Bioxytran, Inc. · OTC:BIXT
Bioxytran — Investor Presentation (March 2020)
51 slides from Bioxytran's investor presentation, Mar 30, 2020
Slide 1: Presentation Trials for BXT-10 against COVID-19
DAVID PLATT david.platt@bioxytraninc.com (617) - 510 - 2539 Presentation Trials for BIXT - 10 against COVID - 19
Slide 2: Forward Looking Statement
FORWARD LOOKING STATEMENT This report contains forward - looking statements concerning possible applications for marketing approval and other regulatory matters, clinical trials, additional information, business strategies, and plans for the development of BioXyTran™. These forward - looking stateme
Slide 3: Mission Statement
3 2 MISSION STATEMENT BioxyTran™’s mission is to develop effective drug treatments that deliver oxygen to biological tissues with potential to improve a myriad of medical conditions including hypoxia (oxygen deficiency).
Slide 4: The case for BXT-10 as a possible galectin inhibitor for SARS-CoV-2
4 3 the case for BXT - 10 (by B ioxytran™) as a possible galectin inhibitor for sars - covid - 2 and therapeutic for covid - 19
Slide 5: Translating Medicine into Therapeutics
Translating Medicine into Therapeutics Researching hypoxia & galectins for 30 years • 30 Patents • 10 Journal Articles • 2 Textbooks • 5 Public Companies • 200 Animal Experiments • 30 Clinical Trials Major Scientific Validation Embraced by Scientific & Medical Minds COMMERCIALIZATION 5 4 David Platt
Slide 6: Pivotal Article First Galectin Inhibitor Structure Analysis
Pivotal Article First Galectin Inhibitor Structure Analysis (1993) Describes how sugar polysaccharides recognize the Galectin Receptor 6 5
Slide 7: Galectins - Explained
Galectins - Explained https://www.pharma - iq.com/pre - clinical - discovery - and - development/articles/why - galectin - 3 - has - emerged - as - a - focus - for - drug - researc h - and - development - 1 A galectin is a protein that recognizes carbohydrates and modulates intracellular and extrace
Slide 8: Explosion in Galectin Research
Explosion in Galectin Research https://www.pharma - iq.com/pre - clinical - discovery - and - development/articles/why - galectin - 3 - has - emerged - as - a - focus - for - drug - researc h - and - development - 1 Dr. Platt - CEO • Research on galectin since 1989 • Name originator of the lectin •
Slide 9: Explosion in Galectin Research
Explosion in Galectin Research https://www.pharma - iq.com/pre - clinical - discovery - and - development/articles/why - galectin - 3 - has - emerged - as - a - focus - for - drug - researc h - and - development - 1 • 2700 papers since 2008 • 60% of all papers on Cancer 9 8 28% Heart Disease 2018 29
Slide 10: Explosion in Galectin Research
Explosion in Galectin Research https://www.pharma - iq.com/pre - clinical - discovery - and - development/articles/why - galectin - 3 - has - emerged - as - a - focus - for - drug - researc h - and - development - 1 Disease Indication Journal s Areas of Focus Cancer 1500 Cervical, Breast, Endometria
Slide 11: Galectins implicated in many chronic diseases
Galectins https://www.frontiersin.org/articles/10.3389/fimmu.2018.03057/full https://www.cell.com/cell/pdf/S0092 - 8674(16)31445 - 3.pdf “Galectins have emerged as amplifiers or silencers of inflammatory responses, capable of orchestrating complex regulatory circuits in innate and adaptive immune ce
Slide 12: Galectin-3 Central to Many Diseases
Galectin - 3 (Gal - 3) • Gal - 3 is a Pro - inflammatory Molecule Inhibiting it blocks cycle of inflammation • Galectin is the KEY modulator of inflammatory molecules Fibrosis http://jpet.aspetjournals.org/content/351/2/336 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752178/ There is little downsi
Slide 13: Galectin-3 a prognosticator in cancer
a prognosticator in cancer ▪ Cancer patients with high Galectin - 3 had a very poor prognosis . ▪ Major validation as a viable target in one of the most widely used drugs (Keytruda). Source: Capalbo C. et al. Predictive Biomarkers for Checkpoint Inhibitor - Based Immunotherapy: The Galectin - 3 Sign
