Hi, good morning to those of you on the West Coast. Good afternoon to those of you on the East Coast. Welcome to the Sidonian Company May Virtual Investor Conference. The next company to present is Tivic Health Systems. With us, we have CEO Jennifer Ernst. As always, there'll be about 30 minutes for the presentation. We should have some time at the end for Q&A, so if you do have a question, you can type it into the Q&A box at the bottom of your screen. That is all yours, Jennifer.
Okay, thank you, Jim. Hello, everyone. I'm Jennifer Ernst, as you heard, the CEO of Tivic Health. What I'm introducing you to today, actually, for some of you that have heard about Tivic before, we are a company that is going through a major transformation, one that we began last year, but we've undertaken very aggressively since February. If you've seen Tivic before, this is a different company. If you haven't seen Tivic before, I hope you'll like what you'll hear that we've done and that we've brought about with the company. I would say that the market hasn't probably quite yet absorbed. Definitely a great time to be looking at, taking a fresh look at Tivic. I did say that we're going through a transformation. We started our life as a device company with an over-the-counter device, single product company.
Didn't quite get the traction on the market that I was hoping for from that particular product as we came to market. But we did build significant expertise in the area of immunotherapeutics, in the area of how the body interfaces with the immune system. Last year, we started reporting out data on a new program inside the company in vagus nerve stimulation, focused particularly on immunotherapeutic type applications of vagus nerve stimulation. I'll talk a little bit more about those later in the presentation. Earlier this year, in February, we licensed in a phase three immunotherapy program, a TLR5 agonist. When I say phase three, I do mean that all of the phase three trial work has been done.
A tremendous opportunity for the company as we reinvented in the immunotherapeutic space to bring in a robust, well-tested biologic asset, and with it, several members of the team that we were able to begin building out from. This particular licensing program included two molecules and included 40-plus clinical trials, 60 patents, and patents pending. It is at the phase three and moving into manufacturing for the first indication, which is acute radiation syndrome. We have five additional indications in the areas of oncology and longevity. Just yesterday, if we're talking about real-time news, just yesterday, we kicked off our GMP manufacturing. A very mature product line as we were beginning to introduce that to market. It complements our internally developed non-invasive vagus nerve stimulation program. What the company has today, we're now squarely, squarely positioned in the immunotherapeutic market.
Our bioelectronic program looks at regulating immunomodulation through the neural pathways, through the systems of the nerves and the electrical signals. This is generally very effective at, generally going to be very effective at downregulating the immune system that is overactive. Think about cardiac disease, think about neurologic. In the area of the biologic, it's focused more on upregulating and quieted immune system. We have two different approaches to be able to target different types of diseases that are related to immune system dysfunction. Whereas 12 months ago, we were a single product company with one commercial product in market, today we are a very diversified immunotherapeutics company with a scalable portfolio.
I'm going to take you through a couple of the line items of this portfolio today, just to give you an idea about the value creation that is possible from where we sit at this moment. The TLR5 program, this is the in-licensing agreement that we struck earlier this year with Statera Biopharma. Statera Biopharma had this asset that was sitting on the OTC, and they were looking for a complementary partner to be able to bring this particular program forward to commercialization and realize significant value out of it. Entolimod and Entolasta, these are the biologic drugs we licensed. These activate the immune system through a mechanism called the toll-like receptors. These are very primitive mechanisms in the immune system. They're very old, and they have pervasive effects.
Over $140 million had previously been invested in this program, government agencies like DARPA, BARDA, DOD, NASA, and a significant number of animal and human trials. For the first indication that we are going after, the acute radiation syndrome area, this results from high-dose short-term exposure to ionizing radiation. Think about nuclear disasters, think about dirty bombs, think about military-type applications, and think about any country that is using nuclear power as part of their power supply system, any kind of accident at a nuclear power site. This is very much a stockpile drug used for emergency situations. Phase three trials are complete. There is a high enough interest in the product that the FDA put Entolimod on a fast track for acute radiation syndrome. It has also received, for pediatric ARS, orphan drug status.
