non-confidential presentation
TRANSCRIPT
NON-CONFIDENTIAL PRESENTATION
2015
Founded February 2009, based in Vancouver, British
Columbia
Formerly AlCana Technologies Inc
Highly experienced team developing lipid nanoparticle
delivery systems
Facilities for chemistry, formulation and preclinical studies
with access to additional resources at the University of
British Columbia (UBC)
2015 2
Systemic lipid nanoparticles for intracellular delivery of
molecular therapeutics – primarily nucleic acids
Pharmaceutical applications:
Protein replacement therapeutics (mRNA or plasmid
delivery)
Protein knockdown therapeutics (antisense)
2015 3
Synthetic chemistry
Design and synthesis of novel cationic lipids and PEG-lipids
Radiolabeled and stable-isotope lipids to support ADME
studies.
Product formulation, scale-up and cGMP manufacture (in
partnership with NLI)
Analytical and biophysical characterization
Preclinical characterization
PK/PD/ADME
2015 4
Multi-component carrier
Small, uniform sized
particles (~80 nm)
Low surface charge in
blood compartment
2015 5
LIPID NANOPARTICLES FORMULATION
2015 6
Substantial improvement in LNP potency for RNAi
payloads
Development of biodegradable LNP components with
significantly improved safety profile
Characterization of LNP Carriers in vivo:
Mechanism of action (receptor mediated uptake and
intracellular pathways)
Plasma interactions and stability
Development of improved LNP carriers for mRNA
therapeutics
ACUITAS ACHIEVEMENTS
2015 7
Receptor-mediated uptake in hepatocytes
Loss of PEG-lipid from the LNP surface allows binding of ApoE
Bound ApoE facilitates receptor binding and endocytosis
ApoE
PEG-Lipid
LNP with bound
ApoE
2015 8
Endosomal Release
Endosomal maturation results in drop in internal pH
LNP cationic lipid becomes positively charged resulting in release of
nucleic acid payload to cytoplasm
Nucleic acid
payload
Translation of RNAi expertise to other molecular
therapeutics (mRNA and plasmids)
Accessing non-liver targets
Carrier access via fenestrated capillaries (e.g. bone marrow,
lymph nodes, spleen, tumors, sites of infection, etc.)
Receptor-mediated entry into target cells
2015 9
mRNA encapsulated in lipid nanoparticles (LNP)
In vivo expression of reporter and therapeutic mRNAs
determine in mice
Luciferase
Factor IX
Erythropoietin
Others
2015 10
2015 11
DOSE RESPONSIVE PROTEIN EXPRESSION
Efficient mRNA delivery to
liver.
Luciferase expression
proportional to mRNA dose
(0.1-3.0 mg/kg)
Acuitas LNP vs Phua et al. LNP
(Phua, Leong and Nair, J.
Control Release, 166(3) 227-
233, 2013)
Luciferase expression in liver 4
hours after iv administration
2015 12
COMPARATIVE LNP POTENCY
13
Dose (mg/kg)
Liv
er
Lu
c (
ng
/g tis
su
e)
0
5000
10000
15000
20000
MC3
ALC-0217
ALC-0218
0.1 mg/kg 0.3 mg/kg 1 mg/kg
Dose (mg/kg)
Liv
er
Luc (
ng
/g tis
sue)
0
5000
10000
15000
20000
MC3
ALC-0217
ALC-0218
0.1 mg/kg 0.3 mg/kg 1 mg/kg
Acuitas has identified
novel LNP components
providing significantly
higher potency for
mRNA expression.
2015
2015 14
mild
severe
moderate
Acuitas mRNA-LNP
can express proteins
at therapeutic levels
in plasma.
2015 15
Focus on partnerships in field of protein replacement
therapeutics (mRNA therapeutics)
Acuitas supports:
Preclinical screening to select Lead Products
Protection of Lead Products through new and existing IP
rights
Analytical, biophysical and preclinical characterization of
Lead Products
Transition from preclinical to clinical development
2015 16
Corporate Contact: Dr. Thomas Madden, President & CEO
Phone: 604-880-6157
Email: [email protected]
Scientific Contact: Dr. Michael Hope, CSO
Phone: 604-837-9239
Email: [email protected]
Website: www.acuitastx.com