Scancell Holdings Plc · LSE:SCLP
Scancell — Investor Presentation (February 2018)
58 slides from Scancell's investor presentation, Feb 16, 2018
Slide 1: A New Frontier in Immuno-Oncology
A NEW FRONTIER IN IMMUNO-ONCOLOGY 16 February 2018 LSE: SCLP.L
Slide 2: Disclaimer
DISCLAIMER The information contained in these slides has been prepared by Scancell Holdings plc (the "Company"). It has not been approved by the United Kingdom Financial Conduct Authority under the Prospectus Rules (made under Part VI of the Financial Services and Markets Act 2000) or otherwise, or
Slide 3: Differentiated Immuno-Oncology Clinical Stage Opportunity
DIFFERENTIATED IMMUNO-ONCOLOGY CLINICAL STAGE OPPORTUNITY Scancell is developing innovative immunotherapies for the treatment of cancer Immuno-oncology is one of the fastest growing sectors in the biopharmaceutical industry Scancell is transitioning towards commercialisation of key assets 2
Slide 4: Two Differentiated Innovative Platforms
TWO DIFFERENTIATED INNOVATIVE PLATFORMS IMMUNOBODY® MODITOPE® DNA-based platform for the generation of Modified citrullinated peptides that deliver high avidity CD8 anti-tumour cells potent killer CD4 T-cells to target neo- epitopes Ref: Chen and Mellman 2013 A NEW FRONTIER IN IMMUNO-ONCOLOGY 4
Slide 5: Development Pipeline
DEVELOPMENT PIPELINE IMMUNOBODY® MODITOPE® SCIB1: Targets malignant melanoma. Phase 1/2 Modi-1: Manufacturing process development study completed with strong survival data. Phase 2 initiated. Phase 1/2 trial in TNBC, ovarian and combination trial with immune checkpoint inhibitor sarcoma planned
Slide 6: Opportunities for New Cancer Immunotherapies
OPPORTUNITIES FOR NEW CANCER IMMUNOTHERAPIES OPPORTUNITIES IMPLEMENTATION Replace or combine with current Identify new cancer targets and/or standard of care (SOC) treatments therapeutic approaches to known targets Provide therapies with an improved safety profile Improve understanding of im
Slide 7: Identified Opportunities in a Range of Treatment Settings
IDENTIFIED OPPORTUNITIES IN A RANGE OF TREATMENT SETTINGS IMMUNOBODY® MODITOPE® SCIB1 Modi-1 & Modi-2 In combination with checkpoint inhibitors in patients with late stage disease to increase Innovative mechanism of action potentially efficacy without compromising safety targets all solid tumour
Slide 8: Validation and Endorsement
VALIDATION AND ENDORSEMENT Cancer Research UK (CRUK) clinical trial partnership announced December 2017 BioNTech research collaboration announced January 2018 CRUK (SCIB2) BioNTech (MODITOPE®) CRUK is one of the world’s leading cancer BioNTech is Europe’s largest private charities biotech co
Slide 9: Progress Since Last Funding (May 2017, £5m)
PROGRESS SINCE LAST FUNDING (MAY 2017, £5m) External validation of ImmunoBody® and Moditope® immunotherapy platforms Internal projects advanced and expanded IMMUNOBODY® MODITOPE® Clinical Development Partnership with BioNTech research collaboration to develop CRUK for SCIB2 in non-small cell
Slide 10: Anticipated Short–Medium Term Milestones
ANTICIPATED SHORT–MEDIUM TERM MILESTONES IMMUNOBODY® MODITOPE® 2018 2018 Q2: SCIB1 IND filed Q1: Modi-1 GMP manufacture starts Q2: SCIB2 manufacturing development Q1: Start evaluation of Modi-specific TCRs starts Q4: Modi-1 CTA filed Q4: SCIB1 Phase 2 starts 2019 Q4: SCIB2 toxicology s
Slide 11: Experienced Management Team
EXPERIENCED MANAGEMENT TEAM CHAIRMAN John is MD of Newstar Ventures Ltd, an investment and advisory firm. Recent transaction experience DR JOHN CHIPLIN includes Benitec Biopharma (US IPO), Adalta and Sienna Cancer Diagnostics (Australian IPOs), Medistem (acquired by Intrexon), Arana (acquired by Cep
Slide 12: Near to Medium Term Value Drivers
NEAR TO MEDIUM TERM VALUE DRIVERS 2 PLATFORMS, 4 LEAD PRODUCTS + 5 CORE ACTIVITIES CLINICAL DATA: Generate meaningful clinical data to address unmet needs: 2 clinical read-outs (SCIB1 Phase 2 & Modi-1 Phase1/2) anticipated in next 2 years PIPELINE Extend utility of Moditope platform beyond Modi-1 an
