ; next generation therapeutics ; novel drug treatments ; novel drugs ; novel therapy ; mouse model ; murine model ; commercialization ; tumor ; therapeutic development ; therapeutic agent development ; FDA approved ; standard of care ; drug candidate ; pancreatic cancer cells ; pancreatic tumor cells ; companion diagnostics ; systemic toxicity ; nanomolar ; nano-molar ; Antibody-drug conjugates ; efficacy study ; first-in-human ; first in man ; pancreatic cancer model ; pancreatic PDX models ; pancreatic tumor model ; KPC model ; KPC genetically-engineered mouse ; KPC mouse ; KPC murine ; LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre ; LSL-KrasG12D/+;LSL-p53R172H/+;Pdx-1-Cre ; pancreatic ductal adenocarcinoma model ; PDA model ; PDAC Model ; therapeutically effective ;
