PRE-CLINICAL CHARACTERIZATION OF MOD-4023, A LONG ACTING GROWTH HORMONE

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 632-648-Pediatric Growth Case Reports
Basic
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-644
Gili Hart*1, Oren Herskovits2, Ahuva Bar Ilan3, Ron G Rosenfeld4, Vivian Hwa5, Leanne Amitzi6 and Eyal Fima1
1Prolor Biotech, Nes Ziona, Israel, 2PROLOR BIOTECH, Nes Ziona, Israel, 3PROLOR BIOTECH, Nes Ziona, 4Oregon Health & Science University, 5Oregon Hlth Sci Univ, Portland, OR, 6PROLOR BIOTECH, Israel
Background: 

Prolor Biotech Inc. is a clinical stage public company developing long acting versions of existing therapeutic proteins, utilizing a technology called CTP. The technology involves fusion of the C terminus peptide of β-hCG to the target protein. CTP enabled the production of a long-acting hGH (MOD-4023), which obviates the need for the numerous daily injections now required for the treatment of GH deficiency and supports single weekly injection in growth hormone deficient patients.

Aims:

To characterize MOD-4023 pharmacology, pharmacokinetics and pharmacodynamics in vitro and in vivo in rodents and monkeys as part of the MOD-4023 non-clinical toxicology program

Methods:

The pharmacological effects of MOD-4023 have been examined in vitro utilizing stable GH receptor expressing cells and in hypophysectomized rats. In addition, MOD-4023 pharmacokinetics and pharmacodynamics (IGF-1) profiles have been extensively evaluated in rats and in Rhesus monkeys following 4 and 16 weeks of weekly subcutaneous injections and compared to a daily hGH regimen, followed by safety evaluation in those animals .

Results:

MOD-4023 potency was assessed in vitro, utilizing cells stably expressing the human growth hormone  receptor. MOD-4023 showed slightly reduced activity as compared to hGH. Weight gain, a primary pharmacodynamic effect of GH, was assessed in single and repeated dose studies in hypophysectomized  rats. The accumulated weight for rats following four days of daily injection of r-hGH, was equivalent to that observed following a single injection of MOD-4023. In comparative long term studies, MOD-4023 demonstrated a greater duration in weight gain response as compared to daily hGH, which is consistent with its prolonged half-life. The results of nonclinical pharmacokinetic studies conducted in rats and Rhesus monkeys consistently demonstrated a dose-proportional exposure and response as reflected by IGF-1. In both rats and rhesus monkeys GLP repeat dose  and reproductive and developmental toxicity studies, the NOAEL was the highest MOD-4023 administered dose ( 180mg/Kg and 90mg/Kg respectively) .

Conclusion:

MOD-4023 demonstrated an excellent safety profile in all relevant pre- clinical models.  Combined with a significant prolonged GH activity compared to the current marketed daily hGH, MOD-4023 has the potential to replace the frequent (daily) injections now required for the treatment of GH deficiency with a weekly regimen.

Nothing to Disclose: GH, OH, AB, RGR, VH, LA, EF

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm