Circio Holding ASA · OSL:CRNA

Circio Holding ASA — Targovax — Investor Presentation (January 2016)

52 slides from Circio Holding ASA's investor presentation, January 2016

  1. Slide 1: Arming the patient’s immune system to fight cancer

    Arming the patient’s immune system to fight cancer January 2016 1 CONFIDENTIAL www.targovax.com

  2. Slide 2: Important notice and disclaimer

    INTRODUCTION Important notice and disclaimer This report contains certain forward-looking statements based on uncertainty, since they relate to events and depend on circumstances that will occur in future and which, by their nature, will have an impact on the results of operations and the financial

  3. Slide 3: The presenting team

    INTRODUCTION The presenting team Gunnar Gårdemyr, CEO Øystein Soug, CFO More than 30 years of international experience Previously CFO at Algeta, where he built up the from the pharmaceutical and biotech industry functions of Finance, IR, Compliance, IT and HR including business development, mergers

  4. Slide 4: Targovax – “Arming the patient’s immune system to fight cancer”

    INTRODUCTION Targovax – “Arming the patient’s immune system to fight cancer” 1  Oncolytic adenoviruses targeted at all solid, injectable tumors An emerging immuno- oncology leader  RAS-mutated peptide immunotherapy, targeted at all RAS- mutated cancers 2  TG01 is the only RAS-specific cancer vacc

  5. Slide 5: Targovax – an emerging immuno-oncology specialist

    INTRODUCTION Targovax – an emerging immuno-oncology specialist June 2015 Today Technology One technology Two promising technologies Studies 2 small Phase l studies Late stage planning of 5 Phase l/ll combination studies Investor base Limited 3x investor base Organization Small Highly experienced int

  6. Slide 6: Candidates and program

    Candidates and program 6 CONFIDENTIAL www.targovax.com

  7. Slide 7: Promising phase I data

    CANDIDATES AND PROGRAM Promising phase I data ONCOS-102 TG01 1  Oncolytic adenovirus with GM-CSF transgene  RAS-mutated peptide immunotherapy Nature of therapy  Mobilising the immune system against cancer  Targeted at most RAS-mutated cancers antigens 2  The virus makes the tumors release tumor

  8. Slide 8: Targovax has differentiated assets with orphan indications

    CANDIDATES AND PROGRAM Targovax has differentiated assets with orphan indications* Indication(s) Program Discovery Pre-clinical Phase I Phase II Phase III Pancreas cancer* TG01 Development Mesothelioma* ONCOS-102 Melanoma ONCOS-102 Colorectal cancer TG02 Exploratory Ovarian cancer* ONCOS-102 Prostat

  9. Slide 9: Current view of the clinical development program 2016 – 2018

    CANDIDATES AND PROGRAM Current view of the clinical development program 2016 – 2018 Cancer Product Study indication candidate details H1 2016 H2 H1 2017 H2 H1 2018 H2 Resected  Combinations: Gemcitabine TG01  Patients: 19 + 13 Phase I/II (ongoing) pancreas Targovax sponsor  Sites: 5 (N, UK, Esp)

  10. Slide 10: Targovax’ technologies

    Targovax’ technologies 10 CONFIDENTIAL www.targovax.com

  11. Slide 11: Solid tumors susceptible to immunotherapy and those with RAS mutations

    TARGOVAX' TECHNOLOGIES Targovax focus on: Solid tumors susceptible to immunotherapy and those with RAS mutations ONCOS: Solid tumors TG: RAS mutations Tumor type Response to CPIs High Pancreas Melanoma ~50% 50% (340,000) Initial focus Incidence of Pan-RAS mutations in cancer3 area Triple Negative Br

  12. Slide 12: Targovax has two unique and complementary technologies

    TARGOVAX' TECHNOLOGIES Targovax has two unique and complementary technologies ONCOS Lymph node Injection: The virus is injected, starts to replicate and lyse the tumor cells Result:  unique tumor antigens T-cells kill the cancer are released Response: The immune system learns to recognize the uniqu

  13. Slide 13: Cancer immunotherapies are combined to maximize efficacy

    TARGOVAX' TECHNOLOGIES Cancer immunotherapies are combined to maximize efficacy Teach the Attack the cancer Wake up the Disarm cancer’s Immuno-oncology mechanisms T-cells at the with T-cells immune system defence lymph nodes systemically Switch on GPS– Ignite engine Press the gas pedal Release brake

