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Vladislav deigin peptide pharmaceuticals in russia and worlwide
 

Vladislav deigin peptide pharmaceuticals in russia and worlwide

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Vladislav deigin peptide pharmaceuticals in russia and worlwide Vladislav deigin peptide pharmaceuticals in russia and worlwide Presentation Transcript

  • Peptide Pharmaceuticals: Development in Russia and Worldwide Vladislav Deigin “ Peptos Pharma” Moscow, Russia Shemyakin & Ovchinnikov Institute of Bioorganic Chemistry Russian Academy of Sciences, Moscow, Russia JV “Pharma Bio”
  • Genomic Proteomic Peptidomic Planet Galaxy Universe Peptides – universal bioregulators
  • Topics for discussion:
    • Peptide drugs: current landscape and perspectives;
    • Pipeline of peptide pharmaceuticals: contribution of Russian science;
    • Novel approach for next generation development of peptide pharmaceuticals
  • Topics for discussion:
    • Peptide drugs: current landscape and perspectives;
  • Total amount of registered API in USA and Europe Non-peptide/protein drugs (over 5000) Peptide/protein drugs (~60 synthetic peptides and ~15 proteins)
  •  
  • Peptide pharmaceuticals – one of the fastest growing segments of the world market Clinical indication for the peptide drugs . Publications related to synthetic peptide preparations Sales volume for 10 the best selling peptide pharmaceuticals Number of peptide products in the development pipeline in 2008
  • Topics for discussion:
    • Pipeline of peptide pharmaceuticals: contribution of Russian science:
    • - Pharmaceuticals
    • - Peptide vaccines
    • - Oral delivery system
  • Topics for discussion:
    • Pipeline of peptide pharmaceuticals: contribution of Russian science:
    • - Pharmaceuticals
  • There are 13 original branded peptide drugs developed and marketed in Russia Peptide pharmaceuticals: Route of administration 1 Dalargin (anti –ulcer) - IM 2 Thymogen (immunomodulator) - IM, Intranasal 3 Semax (neuroprotector, after stroke ) – Intranasal 4 Likopid (immunomodulator) - sublingual tablets 5 Immunofan (immunomodulator) - - Sq. injections 6 Thymodepressin (immunosupressor) – IM, Intranasal 7 Deltaran ( adaptation, neuroprotector) – IM 8 Gepon – (antiviral, immunomodulator) - Sq. injections 9 Sedatin (vet. market) - (stress – and anxiety protector) - IM, Intranasal 10 Bestim – (immunomodulator) – IM 11 Allokin-alfa - Subq. injections 12 Noopept (nootropic) – oral tablets 13 Stemokine (Neogen) – (hemopoietic booster) – IM, Intranasal
  • Latest survey of research areas in modern drug discovery field Over 53% of most active researchers are dealing with immune-related drug - candidates Research related to immune system Published by Bioinformatics LLC
  • Peptides affecting the immune system – the most advanced area of peptide pharmaceuticals approved in Russia Immunoactive Peptide Pharmaceuticals: Indications 1 Thymogen Immunomodulator, antiviral 2 Likopid Immunomodulator, antiviral 3 Immunofan Immunomodulator, antiviral 4 Thymodepressin Immunosupressor 5 Gepon Immunomodulator, antiviral 6 Bestim Immunomodulator 7 Allokin -alpha Immunomodulator, antiviral 8 Stemokine (Neogen) Hemopoietic booster, Immunomodulator
  • Лекарственные препараты разработанные «Пептос Фарма» Immunomodulators Immunosupressor Hemostimulant Approved peptide pharmaceuticals developed by IBCH RAS and “Peptos Pharma Ltd” Thymogen for injections Nasal Spray Thymogen for injections Nasal Spray Stemokine for injections Likopid tablets Neurotropic pharmaceutical for treatment of neurotic and stress related disorders
  • D -GLU – D -TRP Thymogen L - TRP D - D -TRP L -GLU D - G LU Thymodepressin IMMUNOSTIMULATION IMMUNOSUPPRESSION L -GLU – L -TRP CHEMICAL AND OPTICAL STRUCTURES OF GLU –TRP ISOMERS
  • T- cell B-cell L-L ( natural ) D-D ( synthetic antagonist )
  •    1. CONTROL 2. CYCLOSPORIN A ( 50 mg/kg) 3. THYMODEPRESSIN ( 1 0 µg / kg) SUPRESSIION INDEX COMPARISON OF CYCLOSPORIN A AND THYMODEPRESSIN ON GVHD SUPRESSION (MICE SPLENOMEGALY MODEL )
  • * * * Ctrl titers COMPARISON OF CYCLOSPORIN A AND THYMODEPRESSIN ON AUTOANTIBODY SUPRESSION (Mercury inducing antibodies to fibrillarin, prophylactic mode)
  • PASI 68 PASI 6 Patient B. before treatment Patient B. after one month
  • Patient C. before treatment by Thymodepressin Patient C. after 4 month (one cycle of treatment)
  • Neogen/Stemokine: a new generation of immuno and hemo-stimulant
    • Approved in Russia in 2009
    • Stimulates the immune system
    • Stimulates regeneration of hemopoiesis (hemopoietic stem cells) after irradiation or chemotherapy
    • Shows no side effects
  •  
  • Likopid – a potent and safe immunomodulator
    • Pronounced immunomodulatory effect
    • Minimal side effects, high tolerance
    • Convenient formulation (1 or 10 mg tablets)
