Noxopharm Ltd. · ASX:NOX

Noxopharm — Shareholder Meeting (November 2018)

80 slides from Noxopharm's shareholder meeting presentation, Nov 21, 2018

1. Slide 1: Noxopharm 2018 Annual General Meeting Presentations

   Date: 21 November 2018 Sydney, Australia For personal use only ASX: NOX ASX Limited Noxopharm Limited 20 Bridge Street SYDNEY NSW 2000 ABN 50 608 966 123 Registered Office and NOXOPHARM 2018 ANNUAL GENERAL Operational Office: Suite 3, Level 4 MEETING PRESENTATIONS 828 Pacific Highway Gordon NSW 2072

2. Slide 2: Forward Looking Statements

   Investor & Corporate Enquiries: Company Secretary: Prue Kelly David Franks M: 0459 022 445 T: +61 2 9299 9690 E: info@noxopharm.com E: David.Franks@automicgroup.com.au www.noxopharm.com Forward Looking Statements This announcement may contain forward-looking statements. You can identify these statem

3. Slide 3: Letter to Shareholders

   For personal use only 21 November 2018 Dear Shareholders I am pleased to report on a year of considerable activity and growth, with the next year emerging as one of even greater activity and growth. While the past year has had its share of delays, there also have been some unexpected advances. Such

4. Slide 4: Letter to Shareholders (continued)

   With the Company transiting from an early-stage clinical phase to a pre-commercial phase, that means needing to bring onboard additional expertise. The appointment of Dr Greg van Wyk as our Chief Medical Officer is the first of a number of For personal use only steps in that transition. Greg brings

5. Slide 5: 2018 Annual General Meeting

   For personal use only 2018 Annual General Mee/ng DISCOVER DEVELOP DELIVER ASX: NOX 1

6. Slide 6: Disclaimer

   Disclaimer For personal use only This presentation has been prepared by Noxopharm Limited (NOX or the Company). It should not be considered as an offer or invitation to subscribe for or purchase any shares in NOX or as an inducement to purchase any shares in NOX. No agreement to subscribe for securi

7. Slide 7: Noxopharm at-a-glance

   Noxopharm at-a-glance For personal use only • Australian biotechnology company. Offices Sydney, New York, Hong Kong • Playing to our strength…. isoflavonoid drug plaEorm • Aiming to bring Veyonda® to market as a first-in-class companion drug to radiotherapy • Mixture of out-licensing and in-house sales/

8. Slide 8: DARRT: Broad Potential Utility In Solid Tumors

   Veyonda® DARRT: Broad PotenIal UIlity In Solid Tumors For personal use only PROGRAM STRATEGY 2018/2019 DARRT DARRT-1 DARRT-2 DARRT-3 DARRT-4 Prostate cancer Lung cancer Sarcomas Brain cancer (GBM) (current) Q1 2019 Q1 2019 Q3 2019 Major need. Early Major need. Lung Very limited treatment Major need.

9. Slide 9: Strategy For Bringing Veyonda To Market

   Strategy For Bringing Veyonda® To Market For personal use only Primary focus on prostate cancer and sarcoma. Aim for marketing applications for each indication, but sarcomas and other rare cancers (eg cholangiocarcinoma) could be faster path Sarcomas (and rare cancers generally) offer Fast-Track App

10. Slide 10: Veyonda Pre-Commercial Planning

    Veyonda® Veyonda® Pre-Commercial Planning For personal use only Clinical and Regulatory Affairs: ☑ Team in place (CMO: Dr Greg van Wyk) Experienced big pharma medical officer driving strategy and opera7ons. Manufacture: ☑ Experienced big pharma manufacturing team appointed (Dr Lara Babich) ☑ Large-scal

11. Slide 11: Potential commercial value of a radio-enhancer

    Potential commercial value of a radio-enhancer Veyonda® For personal use only DARRT § Long identified need by radiation oncologists and health regulators. § Potential to shift effect of radiotherapy (RT) from mostly palliative to curative. § Potential to allow use of RT in tumors where RT not curren

12. Slide 12: NOX technologies allowing therapeutic potential of isoflavonoid drugs

    NOX technologies finally allowing therapeutic For personal use only potential of isoflavonoid drugs to be exploited Target iden,fied Best fi0ng drug designed LIPROSE delivery technology ensures effective blood levels of active drug and ability to cross blood-brain barrier 8

