Good afternoon. My name is Blake Roberts, my partner at Centri Business Consulting. We're an accounting advisory firm specializing in capital markets transactions. Happy to introduce Adam Mendelsohn from Vivani Medical.
Fantastic. Thanks so much for the introduction. Thank you to everyone for being here today. I'm excited to share the Vivani Medical story with you. We are focused on addressing what we believe is one of, if not the largest unmet needs in chronic disease treatments today, which is people not taking their medicine as recommended. More than half of people do not take their medicine. This is responsible for a lot of health that's left on the table. Clinical trial results, which are fantastic, are not translating in the real world. Some estimates are as much as $500 billion in avoidable costs to the U.S. healthcare system per year because of this challenge. I'm excited to tell you about how we're doing that, what unmet needs we're addressing, and our plans going forward.
We are focused initially in the class of drugs that everyone has heard about nowadays, the GLP-1 agonists. This class has transformed health, I would say, for humanity because we finally have a treatment option that is both highly effective and adequately tolerable. It has truly been remarkable to see the impact that this drug class has had on the health of people in general. There are three approved GLP-1-based injectables today. Wegovy and Zepbound are the ones you've heard about, weeklies. There's also Saxenda, which is a once-daily version. There are currently no FDA-approved GLP-1-based orals, but there will be soon. Eli Lilly has orforglipron, which will likely get approved. Novo Nordisk is working on oral Wegovy for weight loss that will likely get approved. Because of the success of the space, there is a tremendous amount of activity in developing new injectables and orals, greater than 50.
It's probably close to 100. Every week you hear about one company that has decided to discontinue development because the differentiation wasn't quite there. Most of these are not going to be able to succeed. There are going to be a few winners, a lot of losers, and a lot of people competing for a little differentiation that they can try to demonstrate versus the established products. There is no one else that is working on a product that could be both administered very infrequently, once or twice yearly, like our implants, that also has the ability, if someone wanted the peace of mind of knowing that they could stop treatment. As an example, if a woman gets pregnant, that it's contraindicated for continued GLP-1 use as other scenarios where that's the case, that they have the ability to stop treatment.
Right now, the injectables in development are pushing longer and longer acting. That's becoming increasingly recognized as important. I think one example of that is Metsera, which has been the subject of a lot of intense news recently. A few weeks ago, they announced that Pfizer was going to acquire them for $4.9 billion upfront. Just this morning, Novo Nordisk made an unsolicited bid for $6.5 billion. That's trying to interfere with that acquisition. Their lead products are monthly injectables. There are companies working on even longer acting injectables, but as nothing's on the near term, and as I mentioned, even if that were successful, if someone received it, there is no antidote. There's no way that someone could choose to stop treatment if they wanted to.
The implant is the only way that you can provide that kind of infrequent administration while having the possibility, if you the peace of mind that you could stop treatment. There isn't anyone else that's working on that right now. We see ourselves as a highly differentiated asset addressing key unmet needs in this really incredible drug class. Now, let me break down for you what those needs are. Firstly, as I mentioned at the beginning, suboptimal outcomes. These drugs have fantastic clinical trial results. They do not translate to the real world, in large part because people do not take the medicine as much in the real world. The implant will make it difficult for someone to discontinue treatment and easy for them to stay on treatment for the duration of the implant, addressing adherence, and we think improving outcomes. The other need is tolerability.
One of the biggest complaints with GLP-1s are the gastrointestinal side effects that people experience: nausea, vomiting, et cetera. The reason for these side effects is when there is a rapid increase in the drug exposure level, then stomach mobility slows, and people experience nausea and vomiting. Their body needs time to get used to those higher levels of GLP-1 before they can go to even higher doses, which is why all of the approved products and products in development have these long and slow titration schemes to get people from being treatment naive all the way up to the most efficacious doses. What our implant will do is stabilize week-to-week fluctuations that happen between administrations. Even more importantly, for the greater than 50% of people that miss doses, as demonstrated by poor medication adherence, those people have even more severe fluctuations.
When they miss a dose or two, the drug levels get even lower. When they resume treatment, if they resume at the same dose, they're going to have a massive fluctuation that will inspire more tolerability issues. The implant will eliminate missed doses, and we think also address the biggest complaint of this class, which is tolerability. Third, these drugs are amazing, but no one can afford to give everyone who could benefit these drugs the drugs at their current prices. The prices are too high. What we're seeing in this space is that the peptides are really showing to be the most effective form of treatment. The small molecule oral GLP-1s have promised to reduce prices by having lower cost of manufacturing, but they're also showing to have underwhelming efficacy. Earlier this year, Eli Lilly released results for orforglipron in non-diabetic obese patients.
