Adhera Therapeutics Inc. · OTC:ATRX

Adhera Therapeutics — Nastech Pharmaceutical — BMO Capital Markets Focus on Healthcare 2007

72 slides from Adhera Therapeutics's conference presentation, Dec 7, 2007

  1. Slide 1: BMO Capital Markets Focus on Healthcare

    Steven Quay, M.D., Ph.D., Chairman, President and CEO December 5, 2007 / New York BMO Capital Markets Focus on Healthcare

  2. Slide 2: Forward-Looking Statement

    Forward-Looking Statement Statements made in this presentation may be forward-looking statements within the meaning of Federal Securities laws that are subject to certain risks and uncertainties and involve factors that may cause actual results to differ materially from those projected or suggested.

  3. Slide 3: Nastech Pharmaceutical Company Inc.

    Nastech Pharmaceutical Company Inc. Molecular biology-based drug delivery Needle-free delivery of peptide and protein drugs Six clinical stage programs: Diabetes & Obesity (3) Osteoporosis (2) CNS disorders (1) Vertically integrated with important partnerships: Amylin, Novo Nordisk, Par Pharmaceutic

  4. Slide 4: Questions To Be Answered Today

    Questions To Be Answered Today Does Nastech's drug delivery technology work? Does it delivery drugs to the blood stream? Do the drugs work when they get there? Is it safe? What's the value of Nastech's Phase 2 programs & MDRNA, Inc? Insulin for diabetes PTH for osteoporosis PYY for obesity Carbetoci

  5. Slide 5: Response to the P&G termination

    Response to the P&G termination November 6: P&G notice received November 7: Notice to shareholders provided November 7-13: Internal analysis of programs, budgets, people; a plan is formulated November 14: Conference call with shareholders outlining plans for Phase 2 program focus, reduction in force

  6. Slide 6: Nastech Analysis

    Nastech Analysis December 3, 2007: Enterprise Value of $94.4 MM $49.7 MM: Cash/Assets $44.7 MM: Molecular Biology Delivery Technology, 44 Patents, 350 US patent appls., Dedicated People, Programs, State-of-art facilities, Calcitonin & Par Pharmaceutical, PTH Phase 2, Insulin Phase 2, PYY Phase 2, Ca

  7. Slide 7: Molecular Biology-Based Drug Delivery Platforms

    Molecular Biology-Based Drug Delivery Platforms Mucosal delivery of peptides and proteins Cellular delivery of RNAi therapeutics

  8. Slide 8: Molecular Biology-Based Drug Delivery

    Molecular Biology-Based Drug Delivery Preferred administration for injectables Patient-preferred over injectable drugs Safety advantages over pulmonary delivery Clinical validation of science Safety & efficacy supported by 20+ clinical trials and >20,000 human doses Large market opportunity Injectab

  9. Slide 9: Clinical Product Pipeline

    Clinical Product Pipeline Calcitonin Generic - Osteoporosis PHASE I PHASE II PHASE III NDA / ANDA PARTNER CLINICAL STAGE NASTECH PRODUCTS Parathyroid Hormone (PTH1-34) Osteoporosis Insulin Diabetes Exenatide Diabetes Peptide YY3-36 Obesity Carbetocin Autism PRE-CLINICAL

  10. Slide 10: Awaiting FDA Approval: Calcitonin Nasal Spray

    Awaiting FDA Approval: Calcitonin Nasal Spray Current status Nastech has answered all FDA questions FDA has approved ANDA sections including: manufacturing; chemistry, manufacturing and controls FDA has affirmed that Nastech's product is bioequivalent to Miacalcin(r) FDA has completed all final prod

  11. Slide 11: Phase 2 Biomarker Study Data: PTH1-34 for Osteoporosis

    Phase 2 Biomarker Study Data: PTH1-34 (teriparatide) for Osteoporosis Phase 2 biomarker study complete 15% decrease in CTX was equivalent to Forteo Dose response seen for P1NP "Forteo equivalent" dose identified Inter-subject variability of nasal equivalent to Forteo Well-tolerated, sans hypercalcem

