Prescient Therapeutics Limited · ASX:PTX
Prescient Therapeutics — Investor Presentation (November 2022)
76 slides from Prescient Therapeutics's investor presentation, Nov 2, 2022
Slide 1: PTX-100 investor update and additional patient response
PTX-100 investor update and For personal use only additional patient response MELBOURNE Australia, 2 November 2022: Prescient Therapeutics (ASX: PTX), a clinical stage oncology company developing personalised therapies to treat cancer, will be holding an investor briefing on Wednesday 2nd November a
Slide 2: About Prescient Therapeutics (announcement continued)
The targeting ligand can be administered separately to CAR-T cells, creating on-demand T-cell activity post infusion and enables the CAR-T to be directed to an array of different tumour antigens. OmniCAR provides a method for single-vector, single cell product targeting of multiple antigens simultan
Slide 3: Disclaimer and Safe Harbor Statement
Disclaimer and Safe Harbor Statement Certain statements made in this document are forward-looking statements within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These forward-looking For personal use only statements are not historic
Slide 4: In front of the biggest wave in oncology
For personal use only IN FRONT OF THE BIGGEST WAVE IN ONCOLOGY November 2022 1
Slide 5: Disclaimer and safe harbor
Disclaimer and safe harbor Certain statements made in this document are forward-looking statements within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These forward-looking statements are not historical facts but rather are based on
Slide 6: Corporate snapshot
Corporate snapshot For personal use only ASX Ticker PTX Total Issued Capital 705 M shares Listed Options 85.4 M Unlisted Options 38.3 M Share Price1 A$0.17 Market A$120 M Capitalisation1 Market Cap fully A$140 M diluted1 Cash Position2 A$21M Top 20 Own 16% 1 - AS AT 24 OCT 2022 2 – UNAUDITED, POST O
Slide 7: Investment Highlights
Investment Highlights For personal use only World class pedigree. We license from the best; and work with the best Many shots on goal for 2 Cell Therapy platforms substantial value creation Internal & external opportunities 2 Targeted Therapies Upcoming newsflow in clinical trials, showing activity
Slide 8: Very productive Sept quarter
Very productive Sept quarter For personal use only Successful Unveiling capital raising CellPryme-A bolsters cash Strategic adjuvant to $21.9m collaboration QGen to platform with OmniCAR manufacture MD Anderson platform OmniCAR FDA Orphan extensions cells Drug status for PTX-100 Key OmniCAR patent g
Slide 9: Innovative Personalised Oncology Assets
4 Innovative Personalised Oncology Assets For personal use only Cell therapy Next-gen Targeted therapies platforms CAR-T therapies CD33/CLL-1 Acute Myeloid PTX-100 Leukaemia Ras / Rho inhibitor Her2/EGFRviii Glioblastoma Multiforme PTX-200 Novel AKT Her2 inhibition Breast, Ovarian & Gastric cancers
Slide 10: Innovative pipeline in personalised medicine
Innovative pipeline in personalised medicine Platform Program Screening Preclinical Phase IB Phase II For personal use only AML CD33; CLL-1 Novel TCR binder Her2+ solid Her2 tumours GBM Her2; EGFRviii Platform extensions Various CellPryme-M Cell manufacturing enhancement CellPryme-A Adjuvant for cel
Slide 11: Targeted Therapies
For personal use only TARGETED THERAPIES 8
Slide 12: PTX-100 First in class Ras pathway inhibitor
For personal use only PTX-100 FIRST IN CLASS RAS PATHWAY INHIBITOR 9
Slide 13: PTX-100 Phase 1B Summary
PTX-100 Phase 1B Summary Licensed from For personal use only • Licensed from Yale University • Targeting cancers predisposed to Ras & Rho mutations Principal Investigator Phase 1b Expansion cohort in T-cell lymphomas (TCL) • Excellent safety profile • Encouraging signal in TCL • Reponses Professor H
Slide 14: Trial update: continued encouraging responses & time on treatment
Trial update: continued encouraging responses & time on treatment For personal use only CLINICAL REPOSNES & MONTHS ON TREATMENT • 1 VGPR (ongoing) • 3 PRs (1 ongoing) • 2 SDs (both ongoing) • 2 PD Very Good Partial Response (VGPR) Partial Response (PR) • 3 withdrawn Stable Disease (SD) Ongoing treat
Slide 15: Before / After
For personal use only Before After ASX: PTX
