Corporate  Presenta,on  

October  2011  

MISSION  

Edge  was  founded  under  the  belief  that    site-­‐specific,  sustained-­‐release  delivery  of  medicines  directly  to  the  site  of  brain  injury  will  prevent  certain  

delayed  and  life-­‐threatening  condi<ons,  improve  pa<ent  outcomes,  and  decrease  overall  cost  of  care  

DELAYED  CEREBRAL  ISCHEMIA  (DCI)  

Secondary  injury  (DCI)  is  caused  by  a  complex  biochemical  cascade  leading  to  vasoconstric*on,  

ischemia  and,  ul<mately,  neuronal  death  

Primary  injury,  oEen  caused  by  aneurysm  or  head    trauma,  is  rou<nely  addressed  

Source:  American  Heart  Associa<on    3  |  

PRIMARY  EVENT   DAY  1  BRAIN  ARTERIES  

DAY  3-­‐14    VASOCONSTRICTION  

ISCHEMIA  /  NEURONAL  DEATH  

SUBARACHNOID  HEMORRHAGE  (SAH)  

•  Average  age  50  years  old  •  90%  of  pa<ents  arrive  alive  to  the  hospital  •  Poor  30-­‐day  prognosis  •  Costs  exceed  $25B  annually  for  aneurysmal  SAH    

4  |  

2 die 2 permanent brain damage 1 resumes normal activity

4

SAH  is  a  silent  epidemic  that  results  in  staggering  direct  and  indirect  costs  to  society.    

Of patients arriving alive to the hospital…

CURRENT  STANDARD  OF  CARE  ACTIVE  AGENT,  POOR  DELIVERY  

Oral  nimodipine  (Ac,ve  Systemic  Agent)  •  Generic  calcium  channel  blocker  (FDA  approved  in  1989)  rou<nely  given  

to  all  pa<ents    •  Rinkel  et.  al.  (8  trials  reviewed)  showed  improved  outcome  and  reduced  

cerebral  infarc<on  with  minimal  effect  on  angiographic  vasospasm  •  Standard  oral  dose  of  nimodipine  is  60  mg  every  4  hours  x  21  days    However…  Dose  is  sub-­‐op,mal  (Poor  Delivery)  •  Cerebrospinal  fluid  (CSF)  concentra<on  is  0.4  ng/ml  

–  CSF  concentra<on  is  at  least  10x  too  low  to  dilate  arteries  •  Maximal  plasma  concentra<on  of  about  20  ng/ml  

–  Dose-­‐limi<ng  hypotension  in  >30%  of  pa<ents  •  Hypotension  occurs  at  plasma  concentra<on  >30-­‐40  ng/ml  

–  Oral  nimodipine  gets  above  this,  yet  CSF  concentra<ons  too  low    

5  |  

EDGE  TECHNOLOGY  AN  ELEGANT  DELIVERY  SOLUTION  

•  Handling  characteris<cs  –  Minimizes  systemic  side  effects  –  Circumvents  blood-­‐brain  barrier  –  One-­‐<me  administra<on  

•  Administered  during/aEer  surgery  –  Does  not  require  addi<onal  surgery  or  procedures  to  apply  –  Simple  prep/administra<on  does  not  interfere  with  surgery  workflow  –  NOT  an  emergency  care  administra<on  

•  Proven  commercially  feasible  technology  (scaled-­‐up  for  commercial  produc<on)  

•  Backed  by  strong  IP  poriolio  

6  |  

Site-­‐specific,  sustained  release  bioabsorbable  poly(D,L-­‐lac*de-­‐co-­‐glycolide)  (PLGA)-­‐based  micropar*cles  

CONTINUOUS  MICROENCAPSULATION  PROCESS  THRU  FINISHED  PRODUCT  

7  |  

THE  “NIMO”  FRANCHISE  Agent Indication Pre-Clinical Development Phase 2

Formulation Development In Vitro In Vivo Clinical

NimoGel* (EG-1961)

Reduce DCI and improve 30-day outcome in patients with aSAH undergoing neurosurgical clipping (intracisternal)

Moderate to severe head trauma

NimoVent* (EG-1962)

Reduce DCI and improve 30-day outcome in patients with aSAH undergoing endovascular coiling.(intraventricular)

