Prescient Therapeutics Limited · ASX:PTX
Prescient Therapeutics — Investor Presentation (October 2017)
43 slides from Prescient Therapeutics's investor presentation, Oct 5, 2017
Slide 1: Developing Novel Targeted Therapies to Beat Cancer: Spotlight on PTX-100
For personal use only DEVELOPING NOVEL TARGETED THERAPIES TO BEAT CANCER SPOTLIGHT ON PTX-100 Prescient Therapeutics Limited (ASX: PTX) October 2017
Slide 2: Disclaimer and Safe Harbor
DISCLAIMER AND SAFE HARBOR For personal use only 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 b
Slide 3: Company Overview
COMPANY For personal use only OVERVIEW 3 TARGETED THERAPIES YIELDING A DEEP CLINICAL PIPELINE
Slide 4: Investment Highlights
INVESTMENT HIGHLIGHTS For personal use only 2 DRUGS » IMMINENT CATALYSTS » FUNDING IN PLACE » UNDISCOVERED VALUE • 2 targeted therapies with impeccable scientific pedigree • Multiple shots on goal with Akt and Ras pathway inhibitors in multiple trials • One of deepest clinical pipelines on the ASX »
Slide 5: Corporate Snapshot
CORPORATE SNAPSHOT For personal use only KEY METRICS ASX Ticker PTX Market Capitalisation1 A$13.0 M (US$10.3 M) Total Issued Capital 211.3 M shares Cash Position2 A$7.7 M (US$6.1 M) Options 57.8 M Top 20 Own 52% Share Price1 A$0.062 (US$0.049) 6 month turnover1 39 M shares; A$3.0 M (US$2.4 M) SHARE
Slide 6: Deep, Clinical Stage Product Pipeline
DEEP, CLINICAL STAGE PRODUCT PIPELINE For personal use only • PTX-200 currently in three clinical trials (BRCA and OVCA recruitment currently on hold pending SAE response) • Advancing PTX-100 in rare hematological cancers - a transformative opportunity DISCOVERY SCREENING PRE-CLINICAL PHASE 1 PHASE
Slide 7: Continuing to Deliver Meaningful Progress
CONTINUING TO DELIVER MEANINGFUL PROGRESS For personal use only RECENT PROGRESS PLANNED UPCOMING ACTIVITIES PTX-200 PTX-100 AML: Phase 1b study initiated at Moffitt and Yale; first cohort successfully completed • Commence activities in new hematology indication Breast Cancer: Phase 1b completed
Slide 8: Drugs Don't Develop Themselves! PTX Development Team
DRUGS DON’T DEVELOP THEMSELVES! PTX DEVELOPMENT TEAM WITH BENCH TO BEDSIDE SUCCESS For personal use only Proven success from discovery and clinical development, through to FDA approvals • Professor and Chair, Department of Drug Discovery - Moffitt Cancer Center Said Sebti, PhD • Co-inventor of PTX-1
Slide 9: World Class Centers & Collaborations
WORLD CLASS CENTERS & COLLABORATIONS For personal use only CONNECTICUT KANSAS NEW YORK FLORIDA PREVIOUS CLINICAL TRIALS CONDUCTED AT: 9 TARGETED THERAPIES YIELDING A DEEP CLINICAL PIPELINE
Slide 10: PTX-100: First in Class Inhibitor of Ras Pathway
PTX-100 For personal use only FIRST IN CLASS INHIBITOR OF RAS PATHWAY Phase 1 in solid tumors completed; Now pursuing a transformative opportunity in rare blood cancers 10 TARGETED THERAPIES YIELDING A DEEP CLINICAL PIPELINE
Slide 11: Ras Pathway Is an Important but Elusive Target
RAS PATHWAY IS AN IMPORTANT BUT ELUSIVE TARGET For personal use only GROWTH FACTOR • Ras mutated in 30% of all human cancers and 90% RECEPTOR TYR KINASE in certain cancers » A staggering 3 million new cancers diagnosed worldwide Grb2 SoS each year with Ras mutations Ras FGTI • Mutant Ras tumors are
Slide 12: PTX-100 (Geranylgeranyl Transferase) Introduction
PTX-100 (GERANYLGERANYL TRANSFERASE) INTRODUCTION For personal use only • PTX-100 (GGTI-2418) small molecule inhibitor of the GGT-1 enzyme PTX-100 (GGTI-2418) • Geranylgeranyl transferase (GGT-1) is key activator in the Ras pathway via Ral, Rac & Rho » Overcomes failures of Farnesyltransferase inhib
