Biotech Values

[isolution]

Dew, Text of slides at Wilmer

One preliminary remark Dew, remember when you suspected Campochiaro of conflict of interest previously, considering the various trials he is following in different approaches, I don't think there is any problem.

Slide 4

Current National Clinical Trials for Neovascular AMD
AdGVPEDF.11D
GenVec, Inc.
Anecortave acetate (Retaane)
Alcon, Inc.
Anti-VEGF antibody (Macugen)
EyeTech / Pfeizer, Inc.
Rhu Fab V2 (Lucentis, monoclonal Ab fragment)
GenenTech, Inc.
Verteporfin for Minimally Classic (VMC)
QLT, Inc.

Slide 5

Clinical Trials for Neovascular AMD at Wilmer
AdGVPEDF.11D
GenVec, Inc
Anti-VEGF antibody (Macugen)
EyeTech / Pfeizer
Combretastatin A 4 Phosphate
Foundation Fighting Blindness and Oxigene, Inc.
Rhu Fab V2 (Lucentis, monoclonal Ab fragment)
GenenTech, Inc.
Supplemental Oxygen
National Eye Institute
VEGF Trap (recombinant fusion protein)
Regeneron, Inc.
Verteporfin for Minimally Classic (VMC)
QLT, Inc.

Slides 6-11 Genvec trial update
Slide 12

Combretastatin A-4 Phosphate (CA4P) Phase I/II Clinical Trial
CA4P
Colchicine-like, tubulin-binding, naturally-derived, vascular targeting compound
Alters endothelial cell shape in immature blood vessels and promotes thrombosis
Induces tumor necrosis by selectively damage neovascularization

Slide 13
CA4P: Advantages of Vascular Targeting
Damage to a single blood vessel can kill thousands of tumor cells
Do not need to kill all of the endothelial cells
Endothelial cells are adjacent to blood stream, therefore overcoming delivery problems
Endothelial cells are non-malignant, so resistant mutants are unlikely to emerge

Slide 14
Role of Microtubules: Shape
Microtubules are known to be aligned with the long axis of elongated cells, their presence is essential for the maintenance of a cell’s elongated shape

Slide 16
CA4P causes regression of CNV (pictures)

Slide 17
Combretastatin A-4 Phosphate (CA4P) Phase I/II Clinical Trial
PI: Quan Dong Nguyen, MD
Eligibility
Age: > 50 yo
Visual acuity: 20/40- 20/800
Predominantly classic, minimally classic, or occult subfoveal CNV due to AMD
CNV inf 12 MPS DA
Blood and fibrosis  50% of lesion
Must not be candidate for PDT, or refused PDT
Patients allowed to have previous PDT

Slide 18
Combretastatin A-4 Phosphate (CA4P) Phase I/II Clinical Trial
Design
Weekly 10-minute IV infusions x 4
Dose escalation: 3 dose levels for 3 cohorts of patients (5 patients per cohorts)
FA and OCT immediately after first infusion, and just prior to next 3 infusions, and as subsequent study visits
Follow-up visits at 8 and 12 weeks
Outcome variables
Visual acuity
Retinal thickness and subretinal fluid by OCT
Size of CNV

Slide 19
Combretastatin A-4 Phosphate (CA4P) Phase I/II Clinical Trial
Enrollment
Four patients have finished treatment at lowest dose
Other patients await enrollment and treatment
Outcome variables
Visual acuity
Retinal thickness and subretinal fluid by OCT
Size of CNV

Slides 20-26
Genentech update

Slides 27-31
Regeneron update

Hope it will help you
Slide 15