Seminar Overview and Table of Contents

Slide Show Index

Slide 1: Title Page
Slide 2: The Drug
Slide 3: Antiproliferative Activity
Slide 4: Antiviral Activity
Slide 5: Anti-Inflammatory Activity
Slide 6: Exceptional Localization
Slide 7: Large Systemic Safety Margin
Slide 8: Indications of Interest
Slide 9: Drug Production and Cost
Slide 10: Patent Portfolio
Slide 11: Summary

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RNAi / PSR

Dermal and Pulmonary Antiproliferative, Antiviral, and Anti-Inflammatory

The Drug

A Small Molecule Capable of:

• Inhibiting / restricting translation of RNA into Proteins (RNAi / PSR)

•

Molecule binds to peptidyl transferase site on ribosomes

•

Inhibits / restricts translation for ~ 12 hours per administration

• Exceptional Localization

•

Retained where applied

Physiological Activity:

•

Antiproliferative, Antiviral, and Anti-Inflammatory Activity

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© 2010 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved

Antiproliferative Activity
Antiproliferative activity evaluated in 4 Phase I and 7 Phase II trials against cancer
(Diacetoxyscirpenol [DAS] called Anguidine by Bristol-Myers)

•

The drug is a G1 and G2 Phase Cytostatic

•

Prolonged exposure is required for Cytotoxic effect (apoptosis)

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© 2010 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved

Antiviral Activity
Antiviral activity of DAS demonstrated ex-vivo, human cells, HSV2 virus

• Full Spectrum Viral Protein Synthesis Inhibition (IC50 = 2.3 ng/ml, IC99 by 5 ng/ml)
• Viral DNA Synthesis Inhibition (secondary effect of PSR)

•

Viruses require use of host ribosomes (lack the genome to make them)

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© 2010 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved

Anti-Inflammatory Activity
Anti-Inflammatory activity of RNAi / PSR demonstrated in-vivo in mouse models
(contact hypersensitive mice, using structurally related molecule with same RNAi / PSR profile as DAS)

• 44% reduction in ear swelling observed by topical application
•

Dermis resident mast cells and macrophages synthesize pro inflammatory proteins

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© 2010 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved

Exceptional Localization

> 97% of DAS localizes in the Epidermis and Dermis
- (ex-vivo, human skin, without subcutaneous fat)

Estimated Distribution by Layer:
- (ex-vivo, human skin, based on relative % of recovered tritium labeled T2 - one R group off from DAS w/same overall retention as DAS)

• 38% stratum corneum, 40% living epidermis, 22% dermis

• Epidermis is target for Antiproliferative and Antiviral Activity

• Dermis is target for Anti-Inflammatory Activity

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© 2010 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved

Large Systemic Safety Margin

• Even if the entire administered dose goes to blood, it would be very safe

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© 2010 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved

Indications of Interest

• Indications where dual action / localization would be advantageous include:

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© 2010 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved

Drug Production and Cost

Natural Product with established production and purification procedures

• 0.5 grams of DAS per liter of cultured F. sambucinum in 9 days

• F. sambucinum available from USDA

Cost is pennies per dose because of nanogram level potency

• 1 gram = Epidermal IC99 for 1.3 Billion square cm of skin

• 1 gram = 27,000 IC99 lung doses

Patent Portfolio

Issued Dermal and Pulmonary U.S. Patents (method of use)

• Psoriasis Treatment Method (Topical)

• Epidermal Exfoliation Method (Topical)

• Pulmonary Anti-Inflammatory (Inhalable)

• COPD Treatment Method (Inhalable)

Pending U.S. Patent

• Dual Action Dermal and Pulmonary Anti-infective / Anti-inflammatory

Scope of Patents

• Cover more than 150 structurally related natural compounds and ~50 synthetic variants

Summary

• Platform Technology

• Low investment risk - No Research, Development Only

• Low risk / high upside from multiple indications

• Indications include several large, poorly served markets

• Very safe - based on Phase I human data by iv

• Issued Patents

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DISCLAIMER AND IMPORTANT NOTICE: The Compositions and Methods presented on this website are all in preclinical trial stages. They are based only on our understanding of the proposed underlying mechanisms of action and on any available coincidental corroborative empirical evidence, any of which may in fact turn out not to be correct, or may be prevented from functioning as envisioned because of other factors or mechanisms of action not contemplated or considered, or may even cause harm because of factors or mechanisms of action not anticipated. The process of obtaining FDA approvals has not been started in any of the areas disclosed on this website. The disclosures here are purely for scientific information exchange purposes, representing one scientific point of view, and are not intended to suggest, or be used for, any proposed medical treatments.