NfP2X 7 - The Biosceptre Immuno-Oncology Platform - Systemic Antibodies, Topical Antibody Therapeutics - Peptide Vaccine Therapy

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NfP2X 7 - The Biosceptre Immuno-Oncology Platform - Systemic Antibodies, Topical Antibody Therapeutics - Peptide Vaccine Therapy
The Biosceptre Immuno-Oncology Platform

- Systemic Antibodies,
- Topical Antibody Therapeutics
- Peptide Vaccine Therapy

                   targeting

               nfP2X7                                     A Broadly Occurring
                                                          and High Specificity
                                                             Cancer Target
   Q3 2016
                               Commercial in Confidence
NfP2X 7 - The Biosceptre Immuno-Oncology Platform - Systemic Antibodies, Topical Antibody Therapeutics - Peptide Vaccine Therapy
Disclaimer

This presentation has been prepared by Biosceptre International Limited and its affiliates (the Biosceptre Group). The
information contained in this presentation is for informational purposes only. The information contained in this presentation
is not investment or financial product advice and is not intended to be used as the basis for making an investment
decision. This presentation does not constitute an offer or invitation in respect of any sale or purchase of securities. This
presentation has been prepared without taking into account the investment objectives, financial situation or particular
needs of any particular person. Past performance is no guarantee of future performance.

No representation or warranty, express or implied, is made as to the fairness, accuracy, completeness or correctness of
the information, opinions and conclusions contained in this presentation. A number of statements in this presentation have
been based on internal estimates by the Biosceptre Group and have not been independently verified. To the maximum
extent permitted by law, none of the Biosceptre Group and their respective directors, officers, employees, contractors or
agents, nor any other person accepts any liability, including, without limitation, any liability arising out of fault or
negligence, for any loss arising from the use of the information contained in this presentation. In particular, no
representation or warranty, express or implied, is given as to the accuracy, completeness or correctness, likelihood of
achievement or reasonableness of any forecasts, prospects or returns contained in this presentation. Such forecasts,
prospects or returns are by their nature subject to significant uncertainties and contingencies. Actual future events may
vary from these forecasts and you are cautioned not to place undue reliance on any forward looking statement.

The statements in this presentation are made only as at the date of this presentation unless otherwise stated and remain
subject to change without notice. None of the Biosceptre Group and their respective directors, officers, employees,
contractors or agents, nor any other person accepts any obligation to correct or update any information in this
presentation.

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Biosceptre Highlights
Broadly Occurring           •   nfP2X7 identified on the surface of >20 human cancer types.
Validated Target            •   Plays a role in cancer cell survival and proliferation distinct from functional P2X 7

Highly                      •   Biosceptre targets nfP2X7, a receptor critical for cancer cell survival found only on cancer cells.
Specific                    •   Targeting a broad range of cancers including but not limited to lung, breast, prostate and colorectal

                            •   fully human domain antibody for systemic use
3 Therapeutics in                                                                                Single target therefore synergy for
                            •   polyclonal sheep antibody for topical application
Pipeline                    •   peptide-protein conjugate vaccine therapeutic
                                                                                                   mechanism, safety and efficacy

                            •   Indication of efficacy
1 Clinical Trial Complete   •   Excellent human safety
                            •   Validating data supports other products in pipeline

Comprehensive IP
                            13 Granted US patents – global portfolio - various patents from 2022 to 2035
platform

                            •   Safety indicated in humans and appropriate toxicology studies
De-risked and Tractable
                            •   GMP production processes established

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NfP2X 7 - The Biosceptre Immuno-Oncology Platform - Systemic Antibodies, Topical Antibody Therapeutics - Peptide Vaccine Therapy
Science Team

                Shaun McNulty PhD
                Chief Science Officer

 20+ years of experience in Pharmaceutical and Biotech - target identification, drug discovery, portfolio
 management & commercial development for GSK, Pfizer, ImmBio and Syntaxin.

