Bioxytran, Inc. · OTC:BIXT
Bioxytran — Investor Presentation (August 2023)
75 slides from Bioxytran's investor presentation, August 2023
Slide 1: Science of Galectin Antagonists: Road to Ending the Pandemic
Science of Galectin Antagonists Road to Ending the Pandemic Copyright © Bioxytran 2022. All rights. MIKE SHEIKH | mike.sheikh@bioxytraninc.com | (509)-991-0245 Version 2.01.01 1
Slide 2: Forward Looking Statement
Forward Looking Statement This Descriptive Presentation (the "Presentation") has been prepared by Bioxytran, Inc (the "Company") and recipients are not entitled to rely on the accuracy or completeness of the Presentation. Statistical information contained in this Presentation is based on information
Slide 3: Road to Ending the Pandemic
Road to Ending the Pandemic Copyright © Bioxytran 2022. All rights. Version 2.01.01 3
Slide 4: Hypoxia Science Research Won the Nobel Prize in 2019
Hypoxia Science Research Won the Nobel Prize in 2019 BIOXYTRAN World Leaders in the Field of Hypoxia • Bioxytran has the only FDA approved device to measure tissue oxygenation • Its MDX Viewer quantify hypoxia (measuring the efficacy of treatments) • Bioxytran has a molecule (BXT-25) to deliver oxyg
Slide 5: Theory of the Cellular Universe
Theory of the Cellular Universe This is the E=mc2 for cells Delivering Oxygen to Tissues Reduces Hypoxia: Reduced Hypoxia Improves the Condition of Tissues Theory Predicts Cellular Interaction within the Tissue Micro-Environment https://www.nobelprize.org/prizes/medicine/2019/press-release/Nobel Pri
Slide 6: Defeating the Outbreak – A Simple Plan
Defeating the Outbreak – A Simple Plan Time a luxury we don’t have Use of Virus Drugs • Containing the disease takes time Only Viable Option to Treat Symptoms • Developing a vaccine take time • Learning how it transmitted takes time Distribution of drugs a real challenge in • Use of antiretrovirals
Slide 7: The Real Problem – Tissue Oxygenation & Real-time Monitoring
The Real Problem – Tissue Oxygenation & Real-time Monitoring • Late-Stage Coronavirus Patients develop fluid in their lungs. • Respirators force liquid levels of alveoli sacks lower so blood can get closer to O2 (Not very effective). • The blood is physically not close enough to the O2 to get oxygen
Slide 8: Solution: BXT-25 an Oxygen Bridge
Erythrocyte Hemoglobin Heme Solution: BXT-25 an Oxygen Bridge BXT-25 polymer • BXT-25 is a hemoglobin-based polymer; 5,000 times smaller than a red blood cell • It can be used both in Ischemic and Hemorrhagic Stroke • It can penetrate a blood-clot and reach the brain within 3 minutes • Reduction of
Slide 9: Continuous Real-time In-vivo Tissue Spectroscopy
9 Continuous Real-time In-vivo Tissue Spectroscopy Copyright © Bioxytran 2022. All rights. Version 2.01.01 9
Slide 10: FDA Approved Proprietary Companion Diagnostics
FDA Approved Proprietary Companion Diagnostics MDX Viewer - A clinical end-point for measuring oxygen delivery to the brain in real-time Tissue/brain monitored parameters Mitochondrial NADH Brain metabolic score (ATP) 90 Hb Saturation (O2) Cerebral Blood Flow Tissue Reflectance Tissue metabolic scor
Slide 11: Road to Ending the Pandemic
Road to Ending the Pandemic Copyright © Bioxytran 2022. All rights. Version 2.01.01 11 11
Slide 12: SARS Burnt Out – Therapies Never Commercialized
SARS Burnt Out – Therapies Never Commercialized Galectins implicated in the spread of the disease and potentially able to control the viral load of 2019-nCoV and influenza THE CULPRIT WAS FOUND IN 2015 – NO ACTION WAS TAKEN! During the SARS outbreak 8 years ago the Chinese discovered a nearly univer
Slide 13: Inspiration For Glycovirology
Inspiration For Glycovirology Adhesion Drug Entry Inhibitor • Common means of viral adhesion: surface lectins • Galectin Fold discovered on spike protein in a combining with carbohydrates conserved region • Carbohydrates can block surface lectins. • Interfere with spike protein activation • Galectin
