Egetis Therapeutics Ab · OMXSTO:EGTX
Egetis Therapeutics Ab — PledPharma — Investor Presentation (January 2020)
71 slides from Egetis Therapeutics Ab's investor presentation, January 2020
Slide 1: PledPharma Company presentation
PledPharma Company presentation January, 2020 1|
Slide 2: Disclaimer
Disclaimer IMPORTANT: You must read the following before continuing. The following applies to this document, the oral presentation of the information in this document by PledPharma AB (the “Company”) or any person on behalf of the Company, and any question-and-answer session that follows the oral pr
Slide 3: Table of Contents
TABLE OF CONTENTS 1. Introduction 2. Drug candidates in clinical phase a. PledOx® Phase III in CIPN with oxaliplatin b. PledOx® indication expansion - CIPN with taxanes c. Aladote® Phase II in paracetamol overdose 3. Milestones and summary A. Appendix a. Board and management b. Financials c. Additio
Slide 4: Key Leadership Members
KEY LEADERSHIP MEMBERS Nicklas Westerholm CEO Took office in June 2017 and has previously worked in the AstraZeneca Group since 1996 in number of global leadership roles in various business areas such as R&D, Finance & Investor Relations, and Commercial Manufacturing and Supply, most recently as VP
Slide 5: Company history
Company history 2006 2007-2010 2011-2013 2013-2016 2017 2018-2019 PledPharma AB Results from the MANFOL study FDA approves the PLIANT-study Results from the PLIANT-study is Proof-of-concept study of Global Phase III program for presented at ASCO Aladote® in patients with PledOx® initiated is founded
Slide 6: Executive summary
Executive summary PledOx® Aladote® Prevents nerve damage caused by chemotherapy Prevents acute liver injury caused by paracetamol treatment in colorectal cancer patients (acetaminophen) poisoning Phase III Phase II ✓ Huge unmet medical need with No approved drug Paracetamol (acetaminophen) poisoning
Slide 7: Table of Contents
TABLE OF CONTENTS 1. Introduction 2. Drug candidates in clinical phase a. PledOx® Phase III in CIPN with oxaliplatin b. PledOx® indication expansion - CIPN with taxanes c. Aladote® Phase II in paracetamol overdose 3. Milestones and summary A. Appendix a. Board and management b. Financials c. Additio
Slide 8: Neuropathy is associated with standard treatment of Colorectal Cancer patients
Neuropathy is associated with standard treatment of Colorectal Cancer (CRC) patients …. the 3rd most diagnosed cancer Numbness and Tingling Oxaliplatin is associated Burning pain with dose limiting and Cold sensitivity during oxaliplatin treatment debilitating toxicities Problems with sensation Impa
Slide 9: Chemotherapy treatment leads to mitochondrial dysfunction and CIPN
Chemotherapy treatment leads to mitochondrial dysfunction and CIPN • Oxaliplatin binds to mtDNA, leading to inefficient • MnSOD is an enzyme catalysing the degradation energy generation and more superoxide of superoxide 9|
Slide 10: PledOx prevents mitochondrial dysfunction
PledOx® prevents mitochondrial dysfunction • Being a MnSOD mimetic, PledOx® supports • PledOx® binds free iron, inhibiting the Fenton superoxide regulation reaction and thus lipid peroxidation 10 |
Slide 11: PledOx: No approved drug for prevention or treatment of CIPN
No approved drug for prevention or treatment of Chemotherapy Induced Peripheral Neuropathy PledOx® aims to become new standard of care Prevention of chemotherapy induced peripheral neuropathy… PledOx® Chemotherapy … without negative impact on the efficacy of chemotherapy + Easy to administrate as pr
Slide 12: Scientific rationale and results in Phase IIb study (PLIANT)