Slide 13: Moditope therapy
Professor Lindy Durrant Moditope® therapy A NEW FRONTIER IN IMMUNO-ONCOLOGY 13 13
Slide 14: The Moditope Platform
THE MODITOPE® PLATFORM A NOVEL IMMUNOTHERAPY THAT OVERCOMES IMMUNOSUPPRESSION AND DELIVERS UNPRECEDENTED KILLER T-HELPER CELL RESPONSES Post-translational modifications of proteins occur under conditions of cellular stress One such modification involves the process of CITRULLINATION Involves t
Slide 15: Mode of Action
MODE OF ACTION CITRULLINATED PEPTIDES (MODITOPE®) ACTIVATE KILLER T-HELPER CELLS THAT SEEK AND DESTROY CANCER CELLS Citrullinated tumour-associated peptides Primed CD4 killer T-cells enter the tumour (Moditope® peptides) are administered with Stressed tumour cells undergo autophagy and adjuvan
Slide 16: Moditope Lead Candidate
MODITOPE® LEAD CANDIDATE Modi-1 Consists of: Two citrullinated vimentin peptides (Vim-1 and Vim-2) One citrullinated enolase peptide (Eno-1) Vimentin and enolase targets are highly expressed in triple negative breast cancer (90%), ovarian cancer (95%), and sarcoma (100%) - all with high unme
Slide 17: Modi-1 Development: ISA Collaboration
MODI-1 DEVELOPMENT: ISA COLLABORATION Conjugation of peptide to Amplivant® (ISA Pharmaceuticals) enhances responses 10-100 fold Low dose TLR agonist-linked peptides induce responses that show efficient tumour therapy and establish immunological memory to protect from tumour recurrence Peptide-
Slide 18: Modi-1 First in Human Study
MODI-1 FIRST IN HUMAN STUDY PATIENT POPULATION Patients with tumours with high vimentin or enolase expression (e.g., sarcoma, TNBC, ovarian) Failed or intolerant to standard of care therapies Trigger to advance development ≥3 RECIST First patient treated 1H19 responses in 16 patients First effic
Slide 19: Moditope Pipeline
MODITOPE® PIPELINE DEVELOPMENT CANDIDATE Modi-2 Consists of: Citrullinated Modi-2a peptide Citrullinated Modi-2b peptide Citrullinated Modi-2c peptide Citrullinated Enolase peptide Targets are highly expressed in oesophageal, gastric, colorectal, breast (non-TNBC), cervical, prostate, li
Slide 20: CRUK Grand Challenge Award
CRUK GRAND CHALLENGE AWARD Grand Challenge award recognises research proposals that tackle some of the toughest questions in cancer Team’s proposal seeks to leverage a tumour vaccine approach to build a blueprint for effective personalised therapy for patients with most types of cancer Prof Li
Slide 21: Validation and Endorsement: BioNTech
VALIDATION AND ENDORSEMENT BIONTECH RESEARCH COLLABORATION ANNOUNCED JANUARY 2018 BioNTech (MODITOPE®) BioNTech is Europe’s largest private biotech company Initial research focus on Modi-1 epitopes (vimentin and enolase) Incorporates BioNTech platform for cloning and characterisation of TCRs
Slide 22: TCR Transduction and Adoptive T Cell Transfer
TCR TRANSDUCTION AND ADOPTIVE T CELL TRANSFER Advantages of citrullinated antigen specific TCRs TCR recognising citrullinated specific Citrullinated antigens are epitopes expressed by a wide range of tumours Citrullinated antigen-specific T cells recognise the non- polymorphic HLA-DP4 so are app
Slide 23: Summary: Moditope
SUMMARY EXTERNAL VALIDATION OF MODITOPE® IMMUNOTHERAPY PLATFORM INTERNAL PROJECTS ADVANCED AND EXPANDED MODITOPE® Research collaboration to develop T-cell based therapies established with BioNTech Collaboration agreed with ISA Pharmaceuticals for development of Amplivant® Modi-1 conjugate therap
Slide 24: SCIB2 ImmunoBody for lung cancer
Dr Peter Brown SCIB2 ImmunoBody® for lung cancer A NEW FRONTIER IN IMMUNO-ONCOLOGY 24 24
Slide 25: The ImmunoBody Platform
THE IMMUNOBODY® PLATFORM MEETING THE NEED FOR AN EFFECTIVE THERAPEUTIC CANCER VACCINE Key challenge is to stimulate an effective T cell response to reject or kill the growing tumour T-cell epitopes Most vaccine strategies only stimulate low frequency, low avidity T cell responses that fail to co
Slide 26: The ImmunoBody Platform