Slide 14: Galectins Explained
Galectins Explained A Galectin is a protein that recognizes carbohydrates and modulates intra cellular and extracellular interactions primarily related to the immune system. In some cases, Galectins act as a glue bringing molecules such as surface receptors together. The major focus of research is o
Slide 15: Galectin Inhibition MOA
Galectin Inhibition MOA • Binding to the spike protein in Blood • Liver removes carbohydrates drug and virus • Restoration of Adaptive immune system – peel off galectin plaque • Adaptive immune system creates long term immunity Copyright © Bioxytran 2022. All rights. Version 2.01.01 15
Slide 16: Galectin-3 Ideal Target
Galectin-3 Ideal Target Coronavirus Receptor Recognition Pattern • Spikes use one or more S1 domains as receptor binding domains (RBD) • Galectin receptors appear to have no effect on viral entry In the viral evolutionary path it appears that the CoV stole a host galectin gene and inserted it at the
Slide 17: Universal Target – Galectin Fold
Universal Target – Galectin Fold Attaching to the Virus • S1 NTD Region across all Coronaviruses is the ideal Binding site for a Galectin-3 Inhibitor • Monoclonal Antibodies(Mab) cannot take advantage of this spot because the Mab’s are too large. • This includes INFLUENZA Copyright © Bioxytran 2022.
Slide 18: Neutralizing the Spike Protein
Neutralizing the Spike Protein How it Works Galectin Fold Ideal Binding Site No Sugar Shield Shielded in Sugar antibody • Binding to the spike protein prevents viral Conserved entry binding site Common to all • Immensely tighter bond to galectin fold variants vs tip (Prolactin-RX 99% binding affinit
Slide 19: Galectin Antagonist Tags Virus For Elimination
Galectin Antagonist Tags Virus For Elimination Theoretical Mechanism of Action Virus Galectin Antagonist Liver Filtration Human Cells Approach used for the 1st Time in History of Drug Development Bioxytran Copyright ©Copyright © Bioxytran 2022. All rights. 2022. All rights. Version 2.01.01 19
Slide 20: Galectins Linked to Chronic Disease
Galectins Linked to Chronic Disease 30 years of Over 4000 Journal Galectins are a key No approved Galectin research articles on Galectins biomarker of chronic inhibitor - YET disease Disease Indication Journals Areas of Focus Cancer 1500 Cervical, Breast, Endometrial, Pancreatic, Thyroid, CRC, Bioma
Slide 21: Galectin-3: One Molecule for an Alphabet of Diseases
Galectin-3: One Molecule for an Alphabet of Diseases, from A to Z Conditions and diseases in which a role for Gal-3 has been postulated Journal of Molecular Science Vol. 19, Iss. 2, February 2018 (Sciacchitano, Lavra, Morgante, Ulivieri, Magi, De Francesco, Bellotti, Salehi, Ricci) Copyright © Bioxy
Slide 22: Galectin Trouble-Maker
Galectin Trouble-Maker The Center of Inflammatory Feedback Loops • Gal-3 is a Pro-inflammatory Molecule • Inhibiting it blocks cycle of inflammation • Galectin is the KEY modulator of inflammatory molecules http://jpet.aspetjournals.org/content/351/2/336 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC
Slide 23: Galectin Linkage to COVID-19
Galectin Linkage to COVID-19 “People With Underlying Medical Conditions” aka tendency for high galectin serum levels • Cancer • Mental Health Conditions • Kidney Disease • Obesity • Liver Disease • Sickle Cell Anemia • Lung Disease (COPD, • Smoker Asthma, Cystic Fibrosis) • Organ Transplant • Dement
Slide 24: Underlying Conditions Increase Galectin Serum Markers
“Underlying Conditions” Increase Galectin Serum Markers Galectin-3 & Galectin-9 Serum Levels Rise with the Number of Underlying Conditions https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html Copyright © Bioxytran 2022. All rights. Version 2.01.01 24
