Document text
Principal Investigator: Livia Agnes Veress
Organization: CMTX BIOTECH, INC.
Fiscal Year: 2024
Award: $299,993
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
CMTx Biotech is a drug development company working to commercialize a pipeline of proprietary, non-
antibiotic, chemically-modified tetracycline (CMT) compositions and formulations for the host-modulatory
treatment of diseases with high unmet needs, including a proprietary, clinical-stage, orally-administered small-
molecule drug candidate, incyclinide (CMT-3 / COL-3), as a medical countermeasure for the treatment of
exposure to vesicants (blister agents) that may occur in chemical warfare, terrorism or industrial accidents.
Vesicating agents, including distilled mustard (HD), mustard gas (H), mustard/lewisite, mustard/T, nitrogen
mustard, sesqui mustard, and sulfur mustard, can cause moderate to debilitating injuries and pain to the eye,
skin, and mucous membranes. The primary modes of exposure are through contact, inhalation and ingestion.
Depending on the dose, route, and duration of exposure, toxic symptoms can range in varying degrees of
ocular and dermal burns, blister formation, bronchospasm, dyspnea, pulmonary edema, bronchitis, and
immune- and bone marrow suppression. Sulfur mustard is a human-made chemical warfare agent that causes
blistering of the skin and mucous membranes on contact. Vesicating chemicals have been identified by the
U.S. Department of Homeland Security (DHS) and the Department of Health and Human Services (HHS) as
highly toxic chemicals of concern to public health security due to the devastating health effects of exposure.
Unfortunately, no known antidote exists for sulfur mustard exposure. Treatment consists of removing sulfur
mustard from the body as soon as possible and providing supportive medical care in a hospital setting or by
trained emergency personnel. There remains a critical need for safe and effective medical countermeasures
for the treatment of acute and chronic lung injuries caused by the inhalation of SM. The market for treatments
specifically targeting sulfur mustard exposure is relatively limited to purchases by the U.S. Strategic National
Stockpile and international equivalents. However, companies that secure FDA approval for a medical
countermeasure (MCM) against certain chemical, biological, radiological or nuclear (CBRN) threats are eligible
to receive a Priority Review Voucher (PRV), which allows the recipient to expedite the review of a future New
Drug Application (NDA) or Biologics License Application (BLA) for a different product of their choice. PRVs
can be sold or transferred to other companies, with an average value of approximately $100M. Our lead drug
candidate is a pleiotropic matrix metalloproteinase (MMP) modulator which inhibits pathologically-excessive
collagenolysis and resolves systemic inflammation. Safety of the compound has already been demonstrated in
Investigational New Drug (IND)-enabling studies. The drug has been evaluated in several clinical trials for the
treatment of diseases as disparate as AIDS-related Kaposi’s sarcoma, recurrent high-grade gliomas, refractory
metastatic cancer, acne, rosacea and periodontitis. The Specific Aims of this STTR are (a) to demonstrate a
dose-dependent survival benefit of incyclinide (25mg/kg, 50mg/kg, or 100mg/kg by oral gavage) in an
established rat model of sulfur mustard (SM) inhalation with daily treatment initiated 24-hours post-SM
exposure and continued for 28 days, and (b) to evaluate the effect of orally-administered incyclinide on the
pathogenesis of SM-induced lung injury, pulmonary fibrosis and inflammatory biomarkers. Our long-term goal
is to secure FDA approval for incyclinide as a safe and effective medical countermeasure for SM-induced lung
injury. We anticipate that our drug candidate will improve survival and mitigate SM-induced lung injury in
exposed rats, reduce SM-induced injury parameters as assessed through histopathology, as well as lung
fibrosis and key inflammatory biomarkers. Successful completion of these studies will allow CMTx Biotech to
(a) evaluate our drug candidate in non-rodent animal model of SM-induced lung injury, (b) prepare and submit
a pre-IND meeting request and briefing document, and (c) scale-up production of the drug substance and drug
product under current Good Manufacturing Practices (cGMP).