  12. Slide 12: PYY3-36 Program Overview

    PYY3-36 Program Overview 6-month Phase 2 Weight Loss Trial initiated Oct. 2007 510 obese patients (BMI 30-43 kg/m2); 255 patient-years PYY Nasal Spray or placebo 3 per day Patients undergo initial dose optimization period Primary endpoint weight loss over 6 months Secondary endpoints include: Patien

  13. Slide 13: Merck's Phase 1 PYY3-36 Study

    Merck's Phase 2 PYY3-36 Study Study design 43-44 patients per dose group; 133 total; 31 patient-years Study design provides 12% of the exposure of Nastech study 2-week diet and exercise run in period Placebo controlled, randomized, 12-week treatment period Doses: placebo, 200 ug, 600 ug Nasal spray

  14. Slide 14: Merck's PYY3-36 Study Safety / tolerability

    Merck's Phase 2 PYY3-36 Study Safety / tolerability 74% dropout on 600 ug dose compared to 12% for placebo 59% of 600 ug dose patients discontinued due to nausea and vomiting Based on completers, at least 23,000 doses of Nastech's intranasal formulation were administered. "Nasal AEs (dryness, conges

  15. Slide 15: PYY3-36 Study: Efficacy Results

    Phase 2 PYY3-36 Study: Efficacy Results Over 12 weeks with repeated measure ANCOVA: Placebo: -2.8 kg 200 ug: -3.7 kg 600 ug: -1.4 kg >14 week completers: Placebo: 10.3 lbs 200 ug: 13.7 lbs

  16. Slide 16: Nastech's Ongoing PYY3-36 Study

    Nastech's Ongoing Phase 2 PYY3-36 Study Merck study interpretation - and what we are doing differently PYY weight loss appears robust 1 pound per week if 2-week run in period included Continuing separation between PYY 200 group and placebo -no evidence of a weight loss plateau at 3 months Merck stud

  17. Slide 17: PYY3-36 Study: Merck study interpretation

    Phase 2 PYY3-36 Study Merck study interpretation - and what we are doing differently Could behavioral intervention have disproportionately increased the placebo response? We propose a less intensive behavioral intervention Could a nasal spray by itself result in an increased placebo response? Our st

  18. Slide 18: PYY Phase 2 Study Recruitment Status

    PYY Phase 2 Study Recruitment Status

  19. Slide 19: Insulin Nasal Spray Development Program

    Insulin Nasal Spray Development Program IN Insulin Target Product Profile Summary Ultra rapid Convenient meal time dosing Reduced hypoglycemia potential differentiation from SC insulin Critical to primary care physicians (PCPs) No pulmonary exposure, pulmonary function tests, or contraindication for

  20. Slide 20: IN Insulin Pharmacokinetics

    Phase 1 trial comparing nasal spray formulation to rapid-acting subcutaneous Novolog(r) injection and Exubera(r) inhalable insulin IN Insulin Pharmacokinetics

  21. Slide 21: Glucose Tolerance Study: Results to Date

    Phase 2 Glucose Tolerance Study: Results to Date Placebo NovoRapid Nasal

  22. Slide 22: Glucose Tolerance Study: Results to Date

    Phase 2 Glucose Tolerance Study: Results to Date Placebo NovoRapid Nasal

  23. Slide 23: Exenatide for Type 2 Diabetes

    Exenatide for Type 2 Diabetes Current status Undergoing clinical studies $89 million in potential milestone payments Significant royalties upon commercialization Current market Amylin's BYETTA(r) (exenatide), twice-daily injectable Product sales annualizing ~ $600 million Improves blood sugar contro

  24. Slide 24: Carbetocin for Autism

    Carbetocin for Autism Current status Multiple Phase 1 studies complete Phase 2 proof of concept study planned for 1st half 2008 Autism Spectrum Disorder (ASD) is highly prevalent 1 in 150 children diagnosed with ASD by age 8 Carbetocin: long-acting oxytocin analogue Established safety profile Inject

