Welcome back, everyone. Next, we have Tivic Health Systems. It trades on the NASDAQ under the symbol TIVC, and its bioelectronic program is developing a novel, non-invasive medical device designed to target the neural pathways implicated in many prevalent and debilitating diseases. Happy to welcome Co-founder and CEO, Jennifer Ernst. Welcome to the conference today, Jennifer.
Thank you. Thank you. While it is true that we have historically been a bioelectronic company, what I'm going to be talking to you about today primarily is newly licensed assets that have developed and created a strong late-stage pipeline for us in the biopharmaceutical area as well. Good morning, everyone. I'm Jennifer Ernst. I'm CEO of Tivic Health, and I'm pleased to be sharing with you this update about a company that has undergone a significant transformation this year by bringing in some newly licensed assets, developing a strong late-stage portfolio. For investors, I always like to highlight that we have a very clean cap table, no debt, and there are significant value inflection points on the horizon at this point. Obviously, our required safe harbor statements. Tivic is focused on immunomodulation.
That means we use the immune system to fight disease, to improve health outcomes, and hopefully to save lives. There are now in our portfolio two parts of our portfolio. One of them is a bioelectronic area in which we have historically done our development internally, and I'll touch briefly on that at the end of the presentation. The other area and the new updates, the things that have brought our pipeline forward into the very near term, is a biologic licensing agreement that we entered into earlier this year that includes a phase three recombinant protein that has had significant funding from BARDA and developed BARDA, Department of Defense, and other military as a military countermeasure for radiation. From that same asset, being able to extract phase two-ready opportunities for multiple indications in cancer and oncology.
We continue to make very selective investments in the new breakthrough areas of immunotherapy that are represented in our bioelectronic portfolio. At this time, I have a highly Department of Defense risk set of assets. We are operating with a very capital-light model, and there are multiple value inflection points on the horizon. I hope you will see each of these represented as I go through this presentation. Earlier this year, we took the license for what's called a TLR5 agonist, two compounds, Entolimod and Entolasta. These were initially developed as a radiation countermeasure, and so it was very significant funding from the government entities. Immediately after we engaged the license, we began meeting with senior White House officials, FDA officials. We've met with BARDA, with the Armed Forces Radiobiology Research Institute, AFRRI, to ascertain the interest and to recultivate the interest in this particular asset.
We've made significant progress on the customer engagement side around acute radiation syndrome. As part of that, we've entered a GMP manufacturing agreement in May. We've kicked off the production that is part of a BLA filing. This should give you an indication of how far advanced the compound is, for how far advanced Entolimod is for the first indication of acute radiation syndrome. Actually, in September, we just announced that we've completed the cell line verification, which is the very first step in the GMP manufacturing process. We are well underway in the steps that are necessary to move us to a BLA filing and towards approval. As a company now, we have reinvented the portfolio.
Our bioelectronic portion still remains much behind the firewall in terms of the specific applications, but with the biologic, we now also have the addition of phase two-ready and phase three assets with a significant amount of funding that has previously been invested. To explain the licensing agreement, we have licensed two biologic drugs, $190 million previously invested. As part of this agreement, we received two INDs that cover radiation countermeasure applications and advanced cancer applications, 40+ human trials, 60+ patents pending. This is a very robust, worldwide exclusive license. I'm going to dive in briefly on the science of what is a TLR5 agonist and how Entolimod works. In the category for treatment for radiation and in cancer therapeutics, many of you may be familiar with a category called GCSF drugs. The approved drugs in the category only deal with white blood cell production, neutrophil production.
They only address the blood-related syndromes or outcomes of radiation exposure. You have to treat; they can only be effective when they are used after the exposure, so they provide no protective benefits, and multiple doses are required. I'd like to compare that to Entolimod. There's a very robust and well-characterized mechanism on the TLR5 pathway. Currently approved drugs are in the GCSF category, and Entolimod is across the world the most advanced TLR5 agonist. It addresses both the blood-related effects and the GI effects, the GI tract effects, the things that cause wasting syndrome in cancer patients. It's one of the most damaging effects of exposure to extreme radiation. Entolimod offers both a treatment and has been shown a treatment after radiation exposure, but has also been shown because it prevents cell death to have protective properties as well if administered before exposure.
