Slide 1: Unveiling: Novel platform for enhancing cell therapies
Unveiling Novel platform for enhancing cell therapies Prescient Therapeutics Limited (ASX: PTX)
Slide 2: CellPryme-M: Prescient's newest family member
CellPryme-M: Prescient’s newest family member PLATFORM TO ENHANCE PRODUCES SUPERIOR CELLS CELL THERAPIES • Doubles tumour control & survival • Current gen and next gen • Longer lasting • Complementary to OmniCAR • Tumour trafficking & penetration READY FOR DEVELOPMENT OPPORTUNTIES CLINICAL TESTING •
Slide 3: What is CellPryme-M?
What is CellPryme-M? 3
Slide 4: What does CellPryme-M do?
What does CellPryme-M do? CellPryme-M is a single, rapid manufacturing step that produces a better, more effective cell type: LONGER LASTING CELLS FOR CELLS THAT CAN BETTER SUSTAINED TUMOUR KILLING LOCATE THE TUMOUR • 50% more memory T cells • Significantly more chemokine receptors for improved • Do
Slide 5: How does CellPryme-M work?
How does CellPryme-M work? • Rapid, single 24-hour preconditioning step with standard manufacturing protocols • Influences gene expression in immune cells • “Pushes” the cells towards a more favourable phenotype Untrans Untreated duced- Vehicle- PT1 PT2 Vehicle Vehicle- Vehicle- CellPryme-M PT1 PT3
Slide 6: CellPryme-M Complements OmniCAR
CellPryme-M Complements OmniCAR • Multi-targeting • Redirection • Control & safety • Any target; any cell Process that produces a better cell type • Persistence • Trafficking Next generation Current generation Cell therapies cell therapies 6
Slide 7: What problems does CellPryme-M overcome?
What problems does CellPryme-M overcome? 7
Slide 8: CAR-T cells: Not just one cell type!
CAR-T cells: Not just one cell type! T cells are extremely heterogenous, each with their own unique “fingerprint” that dictates where they go and what they do CD8+ T cells deliver the payload to kill cancer cells CD4+ T cells release cytokines and growth factors to sustain CD8+ T cells Nature Immuno
Slide 9: 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 • 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 Naïve T cells Stem memory
Slide 10: Overcoming CAR-T's key challenges
Overcoming CAR-T’s key challenges Conventional Next Next generation CAR-T generation Poor cell expansion; manufacturing time & cost n/a Safety Post infusion control Tumour heterogeneity Escape Trafficking Tumour penetrance Suppressive tumour microenvironment Exhaustion/pers
Slide 11: Persistence, Trafficking, Tumour penetrance
CellPryme-M produces CAR-T cell types with ideal characteristics and attributes Persistence Trafficking CAR-T cells able to find For longevity of effects and their way to the tumour continued tumour control Tumour penetrance Immune memory Cells that can penetrate Central memory T cells typically sol
Slide 12: Compelling data
Compelling data 12
Slide 13: Greater Persistence: 50% more central memory cells
Greater Persistence: 50% more central memory cells than conventional CAR-T CellPryme-M increases central memory T cells 1.5-fold within 24hrs 100 CD8+CAR+ 80 CD8 + N GFR + % Conventional CAR-T CellPryme-M CAR-T Tem (CD44hiCD62Llo) 60 Tcm (CD44hiCD62Lhi) CD8+ CAR+ % 40 CD44 20 TCM TCM 0 1 2 O CD62L 1
Slide 14: Greater Persistence/Less Exhaustion
Greater Persistence/Less Exhaustion 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 p<0.0001 100 % CAR CD4+ T cells % CD8+ CAR T cells p=0.0029 % CD8+ C
Slide 15: Synergy: CellPryme-M doubles proportion of helper T cells
Synergy: CellPryme-M doubles proportion of helper T cells 100 helper • Shift towards dominant helper CD4+ CAR T cells 80 %CD4/CD8 CD4+ CAR T • Helper T cells are known to prevent the exhaustion 60 CD8+ CAR T of cytotoxic CD8+ T cells 40 cytotoxic • Some can also have tumour killing ability 20 0 • He
Slide 16: CellPryme-M retains potency of cytotoxic T cells
CellPryme-M retains potency of cytotoxic T cells Better T cell phenotype does not come at the expense of: Conventional CellPryme-M Control CAR-T CAR-T • Cytotoxic T cells: Potency retained CAR+CD8+ T Cells • Cytokine production: No increased safety risk of CRS 16
Slide 17: Trafficking: greater chemokine receptor expression
Trafficking: greater chemokine receptor expression Chemokine receptor expression on CD8+ cytotoxic CAR-T cells • Effector T cells can downregulate chemokine receptors (CXCR3), limiting the ability of 1.3 p<0.0001 conventional CAR-T cells to locate tumours CXCR3 expression 1.2 • CellPryme-M significa
Slide 18: CellPryme-M doubles tumour control and survival
CellPryme-M doubles tumour control and survival CellPryme-M nearly doubles CellPryme-M significantly CAR-T tumour control increases survival 150 CellPryme-M CAR T Tumour area (mm2) p=0.0140 n.s. 100 Conventional CAR T 50 Control 0 0 5 10 15 20 25 0 10 20 30 Time post treatment (d) Days post tumour i
Slide 19: Steps towards commercialisation
Steps towards commercialisation 19
Slide 20: CellPryme-M integration: rapid, value for money
CellPryme-M integration: rapid, value for money • Integrates seamlessly into standard 3rd party manufacturing protocols • No impact on manufacturing time • Rapid (single administration) 24-hour preconditioning step • Compatible with emerging rapid CAR-T manufacturing protocols • CellPryme-M has been
Slide 21: Next steps and future applications
Next steps and future applications IN-HOUSE DEVELOPMENT EXTERNAL OPPORTUNITIES • Incorporate into 3rd party programs • PTX will be its own first customer • Attractive option for improving existing • Incorporate into internal suboptimal CAR T products OmniCAR programs • Haematological malignancies •
Slide 22: CellPryme-M Summary
CellPryme-M Summary PLATFORM TO ENHANCE PRODUCES SUPERIOR CELLS CELL THERAPIES • 50% more memory T cells • Current gen and next gen • Doubles helper T cells • Complementary to OmniCAR • More CXCR3 = tumour trafficking • Doubles tumour control & survival • Greater genomic stability • Enhanced anti-vi
Slide 23: Coming soon: PTX-100 / PTX-200
PTX-100 PTX-200 Coming soon: A synergistic cell therapy enhancement 23