Everyone, welcome back. We have Citizens, Inc., trades on the New York Stock Exchange under the symbol CIA. Happy to welcome President CEO Jon Stenberg, who's joining us from the phone, as well as CFO Jeff Conklin. Welcome, gentlemen. We're very excited to hear your update today.
We're excited to be here. This is Jon Stenberg, and Jeff is apparently on the video. I could not get my video link to work, so I apologize. No problem. We'll work around that. I'm on page five, Jeff, so I thought we'd just start by giving everybody a quick overview of Citizens. We want to also leave plenty of room for Q&A, so we're not going to cover everything in every single slide. We're going to hit the high points. All right. Overall, basically, we're a life insurance company. That means you get all the advantages of what you might expect from a life insurance company: safety and stability and predictable outcomes. We have a good growth story. That's one of the things we're going to want to talk about today. Real quick, as an overview, we have almost 250 employees.
We have policyholders in more than 75 countries. We're up to 8,000 independent agents, which is a big jump up from 2,000 just a couple of years ago. $1.7 billion in assets, and we've crossed over $5 billion in insurance coverage. Excited about that. Last year, we did $173 million in premium revenue. If you look at the map, you can see four dots there. Austin, Texas, is where our headquarters is. We've got an operation in Puerto Rico that serves our international market. We put a dot on South America just because South America has been so important to our premium revenue. As you can see on the right, most of our non-U.S. countries are South American. You see a dot in Asia. That really represents all of Asia. Most of our premium there comes from Taiwan.
The dot's not on Taiwan, as I was reminded recently in a visit to Taiwan. If you look at the premium revenue distribution, you see Taiwan, the United States, and all the other countries, including most of the others, really is South America, with a little bit of Central America mixed in. Colombia is a big country for us, Venezuela, Ecuador, and Argentina. Why don't we go to the next page? What makes us special internationally is that our whole life insurance, which is your basic, standard, beloved whole life policy, it's in U.S. dollar denominations, though. That makes it very attractive for those who are in regions that have a history of perhaps currency devaluations or political instability.
If you were a successful person or upper middle class in, for example, Colombia or Argentina, you may want the one thing that you really want to be safe and secure, your life insurance, to be in U.S. dollars so that your family is covered really no matter what. That is a key attractiveness to many of our international customers. That is why we have policies in over 75 countries. We have been 45 years in that market. If you look at some of the countries that we are very successful in, Venezuela, Argentina, Colombia, these are countries over the last 45 years, they have gone through a lot. We have been there through the thick and thin. It is kind of a competitive advantage we have because we understand how to do business in countries that go through these instabilities.
We're currently still very successful in Venezuela, for example, which has a reputation for obvious reasons of being a country that's hard to do business in. Domestically, we've really—this is where most of our growth is coming from last year. We'll share some numbers with you how fast we've grown our premium in the last couple of years. Most of that is coming from our domestic life insurance operation. We went from doing business primarily in three states a couple of years ago to—we're up to 43 states now. We've dramatically expanded our agent base from less than a couple thousand to, as you saw on the previous slide, 8,000. We're in the final expense business. I can explain that a little bit more later.
Lastly, we have had a successful operation primarily in Louisiana, but we also do business in Mississippi and Arkansas. That is really for what we call the home service market, which is kind of neighborhood-embedded agents that have a tight relationship with us. We train them, and they sell pretty much exclusively to us. They serve neighborhoods for burial insurance. We have been in that market for 70 years. Let's go to the next page. I talked about the U.S. dollar denominated products. I'd like to just briefly speak to the expertise in Latin markets. Now, if you—roam our halls and anyone on this call is more than happy to—we'd be more than happy for you to ring us up if you're in the area, and we'll give you a tour.
If you got a tour of our home office, you're going to hear different dialects of Spanish because we've got employees from, I think the last count was 25 different countries. A lot of those are Latin countries. We understand the difference between Ecuador and Argentina or Venezuela and Mexico or Puerto Rico and Ecuador. We have folks that were born and have these cultures in them. We can often pair up our clients with somebody that is from their country of birth to service them. That's going to give us a tremendous advantage when we decide in the United States to really decide to grow into the Latin American market, the Latin-speaking market in the United States, the native Spanish-speaking population that is very rapidly growing in the United States. It's a large market. It's an underserved market.