Moderate to severe head trauma

EG-1964 Chronic subdural hematoma

EG-1960*

Post-craniotomy

Spontaneous intracerebral hemorrhage

Moderate to severe head trauma

*Denotes: Department of Defense Interest Potential

NIMOGELTM  FOR  SURGICAL  CLIPPING  

•  Biodegradable  polymer  encapsula<on  of  nimodipine  (FDA  505  (b)(2)  approval)  and  hyaluronic  acid  (HA)  carrier  

•  14  days  release  •  Applied  directly  to  the  injury  site  

(intracisternally)  during    surgical  clipping  to  secure  the  bleeding    aneurysm    

•  Designed  to  provide  consistent  and  therapeu<c  concentra<ons  of  nimodipine  to  prevent  DCI  while  minimizing  side  effects  

APPLICATION:  To  reduce  delayed  cerebral  ischemia  and  improve  30-­‐day  outcome  in  pa8ents  with  aneurysmal  SAH  undergoing  neurosurgical  clipping.  

9  |  

SURGICAL  CLIPPING  

NIMOVENTTM    FOR  ENDOVASCULAR  COILING  

•  Biodegradable  polymer  encapsula<on  of  nimodipine  (505  (b)(2)  approval)  and  buffer    

•  14  days  release  •  Designed  to  reduce  ischemia  deficits  and  

improve  outcomes  in  pa<ents  who  undergo  endovascular  coiling  

•  NimoVent  delivery  is  minimally  invasive  –  No  addi<onal  procedure  required  –  Delivered  in  the  intensive  care  unit  aEer  the  

pa<ent  has  undergone  endovascular  coiling  through  an  exis<ng  intraventricular  catheter  inserted  to  measure  intracranial  pressure  (ICP)    

 

APPLICATION:  To  reduce  delayed  cerebral  ischemia  and  improve  30-­‐day  outcome    in  pa8ents  with  aneurysmal  SAH  undergoing  endovascular  coiling.  

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ENDOVASCULAR  COILING  

DELIVERY  SYSTEM  PROOF  OF  CONCEPT  

Site-­‐specific,  Sustained-­‐release  –  Human  Data    Therapeu*c  Doses  Of  Calcium  Channel  Blockers  Improve  Outcome  

•  Studied  in  252*  pa,ents  in  Japan  and  Germany  (Krischek  2007,  Barth  2007,  Kasuya  2002,  2005,  2011)  –  Angiographic  vasospasm  decreased  from  73%  control  to  7%  nicardipine  

–  Mortality  decreased  from  38%  to  6%  

–  No  side  effects  •  Pellets  not  commercializable,  difficult  to  administer,  cannot  be  injected  

into  ventricles  (endovascular  coiling  /  closed  head  injury)  

11  |  

*  Subarachnoid  nicardipine  in  poly(D,L-­‐lac<de  co  glycolide)  (PLGA)  pellets  

NIMOGEL  &  NIMOVENT  DELIVERY  PROFILE  •  Nimodipine  micropar<cles  (NimoGel  &  NimoVent)  

•  Nimodipine  in  PLGA  micropar<cles  •  Toothpaste-­‐like  gel  to  retain  NimoGel  in  subarachnoid  space,  liquid  

NimoVent  allows  diffusion  from  ventricles  to  subarachnoid  space  •  Easy  to  administer  for  both  clipped  and  coiled  pa<ents  •  Ability  to  scale-­‐up,  easily  sterilized  via  gamma  irradia<on,  stable  

12  |  

EMERGING  TREATMENT  PARADIGM  

13  |  

Delayed Cerebral Ischemia (DCI) Poor Outcome

NIMODIPINE:  A  MULTIPLE  PATHWAY  APPROACH  

Angiographic Vasospasm

Microthrombo-embolism

Cortical Spreading Ischemia

Focal Cerebral Infarctions

Subarachnoid Hemorrhage

Transient Global Ischemia

Subarachnoid Blood

Global Cerebral Atrophy

Oxidative Stress /Inflammation /

Other?

PROOF  OF  PRINCIPLE:    STUDY  DESIGN  •  Dog  double  hemorrhage  model  of  SAH  •  2  doses  of  NimoVent:  30mg  and  10mg  or  placebo  (vehicle)  formula<on  •  Blood  was  injected  into  the  cisterna  magna  (Day  0  and  Day  2)  •  Dogs  underwent  angiography  on  days  0,  7  and  14  •  Endpoints:  angiographic  vasospasm,  behavior,  serum  and  CSF  nimodipine  

concentra<ons,  pathology  

14  |  

Day  0   Day  7  

Safety  Results:  •  Serum  concentra<ons  were  higher  in  30  mg  

dose  compared  to  10  mg  dose  •  Serum  (30  mg  and  10  mg  dose)  showed  highest  

concentra<ons  on  day  2  (8  ng/ml  and  4  ng/ml)  –  Hypotension  occurs  at  plasma  

concentra*on  >  30-­‐40  ng/ml    

Efficacy  Results:  

