Esperanza Peptide Ltd.

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Esperanza Peptide Ltd. BioTherapeutics,
Inc.Immunokines
Immunokines are a family of bioactive molecules
derived from the oxidation of naturally occurring
bioactive plant and animal peptides. Each
immunokine appears to have distinct activity,
often related to the ability of the precursor
molecule to bind to its specific
receptor. www.esperanzapeptide.net
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Immunokines everything Interferons were
supposed to be!
Exciting potential for the treatment of
neurological disorders Major new drug for any
form of Multiple Sclerosis
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a-Immunokine-NNS

• Snake Oil or Science

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History
Began with Dr. Murray Sanders and Bill Haast.

• Post WWII polio studies
• Mixture of venoms from different species
• Could prevent/treat monkeys infected with
  poliovirus
• Introduction of polio vaccines obscured the
  antiviral potential of modified neurotoxins

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Oxidized Venom Properties
Why BioTherapeutics, Inc. chose to investigate
this further.

• Broad spectrum anti-viral activity
• Polio
• Pseudorabies
• Herpes simplex
• Semliki Forest Virus
• Very low toxicity - by design
• No apparent adverse side effects
• Showed promise in Polio, ALS, RA
• Native venom used in MS patients

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Drug Manufacture
Production of Immunokine from Cobratoxin.

• To 99.9 pure Cobratoxin
• Add a specific quantity of ozone dissolved in
  0.9 saline
• Incubate for 1 hour
• Test for toxicity, potency, purity sterility
• Bottle and distribute
• Summary CTX O3 Immunokine

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Neurotoxins In Research
Neurotoxins have demonstrated a number of
interesting properties.

• Employed usually as receptor ligands
• Anti-viral
• Anti-tumor
• Immunomodulatory
• Modulation of cytokine/hormone release
• Modulation of neuro-muscular transmission

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Animal Neurotoxins

• Usually ion channel antagonists - exception
  muscarinic acetylcholine receptors
• Very specific for target receptor
• Range in size from 18 to 80 amino-acids
• No enzymatic activity
• Block by stearic hindrance
• Block voltage and ligand-gated channels

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Cobratoxin Raw Material
Dr. Kent Miller identified active components.

• Active component - Cobratoxin from Naja Naja
  Siamensis
• Cobratoxin 20 of venom composition
• MW 7831, 71 amino acids
• Kills by suffocation
• Long-chain, post-synaptic neurotoxin
• Ligand for acetylcholine receptor - nicotinic
• Purified by CM column chromatography

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Immunokine Properties

• Non-toxic, LD50 gt 300mg/mouse
• Stable, gt 4 years at RT
• Binds to Nicotinic receptor
• Cannot overdose
• No interferon-like reactions
• Very few contraindications with other drugs

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Dosage Format Drug Info
Summary of drug properties and supplies.

• Average starting dose is 300ug
• Reduces to 100ug over time (3 years)
• Injectable and Oral delivery conc is 600ug/ml
• Drug takes effect within 30 minutes (Stabilized
  patients)
• 300ug /day 1g lasts 9.5 years
• 100ug/day 1g lasts 28 years
• Kg quantities available from snakes
• Gene(s) available from US Army (CRADA)

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Multiple Sclerosis
Our primary focus is MS.

• Multiple Sclerosis is the primary focus of our
  current RD and our MS product is the initial
  drug that we envision partnering with Big
  Pharma to bring to market under licensing
  agreement
• Our pipeline of products also include drugs aimed
  at other neurological and infectious diseases and
  disorders
• Incidence increasing in MS - 350K-500K in U.S.
• Globally estimated at 3 million MS sufferers
• Anticipated costs expected to be significantly
  lower than other MS drugs already on the market

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Immunokine MS
What does it do for patients?

• Reverses chronic fatigue - improves stamina
• Alleviates some types of pain
• Improves coordination/dexterity
• Usually improves balance
• Improves walking
• Helps vision
• May help incontinence (frequency gt urgency gt
  hesitancy)

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Immunokine MS
What does it not do?

• It is not a cure - wears off in 24 hours
• Does not help spasticity
• Cannot reverse optic neuritis
• Does not prevent relapses - though minor
• Does not protect from viral infections but
  general health is better

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How Does It Work?
Theory based on literature and observations.

• Possible Mechanisms
• Neuromuscular modulation
• Immune suppression
• Anti-viral
• Endocrine modulation? - Adrenal

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Proposed Immuno-Mechanism Of Action

• Prevents EAE - (T-cell mediated)
• Lymphocytes have acetylcholine receptors
• Chemotactic for macrophages and fibroblasts
• Anti-tumor and retroviral (HIV, FIV, FeLV)
  activity points to T-cell
• Homology to SIRs, a5/6

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The Nervous System
What we understand.

• As CTX is a NachR ligand, we look for the
  receptors and their function
• Nervous system can be divided in two
• Somatic - primary neurotransmittor is
  acetylcholine
• Autonomic - subdivided further into
• Sympathetic - primary transmittor is
  norepinephrine
• Parasympathetic - primary transmittor is
  acetylcholine

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Acetylcholine Receptors
Crash course version.

• 2 general groups
• Nicotinic - 8/9 subtypes defined by alpha subunit
• Muscarinic - 4/5 types similarly defined
• Nicotinic receptors associated with Na channel
• Muscarinic receptors are coupled to G-protein
  cascade
• Toxin and acetylcholine analogues have been
  identified with specific interactions on many
  types of cell many not defined as excitable.

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Acetylcholine Receptors (cont)
Crash course version (continued)

• There are a multitude of animal toxins which
  target the NachR mostly from snakes and sea
  snails
• CTX and BuTX have highest affinity for receptors
  with a1 gt a7 gt a9 gt a3
• a1 found mainly at neuro-muscular, postsynaptic
  junction
• a7 found mainly at presynaptic junction
• a9 found in the ear
• Pharmacology and functionality of these receptors
  not complete

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Proposed Neuro-Mechanism Of Action

• CTX prevents further nerve damage
• Denervation/loss of signalling results in loss of
  receptors. Blockade increases receptor density.
• a7 block may enhance signal transduction if
  acetylcholine has negative action
• Receptors in CNS may also be regulated
• May cross react with muscarinic receptors
• Should be able to measure conductivity

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Potential Uses 1
Neurological disorders

• Multiple Sclerosis
• Amyotrophic Lateral Sclerosis
• Adrenomyeloneuropathy/Adrenoleukodystrophy
• Guillian Barre syndrome - inflammatory
• Huntingtons Chorea - NachR
• Duchennes Muscular Dystrophy - NachR
• Diabetic Neuropathy
• Post-Polio Syndrome

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Potential Uses 2
Immune Disorders

• Multiple Sclerosis
• Chronic Fatigue
• Rheumatoid Arthritis
• Lupus
• Scleroderma
• Keloids
• Psoriasis

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Potential Uses 3
Human Antiviral Applications

• Herpes - EBV, CMV, VZV, severe genital herpes
• Papilloma - severe genital warts
• Retroviruses - HIV/HTLV
• Hepatitis - BC
• Rhabovirus - Rabies
• Others
• Thank you for your time and attention.
• Esperanza Peptide Ltd.
• www.esperanzapeptide.net