The response was, I think they had a $100 billion reduction in market cap on the news because it did not meet expectations for efficacy. They're not achieving the same level of efficacy as the peptide-based drugs are enjoying. As a result, if people want the most effective form of treatment right now, it appears the peptides are the way to go. The peptides require either many devices per year to be manufactured in the auto injector pens, in the case of four doses per pen, 13 devices per year, or in the case of the oral version, like Rybelsus or oral Wegovy, the bioavailability is so low that you need to make like 30 times the amount of drug that the person needs to get enough available for treatment.
What an implant can do is, with one or two devices per year, same cost of the drug, we think gives similar peptide-level efficacy with what we anticipate will be a lower cost of goods, which we think will allow for greater pricing flexibility and allow us to address the pricing and access challenges as well. The last point is that right now, the frequently administered drugs require that that patient population be capable of receiving drugs on that kind of an interval. We think that there are some populations for whom it is very challenging for their caregivers to make sure that those patients receive their medicine in certain psychiatric diseases or motor function diseases or severe autism, where perhaps we may have an opportunity with an implant to expand the market beyond people that are currently receiving this care because of the unique modality that our product represents.
Right now, we are focused at Vivani Medical on the GLP-1 space, enhancing patient outcomes through addressing adherence, tolerability, and convenience. It is based on a platform drug delivery technology that we call NanoPortal that we do intend to explore more broadly across different chronic disease areas as we proceed. Our lead program is a six-month semaglutide implant under development for chronic weight management in people with obesity or overweight with a related comorbidity.
The technology has been in a successful clinical study earlier this year with exenatide, which was our lead program until we decided to prioritize semaglutide earlier this year, in part because of some preclinical data that we have demonstrated, with a semaglutide implant being capable of maintaining about 20% weight loss over a seven-month period after a single implant, with data that we anticipate will ultimately enable one year of weight loss control from a single implant. The value proposition for semaglutide, we think, is more compelling because of the substantial clinical data that semaglutide products have demonstrated, as well as the commercial success that semaglutide products, Ozempic and Wegovy, have enjoyed, hence our now focus on semaglutide going forward. Our lead program, as I just mentioned, is the semaglutide implant. We anticipate initiating clinical development in the 1st half of next year.
We also intend on evaluating the product in patients with Type 2 Diabetes. NPM-115 is the exenatide implant that completed its first human study earlier this year that I just mentioned. We have a partnership with a small animal health company with whom we are collaboratively developing a version of these implants for cats and dogs, which is a different segment that happens to be growing substantially right now. We think it could be additive to our value on top of the human applications that are our focus. Let me tell you a little bit about the technology so you can see what the implant looks like. It's a Titanium Reservoir that is filled with drug. It has a material that controls the release of that drug, which I'll talk about in a second.
We have a custom applicator tool that facilitates insertion of the implant in a primary care in-office procedure that could be accomplished by a Physician, Physician's Assistant, or a Nurse Practitioner, very similar to what's necessary for Nexplanon, the contraception implant, or Eversense, the Commercial Implantable Glucose Sensor. We used this in eight human subjects earlier this year, and it went as expected and encouraging for our future progress. If we break down what the device consists of, there is the titanium reservoir, a high-concentration drug formulation. The gold material represents millions of Titanium Oxide Nanotubes, which is really the core innovation around which the company was founded. These nanotubes are vertically oriented, adjacently attached, forming a membrane. The inner diameter of these nanotubes, which you can see by electron microscopy over here, we can control on the nanometer scale with Angstrom-level precision. We grow these electrochemically.
If you look close, these openings are about 30 nm in size. Using a process called Atomic Layer Deposition, we can coat one atomic layer of Titanium Oxide as many cycles as we'd like to bring that pore size all the way down to zero or anywhere in between with extreme precision over the average pore size. Being able to have millions of openings with a material that's biocompatible and bio-stable, like titanium oxide, that we can control that precisely at the nanoscale is what enables this ultimately to work.
Now, when we get to a size that's close enough in size to a drug molecule where the interactions of the drug and the wall of the nanotube dominate the transport and the formulation properties are appropriately compatible, then we can achieve substantially constant release of a given molecule for many months at a time without any moving parts, without any of the complications that other previous device technologies have had that have led to some challenges with intermittent delivery and things like that. It's a passive, sustained release that can work with Peptides and Proteins like GLP-1s. We're excited about moving forward. Now, we've shown. Substantial in Vitro data on the left here and in Vivo PK data in animals on the right, demonstrating good translation and good performance that we're excited about. We've shown that we can achieve good activity.
