Common use of LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS Clause in Contracts

LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS. ‌‌ The following abbreviations and specialist terms are used in this study protocol. 6MWD 6-minute walk distance 6MWT 6-minute walk test AE Adverse event ACA Anti-centromere ALP Alkaline phosphatase ALT Alanine aminotransferase XXX Anti-nuclear Anti-RNAP Anti-RNA polymerase enzyme Anti-U1RNP Anti-U1 nuclear ribosome Anti-U3RNP Anti-U3 nuclear ribosome Anti-Th/To Anti-ribonucleoprotein Anti-Ds-DNA Anti-double stranded DNA AST Aspartate aminotransferase ATP Adenosine triphosphate ATS American Thoracic Society AUC Area under the concentration-time curve BMI Body mass index BNP B-type natriuretic peptide BP Blood Pressure BUN Blood urea nitrogen CFR Code of Federal Regulations (US) CK Creatine kinase CKD Chronic kidney disease Cmax Maximum drug concentration in plasma CT Computed tomography CTD Connective tissue disease CTD-PAH Connective tissue disease-associated pulmonary arterial hypertension CTEPH Chronic thromboembolic pulmonary hypertension DSMB Data safety monitoring board EC Ethics Committee eCRF Electronic case report form ECG Electrocardiogram ECHO Echocardiogram EDC Electronic data capture eGFR Estimated glomerular filtration rate ERA Endothelin receptor antagonist FADH2 Xxxxxx adenine dinucleotide FDA Food and Drug Administration (US) FEV1 Forced expiratory volume FVC Forced vital capacity GCP Good Clinical Practice GGT Gamma-glutamyl transpeptidase HCV Hepatitis C virus HDPE High-density polyethylene Hgb Hemoglobin ICH International Conference on Harmonization IKKβ Inhibitor of nuclear factor kappa β kinase beta subunit INR International normalized ratio IRB Institutional Review Board IWRS Interactive Web Response System ITT Intent-to-treat Keap1 Xxxxx-like ECH associated protein-1 LDH Lactate dehydrogenase MAR Missing at random MCH Mean corpuscular hemoglobin MCHC Mean corpuscular hemoglobin concentration MCV Mean corpuscular volume MMRM Mixed model repeated measures MRI Magnetic resonance imaging NADH Nicotinamide adenine dinucleotide NF-κB Nuclear factor kappa-light-chain-enhancer of activated B-cells Nrf2 Nuclear factor (erythroid-derived 2)-related factor 2 NT-Pro BNP N-Terminal Pro-Brain Natriuretic Peptide NYHA FC New York Heart Association Functional Classification PAH Pulmonary arterial hypertension PCWP Pulmonary capillary wedge pressure PEF Peak expiratory flow PFT Pulmonary function test PH Pulmonary hypertension PK Pharmacokinetic RBC Red blood cell RHC Right heart catheterization ROS Reactive oxygen species SAE Serious adverse event SAP Statistical analysis plan SLE Systemic lupus erythematosus SRC Sample size re-calculation committee TBL Total bilirubin TLC Total lung capacity Tmax Time when maximum drug concentration in plasma is achieved TV Tidal volume ULN Upper limit of normal US United States V/Q Ventilation-perfusion WBC White blood cell WHO World Health Organization WOCBP Women of child bearing potential

LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS. ‌‌ The following abbreviations and specialist special terms are used in this study protocol. 6MWD 6-minute walk distance 6MWT 6-minute walk test ACE Angiotensin converting enzyme ACR Albumin to creatinine ratio AE Adverse event ACA Anti-centromere ALP Alkaline phosphatase ALT Alanine aminotransferase XXX Anti-nuclear Anti-RNAP Anti-RNA polymerase enzyme Anti-U1RNP Anti-U1 nuclear ribosome Anti-U3RNP Anti-U3 nuclear ribosome Anti-Th/To Anti-ribonucleoprotein Anti-Ds-DNA Anti-double stranded DNA ARB Angiotensin II receptor blocker AST Aspartate aminotransferase ATP Adenosine triphosphate ATS American Thoracic Society AUC Area under the concentration-time curve BMI Body mass index BNP B-type natriuretic peptide BP Blood Pressure BUN Blood urea nitrogen CFR Code of Federal Regulations (US) CGI-I Clinical Global Impression - Improvement CK Creatine kinase CKD Chronic kidney disease Cmax Maximum drug concentration in plasma CT Computed tomography CTD Connective tissue disease CTDCKD-PAH Connective tissue disease-associated pulmonary arterial hypertension CTEPH EPI Chronic thromboembolic pulmonary hypertension DSMB Kidney Disease Epidemiology Collaboration CrCl Creatinine clearance CRO Clinical research organization CV Cardiovascular DMC Data safety monitoring board Monitoring Committee EC Ethics Committee eCRF Electronic case report form ECG Electrocardiogram ECHO Echocardiogram EDC Electronic data capture eGFR Estimated glomerular filtration rate ERA Endothelin receptor antagonist FADH2 Xxxxxx adenine dinucleotide ESRD End stage renal disease FDA Food and Drug Administration (US) FEV1 Forced expiratory volume FVC Forced vital capacity GCP Good Clinical Practice GFR Glomerular filtration rate GGT Gamma-glutamyl transpeptidase HbA1c Hemoglobin A1c hCG-Qual Human chorionic gonadotropin-qualitative HCV Hepatitis C virus HDPE High-density polyethylene Hgb Hemoglobin ICH International Conference on Harmonization IGF-1 Insulin-like growth factor-1 IKKβ Inhibitor of nuclear factor kappa β kinase beta subunit INR International normalized ratio IRB Institutional Review Board IWRS Interactive Web Response System ITT Intent-to-treat J2R Jump to reference KDIGO Kidney Disease: Improving Global Outcomes Keap1 Xxxxx-like ECH associated protein-1 Kf Ultrafiltration coefficient LDH Lactate dehydrogenase MAR Missing at random MCH Mean corpuscular hemoglobin MCHC Mean corpuscular hemoglobin concentration MCV Mean corpuscular volume MMRM Mixed model repeated measures MRI Magnetic resonance imaging NADH Nicotinamide adenine dinucleotide MTLDD Maximally tolerated labeled daily dose NF-κB Nuclear factor kappa-light-chain-enhancer of activated B-cells Nrf2 Nuclear factor (erythroid-derived 2)-related factor 2 NT-Pro BNP N-Terminal Pro-Brain Natriuretic Peptide NYHA FC New York Heart Association Functional Classification PAH Pulmonary arterial hypertension PCWP Pulmonary capillary wedge pressure PEF Peak expiratory flow PFT Pulmonary function test PBO Placebo PGIC Patient Global Impression of Change PH Pulmonary hypertension PK Pharmacokinetic QTc Corrected QT interval RBC Red blood cell RHC Right heart catheterization ROS Reactive oxygen species RNA Ribonucleic acid SAE Serious adverse event SAP Statistical analysis plan SLE Systemic lupus erythematosus SRC Sample size re-calculation committee T2D Type 2 diabetes TBL Total bilirubin TLC Total lung capacity Tmax Time when maximum drug concentration in plasma is achieved TV Tidal volume ULN Upper limit of normal US United States V/Q Ventilation-perfusion WBC White blood cell WHO World Health Organization WOCBP Women of child bearing potential

LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS. ‌‌ The following abbreviations and specialist terms are used in this study protocol. 6MWD 6-minute walk distance 6MWT 6-minute walk test AE Adverse adverse event ACA Anti-centromere ALP Alkaline phosphatase ALT Alanine aminotransferase XXX Anti-nuclear Anti-RNAP Anti-RNA polymerase enzyme Anti-U1RNP Anti-U1 nuclear ribosome Anti-U3RNP Anti-U3 nuclear ribosome Anti-Th/To Anti-ribonucleoprotein Anti-Ds-DNA Anti-double stranded DNA AST Aspartate aminotransferase ATP Adenosine triphosphate ATS American Thoracic Society AUC Area under the concentration-time curve BMI Body body mass index BNP BCGI-type natriuretic peptide BP Blood Pressure BUN Blood urea nitrogen CFR Code I Clinical Global Impression – Improvement CGI-S Clinical Global Impression – Severity Cmax maximum plasma concentration CS clinically significant C-SSRS Columbia-Suicide Severity Rating Scale CYP cytochrome P450 DSM-5 Diagnostic and Statistical Manual of Federal Regulations (US) CK Creatine kinase CKD Chronic kidney disease Cmax Maximum drug concentration in plasma CT Computed tomography CTD Connective tissue disease CTD-PAH Connective tissue disease-associated pulmonary arterial hypertension CTEPH Chronic thromboembolic pulmonary hypertension DSMB Data safety monitoring board EC Ethics Committee Mental Disorders ECG electrocardiogram eCRF Electronic electronic case report form ECG Electrocardiogram ECHO Echocardiogram EDC Electronic data capture eGFR Estimated glomerular filtration rate ERA Endothelin receptor antagonist FADH2 Xxxxxx adenine dinucleotide FDA Food and Drug Administration (US) FEV1 Forced expiratory volume FVC Forced vital capacity GABA γ-aminobutyric- acid GABAA γ-aminobutyric- acid-ligand gated chloride channel GCP Good Clinical Practice GGT GammaGEE generalized estimating equation HAM-glutamyl transpeptidase A Xxxxxxxx Anxiety Rating Scale XXX-X Xxxxxxxx Rating Scale for Depression HBsAg hepatitis B surface antigen HCV Hepatitis hepatitis C virus HDPE High-density polyethylene Hgb Hemoglobin HIV human immunodeficiency virus ICF informed consent form ICH International Conference Council on Harmonization IKKβ Inhibitor Harmonisation of nuclear factor kappa β kinase beta subunit INR International normalized ratio Technical Requirements for Pharmaceuticals for Human Use IEC Independent Ethics Committee IND Investigational New Drug IRB Institutional Review Board IWRS Interactive Web Response System ITT IntentLS least squares MADRS Xxxxxxxxxx-to-treat Keap1 Xxxxx-like ECH associated protein-1 LDH Lactate dehydrogenase MAR Missing at random MCH Mean corpuscular hemoglobin MCHC Mean corpuscular hemoglobin concentration MCV Mean corpuscular volume Xxxxxx Depression Rating Scale MedDRA Medical Dictionary for Regulatory Activities MMRM Mixed mixed effects model for repeated measures MRI Magnetic resonance imaging NADH Nicotinamide adenine dinucleotide NFMTD maximum tolerated dose NCS not clinically significant NF National Formulary PPD postpartum depression QD once daily QTcF QT interval calculated using the Fridericia method SAD single ascending dose SCID-κB Nuclear factor kappaI Structured Clinical Interview for DSM-5 Axis I Disorders SD standard deviation SOC System Organ Class SSRIs serotonin reuptake inhibitors XXXXX suspected, unexpected, serious, adverse reaction TEAE treatment-light-chain-enhancer of activated B-cells Nrf2 Nuclear factor (erythroid-derived 2)-related factor 2 NT-Pro BNP N-Terminal Pro-Brain Natriuretic Peptide NYHA FC New York Heart Association Functional Classification PAH Pulmonary arterial hypertension PCWP Pulmonary capillary wedge pressure PEF Peak expiratory flow PFT Pulmonary function test PH Pulmonary hypertension PK Pharmacokinetic RBC Red blood cell RHC Right heart catheterization ROS Reactive oxygen species SAE Serious emergent adverse event SAP Statistical analysis plan SLE Systemic lupus erythematosus SRC Sample size retmax time at maximum (peak) plasma concentration WHO-calculation committee TBL Total bilirubin TLC Total lung capacity Tmax Time when maximum drug concentration in plasma is achieved TV Tidal volume ULN Upper limit of normal US United States V/Q Ventilation-perfusion WBC White blood cell WHO DD World Health Organization WOCBP Women of child bearing potentialOrganization-Drug dictionary

LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS. ‌‌ The following abbreviations and specialist terms are used in this study protocol. 6MWD 6-minute walk distance 6MWT 6-minute walk test AE Adverse event ACA Anti-centromere ALP Alkaline phosphatase Event ALT Alanine aminotransferase XXX AntiAminotransferase ANCOVA Analysis of covariance AR α2-nuclear Anti-RNAP Anti-RNA polymerase enzyme Anti-U1RNP Anti-U1 nuclear ribosome Anti-U3RNP Anti-U3 nuclear ribosome Anti-Th/To Anti-ribonucleoprotein Anti-Ds-DNA Anti-double stranded DNA adrenoreceptors AST Aspartate aminotransferase ATP Adenosine triphosphate ATS American Thoracic Society AUC Area under the concentrationAminotransferase BDI-time curve II Xxxx Depression Inventory–II BMI Body mass index BNP B-type natriuretic peptide BP Blood Pressure Mass Index BOCF Baseline observation carried forward BUN Blood urea nitrogen CAPS-5 Clinician Administered PTSD Scale (for DSM-5) CA-AF Criterion A – Assessment Form CBP Cyclobenzaprine CSFQ-14 Changes in Sexual Functioning Questionnaire Short Form CFR Code of Federal Regulations CGI-I Clinical Global Impression- Improvement from Initiation of Treatment CI Confidence Interval CMH Xxxxxxx–Mantel–Haenszel CNS Central Nervous System CoC Certificates of Confidentiality CPAP Continuous Positive Airway Pressure CRF Case Report Form CRO Contract Research Organization C-SSRS Columbia Suicide Severity Rating Scale CYP3A4 Cytochrome P450 subtype 3A4 DSM-5 Diagnostic and Statistical Manual of Mental Disorders (USVersion 5) CK Creatine kinase CKD Chronic kidney disease Cmax Maximum drug concentration in plasma CT Computed tomography CTD Connective tissue disease CTD-PAH Connective tissue disease-associated pulmonary arterial hypertension CTEPH Chronic thromboembolic pulmonary hypertension DSMB Data safety monitoring board e.g. Exempli gratia (for example) EC Ethics Committee eCRF Electronic case report form ECG Electrocardiogram ECHO Echocardiogram EDC Electronic data capture eGFR Estimated glomerular filtration rate ERA Endothelin receptor antagonist FADH2 Xxxxxx adenine dinucleotide ET Early Termination FDA Food and Drug Administration (US) FEV1 Forced expiratory volume FVC Forced vital capacity GCP Good Clinical Practice GGT Gamma-glutamyl transpeptidase HCV Hepatitis C GLP Good Laboratory Practice HCl Hydrochloride HEENT Head, Eyes, Ears, Nose and Throat HIPAA Health Insurance Portability and Accountability Act HIV1 Human immunodeficiency virus HDPE High-density polyethylene Hgb Hemoglobin type 1 HIV2 Human immunodeficiency virus type 2 i.e. id est (that is) ICF Informed Consent Form ICH International Conference on Harmonization IKKβ Inhibitor of nuclear factor kappa β kinase beta subunit INR International normalized ratio IDMC Independent Data Monitoring Committee IND Investigational New Drug IRB Institutional Review Board IWRS IR Immediate-release ISAP Interim Statistical Analysis Plan IUD Intrauterine device IWR Interactive Web Response System ITT Intent-to-treat Keap1 Xxxxx-like