Mosaic 545 Pathogen Diagnostic Technology Platform. Immunotrex Biologics, Inc

Transcription

1 Immunotrex Biologics, Inc Syed K. Hasan M.D. Ph.D. CEO/President Immunotrex Michael McDaniel CEO/President Infinity Medical Engineering Immunotrex Biologics, Inc. Infinity Medical Engineering, LLC 2014 Immunotrex Biologics

2 Overview Infectious Disease Control Imperative Mosaic 545 Pathogen Identification Diagnostic Procedure Pathogen Identification Mechanism Mosaic 545 Prototype Design Contract Manufacturing Associates Intellectual Property 2/26/ Immunotrex Biologics 2

3 INFECTIOUS DISEASE CONTROL IMPERATIVE 2/26/ Immunotrex Biologics 3

4 Federal Public Health Mandate Global Intervention Infectious disease is a growing global health threat. As recently as two weeks ago, Health and Human Services Secretary Kathleen Sebelius launched a global effort to prevent, detect and respond to infectious disease threats where they start. (Global Health Security Agenda). Infectious disease epidemics originate largely in developing countries. The United States is susceptible to infectious disease transmission by virtue of the increased mobility and interaction of global populations. Human immunodeficiency virus (HIV) serves as a potent reminder. The United States occupies a lead position as a first responder to humanitarian crises throughout the world, including infectious disease outbreaks. The ability to diagnose a patient quickly and accurately is critical to containing an outbreak. 2/26/ Immunotrex Biologics 4

5 Federal Public Health Mandate Domestic Healthcare The incidence of opportunistic, secondary infection in primary care facilities is increasing at an alarming rate. The costs in patient morbidity and treatment are straining the national healthcare system. A report published in the Journal of Emerging Infectious Diseases, found a 90% increase in reports of MRSA infections among U.S. hospital outpatient admissions from A 2009 Center for Disease Control study review examining the costs of healthcare associated infections in hospitals estimated the excess hospital cost of healthcare associated infections in the US to be between 28 and 45 billion dollars annually. 2/26/ Immunotrex Biologics 5

6 Federal Public Health Mandate National Security In addition to existing and potential infectious disease outbreaks attributable to spontaneous environmental origin, it is incumbent upon the United States to maintain a robust, comprehensive prophylaxis and agile emergency response strategy to combat the possibility of a biological attack. 2/26/ Immunotrex Biologics 6

7 Federal Public Health Mandate Improved Patient Care In each scenario time to diagnosis is critical. Rapid diagnosis facilitates: Identification and quarantine of infected patients Identification of the infectious agent/pathogen Administration of the appropriate treatment regimen Reduction in duration of symptoms and improved prognosis Reduction in patient length of stay Faster diagnosis, prompt and appropriate medical treatment and reduced duration of hospital stay improve patient quality of life, reduce health care expense and facilitate increased access to immediate care facilities. 2/26/ Immunotrex Biologics 7

8 MOSAIC 545 PATHOGEN IDENTIFICATION 2/26/ Immunotrex Biologics 8

9 Current State of the Art Blood Culture for pathogen identification 2/26/ Immunotrex Biologics 9

10 Time is Critical When a patient presents with an infection during emergency or intensive care, blood culture can be a race against time. The typical process of pathogen identification in blood takes at least 24 hours. Current methods include culture techniques using agar plates and culture mediums (c. early 1900s) prolonging the process of identification. Culture methods are dependent on producing additional infectious pathogen. 2/26/ Immunotrex Biologics 10

11 Introducing Mosaic 545 Real-time positive pathogen identification (< 10 minutes) Sterile, self-contained cartridge Simple on-site use model Multiple samples run simultaneously No culturing of infectious pathogens MOSAIC 545 utilizes highly conserved species specific oligomer hybridization of small RNA sequences. 2/26/ Immunotrex Biologics 11

12 Mosaic 545 Components Sterile, self-contained pathogen identification cartridge Multi-slot cartridge reader Signal processing software Pathogen Identification Cartridge Cartridge Reader Signal Processing Software Pathogen Identification Cartridge Model: Lot # Specimen ID: 2/26/ Immunotrex Biologics 12

