PledPharma Nicklas Westerholm, CEO - Corporate update December, 2017
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PledPharma Corporate update December, 2017 Nicklas Westerholm, CEO
PledPharma and initial CEO Priorities 2
CEO & President
Nicklas Westerholm
PledPharma CMO VP Product Strategy
Stefan Carlsson and Development
Christian Sonesson
Founded: Permanent
Employees:
2006 7 CSO CFO
Jaques Näsström Yilmaz Mahshid
Listed: Market cap*:
Nasdaq First North ~900 mkr
CMC Project Director &
Sven Jacobsson Reg Affairs
Malin Nittve
Cash position (Q3): Location:
354 mkr Stockholm
Project Director Clinical Project
Aladote® Director
Dennis Henriksen Marie Bengtsson
3
* 2017-11-20
Scientific Advisory Board established for PledOx®
Prof. Guido Cavaletti, MD Rolf Karlsten, MD, PhD
Head of the Neuroimmunology Center, Head of Rehabilitation Medicine and the
S. Gerardo Hospital, Monza and Senior Multidisciplinary Pain Centre at Uppsala
consultant neurologist, Ita University hospital, Swe
Prof. David Cella
Prof. em. Bengt Glimelius, MD
Ralph Seal Paffenbarger Professor and
Professor Emeritus in oncology at
Chair of the Department of Medical Social
University of Uppsala and Consultant
Sciences at the Northwestern University
at the University hospital, Swe
Feinberg School of Medicine, US
A fifth member of the Scientific Advisory Board
is a non-disclosed American, who is a leading international
expert in chemotherapy induced peripheral neuropathy
4
PledOx® (calmangafodipir) (Phase 3)
Prevents nerve damage caused by
chemotherapy treatment in colorectal
PledPharma’s drug cancer patients
candidates in clinical Aladote® (calmangafodipir) (Phase 1b/2a)
development Prevents acute liver failure
caused by paracetamol
(acetaminophen) poisoning
5
Colorectal Cancer (CRC) is the 3rd most diagnosed cancer
… and standard treatment is associated with neuropathy
~ 500K patients (EU5, US,
Japan) is treated for CRC
yearly
Oxaliplatin based chemotherapy is
standard of care in both metastatic
(stage IV) and adjuvant (stage III)
~1,5M cycles of oxaliplatin patients
yearly
Oxaliplatin is associated with dose
40-60 % of patients get limiting and debilitating toxicities
peripheral neuropathy during and
up to 3 months after chemotherapy
Chemotherapy Induced Peripheral Neuropathy (CIPN)
… often becomes a chronic debilitating condition
Numbness and Tingling
40-60% of patients get Burning pain
peripheral neuropathy
during and up to 3 months Cold sensitivity during oxaliplatin treatment
after chemotherapy
Problems with sensation
Impacts balance with risk of falling
20-30% of patients with
symptoms >7 years Challenge to use computer and key board
post chemotherapy
Difficulty in buttoning buttons
Loss of ability to work
No approved drug for prevention or treatment of
Chemotherapy Induced Peripheral Neuropathy
8
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 pre-treatment to chemotherapy
9
Scientific rationale and results in Phase 2b study (PLIANT)
provide reasons to believe in positive Phase 3
PledOx®
The human body's own enzymatic
defense against oxidative stress
173 patients with 38% lower 77% lower No apparent negative Well tolerated
metastatic CRC investigator patient reported effect on the efficacy
treated with reported CIPN CIPN symptoms of the chemotherapy
PledOx® or symptoms (exploratory treatment
placebo together (p=0.16 n.s) analysis; p=0.014)
with
chemotherapy
FOLFOX
10
(oxaliplatin)Recent PledPharma and PledOx® newsflow 11
Scientific Advisory Board
Design of PledOx® Phase 3 program
12PledOx® Phase 3 program
Two double-blind, randomised, placebo controlled studies:
• POLAR-M (Metastatic CRC): 300 patients in US and EU undergoing chemotherapy (FOLFOX).
PledOx® with the doses 2 μmol/kg respective 5 μmol/kg vs placebo.
• POLAR-A (Adjuvant CRC): 200 patients in EU undergoing chemotherapy (FOLFOX). PledOx® with
the dose 5 μmol/kg vs placebo.
• Two complementary studies: POLAR-A provides CIPN evaluation in a homogenous population.
POLAR-M is central to confirm that PledOx has no detrimental effect on chemotherapy.