  25. Slide 25: Drug Delivery Feasibility Studies

    Drug Delivery Feasibility Studies Establish partnerships that provide alternative delivery for our partner's products Goal is to convert feasibility programs into major development and commercialization agreements Example: Amylin's Exenatide Feasibility studies are funded by partners Current feasibi

  26. Slide 26: Factor IX for Hemophilia B

    Factor IX for Hemophilia B Feasibility study Undisclosed Partner Major plasma products producer Goal: develop an alternative dosage for Factor IX Hemophilia B Factor IX currently intravenous injection National Hemophilia Foundation recommends prophylaxis as optimal therapy for children with severe h

  27. Slide 27: Nastech Financials

    Nastech Financials Q3 2007 (in millions) Total Revenues $ 1.9 Total Expenses ($18.4) Net Loss ($16.5) Cash Balance - Sept. 2007 $58.1 million Shares Outstanding - Sept. 2007 25.8 million Announced corporate restructuring initiatives on Nov. 13, 2007 to more closely manage our cash position

  28. Slide 28: RNA in the Service of Medicine

    RNA in the Service of MedicineTM NASDAQ: redacted

  29. Slide 29: MDRNA Strategy

    MDRNA Strategy RNA-based technology Develop second generation in-house/licensed key technologies, including RNA building blocks, cargos, and delivery components Therapeutics Develop/partner RNAi therapeutics, initially rheumatoid arthritis & influenza Develop/partner microRNA therapeutics, initially

  30. Slide 30: Intellectual Property Strategy

    Intellectual Property Strategy Understand the biology Breakdown the process Patent the steps

  31. Slide 31: Understand the biology

    Understand the biology Dicer with substrate

  32. Slide 32: Understand the biology

    Understand the biology Dicer with substrate Dicer transition state

  33. Slide 33: Understand the biology

    Understand the biology Dicer with substrate RISC with substrate Dicer transition state

  34. Slide 34: Understand the biology: Helicase Mechanism

    Understand the biology Dicer with substrate RISC with substrate RISC transition state Dicer transition state Helicase Mechanism

  35. Slide 35: Understand the biology: Endonuclease Mechanism

    Dicer with substrate RISC with substrate RISC transition state Dicer transition state RISC-Antisense Complex Endonuclease Mechanism Understand the biology

  36. Slide 36: Target mRNA Cleavage by RISC

    Target mRNA Cleavage by RISC Dicer with substrate RISC with substrate RISC transition state Dicer transition state RISC-Antisense Complex Endonuclease Mechanism Understand the biology

  37. Slide 37: Target mRNA Cleavage by RISC

    Target mRNA Cleavage by RISC Dicer with substrate RISC with substrate RISC transition state Dicer transition state RISC-Antisense Complex Nonfunctional mRNA fragments Endonuclease Mechanism Understand the biology

  38. Slide 38: Patent the steps

    Patent the steps RiboT Delivery Dicer substrates RISC-based Meroduplexes Target mRNA & DNA Dicer-based Meroduplexes RiboT-containing RISC substrates

  39. Slide 39: Platform Technology IP

    Platform Technology IP Second generation building blocks RiboTs reduces toxicity Second generation cargos Dicer substrates improve efficacy Meroduplexes reduce toxicity Second generation delivery CCP makes medically relevant RNA delivery possible Trp Cage Phage Display facilitates ZIP code developme

  40. Slide 40: Multi-Parallel Target Patent Universe

    Multi-Parallel Target Patent Universe Multi-Parallel Target Patent Universe The $1.1 B Sirna-Merck target patent estate Claims limited to base modifications MDRNA RiboT Target Estate Claims limited to two strands MDRNA Meroduplex Target Estate

