INmune Bio Inc. Common stock H.C. Wainwright 28th Annual Global Investment Conference

Thank you, Dr. Montgomery, and thank you for having me. My name is David Moss. I am the CEO and founder of INmune Bio. INmune Bio is focused on two late-stage platforms around inflammation and immunology. One of the things that we really focus on in those two areas is the fact that most treatments that treat inflammation are immunosuppressive. The two drug platforms we have today are very potent in treating inflammation and modulating inflammation, and they do it without immunosuppression. That is a very, very big deal. Our two platforms are CORDStrom and XPro. Many of you know XPro and have heard about it. It was the first to treat neuroinflammation as a driver of Alzheimer's disease. In June of last year, it did not hit its endpoint of cognition in a phase II randomized study.

There is only one study I will point out that did that, and that was Eli Lilly's donanemab, which was a large, almost phase III study. It did show very clear signals that there is a drug. It met endpoints from an efficacy standpoint and an effect size on two cognitive endpoints, p-tau, GFAP, two neurodegenerative endpoints on white and gray matter imaging, particularly white matter imaging. It actually had a strong p-value to show that it remyelinates. It also hit things like Neuropsychiatric Inventory. Those are things like sleep disorders, aggression, depression, and so on. This is a program where we met with the FDA at the end of phase II. They granted us Fast Track, and they gave us a clear path for registration phase II-B/III program. As many as you know, that is a very expensive proposition.

That program sits on hold currently while we move CORDStrom forward. CORDStrom is in an ultra-rare disease called recessive dystrophic EB, which I will talk about. It is in the process of submitting regulatory applications for approval, first in the U.K., which is going Q4 this year, and we expect approval sometime in Q2 of next year in the U.K. It will submit its accelerated approval and conditional marketing authorisation approval in the U.S. and in Europe in Q1 of next year. If the program gets accelerated approval in the United States, it comes with a priority review voucher. Guess what we will do with the priority review voucher, is we will use that to help fund the phase II-B program in Alzheimer's. CORDStrom is what we are going to talk about today.

The trade name of the product is called Ebstrocel, and it is the first treatment that treats the systemic nature and then endpoints that are important to the patients in recessive dystrophic EB. Recessive dystrophic EB is a genetic disease. These children are born without collagen VII, and they have chronic skin conditions that you see visibly externally on their skin, but it also happens internally to every organ in their body except for their brain. What you see externally is inside their mouth. It happens on their eyes, as you can see in this top picture. It is in their nose, behind their eyelids, down their esophagus, through their gastrointestinal tract. And they have these chronic wounds. The process is from 0 days to 10 years of age. The wounds heal faster. There is less fibrosis.

As they get 10 to 20 years of age, the wounds take longer to heal. They are more fibrotic. Ultimately, when they get to their second or third decade of life, some of these wounds just do not heal, and they end up developing squamous cell carcinoma, and unfortunately, they pass. Most of these children do not make it past their third decade of life. What is interesting is that the treatments that are approved, there are three, are all topical in nature, and that is understood because most of these patients are treated by dermatologists. Dermatologists, when they look at these diseases, they see it as a topical disease. But if you look at the top complaints, and there were two studies that were done, this is one by DEBRA, and then there was a patient-focused drug development meeting. The patients do not complain about wounds.

They complain about itch or pain as their top two, and then many are gastrointestinal or psychiatric, mental health issues, not being able to sleep, not being able to take a bath, not being able to go to school, things like that. Wounds usually show up at number 6 or number 7. What happens in the disease is you get this inflammation itch cycle. You could actually probably swap one or two back or forth, itch first, then inflammation or inflammation, then itch. They develop this scratching. If it is on their bare skin, they have very weak skin. It is called butterfly skin. It is very susceptible to peeling. They will create wounds. They will introduce bacteria. If they have existing wounds, they will create blisters and prevent wounds for healing. And this helps with prolonging the incidence of the disease.

