NexGen Biomedical’s
Tumor Specific Cell Cycle Synchronous Chemotherapy Protocols (TS-CCSC)
© 2009 Mark Zamoyski & NexGen Biomedical, Inc. , all rights reserved
Slide 2: Overview
The Problem
Best in class S-Phase Cytotoxics can kill 100% of cells in the S-Phase
• However, less than a third of cancer cells are in the S-Phase
The Opportunity
The Next Great Advances Will Come from Best in Class Protocols
• Boosting the S-Phase fraction from < 33% to an eventual 100% ceiling
The Product: CCSC Protocols
Modulate tumor specific mutations and characteristics for:
• S-Phase enrichment and synchronization
• Preventing tumor regrowth between administrations of cytotoxic
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© 2009 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved
Slide 3: Background - The Cell Cycle
The Cell Division Cycle Timeline and Phase Distribution: Average time to complete the cell cycle: Return to Slide Show Index
• Bone Marrow, GI, Hair, Skin: Fairly homogenous cycle time of 1 Day
• Colon Cancer: Heterogeneity of cycle time averaging ~ 20 Days
• Breast Cancer: Heterogeneity of cycle times averaging ~ 30 - 90+ Days
© 2009 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved
Slide 4: Receptors and Receptor Mutations
• Different cells possess different combinations of receptors
• Binding of growth factors (mitogens) with their corresponding receptors activates the receptors
• Activation of receptors results in activation of the Cell Cycle Control System
• Multiple receptor activation is typically required prior to S-Phase entry
• Overexpression of growth factor receptors is a common mutation
• Overexpressed receptors preferentially take up more ambient mitogens
• Mimic elevated levels of mitogens, inappropriately initiating a cell cycle
• Our TS-CCSC protocols target HER1 and HER2 overexpression mutations
• Our TS-CCSC protocols target endocrine dependent cancers
• Preventing receptor activation is used to aggregate cancer cells in the G Phase
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© 2009 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved
Slide 5: The TS-CCSC Protocol Approach
• TS-CCSC aggregates the cancer cells in the G Phase over several weeks
• The cancer cells are then released into the S Phase to be killed by an S Phase cytotoxic
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© 2004 - 2009 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved
Slide 6: TS-CCSC for HER1 & 2 Overexpression
• Reversible HER blockers are used as G1 Phase Oncostatics
• HER blocker inactivators (CYP3A4 inducers) are used to precisely release the cancer cells into the S-Phase
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© 2004 - 2009 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved
Slide 7: TS-CCSC for Endocrine Dependent Cancers
• Estrogen, Progesterone, and Testosterone Dependence are the top 3 targeted
• Endocrine Downregulators serve as G1 Phase Oncostatics
• Endocrines serve as G1 Phase Anti-Oncostatics
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© 2004 - 2009 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved
Slide 8: TS-CCSC S Phase Cytotoxics
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© 2009 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved
Slide 9: TS-CCSC Versus Legacy S Phase Cytotoxic Protocols
• Legacy S Phase Cytotoxic protocols use 7 or 21 day administration intervals
• A Legacy S Phase cytotoxic protocol kills less than a third of cancer cells per administration
• TS-CCSC Cancer kill rate is limited only by the amount of S-Phase enrichment
• Legacy Protocols do not prevent regrowth between administrations, hence kill back is not cumulative
• TS-CCSC inhibits cancer regrowth between administrations, making kill back cumulative
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© 2009 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved
Slide 10: TS-CCSC vs. Concurrent Cytostatic / S Phase Cytotoxic Protocols
• Concurrent use of Cytostatics and S Phase cytotoxics is disclosed in HER1/2 Prescribing Information
• Concurrent use is mechanistically antagonistic
• G Phase arrest = S Phase depletion
• In contrast, TS-CCSC Interlaced Protocols are mechanistically synergistic
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© 2009 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved
Slide 11: TS-CCSC vs. Prior Art Failed Attempts as CCSC
• The enormous therapeutic potential of CCSC is commonly acknowledged
• However, failed prior art attempts at CCSC have had a chilling effect to progress in this area
• Understanding why prior art failed is necessary for understanding why TS-CCSC will succeed and realize the enormous therapeutic potential
• The two biggest reasons for prior art failures:
• Aggregation periods were too short
• Lack of Targeted (tumor specific) aggregation
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© 2009 Mark Zamoyski & NexGen Biomedical, Inc., all rights reserved
Slide 12: Patents Issued / Cancers Covered
Categorized by Mutation or Characteristic Modulated for S-Phase Enrichment
• HER1 Cancers (US 7,507,704)
• HER2 Cancers (US 7,309,486)
• Endocrine Dependent Cancers (US 6,486,146)
Prospective US Patients Annually
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.
© 2002 - 2009 Mark Zamoyski & NexGen Biomedical, Inc.