Good morning, everyone, and thank you for joining us. I'm Arthur He, a senior biotech analyst at H.C. Wainwright. It's a pleasure to introduce Azitra, a clinical-stage company using engineered skin bacteria and recombinant proteins to go after dermatology problems with no good answer today. Led by ATR-04, an FDA Fast Track program for the rash that affects most cancer patients on EGFR targeted therapy. Here to walk you through it is Dr. Travis Whitfill, Co-Founder and the Chief Operating Officer for the company. Travis, the floor is yours.
Great. Thanks so much, Arthur, for that introduction. And hi, everyone. My name is Travis Whitfill. I'm the Chief Operating Officer, as Arthur mentioned, of Azitra. We are a public company. We're traded on the New York Stock Exchange American as AZTR. Just some standard forward-looking statements. We're a company that's using three platforms for precision dermatology. We are creating new products for both consumer health applications as well as unmet needs in dermatology. The first and primary core of our platform is that we have a bacterial cell library that's composed of 1,500 unique skin bacterial strains. Most of these species are Staph epidermidis, which is what we're focused on initially, which is a safe skin bacteria that's found on everyone's skin. But we also have some other species of bacteria in our cell library as well.
We also have a platform for AI and machine learning-driven drug discovery, and this allows us to predict novel microbial-derived proteins, peptides, and small molecules. Finally, we also have a genetic engineering platform that I'll talk more about later in this talk that is licensed from the Fred Hutchinson Cancer Center and allows us to expand the universe of potentially transformable species of bacteria. This is our current pipeline today. Our main focus right now is on ATR-04, as well as cosmetic ingredients. For ATR-COSF, that is our supernatant of Staph epidermidis that contains filaggrin. We're currently in pre-clinical phases with that program, and we'll be moving into a first-in-human study later this year. On the therapeutic side, we have two core programs.
We have ATR-01 that's pre-clinical, which is a filaggrin-secreting strain of Staph epidermidis in development for ichthyosis vulgaris, which is a disease caused by missing filaggrin protein. Secondly, we have a program in the clinic that's currently in a phase I/II clinical trial. That's an engineered strain of Staph epidermidis that's being developed for EGFR inhibitors plus osimertinib . With our ATR-COSF program, we're focused on consumer indications and cosmeceutical indications. Essentially, this is a supernatant of an engineered strain of Staph epidermidis that secretes filaggrin protein. How we do this is we screen strains of Staph epidermidis from our library, encoded filaggrin, and integrated that gene into the chromosome of Staph epidermidis. Then it makes filaggrin, and we took the supernatant of those bacteria, concentrated it down, and that is our active ingredient for this program.
There are actually no live bacteria in this product, but it does contain active human filaggrin as the main ingredient that is active. Filaggrin has a lot of different functions on the skin. It has enormous benefits in normal processing and normal skin structure. Normally, filaggrin is made deeper into the skin layers as profilaggrin. Then as the skin proliferates, the filaggrin moves up and is broken down into filaggrin, which then binds to keratin in the stratum corneum and is responsible for the skin barrier and skin structure. From there, the filaggrin is broken down even more into these free amino acids and natural moisturizing factors. This has a lot of different functions and a lot of different activities in the skin, but mainly it helps with skin hydration by breaking down into the smaller products that can retain water.
It also maintains the skin's pH. It also strengthens the skin barrier and helps protect against UV in the stratum corneum and the stratum granulosum where it binds to keratin. Altogether, this product has a lot of different benefits for the skin for cosmeceutical use. Here is our preclinical data. This is using a skin model in vitro where we knocked down the filaggrin levels. You can see on the left, that is normal human skin. The green is filaggrin, the red is keratin, and the blue is the keratinocytes. When we treated with a cocktail of cytokines, we saw a reduction in the filaggrin levels. That is what we treated with ATR-COSF and looked eight hours after application and 24 hours after application. You can see that there is a marked increase in the filaggrin levels.
What is encouraging about this is that the filaggrin is getting past the stratum corneum. It is getting beneath the skin barrier. We are seeing some colocalization with keratin, and you can see the restructuring of these granules, which are the keratohyalin filaments in the skin. This shows us that we are able to deliver quite a bit of filaggrin, and we are able to get it to the right layers. It appears to be functional because it is binding to keratin in the skin. This is the preclinical data that we have so far. We also have some results that we announced in the past few weeks that we were able to bind keratin in the skin, and that we were able to reduce transepidermal water loss in a dehydrated skin model.
Together, those data serve as the basis for going into a first-in-human study later this year. Now onto ATR-04. This is our program for EGFR inhibitor-associated rash. It is an auxotrophic strain of Staph epidermidis that is in ATR-04. The basis of this program is that we screened our library of Staph epidermidis strains and identified a strain that had activity relevant for this disease, where it reduces IL-36 gamma and also inhibits Staph aureus, both of which are elevated in these patients. A little bit more about the rash itself. This EGFR inhibitor-associated rash is pretty severe in some patients that are undergoing chemotherapy. There are a lot of patients that even discontinue their chemotherapy because of the disease severity of this rash.