Slide 14: Blockers are validated in clinical trials
Blockers are validated in clinical trials Galectin - 3 PET Scan - Detected Melanoma Tumors Resolved 14 13
Slide 15: Galectin-3 expression in tissues
https://www.tandfonline.com/doi/full/10.1080/2162402X.2018.1434467 Expression levels on almost all tissue types 15 14 expression in tissues Galectin - 3
Slide 16: Galectin effect (T-Cell anergy)
Galectin effect (T - Cell anergy) https://www.deduveinstitute.be/sites/default/files/upload/%20Annual%20Report%20DDUV%202017.pdf https://seekingalpha.com/instablog/47560554 - vision - and - value/5210387 - gr - mdminus - 02 - keytruda - s - partner Galectins are responsible for T - cell anergy and p
Slide 17: Galectins and influenza
Galectins and influenza Galectin - 1 Binds to Influenza Virus and Ameliorates Influenza Virus Pathogenesis https://www.ncbi.nlm.nih.gov/pubmed/21795357 “Galectin - 1 was upregulated in the lungs of mice during influenza virus infection. There was a positive correlation between galectin - 1 levels an
Slide 18: A Novel Therapeutic for Influenza
A Novel Therapeutic for Influenza Galectin - 3 Enhances Avian H5N1 Influenza A Virus - Induced Pulmonary Inflammation by Promoting NLRP3 Inflammasome Activation https://www.ncbi.nlm.nih.gov/pubmed/29366678 “We describe galectin - 3 up - regulation in mouse lung tissue after challenges with the H5N1
Slide 19: A Novel Therapeutic for Influenza
A Novel Therapeutic for Influenza Galectins regulate the inflammatory response in airway epithelial cells exposed to microbial neuraminidase by modulating the expression of SOCS1 and RIG1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624043/ “We have previously demonstrated both in vitro and in vivo
Slide 20: A Novel Therapeutic for Influenza
A Novel Therapeutic for Influenza C - Lethal influenza virus (512 HAU) given then treated with recombinant galectin - 1 (50 μg) or NaCl buffer at days 2, 4, and 5. D - Survival of ( gal - 1 +/+ ) vs galectin - 1 knockout ( gal - 1 −/− ) mice. Mice without Gal - 1 were more susceptible to the virus (
Slide 21: A Novel Therapeutic for Influenza
A Novel Therapeutic for Influenza Lung staining shows the bronchial (B) and the alveolus (A) regions. The dark areas in the buffer show a pronounced viral infection and inflammatory cells with possible fluid. The Galectin - 1 treated mice showed inflamed but functioning lung tissue Gal - 1 treatment
Slide 22: A Novel Therapeutic for Influenza
A Novel Therapeutic for Influenza Figure A: Wild Type Mice with H5N1 infection had a zero survival rate vs Galectin - 3 Knockout Mice with a 35% survival rate. Figure B: Weight is a measure of health and the Galectin - 3 Knockout Mice survived and gained their weight back. Inhibiting gal - 3 dramati
Slide 23: A Novel Therapeutic for HIV
A Novel Therapeutic for HIV Host - Soluble Galectin - 1 Promotes HIV - 1 Replication through a Direct Interaction with Glycans of Viral gp120 and Host CD4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209312/ “Galectin - 1… increases HIV - 1 infectivity by accelerating its binding to susceptible cel
Slide 24: A Novel Therapeutic for HIV
A Novel Therapeutic for HIV Proposed Interaction of gp120 (HIV spike protein) and CD4 with Gal - 1. Gal - 1 binds to gp120 and CD4. Galectin - 1 promotes virus attachment to the T - Cell using CD4 as a binding site. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209312/ 24 23
Slide 25: A Novel Therapeutic for HIV
A Novel Therapeutic for HIV HIV exploits the Galectin - 1 cross linking between HIV and CD4. Modulating Galectin - 1 expression at the mucosal sites could lead to a prophylactic. Galectin - 1 keeps the gp120 spike intact. Galectin - 3 spreads it apart making it less efficient to enter https://www.nc
Slide 26: Conclusion: Galectins Modulate Viral Infection
CONCLUSION: Galectins Modulate Viral Infection Galectin - 1, 3, and 9 are modulators of viral infection https://www.sciencedirect.com/science/article/pii/S1684118219301495 Gal - 1 has been reported to participate in the regulation of influenza A virus infection. An in vitro study showed that Gal - 1