THE IMMUNOBODY® PLATFORM MEETING THE NEED FOR AN EFFECTIVE THERAPEUTIC CANCER VACCINE Proprietary patent protected platform Several cancer associated T cell epitopes are engineered into a human antibody framework to make a genetic antigen/antibody complex Delivered as a DNA plasmid using elect
Slide 27: The ImmunoBody Platform
THE IMMUNOBODY® PLATFORM PATHWAY 1 PATHWAY 2 Conventional Direct DNA uptake and Cross Presentation amplification pathway antigen presentation by APCs Cross presentation increases potency 100-fold over direct presentation A NEW FRONTIER IN IMMUNO-ONCOLOGY 27
Slide 28: SCIB2 for Lung Cancer
SCIB2 FOR LUNG CANCER SCIB2 IMMUNOBODY® SCIB2 targets the highly immunogenic NY-ESO-1 cancer antigen, a validated cancer target SCIB2 is broadly applicable to many cancer types, including non-small cell lung cancer, synovial sarcomas, melanoma, oesophageal, liver, gastric, prostate, ovarian, ren
Slide 29: Lung Cancer
LUNG CANCER NEED FOR IMPROVED THERAPY Two main forms of lung cancer: non-small cell (NSCLC; 95% of lung cancers) and small cell (SCLC) Account for 22% of all UK cancer deaths Checkpoint blockade with pembrolizumab (KEYTRUDA®) has changed the treatment of NSCLC . . . “Better than chemotherapy”
Slide 30: SCIB2 Development
SCIB2 DEVELOPMENT SCIB2 INDUCES SUPERIOR RESPONSES COMPARED TO PEPTIDE VACCINE Responses induced in HHDII mice immunised with SCIB2 or NY-ESO-1 peptide SCIB2 induced higher frequency responses than peptide immunisation (p=0.0004) SCIB2 generated a 100-fold higher avidity than peptide S C IB 2
Slide 31: SCIB2 Development
SCIB2 DEVELOPMENT SCIB2 induces PD.L1 Nano-vesicle delivery of SCIB2 induces strong anti- expression on tumour cells tumour responses and generates a memory response p = 0 .0 0 1 6 100 T u m o u r c e lls e x p r e s s in g P D L .1 (% ) 50 0 C o n tr o l S C IB 2 RECHALLENGED A NEW FRONTIER IN IMMU
Slide 32: SCIB2 Development
SCIB2 DEVELOPMENT EXPERIMENTAL DATA SUPPORT THE USE OF SCIB2 IN COMBINATION WITH A CHECKPOINT INHIBITOR SCIB2 boosts the effect of a PD.1 antibody in HHDII mice implanted with NY-ESO-1 positive tumour cells 100% survival rates were seen when SCIB2 treatment was combined with anti-PD.1 * * p=0.00
Slide 33: SCIB2 Clinical Development
SCIB2 CLINICAL DEVELOPMENT Clinical Development Partnership formed with Cancer Research UK (CRUK) to fund and manage a Phase 1/2 study with SCIB2 in combination with a checkpoint inhibitor in NSCLC CRUK responsible for manufacture, regulatory submissions and conducting clinical trial Scancell
Slide 34: SCIB2 Clinical Development
SCIB2 CLINICAL DEVELOPMENT OPPORTUNITY TO OBTAIN CLEAR EFFICACY AND SAFETY SIGNALS Clinical trial would be in 25-33% of NSCLC positive for NY-ESO-1 Clinical benefit in NSCLC is readily determined by CT scan measurement of disease Trial would set targets for exceeding expected objective respons
Slide 35: SCIB2 Clinical Development Summary
SCIB2 CLINICAL DEVELOPMENT SUMMARY Although checkpoint inhibitors are important new therapies – only a relatively small proportion of lung cancer patients will respond to them Failure to respond is related to failure of the patient’s immune system to recognize the cancer and mount an effective r
Slide 36: SCIB-1 in melanoma
SCIB-1 in melanoma Poulam Patel Prof of Clinical Oncology University of Nottingham
Slide 37: Background
Background • Cancer of melanocytes • 14,509 new cases/year UK • 2,459 deaths/year • Increasing incidence 37
Slide 38: Melanoma
Breslow Depth (mm) a Vv Vv wo N Vv Vv Melanoma 2001 Image by Med-Art ~ http://w by ww.med-ars.il The University of Nottingham 38
Slide 39: Melanoma can spread
Melanoma can spread • Lymphatic spread • Blood borne spread – lymph nodes - lung, liver, brain, skin 39
Slide 40: Survival from melanoma
PROPORTION SURVIVING f Survival from melanoma Stage! (n=9175) Stage Il (n=5739) Stage Ill(n=1528) Stage IV(n=1158) 12 3 4 5 6 7 8 9 10 14 12 13 14 15 SURVIVAL (years) The University of Nottingham 40
Slide 41: Cancer Immunotherapy