  14. Slide 14: Oncos Platform and clinical studies

    Oncos Platform and clinical studies 14 CONFIDENTIAL www.targovax.com

  15. Slide 15: The ONCOS Platform

    ONCOS TG TARGOVAX' TECHNOLOGIES The ONCOS Platform A vector that can be loaded with different immune modulating transgenes Virus capsid is Selective replication in modified for cancer cells inducing enhanced cancer Enhanced immune cell infection immunogenic cancer system activation cell death ∆24 bp

  16. Slide 16: Significant immunological marker activation by ONCOS-102 in Phase l study

    ONCOS TG TARGOVAX' TECHNOLOGIES Significant immunological marker activation by ONCOS-102 in Phase l study 1 Innate immune system 2 Adaptive immune system 3 Anti-tumor immune response Recognition of threat T-cell activation Immune attack Induction of proinflammatory cytokines + fever Cytotoxic molecu

  17. Slide 17: Immunological findings were linked to signals of clinical benefit

    ONCOS TG TARGOVAX' TECHNOLOGIES Immunological findings were linked to signals of clinical benefit 40% of evaluable patients showed stabilization of disease (“SD”) after 3 months RECIST1 Patient (3 months) 47% reduction in total tumor burden Tumor specific T-cells in blood = systemic effect FI1-01 Ov

  18. Slide 18: ONCOS-102 is different to Imlygic

    ONCOS TG TARGOVAX' TECHNOLOGIES ONCOS-102 is different to Imlygic ONCOS-102 is the only viral cancer immunotherapeutic shown to induce tumor specific cellular immunity in humans Imlygic (talimogene laherparepvec, T-Vec), Amgen ONCOS-102 Compound Gentically modified human herpesvirus Genetically modi

  19. Slide 19: Malignant Pleural Mesothelioma – opportunity to be 1st line treatment

    Mesothelioma Melanoma Prostate Other TARGOVAX' TECHNOLOGIES Malignant Pleural Mesothelioma (“MPM”) – opportunity to be 1st line treatment Unmet medical need MPM – Incidence cases per year1 MPM is a rare and highly malignant type of cancer in the lining of the lungs Incidences EU 5 US (thousands) Is

  20. Slide 20: ONCOS-102 in Mesothelioma – Study design

    Mesothelioma Melanoma Prostate Other TARGOVAX' TECHNOLOGIES ONCOS-102 in Mesothelioma – Study design PATIENT STUDY TREATMENT POPULATION Experimental group (n=14) Advanced ONCOS-102 (6 administrations) refractory Safety lead-in Non-randomised SoC (6 cycles) Randomised malignant (n=6) pleural GO mesot

  21. Slide 21: Opportunity to be the first immuno-therapy treating CPI refractory melanoma

    Mesothelioma Melanoma Prostate Other TARGOVAX' TECHNOLOGIES Opportunity to be the first immuno-therapy treating CPI refractory melanoma Unmet medical need Malignant melanoma – Incidence cases per year1 Most solid cancers do not respond to CPIs as the patients’ cancers manage Incidences EU 5 US (thou

  22. Slide 22: ONCOS-102 in Malignant Melanoma – Study design

    Mesothelioma Melanoma Prostate Other TARGOVAX' TECHNOLOGIES ONCOS-102 in Malignant Melanoma – Study design PATIENT POPULATION STUDY TREATMENT Non-randomised Patients with advanced Experimental group malignant melanoma n=12 not responding to CPIs CPI ONCOS-102 (every 3 weeks (3 injections) for 6 mont

  23. Slide 23: Collaboration with SOTIO a.s.

    Mesothelioma Melanoma Prostate Other TARGOVAX' TECHNOLOGIES Collaboration with SOTIO a.s. Targovax and the biotech company SOTIO a.s. will design and run a study combining ONCOS-102 and SOTIO’s dendritic cell therapy DCVAC/PCa to evaluate the safety and tolerability of the combination therapy in the

  24. Slide 24: Collaboration with Ludwig Cancer Research and the Cancer Research Institute

    Mesothelioma Melanoma Prostate Other TARGOVAX' TECHNOLOGIES Collaboration with Ludwig Cancer Research and the Cancer Research Institute Ludwig Cancer Research and the Cancer Research Institute (CRI) announced 18.11.2015 an agreement with Targovax to evaluate ONCOS-102, in early phase clinical trials

  25. Slide 25: TG Platform and clinical studies

    TG Platform and clinical studies 25 CONFIDENTIAL www.targovax.com

  26. Slide 26: The TG Platform

    ONCOS TG TARGOVAX' TECHNOLOGIES The TG Platform Peptide cocktails covering hot spot RAS codons 12 and 13 mutations 1 12 13 RAS protein amino acid (AA) sequence: MTEYKLVVVGAGGVGKSALTIQLIQ …… Codon 12 and 13 amino acid substitutions % Pancreas cancer NSC-Lung cancer Colorectal cancer Usually only one