               Julian Barden PhD                      Dr. Angus                              David Chin PhD
               Director of Research                   Gidley-Baird PhD                       Director
                                                      Scientific Director                    Bio Production

 30+ years experience in protein        25+ years research and lecturing       20+ years experience Ops Manager for
 structure analyses, molecular          University of Sydney, 20 + years       National Biologics Facility, Australian
 modeling, protein function studies &   experience in biotech and biomedical   Institute for Bioengineering and
 antibody design – work in calcium      business, Researcher Director of 3     Nanotechnology. 300+ commercial and
 regulation, purinergic receptor        listed companies.                      research projects, Budget +$30m, 30
 structure, cancer diagnostics                                                 collaborations,
 &immunotherapeutics.
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Science Advisory Board

           Dr Sir Gregory Winter
           CBE, FRS, FMedSci, HonFRCP
           • Master of Trinity College, Cambridge University
           • Pioneer of humanised antibodies, phage display technology, founder CAT and
             Domantis
           • Recipient of numerous awards and honours
           Photo Credit: Aga Machaj

           Professor Terence Rabbitts
           FRS, FMedSci
          • Professor of Molecular Biology at the University of Oxford
          • Pioneer of cDNA cloning, antibody gene mapping, oncogene family
            identification

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NfP2X 7 - The Biosceptre Immuno-Oncology Platform - Systemic Antibodies, Topical Antibody Therapeutics - Peptide Vaccine Therapy
Clinical Advocates

Dr. Bob Li                              Prof. Gavin Marx                              Ass. Prof Nick Pavlakis           Dr Tom Borody
MBBS, BSc (Med)                         BSc (Med) MBBS (Hons)                         BSc, MBBS MMed (Clin. Epi)        BSc (MED) (HONS), MBBS (HONS),
MPH, FRACP                              FRACP                                         PhD FRACP                         MD, PhD, FRACP, FACG, FACP,
                                                                                                                        AGAF

Attending Medical                       Head Chair of the Section of                  Head of the Department of
                                                                                                                        Founder and Medical
Oncologist and Clinical                 Oncology at the SAN                           Medical Oncology, Royal
                                                                                                                        Director of Center for
Investigator at Memorial                                                              North Shore Hospital,
                                                                                                                        Digestive Disease
Sloan Kettering Cancer                  Director of the SAN Clinical                  Sydney
Center                                  Trials Unit
                                                                                                                        Reviewer for medical journals, the
                                                                                      Chair of the Scientific
                                                                                                                        American Journal of
ASCO Young Investigator Award           Clinical Director of the SAN                  Advisory Committee of the
American Society of Clinical Oncology                                                                                   Gastroenterology, Digestive
and Conquer Cancer Foundation           Integrated Cancer Centre                      Australasian Lung Cancer          Diseases & Sciences and The
ASCO Merit Award
                                                                                      Trials Group                      Journal for Gastroenterology and
American Society of Clinical Oncology   Associate Professor at the University                                           Hepatology and Digestive and
and Conquer Cancer Foundation           of Sydney                                     Director of the Northern Sydney   Liver Diseases.
                                                                                      Cancer Trials Network

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Executive Team

              Gavin Currie
              Chief Executive Officer

Appointed in October 2012, Board member since 2009. Previously head of a family investment fund with a
biotech focus. Significant experience in M&A, integrating businesses post transaction, cross-border transactions
and investments.

              Daniel Barton                                                                   Brad Miller
              Director Investor Relations                                                     Commercial & Legal Manager
B.Sc (Biochem) LLB – 20 years experience in marketing and                      5+ years with a private international investment fund. Financial
communications across a range of industries. Has managed start ups             management and legal documentation, cross-border transactions
through to acquisitions & board level reporting duties in listed               including mergers and acquisitions, debt financing and equity
companies. Non Executive Board membership experience.                          investments, primarily in the life sciences sector.

