Scancell Holdings Plc · LSE:SCLP
Scancell — Shareholder Meeting (October 2018)
38 slides from Scancell's shareholder meeting presentation, Oct 30, 2018
Slide 1: Scancell AGM presentation
SCANCELL AGM presentation 30th October 2018 Dr Cliff Holloway – CEO Dr Sally Adams – Development Director Professor Lindy Durrant - CSO LSE: SCLP.L A NEW FRONTIER IN IMMUNO-ONCOLOGY
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: Immunotherapy the 5th pillar in the fight against cancer
IMMUNOTHERAPY THE ‘5th PILLAR’ IN THE FIGHT AGAINST CANCER Cells #GOBOLDLY “This is not a video game” - US TV ad showcases the destruction of a cancer cell by immune system A NEW FRONTIER IN IMMUNO-ONCOLOGY 3
Slide 4: Immune checkpoint blockade
IMMUNE CHECKPOINT BLOCKADE 2018 Nobel Prize in Physiology or Medicine awarded to immunologists James Allison and Tasuku Honjo A NEW FRONTIER IN IMMUNO-ONCOLOGY 4
Slide 5: Cancer immunotherapy market
CANCER IMMUNOTHERAPY MARKET $34Bn A NEW FRONTIER IN IMMUNO-ONCOLOGY 5
Slide 6: Immunobody and Moditope potential value drivers
POTENTIAL VALUE DRIVERS FOR SCANCELL IMMUNOTHERAPIES IMMUNOBODY and MODITOPE ► Do not increase Big Pharma seeking novel toxicity drugs or drug-drug ► Do not significantly combinations that: increase overall cost of treatment ► Address the unmet needs in hard to treat cancers ► Provide an increased a
Slide 7: Meeting the need for effective therapeutic cancer vaccines
MEETING THE NEED FOR EFFECTIVE THERAPEUTIC CANCER VACCINES Key challenge is to stimulate an effective T cell response to reject or kill the growing tumour Most vaccine strategies only stimulate low frequency, low avidity T cell responses that fail to control tumour growth Scancell’s novel ther
Slide 8: Development pipeline
DEVELOPMENT PIPELINE IMMUNOBODY® MODITOPE® SCIB1: Targets malignant melanoma. Phase 1/2 study completed with strong Modi-1: Manufacturing process development initiated. Phase 1/2 trial in survival data. Phase 2 combination trial with immune checkpoint inhibitor TNBC, ovarian and sarcoma planned
Slide 9: The development process
THE DEVELOPMENT PROCESS A NEW FRONTIER IN IMMUNO-ONCOLOGY 9
Slide 10: Key development questions
KEY DEVELOPMENT QUESTIONS ► Can we make it? ► Is it safe? ► Does it make patients better? A NEW FRONTIER IN IMMUNO-ONCOLOGY 10
Slide 11: Good development practice
“GOOD DEVELOPMENT PRACTICE” COMPLIANCE WITH LEGAL REQUIREMENT FOR REGULATORY GUIDANCE SPONSOR OVERSIGHT Good Manufacturing Practice Policy documents and procedures Good Clinical Practice Standard Operating Procedures (SOP) Trial Master File (TMF) Good Laboratory Practice Investigator B
Slide 12: SCIB1
IMMUNOBODY® SCIB1 A NEW FRONTIER IN IMMUNO-ONCOLOGY 12
Slide 13: SCIB1-001 Phase 1/2 melanoma study completed
SCIB1-001 PHASE 1/2 MELANOMA STUDY COMPLETED SCIB1 INDUCES POTENT IMMUNE RESPONSES & FAVOURABLE CLINICAL OUTCOME ► Excellent safety profile with no dose-limiting toxicities and no serious adverse events related to SCIB1 study drug or Ichor v1.0 delivery device ► Two patients with tumour present at s
Slide 14: SCIB1 + checkpoint inhibitor combination Phase 2 trial
SCIB1 + CHECKPOINT INHIBITOR COMBINATION PHASE 2 TRIAL 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 safety ru
Slide 15: SCIB1-002 clinical study
SCIB1-002 CLINICAL STUDY ► International trial to be conducted under an Investigational New Drug (IND) application ► Up to 5 sites in US and UK ► New TDS-IM v2.0 electroporation device, designed to support eventual commercial deployment ► US regulatory submissions ► IND for study drug SCIB1 manufact