Slide 13: PTX-100 Is a Highly Effective Anti Tumor Agent in Pre-Clinical Models
PTX-100 IS A HIGHLY EFFECTIVE ANTI TUMOR AGENT IN PRE-CLINICAL MODELS AND PATIENT FRESH BIOPSIES For personal use only Lung tumor1 • PTX-100 inhibits tumor growth and metastasis, 1200 induces tumor regression, and increases 1000 Vehicle survival in various mouse models: 800 » Inhibits tumor growth i
Slide 14: PTX-100: Completed Phase 1 in Advanced Solid Tumors
PTX-100: COMPLETED PHASE 1 IN ADVANCED SOLID TUMORS Patients • 13 For personal use only Trial Centers • University of Pennsylvania & Indiana University • Heavily pre-treated patients with refractory, advanced solid tumors Patient » 5 rectal; 5 colon; 1 hepatocellular; 1 carcinoid; 1 esophageal Inclu
Slide 15: Rare Diseases Can Transform Smaller Companies
RARE DISEASES CAN TRANSFORM SMALLER COMPANIES For personal use only • Rare diseases (<200,000 patients in US) can present big opportunities for smaller companies • Markets may be too small for some Big Pharma, but are big enough to transform smaller companies • Attractions of rare diseases » Typical
Slide 16: Big Opportunity in Rare Hematological Niche
BIG OPPORTUNITY IN RARE HEMATOLOGICAL NICHE For personal use only • Recent discovery that RhoA mutations are a key driver in certain haematological cancers • Some of these conditions are characterized high unmet need: » Rare » Poor prognoses with short median survival » Very few existing treatment o
Slide 17: Ras Pathway and RhoA Implicated in Hematological Malignancies
RAS PATHWAY, AND RHOA IN PARTICULAR, ARE IMPLICATED IN A NUMBER OF HEMATOLOGICAL MALIGNANCIES For personal use only • Angio-immunoblastic T-cell lymphoma (AITL) is a rare lymphoma with a substantial unmet clinical need » Around 70% of AITL patients harbor RhoA mutations • Other heme malignancies whe
Slide 18: AITL Is a Rare Disease with Few Treatment Options
AITL IS A RARE DISEASE WITH FEW TREATMENT OPTIONS AND POOR PROGNOSIS For personal use only • Angioimmunoblastic T-cell lymphoma (AITL) is rare, aggressive type of T-cell lymphoma • Mostly effects the elderly • Accounts for 1-2% of all non-Hodgkin lymphomas • Estimate ~ 1,000 new cases in US per year
Slide 19: RhoA Mutations Play a Prominent Role in AITL Pathogenesis
RHOA MUTATIONS PLAY A PROMINENT ROLE IN AITL PATHOGENESIS For personal use only Schematic of RhoA protein structure, with alterations • AITL originates from follicular T helper cells and is characterized by the presence of RhoA G17V mutation together with genetic alterations • RhoA G17V plays a prom
Slide 20: PTX-100 the Most Advanced Drug Targeting RhoA
PTX-100 THE MOST ADVANCED DRUG TARGETING RHOA • Only 12 RhoA inhibitors in development in For personal use only PTX-100 1 oncology » No others are in the clinic NO. OF DRUGS IN DEVELOPMENT » None are in hematology indications » PTX-100 is the most advanced, with Phase 1 ADDRESSING MUTATION X 7 trial
Slide 21: PTX-200: Novel Akt Inhibition
PTX-200 For personal use only NOVEL AKT INHIBITION OVERCOMING KINASE PROMISCUITY & LIMITATIONS OF PREVIOUS ATTEMPTS AT AKT INHIBITION 21 TARGETED THERAPIES YIELDING A DEEP CLINICAL PIPELINE
Slide 22: Akt Is a Master Switch for Cellular Growth & Survival
AKT IS A MASTER SWITCH FOR CELLULAR GROWTH & SURVIVAL For personal use only 22 ERSAHIN, T. ET AL; MOL. BIOSYST., 2015,11, 1946-1954
Slide 23: Akt Remains an Important Drug Target