  • secretion GMDP – NOD2 : molecular mechanism of action and signal pathways NUCLEUS NOD2 GMDP peptidoglycan RIP2/RISC 1kB NF-kB IL-1  proIL-1  GMDP key: CARD NOD LRR Kinase
  • INFLUENCE OF PEPTIDES ON HEMOPOIESIS Suppression by Thymodepressin Stimulation by Neogen Stimulation by Likopid Stimulation by Thymogen
  • Topics for discussion:
    • Pipeline of peptide pharmaceuticals: contribution of Russian science:
    • - Peptide vaccines
  • В- cells FOOT AND MOUTH DISEASE VIRUS EPITOPES FOR: Т- helpers SYNTHETIC PEPTIDE VACCINE Site responsible for virus reception PATENTED SYNTHETIC FOOT AND MOUTH DISEASE VACCINE APPROVED FOR VETERINARIAN USE IN RUSSIA Active principle - synthetic fragment of the VP1 viral protein acylated by palmitinic acid; Adjuvant – synthetic polymethylsiloxane oil; Duration of the protective immunity – 1 year after single immunization; The vaccine is effective against the А 22 viral strain in sheep.
    • Alzheimer’s disease (AD):
    Vaccination with synthetic peptide fragment of α7-subunit of the AChR provides a new approach to anti-AD drug development.
    • Our proposals:
    • Selected synthetic fragments of Аβ-α7
    • AChR- Receptor can be used for development of anti-Receptor antibodies
    • 2) Antibodies directed against Receptor
    • will prevent the Receptor from binding to β -amyloid
    • 3) Neurons will survive
    • 4) Therapeutic vaccine will be developed
  • The model of the extracellular N-terminal domain of α 7 -subunit of the AChR Peptide I (1-23) 1 GEFQRKLYKEL VKNYNPLER PVA 23 Peptide II (159-16 8 )-(179-188) 159 QMQEADISG Y 168 - 179 IPGKRSER FY 188 Peptide III (173-188) 173 E WDLVGIPGK RSERFY 188 Peptide IV (173-193) 173 EWDLVGIPGKRSERFYECCKE 193 Synthetic fragments of extracellular N-terminal domain of α 7 -subunit of the AChR EWDLVG IPGKRSERFY ECCKE Peptide IV (173-193) with “built-in” adjuvant
  • The level of β -amyloid in brain tissues of experimental AD – mice and control (Ct) mice
  • Topics for discussion:
    • Pipeline of peptide pharmaceuticals: contribution of Russian science:
    • - Oral delivery system
  • WHAT IS THE NEXT STEP IN PEPTIDE DEVELOPMENT? Development of a new generation of small peptide-based pharmaceuticals with increased stability to digestive enzymes resulting in oral availability
    • L-Glu-L-Trp - immunostimulant (Thymogen)
    •  - D-Glu-D-Trp - immuno- and hemosuppresant
    • (Thymodepressin)
    Chemical structure of peptide immunomodulators - high selectivity + - minimal side effects + - stability per os - - solubility in aqueous media + - low toxicity profile + - non immunogenic + - molecular mass below 500 D + - high selectivity - minimal side effects - stability per os - solubility in aqueous media - low toxicity profile - non immunogenic - molecular mass below 500 D Pfizer's “ Ideal formula ” :
  • R R carrier N H C O N H C O Linker 1 Linker 2 C H 2 N H Active molecule 1 o NH C o CH 3 o CH 3 C o H Active molecule 2 Cyclo Technology Platform: Multifunctional biologically active composition Variable building blocks Individual molecules chemically linked to a biocarrier
  • Cyclo Technology Platform : Biocarrier scaffold + Functional derivatives Immunology Hematology Neuro- pharmacology Chemo- pharmacology - Immunostimulation - Adjuvant activity - Vaccination + adjuvant: Conventional vaccines Synthetic vaccines Cancer vaccines
    • - Hemostimulation
    • - Stem cell boosting
    • Blood cell boosting
    • and harvesting
    • Immunosuppression
    • Hemopoiesis suppression
    • - Autoimmune diseases
    • - Transplantation
    • Neuroimmunology
    • Drug addiction
    • Psychopharmacology:
    • Depression, Stress,
    • Anxiety
    Metabolic and toxicity profile improvements for small molecules
    • CycloTechnology platform:
    New generation of peptide derivatives - high selectivity + - minimal side effects + - stability per os + - solubility in aqueous media + - low toxicity profile + - non immunogenic + - molecular mass below 500 D + - high selectivity - minimal side effects - stability per os - solubility in aqueous media - low toxicity profile - non immunogenic - molecular mass below 500 D Pfizer's “ Ideal Formula ” :
  • “ Pharma Bio LLC” Development Plan for 2011-2013 Set up of pilot GMP facility for peptide synthesis of API and nasal spray Thymodepressin – clinical trials for new indications: RA, MS, Asthma Stemokine – clinical trials for new indications : oncology, oncohematology, tuberculosis Sedatin –Phase I –II clinical trials for the treatment of anxiety and stress Opilong –Phase I –II clinical trials for the treatment of alcohol dependence C12-OB – Preclinical development of new synthetic vaccine for the AD immunotherapy
  • Layout of GMP pilot facility for peptide API and Nasal sprays View of future GMP unit of “Pharma Bio”
  • Peptide Pharmaceuticals: Development in Russia and Worldwide JV “Pharma Bio” Thank you!