Easd Stockholm 2010

Development of a once-‐weekly C-‐pep<de product CONFIDENTIAL 1

Disclosure •  James Callaway is an employee and shareholder of Cebix Incorporated

Initial Target Indication An agent for the treatment of mild to moderate peripheral neuropathy in type 1 diabetes Product Proﬁle The therapy of choice in the treatment of this signiﬁcant unmet medical need, based on improvement of sensory function 3

Restores Sensory Nerve Conduc<on Required 4 subcutaneous doses per day SCV (m/s) Healthy Controls C-‐pep<de n=26 56 p<0.05 Placebo n=23 54 52 50 Baseline 6 wks 12 wks Ekberg et al, Diabetes 2003

Drug Product Development   Unmet medical need   Biology -‐ Func<on and Pathophysiology   Safety   Eﬃcacy   Dose -‐ Replacement   Drug manufacturing   Regulatory Path   End Points   Drug delivery 5

Formula<on Criteria PK proﬁle consistent with <20% drug loss in burst once weekly dosing 1 2 3 4 5 6 7 Product load >1% of volume Syringeability ≤ 27 gauge < 20 seconds 6

Selected Formula<on Technologies Pumps Atrigel Nektar PROMAXX Trans-‐ Alkamer Alkermes dermal Enzon patch Halozyme Eryto-‐ pharm Octoplus Altus Syringability ≤ 27 gauge Stable for > 1.5 years at 4°C No more than 20 percent drug loss in burst PK proﬁle consistent with once weekly dosing Product load of at least 1 percent of volume 7

Winning Formula<ons

Slow Release PK Proﬁle (Dog) Lot 1 Lot 2 Aqu C-‐pep<de conc (ng/ml) C-‐pep<de conc (ng/ml)

Depot Characteris<cs •  Approximates 7 day coverage •  2-‐Log span spread from Cmax to Cmin •  Volume of injec<on less than 1 mL •  Viscosity keeps injec<on above 20 second target

Extended half-‐life

Extended Half-‐life PK proﬁle (monkey) Linear scale Semi-‐logarithmic scale 100 100 C-‐pep<de conc (ng/ml) C-‐pep<de conc (ng/ml) 60 40 10 20 T1/2 = 3 days 0 1 0 4 8 12 16 0 4 8 12 16 Time (days) Time (days) 12

Extended Half-‐life or Depot Half-‐life Depot •  Chemically altered •  Natural C-‐pep<de •  Ideal PK proﬁle •  PK Proﬁle not op<mal •  Ideal Presenta<on –  Exceeding Cmax by a Log –  like water •  Presenta<on –  31 G –  Ajrac<ve •  Excellent Tolerability –  Injectability acceptable •  Manufacturing •  Acceptable tolerability –  Simple •  Manufacturing –  Unknown risk

ERK1/2 phosphoryla(on CP versus Long-‐Ac(ng CP Long-‐Ac(ng-‐ CP CP 25 LA-‐CP CP 20 pERK1/2 [AU] 15 10 5 0 0 0.5 1 3 10 100 CP/Long-‐Ac(ng -‐CP [nmol/L] n=6-‐8 Chibalin lab at Karolinska: HEK-‐293 cells

Regulatory & Clinical Path Forward

Pre-‐IND Mee<ng with FDA July 2010 •  Regulatory –  FDA Conﬁrmed qualiﬁca<on of Subpart H •  Allows use of surrogate end point for Pivotal Phase 2b FDA •  Clinical –  Nerve conduc<on velocity accepted as the sole primary endpoint for approval •  Nonclinical –  IND-‐enabling tox plan endorsed by FDA 16

Road to the Clinic 2010 2011 May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr Formula<ons screen Tox supplies Acute monkey tox In life Analysis Acute rodent tox 6-‐month monkey tox In life Analysis 6-‐month rodent tox DS Process Development DS Manufacturing Develop & Qualify analy<cal methods (DS) Methods create/approve (DP) Fill prep Batch Fill records Human PK study IND pre-‐IND mee<ng submission 17

Cebix Development Program 2010 2011 2012 2013 2014 2015 Formula<on Pre-‐clinical Human PK 12-‐mo data: clinical end-‐point Phase 2b NEUROPATHY Conﬁrm surrogate marker 6-‐mo interim data: surrogate marker Phase 3 NEUROPATHY NDA submission 18

Summary •  Clear biological ra<onale for C-‐pep<de replacement •  Company set Target Product Profile for pa<ent to have a once weekly “insulin-‐like experience” •  Established long-‐ac<ng C-‐pep<de which met the profile –  Biological ac<vity confirmed in 3 separate models –  Patents have been filed •  Full development program ini<ated

Easd Stockholm 2010

by Cebix on Oct 24, 2010

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Easd Stockholm 2010 — Presentation Transcript