Slide 16: Before / After
For personal use only Before After ASX: PTX
Slide 17: Before / After
For personal use only Before After ASX: PTX
Slide 18: Before / After
For personal use only Before After ASX: PTX
Slide 19: Favourable safety profile compared to peers
Favourable safety profile compared to peers For personal use only Approved PTCL drugs have troublesome safety profiles % Serious Adverse Events (≥Grade 3) PTX-100 HAS AN for Approved PTCL Drugs EXCELLENT SAFETY PROFILE Mogamulizumab • No serious adverse events Chidamide related to PTX-100 Brentuxima
Slide 20: Now in Expansion Cohort for TCL
Now in Expansion Cohort for TCL For personal use only Case Study • 8 – 12 patients with r/r T cell lymphoma • pralatrexate (Folotyn®) • Expanding number for CTCL patients in • Approved for PTCL light of responses • 5,600 cases/year in US • US$450,540 per patient, per year • Potential bridge to regis
Slide 21: PTX-200 Novel AKT inhibition
For personal use only PTX-200 NOVEL AKT INHIBITION 18
Slide 22: Phase 1B trial underway: Acute Myeloid Leukemia
Phase 1B trial underway: Acute Myeloid Leukemia For personal use only • Building upon encouraging Phase 1 results with PTX-200 (monotherapy) Principal Investigator • PI Professor Jeff Lancet at Moffitt, Key Opinion Leader in AML • 24 patients with cytarabine held constant at 200-400 mg/m2 as continu
Slide 23: Cell Therapy Platforms
For personal use only CELL THERAPY PLATFORMS 20
Slide 24: The CAR-T process
The CAR-T process For personal use only T-Cells are genetically altered to have Blood is collected from 1 the patient 2 T-Cells are isolated 3 cancer-recognising receptors (CARs) CAR-T cells are administered to 4 Millions of CAR-T cells are grown 5 the patient 21
Slide 25: CAR-T is booming
CAR-T is booming GlobalData forecasts CAR-T sales to 2028 exceed US$37bn TODAY For personal use only • 10y+ remissions 2023 GlobalData forecasts • Continued positive data flow Kymriah® sales to exceed US$1bn • Some outstanding results • 100s of companies targeting different antigens to target 2017 m
Slide 26: Penn is a pioneer and world leader in CAR-T
Penn is a pioneer and world leader in CAR-T For personal use only • Novartis licensed CAR-T technology from Penn in 2012 • Kymriah® became the first CAR-T therapy approved by the FDA • Used for certain blood cancers • Cost of treatment in excess of $500,000 per treatment • GlobalData forecasts Kymri
Slide 27: CAR-T's key challenges
CAR-T’s key challenges Challenge For personal use only Safety / Control No control post infusion Difficulties with targeting, Unsafe Targeting antigen heterogeneity Escape Difficulties with mutating antigens Less effective Production efficiency Cost prohibitive & slow Not sustainable Exhaustion Cell
Slide 28: Platforms to overcome CAR-T's key challenges
Platforms to overcome CAR-T’s key challenges Challenge For personal use only Safety / Control No control post infusion - Difficulties with targeting, Targeting antigen heterogeneity - Safe Escape Difficulties with mutating antigens - Effective Production efficiency Cost prohibitive & slow -
Slide 29: Universal, Next Gen CAR-T Platform
For personal use only Universal, Next Gen CAR-T Platform 26
Slide 30: OmniCAR: flexible, modular CAR platform
OmniCAR: flexible, modular CAR platform For personal use only Targeting ligand Using any targeting SpyTag Covalent ligand… bond Spy Catcher Associate Professor Professor Daniel J. Powell, Jr Andrew Tsourkas Signalling domain …with any immune UNARMED ARMED CAR-T cell CAR-T cell cell 27
Slide 31: How OmniCAR works
For personal use only How OmniCAR works 28
Slide 32: OmniCAR can do what conventional CAR-T cannot
OmniCAR can do what conventional CAR-T cannot For personal use only Conventional CAR-T Can be given any map; Armed with any weapon Multiple deployments Including several at once • Soldier with only one map • Single weapon Full communication • Only trained to hit one target and control at all times,
Slide 33: OmniCAR: Control Features
OmniCAR: Control Features For personal use only Modular and covalent architecture of OmniCAR enables true post-infusion control of CAR functionality Dose Titration On/off switch Target Re-direction Multi-Antigen Targeting Control activity to safe Turn therapy on/off/on Re-direct cells from Target mu
Slide 34: Control: Dose-dependent CAR-T activity
Control: Dose-dependent CAR-T activity For personal use only • Ovarian cancer model, using anti-HER2 OmniCAR • Loading more binder results in proportionate killing of cancer… • …and proportionate survival • Lasting effects even when cease dosing of binder 31 Powell, DJ et al, JACS; 2020 = dosing win
Slide 35: OmniCAR cells can be Re-Armed
OmniCAR cells can be Re-Armed T cell activation Transduction Armed Cytotoxicity assay For personal use only Day 0 Day 3 Day 7 Days 8–10 Re-armed Cytotoxicity assay Wash; Rest 2:1 OmniCARDay Her2 12 normalised post-REP Days 13–14 2:1 OmniCAR Her2Anormalised pre-REP B 150 150 Tumour alone Washed Omn %
Slide 36: OmniCAR cell can be Redirected
OmniCAR cell can be Redirected Target Re-direction in Coculture of GBM Cells For personal use only HER2 expressing HER2 or EGFRviii EGFRviii 1 OmniCAR T cells pre-armed with EGFRviii binder → Rapid cytotoxicity to EGFRviii+ cells 2 Add Her2 binder → Rapid switching & cytotoxicity to Her2+ cells No n
Slide 37: OmniCAR cells viable & armable for weeks
OmniCAR cells viable & armable for weeks For personal use only OC25 Mice with tumour growth OC25 tumourscurves Binder administered from day 21 150 Binder administration 25ug every 2 days • Unarmed & armed OmniCAR-T Tumour size (mm2) 100 Untreated cells are viable for weeks Unarmed OmniCAR-T • Can be
Slide 38: Regulatory, manufacturing & COGS advantages
Regulatory, manufacturing & COGS advantages For personal use only Conventional CAR-T 6 INDs 1 IND 1 Optimized Manufacture 6 Manufacturing runs 1 Vector/Transduction 6 Vectors/Transductions 1 Release program 6 Sets of release testing Multiple binders off the shelf No Flexibility No time delay for sub
Slide 39: Next Gen CAR-T Programs
For personal use only Next Gen CAR-T Programs 36
Slide 40: OmniCAR internal program summary
OmniCAR internal program summary Targets Indications OmniCAR features Comments For personal use only • Titration for improved safety • Validated targets; expressed on Acute Myeloid 90%+ of AML blasts & LSCs CD33 + Leukemia • Co-arming against CD33 & CLL-1 CLL-1 • 1 of 5 programs worldwide; the (AML)
Slide 41: OmniCAR progressing towards clinic
OmniCAR progressing towards clinic For personal use only • Steady progress across all programs • OmniCAR AML likely the first program in clinical trials • Q-Gen Cell Therapeutics appointed as cell manufacturer • Clinical grade cells • Autologous T cells expressing SpyCatcher • Incorporating CellPrym
Slide 42: MD Anderson Cancer Center
MD Anderson Cancer Center For personal use only 39
Slide 43: MD Anderson's ECLIPSE platform has yielded novel TCR-like binders
MD Anderson’s ECLIPSE platform has yielded novel TCR-like binders For personal use only MD Anderson’s novel Strategic Collaboration TCR-like binder library • Broad library of samples from leukemia • Strategic collaboration to add novel patients (ECLIPSE platform) TCR binder to OmniCAR • Uncovered un
Slide 44: Adding TCR-like binder to OmniCAR for AML
Adding TCR-like binder to OmniCAR for AML For personal use only CD33 binder • Using “plug & play” features of OmniCAR to combine novel TCR-like binder with CD33 & CLL-1 for AML TCR-like binder • Create an unprecedented level of multivalency and control. CLL-1 binder OmniCAR T cell • For the first ti
Slide 45: Cell Therapy Enhancements
For personal use only CELL THERAPY ENHANCEMENTS 42
Slide 46: The CAR-T process
The CAR-T process For personal use only T-Cells are genetically altered to have Blood is collected from 1 the patient 2 T-Cells are isolated 3 cancer-recognising receptors (CARs) CAR-T cells are administered to 4 Millions of CAR-T cells are grown 5 the patient 43
Slide 47: Complementary cell therapy enhancement platforms
Complementary cell therapy enhancement platforms For personal use only MANUFACTURING ADJUVANT ENHANCEMENT THERAPY • Produces longer lasting, • Overcomes hostile TME more “youthful” CAR-T cells • Reduces Tregs • Doubles helper T cells • Increases expansion of CAR-T • Doubles tumour control cells in v
Slide 48: CellPryme Complements OmniCAR
CellPryme Complements OmniCAR For personal use only • Multi-targeting • Redirection • Control & safety • Any target; any cell Adjuvant therapy Process that produces • Reduces Tregs a better cell type • Primes TME for cell • Persistence therapy • Trafficking • Boosts CAR-T cell expansion in vivo Next
