New Anticancer Agents Targeting the Tumor-Specific Microenvironment - - PowerPoint PPT Presentation

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New Anticancer Agents Targeting the Tumor-Specific Microenvironment - - PowerPoint PPT Presentation

May 02, 2023 158 likes •294 views

New Anticancer Agents Targeting the Tumor-Specific Microenvironment (OTT ID 1277) Inventor: Xiaohua Peng, Associate Professor, Department of Chemistry and Biochemistry UW-Milwaukee For further information please contact: Jessica Silvaggi,

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New Anticancer Agents Targeting the Tumor-Specific Microenvironment

(OTT ID 1277)

Inventor: Xiaohua Peng, Associate Professor, Department of Chemistry and Biochemistry UW-Milwaukee For further information please contact:

Jessica Silvaggi, PhD, CLP Senior Licensing Manager 1440 East North Ave. Milwaukee, WI 53202 Tel: 414-906-4654 Jessica@uwmrf.org

1/8/2018 UWMRF 2018 1

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Current Problems with Cancer Therapies

  • Goal: Improve the selectivity of cancer therapy
  • Problems/Unmet Needs:

 Severe side effects, attack healthy cells

 Prodrug approach: drugs in an inactive or significantly less

active form, metabolized to active form  Previous prodrug approach: low selectivity low levels of activators in necrotic tumor tissue

1/8/2018 UWMRF 2018 2

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Pro-drugs Targeting Tumor Cells

  • Prodrugs are only activated

by unique features inside cancer cells

  • Selective release of toxic drug

in cancer cells

  • U.S. Utility Patents Issued

– Anti-Cancer Agents: 8,637,490 – Anti-Cancer Agents: 8,962,670

1/8/2018 UWMRF 2018 3

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http://www.thepharmaletter.com/article/targeted-cancer-drug-market-set-to-reach-51- billion-by-2015-led-by-pfizer-barriers-to-use-of-oral-cancer-drugs-identified

Targeted cancer drug

Market Size

  • The global oncology market is expected to reach $112B by 2020
  • Targeted cancer drugs now make up 46% of cancer sales
  • The Agency for Healthcare research and Quality (AHRQ) estimates that the direct

medical costs (total of all health care costs) for cancer in the US in 2014 were $87.8 billion

1/8/2018 UWMRF 2018 4

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Market Potential

Applications for our compounds

  • Inhibiting cancer cell growth or causing cell death in leukemia, non-

small cell lung cancer, colon cancer, breast cancer, and renal cancer cell lines (tested in NCI 60 assays)

  • Reducing tumor size in animal models for renal cancer cell lines and

breast cancer cell lines

  • Our tumor-targeting prodrug platform approach can be applied to

thousands of other drugs

1/8/2018 UWMRF 2018 5

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High Level of Hydrogen Peroxide in Cancer Cells

CANCER CELLS:

  • Contain reactive oxygen species (ROS):

hydrogen peroxide and free radicals

  • Rapidly divide and grow
  • Have increased active metabolism
  • Show decreased free radical scavenging

enzymes

*Prodrugs activated by hydrogen peroxide can selectively kill cancer cells

1/8/2018 UWMRF 2018 6

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Designing Prodrugs That Target Tumor Cells

  • Non-toxic until located in cancer cells
  • Hydrogen peroxide trigger

Activation

1/8/2018 UWMRF 2018 7

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Our Drugs Work in vivo

  • They are safe to mice: no obvious toxicity,

no weight loss

  • Reduce tumor size (breast cancer)
  • Drug used during entire treatment

1/8/2018 UWMRF 2018 8

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Our Drugs Also Shrink Established Tumors

1 2 3 4 5 6 100 250 400 550 700 850 Vehicle Compound 2 Week Tumor size (mm3)

  • Compound 2 induces genes involved in apoptosis and cell cycle
  • P21, P53, Bcl2, and CyclinD1 RNA levels were induced
  • Microarrays showed genetic modulation in DNA binding, DNA

repair, and DNA ligation

1/8/2018 UWMRF 2018 9 *Manuscript submitted; related data Wang et al. 2017. EJMC. 133: 197-207.

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Pharmacological proof of concept (PK/Tox/ADME)

  • Animal model studies ($500,000)

Toxicity test () Xenograft mice model study () Transgenic mice model

  • Lead optimization ($300,000)

*metabolic stability () *oral availability *bio-distribution *function of mechanism: in vivo target selectivity

Moving the Program Forward

1/8/2018 UWMRF 2018 10

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Looking for industry partners

  • Transition to clinical/commercial development
  • Further funding required
  • Conducting clinical trials for effective lead compounds
  • Licensing of our technology

Partnering with industry on sponsored research

  • Applying this platform technique for developing novel

pro-drugs

Next Steps Needed

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In Summary

  • The Peng lab has designed and synthesized a series of novel ROS-

activated aromatic nitrogen mustards which selectively kill tumor cells with minimal effects on normal cells

  • Mouse xenograph tumor models using breast cancer show tumor

prevention and regression with lead compounds

  • Lead compounds are not prohibitively toxic to normal cells

1/8/2018 UWMRF 2018 12

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New Anticancer Agents Targeting the Tumor-Specific Microenvironment

(OTT ID 1277)

Jessica Silvaggi Senior Licensing Manager 1440 East North Ave. Milwaukee, WI 53202 Tel: 414-906-4654 Jessica@uwmrf.org

1/8/2018 UWMRF 2018 13