Prescient Therapeutics Limited · ASX:PTX
Prescient Therapeutics — Investor Presentation (October 2021)
36 slides from Prescient Therapeutics's investor presentation, Oct 13, 2021
Slide 1: Creating next-gen cell therapies that are controllable, flexible & adaptable
Creating next-gen cell therapies that are controllable, flexible & adaptable Prescient Therapeutics Limited (ASX: PTX) Cell & Gene Meeting on the Mesa October 2021
Slide 2: 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 3: Corporate Snapshot
Corporate Snapshot OVERVIEW METRICS • HQ in Melbourne, Australia, with activities in Australia and US ASX Ticker PTX • Est 2014 with assets from Yale (PTX-100) and Moffitt/USF Total Issued Capital 643 M shares (PTX-200); and UPenn/Oxford (OmniCAR) in 2020 Listed Options 93.4 M • Programs in US & Aus
Slide 4: Innovative Pipeline in Personalised Medicine
Innovative Pipeline in Personalised Medicine Program Discovery Screening Preclinical Phase I Phase IB Phase II OmniCAR CD33 & CLL-1 AML OmniCAR HER2 Breast, Ovarian & Gastric cancers OmniCAR HER2 & EGFRviii GBM Targeted Undisclosed 1 Therapies Cell Therapy Enhancements Undisclosed 2 PTX - 100 PTCL P
Slide 5: Universal, Next Generation CAR-T
Universal, Next Generation CAR-T 5
Slide 6: Key Challenges Confronting the field of CAR-T
Key Challenges Confronting the field of CAR-T Targets Time and Cost Finding targets that work; of delivering treatment Antigen heterogeneity - esp. in solid tumours Safety Exhaustion CAR-T can have serious Persistent stimulation of CAR- safety concerns Immune cells leads to exhaustion No Control Esc
Slide 7: OmniCAR Universal Immune Receptor Platform
OmniCAR Universal Immune Receptor Platform • Pre-clinical modularised universal immune receptor (UIR) platform • Potential best-in class UIR Co-inventors • Based on multi-disciplinary technology licensed from Penn • Only UIR system with post-translational covalent binding • Unique, powerful and flex
Slide 8: How OmniCAR works
How OmniCAR works 3 1 Results in a complete, 2 armed CAR-T cell Unarmed CAR-T Armed CAR-T cells cells are are activated, administered to resulting in on-demand patient tumour killing viable but inactive Separate administration of targeting ligand CAR-T cell activity is now controllable Target specif
Slide 9: An elegant and effective approach
An elegant and effective approach OmniCAR can Only UIR with spontaneous, use any type autocatalytic, of targeting covalent bond ligand… formation Binds targeting ligand to cell signalling domain …with any immune cell Adapted from Powell, DJ et al, JACS; 2020 9
Slide 10: Safety: Ability Control Dose & Activity
Safety: Ability Control Dose & Activity Conventional CAR-T • Clinicians have no control over CAR-T activity once injected Clinician control post infusion • Estimate optimal dose before infusion Controlling subsequent dose of binder controls CAR-T activity • Half-doses of CAR-T cells provide limited
Slide 11: Safety: Built-in on/off switch
Safety: Built-in on/off switch Proliferation of unarmed OmniCAR cells • Cell activity can be switched off at-will • Cells remain viable but inactive • OmniCAR can be safely reactivated • No uncontrolled activity • Ongoing stimulation for greater efficacy & persistence Concept to be tested in human u
Slide 12: Target Multiple Antigens Sequentially
Target Multiple Antigens Sequentially • Switching binder redirects the T-cell • Uses single vector/cell product • Addresses escape • Useful for rapidly mutating cancers, esp those that cannot afford time for another CAR-T production run • E.g. AML Concept to be tested in human under well controlled
Slide 13: Target Multiple Antigens Simultaneously
Target Multiple Antigens Simultaneously • Multiple antigen targeting with single vector/cell product • Could broaden anti-tumour immune response • Prevents escape • Tailor arming combinations and proportions • Utility in many solid tumours Concept to be tested in human under well controlled clinical
Slide 14: OmniCAR cells + “plug & play” binder library
The future of ACT is efficient yet personalized: OmniCAR cells + “plug & play” binder library Step 3: Pair binders with OmniCAR cells (T cells; NK; auto/allo) Step 2: Step 4: Match patient’s Tailored, antigens to optimised & safe: Library of SpyTagged Binders corresponding binders OmniCAR- induced t
Slide 15: Covalent Binding: Superior tumor killing & other advantages
Covalent Binding: Superior tumor killing & other advantages Covalent Non-Covalent • Covalent binding improves SpyCatcher T-cell loading and tumour cell lysis SKOV3 tumor cells • Covalent binding has additional advantages in: • Efficacy • Predictability • Clinical utility • Regulatory considerations
Slide 16: OmniCAR HER2: predictable cytotoxicity
OmniCAR HER2: predictable cytotoxicity 4:1 HER2 OmniCAR 2:1 HER2 OmniCAR At 2:1, OmniCAR achieves cytotoxicity Tumor Cells at a rate that aims to balance efficacy Unarmed OmniCAR HER2 Armed OmniCAR whilst avoiding CRS and exhaustion 16
Slide 17: Flexible Loading and Dose-Dependent Lysis
Flexible Loading and Dose-Dependent Lysis • OmniCAR T-cells capable of being armed with • Increasing targeting ligand concentration varying amounts of SpyTagged targeting ligand results in increased lytic capacity Powell, DJ et al, JACS; 2020 Non-Confidential – Please do not distribute outside your
Slide 18: Dose response: High potency with less binder required