So that's what we're trying to treat is this rash, which is elevated and localized around the face and mouth and eyes of these patients, making them really uncomfortable, and quite painful sometimes, actually. We're trying to treat this rash so that they can, number one, avoid antibiotics and steroids. And two, so that they can continue their EGFR therapy and have life-saving chemotherapy. This is the mechanism of ATR-04. As I briefly mentioned, both IL-36 gamma and Staph aureus are found in the skin of these patients. IL-36 gamma is typically elevated both in the skin and in the serum of these patients. So we've identified a strain of Staph epidermidis that inhibits both IL-36 gamma and Staph aureus, which we believe will suppress the inflammation, and treat the rash, all while avoiding antibiotics use and steroids use. Our preclinical data showed a reduction of IL-36 gamma.
On the left, this is reconstructed human epidermis, where we took untreated skin and then elevated IL-36 gamma with erlotinib, followed by treatment with ATR-04. We were able to get about a 75% reduction in the IL-36 gamma levels in the higher dose, which is about the same as untreated skin. We then looked at Staph aureus levels in ex vivo pig skin, where we applied a methicillin-resistant strain of Staph aureus topically onto the skin, and we were able to show the highest dose, about a 99% reduction in Staph aureus, compared to untreated skin. With those data, we went into the clinic. We had our IND cleared in August 2024, and began dosing patients last year. This is a multicenter, randomized, double-blind, vehicle-controlled study in 32 adults. It's split into two cohorts.
Cohort 1 is consisting of eight patients, and they will start with a single dose followed by a 28-day multiple dosing period. Once we have the safety data from that, we'll lead into cohort 2, which is a 28-day multi-dosing study. Both of these are randomized 3: 1 to control versus vehicle. The primary endpoints of this study will be safety and tolerability of ATR-04. But we'll also be looking at efficacy signals, which includes modified CTCAE scale, pruritus, pain, things like that. Very excited about this study. A lot of oncologists and oncodermatologists are excited about it. They want to avoid antibiotic use in these patients, and want to avoid steroids. We're also looking at expanding beyond just EGFR inhibitors to other therapies that also cause a very similar rash that are along the EGFR pathway.
We're looking at MEK inhibitors, ERK inhibitors, KRAS inhibitors, things like that. We should have data from the first cohort, which will be safety data, later this year. Looking ahead, we're working on some other programs that are earlier stage. One of the exciting new things that we're working on is genetic engineering that we licensed this platform from the Fred Hutchinson Cancer Center. It's called SIMPLE, Syngeneic DNA Minicircle Plasmid. The problem that we're trying to address here is that the manufacturing process often is unable to overcome bacterial defenses to engineer it, which leads to high costs, inefficiency, limited number of strains that are able to be transformed. Currently, it's thought that out of the 30,000 or so total bacterial species that have been transformed to date, only about 0.3% of them are transformable.
What we are trying to do is leverage this platform to be able to really expand that number to other bacterial species, to look at better efficiency from manufacturing and some other advantages as well. A little bit more about the SIMPLE solution. SIMPLE Technology is designed to evade the bacterial defenses for improved genetic engineering. In traditional engineering, usually you put in a plasmid into a bacterial cell, and the bacterial cell recognizes that that is foreign DNA, and it chops it up. It has foreign motifs and different methylation patterns that it does not recognize, and it cuts and digests the DNA. Whereas with SIMPLE, what we do is we first look at in silico prediction of these recognition motifs and then cut those out of whatever DNA that we are engineering.
It does not have those foreign motifs that are foreign to the bacteria, and so it recognizes it as self and makes whatever protein that we are trying to produce. This really allows for improved genetic engineering, better efficiency, more protein production, et cetera. We are looking at several different markets with this application to start off with. We are first starting with bioidentical filaggrin. Looking at improving our filaggrin yields with our ATR-COSF program, and improving that, the production of filaggrin. We are also looking at mRNA kits with T7 polymerase. We are also looking at recombinant protein A. We will have more updates later this year with this program, this platform, but very excited about what this opens up for us. Here is our current pipeline and our upcoming milestones.
We just finished the repeat-dose ex vivo skin model for ATR-COSF, and we will begin a first-in-human study that will look at wrinkles later this year. The readout for that will be a reduction of fine lines and wrinkles in about 30 subjects. For ATR-01, we are continuing IND-enabling studies. Did not get into that program in these slides, but that is our filaggrin secreting program of Staph epidermidis for ichthyosis vulgaris. We continue working on that, and will lead into GLP toxicology and other things to support an IND in 2027. Then finally, we are continuing to enroll and dose patients in our ongoing phase I/II study in EGFR inhibitor-associated rash for ATR-04. We expect to have the initial safety data from cohort 1 later this quarter or early fourth quarter this year.
Very excited about where we are at and the next couple of months with some additional data. Thank you very much, Arthur, and thanks for listening, everyone.