  27. Slide 27: Promising results from ongoing Phase l/ll resected pancreas cancer clinical trial

    ONCOS TG TARGOVAX' TECHNOLOGIES Promising results from ongoing Phase l/ll resected pancreas cancer clinical trial Immunological results Boosters result in maintained TG01 T cell response Main Group TG01 specific T cell proliferation – blood samples from patient 01-002 (starting TG01 DTH1 response T

  28. Slide 28: Immunological response (DTH) to TG01 leads to increased survival

    ONCOS TG TARGOVAX' TECHNOLOGIES Immunological response (DTH) to TG01 leads to increased survival Retrospective analysis Advanced pancreatic cancer Median survival 1 year survival Evaluable TG01/GM-CSF (mono- (from 1st (from 1st patients therapy) vaccination) vaccination) Detected immune response 14

  29. Slide 29: TG01 is the only RAS-specific vaccine currently in development

    Pancreatic Colorectal TARGOVAX' TECHNOLOGIES TG01 is the only RAS-specific vaccine currently in development Unmet medical need Pancreatic cancer – Incidence cases per year (million) Most pancreatic cancer patients can not be surgically treated and has a life Incidences (thousands) EU 5 US expectancy

  30. Slide 30: TG01 in Pancreatic Cancer – Study design

    Pancreatic Colorectal TARGOVAX' TECHNOLOGIES TG01 in Pancreatic Cancer – Study design PATIENT STUDY TREATMENT POPULATION Main cohort (n=15) TG01 (36 injections) Gemcitabine (6 cycles) Safety cohort Patients with (n=6)  Non-randomised Non-randomised resected adenocarcinoma GO Concomitant cohort (n=4

  31. Slide 31: TG01 in Resected Pancreatic Cancer – ongoing trial

    Pancreatic Colorectal TARGOVAX' TECHNOLOGIES TG01 in Resected Pancreatic Cancer – ongoing trial Description Study design Phase I/II trial of TG01 and Gemcitabine as adjuvant therapy for treating Single arm open label study patients with resected adenocarcinoma of the pancreas Confirmed R0 and R1 res

  32. Slide 32: TG02 is the only other RAS-specific vaccine in development

    Pancreatic Colorectal TARGOVAX' TECHNOLOGIES TG02 is the only other RAS-specific vaccine in development Unmet medical need Colorectal – Incidence cases per year1 Incidences (thousands) EU 5 US Colorectal cancer is one of the most common malignant cancers with 5-year survival between 50% and 80% 350

  33. Slide 33: TG02 in Colorectal Cancer – Study design

    Pancreatic Colorectal TARGOVAX' TECHNOLOGIES TG02 in Colorectal Cancer – Study design PATIENT STUDY TREATMENT POPULATION Non-randomised Non-randomised Patients with PART I PART II locally advanced and reccurent n=10 n=10 GO resectable RAS mutant TG02 TG02 (8 injections TBD) rectal cancer (no. of inj

  34. Slide 34: Straight forward manufacturing and logistics

    LOGISTICS Straight forward manufacturing and logistics TG candidates ONCOS candidates Production processes for TG01, TG02, and Production process for ONCOS-102 currently GM-CSF currently being tailored and optimised being tailored and optimised Manufacturing  Highly reputed CMOs contracted Highly r

  35. Slide 35: Current view of the clinical development program 2016 – 2018

    VALUE INFLECTION POINTS Current view of the clinical development program 2016 – 2018 Cancer Product Study indication candidate details H1 2016 H2 H1 2017 H2 H1 2018 H2 Resected  Combinations: Gemcitabine TG01  Patients: 19 + 13 Phase I/II (ongoing) pancreas Targovax sponsor  Sites: 5 (N, UK, Esp)

  36. Slide 36: Expected news flow 2016 – 2018 shows multiple value inflection points

    VALUE INFLECTION POINTS Expected news flow 2016 – 2018 shows multiple value inflection points ONCOS-102 Initiate Phase l/ll Mesothelioma ONCOS-102 ONCOS-102 ONCOS-102 TG01 Signed agreements w/ Initiate Phase l Initiate Phase l/ll Initiate neoadjuvant CRI/Ludwig and Sotio Prostate Melanoma explorator

  37. Slide 37: Governance and shareholders

    Governance and shareholders 37 CONFIDENTIAL www.targovax.com

  38. Slide 38: Internationally experienced senior management team

    GOVERNANCE AND SHAREHOLDERS Internationally experienced senior management team Gunnar Gårdemyr, CEO Øystein Soug, CFO More than 30 years of international experience from the Previously CFO at Algeta, where he built up the functions pharmaceutical and biotech industry including business of Finance, I