Cancer Immunotherapy • New anti-cancer immuno- therapies licensed • Many more in development • Long term remissions 41
Slide 42: Cells of the immune system
Cells of the immune system antibodies bacteria B-cells T-cells Virus –infected cell 42
Slide 43: Immune cells can kill cancer
Immune cells can kill cancer T- cells tumour cell killing tumour cells 43
Slide 44: Immune response to cancer
Immune response to cancer dendritic cells Tc activation killing tumour site lymph node 44
Slide 45: The immune system has 'brakes'
The immune system has ‘brakes’ Activation Taking the ‘brakes off’ ‘Super’ activation Downregulation CTLA-4 anti-CTLA-4 45
Slide 46: Anti-CTLA4
Anti-CTLA4 Ipilimumab + gp100 Ipilimumab alone gp100 alone Immune-related side effects pituitary skin liver colon 2011 Ipilimumab licensed for treatment of advanced melanoma 46
Slide 47: Immune response to cancer
Immune response to cancer CTLA-4 dendritic cells Tc activation killing Nivolumab PD-1 Pembrolizumab lymph node 47
Slide 48: Anti-PD1 - Nivolumab
Anti-PD1 - Nivolumab Robert C, et al. N Engl J Med. 2015;372:320-330 48
Slide 49: Anti-PD1 checkpoint inhibitors licenced
Anti-PD1 checkpoint inhibitors licenced Pembrolizumab Nivolumab 2014 2014 49
Slide 50: Checkpoint inhibitors in melanoma
Checkpoint inhibitors in melanoma 1 year ~ 30% dendritic cells CTLA 1 year ~ 50% Chemotherapy 2 year ~ 10% Ipilimumab Tc activation 2 year ~ 25% 5 year ~ 4 % 5 year ~20% tumour site lymph node Anti-PD-1 1 year survival ~ 70% dendritic cells Tc activation killing 2 year survival ~ 50% 5 year survival
Slide 51: SCIB1 vaccination
SCIB1 vaccination dendritic cells SCIB1 killing tumour site lymph node 51
Slide 52: SCIB1
SCIB1 • Several melanoma associated T cell epitopes engineered into a human antibody framework • Induces high avidity T cell responses compared with conventional approaches • Novel dual mechanism of action based on direct and cross- presentation • Delivered as a DNA plasmid using electroporation (EP
Slide 53: SCIB1-001: Phase I/II Trial
SCIB1-001: PHASE I/II TRIAL UK study: Nottingham, Southampton, Leeds, Newcastle, Manchester, Guildford Open label, non-randomized study to determine the safety and tolerability of SCIB1 administered intramuscularly Patients with stage III/IV metastatic melanoma Part 1: dose escalation phase
Slide 54: Results
RESULTS SURVIVAL IN RESECTED PATIENTS SCIB1 has an excellent safety profile with no dose-limiting toxicities and no serious adverse events related to study drug or Overall survival with SCIB1 treatment delivery device superior to historical survival rates 14 of 16 resected patients receiving 2-4
Slide 55: Results
RESULTS PATIENTS WITHOUT TUMOUR PRESENT AT STUDY ENTRY Study entry 5 years Disease-free patients Patients with recurrence Deceased patients SCIB1 dose (2/4 mg) Disease recurrence Death Surgery Other therapy -60 -50 -40 -30 -20 -10 0 10 20 30 40 50 60 70 80 Months from study entry
Slide 56: Comparison to Recent Studies in Adjuvant Melanoma
COMPARISON TO RECENT STUDIES IN ADJUVANT MELANOMA Study: SCIB1-001 EORTC 18071 a CheckMate 238 b COMBI-AD c Treatment SCIB1 Ipilimumab Placebo Nivolumab Ipilimumab Braf‡ Placebo Female (%) 56 38 38 43 41 55 55 Median Age (yr) 61 51 52 56 54 50 51 Disease IIIA 19 21 18 0 0 19 16 Stage (%) IIIB 12 45
Slide 57: SCIB1 Boosts Immune Checkpoint Therapy
SCIB1 BOOSTS IMMUNE CHECKPOINT THERAPY IN A MOUSE MELANOMA MODEL, SURVIVAL RATES WERE SIGNIFICANTLY BOOSTED WHEN ANTI-PD-1 THERAPY WAS COMBINED WITH SCIB1 TREATMENT Survival rates for SCIB1 ImmunoBody® monotherapy ≈ anti-PD-1 Monotherapy viable option for resected melanoma patients Combination
Slide 58: SCIB1 Plus Checkpoint Inhibitor Combination Phase 2 Study Design
SCIB1 PLUS CHECKPOINT INHIBITOR COMBINATION PHASE 2 STUDY DESIGN PATIENT POPULATION Histologically confirmed, unresectable AJCC stage III or stage IV melanoma No prior systemic treatment for advanced disease Suitable for treatment with Keytruda (pembrolizumab), with measurable disease Part 1
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