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NfP2X 7 - The Biosceptre Immuno-Oncology Platform - Systemic Antibodies, Topical Antibody Therapeutics - Peptide Vaccine Therapy
OurnfP2X
The  target: nfP2X7
          7
target
                                                                                                        Exposed
                                                                                                      nfP2X7 target

      Normal                                            Abnormal
       trimer                                            trimer
    conformation                                      conformation

P2X7 is a ligand-gated non-selective cation channel          Some forms of P2X7 can not form a large molecular
                                                             weight pore in response to ATP.
P2X7 forms a trimer which opens an ion channel in
response to rapid stimulation and opens a large              These we term nfP2X7 (non functional) BUT critical
molecular weight pore in response to prolonged               signalling functionality is retained
ATP stimulation

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NfP2X 7 - The Biosceptre Immuno-Oncology Platform - Systemic Antibodies, Topical Antibody Therapeutics - Peptide Vaccine Therapy
Pipeline
     Product        Approach                   Indication            Discovery   Pre-clinical      Phase I    Phase II

   CLINICAL PROGRAMS

     BIL03s    Domain Ab               Solid tumours                                        2H16

     BIL06v    Peptide Vaccine         Solid tumours                                        2H16

    BIL010t    Polyclonal Ab           Basal cell carcinoma                                            2H16

   DISCOVERY PROGRAMS

    BIL011t    Topical dAb

     BIL04s    Next gen. systemic monoclonal

     BIL07v    Next gen. peptide vaccine

     BIL03n    Conjugate candidate

    BPM09      IHC Antibody [Diagnostics]

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NfP2X 7 - The Biosceptre Immuno-Oncology Platform - Systemic Antibodies, Topical Antibody Therapeutics - Peptide Vaccine Therapy
Broad Human
Therapeutic Potential
                                 BPM09
                    BIL03s      Diagnostic                       BIL06v
                   Domain Ab        Ab                           Peptide
                                                                Conjugate

         Antibody
             BIL010t                                                   Vaccine
            Polyclonal

                 BIL03s                                               Peptide
                  ADC

                                                                      Dendritic
              Bispecifics

                               Car-T                       NK

                                          Cell                                     *Current
                                                                                  Biosceptre
                                                                                    Activity

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Normal P2X7 – 2 pore states
  State dependent on ATP concentration

             +               small   +++                  large
            ATP              pore    ATP                  pore

                    Normal                     Normal
                     Cell                       Cell

                                                                   Cell
                                                                  death
             Moderate Ca2+ influx        Large molecule influx
                                         Significant Ca2+ entry
    Ca2+          proliferation             Membrane
   Large
molecules          signalling              depolarisation
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nfP2X7 and Cancer
  Loss of response to high ATP concentration

                                                                      Increased
                                                                     proliferation
             +               small   +++                   NO
                                                                      & survival        Cancer
                                                          large
            ATP              pore    ATP                  pore
                                                                                         Cell

                                                                            Cancer
                                                                             Cell

                                              nfP2X7
                    Normal
                                             expressing                                Cancer
                     Cell                       Cell                                    Cell
                                                                            Cancer
                                                                             Cell

             Moderate Ca2+ influx        Large molecule influx      X                Metastatic
                                         Significant Ca2+ entry                      Potential
    Ca2+          proliferation               aberrant            No Cell
   Large
molecules          signalling         proliferation signalling    Death
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BPM09 Binds to Multiple Tumours

                                                                              9
                                   100
                                                                                                              13                               PDX                      IHC on FFPE tumour sections
                                                                                                                                               T u m o u r b io p s y   Performed by External Lab
                                                                                  66

                                                                                                                                                                        50% global
   % p o s it iv e s t a in in g

                                             6                                                                      3
                                                                         13
                                                         65
                                                                                                7

                                    50
                                                 8             50                                                       12
                                                                                                                                                                        average
                                                                    3                                                                                    46

                                                                                          58                                         18
                                                                                                                                               24
                                                                                                    54
                                                     12                                                                                                                 IHC on PDX derived section
                                                                                                          1                                                             performed by Oncotest
                                     0