Slide 49: Cell manufacturing enhancement
For personal use only Cell manufacturing enhancement 46
Slide 50: CellPryme-M Executive Summary
CellPryme-M Executive Summary PROCESS TO ENHANCE For personal use only PRODUCES SUPERIOR CELL THERAPIES CELLS • Incorporate into standard • More “youthful” T cells manufacturing • More effective tumour killing • Current gen and next gen • Longer lasting • Complementary to OmniCAR CellPryme-M IP READ
Slide 51: CellPryme-M produces CAR-T cell types with ideal characteristics
CellPryme-M produces CAR-T cell types with ideal characteristics and attributes For personal use only Immune memory Persistence Central memory T cells typically persist For longevity of effects and 10-20 years and as long as 75 years continued tumour control Trafficking Tumour penetrance CAR-T cells
Slide 52: More memory cells required for clinical efficacy
More memory cells required for clinical efficacy • Clinical efficacy of CAR-T therapy remains dependent on the T cell phenotype For personal use only • It is possible to control this during the manufacturing step We need more of Current CAR-T makes these cells too many of these cells CXCR3 CXCR3 Naï
Slide 53: Greater Persistence: 50% more central memory cells
Greater Persistence: 50% more central memory cells than conventional CAR-T For personal use only Tem (CD44 Tem (CD44 hiCD62L hiCD62L lo) lo) Tcm (CD44 Tcm (CD44 hiCD62L hiCD62L hi) hi) CellPryme-M increases central memory T cells 1.5-fold within 24hrs 100 100 CD8+CAR+ 80 80 %+% CD8+NGFR+% Convention
Slide 54: CellPryme-M doubles tumour control and survival
CellPryme-M doubles tumour control and survival For personal use only CellPryme-M nearly doubles CellPryme-M CAR-T tumour control doubles survival 150 Probability of Survival 100 Tumour area (mm2 ) 80 100 60 40 50 20 0 0 0 5 10 15 20 25 0 10 20 30 40 Time post treatment (d) Days post tumour inoculat
Slide 55: Greater Persistence/Less Exhaustion
Greater Persistence/Less Exhaustion For personal use only Sustained increase in TCM Sustained decrease in TEM for both cytotoxic CD8+ and helper CD4+ for both cytotoxic CD8+ and helper CD4+ CD8+ CAR TCM CD4+ CAR TCM CD8+ CAR TEM CD4+ CAR TEM 100 100 100 100 p<0.0001 % CAR CD4+ T cells % CD8+ CAR T c
Slide 56: Synergy: CellPryme-M doubles proportion of helper T cells
Synergy: CellPryme-M doubles proportion of helper T cells For personal use only 100 100 helper CD4+CD4+ CARCAR T T CD8+CD8+ T • TShift towards dominant helper CD4+ CAR T cells CARCAR 80 80 %CD4/CD8 %CD4/CD8 100 CD4+ CAR T 60 60 80 CD8+ CAR T • Helper T cells are known to prevent the exhaustion %CD4/
Slide 57: Trafficking: greater chemokine receptor expression
Trafficking: greater chemokine receptor expression For personal use only Chemokine receptor expression on CD8+ cytotoxic CAR-T cells • Effector T cells can downregulate chemokine 1.3 receptors (CXCR3), limiting the ability of p<0.0001 conventional CAR-T cells to locate tumours CXCR3 expression 1.2 •
Slide 58: Adjuvant for enhancing cell therapies
For personal use only Adjuvant for enhancing cell therapies 55
Slide 59: CellPryme-A Summary
CellPryme-A Summary For personal use only ADJUVANT PLATFORM TO BREAKS DOWN HOSTILE TME ENHANCE CELL THERAPIES • Two-thirds less intratumoral Tregs • Current gen and next gen • Increases CAR-T cell penetration • Complementary to CellPryme-M & OmniCAR into tumours BOOSTS CAR-T IMPROVES TUMOUR EXPANSIO
Slide 60: CellPryme-A addresses the hostile Tumour Microenvironment
CellPryme-A addresses the hostile Tumour Microenvironment (TME) For personal use only • TME is the complex ecosystem surrounding solid tumours • Protects and nurtures the cancer • Acts as a protective “force field” that bluntens the effectiveness of cancer therapies 57
Slide 61: Treg cells are central players in the TME
Treg cells are central players in the TME For personal use only Tregs are immunosuppressive cells in the TME (i.e. suppresses the immune response) • Causes T cell exhaustion • Causes T cell death • Produces cytokines that cause the tumour to go “cold” • Impairs NK cell function Reducing Tregs is key
Slide 62: Summary of CellPryme-A effects
