Vivani Medical, Inc. Common Stock (DE) H.C. Wainwright 28th Annual Global Investment Conference

Thank you very much for the introduction. It's my pleasure to be here, and thank you for all taking the time to learn more about Vivani Medical. These past few months have been some of the most exciting and productive months in the history of our company, highlighted by the current clinical trial we have with our semaglutide implant that rapidly enrolled and is ongoing right now, as well as a technology evaluation agreement that we recently announced with Novo Nordisk, enabling them to evaluate our semaglutide implant. Before I get into those details, let me just jump forward. Here are our disclaimers, and let me just start the discussion with a little bit of a narrative around how the large obesity market, that I'm sure everyone is familiar with, has been evolving and where we think Vivani Medical can have a prominent place in this future market.

Let me first mention, as I think everyone knows, the GLP-1 class has really transformed the care of obesity as well as type 2 diabetes and likely other additional indications as future clinical work is progressing in the field. Right now, the landscape consists of three FDA-approved GLP-1 injectables for obesity and two FDA-approved orals. It's worth acknowledging that there is a very large and crowded field of companies that are working on new and novel approaches to treating obesity based on GLP-1 and other related biology. Over 50, many of these companies are in late-stage development and are getting a very large amount of attention towards their assets because of the opportunity being so large. What makes Vivani different is that all of these other companies are focused primarily in a couple of different buckets.

One is orals that will be preferable to a certain segment of patients, as opposed to the injectables that were first to market. The other bucket is longer-acting injectables, beyond once-weekly, going to once-monthly, maybe even longer than that. I think one of the most prominent examples of value being associated with the longer-acting injectables was the $10 billion acquisition that Pfizer did of a company called Metsera for their monthly GLP-1 and amylin agonists. What we're developing is a small implant that could be administered once or twice a year, so longer than even the longest-acting injectables that are currently in development.

But with the added benefit that in the instance that someone did need to discontinue a treatment or reduce the drug exposure, which is necessary and still recommended if a woman gets pregnant to discontinue their GLP-1 use or in anticipation of a surgery that would have a high risk for aspiration to discontinue their GLP-1. What our implant would offer is the combination of very infrequent administration and the peace of mind that if the implant's removed, the drug exposure would go down as quickly as a weekly injectable, in our case, with semaglutide, would go down, which we think uniquely positions our product to address a large and growing segment, and help with many of the still unmet and what we expect to be continued to be unmet needs, even with these new other products that are in development as we go forward.

Let me just break that down a little bit. One of the big challenges, and this is true not just with the current weekly injectables but also with the daily orals, and also not just for obesity treatment or GLP-1s but really chronic diseases at large, is really suboptimal outcomes as related to poor adherence. People in the real world do not take their medicine as prescribed at staggering rates. Over 50% of people, generally speaking, do not take their doses according to the schedule that's prescribed. Many of them discontinue treatment for a wide variety of reasons. But what an implant would provide is essentially a set-it-and-forget-it solution for the duration of that implant. Without any effort or any thought or any treatment burden, that patient will get the medicine that they need. Now, getting to tolerability, an issue that's a little more specific to GLP-1s.

The reason that all of the GLP-1s have these long and gradual titration schemes to get to the higher more efficacious doses is because if you have a rapid increase in exposure, people experience severe gastrointestinal events. And when you combine that with the knowledge that over 50% of people don't take their doses as expected, that inevitably leads to more fluctuations in exposure level. So much so that even on the Wegovy label, it states that if 2 or more doses are missed, consider starting at the initiation dose of the sequence in order to avoid the gastrointestinal events that would otherwise likely be present.

What an implant does is not only, we think, have a likelihood of increasing, improving the real-world outcomes, just avoiding the less than effective exposure windows that would happen when people don't take their medicine, but also maintaining more stable levels, which we anticipate will mitigate many of the tolerability effects associated with this class, which, by the way, are the number one complaint that is associated with taking GLP-1s today. And lastly, we believe that there are still underserved and under-addressed populations for whom an option that would allow the caregivers for a particularly severely diseased patient to not have to worry about whether that patient's going to get their medicine on a regular basis, would welcome the ability to use an implant, and then in between doctor's appointments, not have to worry at all about that patient getting the medicine that they need.