•  30  mg  NimoVent  prevented  vasospasm  at  day  7  and  at  day  14  –  CSF  concentra*ons  were  more  than  

200  ng/ml  •  No  local  inflamma<on  or  other  signs  of  

neurotoxicity  were  observed  

PROOF  OF  PRINCIPLE  STUDY  THERAPEUTICS  LEVELS  TO  THE  BRAIN;  LOW  SYSTEMIC  LEVELS  

Average  of  4  blinded  reviewers  

%  change  from

 baseline  (diameter  of  

cerebral  basilar  a

rtery)  

PHASE  2  STUDY  

  FDA  confirmed  505(b)(2)  path  for  NimoGel:    Relevance  is  NimoGel  can  refer  to  prior  toxicity  studies  for  nimodipine,  PLGA  and  HA  

  Edge  has  clear  path  for  IND  and  scale-­‐up  needs  and  <melines  

  FDA  clarified  expecta<ons  &  Edge  is  aligned  with  pre-­‐clinical  studies  for  IND  -­‐  no  change  in  the  general  plan  and  approach  proposed  by  Edge  

  FDA  &  Edge  are  aligned  on  Phase  2  clinical  trial  design  

–  NimoGel  alone  can  be  compare  to  oral  nimodipine  (standard  of  care)  –  First  <me  in  22  years  that  FDA  has  allowed  experimental  drug  vs.  oral  nimodipine  

16  |  

PHASE  2  STUDY  DESIGN  Phase  2a:  Dose  Finding  Study  [Con<nuous  Reassessment  Model  (CRM)]  

•   n=  up  to  63  pa<ents  •  40mg,  120mg,  160mg,  up  to  1120mg  or  toxicity  •  Endpoint  plasma  levels  >40ng/mL  causing  hypotension  •  10  centers  (2  pa<ents  /  month  per  center)  •  9  months  to  complete  (3  months  start-­‐up,  4  months  to  enroll,  3  months  to  analyze  data)  

Phase  2b:  Toxicity  Study  •  n=  88  pa<ents  

•  NimoGel  vs.  standard  of  care  (oral  nimodipine)  •  Primary  endpoint:  toxicity  •  Exploratory  endpoints:  infarc<on  or  neurological  deteriora<on  due  to  vasospasm,  need  

for  rescue  therapy,  mortality,  ICU  LOS,  Hospital  LOS      30-­‐day  endpoint,  90  day  follow-­‐up  

•  15  centers  (2  pa<ents  /  month  per  center)  

•  9  months  to  complete  (3  months  start-­‐up,  3  months  to  enroll,  3  months  to  analyze  data)  

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PHASE  3  STUDY  DESIGN  FDA  &  Edge  are  aligned  on  Phase  3  endpoints  Phase  3:  Efficacy  and  Safety  

•  n=  750  pa*ents  •  NimoGel  vs.  standard  of  care  (oral  nimodipine)  •  Primary  endpoint:  (composite  endpoint)  infarc<on  or  neurological  

deteriora<on  due  to  vasospasm,  need  for  rescue  therapy,  mortality  •  Secondary  endpoint:  posi<ve  trend  modified  Rankin  score  

 30-­‐day  endpoint,  90  day  follow-­‐up  

•  Health  economic  secondary  endpoints:  ICU  LOS,  Hospital  LOS  •  100  centers  worldwide  (1.5  pa<ents  /  month  per  center)  

•  15  months  to  complete  (3  months  start-­‐up,  9  months  to  enroll,  3  months  to  analyze  data)  

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Percentile # of U.S. Hospitals

% Share of patients

1% 50 16%

5% 250 66%

10% 500 85%

Concentrated  Customers  

U.S. 100,000

E.U. 100,000

Japan 70,000

DCI  is  a  great  burden  •  All  SAH  pa<ents  are  at  risk  of  DCI  •  >750,000  people/year  worldwide  are  at  risk  for  DCI  aEer  aneurysmal  SAH  

  Aneurysmal  SAH  is  common  in  U.S.,  E.U.,  and  Japan  •  Head  trauma  also  causes  SAH  and  are  at  risk  •  Concentrated  customer  base;  easily  covered  by  25  –  50  person  specialty  salesforce  

At  Risk  Addressable  Market  

DCI  risk  auributed  to  all  SAH  (aneurysmal  SAH  &  head  trauma)  

DCI  MARKET  OPPORTUNITY  SPECIFIC  AND  ADDRESSABLE  

Acute Neurological Condition

Incidence U.S.