Primary endpoint
• Based on patient reported symptoms using the validated FACT/GOG-Ntx* instrument
• Assessed 9 months after first dose of chemotherapy
Survival data
• Impact on progression free survival (PFS; POLAR-M), overall survival (OS; POLAR M) and disease
free survival (DFS; POLAR A) assessed after 1 and 2 years (and 3 years for OS)
Timelines
• Initiation of studies in 2017
• PledPharma expects existing funds to cover delivery of top-line results, anticipated during 2020
13 * FACT/GOG-Ntx is a validated, relevant & sensitive patient reported outcome instrument for scoring, analysis and
interpretation of neuropathy in a disease specific target patient population used in ~6,700 patients in 34 studiesDesign of POLAR-studies
POLAR-M Top line
(US+EU) N=100 PledOx 5 umol/kg results
+ FOLFOX
N=100 PledOx 2 umol/kg
R Primary
+ FOLFOX
Endpoint PFS PFS OS
N=100 Placebo (CIPN) OS OS
+ FOLFOX
t=0 EoT* 9 months 1 years 2 years 3 years
POLAR-A
(EU)
N=100 PledOx 5 umol/kg
+ FOLFOX Primary
R Endpoint DFS DFS
N=100 Placebo (CIPN)
+ FOLFOX
t=0 EoT* 9 months 1 years 2 years
14
*EoT= End of TreatmentRecent PledPharma and PledOx® newsflow 15
Solasia as a partner for PledOx® in Asia
Development and commercialization of drug for cancer
treatment and supportive care in Asia
Pipeline
Founded: Business model: Product Indication Status JPN Status China In licensed
In licensing of late from
2006 stage programs
SP-01 Sancuso® Chemotherapy No rights NDA Strakan
induced nausea International
Listed: Market cap*: and vomiting Ltd
Tokyo Stock Exchange ~300 MUSD
SP-02 Peripheral T- PII/Pivotal Initiation of ZIOPHARM
darinaparsin cell lymphoma study ongoing PII/Pivotal
study
Pipeline Location:
3 products Japan, China
SP-03 episil® Chemotherapy Approved NDA Camurus AB
induced Pain Launch in 2018
associated with
Oral mucositis
16PledOx® Asia deal structure
PledOx ® for Chemotherapy Induced Perepheral Neuropathy (CIPN) – Colorectal cancer
License to develop and commercialize PledOx® in Japan, China, Hong Kong, Macau, South
Korea, and Taiwan.
Solasia will pay upfront, development, regulatory and sales milestones of up to USD 83 million
(approximately SEK 700 million)*.
Solasia will pay industry standard royalty rates on sales applicable for an in licensed asset in
Phase III development.
Solasia will also fully finance an expansion of the Phase III program (POLAR-A and POLAR-M) to
include Asian patients subject to regulatory consultations.
A Phase I study in Japanese and Caucasian Healthy Volunteers with focus on safety,
pharmacokinetics and tolerability under initiation. Fully financed by Solasia.
17 * JPY 9,3 billionKey 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
18PledOx® – development timelines
Calmangafodipir
composition of matter
patent expires
Initiation of Phase 3 Regulatory
All patients treated 2021 submissions 2032
2017 program 2019
Initiation of Phase 1 start
study JPN
Top line results
2018 First patient randomized 2020 of primary endpoint (CIPN) and key
and recruitment of
safety endpoints (1 year
Patients P3
PFS/OS/DFS)
Phase 1 study JPN
completed
19PledOx® (calmangafodipir) (Phase 3)
Prevents nerve damage caused by
chemotherapy treatment in colorectal
PledPharma’s drug cancer patients
candidates in clinical Aladote® (calmangafodipir) (Phase 1b/2a)
development Prevents acute liver failure
caused by paracetamol
(acetaminophen) poisoning
20Paracetamol (acetaminophen) poisoning
… has no adequate treatment if arriving late at hospital
19 bn units of paracetamol
packages sold every year in the US.
Minimum toxic dose of paracetamol
in adults – only 7.5g 78 000 cases of paracetamol
overdose in US per year
80 000 cases of paracetamol
~50 % of overdoses are overdose in UK per year
unintentional
~ 25% of patients are late arrivals to
hospitals (>8h) with no adequate
Could lead to acute liver failure, treatment
liver transplant or death1960 2017
Aladote®
Acetylcysteine (NAC)
Prevents acute liver failure
Standard of Care treatment
caused by paracetamol
(acetaminophen) poisoning
No well-functioning treatment for patients who arrive more than 8 hours after ingestion
Effective up to ~8h after
overdose
Overdose Time -> Intensive care
Liver transplantation
Acetylcysteine (NAC) Death
Aladote®
22Aladote® pre-clinical data provides reasons to believe…
underpins current clinical study
Pre-clinical data presented at AASLD October 2017 Ongoing Phase 1b/2a Study
F ig 5 . N A C v s . C a M
N-acetylcysteine and Aladote (CaM) Treatment-time post paracetamol overdose
20000
• Randomized Phase 1b/2a in
15000 paracetamol overdosed patients
NS
U n it /L
ALT levels
10000 • Three Aladote® doses versus placebo as
* add-on to NAC regime
5000
*** • Safety and tolerability
***
*** ***
0
• Exploratory efficacy biomarkers for liver
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*** significant vs control
A
23Aladote® – development timelines
Development strategy TBD based on Ph1b/2a data, regulatory
interactions and advice from Scientific advisory Board Calmangafodipir
composition of matter patent
expires
Start P1b/2a study H2 2018 Initiate Ph2 study 2032
2017
/2019
2018 Results Ph1b/2a study
H1
24PledPharma Pipeline Summary and Opportunities
Prevents nerve damage caused Prevents acute liver failure
by chemotherapy treatment in
colorectal cancer patients PledOx® caused by paracetamol
(acetaminophen) poisoning Aladote®
Business opportunity: Business opportunity:
• CRC 3rd most diagnosed cancer – 500K per year • Paracetamol poisoning is a life-threatening condition.