Scientific rationale and results in Phase IIb study (PLIANT) provide reasons to believe in positive Phase III The human body's own enzymatic PledOx® defense against mitochondrial dysfunction 173 patients with 38% effect1 on 77% effect2 on No apparent Well tolerated metastatic CRC investigator patien
Slide 13: PledOx Global Phase III program
PledOx® Global Phase III program Scientific Advisory Board Two double-blind, randomised, placebo controlled studies • POLAR-M (Metastatic CRC), recruitment ongoing: 420 patients in US, EU and Asia undergoing chemotherapy (FOLFOX). PledOx® with the doses 2 μmol/kg respective 5 μmol/kg vs placebo. • P
Slide 14: Design of POLAR-studies
Design of POLAR-studies POLAR-M (US, EU & Asia) - Recruitment ongoing Top line N=140 PledOx 5 umol/kg results + FOLFOX N=140 PledOx 2 umol/kg R + FOLFOX Primary PFS PFS Endpoint OS OS OS Placebo (CIPN) N=140 + FOLFOX t=0 EoT1 9 months 1 year 2 years 3 years POLAR-A (EU & Asia) – Fully recruited Top
Slide 15: PledOx License agreements with Solasia
PledOx®– License agreements with Solasia in Nov 2017 and Sept 2019(1) for development and commercialization in Asia • PledOx® for Chemotherapy Induced Peripheral Neuropathy (CIPN) – caused by any chemotherapy in any cancer type. 1 • License to develop and commercialize PledOx® in Japan (2), China, H
Slide 16: Key value drivers of Asia licensing agreement
Key value drivers of Asia licensing agreement Partnership with Solasia 3-4 years of accelerated and its capabilities development in Asia Expansion of Phase 3 Milestones & Royalties program will further enhance robustness 16 |
Slide 17: PledOx development timeline
PledOx® – development timeline • All patients • randomized POLAR M ✓ Results Ph.1 Study JPN • • Results from pre ✓ Asian expansion of POLAR clinical studies in studies taxanes • POLAR CTAs approved in ✓ • POLAR A - Top line • NDA approvals US, JPN, UK, Spain, Italy, results of primary 2022/ 2018 Fra
Slide 18: Epidemiology - Colorectal cancer is the third most diagnosed cancer
Epidemiology - Colorectal cancer (CRC) is the third most diagnosed cancer “…and its burden is expected to increase by 60% by 2030” 18 | BMJ: Arnold M, et al. Gut 2016
Slide 19: Colorectal Cancer - Common treatment approaches
Colorectal Cancer – Common treatment approaches Stage I & II Stage III (adjuvant) Stage IV (metastatic) • Surgery +/- RT • Surgery + systemic therapy • Systemic therapy +/- RT +/- RT • Surgery + systemic therapy • Surgery + systemic therapy +/- RT (high-risk patients) +/- RT (resectable disease) In
Slide 20: CIPN - Competitive landscape
Chemotherapy Induced Peripheral Neuropathy - Competitive landscape COMMON TREATMENT CIPN EMERGING TREATMENTS APPROACHES FOR CIPN Prevention MN-166 E-52862 (Inflammation target) (Sigma-1 Receptor) No approved drug for prevention or Medicinova PledOx® treatment of Chemotherapy Induced Mundipharma Ph I
Slide 21: PledOx Market Research, Pricing & Reimbursement
PledOx® – Market Research, Pricing & Reimbursement Physicians and Payers expressed high interest in PledOx® as a preventive treatment for CIPN. Payer clinical evidence needs forms strategy for Phase III data collection CIPN market research with US and EU Oncologists Market Research Overview: 1:1, bl
Slide 22: CIPN associated with high health care costs in the US
CIPN associated with high health care costs in the US Increased health care costs for CIPN patient: • Privately insured administrative claims database study (Ingenix Employer db, 4.7 million people) 17,344 USD • Patients with qualifying tumors, and claims for during first year after chemotherapy che
Slide 23: Payer Insight & combined EMA Scientific & Payer Advice
Payer Insight & combined EMA Scientific & Payer Advice - clarifies data collection in Phase 3 to build robust pricing arguments • With PledOx being first-in-class • Important to provide information of disease burden, unmet need, and costs of not treating or inadequately treating CIPN ‘You’re pushing
