Partnership  Opportuni/es  in  Drug  Delivery  

Boston,  October  2012    

Steven  J.  Prestrelski,  CSO

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XERIS    PHARMACEUTICALS

Xeris  Pharmaceu2cals,  Inc.-‐Confiden2al  Informa2on  

Step  1:  Formula/on  

»  Complicated    »  Designed  for  

water-‐based  delivery  

Step  3:  Mix  when  used  

     

»  High  volume    »  Painful  injec2on  

Step  2:  Dry  Powder  

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Xeris  Pharmaceu2cals,  Inc.-‐Confiden2al  Informa2on  

Step  2:  Dry  &  Mix  w/Diluent/Solvent  

Powder   Solvent/Diluent    (FDA  Approved)  

Step  1:  Simplified  Formula2on  

Step  3:    Package  in  Delivery  Device  

»  Lower  volume  »  Highly  stable  »  Easy  to  administer  »  Personalized  dosing  

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XeriSolTM  

• Non-‐aqueous  solu2ons  • For  delivery  of  pep2des  and  small  molecules  

• 5x  to  50x  volume  reduc2on  

• Faster  to  market  • Lead  program:  Glucagon  

XeriJectTM  

• Non-‐aqueous  suspensions  (pastes)  

• For  delivery  of  biologics  • Highly  concentrated  with  100x  to  1000x  volume  reduc2on  

• Opportunity  for  delivery  of  mAbs  

All  non-‐aqueous  solvents  and  diluents  used  in  these  plaZorms  are  approved  for  use  in  a  parenteral  product.  

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Xeris  Pharmaceu2cals,  Inc.  -‐  2012  

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Xeris  Pharmaceu2cals,  Inc.  -‐  2012  

» Non-‐aqueous  solu2ons  of  pep2des  and  small  molecules  

» Biocompa2ble  solvents  Ø  Polar  apro2c  solvent  and  co-‐solvent  systems  Ø  In  FDA  approved  parenteral  products  

» Proprietary  formula2on  process  »  Increased  solubility  and  stability  » Poten2al  for  reduced  injec2on  site  reac2ons  » G-‐PenTM  (glucagon)  is  lead  product  

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Xeris  Pharmaceu2cals,  Inc.  -‐  2012  

» Target  Product  Profile  Ø  Emergency  treatment  of  severe  

hypoglycemia  Ø  Best-‐in-‐class  performance  

Ø No  recons2tu2on  Ø Subcutaneous  injec2on  Ø 200  µl  injec2on  volume  

 vs  1  ml  for  Lilly  glucagon  Ø 2-‐step  auto-‐injector  Ø ~1  second  injec2on  2me  

Ø  Expiry:  2  years,  room  temperature  

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Xeris  Pharmaceu2cals,  Inc.  -‐  2012  

»  Improved  solubility    Ø  Xeris  glucagon  5X  concentrated  for  lower  injec2on  volume  –  

shorter  injec2on  hold  down  2me  

»  Improved  physical  stability  Ø  Glucagon  fibrillates  rapidly  in  aqueous  solu2ons  Ø  XeriSol  formula2on  effec2vely  suppresses  fibrilla2on  

indefinitely  Ø Monomer  is  preferred  thermodynamic  state  

»  Improved  chemical  stability  Ø  Stability  in  non-‐aqueous  solvents  mimics  solid  state  Ø  Very  low  moisture  

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Xeris  Pharmaceu2cals,  Inc.-‐Confiden2al  Informa2on  

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Xeris  Pharmaceu2cals,  Inc.  