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                                    Number of samples tested for a given cancer shown above bars
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nfP2X7 Mediates Survival in Multiple Cancer Cell Lines
                                                  Large pore   P2X7 siRNA induced death
      Cell line   Tumour origin
                                                   opening        A               B
        PC3                                              No       Yes            Yes
       Du145         Prostate                            No       Yes            Yes
       LNCaP                                             No       Yes            Yes
      SK MEL 28                                          No       Yes            Yes
                    Melanoma
      SK MEL 5                                           No       No             No
        PC 9                                             No       Yes            Yes
        H460          Lung                               No       Yes            Yes
        H520                                             No       Yes            Yes
       MCF7           Breast                             No       Yes            Yes
      SK N AS                                            No       Yes            Yes
                  Neuroblastoma
        Kelly                                            No       Yes            Yes
      MiaPaCa2      Pancreas                             No       No             No

       HCT116       Colorectal                           No       Yes            Yes

       HT1080     Fibrosarcoma                           No       Yes            Yes

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Clinical Plans

           Topical                 Systemic             Therapeutic
         Therapeutic               Antibody               Peptide
             BIL010t                   BIL03s               BIL06v

        Phase 1b/2 Q4 2016     Phase 1 Q1 2016          Phase 1 Q3 2016

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Selection of Target Cancers:
Facilitating Focused Clinical Trials
              Target Presence (via IHC)           nfP2X7 critical for cell survival   In Vivo or Human data

   Prostate             ✔                                       ✔                             ✔
   Colon                ✔                                       ✔                             ✔
    Lung                ✔                                       ✔                             ✔
   Breast               ✔                                       ✔                             ✔
    BCC                 ✔                                      No data                        ✔

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Topical
                                 Phase 1
       Therapeutic
                                (completed)
             BIL-010t

Patients         20

Trial Centers    3 USA based Dermatology Treatment and Research Centers

Patient
Inclusion
                 Histological confirmation of superficial or nodular BCC

                 Metered topical dosage twice daily for                     Principal Investigator
Method                                                                      Prof. Scott Glazier
                 28 consecutive days with 10% API

Study            Assess safety, tolerability & pharmacokinetics
Objectives       Observe clinical response

                 Tolerability and safety supported. High compliance, with
Summary
                 efficacy indication – reduction of lesion size.

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Topical                Clinical data - Clearance
 Therapeutic
                          of tumour in patients
     BIL-010t

Informed consent trial                                             Example of SCC with biopsy histology
                                                                       Pre-treatment       Staining of nfP2X7 on
 • 24 non melanoma skin cancer lesions (BCC and                         appearance              cancer cells
   SCC) treated – majority to clearance
 • 15 lesions (62%) showed clinical clearance
 • 62 days median time to clearance

Example of Papulonodular BCC
 • Topical application of BIL010t cleared
   tumour by day 6 with with no recurrence

                                                                     Appearance 2 weeks      No staining post
                                                                     post treatment with       treatment
                                                                           BIL010t
         Day 1         Day 6         Day 16
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Topical
       Therapeutic               Phase 2
             .

             BIL-010t

                 90 patients in polyclonal (+ 30 patients in monoclonal arm*) -
Patients
                 Consideration of orphan indication (Gorlin’s Syndrome)

Trial Centers    3 USA based Dermatology Treatment and Research Centers

                                                                                   Principal Investigator
Patient
Inclusion
                 Histological confirmation of superficial or nodular BCC           Prof. Scott Glazier

                                                                                  *Replacement of BIL-010t
                                                                                  polyclonal API with
                 Metered topical dosage once daily for 60 days 5 days of 7,
Method                                                                            appropriate Monoclonal
                 with 2.5% / 5% API, Expansion cohort post 60 days                Ab candidate via bridging
                                                                                  study approval

Study            Assess safety, tolerability & pharmacokinetics , dosage
Objectives       Observe clinical response - efficacy

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Systemic
       Therapeutic                   Phase 1
                .