Single dose is effective, and no adjunctive care has been administered. Again, from an investor perspective, there is a direct opportunity for Entolimod to take market share away from these GCSF drugs. That is a $7.2 billion accessible market in 2023 and growing rapidly. When I look at this portfolio now, we have multiple applications within a single portfolio. Entolimod is an acute radiation syndrome countermeasure. This is a military countermeasure. Think nuclear disaster, think forces exposed in field, phase three. This is very, very far along to be approved under a specific rule the FDA has designed for this type of treatment, the FDA animal rule. Already have the fast track and orphan designations, and it's considered a stockpile drug. This represents a $5.2 billion market opportunity when you consider the stockpiling and the refresh that is done to the stockpiling.
The use of emergency use authorizations may allow us to stockpile even before an FDA BLA approval. That is still to be determined in conjunction with the FDA as we progress in our conversations. There is a significant opportunity. We are a relatively small company at this point. Significant opportunity for us to engage in the acute radiation syndrome as a means to fund and develop the additional indications. Again, just to touch on the clinical data, a threefold increase in survival with one dose and showing no signs of toxicity. Even at the highest doses, the drug of these side effects were limited and very transient in their effects. This is a pathway we are moving down. As I've highlighted, there are opportunities.
We will be taking the full BLA pathway through, but with a fast track and orphan drug designation, there is also the opportunity to move expediently through the FDA processes. Where we think the biggest market opportunity for this is actually in the cancer therapeutics. Those same drugs that I just described are also used in remediating the syndromes, particularly of neutropenia, so specifically the neutropenia area addressed by GCSF drugs. This is phase two ready to begin investigations in the neutropenia space, increasing both the neutrophils and the platelets, protecting and repairing, protecting the bone marrow, and protecting and supporting the GI tract to avoid the wasting syndromes that we see with cancer. The GI tract is damaged both by radiation and chemotherapy drugs.
The opportunity within Entolimod is to develop it not only to help after this has been developed, but with the protective properties, we would eventually like to see this as a part of the standard of care that could be used preventatively to help prevent damage to begin with. There are future opportunities. Immunosenescence is an area which is related to the gradual decline of our immune system as we age. It's been linked to a number of age-related diseases, so increasing longevity. This is a future opportunity, but there are several of these kinds of future opportunities in the portfolio that we have licensed. I mentioned that many of the specific applications for our vagus nerve technology remain behind the firewall, but I would like to highlight the strategy that we are using. The vagus nerve is an important part of the immune and autonomic nervous system.
It runs from the brain to the stomach, and it touches every major organ in between. Vagus nerve stimulation has been very well established as an implanted technology. A number of companies, multi-billion dollar companies, insert an implant and attach it to the vagus nerve. While there are some wellness companies out there that are ascribing to be vagus nerve stimulators, in reality, they have not shown medically that they actually engage the vagus nerve. We have research coming out of one of the world leaders at the Feinstein Institute for Medical Research. It's actually the Institute for Bioelectronic Medicine, the pioneers in this field, indicating that using the approach we are using, not only are we changing heart rate variability, we're able to change brain signals, and we're able to reproducibly show engagement of the autonomic nervous system, or specifically engagement of the vagus nerve.
We're one of the few, if not the only, company that has demonstrated transcutaneously the ability to concretely engage vagus nerve activation. With that, I would be delighted to open it up to questions. To summarize it, the company has gone through a significant uplift this year as we insourced and integrated a newly licensed asset. We have a strong late-stage portfolio, as well as very promising areas in the early stage, clean cap table, and significant value inflection points across these programs. I'd be happy to open it up to questions.
Thank you, Jennifer. Yes, let's jump into some questions. Starting with Entolimod, will it be stockpiled by the U.S. or only other friendly nations in the near future? Can you talk about that?
That is certainly our hope. Because of the amount of funding that the U.S. government has already put into it, and because of some of the intrinsic advantages of the drug itself, we are looking to work with them. That's what the purpose of the meetings we have taken so far are. I can't at this time forecast when a, quote, "government order" would come in. That would be a forward-looking statement, of course. Also, whether they would stockpile under emergency use or whether they would stockpile under a full FDA approval. There are obviously nations for whom this particular category is of high interest in a war-torn zone. The reality of radiation exposure is very real day-to-day, and we also are engaging outside the U.S. with countries that have a potential for a high interest in the nearer term.
What would Tivic Health Systems like their loyal shareholders to know who are holding short and long term as they're watching the progress of TIVC?
