Oncology Immunotherapy - Nivolumab and other PD-1/PD-L1 Targeted Agents (061213)

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This is a short briefing on the oncology immunotherapy PD-1/PD-L1 targeted agents currently under development. In this briefing we look at the competitive landscape, PD-1/PD-L1 product profiles, positioning, strategy, as well as a development timeline and SWOT on the BMS PD-1 blocker nivolumab. Updates to this briefing will come as newer information is discovered.

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  • Thanks! For better options in treatment, please, visit cancercuremedicine.com, read: http://www.amazon.com/s/ref=nb_sb_noss_1/183-5035389-4416932?url=search-alias%3Daps&field-keywords=travis+christofferson
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  • PD-1/PD-L1 immunology angle to cancer treatment explained in few words & developments related to this are the future in not only in cancer chemo but also in other segments.
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Oncology Immunotherapy - Nivolumab and other PD-1/PD-L1 Targeted Agents (061213)

  1. 1. By  Will  Roettger   Principal  Consultant   20/20  Market  Insights,  LLC   June  12,  2013   CI  Briefing  -­‐  Nivolumab  
  2. 2. Will  Roettger  is  an  established  career  professional  in  the  pharmaceutical  and   biotech  industry.  Having  worked  for  Novartis,  AstraZeneca,  Merck,  Alexion,  and   Dendreon  he  has  developed  expertise  across  the  therapeutic  areas  of  oncology,   hematology,  and  immunology  for  pipeline  and  launch  products.  He  has  been   instrumental  in  establishing  marketing  intelligence  as  a  core  capability  in   support  of  clinical  and  commercial  new  product  development,  solving  the  many   commercial  challenges  that  high-­‐priced  specialty  products  face  from  a  patient,   provider,  and  investor  perspective.  Additionally  he  has  supported  two  specialty   product  launches,  providing  actionable  insights  and  recommendations  by   integrating  market  research  findings  with  competitive  intelligence.  As  a   principal  for  20/20  Market  Insights,  LLC,  he  is  dedicated  to  providing  clients  with   clear  vision  into  competitor  landscapes,  strategies,  and  product  assessments   that  drive  strategic  business  decisions  in  new  drug  development.   Contact  Information:   Will  Roettger   Principal  Consultant   20/20  Market  Insights,  LLC   908-­‐391-­‐4362   will.roettger@gmail.com   2  
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  7. 7. Tumor  Type   Estimated  PD-­‐L1   Prevalence   NSCLC  (SCC)   50%   NSCLC  (adeno)   45%   Colon   45%   Melanoma   40%   RCC   20%   As  one  of  the  highest  prevalent  cancers,  NSCLC  represents  a   significant  opportunity  to  leverage  the  effects  of  PD-­‐1/PD-­‐L1   blocking  agents   7  
  8. 8. Nivolumab   (BMS936558)   Company   Bristol-­‐Myers  Squibb   Lambrolizumab   (MK-­‐3475)   Pidilizumab     (CT-­‐011)   MPDL3280A   Merck   Genentech/Roche   CureTech   PD-­‐1  blocker   (blocks  PD-­‐L1/PD-­‐L2  )   PD-­‐L1  (ligand)  blocker   (blocks  PD-­‐L1  )   PD-­‐1  blocker   Humanized,  IgG4   Human,  IgG1       Humanized,  IgG1   (effector  T-­‐cell  function)   (effector  T-­‐cell  function)   Melanoma   Melanoma,  NSCLC,   RCC,  Colon,  Gastric,   HNSCC,  Lymphoma   Melanoma,   pancreatic,   lymphoma,  CRC,  RCC,   MM   Phase  III/(melanoma)   [PIII  Just  initiated]   Phase  II  (NSCLC)   Phase  II  (NSCLC)   Phase  II  (CRC,   lymphoma,  Hep-­‐C   pancreatic,  PCa   Melanoma   (ORR>38%)   Melanoma  (ORR  29%,   SD  87%  ,  PFS  43%),   NSCLC  (24%)   +50%  increase  in  CD4,   +40%  increase  in  CD8   Data  pending   39%  vs.  13%  all  tumors   100%  vs.  15%    NSCLC   1.  