Aeolus Pharmaceuticals Inc · OTC:AOLS
Aeolus Pharmaceuticals — Investor Presentation (November 2004)
34 slides from Aeolus Pharmaceuticals's investor presentation, Nov 16, 2004
Slide 1: Developing Drugs for Cancer and Neurodegenerative Diseases
Exhibit 99.1 Developing Drugs for Cancer and Neurodegenerative Diseases
Slide 2: Forward-looking statements
Except for historical information, all of the statements, expectations and assumptions discussed in today’s presentation, including statements and expectations regarding Aeolus’ scientific and preclinical studies, FDA filings and clinical trials, are forward-looking statements that involve a number
Slide 3: Aeolus Highlights
Aeolus Highlights Revolutionary Compounds Advancing in Clinic Changing the Paradigm in Cancer Therapy New Management
Slide 4: Aeolus
Aeolus New Class of Small Molecule Antioxidants 10,000 times more potent than current antioxidant therapies ALS Treatment Phase 1 by subcutaneous route started Oct 2004 Preclinical testing of intrathecal route Cancer / Radiation Protection IND filing planned Q4 2004 Phase 1 in 1st half 2005 Phase 2
Slide 5: Antioxidants
Antioxidants aTocopherol Non Enzymatic Efficiency Enzymatic 1,000 – 10,000 Ascorbate ß Carotene NAC Superoxide Dismutase Catalase Mimetics 1,000 – 10,000 AEOL 10150
Slide 6: AEOL 10150
AEOL 10150 M.W. 1033.25 Water Soluble Stable – Long Half-Life Five-Step Synthesis Molecular Formula: C48H56N12Cl5Mn
Slide 7: New Catalytic Antioxidants 200-compound SAR
New Catalytic Antioxidants 200-compound SAR CuZn SOD Enzyme SOD Activity (U/mg) 5,100 Lead Compounds AEOL 10150 AEOL 10113 14,789 10,648 Alternative Compounds AEOL 10123 AEOL 10143 AEOL 10153 AEOL 10158 17,061 14,038 23,467 14,342
Slide 8: Intellectual Property
Intellectual Property 14 Patents Issued 41 Patents Pending Composition Claims for Lead Molecules through 2020 Licenses from Duke University and National Jewish Medical and Research Center
Slide 9: Mechanisms of Action
Mechanisms of Action Redox Active Scavenge Reactive Oxygen Species Cell Signaling NO• NF?B
Slide 10: Aeolus Focus
Aeolus Focus AEOL 10150 SC: ALS AEOL 10150 SC: Cancer-Radiation Rx AEOL 10113 SC: Cancer-Radiation Rx Outlicense Opportunities AEOL 10150 Ex Vivo: Transplant AEOL 10150 IV: Stroke AEOL 10113 IV: BPD AEOL 10113 Aerosol: COPD P/C IND Phase I Phase II Pipeline
Slide 11: Aeolus – The Opportunity
Aeolus – The Opportunity Phase 1 ALS Patients Phase 2 ALS Phases 1 and 2 Cancer Radiation Therapy US 5,000 / year US: 30,000 patients US: 500,000 / year
Slide 12: ALS Amyotrophic Lateral Sclerosis
ALS Amyotrophic Lateral Sclerosis Progressive motor neuron degeneration and muscular atrophy 80% of patients die within 5 years of diagnosis average lifespan 2-3 years post-onset ALS treatments are “Fast Track” drugs eligible for conditional approval based on one clinical study
Slide 13: AEOL 10150 Prolongs Survival in ALS
J.P. Crow, unpublished, 2002-03 AEOL 10150 Prolongs Survival in ALS 2.5 mg/kg/day IP beginning with onset of symptoms 0.0 0.2 0.4 0.6 0.8 1.0 Cumulative Survival Probability Age (days) Control AEOL 10150
Slide 14: G93A Mouse Videos
G93A Mouse Videos White mouse is a control. Black mouse treated since symptom onset with AEOL 10150. Deficit is similar to that seen on first day of symptoms.