Summary of CellPryme-A effects For personal use only Boosts tumour killing by Improved survival conventional CAR-T cells Dramatically increases Reduces problematic CAR-T cell expansion within Treg cells by 66% • 2x ↑ CAR-T cell expansion host • 9x↑ Cytotoxic T cells with CellPryme- • 6x ↑ Helper T c
Slide 63: CellPryme-A significantly boosts CAR-T efficacy
CellPryme-A significantly boosts CAR-T efficacy For personal use only CAR T cells Experimental end point CellPryme-A (twice a week) Tumour size > 150 mm2 or 28 days unless other humane endpoints are reached 0 7 10 Colon cancer cells are transplanted into the mammary fat pad CellPryme-A + CellPryme
Slide 64: CellPryme-A improves survival
CellPryme-A improves survival For personal use only Survival 100 Probability of Survival (%) • Highly aggressive and resistant cancer model • CAR-T cells did not improve survival in this model U • CellPryme-A improved the survival of animals given CAR-T cells by over 20% (5 days) C 50 C • The combin
Slide 65: CellPryme-A significantly decreases problematic Tregs in tumours
CellPryme-A significantly decreases problematic Tregs in tumours For personal use only CellPryme-A significantly reduced intra-tumoural Tregs by two-thirds Conventional Her2 CAR-T cell therapy followed by CellPryme-A adjuvant therapy 62 *p<0.05; Kruskal-Wallis one-way ANOVA
Slide 66: CellPryme-A synergises with CellPryme-M to expand CAR-T cells
CellPryme-A synergises with CellPryme-M to dramatically expand CAR-T cells in vivo For personal use only ↑9x ↑6x CD8+ Cytotoxic T CD4+ T helper cells cells 63
Slide 67: CellPryme-A significantly increases CAR-T cell penetration into tumours
CellPryme-A significantly increases CAR-T cell penetration into tumours For personal use only ↑3x ↑4x CD4+ T helper CD8+ Cytotoxic T cells cells **p<0.01, ****p<0.0001, Mann-Whitney test Tumours collected from parallel cohort of animals at Day 21 64
Slide 68: CellPryme-A ready for the clinic
CellPryme-A ready for the clinic For personal use only CLINIC-READY THERAPY CAR-T cells • Ready for clinical testing as adjuvant/neoadjuvant therapy • Straightforward to incorporate adjuvant into other CAR-T programs • Robust regulatory package • Clinical grade material available 65
Slide 69: Scope, Model & Business
For personal use only SCOPE MODEL & BUSINESS
Slide 70: Prescient's CAR-T platform business model
Prescient’s CAR-T platform business model PTX Programs For personal use only PTX CD33 + CLL-1 PTX platforms PTX HER2 • Huge market PTX HER2 + EGFRviii • “Shovels to CAR-T External partners goldrush” Partner 1 Partner 2 • Diversified risk Partner 3 Partner 4 • Highly scalable Partner 5 • Earlier reve
Slide 71: Commercial models - Partners
Commercial models - Partners For personal use only Partner 1 Agreement Development Sales Upfront fee Milestone fees Royalties & milestone fees Partner 2 Agreement Development Sales Upfront fee Milestone fees Royalties & milestone fees Partner 3 Development Sales Agreement Upfront fee Milestone fees
Slide 72: The End Game: Personalized Plug & Play Cell Therapy Ecosystem
The End Game: Personalized “Plug & Play” Cell Therapy Ecosystem For personal use only Step 4: Step 3: Bespoke therapy with Pair binders with OmniCAR cells post-infusion control (T cells; NK; auto/allo) Step 2: Match patient’s antigens to corresponding binders Step 1: Patient sample to determine indi
Slide 73: Summary
For personal use only Summary 70
Slide 74: Top-down analysis is sensible for investors
Top-down analysis is sensible for investors For personal use only Oncology* 1 Biggest Market in • 2021: US$ 280bn Healthcare? • 2029: US$ 536bn (8.2% CAGR) 2 Fastest growing area Cell Therapies (CAR-T) in oncology? • >US$37bn by 2028^ Prescient Therapeutics 3 Forefront of • Next gen platforms Cell T
Slide 75: Investment Thesis Summary
Investment Thesis Summary 4 blue chip Superior Huge & For personal use only oncology assets positioning & model growing market 2 next gen platforms Internal products + external partnering $280bn industry PTX-100 & PTX-200 Shovels to goldrush Growing demand in clinic Top pedigree Highly scalable Cell
Slide 76: Thank you!
For personal use only Thank you! ASX code: PTX www.ptxtherapeutics.com
Prescient Therapeutics — Investor Presentation (November 2022) on 6ix