US/EU5 and Japan. • ~ 80K cases per year in US and UK respectively.
• High incidence of CIPN (40-60%) in CRC patients. • Limited effect of standard of care for late-arrivals, ~ 25%
• CIPN can lead to discontinuation of cancer treatment. of patients.
• 20-30% of patients with symptoms >7 years later
• No available prevention or treatment/ very limited
competition
• Asia development will further realise PledOx Global
commercial potential
Development status: Development status:
• Phase 2 data provide reason to believe in Phase 3. Published Pre-clinical data supports ongoing study.
• Initiation of Phase 3 before year end 2017. • Ongoing Ph1b/2a study with results expected during H1
• Asian expansion of Phase 3, subject to regulatory 2018.
consultations • Development strategy TBD based on Ph1b/2a data,
• Top-line results in POLAR-studies expected 2020 with regulatory interactions and Scientific Advisory Board.
regulatory submissions starting in 2021.
25 …with opportunities for life-cycle management in to other indications based on its mechanism of actionSignificant shareholder value driving milestones and news
flow*
PledOx®
• FPI (POLAR-M and • All patients included • Top line results (POLAR- • Regulatory
POLAR-A) (POLAR-M and M and POLAR-A) submissions
• Results PI Study JPN POLAR-A) • 1Y PFS, OS and DFS start
• Patient inclusion status • DSMB decisions data in both studies
• DSMB decisions
2018 2019 2020 2021
• Results Phase
1b/2a
• Development
strategy TBD
Aladote®
*All timelines are current best estimates and may be subject to changes
26PledPharma 27
Primary endpoint based on FACT/GOG-Ntx is clinically relevant and interpretable 28
Progression free survival (PFS) and Overall survival (OS)
from Phase 2b study (PLIANT)
PFS OS
1 .0 M e d ia n O S ( m o n t h s )
1 .0 M e d ia n P F S (m o n th s ) P la c e b o : 1 7 . 6
P la c e b o : 6 .8 C a M : 1 8 .0
0 .8
s u rv iv a l (p ro b a b ility )
C a M : 7 .1
P r o g r e s s io n - fr e e
0 .8
O v e ra ll s u rv iv a l
( p r o b a b ility )
0 .6
0 .6
0 .4 0 .4
P la c e b o
P la c e b o
0 .2 0 .2 C a lm a n g a fo d ip ir 2 + 5 + 1 0 m o l/k g
C a lm a n g a fo d ip ir 2 + 5 + 1 0 m o l/k g
0 .0 0 .0
0 6 12 0 6 12 18 24
T im e (m o n th s )
T im e (m o n th s )
No. at risk No. at risk
Placebo 60 38 15 Placebo 60 47 36 24 7
CaM 113 71 21 CaM 113 92 69 44 16
29Robust IP portfolio with composition of matter protection
until end-2032
• Anticancer effect of certain PLED derivatives, 2028, PCT application in
national phase with approved US, Canada, Chinese, Hong Kong, Israel,
Japanese, Korea, Australian, Russian and EU patent
Patent family/ • Manganese and non-manganese compositions and broad therapeutic
Patent use of these new compositions, 2030, PCT application in national phase
applications /
granted
with approved South African, Australian, Canadian, Mexican, Israel,
patents Japanese and Russian patent
• New chemical entity with composition of matter, manufacturing
process and broad therapeutic use of calmangafodipir, with US,
China, Russia and Japan approved, end-2032
• Cancer treatment methods, 2033, PCT application
•
Trademarks PledOx® registered trademark in EU, US, Switzerland, Australia,
Norway, China, Japan and Russia
• Aladote® registered trademark in EU, US, China and Russia
30Board of Directors
Håkan Åström Gunilla Osswald
Chairman of the board Board member
▪ Board member since: 2011 ▪ Board member since: 2017
▪ Other assignments: Chairman of the boards of directors of Affibody Holding AB, ▪ PhD in biopharmacy and pharmacokinetics
Tubulus RP Förvaltning AB and MedCore AB. Board member of Ferrosan ▪ Other assignments: CEO BioArctic AB
Medical Devices A/S and Rhenman & Partner Asset Management
Marie Ekström Trägårdh Elisabeth Svanberg
Board member Board member
▪ Board member since: 2017
▪ Board member since: 2017
▪ MD, PhD, Assoc Professor in surgery
▪ Other assignments: CEO Sectra Imaging IT Solutions and Executive
▪ Other assignments: Chief Development Officer Ixaltis SA
Vice President of the Group Sectra AB
Sten Nilsson
Board member
▪ Board member since: 2013
▪ Professor in oncology with affiliation to the Karolinska Institute
(KI), MD, PhD.
▪ Other assignments: Board member of the Swedish Cancer Society
Research Council and Rhenman & Partner Asset Management
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