13 Mosaic 545 Pathogen Identification Cartridge Specimen ID: Model: Lot # Pathogen Identification Cartridge The Pathogen Identification cartridge is the heart of the Mosaic 545. Retractable injector for specimen acquisition Cartridge is self-contained and sterile All reagents and specimen quarantined Pathogen filtration and rrna isolation Customizable to localized infectious agents Specimen processing eliminates pathogen viability 2014 Immunotrex Biologics 13

14 Mosaic 545 Cartridge Reader On-site, immediate, plug and play processing Barcode on cartridge corresponds to patient ID Simultaneous processing of multiple cartridges Economical significantly lower cost per test 2/26/ Immunotrex Biologics 14

15 DIAGNOSTIC PROCEDURE 2/26/ Immunotrex Biologics 15

16 Specimen Is Collected Specimen collection is performed by a trained phlebotomist, medic, or first responder in accordance with standard healthcare best practices. 2/26/ Immunotrex Biologics 16

17 Specimen Is Injected into Cartridge The Mosaic 545 cartridge has an integral, positive lock injector. The technician engages injector and inserts it into specimen collection tube. 2/26/ Immunotrex Biologics 17

18 Cartridges Are Inserted into Cartridge Reader Pathogen Identification Cartridge Model: Lot # Specimen ID: A technician inserts the cartridges into the cartridge reader. 2/26/ Immunotrex Biologics 18

19 PATHOGEN IDENTIFICATION MECHANISM 2/26/ Immunotrex Biologics 19

20 Targeted Pathogens and Diseases Bacterial Pathogen Bartonella henselae Borrelia burgdorferi Brucella (species) Chlamydia psittaci Clostridium botulinum Clostridium perfringens Cryptosporidium parvum Escherichia coli O157:H7 Rickettsia prowazekii Salmonella (species) Shigella dysentariae Staphylococcus aureus Streptococcus pneumoniae Vibrio cholerae Disease Cat scratch disease Lyme disease Brucellosis Psittacosis Botulism Εpsilon Toxin (ε) Cryptosporidiosis Food poisoning Typhus fever Typhoid fever, food poisoning Severe dysentery Septic shock Multiple, meningitis Cholera gravis 2/26/ Immunotrex Biologics 20

21 Monoclonal Antibody affinity sensors in the cartridge target highly conserved ribosomal RNA (rrna) for each pathogen. The Target: Ribosomal RNA 2/26/ Immunotrex Biologics 21

22 Mosaic 545 Component Functions The specimen is filtered, bacteria is lysed, and conserved ribosomal RNA (rrna) sequences are exposed to reduced graphene oxide (RGO) and fluorescence sensors coated with specific affinity monoclonal antibody mab. Pathogen Identification Cartridge Cartridge Reader Signal Processing Software Pathogen Identification Cartridge Model: Lot # Specimen ID: 2/26/ Immunotrex Biologics 22

23 Mosaic 545 Component Functions An internal control validates the cartridge prior to processing. Impedance and fluorescence at each sensor are continuously monitored. The multi-bay cartridge reader can process up to 12 cartridges simultaneously in less than 10 minutes. Pathogen Identification Cartridge Cartridge Reader Signal Processing Software Pathogen Identification Cartridge Model: Lot # Specimen ID: 2/26/ Immunotrex Biologics 23

24 Mosaic 545 Component Functions Raw data from the cartridge monitoring process is sent directly to a PC. Signal processing identifies valid sensor signals and specific pathogen(s). The specimen bar code links the data to the patient record. Results are transmitted via multiple communication portals. Pathogen Identification Cartridge Cartridge Reader Signal Processing Software Pathogen Identification Cartridge Model: Lot # Specimen ID: 2/26/ Immunotrex Biologics 24

25 Cartridge Schematic CTRL Bimodal Sensor Assembly rrna Antibody Affinity Binding Chamber Electric Terminals Lysis Chamber Sample Reservoir Selective Filters Sample Injector (Retractable) Saline Lysis Solution 2/26/ Immunotrex Biologics 25

26 Blood Sample Components White Blood Cells (7-20 µm) Decreasing Size Red Blood Cells (6-8 µm) Bacteria (3-10µm) Ribosomes, Proteins (<1 µm) Nucleic Acids (nm) (Images not to scale) 2/26/ Immunotrex Biologics 26