13. Slide 13: Pipeline

    Pipeline For personal use only DISCOVERY PRE-CLINICAL PHASE 1b CLINICAL® Veyonda® Radio-enhancement DARRT Veyonda® Radio-enhancement LuPIN Veyonda® Chemo-enhancement CEP PRE-CLINICAL NYX-104 Neuro-protection NYX-205 Peripheral neuropathy NYX-330 LDL-lowering DISCOVERY Inflammatory/autoimmunity casca

14. Slide 14: Veyonda Radiotherapy & Chemo-enhancement

    Veyonda® Radiotherapy For personal use only & Veyonda® Chemo-enhancement Two clinical programs PHASE 1 PHASE 2 Veyonda® Radio-enhancement DARRT Program DARRT - Direct and Abscopal Response to RadioTherapy Veyonda® Radio-enhancement LuPIN Program LuPIN - 177LuteIum-PSMA-617 In CombinaIon with Veyonda

15. Slide 15: Veyonda DARRT Program

    Veyonda® DARRT For personal use only 9 Veyonda® DARRT Program Purpose: § Provide greater shrinkage of irradiated tumors § + shrinkage of non-irradiated tumors (‘abscopal response’) Advantages: § Allowing radiotherapy to be used with cancers (eg. sarcomas) where radiotherapy not commonly used current

16. Slide 16: DARRT treatment regimen

    Veyonda® DARRT For personal use only DARRT – A treatment regimen intended for pa8ents with late- stage solid cancers who are eligible for pallia8ve radiotherapy Maximising death of Prepares cancer cell cancer cells by blocking DNA for maximum repair of DNA. Blocking post-radia8on radia8on damage. DN

17. Slide 17: DARRT – Anticipated Clinical Benefits

    DAART – Anticipated Clinical Benefits Veyonda® DARRT For personal use only 9 DIRECT RESPONSE ABSCOPAL RESPONSE At a minimum, Veyonda® is expected to lead to The best expected outcome would be an improved be7er DIRECT responses to radiotherapy by DIRECT response, plus an ABSCOPAL response funcAoning

18. Slide 18: The Abscopal Response

    Veyonda® DARRT The ‘ABSCOPAL RESPONSE’ For personal use only An ABSCOPAL RESPONSE refers to an an--cancer effect in tumors outside of the field of radia9on An abscopal response can have the following response spectrum: Ø Stable disease - <30% shrinkage; no new tumors Ø Par9al abscopal response - >30%

19. Slide 19: An Abscopal Response Can Be Induced Deliberately

    An Abscopal Response Can Be Induced Deliberately Veyonda® For personal use only 9 DARRT Abscopal responses now recognized as a likely quantum leap forward in the treatment of cancer. Cancer cell damaged by Up to 2010, very rare phenomenon radia8on and dies ….. Since then, the introduc8on of immuno-o

20. Slide 20: DARRT-1: Phase 1b clinical trial in late-stage prostate cancer

    DARRT-1: Phase 1b clinical trial evalua<ng the safety and efficacy of Veyonda® For personal use only Veyonda® in men with late-stage prostate cancer who are eligible for 9 DARRT pallia<ve (low dose) radia<on for pain and symptom management Objec<ves: • To determine safety of Veyonda® + radiotherapy ac

21. Slide 21: Comments on Preliminary DARRT-1 Data

    Comments on Preliminary DARRT-1 Data Veyonda® For personal use only 9 ! Note: All pa*ents entered study with late-stage, metasta*c, progressive disease with no remaining treatment op*ons. Historical survival of such pa*ents is 3-6 months. ! Note: Pa*ents are receiving a pallia*ve dose (20 Gy) of rad

22. Slide 22: DARRT-1: Early Clinical Evidence of Durable Halt to Disease Progression

    DARRT-1: Early Clinical Evidence of Durable Halt to Disease Progression Veyonda® For personal use only Scheduled Dec 9 DARRT 12 weeks 24 weeks Stable Disease and Par2al Response determined by Cohort 1: 400 mg Veyonda® RECIST (Response Evalua-on Criteria in Solid Tumors) • Pa2ent 1 Stable Stable • Pa