Slide 25: Galectins Predict Mortality
Galectins Predict Mortality Highlights • Assess the utility of Galectin-3 for prognosis prediction This was one of many journal articles that served as a • Increased Galectin-3 serum levels are associated with rationale for a Galectin-3 Prognostic Test. higher risk of death, ICU, and Severe ARDS dev
Slide 26: Galectin Serum Test Data Summary
Galectin Serum Test Data Summary Results Galectin-3 correlated with many other prognostic predictors tested in our analysis. Moreover, patients with serum levels of Galectin-3 above 35.3 ng/ml had increased risk for mortality, Intensive Care Unit admission, and severe Acute Respiratory Distress Synd
Slide 27: ROC Curve – Galectin-3
ROC Curve – Galectin -3 High Gal-3 Serum predicting 30 Day Mortality • Receiver Operating Characteristic Analysis • n=39 • Gal-3 Serum >= 35.3 ng/ml • 80% sensitivity and 92.1% specificity for mortality prediction. • AUC = .906 (95% CI .85-.96, p,.0001) Copyright © Bioxytran 2022. All rights. Versio
Slide 28: ROC Curve – WHO Comparison
ROC Curve – WHO Comparison 5 predictive factors vs 20 factors Five Clinical Features • Age • Min O2 saturation • Type of Patient • Hydroxychloroquine use • Max Body Temp NYC – Mount Sinai Health Development Cohort N=3,841 Retrospective Analysis N=961 WHO Recommended Clinical Predictor of COVID-19 Mo
Slide 29: ROC Curve – Other Biomarkers
ROC Curve – Other Biomarkers IL-6 and CD8 counts Combined ROC curves derived from the model of combined elevated IL-6 (A) ROC curves of each category of T lymphocyte subgroup. (B) ROC and reduced CD8+ T cell counts and CURB-65 scores in our curves for each category of serum cytokines. AUC, area unde
Slide 30: Kaplan Meir Curve – COVID-19
Kaplan Meir Curve – COVID-19 Gal-3 Serum Levels 100% SURVIVAL Galectin-3 has shown good diagnostic power for Low to moderate levels of Gal-3 serum severe ARDS (AUC 0.75, p =0.001). In this case, were not good prognosticators of ARDS. using the fixed cut-off of 35.3 ng/ml, we found a sensitivity of 7
Slide 31: Kaplan Meir Curve – Chronic Heart Failure
Kaplan Meir Curve – Chronic Heart Failure Gal-3 Serum Levels Heart Failure Kaplan–Meier curves according to quartiles of baseline galectin-3 values. FDA Approved test shows patient stratification Heart Log-rank P = 0.048. Q1 galectin-3 values <13.63 ng/mL, Disease using Gal-3 serum levels a prognost
Slide 32: Mortality Risk – Galectin-3 Serum Levels
Mortality Risk – Galectin -3 Serum Levels Gal-3 Serum Levels COVID-19 Day 12 there is a 60% mortality with high Gal-3 Similar stratification in Heart Disease based levels upon admission. on serum levels. Copyright © Bioxytran 2022. All rights. Version 2.01.01 32
Slide 33: Galectin-9 Prognosticates Severe COVID-19
Galectin-9 Prognosticates Severe COVID-19 Patients with high levels of Galectin-9 serum are extremely likely to die https://pubmed.ncbi.nlm.nih.gov/33947753/ Copyright © Bioxytran 2022. All rights. Version 2.01.01 33
Slide 34: Galectin-3 Upregulated
Galectin-3 Upregulated Virally infected cells upregulate Gal-3 which is used in the budding process of virion. When cells burst after the nuclear material is used up it goes into the inflammatory environment. Effect of Elevated - Galectin-3 Galectin-3 plaque creates CD8+ T-Cell Anergy. Gal- 3 also p
Slide 35: Galectin Effect (T-Cell Anergy)
Galectin Effect (T-Cell Anergy) Galectins are responsible for T-Cell anergy and prevent the LFA-1 lectins (depicted in blue) from coalescing at the target cell and developing good adhesion in order to destroy it with cytotoxins. SAME MOA IN VIRUSES https://www.deduveinstitute.be/sites/default/files/
Slide 36: Functions of Galectin-3 in Viral Infections
