[ 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 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. 2
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 3
Management Team Executive Management Board of Directors Daniel Gold, Ph.D. Bryan Williams, Ph.D. (Chairman) Director of the Monash Institute of Medical President & Chief Executive Officer Research Former Chief Scientific Officer & Founder of Favrille Leah Cann, MBA Two-time Wall Street Journal All-Star Analyst Thomas Zech Chief Financial Officer Daniel Gold, Ph.D. Former Chief Financial Officer at Pacira Pharmaceuticals President & CEO of Marshall Edwards William Rueckert Robert Mass, M.D. Chairman of Novogen Limited Chief Medical Officer Former Head of Medical Affairs, BioOncology Christine White, M.D. at Genentech Former Senior V.P. of Global Medical Affairs at Biogen Idec 4
Lead Drug Candidates Derived from Proprietary Isoflavone-Based Platform H O O H O O OH O OH OH 1 st Generation: Phenoxodiol Scaffold: Genistein Next Generation H O O H O O OH OH O O H H NADH Oxidase Inhibitor: ME-143 Mitochondrial Inhibitor: ME-344 5
NADH Oxidase (tNOX) Inhibitors Mechanism of Action: Caspase-Mediated Apoptosis 6
Mitochondrial Inhibitors Mechanism of Action: Caspase-Independent Cell Death Drug Mitochondria COX IV ATP AMPK α 1 ADP ROS Endo G mTOR ERK Bax Nucleus LC3-II Caspase- DNA Destructive Independent Fragmentation Autophagy Cell Death 7
Lead Candidates ME-143 & ME-344 Superior Single-Agent Anti-Tumor Activity* Breast Melanoma Lung Ovarian Prostate Compound (SK-BR-3) (MM200) (NCI-H460) (CP70) (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 * IC 50 = M 8
tNOX Inhibitor Clinical Trial Experience Platinum-Resistant or Refractory Ovarian Cancer ME06-0039 ME06-0037 (N=70) (N=20) Route of Phenoxodiol Oral Intravenous Administration Weekly platinum + Weekly platinum + Treatment Phenoxodiol Phenoxodiol Response Rate 0/70 = 0% 6/20 = 30% 9
tNOX Inhibitor Clinical Trial Experience Comparable Patient Demographics (ITT Population) ME06-0039 ME06-0037 Oral Phenoxodiol i.v. Phenoxodiol Chemotherapy Carboplatin Cisplatin Age in years Median: 59 60 Range: 39-78 43-72 Karnofsky performance status Median: 90 90 Range: 60-100 60-100 Histology Serous: 81% 65% Endometrioid: 10% 9% Other: 9% 26% Number of prior regimens Median: 3 3 Range: 2-5 1-7 Months since platinum refractoriness/resistance Median: 9 7 Range: 1-21 1-13 10
tNOX Inhibitor Program Summary • Clinical experience shows insufficient levels of active drug achieved when 1 st 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 11
Mitochondrial Inhibitor Program H O O H O O OH OH Demethylated O O CH 3 H in vivo Prodrug: ME-128 Lead Candidate: ME-344 12
Mitochondrial Inhibitor: Potent Inhibitor of Chemo- Resistant Primary Ovarian Cancer Cell Lines* ME-128 * 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 13
Mitochondrial Inhibitor: Active on KRAS Mutant, Tarceva-Resistant NSCLC Cell Lines* NCI-H1734 NCI-H1299 A549 * Data provided by Dr. Kwok-Kin Wong, Dana Farber Cancer Center, Boston 14
Mitochondrial Inhibitor: As Effective as Rapamycin in Pre- Clinical Studies… R182 Ovarian Xenograft Model 1000 900 ME-128 vehicle control ME-128 (50 mg/kg) 800 RAPAMYCIN vehicle control Tumor Volume (mm 3 ) RAPAMYCIN – 40 mg/kg 700 600 500 400 * * 300 200 * p 0.005 100 0 8 10 12 14 16 18 20 22 Time (Days) 15
…but with Less Toxicity 116 114 ME-128 Vehicle Control Percentage Change - Body Mass ME-128 (50mg/kg) 112 RAPAMYCIN Vehicle Control RAPAMYCIN - 40mg/kg 110 108 106 104 102 * p 0.005 100 98 * 96 94 92 90 8 10 12 14 16 18 20 22 Time (Days) 16
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 17
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 18
Clinical Development Timeline 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 19
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) 20
[ NASDAQ: MSHL ] Southern California Investor Conference August 29, 2011
Recommend
More recommend
