Easd Stockholm 2010

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Cebix Inc's presentation given by James Callaway, COO and President of Research and Development at the 46th Annual Meeting of the European Association for the Study of Diabetes in Stockholm, 20 – 24 September 2010.

For more information about CEBIX please visit:
http://www.Cebix.com

For more information about EASD please see:
http://www.easd2010.com/


Published in: Health & Medicine, Travel
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Easd Stockholm 2010

  1. 1. 1  CONFIDENTIAL   Development  of  a  once-­‐weekly  C-­‐pep<de  product  
  2. 2. Disclosure   •  James  Callaway  is  an  employee  and   shareholder  of  Cebix  Incorporated  
  3. 3. An agent for the treatment of mild to moderate peripheral neuropathy in type 1 diabetes The therapy of choice in the treatment of this significant unmet medical need, based on improvement of sensory function Initial Target Indication 3   Product Profile
  4. 4. Restores  Sensory  Nerve  Conduc<on   Ekberg  et  al,     Diabetes  2003   50 52 54 56 Baseline 6  wks 12  wks SCV  (m/s)   C-­‐pep<de  n=26 Placebo  n=23 Healthy  Controls   p<0.05   Required  4  subcutaneous   doses  per  day  
  5. 5. 5   Drug  Product  Development    Unmet  medical  need    Biology    -­‐    Func<on  and  Pathophysiology    Safety    Efficacy    Dose    -­‐    Replacement    Drug  manufacturing    Regulatory  Path    End  Points    Drug  delivery  
  6. 6. Formula<on  Criteria   6   Product  load  >1%  of  volume   1   2   3   4   5   6   7   Syringeability  ≤  27  gauge                <  20  seconds     <20%  drug  loss  in  burst   PK  profile  consistent  with     once  weekly  dosing  
  7. 7. Selected  Formula<on  Technologies   7   PROMAXX   Atrigel   Pumps   Trans-­‐   dermal   patch   Alkermes   Octoplus   Eryto-­‐   pharm   Halozyme   Altus   Alkamer   Nektar   Enzon   Syringability  ≤  27  gauge     Stable  for    >  1.5  years  at  4°C   PK  profile  consistent  with  once  weekly  dosing   No  more  than  20  percent  drug  loss  in  burst   Product  load  of  at  least  1  percent  of  volume  
  8. 8. Winning  Formula<ons  
  9. 9. Slow  Release  PK  Profile  (Dog)   Lot  1   Lot  2   Aqu   C-­‐pep<de  conc  (ng/ml)   C-­‐pep<de  conc  (ng/ml)  
  10. 10. Depot  Characteris<cs   •  Approximates  7  day  coverage       •  2-­‐Log  span  spread  from  Cmax  to  Cmin   •  Volume  of  injec<on  less  than  1  mL   •  Viscosity  keeps  injec<on  above  20  second   target  
  11. 11. Extended  half-­‐life  
  12. 12. Extended  Half-­‐life  PK  profile  (monkey)   12   Linear  scale   60   100   40   20   0   C-­‐pep<de  conc  (ng/ml)   0   4   8   12   Time  (days)   Semi-­‐logarithmic  scale   100   1   10   C-­‐pep<de  conc  (ng/ml)   0   4   8   12   16  16   Time  (days)   T1/2  =  3  days  
  13. 13. Extended  Half-­‐life  or  Depot   Half-­‐life   •  Chemically  altered   •  Ideal  PK  profile   •  Ideal  Presenta<on   –  like  water   –  31  G   •  Excellent  Tolerability   •  Manufacturing   –  Simple   Depot   •  Natural  C-­‐pep<de   •  PK  Profile  not  op<mal   –  Exceeding  Cmax  by  a  Log   •  Presenta<on   –  Ajrac<ve   –  Injectability  acceptable   •  Acceptable  tolerability   •  Manufacturing   –  Unknown  risk  
  14. 14. Long-­‐Ac(ng-­‐ CP   CP   0   5   10   15   20   25   0   0.5   1   3   10   100   CP/Long-­‐Ac(ng  -­‐CP  [nmol/L]   pERK1/2  [AU]   LA-­‐CP   CP   n=6-­‐8   Chibalin  lab  at  Karolinska:  HEK-­‐293  cells   ERK1/2  phosphoryla(on   CP  versus  Long-­‐Ac(ng  CP    
  15. 15. Regulatory  &  Clinical     Path  Forward  
  16. 16. Pre-­‐IND  Mee<ng  with  FDA   July  2010   •  Regulatory   –  FDA  Confirmed  qualifica<on  of  Subpart  H   •  Allows  use  of  surrogate  end  point  for  Pivotal  Phase  2b   •  Clinical   –  Nerve  conduc<on  velocity  accepted  as  the  sole   primary  endpoint  for  approval   •  Nonclinical   –  IND-­‐enabling  tox  plan  endorsed  by  FDA   16   FDA
  17. 17. Road  to  the  Clinic   17   pre-­‐IND  mee<ng   Acute  monkey  tox   In  life   Analysis   Human  PK  study   IND   submission   Acute  rodent  tox   In  life   Analysis   Formula<ons  screen   Qualify  analy<cal  methods  (DS)   Methods  create/approve  (DP)   Fill  prep   Batch   records   Fill   6-­‐month  rodent  tox   6-­‐month  monkey  tox   DS  Process  Development   Tox  supplies   Develop    &     Dec   Jan   Feb   Mar   2010   2011   Apr  May   Jun   Jul   Aug   Oct   Nov  Sep   DS    Manufacturing  
  18. 18. 2011   Cebix  Development  Program   2012   18   2014  2013   2015  2010   Formula<on   Pre-­‐clinical   6-­‐mo  interim  data:   surrogate  marker   NDA  submission   12-­‐mo  data:   clinical  end-­‐point   Phase  2b  NEUROPATHY   Confirm  surrogate   marker   Phase  3  NEUROPATHY   Human  PK  
  19. 19. Summary   •  Clear  biological  ra<onale  for  C-­‐pep<de   replacement   •  Company  set  Target  Product  Profile  for  pa<ent   to  have  a  once  weekly  “insulin-­‐like  experience”   •  Established  long-­‐ac<ng  C-­‐pep<de  which  met   the  profile   – Biological  ac<vity  confirmed  in  3  separate  models   – Patents  have  been  filed   •  Full  development  program  ini<ated  

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