Functions of Galectin-3 in Viral Infections Drivers of the Cytokine Storm • Innate Immune System – helping the trafficking of cells • Dampening of adaptive immune system (the CD8+ response) • Feeds the inflammatory cycle of fibrosis. Copyright © Bioxytran 2022. All rights. Version 2.01.01 36
Slide 37: Galectin Linkage to Cancer
Galectin Linkage to Cancer • Binding to the spike protein and acting as entry inhibitor • Open Label Clinical Trial demonstrated viral elimination in 2-5 days • Zero safety signals. Increased IgG levels on par with vaccinated • Theoretically Makes Keytruda 100% effective in NSCLC if excluded for hig
Slide 38: High Galectin Expression Leads to Bad Outcomes
High Galectin Expression Leads to Bad Outcomes What if Galectins Were Blocked? Galectins are the Smoking Gun of COVID-19 • Extremely accurate predictors of mortality • Galectin serum levels are more accurate than composite scores • Entire disease pathogenesis explained by their MOA • Responsible for
Slide 39: Road to Ending the Pandemic
Road to Ending the Pandemic Copyright © Bioxytran 2022. All rights. Version 2.01.01 39 39
Slide 40: Clinical Research – Phase 1
Clinical Research – Phase 1 https://www.longdom.org/abstract/galectin-antagonist-use-in-mild-cases-of-sarscov2-pilot-feasibility-randomised-open-label-controlled- trial-61087.html Copyright © Bioxytran 2022. All rights. Version 2.01.01 40
Slide 41: Patients Treated With Galectin Antagonist Experienced Reductions In Viral Load
Patients Treated With Galectin Antagonist Experienced Reductions In Viral Load Viral Load Vs. Time N1+N2 Copies/mL Day 1 3 5 7 Treated Patients PL-CIM-002 137080 6970 13180 16340 7.00 PL-CIM-004 4468590 101170 9660 510 PL-CIM-005 159730 15630 410 600 (Log10(average(N1+N2) Copies/mL)) PL-CIM-008 N/A
Slide 42: Viral Curve Comparison
Viral Curve Comparison Symptom Viral Load Vs. Time Onset Galectin Antagonist Vs. SARS-CoV-2 Historical Control • Historical control is taken from a mathematical Randomization model using longitudinal data across four different 6. studies of symptomatic, untreated cases1 (Log10(average(N1+N2) Copies/
Slide 43: Galectin Antagonist Treatment Results in Spike Protein Specific Antibody Immunity
Galectin Antagonist Treatment Results in SARS-CoV-2 Spike Protein Specific Antibody Immunity Introducing Post Infection Immunization Galectin antagonists clear the blood of viral load thereby reducing the strain on the Innate immune system so the Adaptive immune system can build a robust response to
Slide 44: PCR Test Data (Blinded Phase 2)
PCR Test Data (Blinded Phase 2) • Cycle Threshold (Ct) values are used to assess infectivity of the patient using a nasal pharyngeal test. Lower values are a proxy for higher viral loads and increased infectivity. Values over 29 are considered PCR negative. Starting Ct values of patients were under
Slide 45: PCR Test Phase 2 Data
PCR Test Phase 2 Data • Day 3 – 14 out of 17 were PCR negative (88%) ProLectin-M Ct Values • Day 7 – 17 out of 17 were PCR negative (100%) n = 34 Unblinded Data n=34 • No toxicity signals • Randomized 1:1 • Double Blind Placebo Controlled Trial Actual results show tight grouping btw treated arm and
Slide 46: ProLectin-M vs Pfizer's Paxlovid
ProLectin-M vs Pfizer’s Paxlovid • Day 3 – 14 out of 17 were PCR negative (88%) • Day 20 PCR negative (30%) • Day 7 – 17 out of 17 were PCR negative (100%) n = 34 • Toxicity (Drug to Drug Interactions) • No toxicity signals • Limited to Underlying Medical Conditions • Randomized 1:1 • Double Blind P
Slide 47: Elimination of Viral Rebound
Elimination of Viral Rebound Paxlovid rebound was common after day 10 There were no rebounds within 14 days. 1Galectin approach to lower covid transmission - Drug Development for clinical use (medRxiv.org) Copyright © Bioxytran 2022. All rights. Version 2.01.01 47
Slide 48: Clinical Trial Results Summary