Terms: <(TNF)-α><72-kDa Gelatinase><72-kDa Type IV Collagenase><72kD type IV Collagenase><92-kDa Gelatinase><92-kDa Type IV Collagenase><AIDS with Kaposi's sarcoma><AIDS-Related Kaposi's Sarcoma><ARDS><Acne><Acne Rosacea><Acute Lung Injury><Acute Pulmonary Injury><Acute Respiratory Distress><Acute Respiratory Distress Syndrome><Adult ARDS><Adult RDS><Adult Respiratory Distress Syndrome><Agreement><Animal Model><Animal Models and Related Studies><Antibiotic Agents><Antibiotic Drugs><Antibiotics><Antidotes><Apoptosis-Related Cysteine Protease Caspase 1><Autoimmune Deficiency Syndrome-Related Kaposi Sarcoma><B cell differentiation factor><B cell stimulating factor 2><B-Cell Differentiation Factor><B-Cell Differentiation Factor-2><B-Cell Stimulatory Factor-2><BCDF><BSF-2><BSF2><Biological><Biological Agent><Biological Markers><Biological Products><Biotech><Biotechnology><Bis(beta-chloroethyl) Sulfide><Bleb><Blister><Bone Marrow Suppression><Breathlessness><Bronchial Spasm><Bronchiolitis Obliterans><Bronchitis><Bronchopulmonary Dysplasia><Bronchospasm><Bulla><Bullous Lesion><Burn injury><Burns><CASP-1><CASP1><CASP1 gene><COVID-19 infection><COVID-19 virus infection><COVID19 infection><Cachectin><Caring><Caspase-1><Caspase-1 Gene><Chemical Warfare><Chemical Warfare Agents><Chemicals><Chloramin><Chlorethazine><Chlormethine><Chronic Lung Injury><Chronic Periodontitis><Chronic Pulmonary Injury><Clinical><Clinical Treatment><Clinical Trials><Common Rat Strains><Cricetinae><Da Nang Lung><Department of Health and Human Services><Dermal><Di-2-chloroethyl Sulfide><Dichlorodiethyl Sulfide><Disease><Disorder><Disparate><Disseminated Malignant Neoplasm><Dose><Doxycycline><Drugs><Dysfunction><Dyspnea><Eligibility><Eligibility Determination><Endotoxins><Epidemic Kaposi's Sarcoma><Epithelium><Exposure to><Exudative Bronchiolitis><Eye><Eyeball><Family suidae><Fibrosis><Formulation><Functional disorder><Future><Gelatinase A><Gelatinase B><Gelatinase Neutrophil><General Radiology><Glial Cell Tumors><Glial Neoplasm><Glial Tumor><Glioma><Goals><Good Manufacturing Process><Good manufacturing practice><HN-2><HN2><HPGF><Hamsters><Hamsters Mammals><Health><Hepatocyte-Stimulating Factor><Histologic><Histologically><Histology><Histopathology><Hospitals><Hour><Human><Hybridoma Growth Factor><ICE Protease><IFN-beta 2><IFNB2><IL-1 beta Convertase><IL-1 beta-Converting Enzyme><IL-1BC><IL-1b Converting Enzyme><IL-6><IL1B-Convertase><IL1BC><IL1BCE><IL6 Protein><Immune><Immunes><Industrial Accidents><Inflammasome><Inflammation><Inflammatory><Inflammatory Response><Ingestion><Inhalation><Inhaling><Injury><Interleukin 1-B Converting Enzyme><Interleukin 1-Beta Convertase><Interleukin-1 Beta Converting Enzyme><Interleukin-1 Converting Enzyme><Interleukin-6><International><Intravenous><Investigational Drugs><Investigational New Drugs><Kaposi's Sarcoma Epidemic Type><Knowledge><Lead><Lesion><Licensing><Lung Tissue Fibrosis><Lung damage><MGI-2><MMP-2><MMP-9><MMP-9 Protein><MMPs><Macrophage Gelatinase><Macrophage-Derived TNF><Marketing><Matrix Metalloproteinase-2><Matrix Metalloproteinase-9><Matrix Metalloproteinases><Mechanical ventilation><Mechlorethamine><Medical><Medication><Metastatic Cancer><Metastatic Malignant Neoplasm><Methylchlorethamine><Mice><Mice Mammals><Miscellaneous Antibiotic><Modeling><Modern Man><Monocyte-Derived TNF><Mucosa><Mucosal Tissue><Mucous Membrane><Murine><Mus><Mustard><Mustard Gas><Mustine><Myeloid Differentiation-Inducing Protein><Neuroglial Neoplasm><Neuroglial