23. Slide 23: DARRT-1 Data Read-outs

    Veyonda® DARRT-1 Data Read-outs For personal use only 9 DARRT Cohorts 1, 2 and 3 Cohorts 1, 2 and 3 Cohort 4 6- & 12-week assessments 24-week assessments 12-week assessments End Q1 End of Dec 2018 2019 Q2 2019 Company planning to report 6-week and interim 12- and 24-weeks data from Cohorts 1-3 by ye

24. Slide 24: Preparing for Veyonda clinical program and eventual marketing

    Preparing for Veyonda® clinical program and eventual marke7ng For personal use only Hong Kong office. Outreach to China and SE Asia: • Clinical collaborations • Commercial relationships US office. Exposure to: • US investor markets • Pa:ents/doctors ahead of trials and marke:ng • Outreach to collabora

25. Slide 25: Veyonda LuPIN Program

    Veyonda® For personal use only Veyonda® LuPIN Program 9 LuPIN PSMA-617 is a pep2de that recognizes and targets prostate specific membrane an2gen (PSMA). 85-90% cases of prostate cancer are PSMA +ve Lu-PSMA-617 links radioac2ve lute2um isotope to PSMA- 617, delivering radioac2vity directly to prostate

26. Slide 26: Novartis-Endocyte Deal Shows Growing Interest in Radiopharmaceuticals

    Novar&s-Endocyte Deal Shows Growing Interest Veyonda® For personal use only 9 in Radiopharmaceu&cals and Lu-PSMA LuPIN Novar's pending acquisi'on of EndoCyte for $2.1 billion Provides Novar's access to 177 Lu-PSMA-617 (Lu-PSMA) currently being evaluated by Endocyte in a Phase 3 registra'onal study f

27. Slide 27: LuPIN: Phase 1b dose finding study with Lu-PSMA-617

    LuPIN: Phase 1b invesCgator-iniCated dose finding study evaluaCng Veyonda® For personal use only the safety and efficacy of Veyonda® in combinaCon with Lu-PSMA-617 in LuPIN men with advanced, metastaCc castrate-resistant prostate cancer Patients: Late-stage disease. No remaining standard treatment opti

28. Slide 28: LuPIN Program Rationale

    Veyonda® LuPIN Program RaRonale For personal use only 9 LuPIN That combining Veyonda® with Lu-PSMA-617 will: • Boost the cancer cell-killing effect of Lu-PSMA-617 • Improve the response rates to Lu-PSMA-617 • Mean that the majority of men will complete their full 36-week treatment course (compared to

29. Slide 29: Veyonda CEP Program

    Veyonda® For personal use only Veyonda® CEP Program 9 CEP Ra'onale: • Idronoxil sensi'ses cancer cells to pla'num drugs (carbopla'n, cispla'n, oxalipla'n) by > 2000x • Restores sensi'vity to pla'num drugs in cancers that have become highly drug-resistant • Allows lower dosages of pla'num drugs to be

30. Slide 30: Veyonda CEP-1 Phase 1b Study

    Veyonda® For personal use only Veyonda® CEP-1 Phase 1b Study 9 CEP Headline results: • 19 pa4ents with solid cancers that had stopped responding to therapy including carbopla4n • Pa4ents entered study with progressive disease • Given Veyonda® (400 or 800mg) + carbopla4n (50% or 75% normal dose) • No

31. Slide 31: Pre-Clinical Pipeline

    Pre-Clinical Pipeline For personal use only DISCOVERY PRE-CLINICAL NYX-104 Neuro-protec=on NYX-205 Peripheral neuropathies NYX-330 LDL-Lowering CARDIOVASCULAR AUTOIMMUNITY CANCER 27

32. Slide 32: Three first-in-class drug candidates

    Three first-in-class drug candidates aiming to meet significant For personal use only unmet medical needs NYX-104 NYX-205 NYX-330 STATUS: Lead op*miza*on Lead confirmed Lead op*miza*on First-in-class neuro-protectant First-in-class an?-inflammatory First-in-class small molecule PCSK9 for peripheral neur