What I most want people to know is that we are managing very carefully the time exposure investment for, I mentioned having a capital-light model, and I think it's important to note the experience of the team. With this bringing in a new asset, a new category of therapeutic area, we also brought in a new team, including our Chief Operating Officer, President of the Biopharma area, who has 17 drug launches under his belt. Between the experience we've had in the neuromodulation, already previously launching one product, which we are in the process of exiting, and the experience that has been brought to the table in biopharma, we have a very strong team now to drive this forward, this integrated vision of being able to harness both the electronic and the chemical parts of the human system. Very focused.
We are currently going to be focused, you'll hear mostly about Entolimod in the next 6, 18, 12 months, probably. That doesn't mean we would give up. We are neglecting the investments in other areas that we believe have high potential as they mature. The cancer treatment area, I think, is one that also, because of the intrinsic properties of a TLR5 agonist, highly is a very safe pathway. It's a very unique pathway. It has enormous potential in the cancer therapeutic area, not only for the indications I've described today, but also for other ones we'll be developing and exploring.
Perfect. Thank you. Tivic Health Systems' recent PR announcement for laying out the groundwork for production of Entolimod. In layman's terms, what are the next steps in the process for an ultimate rollout to production?
What we start with when we do a cell validation is actually very small batch lots. We've taken old cell lines that have been frozen. We've now brought them back, tested them, validated that they produce the same protein that was produced in the initial batches. That was a very important milestone for us to be able to show that in the hands of a new process, new people, new owners, we can produce the same protein. Proteins are notoriously finicky. When we announced the cell validation, it was one of these quiet moments that within the company you go, yes, isn't necessarily the one that all investors would see how important that was. That enables us to move now into scale-up. We begin moving into larger batch productions, moving into the kind of scale that will be necessary for process development and commercial scale-up.
We scale one by one lot, then we add the GMP production. That will be a major milestone once we complete the GMP production. There is then some testing work that has to be done. That testing, there's an equivalency or stability testing that has to be done. The stability is about a year after GMP. That is what is necessary then to pull the full package together for a BLA. What's important about what I'm saying here though is you didn't hear me say there's any new discovery work. There's no new scientific breakthrough that's needed. Safety, efficacy have been extensively demonstrated. We are now demonstrating manufacturability and reproducibility in the manufacturing of the drug. That is the necessary last component to prepare the packages for the FDA.
Perfect. With that said, does TIVC see a near-term catalyst that could increase the value price per share of TIVC?
When we make announcements, it's always hard to predict how the market will respond. We have announced patents periodically, and we've seen extreme volumes of uplifts in share price. I don't predict the share price. I will reserve that for the market analysts that are following. With the multiple processes in place, right now we're about a $5 million market cap. I would expect to see, as these are rolling out, more and more of the market taking notice. Right now we're a bit of an undiscovered asset. This is probably the first presentation I've given in this format since we made significant progress in the characterization of the materials and being able to get that into manufacturing. I think the last time I did a presentation was probably just when we announced it.
I expect this will be a combination of both getting more visibility around the company so that can naturally appreciate, as well as the value inflection points that come with catalysts like entering the GMP manufacturing, finalizing GMP manufacturing, meeting with the FDA, taking the pre-BLA meetings, those types of milestones that are associated with moving the regulatory path forward.
Perfect. Carson has a question. What was the % increase in survival after one dose, and what further studies have been done?
It's a 3x increase in survival, so 300% increase in survival. Across the other studies, there's 40 plus studies. Many of them are for the acute radiation syndrome. There's a study done at Mayo Clinic on the immunosenescence area using a vaccine adjuvant, using Entolimod as a vaccine adjuvant. Some of the studies are unpublished, but there actually is quite a bit of published literature out there. If someone is interested, Google Entolimod, and you will start to see papers published by the AFRI. I'm sorry, I had the acronym up there earlier, but the Radiobiology Research Institute, papers published in Nature, papers published across the board in top journals, a really robust body of science. The company, unfortunately, lost its funding source before it was able to make the FDA leap and didn't really have the experience base to make that final commercial step.
We are benefiting from a significant amount of prior research and the fact that we've been able to bring the commercial chops to the table to drive this forward.
Perfect. Can you talk a little bit about your team, previous successes, previous exits?
