Hello everyone, and thank you for joining us today. It's my pleasure to introduce Dr. Adam Mendelsohn, Founder and CEO of Vivani Medical. Dr. Mendelsohn has led Vivani since its founding in 2009 and brings a strong background in bioengineering, drug delivery, and company building. He received his PhD in bioengineering through the joint University of California, San Francisco and UC Berkeley graduate program, where his research focused on new approaches to treating type 1 diabetes. During graduate school, Dr. Mendelsohn also worked at the intersection of science and entrepreneurship, including serving as a director of the Venture Innovation Program in Life Sciences and completing a certificate in Management of Technology through the Haas School of Business. Dr. Mendelsohn, thanks again for joining us today, and I'll turn it over to you.
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 most and 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 two 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 six months, 12 months, and potentially even longer as we proceed in our development. Our lead program, NPM-139, is a six-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 six-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 nm in inner diameter on the right image, all the way to 0 nm 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.
All of this led us to initially evaluate the technology with exenatide, the first drug with which we developed the technology in a clinical trial that was conducted last year called LIBERATE-1. This trial was primarily trying to understand what the implications would be in a human, delivering the drug, and safety and tolerability and procedures. We compared our implant with the once weekly injectable exenatide called Bydureon, as well as semaglutide injections. Overall, the results were very supportive of continued development of the technology. There was no meaningful initial burst. There was no evidence of dose dumping, which is a complication that other implants have experienced in the past. The implant was well-tolerated with no serious adverse events in the study. Its release profile was encouraging and demonstrated the potential for durable long-term delivery.
All of this supported further development of the technology, which we are now doing with semaglutide, instead of exenatide as our focus, for two reasons. The first is that at the same time we generated the exenatide clinical data, we established proof of concept with semaglutide. There is a much larger amount of data available with semaglutide, particularly in weight loss. In addition to that, the manufacturer of the exenatide products discontinued the two that were in the market, which would have made the regulatory path a little bit more hazy. In any event, now we are excited to have the experience in humans that we did proof of concept with exenatide and to be applying that knowledge as we are currently ongoing in a clinical trial with semaglutide. We are calling this program SLIM, Semaglutide Ultra Long-acting Implant in Obesity.
As I'm sure everyone here knows, the revenues being generated by the GLP-1 class in obesity are staggering and growing rapidly. The problems which I had mentioned earlier regarding adherence and persistence are also staggering. Specifically with semaglutide, not only is Wegovy approved for weight management in obese and overweight individuals with a related comorbidity, but in addition, there are other indications, including MASH. Semaglutide was the second drug ever to be approved for MASH. A lot of new data that's being generated that could expand the clinical indications for a semaglutide implant as we proceed. Here's a little bit more granular data on the persistence information that shows only 40% of people in this study remained on semaglutide treatment after a year. This leaves a lot of room for improvement.
The long-term outcomes benefits that people experience on GLP-1s really only happen after much longer durations of treatment. If someone loses weight for six months and then the weight comes right back, which happens when you discontinue, then the cardiovascular benefits and other real health outcomes benefits that translate to value for payers may not be realized. We really need to do something about this so that we can make sure that people realize the long-term benefits of these treatments. We believe that taking the human behavior element out of the equation by using an implant, will make it a lot easier and more effective to achieve that than trying to convince people that they should continue taking their medicine. Here is an example of what happens when someone does discontinue.
This data was taken from the Wegovy clinical program, the STEP 1 trial, after 68 weeks of treatment. Upon removal, relative to placebo, you can see how quickly the weight comes back. This is consistent with all other data that's been generated, with anecdotes that have been reported. When people start this treatment, they cannot discontinue quickly, because then they start to feel starved. There's a hunger rebound mediated weight gain that we think should be avoided. What we've demonstrated so far pre-clinically with our semaglutide implants that are representative of what's currently in the clinical trial and what we intend to work going forward shows really steady, smooth pharmacokinetics over extended periods of time, with a couple different configurations shown on this slide.
Earlier on in our development, before we optimized the early part of the PK profile to be as beautiful and flat as you saw on the prior slide, we did evaluate a prototype version of this implant over an entire year. What we learned was that after the initial spike in this, which we have now mitigated with some changes, what we saw was sustained release that stayed sustained over an entire year with the weight effects that were initially produced by the implant also sustaining over an entire year.
