Neurobiological Technologies Inc · OTC:NTII
Neurobiological Technologies — Investor Day (March 2008)
49 slides from Neurobiological Technologies's investor day presentation, Mar 7, 2008
Slide 1: First Annual Research and Development Day
NTI First Annual Research and Development Day NASDAQ: NTII March 4, 2008
Slide 2: Forward Looking Statements
Forward Looking Statements Except for the historical information, the matters discussed are forward-looking statements that involve risks and uncertainties that could cause actual results to differ materially from those projected. These risks and uncertainties are set forth in the company's reports
Slide 3: NTI Agenda
NTI Agenda Financial Snapshot - Paul E. Freiman, President and CEO, NTI Viprinex™ (ancrod) Scientific and Clinical Update - Warren W. Wasiewski, M.D., Chief Medical Officer, NTI Acute Ischemic Stroke Treatment Overview - Gregory J. del Zoppo, M.D., Professor of Medicine, Division of Hematology and A
Slide 4: Extraordinary Leverage for Knowledgeable Investors
Extraordinary Leverage for Knowledgeable Investors Significant upside potential with limited downside Money to complete Viprinex clinical trials Robust development program Unmet need with one approved therapeutic agent Ongoing revenue stream Powerful management team
Slide 5: NTI is Focused on CNS
NTI is Focused on CNS Engaged in business of acquiring and developing central nervous system (CNS) related drug candidates
Slide 6: Significant Upside, Limited Downside
Significant Upside, Limited Downside Undervalued stock price - Downside capped by cash and royalties in place Cash burn rate is directly correlated to progress of clinical trials Net enterprise value of only $10MM No debt Cash on balance sheet of $52.6MM as of 12/31/07
Slide 7: Largest Public Deal for Small Company in '07
Largest Public Deal for Small Company in ‘07 Raised institutional equity of $55 million net proceeds from top biotech investors - Biotechnology Value Fund, Great Point Partners, Millennium Technology Ventures, SF Capital Partners, Highland Capital Management Investor support fueled by extensive data
Slide 8: Viprinex (ancrod) Overview
Viprinex™ (ancrod) Overview
Slide 9: Viprinex (ancrod) Overview
Viprinex (ancrod) Overview New class of drug - Fibrinogen Reducing Agent (FRA) Novel mechanism of action Widely studied - Nearly 2,000 patients in U.S. and Europe Ancrod Stroke Program (ASP) underway - Enrollment goal: 1,300 stroke patients worldwide Unlike current standard of care - Potential to be
Slide 10: Slide 10
Slide 11: Commercial Strategy
Commercial Strategy Successfully complete clinical development of Viprinex - Fund program through final results in order to maximize long-term shareholder value Seek co-partner to commercialize Viprinex in the United States - Maintain co-promotional rights to maximize potential revenues to NTI Seek
Slide 12: NTI Agenda
NTI Agenda Financial Snapshot - Paul E. Freiman, President and CEO, NTI Viprinex™ (ancrod) Scientific and Clinical Update - Warren W. Wasiewski, M.D., Chief Medical Officer, NTI Acute Ischemic Stroke Treatment Overview - Gregory J. del Zoppo, M.D., Professor of Medicine, Division of Hematology and A
