Therapeutic Focus

Overview

Pathologies of the Retina

The retina is a thin layer of tissue on the inside back wall of your eye. The retina contains millions of light-sensitive cells (rods and cones) and other nerve cells that receive and organize visual information. Your retina sends this information to your brain through your optic nerve, enabling detailed visual perception including colors. Treatment is available for some retinal diseases. Depending on your condition, treatment goals may be to stop or slow the disease and preserve, improve or restore your vision. Untreated, some retinal diseases can cause severe vision loss or blindness.

Resolv ER™ is a novel drug formulation that separates the vitreous from the retina. This is useful in reducing the risk of progression for many different retinal pathologies.

  1. Diabetic Retinopathy
  2. Vitreomacular Traction
  3. Retinal Tear
  4. Retinal Detachment
  5. Macular Hole

Initial Focus

Resolv ER™ is administered as an intravitreal injection of liposome-loaded urea compound for the inducement of a total Posterior Vitreous Detachment for the treatment of Non-Proliferative Diabetic Retinopathy (NPDR).

Diabetic Retinopathy

Diabetic Retinopathy Market

  1. ADA estimates 34-38 million in US have Diabetes, 21 million Diagnosed.  85 million in US are pre-diabetic.
  2. 1.5 million new cases every year.
  3. WHO estimates that 10% of the global population of 7 billion have diabetes.
  4. National Eye Institute estimates 14-16 million in the US with Diabetic Retinopathy with over 7 million currently treated.
  5. Target treatment population for KATO is the 5-6 million in the US with mild to moderate NPDR.

Lucentis and Eyelea average price is $2,000/dose. Potential US market is $20-24 Billion.

Diabetic Retinopathy is the leading cause of blindness in adults. There is no cure and current treatments provide only temporary relief. The condition is progressive advancing from Nonproliferative to Proliferative as the patient ages.

National Eye Institute Facts:

  1. Diabetic retinopathy can lead to other serious eye conditions:
  1. Diabetic macular edema (DME). Over time, about 1 in 15 people with diabetes will develop DME. DME happens when blood vessels in the retina leak fluid into the macula (a part of the retina needed for sharp, central vision). This causes blurry vision.
  2. Neovascular glaucoma. Diabetic retinopathy can cause abnormal blood vessels to grow out of the retina and block fluid from draining out of the eye. This causes a type of glaucoma (a group of eye diseases that can cause vision loss and blindness).
  3. Retinal detachment. Diabetic retinopathy can cause scars to form in the back of your eye. When the scars pull your retina away from the back of your eye, it’s called tractional retinal detachment.
  1. Current Treatments:
  1. Injections. Medicines called anti-VEGF drugs can slow down or partially reverse diabetic retinopathy. Other medicines, called corticosteroids, can also help.
  2. Laser treatment. To reduce swelling in your retina, eye doctors can use lasers to make the blood vessels shrink and stop leaking.
  3. Eye surgery. If your retina is bleeding a lot or you have a lot of scars in your eye, your eye doctor may recommend a type of surgery called a vitrectomy.

Disease Progression

Normal or Minimal NPDR

The patient with a normal retinal examination or minimal NPDR (i.e., with rare microaneurysms) should be re-examined annually, because within one year 5% to 10% of patients without retinopathy will develop it. Existing retinopathy will develop further by a similar percentage.

Mild to Moderate NPDR without Macular Edema

Patients with retinal microaneurysms and occasional blot hemorrhages or hard exudates should be re-examined within 6 to 12 months because disease progression is common. The natural history of Type 1 diabetic patients suggests that approximately 16% of patients with mild retinopathy (hard exudates and microaneurysms only) will progress to proliferative stages within 4 years.

Mild to Moderate NPDR with Clinically Significant Macular Edema (CSME)

CSME is defined by the ETDRS to include any of the following features:

  1. Thickening of the retina at or within 500 µm of the center of the macula
  2. Hard exudates at or within 500 µm of the center of the macula, when associated with adjacent retinal thickening
  3. A zone or zones of retinal thickening one-disc area or larger, where any portion of the thickening is within one-disc diameter of the center of the macula

It is now appropriate to subdivide diabetic macular edema according to involvement at the center of the macula, because the risk of visual loss and the need for treatment is greater when the center is involved. Macular edema is best evaluated by dilated examination using slit-lamp biomicroscopy, OCT, and/or stereoscopic fundus photography. Current treatment for diabetic macular edema includes Anti-VEGF regimens.

Severe NPDR and Non-High-Risk PDR

In eyes with severe NPDR, the risk of progression to proliferative disease is high. Half of patients with severe NPDR will develop PDR within 1 year, and 15% will have high-risk PDR. For patients with very severe NPDR, the risk of developing PDR within 1 year is 75%. Furthermore, 45% will become high-risk PDR in this same time frame. Therefore, these patients should be re-examined within 2 to 4 months.

High-Risk PDR

The presence of any three of the following features characterizes DRS high-risk PDR:

  1. Neovascularization (at any location)
  2. Neovascularization at the optic disc
  3. Severe neovascularization
  4. New vessels within one-disc diameter of the optic nerve head that are larger than one-quarter to one-third disc area in size
  5. New vessels elsewhere that are at least one-half disc area in size
  6. Vitreous or preretinal hemorrhage

Current treatment for PDR include panretinal laser therapy, Anti-VEGF treatment regimens, and Vitrectomy.

Follow On Indications

Diabetic Macular Edema (DME) is an accumulation of fluid in the macula due to leaking blood vessels in the retina, the part of the eye responsible for detailed central vision, resulting in vision impairment. Left untreated, these blood vessels begin to build up pressure in the eye and leak fluid causing DME

Vitreomacular traction (VMT) syndrome is a potentially visually significant disorder of the vitreoretinal interface characterized by an incomplete posterior vitreous detachment with the persistently adherent vitreous exerting tractional pull on the macula and resulting in morphologic alterations and consequent decline of visual function.

Retinal tear. A retinal tear occurs when the vitreous shrinks and tugs on the retina with enough traction to cause a break in the tissue. It’s often accompanied by the sudden onset of symptoms such as floaters and flashing lights.

Retinal detachment. A retinal detachment is defined by the presence of fluid under the retina. This usually occurs when fluid passes through a retinal tear, causing the retina to lift away from the underlying tissue layers.

Macular hole. A macular hole is a small defect in the center of the retina at the macula. The hole may develop from abnormal traction between the retina and the vitreous, or it may follow an injury to the eye.