NfP2X 7 - The Biosceptre Immuno-Oncology Platform - Systemic Antibodies, Topical Antibody Therapeutics - Peptide Vaccine Therapy
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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
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. Commercial in Confidence
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 Commercial in Confidence
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. Commercial in Confidence
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 Commercial in Confidence
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 Commercial in Confidence
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. Commercial in Confidence
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 Commercial in Confidence
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] Commercial in Confidence
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 Commercial in Confidence
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 Commercial in Confidence
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 Commercial in Confidence
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 h g r t n te a r y c n s e la c ti n e lo m a ta a d a 45% global average ri n u a u o re o d m re s id L a c n C la ro ti v B to la K c O B s n P S e e a M T P T u m o u r ty p e Number of samples tested for a given cancer shown above bars Commercial in Confidence
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 Commercial in Confidence
Clinical Plans Topical Systemic Therapeutic Therapeutic Antibody Peptide BIL010t BIL03s BIL06v Phase 1b/2 Q4 2016 Phase 1 Q1 2016 Phase 1 Q3 2016 Commercial in Confidence
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 ✔ Commercial in Confidence
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. Commercial in Confidence
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 Commercial in Confidence
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 Commercial in Confidence
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 Commercial in Confidence
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 Commercial in Confidence
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 Commercial in Confidence
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. Commercial in Confidence
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 ✔ ✔ ✔ Commercial in Confidence
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) Commercial in Confidence
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 Commercial in Confidence
Thankyou Commercial in Confidence
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