Several pathways can accelerate the pathway through the FDA. Considered a stockpile drug, and we are looking at emergency use designation opportunities that would allow us sales inside the U.S. and outside the U.S. prior to stockpiling under a full FDA approval. Manufacturing validation was initiated in May 2025. To look just briefly at clinical data, one dose of Entolimod administered 25 hours after radiation increased survival by threefold. The current drugs that are authorized for this use take multiple doses over that time and require additional supportive care. Entolimod itself had no signs of toxicity even at the highest dosing levels. Very safe drug and also showing very profound effects. Our key milestones as we look at acute radiation syndrome specifically, I've got two pathways on here. We started with the product in February.
We closed the license with Statera Biopharma. In April, we were able to secure meetings with the White House, with the senior leadership at the White House and FDA to be able to validate the pathways and to be able to talk about the emergency use opportunities. In May, we kicked off our GMP manufacturing. Several important mile markers come out of that, including the emergency use applications that we would be filing both in the U.S. and overseas, the FDA, the completion of our first GMP lot and moving into an FDA BLA process. If the emergency use is granted, that can greatly accelerate our time to a stockpile order. In one case, an accelerated pathway across the top. If the emergency use were not granted, we would be looking then at a standard BLA process, but under a fast track application.
That again can accelerate the time through the Biologic Licensing Application, through a BLA grant, and to achieve stockpile orders. I'd like to give an order of magnitude kind of idea about what we talk about stockpile orders. For example, Ukraine received $1.8 billion earmarked in the aid package for radiation countermeasures. Countries around the globe that use nuclear power, countries around the globe that have exposure during warfare to these types of hazards for their soldiers and for their citizens have already been approaching the company in order to talk about the opportunities to begin stockpiling. Stockpile orders are great for a company like us as we begin to build out our portfolio because with a stockpile order, we're not waiting for the doctor to decide, it's not getting it into continuum of care.
These are types of orders that can be in large quantity batches, begin to be filling those orders, and begin to stockpile immediately. While the acute radiation syndrome is an excellent economic instrument for the company in order to create a more or less self-financing opportunity, the real market we believe is probably in the oncology space. When we look at neutropenia, this is part of the cell damage that happens, low white blood cell counts when people are exposed to radiation, whether that's under the conditions I just described or more often in the medical use, the use of radiation in medical treatment, chemotherapy, radiation, there are some bone marrow disorders as well. This market alone, in terms of other indications that we can go after with the TLR5 program, this indication alone is projected to be over a $20 billion market by 2032.
Two-thirds of that market are in this category of drugs called the G-CSF drugs. Neupogen, Neulasta, these are brand names that you might be familiar with. Much of that market share is also in the biosimilars category. I'd like to show you a little bit about the mechanism of action behind the G-CSF and how it compares to TLR5 drugs. G-CSF drugs, the dominant drugs in the category today for treatment of neutropenia, can restore bone marrow function, treat after, but they can be used after exposure, and they basically run along this very narrow pathway across the top that I'm showing here. Entolimod, which is a new class, the TLR5 class of drugs, has a much broader mechanism of action, starts further upstream.
If you follow the TLR5 pathway here, it encompasses the same pathway as G-CSF drugs, but also has a number of other treatment parameters that it kicks off, including anti-apoptotic factors. This prevents the cell death, and this is why, as a mechanism, the TLR5 program is believed to be able to deliver both, has been shown to deliver effects on the bone marrow and the GI tract. Now, that's important when you're looking at cancer, particularly in the cancer treatment, many patients suffer long-term and die eventually from GI tract disorders where you can't get nutrients into the system. It's not about how much you eat. It's about whether your body can actually absorb the nutrients you receive. Being able to restore GI tract function and be able to offer a protective feature, a protective benefit, has significant clinical implications.