27 Intra-Cartridge Specimen Processing Within the Pathogen Identification cartridge: 1) The specimen is filtered, excluding components > 10µm; bacteria pass through the filter. 2) The pathogenic bacteria are lysed, releasing cellular components, including targeted ribosomal RNAs (rrnas). 3) The specimen is filtered, removing lysis debris >1µm; proteins, ribosomes and nucleic acids pass through the filter. 4) Specimen rrnas are exposed to multiple reduced graphene oxide (RGO) sensors, each coated with a unique specific affinity monoclonal antibody. 10 µm Filter Target rrna 2/26/ Immunotrex Biologics 27

28 Intra-Cartridge Specimen Processing Within the Pathogen Identification cartridge: 1) The specimen is filtered, excluding components > 10µm; bacteria pass through the filter. 2) The pathogenic bacteria are lysed, releasing cellular components, including targeted ribosomal RNAs (rrnas). 3) The specimen is filtered, removing lysis debris >1µm; proteins, ribosomes and nucleic acids pass through the filter. 4) Specimen rrnas are exposed to multiple reduced graphene oxide (RGO) sensors, each coated with a unique specific affinity monoclonal antibody. < 1 µm Filter Target rrna 10 µm Filter 2/26/ Immunotrex Biologics 28

29 Intra-Cartridge Specimen Processing Within the Pathogen Identification cartridge: 1) The specimen is filtered, excluding components > 10µm; bacteria pass through the filter. 2) The pathogenic bacteria are lysed, releasing cellular components, including targeted ribosomal RNAs (rrnas). 3) The specimen is filtered, removing lysis debris > 1µm; proteins, ribosomes and nucleic acids pass through the filter. 4) Specimen rrnas are exposed to multiple reduced graphene oxide (RGO) sensors, each coated with a unique specific affinity monoclonal antibody. Target rrna < 1 µm Filter Ribosome Protein 2/26/ Immunotrex Biologics 29

30 Intra-Cartridge Specimen Processing Within the Pathogen Identification cartridge: 1) The specimen is filtered, excluding components > 10µm; bacteria pass through the filter. 2) The pathogenic bacteria are lysed, releasing cellular components, including targeted ribosomal RNAs (rrnas). 3) The specimen is filtered, removing lysis debris > 1µm; proteins, ribosomes and nucleic acids pass through the filter. 4) Specimen rrnas are exposed to multiple reduced graphene oxide (RGO) sensors, each coated with a unique specific affinity monoclonal antibody. Target rrna Nucleic Acids 2/26/ Immunotrex Biologics 30

31 Intra-Cartridge Specimen Processing Within the Pathogen Identification cartridge: 1) The specimen is filtered, excluding components > 10µm; bacteria pass through the filter. 2) The pathogenic bacteria are lysed, releasing cellular components, including targeted ribosomal RNAs (rrnas). 3) The specimen is filtered, removing lysis debris > 1µm; proteins, ribosomes and nucleic acids pass through the filter. 4) Specimen rrnas are exposed to multiple reduced graphene oxide (RGO) sensors, each coated with a unique specific affinity monoclonal antibody. Target rrna mab binds target rrna 2/26/ Immunotrex Biologics 31

32 MOSAIC 545 PROTOTYPE DESIGN 2/26/ Immunotrex Biologics 32

33 Bacterial Pathogens Nominal Size Electron micrograph - S. aureus, the strain responsible for MRSA Bacterial Pathogen Diameter (µ) Length (µ) Bartonella henselae Borrelia burgdorferi Brucella (species) Chlamydia psittaci Clostridium botulinum Clostridium perfringens Cryptosporidium parvum Escherichia coli O157:H Rickettsia prowazekii Salmonella (species) Shigella dysentariae Staphylococcus aureus Streptococcus pneumoniae Vibrio cholerae /26/ Immunotrex Biologics 33

34 Sensor Function The baseline impedance of each sensor is established prior to sample processing. At this point, the specimen is intact, and no antibody binding has occurred. The Mosaic 545 monitors the impedance across each sensor continuously in real-time, detecting and identifying changes resulting from antibody-pathogen binding. Localized sensor fluorescence is measured, confirming binding interaction at the sensor. 2/26/ Immunotrex Biologics 34