This makes us very optimistic that when we get longer duration data with the developments that enabled the beautiful PK profiles you saw on the last slide, we will be able to extend this ultimately to a year based on the stability of the drug and the long-term durability of the release that we have been able to observe in an in vivo setting. A little bit of information on the market. There has been some patient survey data in relation to a six-month GLP-1 implant that was highly supportive of interest in an implant. In this case, 56% of GLP-1 patients responded that they would likely or definitely get an implant if FDA-approved, prescriber recommended, and covered by insurance.
We have done our own prescriber research that provided us with some good optimism when they provided an average rating of 8.3 on a 10-point scale regarding the likelihood of prescribing a long-acting implant. Another piece of information that we think is relevant as an analog is the contraception market, which has a lot of similarities to GLP-1s in many ways as far as requiring chronic dosing and multiple different therapeutic options. What we find highly intriguing is that for women who are using prescription contraceptive drugs or devices, 90% of them use either the pill or a long-acting reversible option like an IUD or NEXPLANON. Nearly as many women choose the long-acting reversible as an easy to take, inexpensive, very convenient pill. NEXPLANON, which is the implant within this category, demonstrates almost $1 billion in annual sales.
We believe that this provides good evidence that there will be some interest in adoption of a small implant similar to NEXPLANON, if and once we are able to make that available. We have had rapid progress in the last few months. It was a year ago that we reported our preclinical proof of concept with the semaglutide implant in animals, and we started our path to clinical development. We received regulatory approval to start the trial that is now ongoing in June. We had also announced an agreement with Novo Nordisk in which they are evaluating our semaglutide implant two months ago. We have just recently announced full enrollment and all patients successfully dosed in the SLIM-1 trial, the results of which we expect will be available in November and anticipate that enabling the initiation of a dose-ranging study sometime next year.
The design of the SLIM-1 trial, we are looking at a low-dose implant for four weeks compared to the starting dose of Wegovy. This, we think, will give us the safety and tolerability and PK characterization that we need to have confidence in running the larger, higher dose, longer duration, phase II-oriented study that will be coming up, that we will be conducting subsequently. This is our current proposed concept for what that phase II study design would look like after titrating patients up to a maintenance dose, randomizing them to three different doses of our semaglutide implant, a placebo, and the continued Wegovy treatment for periods of up to six months in this next trial. Lastly, I will just briefly mention we have been generating some good data with newer molecules.
In this case, we've been studying our technology with retatrutide, which is Eli Lilly's triple agonist that they expect to file for approval next year, generating very smooth pharmacokinetics. Now that we've been able to show the technology working with exenatide, semaglutide, and retatrutide, we believe it's well-positioned to continue to compete with newer molecules as they're developed as we go forward. We have our own facility in Alameda, California, in which we are manufacturing these implants. We have very specialized processes that we've developed and represent another layer of protection as far as being able to develop these processes. We have a very experienced and seasoned leadership team from all aspects and all functional areas of the company. Very excited and pleased to have this group working with me on this project.
Lastly, I'll just close by reiterating that we are the only GLP-1 implant in development for obesity and chronic weight management. Convenient once or twice-yearly dosing, we anticipate, uniquely addresses some of the primary GLP-1 market challenges. It's a unique modality that we expect to reach certain underserved markets. Lastly, before I fully close, I'll mention it's not part of our core business, but we did recently announce that a wholly owned subsidiary of ours, Cortigent, entered into a merger agreement with ClearOne that we expect will close in the third quarter of this year and leave Vivani as a majority owner of a neurostimulation company that would be separately and publicly listed. So, feel free to look up information about that as additional color regarding our company as a whole, even though our key focus is on these GLP-1 implants right now.
With that, thank you very much for your time and attention, and that's all. Thank you.
Dr. Mendelsohn, thanks again for joining us today and for giving this fantastic, really interesting presentation. It was especially interesting to hear about how Vivani is thinking about the role that a long-acting implant could play in obesity. From the adherence and persistence challenge to the preclinical work and the development path for NPM-139. So once again, this closes out the session, and we really appreciate the perspective and your time today.
Thank you, Jan. Thank you very much