Melanoma   1.  NSCLC   ADCC/CDC  Toxicity   none   none   none   Pneumonitis   3-­‐4%   3-­‐4%   none   MOA   PD-­‐1  blocker   (blocks  PD-­‐L1/PD-­‐L2  )   Antibody   Human,  IgG4   Targeted  Tumors   Melanoma,  NSCLC,   RCC   Latest  Clinical  Phase   Phase  III/(melanoma,   Development   NSCLC,  RCC)   [6-­‐phase  III  trials]   Activity/response  rates   Melanoma  (ORR  31%,   RR  67%),  NSCLC  (17%),   RCC  (29%)   Efficacy   Melanoma:  21.1  vs.   12.5  mos   Fast  Approval  Strategy   1.  Squamous  NSCLC   (conditional  w/phase  II  data)   2.  RCC   -­‐   none  
  9. 9. Trademark:   Generic  Name:   nivolumab   Synonyms:   BMS-­‐936558,  MDX-­‐1106,  ONO-­‐4538   MOA:   PD-­‐1  checkpoint  inhibitor,  fully  human  mAb  anti-­‐PD-­‐1  IgG1  receptor  blocker.  Blocks   binding  of  PD-­‐1  to  PD-­‐L1  and  PD-­‐L2   Originating  Company   Ono  Pharmaceuticals,  Ltd./   Licensing  Company   Bristol-­‐Myers  Squibb   Formulation/Dose   IV  infusion,  3  mg/kg  solution  intravenously  every  2  weeks   1st  Launch/Indication   /Metastatic  NSCLC   2nd  Launch/Indication   /Metastatic  RCC  or  Metastatic  melanoma   Patent  No./Expiration   Sales  Force  Size   Cost   Comments   Pneumonitis  AEs  of  3-­‐4%,  3-­‐deaths  to  date,  1-­‐CRC,  2-­‐nsclc.     9  
  10. 10. Trademark:   Generic  Name:   Synonyms:   BMS-­‐936559,  MDX-­‐1105   MOA:   Fully  human  mAb,  PD-­‐L1  IgG4  ligand  blocker.  Blocks  binding  of  PD-­‐L1  to  PD-­‐1  and   B7-­‐1.  Does  not  block  binding  of  PD-­‐L2  to  PD-­‐1   Originating  Company   Ono  Pharmaceuticals,  Ltd./   Licensing  Company   Bristol-­‐Myers  Squibb   Formulation/Dose   1st  Launch/Indication   2nd  Launch/Indication   Patent  No./Expiration   Sales  Force  Size   Cost   Comments   Development  was  dropped  in  option  to  move  ahead  with  nivolumab  –  a  PD-­‐1   receptor  blocker.  No  reported  pneumonitis  in  BMS-­‐936559.   10  
  11. 11. Trademark:   Generic  Name:   lambrolizumab   Synonyms:   MK3475,  SCH900475   MOA:   Humanized  mAb  anti-­‐PD-­‐1,  IgG4,  receptor  blocker.  Blocks  binding  of  PD-­‐1  to  PD-­‐ L1  and  PD-­‐L2   Originating  Company   Licensing  Company   Merck/Schering   Formulation/Dose   IV  infusion  over  30  minutes  …   1st  Launch/Indication   /Metastatic  Melanoma   2nd  Launch/Indication   /Metastatic  NSCLC   Patent  No./Expiration   Sales  Force  Size   Cost   Comments   Pneumonitis  AEs  of  3-­‐4%,     11  
  12. 12. Trademark:   Generic  Name:   Synonyms:   MPDL3280A   MOA:   A  Human  Fc  optimized  anti-­‐PD-­‐L1  mAb,  IgG1,  ligand  blocker    -­‐    binds  to  PD-­‐L1,   blocking  its  binding  to  and  activation  of  its  receptor,  PD-­‐1.  Fc  optimization  does  not   induce  either  antibody-­‐dependent  cytotoxicity  (ADCC)  or  complement-­‐dependent   cytotoxicity  (CDC).   Originating  Company   Licensing  Company   Genentech/Roche   Formulation/Dose   IV  Infusion  of  1200  mg  on  Day  1  of  21-­‐day  cycles  for  a  maximum  of  16  cycles   1st  Launch/Indication   /Metastatic  NSCLC   2nd  Launch/Indication   /Metastatic  Melanoma   Patent  No./Expiration   Sales  Force  Size   Cost   Comments   20%  clinical  benefit  in  PD-­‐L1  negative  tumors  has  been  shown.  The  Fc  portion  of   anti-­‐body  is  engineered  to  prevent  depletion  of  effector  T-­‐cells  by  ADCC  thereby   allowing  PD-­‐1  and  PD-­‐L2  interaction  to  remain  intact  in  pleural  tissues.  As  a  result   no  pneumonitis  has  been  12   seen.  