It's in a market that we intend to tackle before too long. Okay. Niche markets. Internationally, we do a lot of professional athletes. We work with international brokers. I really want to tackle our white-label strategy. That's our strategy in the United States. If you make a certain level of a commitment to us, we will white-label our products for that distributor so they have a unique name that they can take into the market. We administer that. We underwrite it. We pay the claims. We do all the work. It's their name that they selected. That gives them a unique edge as they recruit folks into their distribution operation. It makes them phenomenally loyal to us because we're the ones that are providing them with their specially named product.
It's a capability that is difficult to do unless you bake it in from the very beginning. That's exactly what we did. That's not an option that a large company would offer a distributor, typically. Product development. We're expanding our product base and our capabilities to serve markets around the world. That's something that we intend to continue to do over the years. We've been investing in our technology capabilities in order to be able to do that. Okay. Why don't we do a quick mention here? We have end-to-end capability for customers in Spanish, Mandarin, and English. We'll be adding or re-adding Portuguese to that list soon. I'll explain why. Okay. Why don't we touch briefly on page nine, the company timeline? I just want to show that we've been around for quite a while internationally.
Our journey has really led to us having a tremendous amount of international capabilities. We are not in a lot of countries. Our model, it's very easy to grow. We can grow with the current products. We can grow with the current people and processes into new countries without a huge investment. That is a key growth opportunity that we intend to take advantage of in the years to come. Okay. Let's go to the strategic roadmap here. You can see we have projected growth. The growth really is going to be driven by two things. First, we are growing tremendously fast domestically. Our revenues used to be—our first-year sales used to be—and our revenues used to be 70% international, 30% domestic. Our first-year sales in 2024 were flipped around.
It was more like 70/30, 70% domestic and 30% international because we grew our domestic operations so quickly. The long term, I would expect that to settle around 50/50 for our overall premium revenue. That gives you a good mix of the stability of the domestic markets along with the growth opportunity in international. I think that's a good place for us to strive towards long term. We have a lot of opportunity to grow internationally. I mentioned earlier we can grow into new countries without a huge investment. You want to make sure you have the capabilities for language. We don't have to set up a lot of brick and mortar. There are a lot of things we don't have to invest in for our model to work into new countries. We have identified 50 countries that have near or mid or long-term growth opportunities for us.
We have a long roadmap of potential growth that goes well past the next decade. Why don't we go to the next slide?
Slide 11, Jon.
Yeah. Slide 11. We'll do a little bit of bragging. We issued more insurance than we ever have before, $1.1 billion. That is a 54% year-over-year increase. For a 50-year-old company, I've never seen that kind of growth in my career. This is my 35th or 36th year doing this. I can just say that's incredibly fast growth. We're really excited to be able to report that much growth last year. We cover more policyholders and more face amount than we ever have before. Our number of producers has really grown, 72% year-over-year. Nine consecutive quarters of first-year sales growth is really something to be proud of.
What are our priorities for this year? We want to continue to grow premium revenues, yes. We really want to focus on quality and make sure that our level of productions are sustainable and profitable. That is a big part of our efforts this year. We want to make sure that we rein in expenses as we grow. Obviously, for obvious reasons, we do not want expenses to grow as fast as revenue. We are looking at things like taking advantage of international labor markets and things like that to provide excellent customer service without having expenses rise as fast or faster. That is a key focus of ours, expense management. Obviously, that will lead to increased book value per share, which is, in the end, what we really do focus on. Okay.
Okay. I can take it from here, unless you have something.
Yeah. We'll let Jeff take it from here. I'll be open for Q&A later.
This slide is busy. It has a lot of information. It's more for the reading of information. I do want to touch a couple of things that Jon did not already hit on. We've had over 20 years of positive net operating cash flows. We do have a share repurchase program available and authorized. We currently do not have any debt. Kind of a proud thing that we had two years ago was we got our first A.M. Best rating for the first time ever in the corporation. This is for you to read offline. I'm not going to hit all the components of this slide. Jon's already told you about the $1.1 billion.
That is really due to our improved sales, our new products, both domestically and internationally, that we have come out with the last couple of years, as Jon said earlier in the company timeline, over 20 new products and enhancements. I am going to skip that slide. Shareholder returns, a focus of ours is to grow book value per share. It is a management incentive as well to continue to make sure our book value per share, excluding changes in fair value on our fixed maturity securities, continues to grow. As you can see, we have had that grow for four straight years and would anticipate this to continue. We are constantly making process improvements, technology, and some efficiencies. I think one of the biggest things we did this year, actually, there are two things, is in underwriting.