Slide 13: Scientific and Clinical Overview
## Scientific and Clinical Overview NASDAQ: NTII N EUROBIOLOGICAL T ECHNOLOGIES, I NC.
Slide 14: Viprinex (ancrod) -- A New Class
Viprinex (ancrod) -- A New Class Fibrinogen Reducing Agent (FRA) Combines anticoagulation, blood viscosity reduction and potential thrombolytic effect Reduce stroke related disability Potential to double the time-to-treatment window compared to existing therapy
Slide 15: Reperfusion Agents vs. Neuroprotectants
Neuroprotectants Reperfusion Agents Reperfusion Agents vs. Neuroprotectants There are two broad categories of investigational stroke treatments: Over 100 studied None have demonstrated efficacy in Phase 3 trials (1) Fewer than 15 studied Three of which have resulted in successful Phase 3 trials Tria
Slide 16: Slide 16
Slide 17: Clot formation: the role of Fibrinogen
Clot formation: the role of Fibrinogen Fibrinogen Fibrin -- cross linked Thrombin - a b chains Factor XIII activated Stabilizes clot Normal crossed linked fibrin clot
Slide 18: Viprinex: Mechanism of Action (MOA)
Viprinex: Mechanism of Action (MOA) Primary mechanism of action: Cleaves a chains off fibrinogen - Cleaves at the arg-gly sequence Leaves b chains intact - Chemotactic side chain
Slide 19: Viprinex: Mechanism of Action
Viprinex : Mechanism of Action Removal of a chains - desA profibrin and desAA fibrin Soluble fibrin polymers - Cannot crosslink Does not activate factor XIII
Slide 20: Mechanism of Action
Mechanism of Action Fibrinogen Fibrin -- cross links to form clot Thrombin Ancrod desA fibrin desAA fibrin No clot - One a chain - both a chains - a b chains
Slide 21: Normal Blood Clot Formation
Fibrinogen Thrombin a - chains removed b - chains removed Clot Grows Normal Blood Clot Formation
Slide 22: Direct Mechanism of Action of Ancrod
b - chains remain intact Viprinex™ Fibrin monomers can only attach end-to-end a - chains removed Direct Mechanism of Action of Ancrod Clot size remains same
Slide 23: Indirect Mechanism of Action of Ancrod
Plasminogen Plasmin Indirect Mechanism of Action of Ancrod Viprinex™-cleaved monomers/polymers activate conversion of Plasminogen to Plasmin Plasmin dissolves fibrin clot
Slide 24: Stroke Study Endpoints
Scoring Description Scale Stroke Study Endpoints 0-6 (0 is complete recovery) Global Disabilities scale Modified Rankin Scale (mRS) 0-42 (0 is complete recovery) Measurement of Neurologic Examination National Institute of Health Stroke Scale (NIHSS) 0-100 (100 is complete recovery) Measures activiti
Slide 25: Overview of Previous Viprinex Clinical Trials
Overview of Previous Viprinex Clinical Trials Five previous clinical trials - 1,924 patients; 951 patients treated with Viprinex Knoll trials were designed to maintain a low target fibrinogen level for several days - One successful Phase 3 clinical trial (STAT) - One neutral Phase 3 clinical trial (
Slide 26: Previous Viprinex Trials
Phase Primary Endpoint Treatment Window Dosing Regimen Patients Sponsor Trial Previous Viprinex Trials Functional Success as defined by the Barthel Index Functional Success as defined by the Barthel Index Neurologic Recovery 6 hours 3 hours 6 hours Infusion over several days Infusion over several da
Slide 27: Retrospective Analysis: Key Hypotheses
Retrospective Analysis: Key Hypotheses Symptomatic Intracranial Hemorrhage (SICH) occurred more frequently in patients with prolonged low fibrinogen levels Safety: Rapid lowering of fibrinogen results in better outcome Fibrinogen level needs to drop well below normal at six hours Efficacy :
Slide 28: Knoll Dosing Strategy
Knoll Dosing Strategy Hours after Beginning Treatment Infusion over 5 days Maintain fibrinogen at low level
Slide 29: Efficacy: Rate of Defibrinogenation
STAT (Viprinex Treated) Efficacy: Rate of Defibrinogenation The rate at which the fibrinogen level decreases emerged as the most important variable in determining a better outcome In the STAT trial, rapid defibrinogenation rate produced a better outcome for patients than a slower rate Rapid defibrin
Slide 30: Efficacy: Fibrinogen Level
A-20 STAT Efficacy: Fibrinogen Level The lower the 6 hour fibrinogen level, the better the outcome Viprinex treated – Low fibrinogen ( 130 mg/dL; n=32) Viprinex treated – High fibrinogen (>130 mg/dL; n=32) Placebo (n=68) V iprinex treated – Low fibrinogen ( 130 mg/dL; n=70) V iprinex treated – High
Slide 31: Safety: Reduction of SICH
STAT Efficacy maintained despite higher fibrinogen level Safety: Reduction of SICH Low fibrinogen levels over several days was the most important determinant of symptomatic intracranial bleeding Higher average fibrinogen level ( 60 mg/dL; n=160) Lower average fibrinogen level (<60 mg/dL; n=31) In th