  41. Slide 41: Rheumatoid Arthritis

    Rheumatoid Arthritis Multi-billion dollar therapy class Existing therapies (Remicade(r), Humira(r), Enbrel(r)) neutralize Tumor Necrosis Factor-alpha (TNF-^): Stabilizes TNF-^ protein in the bloodstream RNA-based therapy potentially reduces TNF-^ mRNA Analogy: "The difference between arresting a gun

  42. Slide 42: TNF-α mRNA Is Up-regulated by Existing MAb Therapy

    TNF-^ mRNA Is Up-regulated by Existing MAb Therapy TNF-^ mRNA Is Up-regulated by Existing MAb Therapy Study design: Serum/monocytes from RA patients (n=42)

  43. Slide 43: elevated

    elevated TNF-a. protein elevated TNF-a mRNA

  44. Slide 44: elevated

    elevated TNF-a. protein elevated TNF-a mRNA IMAb

  45. Slide 45: elevated

    elevated TNF-a, protein elevated TNF-a mRNA IMAb

  46. Slide 46: Further TNF-α protein up-regulation

    Further TNF-a protein up-regulat, of mRNA elevated TNF-a mRNA IMAb

  47. Slide 47: elevated

    elevated Further TNF-a protein elevated TNF-a mRNA IMAb

  48. Slide 48: Further elevated

    Further elevated up-regulat TNF-a protein of mRNA incised TNF Pro Production elevated TNF-c. mRNA IMAb Treatment Worsening Sympto

  49. Slide 49: RNAi Breaks the Cycle

    RNAi Breaks the Cycle RNAi Breaks the Cycle 4% 96% Significant (>50%) TNF-^ mRNA knockdown with RNAi (n=28) IC50 below 100 pM

  50. Slide 50: elevated

    elevated TNF-a. protein elevated TNF-a mRNA

  51. Slide 51: elevated

    elevated TNF-a. protein RNAi elevated TNF-a mRNA

  52. Slide 52: elevated

    elevated TNF-a. protein RNAi elevated TNF-a mRNA

  53. Slide 53: elevated

    elevated TNF-a. protein

  54. Slide 54: elevated

    elevated NF-a.

  55. Slide 55: Influenza RNA Delivery

    CCP-Cargo localize to bronchial epithelial cells & alveolar cells Influenza RNA Delivery

  56. Slide 56: Influenza Knockdown Efficacy with Dicer Substrate Conjugates

    Influenza Knockdown Efficacy with Dicer Substrate Conjugates > Million times more potent than 1st generation Efficacy against Tamiflu resistant flu demonstrated Efficacy against pandemic H5N1 demonstrated 1st Generation Cargo 2nd Generation Cargo and 1st Generation Delivery 2nd Generation Cargo and

  57. Slide 57: In vitro Knockdown

    In vitro Knockdown 2006 Alnylam ApoB RISC Conjugate 2007 Meroduplexs Dicer conjugates improve efficacy

  58. Slide 58: ZIP Code Program: Rationale Design

    ZIP Code Program: Rationale Design Over 500 unique peptides tested PN73 Forms a complex with siRNA Interacts with cell surface Enhances macropinocytosis Facilitates endosomal release Percent Uptake Percent Uptake Peptide 9L/lacZ Cell Line Primary MTF Cells PN27 86 61 PN28 79 81 PN29 87 not tested Pe

  59. Slide 59: ZIP Code Program: Trp Cage Phage Display

    ZIP Code Program: Trp Cage Phage Display Trp Cage Phage display permits novel cell specific binding peptides to be developed M13 system (7, C7C, 12) T7 system (defined structural motifs) In vivo & in vitro selection siRNA-peptide conjugates

  60. Slide 60: Licensed Patent Rights

    Licensor/Owner Subject Matter Priority Date Inventor MDRNA Rights Alnylam dsRNA having overhangs 12/01/00 Tuschl et al. Non-exclusive broad rights; Exclusive rights for TNF- a Alnylam dsRNA as therapeutics 1/30/99 Kreutzer-Limmer et al. Non-exclusive broad rights; Exclusive rights for TNF- a Alnylam