We continue to simplify, advance into kind of third-party information to allow us to underwrite faster and continue to always mitigate risk when you're in the life insurance business. Reinsurance, so we continue to expand our reinsurance strength with a new treaty that we put in place with RGA during the year to support our growth initiatives. Overall, we have a kind of a low-risk profile balance sheet. We really sell traditional products. We don't have any exotic products like many other insurers may have. We have a very conservative investment approach. We want to be prudent with our money. Yet we will try to seek yield enhancements as we see fit to at least preserve our principal and maintain all within the state guidelines that we have to follow. We use global reinsurers.
I said reinsurers earlier, but these are well-known large global reinsurers: Swiss Re, AmTrust, RGA, and Munich Re that we use both internationally and domestically. The majority of our assets are high-quality, well-diversified fixed income securities. It makes up almost 87% of our portfolio. 99% of that are investment grade. We are very diversified across asset class, sector, and power, with an overall credit rating of average of A-rated bond portfolio. Life insurers are primarily regulated, of course, by state insurance departments. In our case, we have a Puerto Rico regulator. There are specific regulatory guidelines we need to follow to stay within regulatory capital requirements. On the left side, that's our RBC calculation. That's our U.S. rating. Our capital ratio is 623%. We focus on not going below a 350% RBC. If you looked at last year's deck, this actually increased over 150% from last year.
On our Puerto Rico company, the ratio of 6.6 is conservative, and it's within our targets of where we want to be as a company. The thing I don't remember if I touched on this on an earlier slide, but we do have the ability to raise capital or raise, sorry, grab. We have a line of credit of $20 million. In addition, Citizens is an insurance holding company. They have their own cash equivalents. They have right around $20 million that can help deploy to support growth initiatives for the organization. Last slide I wanted to hit before we hit Q&A. We're going to show you kind of non-GAAP revenues. This is a, sorry. This is revenues. And this is a non-GAAP measure. We've adjusted revenues for investment-related gains or losses, in this case, primarily losses in 2024.
These happen to be non-cash-related losses, kind of fair value instruments that we have to help diversify our portfolio. If you back out those fair value fluctuations, our revenues have increased year-over-year. For those of you who have read our press release and maybe the 10-Q, this is our first increase in revenues in seven years. If you go back to the company timeline, the focus since 2021 is to get revenues growing again. Everything that Jon touched on is what is leading us to start growing again, which has been a focus, primarily since 2021 when we became a non-controlled organization. Anna, you can come in.
All right. Great. Thank you, guys. Domestically, what differentiates the life insurance and final expense products leading to new sales? Who is the target market?
Jeff, I can take that. Final expense, it's really a term that is meant to distinguish life insurance. It's life insurance, like any other life insurance would be in the United States. It's a term meant to distinguish policies that are meant to be sold to often underserved markets. They're smaller policies. They're affordable policies. They're often for folks that relied on workplace life insurance for their entire career. They retire, and at age 60-something, they realize they don't have any life insurance. They often don't need a huge policy at that point. They'll turn to a company like us. That's the market that we focus on currently. There's lots of opportunity to grow northward socioeconomically and also into younger ages. That's something that we might be exploring over the months and years.
Sure. If you can elaborate on your strategy for supporting current international agents to expand within Latin America, specifically growth opportunities, where do you see that in the regions contributing to your long-term growth prospects?
Yeah. There are two questions in one there. I'll first tackle the how are we supporting the agents. There are two ways we do that. There are our ease-of-use efforts. A lot of our technology spending right now is for what I call agent ergonomics, making their life easier. Also, product development, offering them new products to sell to their clients so they can often solve more than one problem for each visit with the family. There is a tremendous amount of growth opportunity. As a matter of fact, this year, we're launching what we internally call Americas Growth Plan.
That is to really make sure that we have exposure to and are growing in countries that we see as having a lot of opportunity. El Salvador, for example, is a country that most life insurance, and many still do, avoided like the plague because of their high crime rate. That has largely been solved. That is in the news, obviously. Life insurance companies have not reentered. We have an opportunity there. Honduras and Guatemala are in the beginning stages of their, I would guess, lowering crime trend, like El Salvador's has. We see tremendous opportunity there. Belize is awash in retiree dollars. There are opportunities there. Panama, Costa Rica, Nicaragua, also opportunities. The Caribbean. The big one, which is Brazil in South America. We are not currently selling in Brazil. We intend to reenter.
