The BiosceptreImmuno-Oncology Platform...Q3 2016 - Systemic Antibodies, - Topical Antibody...

CommercialinConfidence

A Broadly Occurring and High Specificity

Cancer TargetQ32016

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

targeting

nfP2X7

TheBiosceptre Immuno-OncologyPlatform


Disclaimer

This presentation has been prepared by Biosceptre International Limited and its affiliates (the Biosceptre Group). Theinformation contained in this presentation is for informational purposes only. The information contained in this presentationis not investment or financial product advice and is not intended to be used as the basis for making an investmentdecision. This presentation does not constitute an offer or invitation in respect of any sale or purchase of securities. Thispresentation has been prepared without taking into account the investment objectives, financial situation or particularneeds 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 ofthe information, opinions and conclusions contained in this presentation. A number of statements in this presentation havebeen based on internal estimates by the Biosceptre Group and have not been independently verified. To the maximumextent permitted by law, none of the Biosceptre Group and their respective directors, officers, employees, contractors oragents, nor any other person accepts any liability, including, without limitation, any liability arising out of fault ornegligence, for any loss arising from the use of the information contained in this presentation. In particular, norepresentation or warranty, express or implied, is given as to the accuracy, completeness or correctness, likelihood ofachievement 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 mayvary 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 remainsubject 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 thispresentation.


Biosceptre HighlightsBroadly Occurring Validated Target

• nfP2X7 identified on the surface of >20 human cancer types.• Plays a role in cancer cell survival and proliferation distinct from functional P2X7

Highly Specific

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

3 Therapeutics in Pipeline

• fully human domain antibody for systemic use • polyclonal sheep antibody for topical application • peptide-protein conjugate vaccine therapeutic

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

Comprehensive IP platform

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

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

Single target therefore synergy for mechanism, safety and efficacy


Science Team

Shaun McNulty PhDChief 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 PhDDirector of Research

30+ years experience in protein structure analyses, molecular modeling, protein function studies & antibody design – work in calcium regulation, purinergic receptor structure, cancer diagnostics &immunotherapeutics.

25+ years research and lecturingUniversity of Sydney, 20 + yearsexperience in biotech and biomedicalbusiness, Researcher Director of 3 listed companies.

Dr. Angus Gidley-Baird PhDScientific Director

20+ years experience Ops Manager for National Biologics Facility, Australian Institute for Bioengineering and Nanotechnology. 300+ commercial and research projects, Budget +$30m, 30 collaborations,

David Chin PhDDirector Bio Production


• Master of Trinity College, Cambridge University • Pioneer of humanised antibodies, phage display technology, founder CAT and

Domantis• Recipient of numerous awards and honours

Science Advisory Board

Dr Sir Gregory WinterCBE, FRS, FMedSci, HonFRCP

• Professor of Molecular Biology at the University of Oxford• Pioneer of cDNA cloning, antibody gene mapping, oncogene family

identification

Professor Terence Rabbitts FRS, FMedSci

Photo Credit: Aga Machaj


Clinical Advocates

Prof. Gavin MarxBSc (Med) MBBS (Hons) FRACP

Head Chair of the Section of Oncology at the SAN

Director of the SAN Clinical Trials Unit

Clinical Director of the SAN Integrated Cancer Centre

Associate Professor at the University of Sydney

Dr. Bob LiMBBS, BSc (Med)MPH, FRACP

Attending Medical Oncologist and Clinical Investigator at Memorial Sloan Kettering Cancer Center

ASCO Young Investigator AwardAmerican Society of Clinical Oncology and Conquer Cancer Foundation

ASCO Merit AwardAmerican Society of Clinical Oncology and Conquer Cancer Foundation

Dr Tom BorodyBSc (MED) (HONS), MBBS (HONS), MD, PhD, FRACP, FACG, FACP, AGAF

Founder and Medical Director of Center for Digestive Disease

Reviewer for medical journals, the American Journal of Gastroenterology, Digestive Diseases & Sciences and The Journal for Gastroenterology and Hepatology and Digestive and Liver Diseases.

Ass. Prof Nick PavlakisBSc, MBBS MMed (Clin. Epi) PhD FRACP

Head of the Department of Medical Oncology, Royal North Shore Hospital, Sydney

Chair of the ScientificAdvisory Committee of the Australasian Lung Cancer Trials Group

Director of the Northern Sydney Cancer Trials Network


Executive Team

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

Daniel BartonDirector Investor Relations

Brad MillerCommercial & Legal Manager

Gavin CurrieChief Executive Officer

B.Sc (Biochem) LLB – 20 years experience in marketing and communications across a range of industries. Has managed start ups through to acquisitions & board level reporting duties in listed companies. Non Executive Board membership experience.