  39. Slide 39: Experienced Board of Directors

    GOVERNANCE AND SHAREHOLDERS Experienced Board of Directors Jónas Einarsson, MD Johan Christenson, MD, Per Samuelsson Eva-Lotta Allan CEO of Radiumhospitalets PhD Partner of HealthCap Currently Chief Business Forskningsstiftelse Partner of HealthCap Officer at Immunocore Prior to joining HealthCap On

  40. Slide 40: Strong shareholder base

    GOVERNANCE AND SHAREHOLDERS Strong shareholder base Shareholder structure Shareholder No. of shares Ownership HealthCap 8,488,918 31.6% Radiumhospitalets Forskningsstiftelse 3,410,589 12.7% Datum Invest AS 2,462,000 9.2% Arctic Funds Plc 907,000 3.4% 26,858,808 ordinary shares Timmuno AS 724,650 2.7

  41. Slide 41: Unique immuno-oncology portfolio with promising data

    SUMMARY Unique immuno-oncology portfolio with promising data 1 Immuno-oncology is the fastest growing life science segment 2 Unique portfolio with promising phase I data 3 Multiple value inflection points 4 Experienced management team 5 Backed by leading life science investors 41 CONFIDENTIAL www.ta

  42. Slide 42: Appendix

    Appendix 42 CONFIDENTIAL www.targovax.com

  43. Slide 43: Appendix

    APPENDIX 43 CONFIDENTIAL www.targovax.com

  44. Slide 44: Resected pancreatic cancer: retrospective analysis showed encouraging long-term survival

    APPENDIX Resected pancreatic cancer: Retrospective analysis showed encouraging long- term survival for patients treated with TG01 or single TG peptides Combination of 2 trials with RAS peptide mono-therapy with 20 patients1 – Survival curve typical for effective immunotherapy 100 90 80 70 Survival (

  45. Slide 45: GM-CSF – Powerful immune stimulator produced in e-coli

    APPENDIX GM-CSF – Powerful immune stimulator produced in e-coli Targovax recombinant human GM-CSF produced in e-coli is a 128 amino acid protein Immune stimulator is needed Peptides used as antigens in therapeutic cancer vaccines (TCV) lack inherent immunogenicity An adjuvant or immune stimulator is

  46. Slide 46: Appendix

    APPENDIX 46 CONFIDENTIAL www.targovax.com

  47. Slide 47: Internationally renowned scientific experts supporting Targovax’s R&D

    APPENDIX Internationally renowned scientific experts supporting Targovax’s R&D Oncology viruses Pancreatic cancer Colorectal cancer Name Institution Name Institution Name Institution KAPital Consulting Lurie Comp Cancer Center of Kapil Dingra Vanderbilt University Medical Munchen, Germany Jordan Ber

  48. Slide 48: IP overview (1/2)

    APPENDIX IP overview (1/2) Patent/patent Application Priority date Status Area covered Geographic area Expiry date application date EP15172418.4 16 June 16 June Pending New peptides targeting RAS exon 4 mutations and Currently EU, but will proceed to 16 June 2015 2015 mixtures of defined RAS-mutated

  49. Slide 49: IP overview (2/2)

    APPENDIX IP overview (2/2) Patent/patent Application Priority date Status Area covered Geographic area Expiry date application date WO 2010072900 (A1) 21 December 22 December Granted / ONCOS-102 viral construct and its uses. Composition of Granted in Finland, Russia, 24 September 2009 2008 pending m

  50. Slide 50: Orphan drug designations

    APPENDIX Orphan drug designations Product Indication Granted by EMA Granted by FDA TG01 Pancreatic cancer 5 August 2011 7 June 2011 ONCOS-102 Malignant mesothelioma 16 December 2014 22 December 2014 ONCOS-102 Ovarian cancer 29 April 2014 17 March 2014 ONCOS-102 Soft tissue sarcoma 19 June 2013 24 Ju

  51. Slide 51: Partnership and collaboration strategy

    APPENDIX Partnership and collaboration strategy Not actively pursuing out-licensing opportunities prior to Proof-of-Concept, but ready to react opportunistically to prospects with good terms to maximize shareholder value Build on existing strong relationship with well-known research centers in Europ

  52. Slide 52: Definitions and glossary of terms

    APPENDIX Definitions and glossary of terms Immuno-oncology is treatment that uses the body's own immune system to fight cancer Immune response is how the body recognizes and kills threats that appear foreign or harmful such as bacteria, virus or cancer cells T cells are cells of the immune system th

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