Results

Examples of PK/PD Results Using PGC with a Variety of Peptides and Proteins

PGC extends half-life of both ANP and BNP in murine model

PGC extends dosing interval and efficacy of GLP-1

Extended Bioavailability

Subcutaneous 1 mg/kg, n=10
Sprague-Dawley rats

Similar effect on HbA1c with far fewer injections

After 7 weeks of treatment

PGC modulates acute side-effects of bolus injection (VIP)

Extended Bioavailability

 

PGC prevents the severe drop in blood pressure (side effect of VIP) due to larger PGC size targeting mainly to endothelium vs. smooth muscle

Subcutaneous VIP PK (n=5, BALB/c mice). PGC was loaded 0.5% w/w with VIP, mice were dosed at 100 ug/kg VIP.

Reichstetter et al; Pharmaceutical Research, 30:670-682, 2013

PGC-HBEGF plus oral Omeprazole given once a day reverses MLDS diabetes

Extended bioavailability

 

Subcutaneous HB-EGF PK (n=3, BALB/c mice). PGC was loaded 0.5% w/w with HBEGF, mice were dosed at 300 μg/kg HBEGF.

PGC improves efficacy in type 1 diabetes

 

Multiple Low Dose Streptozotocin Diabetic Mice model: Five consecutive days of Streptozotocin to induce diabetes, then followed by 28-day treatments. (n=10) Gr 1: Saline non-diabetic control  Gr 2: Saline diabetic control Gr 3: HBEGF once a day (0.3 mg/Kg) Gr 5: Omeprazole (50 mg/Kg Gr 6: Omeprazole (50 mg/Kg) and PGC-HBEGF (0.3 mg/Kg at 0.5% loading) once a day.

Larger Proteins (Leptin) can also bind to PGC for extended bioavailability

Subcutaneous Leptin PK (n=5, Sprague-Dawley rats). PGC was loaded 2% w/w with Leptin; Rats were dosed at 1 mg/kg Leptin.

A. Computer-generated model of PGC fragment with MPEG protective chain and hydrophobic elements represented by fatty acid residues.

B. A computer simulated representation of a leptin molecule binding to the hydrophobic “core” of PGC.

PGC extends FGF4 and FGF7 bioavailability and mitigates the lethality of partial body irradiation injury

Extended bioavailability
FGF (Fibroblast growth factor) 7

Subcutaneous FGF 7 PK (n=3, CD-1 mice). PGC was loaded 5% w/w with FGF 7, mice were dosed at 0.6 mg/kg FGF 7.

Kaplan-Meier Survival curves, GI irradiated with 15.7 Gy (LD50/30)

24 hours after irradiation mice were treated daily with SC injections for 7 days; C57BL/6J mice, n=30.
Amifostine is a pretreatment control
PF4=PGC-FGF4 (3 mg/Kg);  PF7=PGC-FGF7 (3 mg/Kg)