100  

1000  

10000  

100000  

0   10   20   30   40   50  

Plasma  Glucagon  (pg/mL)  

Time  aPer  injec/on  (min)  

Glucagon  +  NMP  

Glucagon  +  DMSO  

Glucagon  +  Neat  DMSO  Control  (aq)  

XeriSol  Glucagon  pharmacokine/cs  (Cmax,  Tmax,  AUC)    and  pharmacodynamics  are  equivalent  to  aqueous  control  (SD  rat  model;  n=6  per  treatment)  

60  

80  

100  

120  

140  

160  

180  

0   10   20   30   40   50  

Bloo

d  Glucose  (m

g/dL)  

Time  aPer  injec/on  (min)  

»  IND-‐enabling  program  agreed  with  FDA  »  Lead  clinical  formula2on  chosen;  scaled  to  clinical  scale  

»  Toxicology/engineering  batch  manufactured  &  released  

»  Clinical  batch  manufactured;  in  tes2ng  Ø  2000  syringes  

»  Bridging  pharm-‐tox  study  ini2ated  in  rodent  model  (Compara2ve  Biosciences)  Ø  No  systemic  or  injec2on  site  issues  noted  

»  P2  Clinical  trial  to  begin  in  4Q12  Ø  Texas  Diabetes  Ins2tute;  Dr.  Ralph  DeFronzo  10/

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     Xeris  Pharmaceu2cals,  Inc.  

Glucagon  Rescue  Pen  (G-‐PenTM)  •  Treatment  of  severe  hypoglycemia  •  Replace  exis2ng  glucagon  emergency  kit  (GEK)  

Glucagon  Mini-‐Dosing  Pen    •  Treatment  of  moderate  hypoglycemia  •  Personalized  glucagon  administra2on  •  Strong  market  poten2al  

Ar/ficial  Pancreas  (Bi-‐hormonal  pump)  •  For  use  in  dual-‐chamber  pump  (insulin  and  glucagon)  •  Automated  glucose  control  

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Xeris  Pharmaceu2cals,  Inc.  -‐  2012  

» XeriSol  reformula2on  reduces  ISRs  significantly  Ø  Reduced  volume  Ø  Solvent  effect  

» Partnered  with  immunology  company  

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Local Injection Site Reaction Model

0.00

0.25

0.50

0.75

1.00 46% reduction p

» Highly  concentrated  solu2ons  of  small  molecule  drugs  for  injec2on  Ø Up  to  50X  higher  concentra2on  

» Highly  stable  » Mul2ple  solvent  systems    

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Xeris  Pharmaceu2cals,  Inc.-‐Confiden2al  Informa2on  

VERSUS    

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Xeris  Pharmaceu2cals,  Inc.  -‐  2012  

» Highly  concentrated  suspensions  of  dry  powders  –  pastes  

» Two  categories:  Ø  Highly  potent  drugs/ultra-‐low  volumes  –  up  to  3  mg  

Ø Drug  placed  in  lumen  of  syringe  Ø  Large  doses  -‐  up  to  500  mg/ml  

Ø Delivery  of  100s  of  mg  in  a  subcutaneous  injec2on  

» Opportunity:  Ø  Improve  stability  profile  and  further  reduce  injec2on  

volume  Ø  Self-‐administra2on  

Xeris  Pharmaceu2cals,  Inc.-‐Confiden2al  Informa2on  

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» Small  volumes  Ø  Fill  the  needle  lumen  Ø  Have  developed  specialized  

equipment  

» Larger  volumes  Ø  Direct  transfer  from  a  filling  

syringe  

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Xeris  Pharmaceu2cals,  Inc.-‐Confiden2al  Informa2on  

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Xeris  Pharmaceu2cals,  Inc.  -‐  2012  

1.  Develop  XeriSol™  and/or  XeriJect™  formula2ons  of  a  selected  biological  

2.  Demonstrate  injec2on  delivery  of  candidate  formula2ons  

3.  Demonstrate  short-‐term  stability  and/or  biological  effect    

4.  Work  with  partner  to  demonstrate  in-‐vitro  &  pre-‐clinical  pharmacology  

Xeris  Pharmaceu2cals,  Inc.-‐Confiden2al  Informa2on  

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Xeris  Pharmaceu2cals,  Inc.-‐Confiden2al  Informa2on  

XeriJectTM  

Base  Technology  

Base  Tech  Addi2ons  

Glucagon  

XeriSolTM  

Pep2de  Formula2ons  

Small  Molecule  

Formula2ons  

Products  

XeriSolTM  Glucagon  

XeriSolTM  uRAI  

Glucagon  Mini-‐Dose  

Patent  Filed   Provisional  Filed  Patent  Issued  

 

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