ECH associated protein-1 LDH Lactate dehydrogenase MAR Missing at random LEC-5 Life Events Checklist for DSM-5 LOCF Last observation carried forward M.I.N.I. Mini International Neuropsychiatric Interview MCH Mean corpuscular hemoglobin MCHC Mean corpuscular hemoglobin concentration mCPP meta-chlorophenylpiperazine MCV Mean corpuscular volume MDD Major Depressive Disorder MDE Major Depressive Episode MedDRA Medical Dictionary for Regulatory Activities Mg Milligram(s) MI Multiple imputation mITT Modified Intent-to-Treat MMRM Mixed model repeated measures MRI Magnetic resonance imaging NADH Nicotinamide adenine dinucleotide NFModel Repeated Measures msec Millisecond(s) MTRSS Morning Treatment-κB Nuclear factor kappaRelated Sedation Scale N, n Number (of patients) NA Not applicable NDA New Drug Application NREM Non-lightrapid eye movement OEF Operation Enduring Freedom OIF Operation Iraqi Freedom OND Operation New Xxxx PCL PTSD Checklist PGIC Patient Global Impression of Change (Since Baseline) Scale PI Principal Investigator PO per os (by mouth) PRN pro re nata (as needed) PROMIS Patient-chainReported Outcome Measurement Information System PTSD Post-enhancer of activated B-cells Nrf2 Nuclear factor (erythroid-derived 2)-related factor 2 NT-Pro BNP N-Terminal Pro-Brain Natriuretic Peptide NYHA FC New York Heart Association Functional Classification PAH Pulmonary arterial hypertension PCWP Pulmonary capillary wedge pressure PEF Peak expiratory flow PFT Pulmonary function test PH Pulmonary hypertension PK Pharmacokinetic Traumatic Stress Disorder QTcF QT corrected for heart rate using Xxxxxxxxxx’s formula RBC Red blood cell RHC Right heart catheterization ROS Reactive oxygen species REM Rapid eye movement SAE Serious adverse event Adverse Event SAP Statistical analysis plan SLE Systemic lupus erythematosus SRC Sample size re-calculation committee TBL Total bilirubin TLC Total lung capacity Tmax Time when maximum drug concentration in plasma is achieved TV Tidal volume ULN Upper limit of normal Analysis Plan SD Standard deviation SDS Xxxxxxx Disability Scale SL Sublingual SOP Standard Operating Procedures SPI Safety Planning Intervention SWS Slow wave sleep TBI Traumatic brain injury TEAE Treatment Emergent Adverse Event TNX-102 SL Cyclobenzaprine HCl sublingual tablets TSH Thyroid Stimulating Hormone US United States V/Q Ventilation-perfusion VA Veteran’s Administration WBC White blood cell count WHO World Health Organization WOCBP Women of child bearing potentialOrganization

LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS. ‌‌ The following abbreviations and specialist terms are used in this study protocol. 6MWD 6-minute walk distance 6MWT 6-minute walk test ADR adverse drug reaction AE Adverse adverse event ACA Anti-centromere ALP Alkaline phosphatase ALT Alanine aminotransferase XXX Anti-nuclear Anti-RNAP Anti-RNA polymerase enzyme Anti-U1RNP Anti-U1 nuclear ribosome Anti-U3RNP Anti-U3 nuclear ribosome Anti-Th/To Anti-ribonucleoprotein Anti-Ds-DNA Anti-double stranded DNA AST Aspartate aminotransferase ATP Adenosine triphosphate ATS American Thoracic Society AUC Area area under the concentration-time curve BMI Body body mass index BNP BCBD Cannabidiol CGI-type natriuretic peptide BP Blood Pressure BUN Blood urea nitrogen CFR Code I Clinical Global Impressions – Improvement CGI-S Clinical Global Impressions – Severity Cmax maximum observed concentration CS clinically significant CSR clinical study report CYP cytochrome P450 DSM-5 Diagnostic and