And this, you get more inflammation and on and on and on you go. What Ebstrocel does is it reduces the itch and inflammation, and it introduces growth factors that change the immunology of the patient's macrophages at the wound, and it also introduces growth factors to improve wound healing. So it addresses the top complaints of these patients, which are itch and pain, and it reduces inflammation, and it helps with wound healing. Now, this is really that chart in a long bar format. If you reduce itch and scratching, you improve wounds over time, and you should reduce the incidence of fibrosis and ultimately squamous cell carcinoma. Now, no one is ever going to do this study because it takes so long, and I use the word should reduce.

But if you look at the quote at the very bottom here, this is from our lead PI, and she's one of the leading people who treats RDEB in the U.K. And her quote was, "Treatment with Ebstrocel in RDEB patients is likely to be disease-modifying, improving itch, skin healing, quality of life, and reducing the risk of squamous cell carcinoma later in life." Should reduce the risk later in life. This is not something we will test, but the clinicians know that by reducing the top important endpoints of itch and pain will make a difference in these patients. So this was the study that we ran. It was the largest blinded randomized trial ever run in recessive dystrophic EB. It had two groups. It had a treated group that was then washed out and given placebo, and then it had group 2, which had placebo and then was washed out and given drug.

It's a double-blind crossover study. What's very interesting is that the patients in group 1 who received placebo had an ongoing effect of drug treatment and fared much better than the patients who got placebo in group 2, who worsened and worsened and worsened until they got drug. So comparing placebo to placebo and drug treatment to drug treatment between groups 1 and group 2 is quite fascinating. This is the data. Early on in month 3, there was a significant reduction in itch. We did not see improvements in wounds at this stage. That itch was maintained at 6 months and slightly improved, and then we started to see improvements in skin integrity. That's the iscorEB. So what happens if you think about it is if you're not itching, it takes a while for you to pick that up in terms of your skin integrity.

One of the most potent and powerful developments here was the patient-reported outcomes. As many as you know, in ultra-rare and rare diseases, patient-reported outcomes can be significant drivers in regulatory decisions. It's too small to read, but the patients, if you read some of it will tell you they had significant improvements in the ability to take a bath, the quality of the wounds, less pain, less itch, being able to go to school, do activities, and so on to that sort. There was a child that happened to do a report, an article at the BBC.

If you type in BBC and RDEB, it'll pop up, and he talks about these experiences of being able to go to the beach, kick a soccer ball, et cetera. So tremendous patient-reported outcomes. When we met with the MHRA, we filed a pre-marketing authorization application. They asked us to lead with the patient-reported outcomes first as part of our marketing authorization application. So this is itch. This is how it's measured. It's called the Itch Man Scale. This is a validated scale of itch. It has five different levels. It goes from 0 to 4. All of us in this room are sitting at a 0. If you have several mosquito bites or a very bad case of psoriasis, you might be at a 1. All of our patients in the trial were either at a 2 or a 3.

Two is where the itch is so bad that it's hard to concentrate, hard to sit still. Three is where it's very difficult to even sleep, to concentrate, to be still, et cetera. One of the children described it as having RDEB as being bitten by a mosquito a thousand times a day. The itch is just a tremendous driver of the psychological impact of these children. Patients who took placebo had an increase in itch. They went from level 2 to level 3, and patients who took Ebstrocel had almost a 70% reduction, significant reduction moving from level 3 to level 2. What this resulted in is the green and the red bars are Ebstrocel at 3 and 6 months, and the black and the gray are your placebo.

What this resulted in was less inflammation in the joints, better feeling and able to use their hands, less pain in their joints, their eyes, their mouth. That results in better eating, doing tasks that all of us take for granted every day, like going to school, doing leisure activities, sleeping, just general activities. Significant improvement in the children's wellbeing. This was a single trial. It was the largest randomized trial that's ever been done in RDEB. If you look at the conditional framework in the U.K. and Europe, and it's very similar for the accelerated pathways in the United States, if you have a drug that you can show clear benefit risk profile, which clearly we talked about here, the drug's been given more than 200 administrations with no SAEs whatsoever.