33. Slide 33: Drug Discovery Program IRAK4 and TPL2

    DRUG DISCOVERY PROGRAM IRAK4 AND TPL2 For personal use only Involved in: Chronic inflammatory diseases: • Ankylosing spondyli7s • Pulmonary fibrosis Autoimmune diseases: • Rheumatoid arthri7s • Psoriasis • Lupus • IBD, ulcera7ve coli7s • Motor neurone disease N2a neuronal cell culture Cancer: • B-cell

34. Slide 34: NOX Isoflavonoid Technology Platform

    NOX Isoflavonoid Technology Pla7orm For personal use only Major opportunity to develop highly selec?ve IRAK4 and TPL2 inhibitors Targets Inflammation Autoimmunity Cancer Existing inhibitors and Competition IRAK4 ++ +++ ++ Compound name: PF-06650833 Diabetes, Rheumatoid arthritis, Company: Pfizer Athe

35. Slide 35: Expected Upcoming Milestones

    Expected Upcoming Milestones For personal use only Dec 2018 DARRT 12-week assessments (Cohorts 1,2,3) 1Q 2019 DARRT 24-week assessments (Cohorts 1,2,3) 1Q 2019 Completion of LuPIN-1 enrolment 1Q 2019 Initiation of DARRT-2 (lung cancer) 1Q 2019 Initiation of DARRT-3 (sarcomas) 1Q 2019 DARRT 12-week a

36. Slide 36: Experienced Leadership Team

    Experienced Leadership Team For personal use only Executive Title Prior Experience Novogen, Marshall Graham Kelly, PhD Founder and CEO Edwards Inc (MEIP) Greg van Wyk, MD Chief Medical Officer Eli Lilly Chief Scientific Officer John Wilkinson PhD Biotron (Oncology) Chief Scientific Officer James Bon

37. Slide 37: Key metrics

    Key metrics For personal use only 24 Number of Shares 121.9M : Free float 66.8% Market Cap (1 Nov 2018) AU$73M CEO IPO price 20 cents Directors 12 month high/low $1.80/0.48 Other founders8 Others Average daily turnover $0.54M Cash position AU$ 9.6 (30 Sept 2018) 33

38. Slide 38: Dr. Graham Kelly, Chief Executive Officer

    For personal use only Dr. Graham Kelly Chief Executive Officer graham.kelly@noxopharm.com DISCOVER DEVELOP DELIVER ASX: NOX 34

39. Slide 39: Theranostics

    For personal use only THERANOSTICS Dr Nat Lenzo BMedSci(Hons) MBBS MMed EMBA FRACP FAANMS Clin. Assoc. Prof. in Medicine - Dept. of Medicine, University of WA Hon Fellow in Medicine - Macquarie University, Sydney NSW General Physician & Nuclear Physician

40. Slide 40: Theranostics

    For personal use only Theranostics

41. Slide 41: Theranostics

    Theranostics For personal use only •September 25, 1998 - key day • FDA granted simultaneous approval for Genentech’s Herceptin® for the treatment of Stage IV breast cancer and Dako’s HercepTest® for diagnosis of Her2 overexpression

42. Slide 42: Theranostics in Nuclear Medicine

    Theranostics in Nuclear Medicine For personal use only •Not a new paradigm •Dr S Seidlin (1895-1955) Montefiore Hospital New York City 1943 • Radioactive iodine (I-131) for metastatic thyroid cancer •Tracer dose followed by therapeutic dose • Low dose I-131 or I-123 still used

43. Slide 43: Thyroid Cancer

    Thyroid Cancer For personal use only Ablative Dose Image 1 year later

44. Slide 44: Targeted Radionuclide Therapy

    Targeted Radionuclide Therapy For personal use only • Benefits • Higher radiation dose deposited directly to target tissue (10-100x greater than external beam) • Decreased toxicity to adjacent tissue – short pathway • Selective targeting possible – e.g. anti-CD20, SSTR • Dosimetry possible • Can com

45. Slide 45: Radionuclide isotopes

    1-131 Sm-153 Re-186 2. 58d beta/gamma 8.04d beta/gamma 1.95d_ beta/gamma 3.8d beta/gamma ie id beta beta/garmma ‘beta/gamma 2.67 beta GenesisCare