Slide 27: COVID-19 Linkage to Galectin
Linkage to Galectin - 3 ▪ Sugar binding sites of the CoVs are located on the spike proteins anchored to the CoV. ▪ CoVs are classified by the receptor recognition patterns of their spike proteins Similar structural topology of S1 - NTDs of alpha & gamma genus function as lectins. DISCOVERY sugar bin
Slide 28: A universal target: the galectin fold
A universal target: The galEctiN fold ▪ 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 MABs are too large. ▪ This includes INFLUENZA antibodies. 28 covid - 19 27
Slide 29: The ideal target: Galectin
The ideal target: Galectin - 3 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
Slide 30: Theory: Gal-3 inhibitor mechanism of action COVID-19
Theory: Gal - 3 inhibitor mechanism of action COVID - 19 1. Bind to the virus, acting as an entry inhibitor. 2. Binding to the virus soaks up the virion. The liver filters out the galectin inhibitor with virion still attached. 3. Throttle the trafficking of macrophages to the site of infection. 4. R
Slide 31: Theory: Gal-3 inhibitor better immune response
Theory: Gal - 3 inhibitor better immune response COVID - 19 Lower galectin - 3 Concentrations = Better Immune Response ▪ High galectin - 3 forms plaque on the T - cell resulting in poor viral control. ▪ Removing galectin - 3 results in better viral control. ▪ Eliminates T - cell anergy and galectin
Slide 32: Patients at greatest risk COVID-19
Patients at greatest risk COVID - 19 According to the CDC: 51% of of older males 55+ have underlying medical conditions https://www.thelancet.com/action/showPdf?pii=S0140 - 6736%2820%2930211 - 7 https://www.sciencedirect.com/science/article/pii/S0165247814001801 Predictive biomarker severe asthma ht
Slide 33: Galectin-1 immunoregulatory signature
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3311782/ Gal - 1 triggers and immunoregulatory signature https://www.jimmunol.org/content/199/11/3721 Galectin - 1: A Jack - of - All - Trades in the Resolution of Acute and Chronic Inflammation ➢ GALECTIN - 1 Upregulated in the lungs polarizes the macrop
Slide 34: Recommendation: A Galectin Inhibitor
RECOMMENDATION Until a vaccine is available the IDEAL DRUG will have the following qualities: 1. Prophylactic properties that allow a person to be exposed yet stop the viral expansion dead in its tracks 2. Drug must reduce the viral load of those who are infected 3. Stoppage of the trafficking of su
Slide 35: Galectin antagonist BXT-10
Galectin - 3 antagonist BXT - 10 ▪ BXT - 10 is a well - characterized, complex carbohydrate ▪ BXT - 10 binds to and neutralizes galectin - 3 and galectin - 1. Binding activity is localized to the galactose containing side branches ▪ BXT - 10 has a neutral charge and invisible to the immune system ▪
Slide 36: BXT-10 reverses galectin-3 T-cell suppression
BXT - 10 ▪ T - Cells were collected from 4 ovarian cancer patients and tested for their ability to kill the tumor (T - cell Activity). Untreated cells have little activity. After treating the T - Cells with either an antibody to galectin - 3 (purple) or with BXT - 10 (blue), the T - Cells regain the
Slide 37: BXT-10 improves melanoma cancer vaccine
BXT - 10 ▪ Animals treated with BXT - 10 in addition to a vaccine against the tumor live much longer than untreated animals or animals treated with vaccination or BXT - 10 alone. Source: Dermotte et al. A Galectin - 3 Ligand Corrects the Impaired Function of Human CD4 and CD8 Tumor - Infiltrating Ly
Slide 38: BXT-10 Clinical summary
BXT - 10 Clinical summary ▪ Over 140 patient dosed in 9 Phase 1 and Phase 2 clinical trial ▪ Significant clinical activity in multiple cancers, including chronic lympocytic leukemia (CLL), multiple myeloma (MM), renal cell carcinoma ▪ Pharmacokinetic parameters established ▪ Single and multiple dose
Slide 39: BXT-10 side effects consistent with immune modulation