Clinical Trial Results Summary Elimination of the viral load and symptoms within 5 days Reduction of infectivity Quieting the cytokine storm Robust antibody response (Post Infection Immunization Copyright © Bioxytran 2021. 2022. All rights. Version 2.01.01 48
Slide 49: Road to Ending the Pandemic
Road to Ending the Pandemic Copyright © Bioxytran 2022. All rights. Version 2.01.01 49
Slide 50: Complex Carbohydrate Design Using Advanced NMR Spectroscopy Techniques
Complex Carbohydrate Design Using Advanced NMR Spectroscopy Techniques 1 Galectin approach to lower covid transmission - Drug Development for clinical use Copyright © Bioxytran 2022. All rights. Version 2.01.01 50
Slide 51: Road to Ending the Pandemic
Road to Ending the Pandemic Copyright © Bioxytran 2022. All rights. Version 2.01.01 51
Slide 52: Proposed Clinical Trial Design
Proposed Clinical Trial Design Clinical Trial • 408 participants • Double Blind Randomized Controlled Trial (DBRCT) • Change in seropositivity at day 14 • Broad inclusion criteria (Vaccination status irrelevant) Copyright © Bioxytran 2022. All rights. Version 2.01.01 52
Slide 53: Road to Ending the Pandemic
Road to Ending the Pandemic Copyright © Bioxytran 2022. All rights. Version 2.01.01 53
Slide 54: What is Long-COVID?
What is “Long-COVID”? Terminology Long COVID, Long Haulers, Long-term COVID, Post-COVID conditions (PCC), Post-acute sequelae of SARS-CoV-2 infection (PASC), Post COVID-19 Syndrome (PCS) An Insidious COVID that Lingers • Lack of return to the usual state of health • Not explained by an alternative d
Slide 55: 1 in 5 with COVID have Long COVID
55 Long Covid: Disabling America • 651-1002 million estimated cases worldwide • Lost work days: 1.6 million full-time equivalent workers • $3.7 trillion3 estimated economic burden • 7.5%4 of people report having long-COVID 1 in 5 with • Quality of life decreases5 COVID have • CDC estimates that 6% o
Slide 56: Long Covid
Long Covid Heart Chest Tightness Head symptoms Chest Pain Palpitations Tinnitus Earache Sore throat The Most commonly reported symptoms Lungs Sinus pain Dizziness of ongoing symptomatic COVID-19 and Breathlessness Loss of taste and/or smell Symptoms of depression post-COVID-19 Syndrome Include (but
Slide 57: Mapping ACE2 (72 Tissues)
Mapping ACE21 (72 Tissues) ACE2 Facilitates Viral Spread to Organs Residual infection in affected tissues lead to Long-COVID symptoms 1https://www.frontiersin.org/articles/10.3389/fmed.2020.594495/full Copyright © Bioxytran 2022. All rights. Version 2.01.01 57
Slide 58: Heterogeneous Disease = Clinical Trial Challenge
Heterogeneous Disease = Clinical Trial Challenge Testing Long COVID & Determining Endpoints • No validated tests/diagnostics • No industry guidance on endpoints Short Long-Haulers: 9 months Long Long-Haulers: Over 9 months Copyright © Bioxytran 2022. All rights. Version 2.01.01 58
Slide 59: Long-COVID Theories
Long-COVID Theories Viral Persistence Organ Damage Microclots Autoimmune response Dysbiosis Copyright © Bioxytran 2022. All rights. Version 2.01.01 59
Slide 60: Viral Persistence/Pathogen Remnants
60 Viral Persistence/Pathogen Remnants • Evidence that there’s active virus in tissues up to 9 months after infection1. • Paxlovid treatment lowers incidence of long-COVID2. (9.43 lowered to 7.11 per 100) • Ongoing viral replication/viral reservoirs might drive Long-COVID. • Persistence of viral rem
Slide 61: Tissue Damage and Microclots
61 Tissue Damage and Microclots • Galectin-3 is a DAMP and promotes coagulation • Galectins promote fibrosis/scarring and are being studied as antifibrotics • ProLectin-I blocks various galectins including 1 and 3 1https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4357586/ 2https://www.sciencedirect.com/
Slide 62: Microclots
62 Microclots A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications1 • Microclots formed by aberrant amyloid fibrin triggered by the spike protein. • Microclots present novel antigens that lead to production of autoantibodies, exacerbating symptoms. Fl