Statistical Manual of Federal Regulations (US) CK Creatine kinase CKD Chronic kidney disease Cmax Maximum drug concentration in plasma CT Computed tomography CTD Connective tissue disease CTD-PAH Connective tissue disease-associated pulmonary arterial hypertension CTEPH Chronic thromboembolic pulmonary hypertension DSMB Data safety monitoring board EC Ethics Committee Mental Disorders, Fifth Edition IEC independent ethics committee IRT interactive response technology eCRF Electronic electronic case report form ECG Electrocardiogram ECHO Echocardiogram EDC Electronic data capture eGFR Estimated glomerular filtration rate ERA Endothelin receptor antagonist FADH2 Xxxxxx adenine dinucleotide EPDS Edinburgh Postnatal Depression Scale ET early termination FDA Food and Drug Administration (US) FEV1 Forced expiratory volume FVC Forced vital capacity GABA γ-aminobutyric acid GCP Good Clinical Practice GGT GammaGMP Good Manufacturing Practice GEE generalized estimating equation HAM-glutamyl transpeptidase HCV Hepatitis C virus HDPE HighA Xxxxxxxx Rating Scale for Anxiety XXX-density polyethylene Hgb Hemoglobin X Xxxxxxxx Rating Scale for Depression IB Investigator’s Brochure ICF informed consent form ICH International Conference on Harmonization IKKβ Inhibitor Council for Harmonisation of nuclear factor kappa β kinase beta subunit INR International normalized ratio Technical Requirements for Pharmaceuticals for Human Use IP investigational product IRB Institutional Review Board IWRS Interactive Web Response System ITT Intentinstitutional review board LDH lactate dehydrogenase LS least squares XXXXX Xxxxxxxxxx Åsberg Depression Rating Scale MDD major depressive disorder MedDRA Medical Dictionary for Regulatory Activities MMRM mixed-to-treat Keap1 Xxxxx-like ECH associated protein-1 LDH Lactate dehydrogenase MAR Missing at random MCH Mean corpuscular hemoglobin MCHC Mean corpuscular hemoglobin concentration MCV Mean corpuscular volume MMRM Mixed effects model for repeated measures MRI Magnetic resonance imaging NADH Nicotinamide adenine dinucleotide NFMTD maximum tolerated dose NCS not clinically significant NOAEL no-κB Nuclear factor kappaobserved-lightadverse-chaineffect level OS oral solution PCS potentially clinically significant PHQ-9 9-enhancer of activated B-cells Nrf2 Nuclear factor (erythroid-derived 2)-related factor 2 NT-Pro BNP N-Terminal Pro-Brain Natriuretic Peptide NYHA FC New York Heart Association Functional Classification PAH Pulmonary arterial hypertension PCWP Pulmonary capillary wedge pressure PEF Peak expiratory flow PFT Pulmonary function test PH Pulmonary hypertension PK Pharmacokinetic RBC Red blood cell RHC Right heart catheterization ROS Reactive oxygen species item Patient Health Questionnaire PPD postpartum depression PV Pharmacovigilance SAE Serious serious adverse event SAP Statistical statistical analysis plan SLE Systemic lupus erythematosus SRC Sample size reSCID-5-calculation committee TBL Total bilirubin TLC Total lung capacity Tmax Time when maximum drug concentration in plasma is achieved TV Tidal volume ULN Upper limit of normal US United States V/Q VentilationCT Structured Clinical Interview for Diagnostic and DSM-5 Clinical Trial Version SD standard deviation SSRI selective serotonin reuptake inhibitors SUSAR suspected unexpected serious adverse reaction TEAE treatment-perfusion WBC White blood cell emergent adverse event TSH thyroid stimulating hormone WHO World Health Organization WOCBP Women of child bearing potentialOrganization