Oh, excellent question. My last company, actually, let me talk first about myself. I spent a good portion of my career in translating science into business opportunities. That was 20 years at Xerox PARC across the areas of physical, computational, and human sciences, also including some work in the biologic area. My last company was a Norwegian company. I founded the U.S. subsidiary at the Norwegian company. We took that from eight people to a $500 million market cap in about five years. Prior, I mentioned 17 drug launches of our COO. That includes the launch of Neupogen, Neulasta, the drugs that we would be looking to displace, the launch of Avast, so some of the ones more brand names that you would know under his belt. Really, I would say at the moment the two of us are the key.
We also have our CFO, of course, who's managing the forecast, all of the financial engines, and has had a certain amount of experience in biopharma planning as well. The core of the team really is myself and the Chief Operating Officer with our experience building companies, building companies, exiting. I actually did not exit that company, but we are in the process of doing an exit. I built companies through licensing, through acquisition, and through internal development.
Perfect. Thank you for that. Mark wants to talk about scaling your production. What did your production look like when you started, and where is it today? Does this mean you will go to the market on your own?
Two different questions. The first one is scaling up the process. We started with frozen cells that had been on ice for quite some time, bringing those cells back and having a process for them to begin to grow. This is a recombinant protein that's grown in an E. coli bacteria for the cells to begin reproducing and reproduce the right protein. We were really, really happy with the outcomes of the initial batches, small batch, small batch. At this point, we would be moving up the production. In terms of going to market ourselves, we are certainly equipped to do it. We have the skill base. We have the background with multiple drug launches now under the team, in the team. It is also very common, though, to partner with a larger organization.
The possibility, if we want to get this to really scale, to scale at the largest amount, it makes a lot of sense to partner, license out to a company that has the 800 to 3,000 person sales force to call on the doctor's offices. That would be a perfectly viable outcome for us as well.
Perfect. Can you talk about your burn funding? Any issues with remaining funded in this environment?
No, we've got a very strong funding partner behind us. The partner has remained largely confidential, but we have an agreement with them that has been public where we basically get a tranche of funding about every, roughly every 25 days on that order. That has allowed us to build up, build up, fund the manufacturing. They're very pleased with the performance of the company. I feel highly confident in the ability to grow, to continue with a good financing partner behind us. That doesn't mean we would not welcome other partners at the table as we want to accelerate some of the other areas like the neutropenia and the cancer treatments. There is actually opportunity to work with the company, but I am feeling very comfortable about where we are with our financing partners at this point.
Great. Sam asks, can you name some current solutions that your product will replace?
The biggest and most direct would be the GCSF drugs. Going back to the science of this, the GCSF drugs, depending on where you look, are approximately a $7 billion market. Neutropenia itself is about a $20 billion market. This is a subset of the neutropenia market. We actually could probably take a larger portion of that market and additional market based on the GI tract effects. I consider the $7.2 billion market that is accessible to the Entolimod drug to be kind of a base of it because the Entolimod product has, Entolimod as a product, will have benefits that the current drugs don't have. There is no treatment today for the GI tract. There is nothing that offers protective benefits, nothing that really offers any significant order of protective benefits.
This little line right here in the slide, the bottom of it says NF kappa B, and it goes down and says anti-apoptotic factors. That is a really important little line buried in this graph here because that is the prevent cell death. Preventing the cell death that would come from chemotherapy and preventing the cell death from radiation is why the drug has shown to have both the strong survival effects in the extreme cases of acute radiation syndrome, but also the benefits of the protective factors.
Perfect. Last questions for you. Talk a little bit about where does Tivic Health Systems, where do you see yourself in 2026?
2026 is when a lot of this starts to come to converge. We should, by the end of 2026, I would expect to have our GMP materials. I expect to have had our FDA meetings. I expect then to really also have strong customer. We'll have really good indications by the end of 2026 of the customer interest and where the groups that we're talking to right now would like to take it. If all goes well and the funding is right, I would hope to have our neutropenia studies up and running by next year as well. There is continuing progress we can make in the vagus nerve stimulation area or some of the adjacent areas in bioelectronic. Mostly when you have a relatively small team, we still need to focus and execute.
The focus and execution will be on the Entolimod compound with a selective investment in advancing the earlier stage prospects.
Perfect. Jennifer, thank you so much for your time and presentation. Very important work you're doing. We appreciate you being on our conference.
Thank you.
All right, everyone. We'll be right back with our next presenter.