Slide 63: Autoimmunity
63 Autoimmunity • Inflammation or autoimmunity might drive Long-COVID symptoms • Galectins are drivers of inflammation and are implicated in autoimmunity • Prolectin-I may have a beneficial effect in reducing autoimmune reactivity • Iwasaki says galectin-1 is elevated in long-COVID2 https://www.medr
Slide 64: Dybiosis/Reactivation
Dybiosis/Reactivation • Disruption of flora and subsequent reactivation of latent viruses (EBV) may cause long-COVID symptoms • ProLectin has not been tested against EBV yet, but has demonstrated broad-spectrum activity with other viruses Copyright © Bioxytran 2022. All rights. Version 2.01.01 64
Slide 65: Road to Ending the Pandemic
Road to Ending the Pandemic Copyright © Bioxytran 2022. All rights. Version 2.01.01 65
Slide 66: Glycovirology – Broad Spectrum Antiviral Activity
Glycovirology – Broad Spectrum Antiviral Activity Galectin-1,3, and 9 are modulators of viral infection Gal-1 has been reported to participate in the regulation of influenza A virus infection. An in vitro study showed that Gal-1 expression inhibited the Influenza A (H1N1) virus infection on BEAS-2B
Slide 67: Road to Ending the Pandemic
Road to Ending the Pandemic Copyright © Bioxytran 2022. All rights. Version 2.01.01 67
Slide 68: Glycovirology Pipeline
Glycovirology Pipeline Drug & Process Development Cleared Completed Planned IND Product Indication Preclinical Phase I Phase II Phase III Phase IV Submission Virology – Mild to Moderate ProLectin-M Oral • Covid-19 Virology – Severe cases ProLectin-I • Covid-19 Intravenous • Long Covid Fibrosis: ProL
Slide 69: What is the Impact of Shortening the Contagious Period of COVID-19?
What is the Impact of Shortening the Contagious Period of COVID-19? Copyright © Bioxytran 2022. All rights. https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1008470 Version 2.01.01 69
Slide 70: Product Benefits
Product Benefits Eliminates virus and Promotes stops the spread immunity Easy to transport No adverse and administer effects Conserved binding Universally region resistant to compatible with mutations other therapies Copyright © Bioxytran 2022. All rights. Version 2.01.01 70
Slide 71: BioXyTran, Inc. Contact
BioXyTran, Inc. 233 Needham St., Suite 300 Newton MA, 02464 (617)-454-1199 www.bioxytraninc.com info@bioxytraninc.com Mike Sheikh mike.sheikh@bioxytraninc.com (509)-991-0245 71 Copyright © Bioxytran 2022. All rights. Version 2.01.01 71
Slide 72: Appendix
Appendix MDX Monitoring for Acute Respiratory Distress Syndrome (ARDS) Therapeutic Approaches for COVID 19 Science Behind Galectin Antagonists Copyright © Bioxytran 2022. All rights. Version 2.01.01 72
Slide 73: MDX Monitoring for Acute Respiratory Distress Syndrome (ARDS)
MDX Monitoring for Acute Respiratory Distress Syndrome (ARDS) Systemic vital parameters (probe 3) Power Electronics Supply Light Source Unit & Embedded Photoplethysmography Computer analysis Detection Unit System Systemic vital parameters (probe 2) Panel Computer Parameters: Core Temperature Copyrig
Slide 74: Therapeutic Approaches for COVID-19
Therapeutic Approaches for COVID-19 Immunomodulatory Antiretrovirals (Compete for polymorphism) Vaccines ProLectin-Rx • Unique Galectin Antagonist – Oral/IV Polysaccharide • It’s not a vaccine, nor an antiretroviral drug Oxygenation (Ventilators) Regenerative Medicine (Stemcells) Copyright © Bioxytr
Slide 75: Science Behind Galectin Antagonists
Science Behind Galectin Antagonists Clinical Research 4000+ Journal Articles on Target Proven Safety Profile in Drug Class Receptors Peer-reviewed clinical trial in COVID-19 Galectin Inhibitors in phase 2 & 3 trials for IPF, NASH, Cancer, Atopic Dermatitis, Psoriasis, Covid-19 30+ years of research