The market in this area, again, the G-CSF drugs alone, the Neupogen, Neulasta, and biosimilars are approximately a $7.2 billion market today and forecasted to grow to about $14.5 billion by 2032. They represent about two-thirds of the category of neutropenia drugs, and the TLR5 Entolimod that we have licensed has the opportunity to address and take market cap there. Two very exciting opportunities in our biologics portfolio. Finally, I'd like to speak briefly about our vagus nerve work. The vagus nerve is a particularly valuable medical target. It regulates most of the immune system. It runs from the brain to the gut, and it touches every single major organ in between. Vagus nerve stimulators as implanted devices have already been established as a treatment protocol in a number of different indications.
For an implanted device, you basically have to open up the neck, slicing open the neck, running the leads up onto the nerve fiber, and attaching directly to the nerve. These are surgical. These require surgical validation, and there's a limited number of use cases for which you will want to go through that pathway. Tivic has now demonstrated a medical-grade non-invasive VNS. One of the data points that researchers will look at is how big of a pupil constriction you get. Are you actually activating the vagus nerve? When we look at VNS in an implanted device, we see a pupil constriction of approximately 7-7.5%. What we saw in ours, in our clinical trial, was a 9% constriction.
This is considered a definitive marker that we are actually activating the vagus nerve and engaging the vagus nerve as a target with a unique non-invasive approach. Out of our first clinical trials, we saw with the 20-minute treatment, we were able to deliver a 2x increase in heart rate variability. Now, this factors in the morbidity and mortality rates of cardiac disease. We also saw a 60% decrease in gamma waves. These are marked changes, remarkable changes in a 20-minute treatment protocol. We saw increases in theta waves, increases in the concentration in brain waves. What we are doing right now, what I have running at the moment, is a clinical study that is designed to optimize the response of the autonomic nervous system to the stimulation parameters. With that, I expect a data readout here in the coming weeks or month or so, clinical optimization study.
We have reported that we are seeing the benefits of personalizing and being able to further and further optimize that platform to be able to target very specific disease targets. We are in the process of now matching up the clinical results that are coming out of the work we are doing with The Feinstein Institute with the clinical needs that came out of the market research and identify key areas to target for this particular program. Later this year, we will begin disease-specific, the disease-specific targets. Just to give you an idea about strategically how we're approaching this, there are, as I mentioned, there are vagus nerve stimulators in market today. They are implanted technologies. If you look at LivaNova, it's approximately a $2 billion company. They're really only penetrating maybe 1%-2% of the total market, the addressable market, because it's an implanted technology.
Now, for epilepsy, you probably do want an implant. Those are real-time stimulation responses. For depression, the possibility of being able to do something non-invasively is a very powerful alternative. Similarly, clinical stage rheumatoid arthritis, Setpoint Medical is going through FDA approval today for a device that only stimulates for about a minute a day. To be able to, there's not necessarily a strong motivation if we can deliver that same effect with a non-invasive device. Similar for stroke rehabilitation with patients that have undergone a stroke, Microtransponder has proven effectiveness of VNS with an implanted technology, but every doctor we've spoken with would like not to have to wait six months after a stroke to begin using VNS, but to begin using it with their patients almost immediately after the stroke.
This area, as it unfolds, the implanted technology has basically paved the way, and we can strategically align ourselves to bring technology into market in a non-invasive approach that then can significantly open the market landscape up and move these types of stimulation parameters from last line, last course of action into further up in the treatment stream. As I said, I've been taking the company through a very significant repositioning as into becoming a diversified immunotherapeutics company. We have monitored very carefully, and as we've done that, I've watched very carefully the structure of the cap table. Today we have gotten, we've had some volatility in the stock. We do have eyes on the share. I don't shy away from that. We do have volatility. After we resolved our NASDAQ deficiencies earlier this year, we have stayed very stable.
We've gone through, we have had a very nice stable support now at where we are. We have strong trading volume. We have no debt. The warrants that are on the cap table are plain vanilla warrants, no ratchets, no resets, no anti-dilution. A large percentage of the shares are held by Statera Biopharma, who is the licensor of the TLR5 program, from whom we licensed that. We do now have financing lined up. These are publicly announced financing vehicles that have already been adjusted into the share and adjusted into the market. These are structured such that there is nothing that really hits the cap table in a large quantity at any given time. We have been very deliberate about structuring this in a way that we can provide long-term value appreciation as we move through this transition.