Slide 24: PledOx Commercial potential in CRC patients
PledOx® – Commercial potential in CRC patients ~700k ~225k ~1.5m Drug Number of oxaliplatin Number of oxaliplatin treated CRC patients treated patients in cycles in US, EU5 & in US, EU5 & US, EU5 & JPN/ /year JPN /year JPN/year Pricing COGS assumption assumption +60% in CRC 1,000 Low single digit in
Slide 25: PledOx Summary and Opportunities in CIPN with oxaliplatin
PledOx® Summary and Opportunities in CIPN with oxaliplatin PREVENTS NERVE DAMAGE CAUSED BY OXALIPLATIN TREATMENT DEVELOPMENT STATUS BUSINESS OPPORTUNITY • Phase II data provide reason to believe in Phase III • CRC 3rd most diagnosed cancer • Global Phase III POLAR studies approved in US, EU • ~1.5M
Slide 26: Table of Contents
TABLE OF CONTENTS 1. Introduction 2. Drug candidates in clinical phase a. PledOx® Phase III in CIPN with oxaliplatin b. PledOx® indication expansion - CIPN with taxanes c. Aladote® Phase II in paracetamol overdose 3. Milestones and summary A. Appendix a. Board and management b. Financials c. Additio
Slide 27: Expand into CIPN with taxanes
Expand into CIPN with taxanes - Unmet medical need is similar to that for oxaliplatin Oxaliplatin Paclitaxel • Similar percentage of patients • Similar type of chronic CIPN symptoms are experience CIPN with oxaliplatin and experienced, i.e. numbness, tingling in paclitaxel(1) hands and feet(2) • Lea
Slide 28: Mitochondrial dysfunction a contributing factor to CIPN by taxanes
Mitochondrial dysfunction a contributing factor to CIPN by taxanes give reasons to believe in PledOx® Platinum compounds Taxanes Vinca alkaloids Dorsal root ganglion Thalidomide Taxanes Vinca alkaloids Microtubules Bortezomib Platinum compounds Mitochondria Taxanes Bortezomib Ion channels Oxaliplati
Slide 29: Attractive commercial opportunity in CIPN/taxanes
Attractive commercial opportunity in CIPN/taxanes Market size: Taxanes have a significant use in clinical practice across several different cancer types (e.g. breast and ovarian cancer) with approximately 400,000 patients treated yearly in the US, EU5 and Japan Use of platinum-based chemotherapy by
Slide 30: Next steps in development path for CIPN/taxanes
Next steps in development path for CIPN/taxanes Regulatory Pre-clinical studies and Scientific Advisory interactions and Board for Clinical development Clinical study (2019/2020) (2020→) Clarify development path, including Pre-clinical studies in collaboration with Prof Cavaletti, Univ Milano-Biocca
Slide 31: Table of Contents
TABLE OF CONTENTS 1. Introduction 2. Drug candidates in clinical phase a. PledOx® Phase III in CIPN with oxaliplatin b. PledOx® indication expansion - CIPN with taxanes c. Aladote® Phase II in paracetamol overdose 3. Milestones and summary A. Appendix a. Board and management b. Financials c. Additio
Slide 32: Paracetamol poisoning: no adequate treatment for high risk patients
Paracetamol (acetaminophen) poisoning … no adequate treatment for high risk patients 19bn units of paracetamol packages sold every year in the US. Minimum toxic dose of paracetamol in adults – only 89,000 cases of paracetamol 7.5g overdose in US per year 105,000 cases of paracetamol ~50 % of overdos
Slide 33: Aladote protects the liver and reduces risk of acute liver failure
Aladote® – protects the liver and reduce the risk of acute liver failure Aladote® aims to become new standard of care for high risk patients Prevents acute liver injury caused by paracetamol (acetaminophen) poisoning… Aladote® Acetylcysteine (NAC) … in high risk patients where treatment of NAC is no