Incidence World

Average Age

30-Day Mortality

Rate

30-Day Mortality Rate or Brain

Damage Ruptured Brain Aneurysm – NimoGel & NimoVent

>40,000 >750,000 50 50% 75%

Chronic Subdural Hematoma – EG-1964 >70,000 >1.5 Million 65 20% 40%

Intracerebral Hemorrhage – EG-1960 100,000 >2 Million 60 45% 80%

Craniotomy – EG-1960 >180,000 >2 Million Variable on condition

Variable on condition

Variable on condition

Moderate & Severe Head Trauma – NimoGel, NimoVent, EG-1960

>250,000 >3 Million 40 20% 50%

BROADER  MARKET  OPPORTUNITIES  

20  |  

*  Source:  Leng,  L.,  Fink,  M.,  Iadecola,  C.  2010.  Spreading  Depolariza8on:  A  Possible  New  Culprit  in  the  Delayed  Cerebral  Ischemia  of  Subarachnoid  Hemorrhage.  Neurological  Review    

DoD  APPLICATION  

•  A  study  evaluated  all  in-­‐pa<ents  with  blast-­‐  related  neurotrauma  from  Opera<on  Iraqi    Freedom  and  found  that  47%  had  blast-­‐related    vasospasm  

•  In  addi<on  to  the  vasospasm  caused  by    neurotrauma,  “blast  vasospasm”  is  a  recent    phenomenon  recently  documented  in  the    medical  literature  

•  DoD  has  maintained  an  ac<ve  research  program  in  reducing  injury  caused  by  hemorrhage  

•  DoD  has  recognized  the  poten<al  use  of  all  of  Edge’s  products:  –  Combat  Casualty  Care  Unit  has  invited  Edge  to  submit  a  full-­‐proposal  for  NimoVent  ($4.0MM)    –  Awai<ng  an  invita<on  for  a  NimoGel  full-­‐proposal  ($4.5MM)  –  Submiued  pre-­‐proposal  to  DoD-­‐Telemedicine  &  Advanced  Technology  Research  Center  (TATRC)    –  Awai<ng  an  invita<on  from  Veteran’s  Administra<on  (VA)  for  EG-­‐1964  

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WELL  PROTECTED  FRANCHISE  

Layered  Intellectual  Property    “Nimo”  Franchise  

Polymorphs  =  Composi<on  of  Mauer  

Devmt.  of  “Nimo”  Franchise  =  Composi<on  &  Process  Patents  

SurModics  Process  Patent  

Method  of  Use  –    NimoGel  /  NimoVent  

Commercial  Barriers  

•  Orphan  drug  •  SurModics  

  License,  exclusive  &  worldwide  

  Produc<on  is  difficult  

•  Mfg.  polymers  &  micropar<cles  

•  Investment  scale-­‐up  and  cGMP  

•  FormEZE  process  

•  Trade  secrets  

NIMO  

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KEY  PERSONNEL  

Management   Board  &  Key  Advisors   Key  Scien,fic  Advisors  Brian  A.  Leuthner,  President  &  CEO,  Co-­‐founder  20+  years;  Pharma  &  Specialty  Pharma,  GlaxoWellcome,  Ortho  Biotech,  ESP  Pharma,  The  Medicines  Company,  Fontus  Pharmaceu<cals  

R.  Loch  Macdonald,  MD,  PhD,  CSO,  Co-­‐founder  Keenan  Endowed  Chair  of  Neurosurgery,  St.  Michael’s  Hospital,  Toronto,  Canada;  20-­‐years  Of  Research  Led  Us  To  NimoGel  &  NimoVent;  >400  Peer-­‐reviewed  Ar<cles  On  Secondary  Brain  Injury  

Priya  Jambhekar,  MS,  Execu,ve  Vice  President,  Regulatory  and  Quality  20+  years;  Pharma  &  Specialty  Pharma  in  product  development,  product  safety,  quality  assurance,  quality  compliance  and  U.S.  and  interna<onal  regulatory  affairs;  BMS,  J&J,  Baxter,  and  Alkemes  