With that, as I said, we've gone from being a single product company with an over-the-counter product, an over-the-counter device for sinus pain and congestion, to now a fully diversified immunotherapeutics company with multiple modalities, with different opportunities to scale the platform over time, and with a financing structure that allows us to appreciate the company and value. With that, I would be delighted to take any questions.
Great. Thank you, Jennifer. Let's talk about the TLR5 product. You said you're through phase three on that product. You're starting manufacturing. What's the plan for distribution?
That is a government-focused sale. Rather than it being something where we need to build up a large sales team, we simply need a few well-placed consultants. Those are people that we have in our roster now. We're bringing those consultants on board.
They're part of what helped us secure meetings at the White House, for example. For distribution, that is a, you're selling to a relatively limited, you're selling to national entities. We're selling to a Department of Defense. We're selling to a Ministry of Health.
What's the timeline to start generating revenue?
The timelines I laid out there are dependent somewhat on whether we get into that emergency use designation. It's possible 12-18 months on an emergency use, we could start to see revenue. It's also possible if we're on a longer timeline, that full timeline, if there were no accelerated pieces of it, could be a three-year timeline.
All right. A similar question for the VNS device. I know I used to cover Cyberonics prior to the acquisition. Their path for treatment-resistant depression was not exactly straightforward.
They had a lot of hiccups on the way. Do you think you'll have a little more success there now that they're through that process? What do you think the timeline is for that?
I'm looking at the VNS as probably about three years to market. Once we do, in the case that we are doing first disease-specific trials starting this year, that would take us into what would be considered your phase two or pivotal. There are devices that have been able to use what would be considered their phase two as their pivotal because the results, interestingly, with the neuromodulation products, the results can be so strong. I will count that depression is an interesting area because it is very fiercely defended by pharmaceutical companies. It is a little unique in the regulatory pathway that it's considered a phase three device.
Most of these are considered phase two devices, and I would probably start with something in the phase two category.
Okay. And then similarly for Crohn's disease and some of the other applications for the VNS device, do you think they're on similar timelines, or do you think that they'd be a little bit further out?
That's really more of a financing question, actually, than a some of them, it depends on follow-up. For Crohn's disease, for example, I believe the follow-up timeline for patients is about a year of treatment, a year of follow-up, if I remember correctly on that one. You do have a longer timeline development. MS would be similar to that. For something like PTSD, we can get patients through, and we may not have as long of a follow-up. Chronic stroke needs a longer period in the study itself.
There's a study design question embedded in there. That's going to vary by the indication specifically and financing, when do we kick it off? At the moment, we're focused on, we are focused with the financing we have secured. We're focused on bringing the TLR5 program forward for the market. That doesn't mean that we wouldn't be open to, in the right structure and in the right way, being able to accelerate some of the other programs.
For a device like that, would you look for a partnership for distribution, or would you build your own sales force, or how would that work?
Both our devices and our pharmaceuticals are, excuse me, they're on the prescription pathway. The devices, these devices are not like a capital equipment or an in-office treatment. They're something you would prescribe.
They're very much channel aligned between the biologic and the devices. Those type of markets, it's not uncommon by the time you get to a phase two to be partnered up with somebody. What we're doing right now is looking at that as a, it's certainly a valid outcome with the neutropenia. The same thing I would say for the VNS technology is developing the right sales channel partnerships. I don't necessarily see that we need to build, we don't necessarily need to build with an Amgen, a Regeneron, or a Sanofi already in place.
I assume that should those partnerships deals come to fruition, they would include some kind of upfront payment to help get through the remainder of the clinical or the regulatory process.
That is generally pretty common for those type of deals, yes. Absolutely.
Okay. All right.
In the meantime, you've cleaned up the balance sheet quite a bit, but what capital do you have available to keep you going until some of those things start to happen?
We did close $1.7 million. I think that might have come in after the queue. That is funding us just fine on our burn rate through those capital, through getting those additional ones in. The ELOC is active today. That has already gone through the SEC.
You think you're good for the next 12 months, 12-18 months?
I feel very comfortable for the next 12 months.
