asent annual meeting 2009
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February 23rd 2009
CREATING BREAKTHROUGH DRUGS TO TREAT BRAIN DISEASES
March 6, 2009 Confidential
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ASENT Annual Meeting 2009
New Peptide Engineered Compounds able to cross the blood-brain barrier to treat brain diseases
March 6, 2009 Confidential
Many drug candidates (mostly biologics) have been identified BUT they do not cross the BBB
• Angiochem’s technology platform allows for the synthesis of novel drug candidates which are designed to cross the BBB;
• Using this platform AngioChem has developed a portfolio of drug candidates reaching therapeutic concentration in the brain which have been validated in animal models and in human clinical trials
March 6, 2009 Confidential
AngioChem’s Solution for Crossing the BBB
• We identified the consensus sequence of amino acid responsible for binding to the LRP receptor, which naturally transports proteins to the brain
• We design new chemical entities incorporating that sequence which have the ability to bind to LRP and cross the BBB physiologically
March 6, 2009 Confidential
LRP Receptor and Major Ligands
2-Macroglobulin
ß
Thyroglobulin
RAP
AngiopepTPA
(tissue plasminogen activator)
Lactoferrin
• LRP transport small and large molecules
• LRP is highly expressed at the surface of the BBB
• LRP has a very fast endocytosis rate t1/2 (~30 sec)
• LRP is robust and has a high capacity
March 6, 2009 Confidential
Development Pipeline
DISCOV. PRECLIN. PHASE 2PHASE 1/2ANG-Cytotoxic
ANG 1005 : Antimicrotubule
Primary (glioma) and metastatic brain tumors
Undisclosed MAbNeurodegenerative diseases
ANG-Peptide
ANG-siRNA
Undisclosed siRNA Neurodegenerative diseases
DNA intercalation
ANG-MAb
GLP-1 receptor agonistMetabolic diseases
Internal Program
Joint Research Collaboration with Partner Leader in the Field
Situation in 12 months from now
STATUS
Internal Program
Internal Program
Joint Research
Collaboration
Joint Research
Collaboration
ANG Leptin Peptide
Topoisomerase II inhibitor
February 23rd 2009
CREATING BREAKTHROUGH DRUGS TO TREAT BRAIN DISEASES
March 6, 2009 Confidential
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Proof of conceptBrain Uptake
March 6, 2009 Confidential
Brain Uptake of Engineered Peptides
Compounds
ENGINEERED PEPTIDES WITH CY5.5
CAPILLARIES STAINED WITH VESSEL GREEN (FITC-LECTIN)
NUCLEI OF BRAIN CELLS STAINED WITH DAPI BLUE
March 6, 2009 Confidential
Homogenous Uptake of ANG1005 in the Brain
37.2 nCi/g22.36 nCi/g
20.9 nCi/g28.6 nCi/g
22.8 nCi/g
28.6 nCi/g
March 6, 2009 Confidential
Angiochem products Shows
Superior Brain Uptake
Drug Brain Kin (mL/s/g) Reference
Glucose 9.5 x 10-3 Mandula et al.(2006)
ANG1005 8.8± 0.6 x 10-3 Q. Smith, present work
Ang-GLP-1 receptor agonist 8.8±1.1 x 10-4 Internal work
Morphine 1.6 x 10-4 Seelbach et al. (2007)
Ang-siRNA 1.1 ± 0.1 x 10-4 Internal work
Insulin Rec Antibody 1 ± 0.3 x 10-4 Pardridge (1997)
Paclitaxel and Doxorubicin ~5 x 10-5 Muldoon et al. (2007)
RAP 1.0 ± 0.1 x 10-5 Pan (2004)
Etoposide ~4 x 10-6 Muldoon et al. (2007)
TNF-α 4.3 ± 0.1 x 10-6 Pan (2002)
Vasopressin 2.5 ± 0.1 x 10-6 Tanabe (1999)
March 6, 2009 Confidential
ANG1005 : Activity in Glioblastoma compared to
Paclitaxel
Day 17
Vehicle
Day 24
Paclitaxel
ANG1005
Day 10
Rat Brain MRI
February 23rd 2009
CREATING BREAKTHROUGH DRUGS TO TREAT BRAIN DISEASES
March 6, 2009 Confidential
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Proof of conceptClinical
March 6, 2009 Confidential
ANG1005Phase 1 Clinical Program
Two Protocols Conducted in Parallel in 9 centers in the USA
ANG1005-CLN-01: A Phase I, Open-Label, dose escalation study of ANG1005 in patients with Malignant Glioma and a surgical sub-study where patients are dosed prior to surgical debulking (level of product is measured in the extracted tumor)
ANG1005-CLN-02: A Phase I, Open-Label, dose escalation study of ANG1005 in patients with Solid Tumors and Metastatic Brain Cancer
March 6, 2009 Confidential
Clinical Highlights
Limiting toxicity• Bone marrow (mostly neutropenia)
No CNS Toxicity• Neurocognitive results are negative to date (n=18)
Immunogenicity• Results are negative for antibodies to date (n=31)
Validation in Humans• Data collected from the clinical trial confirm preclinical data and
strongly validate the platform technology. These data will be
published in a peer reviewed journal.
March 6, 2009 Confidential
Beyond the Blood Brain Barrier
BBBCROSSING
AHEAD
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