Slide 34: Aladote potential for reducing APAP-induced acute liver injury
Aladote has potential for reducing APAP-induced acute liver injury in high risk patients • APAP overdose leads to formation of the toxic metabolite NAPQI • In the metabolic phase, this leads to depletion of reduced glutathione (GSH) and binding of NAPQI to liver proteins ▪ NAC is effective in this p
Slide 35: Design of Aladote Phase Ib/IIa clinical study
Design of Aladote Phase Ib/IIa clinical study completed in 2018 Randomised Open Label Exploratory, Safety and Tolerability Study with Calmangafodipir in Patients Treated with the 12-hour Regimen of N-Acetylcysteine (NAC) for Paracetamol Overdose Cohort 3 Design • Single ascending dose study in Alado
Slide 36: Aladote positive pre-clinical and clinical data
Aladote® positive pre-clinical and clinical data provides reasons to believe … motivates further development Phase Ib/IIa Study – Positive results announced in 2018/19 • Randomized Phase Ib/IIa in paracetamol overdosed patients • In total 24 patients, were recruited to three Aladote® doses as add-on
Slide 37: Met the primary endpoint of safety and tolerability
Met the primary endpoint of safety and tolerability in the combination of Aladote® and NAC Event NAC alone NAC + NAC + NAC + 2 μmol/kg 5 μmol/kg 10 μmol/kg Aladote Aladote Aladote Any adverse 6 (100%) 6 (100%) 6 (100%) 6 (100%) event Any serious 2 (33%) 4 (67%) 2 (33%) 3 (50%) adverse event Serious
Slide 38: Liver injury (pre-defined secondary outcome)
Liver injury – (pre-defined secondary outcome) Event NAC alone NAC + NAC + NAC + 2 μmol/kg 5 μmol/kg 10 μmol/kg Aladote Aladote Aladote 50% ALT 2 (33%) 0 (0%) 0 (0%) 1 (17%) increase 100% ALT 1 (17%) 0 (0%) 0 (0%) 1 (17%) increase ALT >100 U/L 2 (33%) 0 (0%) 0 (0%) 0 (0%) at 10 hours ALT >100 U/L 2
Slide 39: Liver injury (pre-defined secondary outcome)
Liver injury – (pre-defined secondary outcome) K18 ccK18 Relative change from baseline 10 10 Relative change from baseline * NAC alone * NAC alone NAC and 2umol/kg NAC and 2umol/kg NAC and 5umol/kg NAC and 5umol/kg 1 1 NAC and 10umol/kg NAC and 10umol/kg 0.1 0.1 0 10 20 0 10 20 Time (hours) Time (ho
Slide 40: Liver injury (pre-defined secondary outcome)
Liver injury – (pre-defined secondary outcome) All patients with NAC alone had an increase in both K18 isoforms (FLK18 and CCK18) • K18 (Patients with decreased levels from baseline to 20hrs: n (%)): − NAC alone: 0 (0%); NAC+Aladote: 6 (33%) • NAC+2µmol/kg: 2 (33%); NAC+5µmol/kg: 3 (50%); NAC+10µmol
Slide 41: Aladote granted Orphan Drug Designation by the FDA
Aladote® granted Orphan Drug Designation by the FDA (March 18, 2019) ODD benefits • Lowered development cost – driven by patient safety and efficacy requirements (typically < 300 patients in Phase II / III studies) • Shortened development time • Commitment of the regulators to support development •
Slide 42: One pivotal Phase II/III study with Aladote
One pivotal Phase II/III study with Aladote® for marketing authorisation application in both US and EU. Tentative study design pending regulatory interaction to finalize specific study details(1) Patient population High risk POD patients, Late arrivals (>8h) requiring treatment with NAC NAC regims S
Slide 43: Aladote timeline
Aladote® – timeline ✓• Orphan Drug Designation granted in the US • ✓ Presentation of study results at Society of Toxicology ✓• Presentation of study results EASL ILC • Regulatory ✓• Presentation of results in 2022/ submissions 2032(1) 2019 start Lancet EBiomedicine 23 ✓• Regulatory interactions – de
Slide 44: POD incidence in EU5 and US
POD incidence in EU5 and US – Hospital visits 2018 105,000 26,000 26,000 9,000 89,000 16,000 44 | Note: Paracetamol (acetaminophen) Overdose 2018 estimate Epidemiology.