The over-the-counter product that you had, I know you said you were not thrilled with the way that performed, but I mean, is that something that's profitable for you right now?
It's running basically break-even, more or less break-even at a product level, not at a business level. It is something we will be taking some steps to look at other alternatives with that particular product line. It's a good product. It has a very powerful effect for people. There's 25% of people, it's almost a miracle the first time they use it. It is also an over-the-counter consumer marketing play, which is not as strategically aligned with the channel strategy that we're developing for the other parts of the portfolio.
I mean, is that you're looking at strategic alternatives? Is that an asset that maybe you might like putting in somebody else's hands?
It could very easily be, yes.
Okay. All right. A question for the audience. You mentioned a potential for a stockpile order for the ARS.
Do you have any idea on the timing and how much revenue that could generate?
I'll give order of magnitude. I don't want to speculate on timing. I just don't want to try to forecast something as unpredictable as when governments spend money. For an order of magnitude, a modest-sized country would be 100,000-300,000 unit type order. We'd be looking at about $800-$1,000 per dose on that. That gives you an idea of an order of magnitude for a modest-sized country. For the U.S., stockpile dosing, there's approximately $9 billion, is what we understand, in stockpile right now, rotates out about every two years. That's our two-year rotation. Those orders, you might be looking at something more like 1 million doses eventually to get stockpiled.
If you'd resell the product outside the U.S., do you go to the U.S. first to get approval for that, or how does that process work?
Because it is under an IND, we would need approval from FDA and from certain departments that we are already speaking with.
With the VNS product, is that something you plan to manufacture on your own, or would you outsource that?
We don't need to do the manufacturing ourselves. In fact, for ClearUP, we have outsourced manufacturers. Same for the drug. We are outsourcing the manufacturing. There's no reason with my last company, we were developing a new infrastructure for electronics. With as robust as the global electronics infrastructure is, there's no reason for us to do in-house manufacturing. What we would do, though, is look at carefully structuring the supply chain.
That is, it's always something you want to look at when you're looking at an electronic product. ClearUP is manufactured domestically. We were able to get good pricing. We have one partner in Canada and assembly in the U.S.
Okay. With the recent, all the noise about tariffs lately, I mean, does that go into your decision as to where to manufacture that?
It would, except that we have a significant stockpile of, excuse me, we have a significant stockpile of inventory at the moment. From 2022, we were at a point when you kind of had to buy a lot or you couldn't buy at all. We do have a stockpile of inventory and electronic component parts that we already owned. We have inventory that we prebuilt. I went through restructuring our manufacturing chain last year.
We did a prebuild of inventory, and it's basically available for sale now.
I know you said for depression that the pharmaceutical companies keep tight control over that. I mean, are there any clinical studies planned to combine the VNS with some of the available treatments now, maybe partner with some of those companies?
Nothing that we've announced.
Okay. All right. Potentially, that could be an option.
It could certainly. Again, we're looking at this as a modality-agnostic opportunity. It's always kind of struck me when I look at healthcare that, oh, if you're a small molecule company, you only think about small molecule solutions. That doesn't mean that there isn't something where you can combine a cellular therapy and a device and still have a better solution for the patient.
That is the type of ethos that we are looking to build into the company. We have the experience in modulating the immune system. We have different modalities to do it. We have the scientific basis to look at what would be the best solution for the best solution. If that means involving in a partnership, pairing drugs and devices, then by all means, that is how we should tackle the problem. We do not have to bring all the expertise to the table.
Right. We are just about out of our time limit. Are there any closing comments you want to make before we sign off?
No, I do want to thank everybody for your time today. Thank you for listening. I hope that this has been of interest for you ir.tivichealth.com
If you are interested in more information, please feel free to reach out. We do get that, and it keeps it from getting lost in my inbox. We'd love to hear from anybody that would like to hear and learn more about the company.
All right. Thank you for your time. I know we've kept you busy the past couple of days, and we appreciate what you've done. Thank you.
It's been fun. You can hear it in my voice. I appreciate everybody speaking with. Thank you, Jim.
Bye-bye.