46. Slide 46: Radionuclide Therapy

    For personal use only Radionuclide Therapy

47. Slide 47: Personalised Medicine, Theranostics & Radiopeptide Therapy

    PERSONALISED MEDICINE, THERANOSTICS & RADIOPEPTIDE THERAPY (RPT) For personal use only Therapy Diagnostics Ga68 Theranostics Lu177 Targeted Molecular therapy receptor

48. Slide 48: Gallium PET Radiotracers

    Gallium PET Radiotracers For personal use only Germanium - Gallium 68 Generators

49. Slide 49: For personal use only

    For personal use only

50. Slide 50: Gallium-68 Products

    Gallium-68 Products For personal use only •Gallium Citrate •Gallium MAA •Gallium DTPA •Gallium Octreotate •Gallium PSMA •Gallium Pentixafor •Gallium Herceptin •Gallium Exendin •Gallium Satareotide •Etc.

51. Slide 51: Ga-68/Lu-177 octreotate

    Ga-68/Lu-177 octreotate For personal use only

52. Slide 52: Metastatic Insulinoma Treated with Lu-177 octreotate

    Metastatic Insulinoma Treated with Lu-177 octreotate For personal use only A. Initial B. 4 months C. 9 months after treatment (Ong, Henley, Hurley, Turner et al. Eur J Endocrinol May 1, 2010 162 1001-1008)

53. Slide 53: Netter I Study

    Netter I Study AAA For personal use only • Lu-177 octreotate vs sandostatin (standard of care)

54. Slide 54: NETTER-1 Trial

    NETTER-1 Trial For personal use only (c) Copyright 2014 SNMMI; all rights reserved Jonathan Strosberg et al. J Nucl Med 2016;57:629

55. Slide 55: Lutathera approvals and Novartis tender offer

    For personal use only September 29, 2017 Advanced Accelerator Applications Announces European Approval of Lutetium (177Lu) Oxodotreotide (Lutathera®) for Gastroenteropancreatic Neuroendocrine (GEP-NET) Tumors – Completes First Thera(g)nostic Radiopharmaceutical Pairing in Oncology October 30, 2017 A

56. Slide 56: Prostate cancer imaging with PSMA-ligands

    Prostate cancer imaging with PSMA-ligands For personal use only •PSMA: prostate-specific membrane antigen • cell surface protein with overexpression in prostate cancer •transmembraneous localization including large extracellular part • promising target for prostate cancer specific imaging and therap

57. Slide 57: For personal use only

    For personal use only

58. Slide 58: Why the explosion?

    Why the explosion? For personal use only • Prostate cancer • Worldwide problem - approx. 20 000 cases diagnosed annually in Australia; more than 300 000 new cases annually in Europe • Approx. 1.4 million men die worldwide yearly; 4th most common cause of cancer death worldwide • Most common cancer d

59. Slide 59: Status of PCa treatments –EJNM 2015

    Status of PCa treatments –EJNM 2015 For personal use only

60. Slide 60: Lutetium-177 PSMA

    For personal use only Lutetium-177 PSMA

61. Slide 61: Systemic radioligand therapy with 177Lu-PSMA-I&T

    Systemic radioligand therapy with 177Lu-PSMA-I&T in patients with metastatic castration-resistant prostate cancer. H. Wester & M. Schwaiger Munich March 2016 For personal use only Material and Methods 22 mCRPC patients treatment failure with both chemotherapy and novel androgen- receptor targeted th

62. Slide 62: Lu-177 PSMA in Treatment

    24 Lu-177 PSMA in Treatment For personal use only [(177)Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Ping Thang S, Akhurst T, Iravani A, K

63. Slide 63: Proof of Concept study shows PSA response

    Proof of Concept study shows PSA response in 29 out of 30 patients For personal use only SNMMI Image of the Year: 68Ga-PSMA-11 PET maximum intensity projection (MIP) images at baseline and three months after 177Lu-PSMA-617 in eight patients with PSA decline > 98 percent. 25 Source: Endocyte Inc Hofm

64. Slide 64: Lu-177 PSMA in Treatment

    26 Lu-177 PSMA in Treatment For personal use only • 177Lu-PSMA has been used safely in advanced metastatic prostate cancer patients (>3000 worldwide – mostly Germany) with promising results. • Theranostics Australia – Hollywood Private Hospital and Macquarie University Hospital Sydney. ~200 patients

65. Slide 65: Lu-177 PSMA Side Effects

    27 Lu-177 PSMA Side Effects For personal use only •10-15% nausea •10-15% bone “flare” •Transient mouth dryness •Tiredness •Bone marrow dysfunction – usually self limiting •Financial toxicity!

