asent annual meeting 2009

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


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


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


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


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





Proof of conceptBrain Uptake


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


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


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)


ANG1005 : Activity in Glioblastoma compared to

Paclitaxel

Day 17

Vehicle

Day 24

Paclitaxel

ANG1005

Day 10

Rat Brain MRI

February 23rd 2009





Proof of conceptClinical


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


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.


Beyond the Blood Brain Barrier

BBBCROSSING

AHEAD

asent annual meeting 2009

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