BXT - 10 side effects consistent with immune modulation ▪ Doses up to 160 mg/m² well tolerated in 24 - patient solid tumor study ▪ No hematological toxicity ▪ Only drug - related grade 3 AEs = rash (8%), arthralgia (8%) and myalgia(4%), all consistent with immune effects ▪ Dose - Limiting Toxicity ▪
Slide 40: BXT-10 Phase 2A single-agent CLL study design
BXT - 10 phase 2A single - agent cll study design ▪ Enrolled 24 patients with one or two prior therapies ▪ Median age 67 years old; 15 patients > 67 years, 4 > 80 years ▪ Prior therapies include Fludara - , Rituxan - and chlorambucil - containing regimens ▪ Dosing regimen ▪ 160 mg/m² i.v. daily for
Slide 41: BXT-10 Phase 2A single-agent CLL study results
BXT - 10 phase 2A single - agent cll study results ▪ BXT - 10 well tolerated ▪ Minimal hematological toxicity ▪ Only 1 patient discontinuation due to grade 3 rash ▪ No drug - related SAEs ▪ In vivo evidence of caspase activation and apoptotic cell death observed 1 ▪ Preliminary data indicates 6/24 p
Slide 42: BXT-10 viruses evolved from galectins
BXT - 10 viruses evolved from galectins “In the viral evolutionary path it appears that the CoV stole a host galectin gene and inserted it at the end of their spike gene. The S1 - NTD CoV has a galectin fold that is likely shared amongst different CoV genus but they are programmed to recognize diffe
Slide 43: BXT-10 for COVID-19 galectin tests for COVID-19
BXT - 10 for COVID - 19 galectins tests for covid - 19 The BGM Galectin - 3 assay is an FDA approved test for use in patients with chronic heart failure. Thousands of peer reviewed journal articles suggest that Galectin - 3 is implicated in cancer, fibrosis, and many chronic diseases. Since Gal - 3
Slide 44: BXT-10 for COVID-19 Trial Strategy
BXT - 10 for COVID - 19 TRIAL STRATEGY Study Type: Interventional Enrollment: 60 participants Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment Title: A Phase 2 Single Center Randomized Blinded Controlled Trial to Ev
Slide 45: Trial Strategy (cont'd) Secondary Endpoints
BXT - 10 for COVID - 19 TRIAL STRATEGY (cont’) Secondary Endpoints: 1. All cause mortality [Time Frame: up to 28 days] baseline SpO2 during screening, PaO2/FiO2 300mmHg or a respiratory rate ≥ 24 breaths per min without supplemental oxygen 2. Frequency of respiratory progression [Time Frame: up to 2
Slide 46: Trial Strategy (cont'd) Eligibility Criteria
BXT - 10 for COVID - 19 TRIAL STRATEGY (cont’) Eligibility Criteria 1. Males and females, age ≥18 years 2. Receiving combination antiretroviral therapy for last 24 weeks 3. No change in ART within last 4 weeks prior to Screening Visit 4. Subject has two or more potential alternative approved ART dru
Slide 47: Trial Strategy (cont'd) Exclusion Criteria
BXT - 10 for COVID - 19 TRIAL STRATEGY (cont’) Exclusion Criteria 1. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study 2. Unexplained fever or clinically significant illness within 1 week prior to the first study dose 3. Any vaccination within 2 w
Slide 48: BXT-10 for COVID-19 Trial design
BXT - 10 for COVID - 19 Trial design Animal Study - 1 - day Toxicity Type of Clinical Trial: Physician Sponsored IND Sites: Boston, NYC or Pittsburg Proposed Trial Design (Phase 2 Randomized ) Mild to Moderate COVID - 19 Disease (n=30) Randomized (1:1) Day1 Day2 Day3 Day4 Day5 Experimental 130 mg/m2
Slide 49: Rationale behind BXT-10 in COVID-19 planning
rationale behind BXT - 10 in COVID - 19 planning ▪ BXT - 10 (140 Patients) ▪ Minimal hematological toxicity ▪ No drug - related SAEs ▪ Has E vidence of Immune Modulation in Cancer ▪ Quick Scalable Manufacturing Capacity ▪ Multiple Pre - Clinical Study Implicate the Gal - 1/ 3 Receptor in COVID - 19
Slide 50: Leadership
leadership MANAGEMENT David Platt, Ph.D/CEO Ph.D in Chemical Engineering, Hebrew University of Jerusalem; Weizmann Institute; Founder of five public Bio - Tech companies over a 25 year period with a combined market capitalization of more than $1.5 billion Elena Chekhova, Ph.D/Chief Scientist Ph.D in
Slide 51: BioXyTran, Inc. contact
BioXyTran, Inc. 233 Needham St., Suite 300 Newton MA, 02464 (617) - 454 - 1199 www.bioxytraninc.com David Platt david.platt@bioxytraninc.com (617) - 510 - 2539