That's going to be a tremendous opportunity for growth just in the Americas.
Sure. Absolutely. Maybe talk about what investors might be misunderstanding about Citizens and why now is a good time to look at the stock.
I'd first start off by saying we're not a bank company. We're not a P&C company in Florida. There are a couple of Citizens out there that have often had bad news associated with them. We're not those Citizens. We've stayed out of the news. We happily and quietly are doing our life insurance business in a safe and secure way. As I mentioned before, we really like the fact that we run ourselves conservatively. Our investments are conservative, as you heard from Jeff. Our capital ratios are conservative. Our cash management and everything we do is conservative.
We have this tremendous growth opportunity with as many as 50 countries that we could be growing into in the next years and decades to come, in addition to the growth we have domestically. It is a really, I think, a powerful combination of the safety and security of a life insurance company, which normally grows at, I would say, maybe the pace of inflation, combined with a company that has all these growth opportunities and special capabilities that others do not have.
With your rapid agent recruitment growth, what steps are you taking to maximize agent productivity?
Ease of use. We really take the time to listen to agents and figure out what are they not getting. In the markets that we are at in the United States, for example, it is kind of dominated by smaller players that are regional. They are not high technology.
They're certainly a little bit slow-moving, I might say, when it comes to seeing what's going on in the market and figuring out new ways of doing things. We're looking at making the lives of our agents a lot easier. They appreciate that. We still have a lot to do on that. I think we'll be ahead of the curve in ease of use for years to come.
I know you've been traveling around the world. Tell us, what's the current political climate like? Posing any hurdles or opportunities?
Yeah. I hit nine countries in the last month. In almost every place I've gone, obviously, there's a lot going on in the news in the United States politically. Most of our customers that buy our U.S. dollar denominated products are going to be fiscally conservative in their lives and conservative in general.
They see what's going on in the U.S. with DOGE and a lot of the cutting of the expenses. They're looking towards a potential balanced budget. They really like that in terms of the strength of the dollar long-term. That's something that would worry you if the U.S. is in out-of-control spending with spiraling debt and you're stuck in a contract you're expected to have for the next 50 years. If anything, that has created an opportunity because a lot of our customers, they don't listen to economists, and they don't listen to the news on this. They listen to their gut instincts, really see the potential for a more balanced budget as a great opportunity long-term. There is a lot of political instability that continues internationally [crosstalk]. That's really where our opportunities lie.
It's a lot of currency devaluation over the years, a lot of political instability in countries that we are growing into or are successful at. All that opportunity, good and bad, whether it's good, it creates an opportunity for us because they really want the stability that they're not getting in their home country. Even when things are going well, like things are looking up in Argentina, for example, that gives them, often will give them, the liquidity to buy the life insurance that they couldn't afford when times are bad. Either way, it really does help a company like ours that is there to be the safety net for a lot of the world.
Good to know and good to hear that, Jon. Thank you, Jon and Jeff. We are out of time, but we appreciate this update. Congratulations on all of this. Please come back, hopefully, again, real soon with some more good updates like this.
Thank you. Great. Thank you.
All right, everyone. We'll be right back.
Next, we have Vivani Medical Inc. It trades on the NASDAQ under the symbol VANI. Through leveraging its proprietary NanoPortal platform, it develops biopharmaceutical implants designed to deliver drug molecules steadily over extended periods of time with the goal of guaranteeing adherence and potentially to improve tolerance to their medication. Please welcome its CEO, Adam Mendelsohn. Nice to see you today, Adam. Welcome to the conference.
Good to see you as well. I'm happy to be here.
The floor is yours [crosstalk]. Call me back when you're ready for questions.
Fantastic. It is a pleasure to be back here at the Emerging Growth Conference.
I look forward to sharing some really exciting updates with regards to what our company has been doing so far this year and also provide an overview of what Vivani Medical is working on. Before I get to the slides, I'll just start by mentioning, as Anna mentioned, we're developing miniature implants that can be placed under the skin and provide steady delivery of chronic disease medications. We're focused initially on the GLP-1 class, which everyone is now familiar with because of the blockbuster success of products like Ozempic and Wegovy and Mounjaro and Zepbound.
