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ASENT Annual Meeting 2009

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.

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ASENT Annual Meeting 2009

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  1. ASENT Annual Meeting 2009 New Peptide Engineered Compounds able to cross the blood-brain barrier to treat brain diseases

  2. 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

  3. 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

  4. ß LRP Receptor and Major Ligands • 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 TPA (tissue plasminogen activator) Angiopep 2-Macroglobulin RAP Thyroglobulin Lactoferrin

  5. Development Pipeline DISCOV. PRECLIN. PHASE 1/2 PHASE 2 STATUS ANG-Cytotoxic ANG 1005 : Antimicrotubule Primary (glioma) and metastatic brain tumors Internal Program DNA intercalation Topoisomerase II inhibitor ANG-Peptide Metabolic diseases GLP-1 receptor agonist Internal Program ANG Leptin Peptide ANG-MAb Joint Research Collaboration Neurodegenerative diseases Undisclosed MAb ANG-siRNA Joint Research Collaboration Neurodegenerative diseases Undisclosed siRNA Internal Program Joint Research Collaboration with Partner Leader in the Field Situation in 12 months from now

  6. Proof of conceptBrain Uptake

  7. 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

  8. Homogenous Uptake of ANG1005 in the Brain 22.8 nCi/g 28.6 nCi/g 37.2 nCi/g 22.36 nCi/g 20.9 nCi/g 28.6 nCi/g

  9. Angiochem products ShowsSuperior Brain Uptake

  10. ANG1005 : Activity in Glioblastoma compared to Paclitaxel Vehicle Paclitaxel ANG1005 Day 10 Day 17 Day 24 Rat Brain MRI

  11. Proof of conceptClinical

  12. 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 Gliomaand 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

  13. 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.

  14. Beyond the Blood Brain Barrier BBB CROSSING AHEAD

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