At a high level, right now at Vivani Medical, our focus is on the GLP-1 market with our miniature subdermal implants focused on addressing adherence, tolerability, and convenience with care. This is based on a platform technology that we call NanoPortal, which can enable very infrequent dosing, we think, ultimately for a wide range of different molecules, including every 6 months, 12 months, and potentially even longer as we proceed in our development. Our lead program, NPM-139, is a 6-month semaglutide implant being designed for obesity treatment. We do intend to evaluate that in patients with type 2 diabetes as well. We are at an exciting juncture within our company. Our first phase I trial with our semaglutide implant, which we call SLIM-1, recently rapidly enrolled, and we expect top-line data to be available in November of this year.

We anticipate that the results of this phase I will pave the way for us to conduct a dose-ranging, efficacy-oriented phase II study that we could begin sometime next year. This is all based on some proof of concept preclinical data that we demonstrated with our semaglutide implant, resulting in 20% weight loss being observed over an entire year after a single implant. Our pipeline right now is led by NPM-139, but we do have some activities in next-generation incretins. Again, while we expect that for a 6-month semaglutide implant, there to be a space in the future market by the time we're ready to get approved. Again, it is a platform technology that we intend to apply to all the newer molecules as they become developed by other companies, in order to be able to demonstrate even better efficacy and other effects as they are available.

We did do a clinical study with our exenatide implant a year ago, which had favorable results. That remains on our pipeline, although our focus right now is semaglutide. We do have a partnership with an animal health company, with whom we are developing a version of these GLP-1 implants for cats and dogs as well. Now, what does the product look like and how does it work? You can see that's my hand holding our implant on the left portion of the screen. It's a small titanium cylinder that contains a high-concentration drug formulation and has a material that controls the release of the medicine at one end of the reservoir. I'll tell you more about that in a second. This is placed in a simple in-office primary care procedure, very similar to the procedures for the widely used contraception implant NEXPLANON.

A schematic of our applicator that we use to facilitate insertion is on the bottom left. Going to the center of the screen, the reservoir, as I said, from titanium, contains the drug formulation. The gold-colored material that you see here represents millions of titanium oxide nanotubes, and this is really the magic that enables the device to perform the way that it does. These are millions of vertically oriented and adjacently attached nanotubes whose inner diameter at the nanometer scale can be precisely controlled to be close enough to the size of an individual drug molecule, which enables very desirable release profiles to exist that would not occur in standard conventional membranes that have openings that are much larger in size.

On the right, you can see what those nanotubes look like up close by electron microscopy, ranging from 30 nanometers in inner diameter on the right image, all the way to zero nanometers on the left image, and we can tune it precisely anywhere in between. When we get the right size ratio to the molecule, the right formulation, and the right other characteristics of the product, then we can achieve substantially constant release over many months at a time. This is not what one typically expects from a membrane-based diffusion device, in which you would expect the rate to decrease as the concentration decreases. But leveraging the nano-sized geometry of our material, which in our case is biocompatible and biostable because it is titanium oxide, and there is a large patent portfolio associated with this as well, is what enables this to work for this application.

This data here is with exenatide. Here is both some additional in vitro data on the left, as well as some vivo data that was generated in diet-induced obese mice on the right, demonstrating the ability to provide sustained release, including in an in vivo setting over many months at a time. We have also shown sustainable and durable weight loss effects after a single implant. In this particular study, we have shown 16 weeks of sustained weight loss that after the implants were removed, the weight started to come back, which is what you expect when GLP-1 levels have discontinued. Also in addition, demonstrating the activity associated with the delivered drug, these implants were able to reduce liver fat by 82% after a 12-week treatment duration preclinically, which is consistent with what one could get with frequent administration of the injectables in the same model.