5+ years with a private international investment fund. Financial management and legal documentation, cross-border transactions including mergers and acquisitions, debt financing and equity investments, primarily in the life sciences sector.


Our target: nfP2X7

Normaltrimer

conformation

Abnormaltrimer

conformation

P2X7 is a ligand-gated non-selective cation channel

P2X7 forms a trimer which opens an ion channel in response to rapid stimulation and opens a large molecular weight pore in response to prolonged ATP stimulation

Exposed nfP2X7 target

The nfP2X7target

Some forms of P2X7 can not form a large molecular weight pore in response to ATP.

These we term nfP2X7 (non functional) BUT critical signalling functionality is retained


Product Approach Indication Discovery Pre-clinical Phase I Phase II

CLINICAL PROGRAMS

BIL03s Domain Ab Solid tumours

BIL06v Peptide Vaccine Solid tumours

BIL010t Polyclonal Ab Basal cell carcinoma

DISCOVERY PROGRAMS

BIL011t Topical dAb

BIL04s Next gen. systemic monoclonal

BIL07v Next gen. peptide vaccine

BIL03n Conjugate candidate

BPM09 IHC Antibody [Diagnostics]

2H16

2H16

2H16

Pipeline


Broad Human Therapeutic Potential

BIL03sDomain Ab

BIL010tPolyclonal

Vaccine

Cell Car-T NK

Antibody

BIL06vPeptide

Conjugate

BIL03sADC

Peptide

Dendritic

*Current Biosceptre

Activity

Bispecifics

BPM09Diagnostic

Ab


Normal P2X7 – 2 pore states State dependent on ATP concentration

Ca2+

NormalCell

Large molecule influxSignificant Ca2+ entry

NormalCell

Cell death

Largemolecules

+ATP

+++ATP

small pore

large pore

Moderate Ca2+ influx

Membranedepolarisation

proliferationsignalling


nfP2X7 and CancerLoss of response to high ATP concentration

Increased proliferation & survival

MetastaticPotential

CancerCell

CancerCell

CancerCell

CancerCell

No Cell Death

nfP2X7expressing

Cell

NormalCell

NO large pore

+ATP

+++ATP

small pore

XLarge molecule influxSignificant Ca2+ entry

Moderate Ca2+ influx

aberrant proliferation signalling

proliferationsignalling

Ca2+Large

molecules


IHC on PDX derived section performed by Oncotest

45% global averageB lad d e r

B rea s t

C o lon

K idn e y

L u n g

Ov a r ia

n

P ros ta

te

T e s t icu la

r

S tom

a c h

Me la

n o ma

P a n c rea t ic

0

5 0

1 0 0

T u m o u r ty p e

% p

os

itiv

e s

tain

ing

P D X

T u m o u r b io p s y

8

6 5

3

9

5 8

5 4

1 3

1 2

1

6

1 2

6 6

1 3

5 07

3

1 82 4

4 6

Number of samples tested for a given cancer shown above bars

BPM09 Binds to Multiple Tumours

IHC on FFPE tumour sectionsPerformed by External Lab

50% global average


nfP2X7 Mediates Survival in Multiple Cancer Cell Lines

Cell line Tumour originLarge pore opening

P2X7 siRNA induced death

A B

PC3

ProstateNo Yes Yes

Du145 No Yes Yes

LNCaP No Yes Yes

SK MEL 28Melanoma

No Yes Yes

SK MEL 5 No No No

PC 9

LungNo Yes Yes

H460 No Yes Yes

H520 No Yes Yes

MCF7 Breast No Yes Yes

SK N ASNeuroblastoma

No Yes Yes

Kelly No Yes Yes

MiaPaCa2 Pancreas No No No

HCT116 Colorectal No Yes Yes

HT1080 Fibrosarcoma No Yes Yes


Systemic Antibody

BIL03s

Phase 1 Q1 2016

TherapeuticPeptide

BIL06v

Phase 1 Q3 2016

TopicalTherapeutic

Phase 1b/2 Q4 2016

BIL010t

Clinical Plans


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 ✔


TopicalTherapeutic

BIL-010t

Principal InvestigatorProf. Scott Glazier

Patients 20

Trial Centers 3 USA based Dermatology Treatment and Research Centers

Patient Inclusion Histological confirmation of superficial or nodular BCC

MethodMetered topical dosage twice daily for 28 consecutive days with 10% API

Study Objectives

Assess safety, tolerability & pharmacokinetics Observe clinical response

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

Phase 1(completed)