AKT REMAINS AN IMPORTANT DRUG TARGET For personal use only • Akt pathway promotes cellular survival and growth • Hyperactive Akt signaling has two deleterious effects: » Plays key role in the development of many cancers including breast, ovarian, colorectal, prostate, pancreatic and hematologic canc
Slide 24: PTX-200 (Triciribine Phosphate Monohydrate) Introduction
PTX-200 (TRICIRIBINE PHOSPHATE MONOHYDRATE) INTRODUCTION For personal use only • PTX-200 (TCN-P) is a small molecule Akt activation inhibitor that is highly selective for killing tumors with hyperactivated Akt PTX-200 (TCN-P) • Inhibits Akt without the toxicity of other attempts • Anti-proliferative
Slide 25: PTX-200: Novel Akt Inhibition via PH Domain Binding
PTX-200: NOVEL AKT INHIBITION VIA PH DOMAIN BINDING For personal use only • PTX-200 is NOT an ATP mimic/direct kinase inhibitor, and therefore avoids off target effects associated with ATP mimic inhibitors. » By binding to the PH domain, PTX-200 prevents binding to the plasma membrane, thus inhibiti
Slide 26: Acute Myeloid Leukemia Overview
ACUTE MYELOID LEUKEMIA OVERVIEW For personal use only • AML is a type of cancer that affects the blood and bone marrow » Patient cannot produce normal blood cells » Blood cells cannot function properly nor fight disease • Progresses very quickly; 5 year survival only 25% • More common in adults over
Slide 27: PTX-200 in AML – Executive Summary
PTX-200 IN AML – EXECUTIVE SUMMARY For personal use only • Akt is highly relevant in AML • PTX-200 address the “phenotype, not the genotype” in AML mutations • Like other recent successful strategies in AML, PTX-200 is a targeted therapy complementing a “backbone” of standard chemotherapy • PTX-200
Slide 28: Mutational Complexity of AML
MUTATIONAL COMPLEXITY OF AML For personal use only • Although AML is a mutationally complex disease, many different types of mutations (and combinations of mutations) result in hyperphosphorylation of Akt » In fact, 72% of AML patients have high p-Akt • Previous Akt drugs have failed because of the
Slide 29: High p-Akt Correlated with Inferior Survival in AML
HIGH P-AKT CORRELATED WITH INFERIOR SURVIVAL IN AML • Frequent constitutive Akt activation (phosphorylation) in AML For personal use only » Constitutive phosphorylation (Ser473 and Thr308) of Akt in AML compared to normal bone marrow cells in 44 out 66 of patients (72%) • Implications for Akt as a m
Slide 30: PTX-200 Synergizes Cytarabine in AML Cells
PTX-200 SYNERGIZES CYTARABINE IN AML CELLS For personal use only • PTX-200 highly synergistic with the current standard of care (cytarabine) in AML cells » PTX-200 + cytarabine = much more effective effect than the simple additive effect of either compound (i.e. 1 + 1 ≥ 2) • As cytarabine is the cur
Slide 31: PTX-200: Completed Phase 1 Monotherapy in Hematologic Malignancies
PTX-200: COMPLETED PHASE 1 MONOTHERAPY IN HEMATOLOGIC MALIGNANCIES (MAINLY AML) For personal use only Patients • 32 Trial Centers • MD Anderson & Moffitt Patient • Advanced hematologic malignancies (mainly AML) Inclusion Study • To establish dosing regime and biological dose Objectives • 1 hour IV i
Slide 32: PTX-200 Reduced p-Akt in AML Blasts
PTX-200 REDUCED P-AKT IN AML BLASTS For personal use only • Phase 1 trial demonstrated that blast cells with high p-Akt from AML patients are more sensitive to PTX-200’s ability to reduce p-Akt levels » p-Akt/Akt in AML » Action of PTX-200 on Akt samples before therapy phosphorylation in AML blasts