Slide 16: SCIB1 IND submission
SCIB1 IND SUBMISSION Form 1571 CSR = 2,688 pages IND application RECORDS Research reports, toxicology reports, manufacturing batch records, raw materials CoAs, SOPs, QC analysis, compliance reports, analytical validation reports, release documents, environmental monitoring reports, cleaning valida
Slide 17: SCIB1 IND review process
SCIB1 IND REVIEW PROCESS ► IND submitted ► Reviewed by FDA ► SCIB1 clinical and toxicology questions answered during review process ► CMC questions under control ► Deficiencies in cross-referenced Ichor TriGrid v2.0 device Master File ► Device-specific questions ► Responses being prepared by I
Slide 18: Core clinical trial management activities
CORE CLINICAL TRIAL MANAGEMENT ACTIVITIES Clinical Medical Project/Study Regulatory & Monitoring & Monitoring & Biometrics Management Ethics Supplies Safety Clinical Scientific Monitoring Biometrics Development ► Protocol development ► Protocol submission ► Site selection ► Therapeutic training ► El
Slide 19: SCIB1 development
SCIB1 DEVELOPMENT ► IND submitted ► SCIB1-specific questions under control ► Device-specific questions in hand ► Operational activities underway ► UK regulatory submissions in progress ► Trial ready to start as soon as approval received A NEW FRONTIER IN IMMUNO-ONCOLOGY 19
Slide 20: Modi-1
MODITOPE® MODI-1 A NEW FRONTIER IN IMMUNO-ONCOLOGY 20
Slide 21: Modi-1 development
MODI-1 DEVELOPMENT THREE DRUG SUBSTANCES = ONE DRUG PRODUCT Vimentin 415 peptide Vimentin 28 peptide Enolase 241 peptide A NEW FRONTIER IN IMMUNO-ONCOLOGY 21
Slide 22: Modi-1 manufacturing
MODI-1 MANUFACTURING ► Modi-1 conjugates - novel cutting-edge products ► Strong bias toward hydrophobic amino acids at T-cell receptor contact residues within immunogenic epitopes (Chowell et al 2015) P o te n c y ► Hydrophobic peptides ► Challenging synthetic properties H y d r o p h o b ic it y ►
Slide 23: 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, triple negative breast cancer, ovarian) ► Failed or intolerant to standard of care therapies EXPANSION PHASE n Sarcoma DOSE ESCALATION Dosing regime n Dose escalation: 10,
Slide 24: From research to development
FROM RESEARCH TO DEVELOPMENT… Does it New work? idea! Can we Can we measure make it? it? Is it safe? A NEW FRONTIER IN IMMUNO-ONCOLOGY 24
Slide 25: Modi-2
MODITOPE® MODI-2 A NEW FRONTIER IN IMMUNO-ONCOLOGY 25
Slide 26: The Moditope platform
THE MODITOPE® PLATFORM ► One such modification involves the process of CITRULLINATION ► The alteration of proteins due to enzymatic conversion of arginine residues to citrulline ► Citrullination occurs as a result of a degradation and ‘recycling’ process called autophagy that is induced in stressed
Slide 27: Mode of action
MODE OF ACTION HOMOCITRULLINATED PEPTIDES ACTIVATE T-HELPER CELLS THAT SEEK AND DESTROY CANCER CELLS ► Homocitrullinated tumour-associated peptides (Moditope peptides) are administered with adjuvant to activate antigen presenting cells (APCs) ► Moditope peptides are taken up by activated APCs ► APCs
Slide 28: T cell responses to homocitrullinated vimentin and aldolase
Aldolase 74 Hcit - DP4 Adolase 140 Hcit - DP4 Vimentin 116 Hcit - DR4, DR1 Responses are blocked by anti-CD4 mabs A v e r a g e IF N γ s p o t s / m illio n s p le n o c y t e s A v e r a g e IF N γ s p o t s / m illio n s p le n o c y t e s V 0 200 400 600 800 1000 im co 1 n 1 0 200 400 600
Slide 29: Depleting Ly6G+ and Ly6C+ cells reduces anti-tumour response