  61. Slide 61: In-House Developed IP Rights

    In-House Developed IP Rights 2004 2005 2006 2007 Total Patent Apps 5 23 11 65 Intl Patent Apps 4 18 5 1 US Patent Apps 1 5 6 64 2004 2005 2006 2007 Cumulative 5 28 39 104 Intl Patent Apps 4 22 27 28 US Patent Apps 1 6 12 76 Filing US/foreign patents since 2004 104 total as of Q2 2007 Patent topics:

  62. Slide 62: Collaborations and Relationships

    Collaborations and Relationships Collaborations and Relationships

  63. Slide 63: Track Record of Achievements 2003-2004

    Track Record of Achievements 2003 Tight junction (TJ) protein RNAi, demonstrating that TJ proteins are important in drug delivery 2nd generation technology, RiboT-containing RNA, increases serum/plasma stability 2004 1st generation peptide delivery technology presented to European Peptide Society an

  64. Slide 64: Track Record of Achievements 2005

    Track Record of Achievements 2005 Made key improvements in phage display technology to identify new drug-targeting peptides 2nd generation delivery CCPs presented to ASBMB and American Peptide Society Identified lead targets for TNF-^ and demonstrated activity in RA animal model Initiated collaborat

  65. Slide 65: Track Record of Achievements 2006

    Track Record of Achievements 2006 Acquired influenza-related IP assets from Galenea and MIT Key discovery of 1st generation RISC conjugate indigestion leads to 2nd generation Dicer conjugates Validated lead siRNA candidates in influenza and human metapneumovirus infections Awarded two grants totalin

  66. Slide 66: Track Record of Achievements 2007

    Track Record of Achievements 2007 New lipid and peptide delivery agents invented Collaborations on CCP development Established CRADA with the Centers for Disease Control (CDC) and obtained first results demonstrating activity of siRNAs against pandemic influenza (H5N1) RNA-based drugs have improved

  67. Slide 67: Competitive Analysis: Overview

    Competitive Analysis: Overview MDRNA MDRNA MDRNA MDRNA MDRNA Antisense Isis Genta Lorus Santaris Alnylam Silence Tx RXi Calando Protiva Tekmira Mirus Bio Intradigm Kylin MDRNA MDRNA SiRNA/Merck Dicerna Px

  68. Slide 68: Transaction Overview

    Transaction Overview Following a partial sale to private investors, MD-RNA is spun-off from Nastech through a partial or full divestiture of ownership to existing Nastech shareholders Inia knvertentin Subairy Fara Divestiture Spin ot =. "eon | os = a

  69. Slide 69: Establish MDRNA, Inc. as Independent Company

    Establish MDRNA, Inc. as Independent Company MDRNA, Inc. Timeline Q4 2007 Q1 2008 Q2 2008 Nastech's BOD Approval Establish Advisory Board Transfer IP & Agreements ? ? Announce Management Team Independent Investment to MDRNA Transfer Employees into MDRNA Dividend to Nastech Shareholders Initiate Publ

  70. Slide 70: Nastech's Key Value Drivers

    Nastech's Key Value Drivers Multiple Phase 2 clinical programs 3 Phase 2 programs 1 compound awaiting FDA approval > 4 pre-clinical programs Partnerships with leading pharma and biotech companies Potential for significant future milestones/fees and royalties Establishing MDRNA, Inc. as an independen

  71. Slide 71: Nastech Analysis

    Nastech Analysis December 3, 2007: Enterprise Value of $94.4 MM $49.7 MM: Cash/Assets $44.7 MM: Molecular Biology Delivery Technology, 44 Patents, 350 US patent appls., Dedicated People, Programs, State-of-art facilities, Calcitonin & Par Pharmaceutical, PTH Phase 2, Insulin Phase 2, PYY Phase 2, Ca

  72. Slide 72: For More Visit Nastech.com

    FOR MORE VISIT NASTECH.COM (© NASTECH

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