Slide 33: Compelling Evidence for PTX-200 in AML
COMPELLING EVIDENCE FOR PTX-200 IN AML For personal use only Efficacy hypothesis PTX-200 Evidence • High p-Akt is correlated with inferior survival in AML • PTX-200 decreased pAkt in AML blasts • Inhibiting p-Akt improves response to chemo in the clinical • PTX-200 decreased pAkt in AML blasts, sugg
Slide 34: Phase 1b AML Trial Underway
PHASE 1B AML TRIAL UNDERWAY For personal use only • Phase 1 results with PTX-200 (monotherapy) very encouraging • Now PTX-200 + cytarabine in refractory or relapsed acute leukemia » 15 -18 patients » 3+3 design, single arm » Up to 4 dose levels of PTX-200 starting at 25 mg/m2 (days 1, 8, 15) » Cytar
Slide 35: Breast Cancer Overview
BREAST CANCER OVERVIEW For personal use only • Breast cancer market currently US$10 B; due to double by 2023 • HER2- breast cancer has “flown under the radar” of drug developers, due to high profile successes in HER2+ drugs…but ~80% of breast cancers are still HER2- (TNBC & ER+) • Comparative lack o
Slide 36: Phase 1b Breast Cancer Trial Completed
PHASE 1B BREAST CANCER TRIAL COMPLETED • For personal use only PTX-200 in combination with paclitaxel, followed by AC (doxorubicin & cyclophosphamide) • Patients with metastatic and locally advanced HER2- breast cancer » Albert Einstein College of Medicine Montefiore Medical Center and the H. Lee Mo
Slide 37: Ovarian Cancer Overview
OVARIAN CANCER OVERVIEW For personal use only • One of the most common cancers in women - increasing with an ageing population • Due to reach US$1.7 B by 2019 » Market size currently constrained by old generic drugs that just aren’t good enough • Standard of care has not changed in decades (often ge
Slide 38: Phase 1b Ovarian Cancer Trial
PHASE 1B OVARIAN CANCER TRIAL For personal use only • Significant need for new products to treat platinum-resistant ovarian cancer • Testing PTX-200 plus carboplatin in patients with platinum resistant ovarian cancer • PTX-200 already proven overcome cisplatin resistance and synergize with cisplatin
Slide 39: Value Proposition
VALUE For personal use only PROPOSITION 39 TARGETED THERAPIES YIELDING A DEEP CLINICAL PIPELINE
Slide 40: PTX Operates in Areas with Rich Deal Activity
PTX OPERATES IN AREAS WITH RICH DEAL ACTIVITY For personal use only Deals1 since Jan 2016 Median deal size # transactions (US$M) AML 44 143 Ovarian cancer 36 234 Breast cancer2 30 255 Rare diseases (oncology)3 972 154 1. Deals defined as mergers, acquisitions, licenses and strategic alliances 2. Bre
Slide 41: Significant Valuation Arbitrage
SIGNIFICANT VALUATION ARBITRAGE For personal use only Significant valuation arbitrage …Arbitrage against US AML peers is even against comparable ASX peers… 1,000 more pronounced 900 800 400 700 350 MARKET CAP US$M 600 300 MARKET CAP A$M 500 250 ASX peer average A$181M 400 200 300 US AML peer average
Slide 42: Investment Highlights
INVESTMENT HIGHLIGHTS For personal use only 2 DRUGS » IMMINENT CATALYSTS » FUNDING IN PLACE » UNDISCOVERED VALUE • 2 targeted therapies with impeccable scientific pedigree • Multiple shots on goal with Akt and Ras pathway inhibitors in multiple trials • One of deepest clinical pipelines on the ASX »
Slide 43: Contact
For personal use only CONTACT Steven Yatomi-Clarke e: steven@ptxtherapeutics.com CEO & Managing Director t: +61 417 601 440 Prescient Therapeutics Limited w: ptxtherapeutics.com 43 TARGETED THERAPIES YIELDING A DEEP CLINICAL PIPELINE
Prescient Therapeutics — Investor Presentation (October 2017) on 6ix