xeris · 2012. 10. 4. · xeris"pharmaceu2cals,"inc.8confiden2al"informaon" step!1:!formula/on!...
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Partnership Opportuni/es in Drug Delivery
Boston, October 2012
Steven J. Prestrelski, CSO
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10/4/12
XERIS PHARMACEUTICALS
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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
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» 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
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» 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
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» 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)
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» 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/
4/12
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Xeris Pharmaceu2cals, Inc.
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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
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» 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
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» 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
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» 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
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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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10/4/12
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