Lakewood-Amedex Biotherapeutics Inc. Common Stock The ThinkEquity Conference

I'm actually on a lapel mic.

Oh I should be good, thanks.

Thanks for showing up this afternoon, and I'd like to thank Jon and ThinkEquity for letting me give this talk to everyone. I'm going to be talking today about a new class of antimicrobial agents which we discovered. They're our own compounds, in-house developed. To do this, I first of all wanted to introduce the problem that we're trying to solve. These are the usual forward-looking statements which I'm required to put in. The big issue we're trying to deal with is antimicrobial resistance. If you don't know what that means, it means that the current medicine chest of antibiotics really is severely compromised, and most of them have some kind of resistance mechanism which makes them completely ineffective. The scope of this problem is enormous. Worldwide, there are 4.7 million people die because of an antimicrobial resistant problem.

It's actually more than the combined deaths of HIV, malaria, and AIDS combined. It's a massive issue. I worked at Pfizer for 30 years, and I was in infectious disease during that time. At the time, it was a scare that people said, "Oh, it's going to be a terrible problem. Antimicrobial resistance is coming." Well, now it's here, and if you've ever heard of something called methicillin-resistant Staphylococcus aureus, MRSA as they abbreviate it's an extremely serious infection, which if not treated with a narrowing number of drugs that can work, it can be fatal. The reason is because the systemic antibiotics are used. If your child gets sick, you go to the doctor, you want them to prescribe something, even if it's not really a bacterial disease. You'll get an antibiotic, and that leads to additional resistance being developed.

Just being treated once in the last 10 years with an antibiotic leads to a form of resistance being developed in your microbiome. It is a very serious problem. Antibiotics are used regularly in agriculture, so they are used not as antibiotics but as growth promotants. They stop animals from getting sick, and they get bigger and more muscular. This is a big issue. The big problem we have is that systemic antibiotics, typical oral or IV antibiotics right now, are extremely vulnerable to resistance. What has happened is there are lots of companies developing additional antimicrobials, but the problem is they have from the same classes, same resistance profiles. What happens is these medicines are put on the shelf.

They are not used because there is a scare that resistance will emerge against them, and so these are last resort medicines, which makes it quite difficult to develop this kind of drugs because it is difficult to get people interested. Why are we interested in this then? What we have got is a new class of agents which work completely differently from the current antibiotics. They kill bacteria rapidly, and because of that, we do not believe that resistance is going to be emerging against these bacteria. We have tried in the lab to generate resistance to the bacteria and have failed. The way you do that is you treat bacteria at a low concentration of drug for 3 weeks, and at the end of it, you see if there is now resistance to the drug you are using.

We couldn't develop resistance, whereas a ciprofloxacin, which is a common antibiotic, we had it as a control in that experiment. It got 2,000-fold resistance to the bugs that we were using. We used MRSA as one of our example bacteria, which is very difficult as I said earlier on. They are also broad spectrum. They hit gram-positives, gram-negatives, and all the multi-drug resistant organisms. They are what we call cidal against biofilm. Biofilm is a big issue in repetitive infections, so you may know someone who gets repetitive UTIs or repetitive lung infections. What happens is the bacteria go quiet. They hang around, they are not reproducing anymore, they are not growing anymore, and they wait until the environment is right, then they reemerge, and that has been a big issue. Our drugs kill biofilm organisms as well. We have already covered the resistance thing. What we do is deliver locally as well.

Instead of going systemic, where you are likely to cause some kind of side effects, your typical side effects, antibiotic GI side effects, but it also, as I mentioned earlier, induces resistance and impacts your immune system. So we go local, and that means if skin, soft tissue infections directly on the wound, whether it be a surgical wound, a burn wound, or anything, a wound like that. If it is a lung infection, it goes directly into the lung. A urinary tract infection directly into the bladder, and they will not get systemic exposure. It will not affect the microbiome, and you do not get the side effects. So that is what we claim. We have evidence obviously, and I will show you some of that evidence. How do they work? What we think they do is that this is a picture of a membrane that goes around a bacteria.

These compounds invade the membrane and just basically blow it apart, which kills the bacteria rapidly. As I said, we hit all the resistant strains, whether it's methicillin-resistant, vancomycin-resistant. In fact, we work against the biodefense pathogens. It's kind of interesting. The recent Russian lab Yersinia pestis potential infection, our drug works against Yersinia pestis. If that ever becomes a problem as an inhaled drug, we've got something ready. What we're focusing on is a skin and soft tissue infection. We've targeted diabetic foot ulcers, and the reason for targeting diabetic foot ulcers is because there's a huge medical need here that's unmet.

830 million people have diabetes around the world, and about a third of those are going to develop a diabetic foot ulcer at some point in their life. Of those, half become infected. If you don't treat that infection properly, that will lead eventually to an amputation. In fact, 1 out of 5 diabetics that have a foot ulcer will have an amputation. 1 in 5, which is an amazing number of people. If you have an amputation, your life expectancy for 5 years is less than 30%. Anyone with a diabetic foot ulcer has a life expectancy reduced by 30% for 5 years. So it's a very serious disease. The current treatment doesn't really work that well. It's basically just wound care.

People do give oral antibiotics because that's the standard of care, but it's well documented these don't actually have any clinical evidence that they work. It makes sense. There's low peripheral circulation at a foot ulcer, and that's part of the reason why you get a foot ulcer is the blood supply is very low. Actually, your innervation, your nerves, are also poorly supplied with blood, and they start to die. So you can't actually feel your foot. If you're walking around bare feet and scuff it, because of the low blood supply, the skin is thin, it'll break, and you'll get an ulcer. Trying to give an antibiotic with low blood supply means the drugs just don't get there in a high enough concentration to work. We go directly on to the wound, directly where the infection is, and kill the bacteria.

We have selected one compound, a compound we call Nu-3. It's got broad spectrum, just like the rest of the class. In vitro shows all activity against all the resistant strains and biofilm, which in diabetic foot ulcers is also a big issue. If you're treating, the bacteria just go quiet on the wound, and then in the right conditions, they'll just grow back again. We kill biofilm. We've got skin infection models, robust activity, and I'll show you a little bit of data on that. We've got a formulation that's designed for local administration. We did some early trials with a solution, but if you can imagine putting a solution on the bottom of your foot, it's going to come off pretty quickly. We now developed a gel formulation. We've done all the correct toxicology program.

The FDA required us to show that the drug does not impact wound healing at all. We have done that study. FDA is quite happy with what we have done, and we did it at very high topical doses. We have also given the drug IV, and it is, again, no systemic side effects. This is a very safe drug. We have an open IND. It is an Investigational New Drug application with the FDA, and it is open, and we are active. I am going to give you a little bit of a biology lesson. This is the in vitro profile. What we are looking at here is the time to kill about 300,000 bacteria. The top line is no drug, and then these lines are the various concentrations that we put in the solution. Along the bottom is the minutes.