Southern California Investor Conference August 29, 2011 - - PowerPoint PPT Presentation

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Southern California Investor Conference August 29, 2011 - - PowerPoint PPT Presentation

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[ NASDAQ: MSHL ] Southern California Investor Conference August 29, 2011 Forward-Looking Statements These slides and the accompanying oral presentation contain forward-looking statements. Actual events or results may differ materially from

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Southern California Investor Conference August 29, 2011

[ NASDAQ: MSHL ]

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Forward-Looking Statements

These slides and the accompanying oral presentation contain forward-looking statements. Actual events or results may differ materially from those projected in any of such statements. Additional information concerning factors that may cause actual events or results to differ from those projected is contained in Marshall Edwards’ most recent annual report on Form 10-K and quarterly reports on Form 10-Q, as well as other subsequent filings with the SEC.

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Marshall Edwards (Nasdaq: MSHL)

  • Oncology company focused on the clinical development of novel

therapeutics targeting cancer metabolism

  • Extensive clinical experience with multiple compounds developed

from proprietary technology platform

  • Two lead compounds show robust activity against broad range of

tumor cell lines

  • ME-143 expected to enter clinic by September; ME-344 by Q1 2012
  • Worldwide rights to lead compounds as well as other potential

drug candidates and indications

  • Headquartered in San Diego
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Management Team

Executive Management

Daniel Gold, Ph.D. President & Chief Executive Officer

Former Chief Scientific Officer & Founder of Favrille

Thomas Zech Chief Financial Officer

Former Chief Financial Officer at Pacira Pharmaceuticals

Robert Mass, M.D. Chief Medical Officer

Former Head of Medical Affairs, BioOncology at Genentech

Board of Directors

Bryan Williams, Ph.D. (Chairman)

Director of the Monash Institute of Medical Research

Leah Cann, MBA

Two-time Wall Street Journal All-Star Analyst

Daniel Gold, Ph.D.

President & CEO of Marshall Edwards

William Rueckert

Chairman of Novogen Limited

Christine White, M.D.

Former Senior V.P. of Global Medical Affairs at Biogen Idec

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Lead Drug Candidates

Derived from Proprietary Isoflavone-Based Platform

O O H O OH H

NADH Oxidase Inhibitor: ME-143 1st Generation: Phenoxodiol

O O H OH O O H OH O OH

Scaffold: Genistein

O O H O OH H

Mitochondrial Inhibitor: ME-344

Next Generation

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NADH Oxidase (tNOX) Inhibitors

Mechanism of Action: Caspase-Mediated Apoptosis

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Mitochondria

Drug

 COX IV  ATP  ADP  AMPKα1 Caspase- Independent Cell Death Destructive Autophagy DNA Fragmentation  mTOR  LC3-II  Bax  ERK

Mitochondrial Inhibitors

Mechanism of Action: Caspase-Independent Cell Death

Endo G

Nucleus  ROS

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Lead Candidates ME-143 & ME-344

Superior Single-Agent Anti-Tumor Activity*

Compound Breast (SK-BR-3) Melanoma (MM200) Lung (NCI-H460) Ovarian (CP70) Prostate (PC3) Phenoxodiol 16.95 9.88 4.4 4.1 6.46 ME-143 0.07 0.53 0.58 0.28 0.27 ME-344 0.03 0.26 0.11 0.12 0.09

* IC50 = M

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tNOX Inhibitor Clinical Trial Experience

Platinum-Resistant or Refractory Ovarian Cancer

ME06-0039 (N=70) ME06-0037 (N=20) Route of Phenoxodiol Administration Oral Intravenous Treatment Weekly platinum + Phenoxodiol Weekly platinum + Phenoxodiol Response Rate 0/70 = 0% 6/20 = 30%

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tNOX Inhibitor Clinical Trial Experience

Comparable Patient Demographics (ITT Population)

ME06-0039 Oral Phenoxodiol ME06-0037 i.v. Phenoxodiol Chemotherapy Carboplatin Cisplatin Age in years Median: Range: 59 39-78 60 43-72 Karnofsky performance status Median: Range: 90 60-100 90 60-100 Histology Serous: Endometrioid: Other: 81% 10% 9% 65% 9% 26% Number of prior regimens Median: Range: 3 2-5 3 1-7 Months since platinum refractoriness/resistance Median: Range: 9 1-21 7 1-13