Slide 32: Fibrinogen levels: Efficacy
Fibrinogen levels : Efficacy Post hoc analysis shows: The greater the rate of fibrinogen reduction, the better the outcome Fibrinogen levels that are well below normal at 6 hours are associated with a better outcome
Slide 33: Fibrinogen levels: Safety
Fibrinogen levels : Safety Post hoc analysis shows: Low fibrinogen levels over 72 hours is associated with bleeding in the brain - Symptomatic intracranial hemorrhage - Frequently fatal
Slide 34: Treatment Objective: Restore Blood Flow Safely
Treatment Objective: Restore Blood Flow Safely Hours after Beginning Treatment NTI ASP Dosing Strategy 3-hour infusion Efficacy Safety
Slide 35: Ancrod Stroke Program (ASP) Trials
Ancrod Stroke Program (ASP) Trials NASDAQ: NTII
Slide 36: End-of-Phase Meetings
End-of-Phase 2 Meetings Granted Fast Track status Two End-of-Phase 2 meetings with the FDA - Clinical - CMC NTI and the FDA agreed: - on the design of the ASP trials - that the ASP dosing regimen was reasonable - that manufacturing plans were adequate for Phase 3
Slide 37: ASP Trials Overview
ASP Trials Overview ASP 1 and ASP 2 1,300 total patients; 650 patients in each trial Identical, randomized, double-blind, placebo-controlled trials Admission criteria allow for broad stroke population - Mild to severe cases - No upper age limit
Slide 38: Robust Trial Design
Robust Trial Design State-of-the-art design - Patient selection - End point selection - Classification of hemorrhages Accelerating enrollment - 14 countries - Targeting 200 sites Overseen by a management team with industry-leading stroke trial experience
Slide 39: Primary Endpoint
Primary Endpoint ASP Endpoints Responder analysis mRS at day 90 - 0, 1 or 2 considered a responder NIHSS at day 90 - 0,1 or an 11 point improvement relative to screening Barthel Index at day 90 - 95-100 or a BI score that is no less than the pre-stroke score Secondary Endpoints
Slide 40: ASP Endpoints
ASP Endpoints Safety: - AEs, SAEs and mortality - Incidence of ICH, bleeding events, drop in hemoglobin - New physical findings - Lab data including neuroimaging
Slide 41: Data Safety Monitoring Board (DSMB)
Data Safety Monitoring Board (DSMB) Monitored by a Data Safety Monitoring Board (DSMB) - Reviews the study at pre-specified enrollment numbers for safety signals - Can recommend changes to the protocol, i.e changes to inclusion or exclusion criteria - Can recommend trial continue as planned - Can re
Slide 42: Interim Analysis
Interim Analysis 650 patients combined from both studies Futility analysis Safety analysis Go – No Go decision point Must show evidence of a treatment effect for Viprinex
Slide 43: Acute Ischemic Stroke Treatment Overview
Acute Ischemic Stroke Treatment Overview Acute Ischemic Stroke Treatment Overview - Gregory J. del Zoppo, MD, Professor of Medicine, Division of Hematology and Adjunct Professor of Neurology, University of Washington, Seattle
Slide 44: Extraordinary Leverage for Knowledgeable Investors
Extraordinary Leverage for Knowledgeable Investors Significant upside potential with limited downside Money to complete Viprinex clinical trials Robust development program Unmet need with one approved therapeutic agent Ongoing revenue stream Powerful management team
Slide 45: XERECEPT / Celtic
XERECEPT® / Celtic Indicated for brain tissue swelling caused by tumor, residual tumor and tumor treatments - Currently in Phase 3 trials Sold rights to Celtic Pharma Management LP in 2005 - Received $33 million upfront payment - Retained rights to future milestone payments, profit sharing and royal
Slide 46: Continually Pursuing Early Stage IP
Continually Pursuing Early Stage IP Partnership with Buck Institute for Age Research: - High potential for low investment - Preclinical Development of drug to treat Huntington’s Disease - Fatal hereditary brain disorder affecting ~ 30,000 Americans - Fibroblast growth factor (FGF-2) involves natural
Slide 47: Powerful Management Team
Powerful Management Team CEO has history of making profitable transactions for shareholders Paul E. Freiman engineered sale of Syntex to Roche for $5.3B (’98) - Oversaw marketing of anti-platelet compound, Ticlid (ticlopidine) - Instrumental in the sale of Syntex’s lead product, Naprosyn and was res
Slide 48: Extraordinary Leverage for Knowledgeable Investors
Extraordinary Leverage for Knowledgeable Investors Significant upside potential with limited downside Money to complete Viprinex clinical trials Robust development program Unmet need with one approved therapeutic agent Ongoing revenue stream Powerful management team
Slide 49: Questions and Discussion
Questions and Discussion NASDAQ: NTII
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