Slide 45: Burden on society - POD US Healthcare Costs
Burden on society - POD US Healthcare Costs were $1bn in 2010 In the US the annual cost in 2010 The POD Emergency was estimated at $1,059 million Department and inpatient cost is to treat Patients with POD around $13K-40K The average POD inpatient length of stay was 3.1 Days, with US liver transplan
Slide 46: No competitor in development
No competitor in development TREATMENT APPROACHES FOR POD EMERGING TREATMENTS POD Active Charcoal N-Acetylcysteine (NAC) Liver transplant Aladote® PledPharma Phase I Phase II Phase III 46 |
Slide 47: Aladote Initial Market Research, Pricing & Reimbursement
Aladote® – Initial Market Research, Pricing & Reimbursement Market research with US and EU Physicians and Payers to gain insight into unmet needs, validate Target Product Profile and Pricing & Reimbursement POD CIPN Background Background TPP & IDI Guide Testing Team Expertise Development Efficacy vs
Slide 48: Aladote Commercial potential in POD patients
Aladote® – Commercial potential in POD patients Pricing assumption ~135k Hospital admissions ~5,000 POD patients in US USD/dose in the and EU5 /year US¹ COGS assumption Low single digit percent 48 | Note: (1) Up to $5000 based on initial and limited research
Slide 49: Aladote Summary and Opportunities
Aladote® - Summary and Opportunities PREVENTS ACUTE LIVER FAILURE CAUSED BY PARACETAMOL (ACETAMINOPHEN) POISONING DEVELOPMENT STATUS BUSINESS OPPORTUNITY • Positive study results Ph Ib/IIa announced in September • Paracetamol (acetaminophen) poisoning is one of the most 2018. common sorts of overdos
Slide 50: Table of Contents
TABLE OF CONTENTS 1. Introduction 2. Drug candidates in clinical phase a. PledOx® Phase III in CIPN with oxaliplatin b. PledOx® indication expansion - CIPN with taxanes c. Aladote® Phase II in paracetamol overdose 3. Milestones and summary A. Appendix a. Board and management b. Financials c. Additio
Slide 51: Summary - Direction, opportunities and enablers to enhance value
Summary - Direction, opportunities and enablers to enhance value PledOx® Aladote® Business development • Huge unmet medical • Substantial unmet medical • Strategic partnerships 1 need with no treatment 2 for patients where NAC is 3 • Maximise PledOx value approved today not adequate • Global phase I
Slide 52: Table of Contents
TABLE OF CONTENTS 1. Introduction 2. Drug candidates in clinical phase a. PledOx® Phase III b. Aladote® Phase II 3. Milestones and summary A. Appendix a. Board and management b. Financials c. Additional company information 52 |
Slide 53: Key management members
Key management members Nicklas Westerholm Helene Depui Ekdal CEO Clinical Development Director ▪ Before joining the PledPharma team in 2017, Nicklas worked in the ▪ Before joining PledPharma, Helene worked as Senior Director, AstraZeneca Group in various roles and business areas, most Global Value C
Slide 54: Scientific advisory board
Scientific advisory board Established for PledOx® Established for Aladote® Professor Guido Cavaletti Dr. Richard C. Dart ▪ MD, Ph.D. and Head of the Neuroimmunology Center at S. ▪ Ph.D., Chair of the Department of Medical Social Sciences at Gerardo Hospital and the Experimental Neurology Unit at the
Slide 55: Board of directors
Board of directors Håkan Åström Chairman of the board Gunilla Osswald ▪ Board member since: 2011 Board member ▪ Other assignments: Chairman of the boards of directors of ▪ Board member since: 2017 Affibody Holding AB, Tubulus RP Förvaltning AB and MedCore ▪ Ph.D. in biopharmacy and pharmacokinetics
Slide 56: Income statement
Income statement KSEK 2019 2018 2019 2018 2018 Jul-Sep Jul-Sep Jan-Sep Jan-Sep Jan-Dec Revenue Sales 6,171 6,715 65,509 17,113 28,211 Other operating income 11 - 11 2 2 6,182 6,715 65,520 17,114 28,212 Operating expenses Project costs -33,633 -17,991 -85,974 -59,607 -83,855 Other external costs -3,2
Slide 57: Balance sheet and cash flow statement
Balance sheet and cash flow statement KSEK 9/30/2019 9/30/2018 12/31/2018 ASSETS Non-current assets Tangible non-current assets 176 - - KSEK 2019 2018 2019 2018 2018 Total non-current assets 176 - - Jul-Sep Jul-Sep Jan-Sep Jan-Sep Jan-Dec OPERATING ACTIVITIES Result after financial net -31,893 -18,8
Slide 58: Shareholder list
Shareholder list 58 | Source: Nov 2019 Holdings.com