66. Slide 66: Mr J – cycles

    Mr J – 3 cycles: 17 GBq For personal use only

67. Slide 67: Mr J – cycles

    For personal use only Mr J – 3 cycles: 17 GBq

68. Slide 68: Mr J – cycles

    Mr J – 3 cycles: 17 GBq For personal use only Lenzo, Meyrick and Turner. Diagnostics. 2018 Feb 11;8(1).

69. Slide 69: Video

    For personal use only •VIDEO 1 •VIDEO 2 CONFIDENTIAL

70. Slide 70: For personal use only

    For personal use only 32

71. Slide 71: For personal use only

    For personal use only 33

72. Slide 72: Lu-PSMA trial and deal timeline

    February 06, 2017 | First U.S. Multi-center Investigational Clinical Trial of 177 Lu PSMA-617 Targeted Radioligand Therapy in For personal use only Metastatic Castration Resistant Prostate Cancer Receives FDA Clearance Source: RadioMedix Inc. November 2017 / Endocyte Announces Exclusive Worldwide Li

73. Slide 73: The GenesisCare Theranostics Team

    The GenesisCare Theranostics Team For personal use only Bernard Phelan Assoc. Prof Nat Lenzo Dr. Danielle Meyrick David Macfarlane Julie Crouch General Manager Nuclear Medicine Physician Radiochemist Nuclear Medicine Physician Operations Manager Theranostics Clinical Director Chief Scientist Therano

74. Slide 74: Theranostics Strategy

    Theranostics Strategy – become the leading private provider of theranostics treatments and as a respected clinical research partner For personal use only Lead the way in GC supports new Clinical Trials revenue providing treatment to agents coming to support funding of GC patients in need market thro

75. Slide 75: Established partnerships supporting bringing theranostics agents to market

    Established partnerships supporting bringing theranostics agents to market For personal use only Queensland University

76. Slide 76: Theranostics Clinical Trials at Genesis Care

    Theranostics Clinical Trials at Genesis Care For personal use only • Ipsen OPS201 – Lu-OPS201 in somatostatin receptor positive neuroendocrine tumours • TARGET – A GC sponsored and funded RCT. External Beam Radiation Therapy (EBRT) Alone versus EBRT in Combination with 177Lu-PSMA in Patients with Bi

77. Slide 77: NETTER-1 RCT 177Lu-OCT PRRT

    NETTER-1 RCT 177Lu-OCT PRRT PROGRESSIVE MID-GUT NET For personal use only n CR % PR % SD % PD % PFS (m) 1 Control 113 0 3 42 68 8.4 1 PRRT 116 1 17 75 23 NR (@ 20) 2 PRRT 94 1 30 53 10 24 3 PRRT/ 15 13 13 67 7 31 CAP/TEM 1. Strosberg J et al. N Engl J Med 2017:376;125-135 2. Brabander T, Kwekkeboom

78. Slide 78: Combination PRRT-Chemotherapy

    COMBINATION PRRT-CHEMOTHERAPY PROGRESSIVE PANCREATIC NETS For personal use only 177Lu-OCT-CAPECITABINE-TEMOZOLOMIDE n CR % PR % SD % PD % PFS (m) 1 PRRT 66 3 55 23 15 31 2 PRRT 30 13 67 20 0 48 CAP/TEM 1. Brabander T, Kwekkeboom DJ. Clin Cancer Res 2017 2. Claringbold PG, Turner JH. Cancer Biother R

79. Slide 79: The Future of Theranostics

    The Future of Theranostics Actinium-225 PSMA Lu-177 PSMA failure For personal use only • No longer a ‘cottage industry’ • New molecules with multiple-tumour indications developed by multinational companies • Registered and reimbursed products coming on line • Comprehensive clinical trials programs s

80. Slide 80: Thank you

    For personal use only Thank you 42 20/11/2018 CONFIDENTIAL

Noxopharm — Shareholder Meeting (November 2018) on 6ix