With over a billion people living with obesity and these highly effective treatments available for allowing people to lose and maintain that weight loss for extended periods of time, what we're focused on is how we can help make sure that people can maximize the benefits of these treatments by removing the human element that gets in the way of real-world health outcomes with only about half of people regularly taking the doses as recommended. This has both efficacy as well as tolerability consequences that I'll talk about in the deck. We are very excited about the prospects for our implant to potentially improve significantly on both of these elements in the blockbuster GLP-1 class. A couple of disclaimers here on this slide. I'll move to slide three here.
We do have an outstanding team with decades of experience developing drug-device combination products, including the world's first inhaled insulin product, as well as being involved in the approval of the first GLP-1 products that were ever marketed and commercialized. We are prepared with the capabilities and experience of our team to continue to execute on our plans, ultimately towards success. Let me just, before I get into more of the detailed slides, who are we? What are we doing? We are a clinical stage company. We started our first clinical trial at the end of last year. It rapidly enrolled. We have implanted a number of people who have all tolerated the implant procedure well. This is part of a portfolio of ultra-long-acting drug implants that are designed to address, as I mentioned at the beginning, the challenge of medication adherence.
I'll show some data a little bit later. Potentially, we think by eliminating missed doses and providing steady exposure levels, reducing some of the side effects, which represent the largest complaint associated with this class of treatment. Our lead program is NPM-115, which is an exenatide implant that's currently in our clinical study, which we've branded Liberate One. We are also prioritizing the development of NPM-139, which is our semaglutide implant, for which just yesterday we announced some very positive preclinical weight loss data. Semaglutide is the drug which is in the drug products Ozempic and Wegovy. Exenatide is also a GLP-1 agonist that was in the first commercialized GLP-1 products, Byetta and Bydureon. These products are being developed for obesity treatment, chronic weight management, and are being designed for once or twice yearly dosing. NPM-115, twice yearly dosing.
NPM-139, we think, has the potential for once yearly dosing. We also have in our pipeline NPM-119, which is being developed for type 2 diabetes. The first indications of GLP-1 agonists were for the treatment of type 2 diabetes. They have expanded to treat obesity more recently. That is where a lot of the market excitement has been. These are still highly effective treatments for type 2 diabetes. We want to make the product available as widely as we can. During this year, we anticipate possibly multiple, potentially transformative milestones, including the results of our first clinical study, which is currently ongoing, continued development of our pipeline programs.
With the cash that we had, $18.5 million at the end of last year and an $8.25 million financing that we just announced this morning, we have runway into the second quarter of 2026, plenty of runway to be able to meet many of our near-term milestones and continue developing the programs. As I mentioned, NPM-115 is in a phase one clinical study. I'll tell you more about that as we proceed. NPM-119 has had a study cleared with an IND that's cleared by the FDA. Our strategy is to prioritize the obesity and weight management application of the technology, which is NPM-115. As we proceed in development, incorporate the evaluation on the treatment of type 2 diabetes in addition as part of the NPM-119 development program. NPM-139, the semaglutide implant, we just showed some very positive weight loss data in a preclinical study.
That has now moved from the feasibility stage into the preclinical stage. We're advancing that ultimately towards clinical development. We're very excited about that. We have a partnership with an animal health company to develop a version of these GLP-1 products to treat companion felines who have diabetes and obesity. We're excited about making this technology as widely applicable, including to our animal friends as well. Let me tell you about the product and the technology. This is the first of its kind technology to now be in a clinical study based on a nanoporous membrane consisting of titanium oxide nanotubes that control the release of medicine from a high-concentration reservoir constructed of titanium. When fully assembled, the only path for drug molecules is to go through the nanotubes, which ultimately results in very steady and substantially constant release of the molecules.
The implant is placed just under the skin for the first clinical study. It's going in the inside of the upper arm, which is a similar location as both the contraception implant Nexplanon as well as the implantable glucose sensor Eversense, both commercial products administered in an outpatient setting with few complications. The product that we're evaluating in the first clinical study is, you can see on the top right, very small, about the width of a dime. And we have a custom applicator tool that facilitates the insertion of the implant to make sure that it's placed shallow, which is ultimately important, and to facilitate the ease of the procedure for the healthcare practitioner. The technology is based on, as I mentioned in the last slide, this array of titanium oxide nanotubes represented in the gold-colored material that you see on the right half of this slide.