Slide 59: Summary of key neuropathy efficacy endpoints in Phase IIb PLIANT study
Summary of key neuropathy efficacy endpoints in Phase IIb PLIANT study PLIANT study: 173 patients with metastatic CRC treated with PledOx® or placebo together with chemotherapy FOLFOX (oxaliplatin) Type of CIPN Dose vs Placebo 2 µmol/kg 5 µmol/kg 2+5+10 µmol/kg assessment (Study Part†) (2a+2b) (2b)
Slide 60: PFS and OS from Phase IIb study (PLIANT)
Progression free survival (PFS) and Overall survival (OS) from Phase IIb study (PLIANT) Comment Comment • No detrimental effect of PledOx® on the anti-tumor effect (PFS) of • No detrimental effect of PledOx® on the anti-tumor effect (OS) of chemotherapy chemotherapy 60 |
Slide 61: The basis for evaluation of CIPN in the POLAR program
The basis for evaluation of CIPN in the POLAR program Primary Endpoint Description FACT/GOG-NTx-4 4-question PRO instrument addressing key CIPN symptoms of numbness, tingling and discomfort in hands and feet Secondary & Exploratory Description Endpoints FACT/GOG-NTx-13 13-question PRO instrument add
Slide 62: Primary endpoint based on FACT/GOG-Ntx is clinically relevant
Primary endpoint based on FACT/GOG-Ntx is clinically relevant and interpretable 62 |
Slide 63: FACT/GOG-NTx-4 captures the majority of relevant chronic CIPN symptoms
FACT/GOG-NTx-4 captures the majority of relevant chronic CIPN symptoms Note: “A” in Figure refers to the questions in Ntx-4 (1) Kopec et.al (2006) Validation of a self-reported neurotoxicity scale in patients with operable colon cancer receiving oxaliplatin 63 | (2) Huang et al. (2007) Validation an
Slide 64: Results in SCOT study confirm sensitivity of FACT/GOG-Ntx-4
Results in SCOT study confirm the sensitivity of FACT/GOG- Ntx-4 in CRC patients treated with oxaliplatin HANDS FEET Numbness or tingling Discomfort 64 |
Slide 65: A robust IP portfolio with composition of matter protection until end-2032
A robust IP portfolio with composition of matter protection until end-2032 • New chemical entity with composition of matter, manufacturing process and broad therapeutic use of calmangafodipir, with US, EU, China, Russia and Japan Patent family/ approved, end-2032 Patent applications / • Application
Slide 66: PledOx is based on a previously used MRI contrast agent, mangafodipir
PledOx® is based on a previously used MRI contrast agent, mangafodipir New compound Comments Comments • Clinically proven MRI contrast medium with good safety profile • Mangafodipir’s potential for manganese accumulation lead to modification into calmangafodipir • >240,000 patients treated and sever
Slide 67: Mechanisms underlying CIPN are diverse and complex
Mechanisms underlying CIPN are diverse and complex Platinum compounds Taxanes Vinca alkaloids Dorsal root ganglion Thalidomide Taxanes Vinca alkaloids Microtubules Bortezomib Platinum compounds Mitochondria Taxanes Bortezomib Ion channels Oxaliplatin Bortezomib Myelin Thalidomide Blood vessels Vinca
Slide 68: In healthy cells, mitochondrial homeostasis is maintained by MnSOD
In healthy cells, mitochondrial homeostasis is maintained by MnSOD • Superoxide is generated as a by-product of • MnSOD is an enzyme catalysing the energy production in the mitochondria degradation of superoxide 68 |
Slide 69: Chemotherapy effect on the mitochondria
Chemotherapy effect on the mitochondria Comments Chemotherapy anticancer drugs, such as platinum-based compounds, taxanes, vinca alkaloids, all generate chemotherapy induced peripheral neuropathy (CIPN). - CIPN is frequently seen as a side-effect in cancer patients, - Mitochondrial dysfunction mainl
Slide 70: CRC clinical development landscape
CRC Stage IV (and III) Phase 3 Clinical development landscape 1L mCRC KEYTRUDA [pembrolizumab] TECENTRIQ [atezolizumab] (PD-1; Merck) (PD-L1; Roche) • Active, Not Recruiting: 1L dMMR or MSI-H mCRC; n=308 (May 2018) • Recruiting: 1L dMMR or MSI-H mCRC • Primary completion: August 2019 • Primary compl
Slide 71: Aladote: About biomarkers
Aladote®: About biomarkers ALT Alanine transaminase (ALT) is a transaminase enzyme also called alanine aminotransferase (ALAT). ALT is found in plasma and in various body tissues especially the liver’s hepatocytes. Serum ALT is commonly measured clinically as part of a diagnostic evaluation of hepat