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tNOX Inhibitor Program Summary

  • Clinical experience shows insufficient levels of active drug

achieved when 1st generation Phenoxodiol is administered orally

  • Strong Phase 2 data that suggest Phenoxodiol is active when

administered intravenously

  • Next-generation ME-143 significantly more active in pre-clinical

studies

  • Expect to initiate Phase I trial of ME-143 by September 2011
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Mitochondrial Inhibitor Program

O O H O OH CH3

Prodrug: ME-128

O O H O OH H

Lead Candidate: ME-344

Demethylated in vivo

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Mitochondrial Inhibitor: Potent Inhibitor of Chemo- Resistant Primary Ovarian Cancer Cell Lines*

* Alvero, Montagna, Mor, et al. 2009. ME-128, a novel isoflavone derivative, induces caspase independent cell death through Akt/mTOR pathway. Cancer. 115:3204-3216

ME-128

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* Data provided by Dr. Kwok-Kin Wong, Dana Farber Cancer Center, Boston

A549 NCI-H1734 NCI-H1299

Mitochondrial Inhibitor: Active on KRAS Mutant, Tarceva-Resistant NSCLC Cell Lines*

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100 200 300 400 500 600 700 800 900 1000 8 10 12 14 16 18 20 22 Time (Days) Tumor Volume (mm3)

* *

ME-128 vehicle control ME-128 (50 mg/kg) RAPAMYCIN vehicle control RAPAMYCIN – 40 mg/kg

Mitochondrial Inhibitor: As Effective as Rapamycin in Pre-Clinical Studies…

R182 Ovarian Xenograft Model

*p  0.005

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90 92 94 96 98 100 102 104 106 108 110 112 114 116 8 10 12 14 16 18 20 22

Time (Days) Percentage Change - Body Mass

ME-128 Vehicle Control ME-128 (50mg/kg) RAPAMYCIN Vehicle Control RAPAMYCIN - 40mg/kg

* *p  0.005

…but with Less Toxicity

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Mitochondrial Inhibitor Program Summary

  • Dual mechanism of action → caspase-independent cell death via

DNA fragmentation and destructive autophagy

  • Active against a broad range of major cancer cell lines, including:
  • Chemotherapy-resistant ovarian cancer stem cells
  • KRAS-mutant, Tarceva-resistant non-small cell lung cancer
  • Next-generation ME-344 significantly more active in pre-clinical

studies

  • Expect to submit IND application for ME-344 by Q1 2012
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Clinical Development Strategy

  • Goal: Establish clear evidence for clinical activity in combination

with standard chemotherapy regimens

  • Randomized/controlled Phase II trials
  • Assumption: Mechanism of action and preclinical results do not

predict specific tumor type or chemotherapy combination

  • Focus: Common tumors with unmet medical need, unambiguous

assessment of clinical benefit and weekly/bi-weekly chemotherapy regimens

  • e.g., metastatic breast, metastatic colorectal, ovarian
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19 Q1 2011 Q2 2011 Q3 2011 Q4 2011 Q1 2012 Q2 2012 Q3 2012 Q4 2012

NADH Oxidase Inhibitor Program Drug manufacturing of ME-143 IND-enabling preclinical studies Single agent Phase I trial Phase II trials + chemotherapy Mitochondrial Inhibitor Program Lead candidate selection Drug manufacturing of ME-344 IND-enabling preclinical studies Single agent Phase I trial

Clinical Development Timeline

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Milestones

 Establish headquarters in the U.S.  Add oncology expertise to Board of Directors  Acquire rights to lead product candidates  Appoint experienced Chief Medical Officer

  • Bolster intellectual property portfolio

NADH Oxidase Inhibitor Program  Complete drug manufacturing of ME-143  Submit IND application to FDA for ME-143

  • Initiate Phase I safety trial of ME-143 (Q3 2011)

Mitochondrial Inhibitor Program

  • Complete drug manufacturing of ME-344 (Q3 2011)
  • Submit IND application to FDA for ME-344 (Q1 2012)
  • Initiate Phase I safety trial of ME-344 (1H 2012)
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Southern California Investor Conference August 29, 2011

[ NASDAQ: MSHL ]