Bert  Marchio,  MBA  –  CFO  17+  years;  Specialty  Pharma  in  senior  financial  leadership  posi<ons  in  both  the  public  and  private  sectors;  Informed  Medical  Communica<ons,  MedPointe,  and  Alpharma    

Carl  J.  Soranno,  Esq.,  Execu,ve  VP,  Corporate  Development,  Co-­‐founder  18+  years;  prac<ce  of  law;  11  years;  Financial  career  on  Wall  Street  

Sol  Barer,  PhD,  Board  Director  Founder,  Former  CEO  &  Execu<ve  Chairman,  and  Chairman,  Celgene  Corpora<on    

Kurt  Con,,  Board  Director  Chairman,  The  Con<  Group,  Serial  entrepreneur  

James  Louglin,  Board  Director  Former  Chairman,  Pension  and  Investment  Commiuee  of  the  KPMG  Board,  Celgene  Director,  Heads  Audit  Commiuee  

Geert  Cauwenburgh,  PhD,  Advisor  Former  CEO,  Barrier  Therapeu<cs,  Former  VP,  R&D  Johnson  &  Johnson    

Arthur  Klausner,  Advisor  Life  sciences  venture  capitalist;  Domain  Associates  and  Pappas  Ventures  

Neal  F.  Kassell,  MD,  University  of  Virginia  Health  Sciences  Center  

Daniel  Hanggi,  MD,  Heinrich-­‐Heine-­‐University,  Dusseldorf,  Germany  

Hidetoshi  Kasuya,  MD,  Tokyo  Women’s  Medical  University,  Tokyo  

Peter  D.  LeRoux,  MD,  FACS,  Hospital  of  the  University  of  Pennsylvania  

Stephan  A.  Mayer,  MD,  Columbia  University  Medical  Center    

J.  Javier  Provencio,  MD,  Cleveland  Clinic  Hospitals  

Peter  Vajkoczy,  MD,  Charite  Hospital,  Berlin,  Germany  

Paul  M.  Vespa,  MD,  David  Geffen  School  of  Medicine  at  UCLA  

Bryce  Weir  OC,  MSc,  FRCSC,  FACS,  FRCS  (Ed)  hon.,  Goldblau  Professor,  The  University  of  Chicago  Pritzker  School  of  Medicine  

MILESTONES  Corporate  development  and  capitaliza,on  to  date  –  Raised  almost  $4M  in  financing  from  a  small  group  of  private  investors  

and  non-­‐dilu<ve  sources  –  Alliance  with  SurModics  (NASDAQ:  SRDX)  –  Proof  of  concept  in  a  dog  model  –  Successful  pre-­‐IND  mee<ng  (clear  endpoints)  –  Manufactured  large-­‐scale  batch  of  NimoGel  and  NimoVent  

Timeline  &  ac,vi,es  moving  forward  –  cGMP  NimoGel  &  NimoVent  (4Q  2011)  –  Clinical  trial  –  Inves<gator  ini<ated  trial  (FPI  1Q  2012)  –  U.S.  IND  (1H  2012)  –  Orphan  drug  designa<on  (1H  2012)  –  Phase  2  Study  –  2012    –  Phase  3  Study  –  2013/2015    

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SUMMARY  

•  Well-­‐defined,  addressable  unmet  worldwide  medical  need  •  De-­‐risked  lead  assets  with  proof-­‐of-­‐concept  successfully  established  •  Clear  and  abbreviated  clinical  and  regulatory  path  

–  FDA  confirmed  505(b)(2)  path  for  NimoGel  –  Orphan  drug  designa<on  eligibility  –  90  day  trial  follow  up,  short  clinical  trial  dura<on  (Phase  2  for  NimoGel  

and  NimoVent)  •  High  legal,  regulatory,  R&D,  and  commercial  barriers  to  

compe<<on  •  Highly  concentrated  market  and  clear  pathway  to  2015/2016  

launch  •  Opportunity  for  new  indica<ons  and  addi<onal  first-­‐in-­‐class  

products  

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LIMITED  INVESTMENT  /  LARGE  UPSIDE    

NimoGel  aSAH    

NimoVent  aSAH     EG-­‐1964   EG-­‐1960   NimoVent  

TBI  

$15MM   Phase  3   Phase  3   Phase  2   -­‐   -­‐  

$20MM   Phase  3   Phase  3   Phase  3   Phase  2   -­‐  

$25MM   Phase  3   Phase  3   Phase  3   Phase  2   Phase  2  

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Development  Timeline:  2.5  to  3  years  

Corporate  Presenta,on  October  2011