35 Bimodal Sensor Assembly Impedance Sensor Fluorescence Sensor mab-coated RGO Targeted rrna binding increases electrical impedance through mab-coated reduced graphene oxide (RGO) sensor. Fluorophore emission from rrna-mab binding confirms impedance sensor identification of pathogen. Resonant frequency Change in resonance due to introduction of pathogen 2/26/ Immunotrex Biologics 35

36 Impedance Sensor Target rrna Monoclonal Antibody mab + rrna Nucleic Acids (+) (-) mab-coated RGO (Reduced Graphene Oxide) 2/26/ Immunotrex Biologics 36

37 Fluorescence Sensor Mosaic 545 Fluorescence Target rrna Monoclonal Antibody mab + rrna (+) (-) mab-coated RGO (Reduced Graphene Oxide) 2/26/ Immunotrex Biologics 37

38 Cartridge BARDA Pathogen Profile CTRL 1. Clostridium botulinum 2. Brucella (species) 3. Clostridium perfringens 4. Salmonella (species) 5. Escherichia coli O157:H7 6. Shigella dysentariae 7. Chlamydia psittaci Staphylococcus aureus 9. Rickettsia prowazekii 10. Vibrio cholerae 11. Cryptosporidium parvum 12. Bartonella henselae 13. Borrelia burgdorferi 14. Streptococcus pneumoniae 2/26/ Immunotrex Biologics 38

39 Multi-Slot Cartridge Reader Mosaic 545 Plug and play Technician inserts cartridge(s) into Mosaic 545 card reader and initiates the processing run. Cartridge is validated prior to processing specimen. Current design offers 12 cartridge slots processes up to 12 samples simultaneously, in < 10 minutes. Bar code reader syncs test result to patient. Multiple data transmission options to PC, wireless network, Radio Frequency Identification (RFID), onboard LCD display, Short Message Service (SHS), Multimedia Messaging Service (MMS) 2/26/ Immunotrex Biologics 39

40 Signal Processing Software Mosaic 545 combines well established scientific elements with cutting edge technologies to identify the presence of pathogens at a sub-specific (strain) level. The mechanism of detection is two-fold: I. Change in impedance across a reduced graphene oxide (RGO) sensor II. Optical measurement of fluorescence emission Changes are due to specific ribosomal RNA (rrna) monoclonal antibody (mab) binding. The sensor array is coded and activated sensor(s) identify the pathogen(s). 2/26/ Immunotrex Biologics 40

41 Traditional Culture vs. Mosaic 545 Features Traditional Culture Methods Mosaic 545 Speed hours 5 10 minutes Safety Incubation, growth, and handling of specimen pathogen; complex disposal process Specimen pathogen quarantined and destroyed; simple disposal of cartridge Simplicity Multi-step protocol Unitary cartridge processing 2/26/ Immunotrex Biologics 41

42 Contract Manufacturing Associates Immunotrex has pending proposals from two contract manufacturing firms: Enercon Technologies, Inc. for development of the Mosaic 545 cartridge and multi-bay reader Precision Antibodies, Inc. for custom monoclonal antibodies Submitted proposals include pilot program development through to multiple working prototypes for internal and external testing. Time to completion of prototype 6 months from project initiation. Immunotrex maintains all rights to any and all contracted works. Enercon Technologies, Inc. Gray, ME ISO 13485:2003 FDA Registered 21 CFR Part 820 GMP ISO 9001:2008 ESD S20.20 UL, ETL, TUV Precision Antibody, Inc. Columbia, MD AAALAC accredited Custom mab development One Stop Shop FDA, NCI, EPA contractor 2/26/ Immunotrex Biologics 42

43 Intellectual Property US Patent Application Serial No. 13/894,971 (Newly Filed) Continuation Application of USSN 12/426,470 Title: METHODS FOR MICROORGANISM DETECTION AND IDENTIFICATION M&G Ref: USC3 2/26/ Immunotrex Biologics 43

44 Thank You Immunotrex Biologics appreciates the opportunity to present our Mosaic 545 pathogen diagnostic technology platform. Questions? 2/26/ Immunotrex Biologics 44