Clinical data - Clearance of tumour in patients

Informed consent trial

Day 6

Example of Papulonodular BCC• Topical application of BIL010t cleared

tumour by day 6 with with no recurrence

Example of SCC with biopsy histologyPre-treatment appearance

Staining of nfP2X7 on cancer cells

Appearance 2 weeks post treatment with

BIL010t

No staining post treatment

Day 16Day 1

• 24 non melanoma skin cancer lesions (BCC and SCC) treated – majority to clearance• 15 lesions (62%) showed clinical clearance• 62 days median time to clearance

TopicalTherapeutic

BIL-010t


Patients90 patients in polyclonal (+ 30 patients in monoclonal arm*) -Consideration of orphan indication (Gorlin’s Syndrome)

Trial Centers 3 USA based Dermatology Treatment and Research Centers

Patient Inclusion Histological confirmation of superficial or nodular BCC

MethodMetered topical dosage once daily for 60 days 5 days of 7, with 2.5% / 5% API, Expansion cohort post 60 days

Study Objectives

Assess safety, tolerability & pharmacokinetics , dosageObserve clinical response - efficacy

.

*Replacement of BIL-010t polyclonal API with appropriate Monoclonal Ab candidate via bridging study approval

Principal InvestigatorProf. Scott Glazier

Phase 2Topical

TherapeuticBIL-010t


.

Systemic Therapeutic

BIL-03s

Patients 20-30

Trial Centers2 Australian centres – San Hospital, Royal North Shore Hospital.

Patient Inclusion All comers basket trial - focus on lung, prostate, colorectal.

Method Systemic Infusions

Study Objectives

Assess safety, tolerability & pharmacokinetics Observe clinical response, evaluate the preliminary anti-tumour activity including ORR, DOR, DCR, PFS, QoL

Phase 1

Principal Investigator

Prof. Gavin Marx

Co-PrincipalAss. Prof Nick

Pavlakis

Oncology Consultant Dr. Bob Li


.

Patients 20-30

Trial Centers2 Australian centres – San Hospital, Royal North Shore Hospital.

Patient Inclusion All comers basket trial – prostate and lung

Method Injection

Study Objectives

Primary - is to monitor safety, serum antigen-specific antibody titres and other immune functions.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

Co-PrincipalAss. Prof Nick

Pavlakis

Principal Investigator

Prof. Gavin Marx

Therapeutic VaccineBIL-06v

Phase 1


Clinical SAS Case Study 1

• Patient with follicular lymphoma in the terminal ileum and lymph nodes

• Vaccination with peptide conjugate

• Increased specific antibody titer after vaccination

Ileum pre-vaccination showing tumour extent.

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

During VaccinationInitial Vaccination

Therapeutic VaccineBIL-06v


Safety: Across the Portfolio

All data confirms safety, as predicted by the specificity of our target for cancerous tissue.

Data from Sheep used to generate BIL010t

Clean formal toxicology study facilitating phase I

Clean formal toxicology study

Multiple in vivo mouse experiments

Good phase I trial safety & tolerability outcomes

Use in veterinary patients

Use in Category A patients

Well characterised product with appropriate CMC assays

Therapeutic Vaccine

BIL06v

Systemic Antibody

BIL03s

TopicalTherapeutic

BIL010t


Drug Product Manufacturing Completed – Minimal CMC Risk

Systemic AntibodyBIL03s

Therapeutic VaccineBIL06v

Topical PolyclonalBIL010t

API Manufacturer

Purification

Fill & Finish–Final Product

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

Reference Standard ✔✔

✔

GMP ManufacturingBio-Process ✔ ✔

Products Used in Man ✔ ✔ ✔


Protection to 2035

+100 granted patents

Global IP Strategy

Europe

Includes: diagnostic, antibodies distinguishing P2X7 & nfP2X7,sequence, use of receptor as vaccine, animal Abs, Abs in topical,specific monoclonal, epitopes for Abs, epitope peptides,production of monoclonal antibodies, high Affinity Dabs

Protection applicable to cell therapies(CAR-T, NK cell, etc)

13 US patents granted

ROW

13 Patent Series


Upcoming Value Catalysts

Financial

Q1 2016 2 MTAs with Pharma

Q1 2016 1 Due Diligence

Q1 2016 3 ongoing Pharma discussions

H2 2016 H1 2017

Potential for multiple licensing events

Q3 2016 Private Round Fund Raise (£25m)

H2 2016 Commence 2 X Phase 1 systemic clinical trials

H2 2016 Start of 1 X Phase 2 topical clinical trial

Q416, Q117 Initial Data from clinical trials

Clinical

Commercial

Publication


Thankyou

The BiosceptreImmuno-Oncology Platform...Q3 2016 - Systemic Antibodies, - Topical Antibody...

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