When the membrane is welded, the titanium portion of the membrane is welded to the titanium reservoir, then the high-concentration drug formulation has to go through these very high aspect ratio nanostructures to ultimately become available. To give you a sense of scale, these nanotubes, which are vertically oriented and adjacently attached, if the opening was the size of a golf ball, the length would be about 10 stories tall. You have a very narrow path that the drugs have to traverse in order to be able to become available. There are millions of these openings. What we've shown is that as grown, the nanotubes have an opening that's about 30 nanometers in size. 100,000 nanometers would be the width of a human hair. These are very, very small openings.
We can precisely tune the size of this opening at the nanometer scale using a process called atomic layer deposition, where we take on the top right, you can see an electron micrograph of what the material looks like as grown initially by growing its anodization process, kind of like a chrome plating a rim that goes on a tire. We can deposit one layer of pure titanium oxide along the entire length of all the nanotubes to bring that 30 nanometers all the way to 0 nanometers or anywhere in between with extreme precision over the average pore size. Titanium oxide is both biocompatible and biostable, which enables it to ultimately be applied to this particular application.
Now, when this happens, above a certain concentration in the reservoir, the rate of delivery can't be any faster because the nanotube, that long, narrow structure, ultimately constrains the transport of the molecules. Standard concentration gradient-based diffusion breaks down. You end up with substantially constant release, as we've shown here on this next slide with a couple of different doses. On the top on the left, you see a three-month substantially constant dose. On the bottom, you see six months of constant delivery, even as the concentration is decreasing in the reservoir. That really is the fundamental technological development that this nanostructure was able to provide without moving parts or electronics to be able to achieve a passive, constant rate delivery of drugs.
Now, on the right half of this slide, we think particularly important for GLP-1 agonists and possibly other drugs as well is, even at very short time intervals, the change in delivery rate is very small. It is very minimally or almost non-fluctuating, which is what you would expect based on how the physics of this kind of system would work. It is passive. Once it is in the body, it is just this material that is constraining the motion of the drugs. What that enables is the absence of fluctuations in exposure, which can be responsible both for, in the case of GLP-1s, when the exposure level goes low, then people get hungry and they eat more. They experience something called hunger rebound. When the exposure comes up quickly, they can get the side effects, the gastrointestinal effects.
The technology is really, we think, perfectly suited to the delivery of GLP-1 agonists. To the extent this is important for other drugs, we're also excited about its possibility. Although most of the rest of the presentation is going to focus on our lead products, it is a platform technology that we expect to ultimately apply widely across multiple disease areas as we proceed. The opportunity in the GLP-1 class for type 2 diabetes and obesity and many of the other indications that are being explored with great promise is too enticing and exciting that that's where we've decided to keep our focus for the time being. There was a—we aren't the first company to think about applying a long-term implant to the GLP-1 class.
There was a company which, at the time, was developing a product with a lot of excitement around it that ultimately met its demise because of what the FDA indicated in a hearing were fluctuating release profiles associated with the delivery technology, which is why the graph that I showed you earlier demonstrating very steady delivery associated with this different delivery technology is critical and addresses the fundamental reason why this other company's product on the left did not get approved. We believe it enables us a good chance to obtain regulatory approval and test the commercial hypothesis, which both they and us think is extremely attractive. Moving on, our lead program, NPM-115, is exenatide for chronic weight management. There are actually almost a billion people living with obesity now. That figure is a little bit outdated.
With the opportunity for a six-month product to have a beneficial impact by guaranteeing medication adherence and steady drug levels, we think it can be a very attractive alternative to needing to take lifelong weekly injections or pills, which are in development, and for a meaningful segment of the population be the choice that they ultimately select when we get through the approval process. Now, I've mentioned poor medication adherence. There's also persistence, which is people discontinuing their treatments. Here is some data showing with semaglutide, which is the drug in Ozempic and Wegovy, after one year, only about 40% of people are still on therapy. Actually, more recent data has shown after two years, only about a quarter of people are still on therapy.
The problem when people discontinue is that they increase their food consumption and they gain the weight back, which we believe an implant can provide an attractive option that can help keep the weight off and provide a more convenient long-term maintenance solution for people that are seeking long-term maintenance of the weight that they've lost on these therapies. Here is a little bit of data demonstrating what's happened in a clinical study with semaglutide that when discontinuation occurred, the weight came back quickly. That's what you see on the left of this slide and on the right.