Tumor><Nitrogen Mustard><Nuclear><Oral><Oral Administration><Oral Drug Administration><Ovine><Ovis><Pain><Painful><Pathogenesis><Pathologic><Patients><Pb element><Peer Review><Periodontitis><Pharmaceutical Agent><Pharmaceutical Preparations><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Phase><Physiopathology><Pigs><Plasmacytoma Growth Factor><Poison><Pre IND FDA meeting><Pre-IND mtg><Prevention><Proliferative Bronchiolitis><Protocol Screening><Public Health><Publications><Pulmonary Edema><Pulmonary Fibrosis><Radiology><Radiology Specialty><Rat><Rats Mammals><Rattus><Recurrence><Recurrent><Refractory><Rosacea><Route><SARS-CoV-2 infection><SARS-CoV2 infection><STTR><Safety><Scientific Publication><Secure><Security><Sepsis><Severe acute respiratory syndrome coronavirus 2 infection><Sheep><Shock Lung><Skin><Small Business Technology Transfer Research><Stiff lung><Suidae><Sulfur Mustard><Swine><Symptoms><TNF><TNF A><TNF Alpha><TNF gene><TNF-α><TNFA><TNFα><Terrorism><Tetracyclines><Therapeutic><Theriacs><Toxic Chemical><Toxic Substance><Training><Tumor Necrosis Factor><Tumor Necrosis Factor-alpha><Type V Collagenase><United States Department of Health and Human Services><United States Dept. of Health and Human Services><Vesicants><Vesication><Vibramycin><Work><Yellow Cross Liquid><Yperite><aerosolized><alpha-6-Deoxyoxytetracycline><bio-markers><biologic><biologic marker><biologics><biomarker><biopharmaceutical><biotherapeutic agent><blood infection><bloodstream infection><burned><chemical attack><chemical warfare substances><chloromethine><chronic lung disease in infants><chronic lung disease in neonatal infants><chronic lung disease in neonates><chronic lung disease in newborns><chronic lung disease in prematurity><chronic lung disease in preterm infants><chronic lung disease of infancy><chronic lung disease of prematurity><commercial application><commercial scale manufacturing><commercialization><coronavirus disease 2019 infection><cytokine><drug candidate><drug development><drug production><drug/agent><effective therapy><effective treatment><emergency personnel><emergency responder><emergency service personnel><emergency service responder><expedited review><fibrosis in the lung><forging><glial-derived tumor><guinea pig model><heavy metal Pb><heavy metal lead><hemodynamics><improved><infant chronic lung disease><infants with chronic lung disease><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><inflammation marker><inflammatory marker><ingest><injuries><interferon beta 2><intraoral drug delivery><lewisite><lung edema><lung fibrosis><lung injury><manufacturing ramp-up><manufacturing scale-up><mechanical respiratory assist><mechanically ventilated><medical countermeasure><model of animal><neonatal chronic lung disease><neuroglia neoplasm><neuroglia tumor><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><newborn chronic lung disease><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><pathophysiology><pharmaceutical><porcine><post-prematurity respiratory disease><pre-IND consultation><pre-IND discussion><pre-IND meeting><pre-Investigational New Drug meeting><preterm infants with chronic lung disease><pulmonary damage><pulmonary injury><pulmonary tissue damage><pulmonary tissue injury><scale up batch><scale up production><small molecule><smoke inhalation><suid><systemic inflammation><systemic inflammatory response><terrorist attack><toxic compound><trial regimen><trial treatment><upscale manufacturing><voucher><wet lung>