Article | December 12, 2013

A Q&A With MacuCLEAR

Source: Life Science Leader
wayne koberstein

By Wayne Koberstein, Executive Editor, Life Science Leader magazine
Follow Me On Twitter @WayneKoberstein

This is extra content related to the blog "3 Companies To Watch - Part 2."

Excerpts from an interview with Phil Ralston, CEO, MacuCLEAR.

SUCCESSFUL DRUGS FOR AGE-RELATED MACULAR DEGENERATION (AMD) TREAT WET AMD. DRY AMD IS MUCH SLOWER PROGRESSING AND HAS FEWER OBVIOUS SYMPTOMS. WHAT IS THE NEED FOR A DRY AMD TREATMENT?
Our CSO Dr. Chiou realized that the best way to treat AMD overall was at the dry stage. It is a progressive disease. Everyone who gets wet AMD had dry AMD to begin with, if only for a short time. Though typically dry AMD progresses very slowly, there is no treatment to this day and the opportunity was great. So he said, “What can I do to prevent the progression of the disease?”

HOW DOES DRY AMD LEAD TO WET AMD?
In general, blood brings nutrients to the tissues and takes waste away. When blood flow is reduced, tissues do not get sufficient nutrients, and the body creates secondary collateral vessels trying to restore flow. Wet AMD only occurs when the choriocapillares, the little cradle of capillaries in the back of retina, are occluded and restrict blood getting to retina, and new blood vessels form. There’s a critical blood barrier between the blood vessels and the retina called the Bruch’s Membrane that ends up getting plugged with the waste material no longer washed away with normal blood flow. It thickens and cracks, and the vascular endothelial growth factor (VEGF) is triggered to grow new blood vessels by the body’s demand to solve this hypoxia problem in the retina, or choroidal neovascularization (CNV) The new vessels are small and fragile and grow through the Bruch’s Membrane like grass between the cracks in the sidewalk. There they break down, bleed, and you get wet AMD. So Dr. Chiou said we’ve got to restore the blood flow in the back of the eye, and if we can do that and maintain the integrity of the Bruch’s membrane, then the patient will not develop wet AMD and eventual blindness.

HOW WILL YOUR DRUG CHANGE THE CURRENT TREATMENT OPTIONS?
If a 72-year-old person comes into the doctor’s office today, and he’s got what is called drusen, fatty deposits under the retina, the doctor will say, “Go home, take vitamins, and pray that it doesn’t progress to the wet form. When it’s the wet, we can give you shots in your eye.” With our drug, we will say you won’t progress to the wet form. We don’t claim, because we don’t know, that it will reverse the condition in any way.

WHY DO YOU HAVE SO LITTLE APPARENT COMPETITION IN THE DRY AMD AREA?
All competition have focused on the various symptoms of the problem, or the various waste products found naturally in the eye. For example,the National Eye Institute ARED (Age-Related Eye Disease) study found that anti-oxidant vitamin therapy could slow the progression of dry AMD, but for the others who didn’t benefit, some companies tried to develop an anti-oxidant drug. Like Othera, they spent a lot of money on finding an anti-oxidant that would deal with the hypoxia in the back of the eye, but they went out of business because they couldn’t stop progression. If you look at all of the metabolic pathways that are occurring in the back of the eye, the retina demands more oxygen than any other tissue from the day we’re born. As you get older, and there’s less and less oxygen, you’re going to have this metabolic race. No one has been addressing the fundamental problem: the reduction of blood flow which causes accumulation of the various waste products that form in the eye.


HOW DID YOU CHOOSE TO DEVELOP THIS PARTICULAR COMPOUND FOR DRY AMD, AS WELL AS OTHERS IN YOUR PIPELINE?
Dr. Chiou looked at thousands of compounds, and our IP covers a dozen different kinds of compounds. Our lead drug, MC-1101 is a “new-purpose” drug now on Fast Track Status for dry AMD, and we chose it because it has a track record of safety, and thus it should be easier to go through FDA review. FDA loved it. VCs typically say they don’t like new-purpose drugs; they want new compounds. But they don’t understand the  importance of a drug’s risk profile in this area. All of Dr. Chiou’s compounds have three qualities: one, they increase blood flow; two, they are anti-inflammatory; and third, they have anti-oxidant properties.

WHAT CONVINCED THE FDA TO ALLOW YOU TO SKIP A PHASE 2 TRIAL FOR MC-1101 AND GO STRAIGHT TO PHASE 3?
Our first clinical trial was managed by Ora Clinical Research(?) of Andover, Massachusetts. They’ve put more than 30 ophthalmic drugs through the FDA. Ora’s founder, Dr. Mark Abelson, (?) said, “Phil, if you do a safety and proof-of-concept study, a Phase 1 trial, you won’t be wasting your money. You know the drug is safe; it’s been 50 years in the marketplace, but we need to show some sort of physiological activity.” We bought a laser doppler instrument from Switzerland that was designed to measure the shift in blood flow speed. We included the laser doppler test as a test that would be done safely in what was a safety study. It showed that, one hour after one drop of our drug, we had a 500(?)% increase in the blood flow. With that data along with the safety data, the fact that we had only one dose regimen, and our label claims would not change, we petitioned the FDA to approve going to a Phase 3 trial for efficacy, and the agency granted our request based on that data, and the proviso our novel endpoint, based on visual function is validated, before proceeding to the second registration trial that will bring the total subjects to 500.

WILL THE PHASE 3 TRIAL IMPROVE YOUR PARTNERING PROSPECTS?
We have 16 Big Pharma companies looking over our shoulder, who have told us, “If you have efficacy data, we’ll write you a big check. But we won’t write you a big check to get that efficacy data.” So, any trial that yields efficacy will improve our prospects.

YOU HAVE OBVIOUSLY REACHED OUT TO THE TRADE PRESS TO TELL YOUR STORY. WHAT IS YOUR AIM IN DOING SO?
Dr. Chiou has never been one to hype a drug, but we’re interested in making people aware of it. So when we have an opportunity to be published, we pursue it. For example, we won the Frost & Sullivan New Product Innovation Award for 2011 for retinal diseases.

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