What we've shown ourselves, and this is consistent with others, is when we removed an exenatide implant in an animal study and measured food consumption, these mice ate 50% more food than the control mice ever had eaten, which is consistent with this hunger rebound response being ultimately responsible for the challenges associated with discontinuing treatment. Now, with our exenatide implant, we've shown comparable weight loss, 20%, compared to a sham implant control with injections of semaglutide. Our weight loss curve is extremely smooth, which is what you would expect from a product that delivers very steady doses of the medication. We've also shown a significant reduction in liver fat in obese mice after 12 weeks of treatment with a single administration of our exenatide implant. The GLP-1s are showing promise in fatty liver disease and MASH as well as obesity and type 2 diabetes.
have also shown very durable weight loss. This is a study in which we have, for a four-month duration, we had an implant. This was in rats. The weight loss was significant and maintained over the entire four-month duration. In a recovery group on the right half, you can see when we removed the implants, the weight came back, as you would expect, which is consistent with the need for consistent and sustained medication delivery. We have shown the ability to deliver this compound for a six-month duration, which is the target commercial product profile for the exenatide implant and the initial version of the semaglutide implant. Now, our first clinical study, which is ongoing right now, rapidly enrolled in just four weeks, 24 subjects across two sites. This is very fast enrollment.
We were very pleasantly surprised with how much interest there was from people to participate in our study. Most of the subjects have gone through the titration period with 0.25 milligram semaglutide and 0.5 milligram semaglutide before being randomized to receive either our exenatide implant, the once-weekly marketed exenatide Bydureon, or continued semaglutide treatment. We have had several subjects that have been implanted, all of whom have tolerated the insertion procedure well. I very much look forward to sharing results when they are available as we proceed with the study. I do expect to have the top-line data around the middle of this year. On this slide, you can show the history of how we got to this point. Last year, we announced some very compelling preclinical weight loss data, which led us to shift our strategy from diabetes to focus on obesity.
We are in the middle of our first clinical study and very excited about those prospects. I am going to talk a little bit about the diabetes application, which is NPM-119. I will not spend too much time, and I'll make sure there's time for questions afterwards. The adherence rate of diabetes products, and adherence is defined as how consistently people are taking their medicine, are only around 50%, which, as described before, can have significant consequences, not just in terms of efficacy, but also intolerability when people resume treatment after they've allowed their drug exposure levels to go down.
The opportunity in diabetes, we think, remains worth discussing for a number of reasons, including some patient research, which was conducted with a six-month GLP-1 implant, in which 56% of patients who had been asked whether they would likely or definitely get and use such an implant, who had already been on GLP-1 treatment, if it were approved by the FDA, recommended by their physician, and covered by insurance, said that they would.
This is a very large proportion of the population and motivates us, in particular, because the number of people that were on a GLP-1, as opposed to never been on a GLP-1, who suggested that they would use an implant, was greater, which motivates us to initially target the maintenance phase of treatment, where people who already know that they like and can adequately tolerate the drug, who are willing to commit to six months or a year at a time. The opportunity there, we think, is truly tremendous. Lastly, I'll quickly mention the program for which we had a data update yesterday morning, which is NPM-139, which is the application of this technology to semaglutide, which, between Ozempic and Wegovy, generated $25 billion in sales last year.
We think the opportunity to present an implant that can make sure for once or twice yearly administration, the semaglutide treatment can be provided is really tremendous. We showed over a 91-day period, nearly 20% weight loss by day 14. That was maintained through the 91-day treatment period after a single administration of the implant. We have shown six months of therapeutic levels with the semaglutide implant as well. We are looking forward to extending the duration of demonstrated weight loss and ultimately advancing this program into human studies. With that, I'll just wrap up with reminding everyone we are a clinical stage biopharma company developing a portfolio of miniature ultra-long-acting drug implants addressing what we think are the largest reasons for poor real-world health outcomes for chronic diseases, mainly medication adherence. We have our lead program in a clinical study now.
We're very excited about how that is going, how quickly it was enrolled. Expect to have top-line data in the middle of this year. We will be advancing our semaglutide implant, NPM-139, on the heels of some positive data that was announced yesterday. We're really, really excited about what the rest of this year can bring for us as we advance our pipeline of implantable GLP-1 products. With that, I'll take any questions that the audience may have.
Great. Adam, thank you so much. We do have some questions. First of all, Yana says, "Congratulations on the first trial. Can you give a little bit more detail, specifically size, duration, and what you are expecting?