In this case, we looked at liver fat that was reduced by 82% after a 12-week treatment duration from a single implant, which is consistent with what GLP-1 Monotherapies have shown in this animal model. We've shown durable weight loss after a single administration of an implant. This is preclinically, in this case, a 16-week treatment duration. We showed that when the implants are removed, the weight comes back, which demonstrates that we were delivering indeed active drug the entire time. The weight rebound is consistent with what happens when someone discontinues GLP-1 treatment. We tested this in a first-in-human study earlier this year that was primarily designed to assess safety and tolerability, to characterize the PK, and to understand translation. The doses were low. We were measuring weight loss, but we weren't expecting weight loss with these doses. This study completed earlier this year.
I'll show you the highlights on the next slide. We were able to demonstrate there were a couple of key things that we were looking for. First, we were looking for whether there would be any meaningful initial burst, which is something that implant technologies often have experienced. The second was, and this is a challenge that a different implant technology had faced in the past, intermittent dose dumping. In that case, the FDA attributed this to some of the clinical safety signals that were demonstrated. We had a very robust PK sampling plan in which we observed the absence of any evidence of intermittent dose dumping in the study. The implant was well tolerated. There were no serious adverse events in the study. The release profile was encouraging, demonstrating the potential for durable long-term delivery in a human based on what we had seen in our animal studies.
All of this data really just supported additional clinical development of the technology. Now, we are applying this today to our semaglutide implant, NPM-139, which is our focus going forward for a variety of reasons. The GLP-1 products, including semaglutide, have generated substantial sales with a remarkable 32% compounded annual growth rate expected. I don't think this is a surprise to anyone, given all the news around GLP-1 products. As I mentioned earlier, the adherence and persistence data is remarkably poor with these products, more than 50% regularly missing doses, more than 50% discontinuing by year one, and 75% discontinuing by year two. We're designing the initial studies to support additional applications such as Type 2 Diabetes. Other indications that are approved for semaglutide, CKD, and Type 2 Diabetes, MASH. semaglutide was the 2nd drug ever to get an indication for MASH.
Alzheimer's, Novo is expected to announce results of its phase III study in Alzheimer's patients, possibly by the end of this year. If that proves successful, the rationale for an implant in that patient population, we think, is pretty obvious, in addition to addiction and other indications that semaglutide and the GLP-1 class are pursuing. Now, the consequences of this persistence, sorry, the persistence data, just a little bit of a deeper dive here. 40% on semaglutide after a one-year period. As I mentioned in the last slide, only 25% staying with therapy over the course of two years. While this data was presented in the context of being better than older generation weight loss drugs, which is true, there's still a large opportunity to improve on the persistence that these products are experiencing and what is possible and what would benefit people, we think, as much as possible.
The consequence when someone discontinues treatment is severe. The weight comes back, and it comes back fast. There's a response that anyone, animal or human, experiences when their body is used to high levels of GLP-1 that are immediately withdrawn that causes them to feel starved. We've seen when food consumption has been measured, larger food consumption than had ever been the case. In our own studies in mice, when we put exenatide implants in, when we removed them, those mice ate 50% more food than the control mice ever did. There is this biological response that causes this hunger-mediated weight rebound. This data came from the Wegovy Clinical Program, STEP one, in which they measured after 68 weeks of treatment, and then they discontinued how quickly the weight comes back.
It's a real problem when you have 50% of people not taking the medicine as recommended, when you have 75% discontinuing. The long-term outcomes, benefits of the class, were demonstrated with trials that ran for years. The cardiovascular benefits, all of those outcomes require that people continue to use it. If they yo-yo with their weight, they go on it for six months, the weight comes back a couple of months later, the cost-effectiveness of treatment goes out the window. We really need to find a way of sustainably keeping the weight off so that the long-term outcomes can be realized. That's where we think these implants have a real place. We've done some of our own preclinical weight loss data with semaglutide in our implant. We've been able to sustain 20% weight loss over, in this case, a seven-month duration after a single implant.
We did remove animals for characterization purposes along the way, which led in part to the error bars increasing. Overall, we were able to maintain the 20% weight loss. The data is trending in a way that we anticipate being able to get this to become a one-year implant as well. Thank you. A little bit more stakeholder adoption data that we think is relevant. There have been patient surveys. On the left, there's some data with patients who were asked whether they would likely, definitely, unlikely, or definitely not get and use a six-month exenatide implant. For those familiar, this was data that came from Intarcia's device, ITCA 650, but a six-month GLP-1 implant.
What we noticed from this data was, first of all, the numbers of people that said they would likely or definitely get and use an implant were pretty high if it was FDA approved, prescribed or recommended, and covered by insurance. More interestingly, we saw that those that were currently on a GLP-1 were more likely than those that were naive to treatment. This supports our initial intention to position this in the maintenance-phase treatment. People that are already titrated, they already know that they like the drug, are willing to commit to 6 or 12 months at a time, that would then use an implant for maintenance and potentially on the back of treatment by any of the 50 or more compounds that are in development. Initially, putting it on the back of semaglutide initiation makes sense.
We think that there could be a role for this on the back of any of the newer medicines that are being developed to enable faster, more tolerable weight loss, of which there are numerous. The last couple of months have been busy for us. Two couple of months ago, we announced that the clinical study was complete. We announced preclinical weight loss data with the semaglutide implant. Last month, we disclosed the initial intended clinical program details for the semaglutide implant and that we anticipated initiating that program in the 1st half of next year. The clinical study designs that we intend at the moment are to start with a phase I study that is intended to de-risk a phase II study.
We are preparing to be ready to conduct the phase two in parallel based on the results we got from LIBERATE-1, the first-in-human study, and the preclinical data we have with semaglutide. We do think it's important to demonstrate that semaglutide is being delivered in the way that we expect in a human before we proceed with the larger phase two study. We think we can get adequate confidence with a relatively short study, comparing an exposure, a dose that we expect to achieve similar exposure to the starting dose in the Wegovy titration schedule for a 28-day period. We intend to start this in the early part of next year.
This is all part of a march to get to a phase II study where, consistent with our strategy of positioning this in maintenance to titrate subjects up to the highest approved dose of semaglutide and then randomize to three different doses of the implant for four or six months. Six months is what our commercial target would be, but for a long enough period of time for us to establish which dose we would want to move forward with in subsequent potentially registrational studies, and to compare this with placebo as well as with continued Wegovy treatment. We want to understand what dose is necessary in maintenance for keeping weight loss off, which is still an unanswered question. There are companies running studies where they've downtitrated after weight has been lost to understand.
We don't know what dose we're going to need, but that's part of what the study will reveal. We have a seasoned team of leaders. I'll quickly mention Lisa Porter, our Chief Medical Officer, who oversaw the successful approval of Bydureon and the once-weekly exenatide when she was at Amylin years ago, had a lot of extensive drug development experience in the metabolic space, knows GLP-1s extremely well. Truckley, who is our COO, has overseen successful development and approvals of complex drug device products, including Exubera, the 1st inhaled insulin product that was approved. Not commercially successful, but successful from a manufacturing operations FDA inspection perspective. We have a deep, seasoned team to help us succeed in our efforts going forward.
We have a manufacturing facility in Alameda, California, in which we produced our clinical materials for the first-in-human study earlier this year and which has the capacity to support early commercial-scale manufacturing as we proceed and start to get ready to think about late-stage clinical and ultimately commercial. We already have the facility and a lot of the team that we would need to be able to succeed in those efforts. I will just finish by reiterating, we are the only GLP-1 implant actively in development for obesity, utilizing what we anticipate to be a convenient once or twice-yearly dosing that we think will address some of the key unmet needs in the space. With the unique modality, we think this may enable us to expand the market to get to some of the underserved and unaddressed populations that exist today.
I think I had one minute left, so I'll finish 45 seconds early. Thank you.
Adherence is such a phenomenal problem in the industry, right?
Yes.
How do you know when you are going to inject in it? You have to discuss all medicines are compatible with it. Sometimes the doctors have to change the medicine because of how do you manage that when it is implanted? Do you do a Preclinical trial test, a Pre-implantation test with the patient so that then you can implant it or are you pulling back and forth the implant?
I think that helps support the rationale for Maintenance-phase treatment, right? The patients would have to be titrated on the drug for that period before they switch to Maintenance-phase treatment. If someone is titrated on a different drug, then the question is, switching studies have been done without problems before.
Intarcia did a trial with liraglutide to their exenatide implant. Other companies have done the switching studies. GLP-1 activity is reasonably maintained across the different molecules. Off-target effects of peptides are much more rare than they are with, say, small molecules. Your point's a good one, but I think that there is ample evidence to suggest it's unlikely to be a massive problem.
The other thing is that implant always occurs in a Gaussian manner. It doesn't matter. You cannot change science. You are making implant on a flat step. How is that possible? When you implant something scientifically, you either get a peak in a Gaussian curve. Therefore, depletion will occur in that basis. You are saying that it's on a step basis.
Below a certain concentration, the membrane restricts the ability for the rate to be any faster than it would have been. All the nanotubes are saturated.
As soon as a single vacancy occurs, there are many molecules in the reservoir competing to fill that single vacancy. That's the interesting observation that occurred that explains why these nano.