Slide 15: Conclusions – ALS
Conclusions – ALS G93A Mouse – Enhanced Survival with Good Function – Dr. John Crow Need to Determine if Efficacy Can Be Further Improved with Intrathecal Therapy
Slide 16: Cancer – Radiation Therapy: A Unique Dual Mechanism
Cancer – Radiation Therapy A Unique Dual Mechanism Protects Normal Tissues Prevents Tumor Regrowth after Radiation Therapy
Slide 17: Cancer Radiation Therapy – Dual Mechanisms of Action
H2O H OH DNA Damage O2- TGFB Inflammation Tissue Injury Tumor O2- HIF-1 VEGF Vessel Regrowth (angiogenesis) Tumor Regrowth X X Cancer Radiation Therapy – Dual Mechanisms of Action
Slide 18: Mimetics Prevent Tumor Regrowth following Radiation Therapy
Cancer – Radiation Therapy Mimetics Prevent Tumor Regrowth following Radiation Therapy Adenocarcinoma 4T1 RP9 Prostate Carcinoma
Slide 19: Aeolus Compounds Inhibit Adenocarcinoma Regrowth
Aeolus Compounds Inhibit Adenocarcinoma Regrowth R3230 Mammary Adenocarcinoma in F344 Rats 0.8 1.2 1.4 1.6 1.8 2.2 2.4 Relative tumor size Days AEOL 10113 stopped * Radiation Control AEOL 10113 * *
Slide 20: Aeolus Compounds Inhibit 4T1 Tumor Regrowth
Aeolus Compounds Inhibit 4T1 Tumor Regrowth Moeller et al. Cancer Cell 5:429, 2004 Time Post-Rx (Days) Radiation + AEOL 10113 10mg/Kg at 0, 24 + 48 hr. Radiation Sham Relative Tumor Volume Radiation = 15 Gy in 3 fractions at 24-hour intervals in mice
Slide 21: Our Compounds Inhibit Prostate Tumor Regrowth
Our Compounds Inhibit Prostate Tumor Regrowth RP9 Tumors, 1-2 mice/group AEOL 10150 injected i.p. daily from days 0-11 3500 3000 2500 2000 1500 1000 Days after 10 Gy Irradiation Sham Radiation Radiation + AEOL 10150 Tumor Volume (mm3) Gridley et al., Loma Linda
Slide 22: Tumor Adaptation to Radiation Therapy
Tumor Adaptation to Radiation Therapy HIF-1 Transillumination
Slide 23: Tumor Adaptation to Radiation Therapy
Tumor Adaptation to Radiation Therapy HRE-GP White light RT +24 hours +48 hours
Slide 24: Tumor Adaptation to Radiation Therapy
Tumor Adaptation to Radiation Therapy HRE-GFP white light RTSOD +24 hours +48 hours HRE-GFP white light
Slide 25: HIF-1 Activation and Angiogenesis Blocked by Mimetic
HIF-1 Activation and Angiogenesis Blocked by Mimetic Tumor Adaptation to Radiation Therapy HRE-GFP white light RTSOD +24 hours +48 hours HRE-GFP white light
Slide 26: Aeolus Compounds Protect Normal Tissues
Aeolus Compounds Protect Normal Tissues Oral Mucosa Lung Brain Rectal Mucosa
Slide 27: Aeolus Compounds Protect Lung against Radiation Damage
28 Gy of right hemithoracic irradiation p < 0.02 Rx 5 days Aeolus Compounds Protect Lung against Radiation Damage Breathing Rate Weeks Control Radiation + AEOL 10113 Radiation 6 mg/kg/d IP for 5 days; n=9 rats per treatment
Slide 28: Lung Histology: Protection against Radiation Damage
CONTROL Lung Histology Radiation Radiation + AEOL10113 Aeolus Compounds Protect Lung against Radiation Damage 28 Gy of right hemithoracic irradiation 6 mg/kg/d IP for 5 days; n=9 rats per treatment
Slide 29: Conclusions: Cancer – Radiation Rx
Conclusions: Cancer – Radiation Rx Protection of Normal Tissues No effective radioprotectant currently available Inhibition of Tumor Regrowth following Radiation Therapy Blocks tumor angiogenesis following radiation therapy Clear Development Pathway Phase 2 trial opportunities in multiple tumor type
Slide 30: Development Timeline
Development Timeline AEOL 10150: ALS AEOL 10150: AEOL 10113: 2004 2005 2006 2007 Phase 2 Phase 1b Phase 1 SC P 1 Phase 1 Phase 2 Cancer Radiation Rx Cancer Radiation Rx Phase 3 Phase 3 Phase 2 Phase 2 Safety
Slide 31: Management team
CEO – James Crapo CFO Richard Reichow CSO Brian Day President, COO Regulatory Clinical Affairs Shayne Gad Administrative Assistant Asst Director Administration Ann Redick SVP R&D Being Recruited VP Chemistry Bushra Agha
Slide 32: Scientific Collaborations
Scientific Collaborations Cancer Mark Dewhirst, Ph.D. Duke University Zeljko Vujaskovic, M.D., Ph.D. Duke University James Slater, M.D. Loma Linda University Neurodegenerative Disease David Warner, M.D. Duke University John Crow, Ph.D. University of Arkansas Robert Brown, M.D. Massachusetts General
Slide 33: Aeolus – Current Funding
Aeolus – Current Funding $10,000,000 Institutional Support – April 2004 Phase 1 Safety Testing in ALS Patients Scale Up and Synthesis of AEOL 10150 Support through 3rd Q 2005 SBIR from National Cancer Institute $850,000 through May 2006 IND Filing for Cancer/Radiation Therapy
Slide 34: Aeolus – The Future
Aeolus – The Future Phase 1 2004 in ALS Patients Phase 2 ALS Phase 1/2 – 1st half 2005 Cancer Radiation Therapy Islet Cell Transplantation Diabetes COPD Stroke Cancer Chemotherapy
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