Yes. Let me go to that trial. This trial is primarily designed to determine how the performance of the implant will translate from the animal studies that we've conducted into humans. We've designed for it to have a nine-week treatment duration. There are eight subjects that were enrolled that intended to go into each of the treatment groups, which includes the exenatide implant treatment group, the NPM-115 treatment group, the Bydureon treatment group, and the semaglutide treatment group. We're primarily assessing safety, tolerability, and characterizing what the pharmacokinetics are of our implant in these subjects over this period of time.
Because we expect that the dose that's going to be delivered will have some effect, we are measuring weight, and we are comparing the results with the marketed once-weekly exenatide and continued semaglutide treatment so that we will be able to understand, based on the exposure levels that are measured in the implant group, what kind of weight effects are observed relative to continued semaglutide treatment. We'll be able to assess any tolerability differences compared to semaglutide. We think that after the first administration, the fluctuations that happen with each dose of semaglutide could lead to more side effects that we think might not be as present in the implant, which will provide a steady delivery over that duration.
We are also going to be comparing the pharmacokinetics to the Bydureon group, ultimately as part of what we anticipate being a 505(b)(2) approval pathway to reference the safety data that Bydureon has already established, which should make for a much leaner and more efficient approval pathway than would be the case for a kind of a new chemical entity. That is why we have Bydureon in this group. Just to be clear, what we do not expect is to have demonstrated maximum potential weight loss with our implant at this dose. We will follow this study with a second study that will be dose ranging, where we intend to evaluate higher doses of NPM-115 that we would anticipate to ultimately demonstrate the maximum weight loss capability to identify the dose that would ultimately be the most effective.
After that second study, to design the third potentially registrational trial to evaluate that dose and generate the data that could ultimately support an approval.
Mark asks, "Is the delivery through the reservoir proprietary technology? And if so, how is it protected?
Yeah, great question. The nanotube layer itself, just the composition of the nanotubes, titanium oxide nanotube directly attached to a titanium substrate, that's the subject of a patent which is issued in the U.S. and in multiple countries. That was really how the company got its initial start. There is also another patent on the deposition using atomic layer deposition to tune the size of the nanotubes, which is also in a U.S. patent that is issued. There are many patents on the formulation of the drug that maintains its stability within the device that came later that further push out the expiration of the patents and even more that are in prosecution. What I will say is, I mean, all of our patents are mentioned in the 10-K. We will be shortly filing our next 10-K with a refresh of the patent landscape.
You can take a look at that for more details. It is very well protected out into the 2030s with some that could provide protection into the 2040s.
Vicky asks, "What other applications can this technology be used for? Can it be licensed?
Yeah, I think it can be used for really any application for which the drug molecule is adequately potent such that a clinically meaningful duration can fit into an acceptably sized device, where the drug can be made to be adequately stable so that it can stay active over the duration of treatment, and for which steady levels in the bloodstream are effective. There are a number of possible applications outside of GLP-1s. Each new drug molecule does carry new technical risk in formulation development. The formulation development work also typically would lead to new intellectual property. Because of how exciting the GLP-1 indications are and us already having demonstrated and reduced the technical risk of creating formulations that allow the technology to work with those drugs, that is where we are focused now.
As we expand, we will look to licensing opportunities, partnership opportunities to maximize the potential applicability of the technology.
Last question from Ari, "Will patients in the clinical study be placed on a full-service obesity management program, or will their diet and exercise program be at their own discretion?
Yes. Yeah. The recommendations to the subjects in the study are no different from anyone that is beginning GLP-1 treatment. There is no additional diet and exercise counseling associated with this study. It is a controlled study with different groups, with subjects who are all receiving the same recommendations. One thing I should caution is that it is also a small study with only eight subjects in each arm. It is not powered for us to really demonstrate with statistically significant differences between the groups. Again, it is primarily designed for us to characterize how well the technology is working in humans. The second study, once we confirm the performance of the technology, will be designed with enough power to make those kinds of comparisons.
We will consider including diet and exercise counseling to maximize the weight loss effects that will happen with studies that are designed to demonstrate maximum weight loss.
Sure. Fascinating time to be in this industry, for sure.
Yes. It's [crosstalk] definitely a rapid-changing but exciting time.
Yes, it is. All right, Adam, thank you for this thorough presentation. We'll send you the rest of the questions so you can answer on your own. Please come back to the conference in the near future with some more updates.
OK. Thank you, Anna. Thanks, everyone.
All right, everyone. We'll be right back.