             BIL-03s

Patients            20-30                                                                   Principal
                                                                                          Investigator
                                                                                        Prof. Gavin Marx
                    2 Australian centres – San Hospital, Royal North Shore
Trial Centers
                    Hospital.
Patient
Inclusion
                    All comers basket trial - focus on lung, prostate, colorectal.
                                                                                         Co-Principal
                                                                                         Ass. Prof Nick
Method              Systemic Infusions                                                     Pavlakis

                    Assess safety, tolerability & pharmacokinetics
Study
Objectives
                    Observe clinical response, evaluate the preliminary anti-
                    tumour activity including ORR, DOR, DCR, PFS, QoL
                                                                                     Oncology Consultant
                                                                                          Dr. Bob Li

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Therapeutic
           Vaccine               Phase 1
             .

             BIL-06v

Patients         20-30                                                             Principal
                                                                                 Investigator
                                                                               Prof. Gavin Marx
                 2 Australian centres – San Hospital, Royal North Shore
Trial Centers
                 Hospital.
Patient
Inclusion
                 All comers basket trial – prostate and lung

Method           Injection                                                      Co-Principal
                                                                                Ass. Prof Nick
                                                                                  Pavlakis
                 Primary - is to monitor safety, serum antigen-specific
Study            antibody titres and other immune functions.
Objectives       Secondary - monitor known biomarkers of disease severity
                 for indications of efficacy.

Status           Protocol in development; ready to initiate Q1 2016         Oncology Consultant
                                                                                 Dr. Bob Li

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Therapeutic
  Vaccine                    Clinical SAS
                             Case Study 1
    BIL-06v

• Patient with follicular lymphoma                Ileum pre-vaccination showing tumour extent.
  in the terminal ileum and lymph
  nodes
• Vaccination with peptide
  conjugate
• Increased specific antibody titer
  after vaccination

                                                  Same regions post vaccination, showing tumour volume
       Maximal Response                           reduced by 50%
       During Vaccination
       Initial Vaccination

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Safety:
Across the Portfolio

          Systemic                      Therapeutic                         Topical
          Antibody                        Vaccine                         Therapeutic

            BIL03s                           BIL06v                           BIL010t
          Clean formal toxicology          Data from Sheep used to                Clean formal
          study facilitating phase I          generate BIL010t                  toxicology study

                               Multiple in vivo                            Good phase I trial safety &
                              mouse experiments                              tolerability outcomes

                                         Use in veterinary patients

                                        Use in Category A patients

                          Well characterised product with appropriate CMC assays

      All data confirms safety, as predicted by the specificity of our target for cancerous tissue.
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Drug Product Manufacturing
Completed – Minimal CMC Risk

                                  Systemic Antibody              Therapeutic Vaccine      Topical Polyclonal
                                      BIL03s                          BIL06v                  BIL010t

        API Manufacturer

           Purification

    Fill & Finish–Final Product

             Stability            18 months (ongoing)            API 6 months (ongoing)   API 5 years (ongoing)

       Reference Standard                                                 ✔
                                           ✔                                                       ✔

       GMP Manufacturing
         Bio-Process                       ✔                                                       ✔

      Products Used in Man                ✔                               ✔                       ✔

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Global IP Strategy

         13 US patents
            granted
                                        Europe

                                                             ROW

         Protection to 2035                  Includes: diagnostic, antibodies distinguishing P2X7 & nfP2X7,
                                             sequence, use of receptor as vaccine, animal Abs, Abs in topical,
        +100 granted patents                 specific monoclonal, epitopes for Abs, epitope peptides,
                                             production of monoclonal antibodies, high Affinity Dabs
           13 Patent Series
                                             Protection     applicable          to       cell      therapies
                                             (CAR-T, NK cell, etc)

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Upcoming Value Catalysts

    Financial                                                                 Commercial

  Q3 2016       Private Round Fund Raise (£25m)                            Q1 2016   2 MTAs with Pharma

                                                                           Q1 2016   1 Due Diligence
    Clinical
                                                                           Q1 2016   3 ongoing Pharma discussions
                Commence 2 X Phase 1
  H2 2016       systemic clinical trials
                                                                           H2 2016   Potential for multiple
                Start of 1 X Phase 2                                       H1 2017   licensing events
  H2 2016       topical clinical trial

 Q416, Q117     Initial Data from clinical trials                             Publication

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