DEPLETING Ly6G+ AND Ly6C+ CELLS REDUCES ANTI-TUMOUR RESPONSE CD11b+ Ly6G+ Ly6Clo = Antibodies which deplete MDSC abrogate the anti- granulocytic MDSC tumour response to homocitrullinated peptides CD11b+ Ly6G- Ly6Chi = Ly6C+ cells are more potent than Ly6G+ cells monocytic MDSC 100 100 p = 0 .0 4
Slide 30: Using prediction algorithms to select epitopes
USING PREDICTION ALGORITHMS TO SELECT EPITOPES ► IEDB prediction http://www.iedb.org/ ► High predicted binding to HLA alleles ► Peptides that contained lysine residues within the predicted binding core ► PEP-FOLD3 http://mobyle.rpbs.univ-paris-diderot.fr/cgi-bin/portal.py#forms::PEP-FOLD3 ► Peptides
Slide 31: Example: Cytokeratin 8
EXAMPLE: CYTOKERATIN 8 Co- Sequence DP4 DP4 DR4 DR4 DR1 DR1 Spiral T cell ordinates prediction predicted prediction predicted prediction predicted response score cores score cores scores cores 0.97 – 17.18 IDKVRFLEQ 5.06 FLEQQNKML 12.27 FLEQQNKML 101-120 KFASFID-Hcit-VRFLEQQN- Yes 0.97 – 1.68 SFIDKV
Slide 32: T-cell responses to Cyk8 epitopes selected using algorithms
T-CELL RESPONSES TO Cyk8 EPITOPES SELECTED USING ALGORITHMS INITIAL SCREEN (HHDII/DR1) RE-SCREEN (HHDII/DR1) All 5 peptides showed good responses when Responses that have been re-screened as administered as a pool homocitrulline-specific 800 **** **** *** 1000 m e d ia a v IF N γ s p o ts /m illio n
Slide 33: Homocitrullination summary
HOMOCITRULLINATION SUMMARY A NEW STRESS-INDUCED POST-TRANSLATIONAL MODIFICATION (siPTM) ► Homocitrulline is a new modification that is an excellent target for tumour immunotherapy ► Strong patent protection ► Targets a different range of cancers to citrullination (Modi-1) ► Different mechanism of ac
Slide 34: T cell receptor (TCR) therapy
T CELL RECEPTOR (TCR) THERAPY MODITOPE® PROVIDES A NOVEL PATHWAY FOR CD4-BASED TCR THERAPY ADVANTAGES ► Moditope® targets epitopes recognised in the context of MHC class II/cytotoxic CD4 T cells ► Recognises widely expressed modified antigens on widely expressed MHC, so has broad utility against a w
Slide 35: T cell repertoire to Modi-1 epitopes in humans
T CELL REPERTOIRE TO MODI-1 EPITOPES IN HUMANS RESPONSES IN HEALTHY DONORS SHOW AN OLIGOCLONAL RESPONSE TO CITRULLINATED PEPTIDES Vim28cit (BD0011) Vim415cit (BD0008) Eno241cit (BD00041) TCR Vα TCR Vβ TCR Vα TCR Vβ TCR Vα TCR Vβ CFSE CFSE CFSE high high high CFSE CFSE CFSE low low low Repertoire dat
Slide 36: T cell repertoire to Modi-2 epitopes in humans
T CELL REPERTOIRE TO MODI-2 EPITOPES IN HUMANS RESPONSES IN HEALTHY DONORS TO HOMOCITRULLINATED PEPTIDES Aldo 74Hcit (BD0016) Aldo 140Hcit (BD0016) Vim116Hcit (BD0016) TCR Vα TCR Vβ TCR Vα TCR Vβ TCR Vα TCR Vβ CFSE CFSE CFSE high high high CFSE CFSE CFSE low low low Repertoire data for TCR Vα and Vβ
Slide 37: TCR transduction and adoptive T cell transfer
TCR TRANSDUCTION AND ADOPTIVE T CELL TRANSFER Single cell sorting T cell CFSE-A T cells infused stimulation into cancer with antigen patient Normal donor T cells CD4 Transfected mRNA capture into human T cells and TCR cloning by population PCR & expanded sequencing Recombinant antigen- specific TCR
Slide 38: Moditope TCR approach
MODITOPE® TCR APPROACH T cells infused ADVANTAGES OF CITRULLINATED & into cancer HOMOCITRULLINATED ANTIGEN-SPECIFIC TCRS patient Citrullinated & homocitrullinated antigens are expressed by a wide range of tumours Citrullinated & homocitrullinated antigen-specific T cells recognise the non-polymo
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