  13. 13. Trademark:   Generic  Name:   pidilizumab   Synonyms:   CT-­‐011,     MOA:   Humanized  mAb  anti-­‐PD-­‐1,  IgG4,  receptor  blocker.  Blocks  binding  of  PD-­‐1  to  PD-­‐ L1  and  PD-­‐L2  resulting  in  the  attenuation  of  apoptotic  processes  in  lymphocytes,   primarily  effector/memory  T  cells,  and  the  augmentation  of  the  anti-­‐tumor   activities  of  NK  cells.   Originating  Company   CureTech   Licensing  Company   Formulation/Dose   IV  infusion   1st  Launch/Indication   2nd  Launch/Indication   Patent  No./Expiration   Sales  Force  Size   Cost   Comments   As  of  January  2013,  Teva  dropped  their  development  agreement  with  Curetech  on   this  product.  At  this  point  Teva  is  without  a  development  partner  and  continues   ahead  with  phase  II  trials.  13  
  14. 14. 14  
  15. 15. Nivolumab  Clinical  Trials   NSCLC   RCC   Melanoma   Phase II Trials Phase II Trials Phase II Trials 1.  Nivolumab in advanced or metastatic squamous cell NSCLC, NCT01721759, n=100, i=11/2012, f=2/2014 1.  Nivolumab in clear cell advanced RCC, NCT01354431, n=150, i=5/2011, f=5/2013 1.  Nivlumab w/ipilimumab in advanced or metastatic melanoma, NCT01783938, n=80, i=4/2013, f=8/2014 Phase III Trials Phase III Trials Phase III Trials 1.  Nivolumab vs. docetaxel 2L advanced or metastatic squamous cell NSCLC, NCT01642004, n=264, i=10/2012, f=8/2015 1.  Nivolumab vs. everolimus 2L advanced or metastatic clear cell RCC, NCT01668784, n=822, i=10/2012, f=2/2016 1.  Nivolumab + ipilimumab – 1L Advanced Melanoma, NCT01844505, n=915, i=6/2013, f=1/2017 2.  Nivolumab vs. dacarbazine or carbo/paclitaxel in advanced melanoma following anti CTLA-4, NCT01721746, n=390, i=12/2012, f=5/2015 2.  Nivolumab vs. docetaxel 2L advanced or metastatic nonsquamous NSCLC, NCT01673867,n=574, i=11/2012, f=11/2014 15   3.  Nivolumab vs. dacarbazine, 1L metastatic melanoma, NCT01721772, n=410, i=1/2013, f=6/2020
  16. 16. 2013 2014 2015 Complete 11/2014 NSCLC (2nd Line advanced metastatic) 2nd RCC Line (advanced metastatic) File 4/2015 Non-Squamous Cell NCT0167387 2017 Estimated approval 10/2015 (PDUFA V, 6-mth priority review) Complete 8/2015 File 1/2016 Estimated approval 7/2016 (PDUFA V, 6-mth priority review) Squamous Cell NCT0167387 Complete 2/2016 File 7/2016 Estimated approval 1/2017 (PDUFA V, 6-mth priority review) clear cell NCT01668784 Complete 11/2014 Melanoma (1st Line advanced metastatic) 2016 File 5/2015 Vs. dacarbazine,or c/p NCT01721746 Complete 8/2015 + ipilimumab NCT01844505 Estimated approval 12/2015 (PDUFA V, 6-mth priority review) File 1/2016 Estimated approval 7/2016 (PDUFA V, 6-mth priority review) Estimated approval 3/2021 (PDUFA V, 6-mth priority review) Vs. dacarbazine NCT01721772
  17. 17. 2013 2014 2015 Complete 11/2014 NSCLC (2nd Line advanced metastatic) 2nd RCC Line (advanced metastatic) 2016 File 4/2015 Non-Squamous Cell NCT0167387 Phase II Study Complete 2/2014 Fast  Track   Estimated approval 10/2015 (PDUFA V, 6-mth priority review) Complete 8/2015 File 1/2016 Estimated approval 7/2016 (PDUFA V, 6-mth priority review) Squamous Cell NCT0167387 Phase II Study Complete 5/2013 Fast  Track   Complete 2/2016 File 7/2016 Estimated approval 1/2017 (PDUFA V, 6-mth priority review) clear cell NCT01668784 Complete 11/2014 Melanoma (1st Line advanced metastatic) 2017 File 5/2015 Vs. dacarbazine,or c/p NCT01721746 Phase II Study Complete 8/2014 + ipilimumab NCT01844505 Vs. dacarbazine NCT01721772 Fast  Track   Complete 8/2015 Estimated approval 12/2015 (PDUFA V, 6-mth priority review) File 1/2016 Estimated approval 7/2016 (PDUFA V, 6-mth priority review) Estimated approval 3/2021 (PDUFA V, 6-mth priority review)
  18. 18. 18  
  19. 19. Lambrolizumab  Clinical  Trials   NSCLC   Phase II Trials RCC   Phase II Trials 1.  MK3475 vs. Docetaxel, n=920, T0=Augst 2013, Tf=September 2015, Primary=OS, PFS, secondary=ORR, RR, US Trial 19   Melanoma   Phase II Trials
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  22. 22. Will  Roettger   Principal  Consultant   20/20  Market  Insights,  LLC   908-­‐391-­‐4362   will.roettger@gmail.com   22  

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