Dose response: High potency with less binder required 2:1 ST-EGFRviii binder vs U251 EGFRviii cells • Dose-dependent CAR-T activity • V3 OmniCAR significantly more potent, and likely safer, than V1 system and competitor UIRs • Potency with 60 fold less binder (low nM range) • Means improved safety a
Slide 19: Control: Dose-dependent CAR-T activity
Control: Dose-dependent CAR-T activity • 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 Powell, DJ et al, JACS; 2020 = dosing window of binder 19
Slide 20: Re-Arming: OmniCAR Her2 can be Re-Armed
Re-Arming: OmniCAR Her2 can be Re-Armed T cell activation Transduction Armed Cytotoxicity assay 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 OmniCA % live cel
Slide 21: Equal Arming & Equal Tumour Killing
Equal Arming & Equal Tumour Killing Equal arming Specifically directed, at-will killing anti-HER2 anti-EGFR Both anti- EGFR + anti-HER2 CAR-T equally armed with: • Only kills cells that the CAR-T is armed against Both anti-EGFR + anti-HER2 anti-EGFR anti-HER2 control • OmniCAR CAR-T cells have simil
Slide 22: Redirection: Adding new ST-binder can re-direct cytotoxicity
Redirection: Adding new ST-binder can re-direct cytotoxicity Antigen Target Re-direction in Coculture of U251 GBM Cells expressing HER2 or EGFRviii • Rapid cytotoxicity to EGFRviii • Rapid switching and cytotoxicity against HER2+ tumours upon administration of new binder • OmniCAR cells can be re-di
Slide 23: In-silico immunogenicty on par with Human mAbs
In-silico immunogenicty on par with Human mAbs MHC Class II MHC MHCClass Class I 1 MHC Class 2 8000 8000 6000 6000 4000 4000 2000 2000 1200 1200 1100 1100 1000 1000 iTrop-AI score iTrop-AI score 900 900 800 800 700 700 600 600 500 500 400 400 300 300 200 200 SpyCatcher 100 100 SpyCatcher SpyTag (L+H
Slide 24: OmniCAR Internal Program Summary
OmniCAR Internal Program Summary Targets Indications OmniCAR features Comments • 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 (AML) • 1 of 3 programs worldwide; the • Sequential targetin
Slide 25: AML: OmniCAR CD33/CLL-1
AML OmniCAR CD33/CLL-1 25
Slide 26: For CAR-T to succeed in AML, it must overcome:
For CAR-T to succeed in AML, it must overcome: Safety Rapid Mutations Rapid Disease Progression AML patients are AML can mutate mid- Even if multiple current generation especially ill with many therapy, quickly CAR-T therapies were available, unable to tolerate rendering single CAR- resistant patien
Slide 27: CD33 & CLL-1 are excellent AML targets for CAR-T
CD33 & CLL-1 are excellent AML targets for CAR-T • CD33 ▪ Validated target in AML with approved anti-body drug conjugate (gemtuzumab ozogamicin, or Mylotarg) ▪ CD33 is constantly expressed on both normal and malignant myeloid cells ▪ CD33 expressed on >90% adult and childhood AML blasts and on leuke
Slide 28: Targeting Multiple Antigens Sequentially OR Simultaneously
Targeting Multiple Antigens Sequentially OR Simultaneously Sequentially Simultaneously CD33 CLL-1 binder binder • Co-Arming against CD33 & CLL1 on a single T-cell product • Address antigen escape by redirecting T- cells without new dose of T-cells • Target several cancer cell populations at once: •
Slide 29: Solid Tumors
"4. Prescient Gut Therapeutics
Slide 30: Key challenges for CAR-T in solid tumours
Key challenges for CAR-T in solid tumours Targets Safety Trafficking TME Limited targets that Ability to titrate doses Inability of T-cells to Overcoming an are cancer-specific safely and switch off in reach tumour sites immunosuppressive the event of adverse and penetrate Tumour Leads to on-target,
Slide 31: Huge market opportunities for HER2+ cancers
Huge market opportunities for HER2+ cancers New cases/year Proportion that New HER2+ worldwide1 are HER2+ 2,3,4 cases/year Ovarian Cancer 300,000 29% 87,000 Breast Cancer 1,700,000 20% 340,000 Gastric Cancer 952,000 22% 209,440 • OmniCAR T cells armed against HER2 • Builds upon the encouraging work
Slide 32: GBM: OmniCAR HER2/EGFRviii
GBM OmniCAR HER2/EGFRviii 32
Slide 33: CAR-T challenges in GBM: single antigen targeting
CAR-T challenges in GBM: single antigen targeting • Composition of GBM, and its ability to rapidly mutate, limits the effectiveness of CAR-Ts only targeting a single antigen • Targeting a single antigen targeting can result in relapse “A major limitation of a single-antigen targeting in GBM is the i
Slide 34: Two targets are better than one in GBM
Two targets are better than one in GBM • Single antigen targeting has been inadequate in GBM HER2 EGFRviii • By contrast, combination of HER2 and other antigen targeting shows early promise in overcoming relapse • HER2 occurs in • EGFRviii occurs in 80% of GBM 45% of GBM • Linked with • Importantly,
Slide 35: Summary
Summary • OmniCAR addresses problems encountered by current generation CAR-T • 3 in-house OmniCAR programs, all highly differentiated and representing large opportunities • CD33/CLL-1 for AML • HER2+ solid tumours • HER2/EGFRviii for GBM • Prescient is open to licensing and collaboration. OmniCAR ca
Slide 36: CONTACT
CONTACT Dr. Daniel Shelly, MBA E : dshelly@ptxtherapeutics.com Vice President Business T : 513-309-7409 Development and Alliances W : ptxtherapeutics.com Prescient Therapeutics Limited Steven Yatomi-Clarke E : steven@ptxtherapeutics.com Chief Executive Officer & T : +61 417 601 440 Managing Director
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