Hi Jennifer, how are you?
Good, and you?
I'm going to have you unmute.
I'm sorry, I couldn't get in.
No, I needed to promote you, so you were good.
Oh, okay. Okay, perfect. Thank you.
We're all good. Yeah. We're going to start in about two minutes. There are people on the call listening, hearing us.
Hi, Jennifer.
... just to point that out.
Hi, Steven. How you doing?
Great. How are you?
We're good. I'm good.
Super. Great to see you. Dr. Plott, one of the things I was wondering is, when it comes to skin cancer, in your practice, what are some of the unexpected ways that people get skin cancer? Are there things people don't normally think about on a day-to-day basis where it gets them?
Well, no, I think that people are always surprised that they have skin cancer because they just don't think that would be them. That's going to be other people, right? They'll get something they often think, "Oh, this is just a pimple," or, "It's not going away. It's a bug bite." They think it's something else. They don't think that it would be a skin cancer. I think often, especially the first time someone's gotten skin cancer, they're pretty surprised that that is them.
Right.
It's not surprising how they come to that because it's years of sun exposure and having, often, the type of skin that's susceptible to that.
Right.
It's not so surprising for the dermatologists that find it, because that's what we do every day. It's really surprising for them.
Bob, I think you need to get swag. Swag, is that how you say it? Your swag should be bucket hats that say Phio on them. That's my recommendation.
That's a good idea. Right, to cover the ears?
Yeah. I'll wear the Phio bucket hat.
You're on mute, so just make sure you unmute.
I like that idea.
What's the next conference you're going to, Jennifer?
Wait, hold on. Let me get Bob unmuted. Lower left, just click that audio to unmute yourself.
There you go, Bob.
Okay, great.
Yeah.
We're about to get started.
Oh, okay, Callie.
Okay, listen. I have a job to do.
I love it. Full respect. Full respect.
Okay, hold on. Hi, everyone. Thank you so much for joining us today. Before we kick this off, I do want to point out to the audience that we welcome questions. Please post them in the Q&A section at the bottom of your screen. Type them in as they come to you, and we will address those questions at the end of today's Fireside Chat. I'd now like to turn this over to Steven Saltzstein, FORCE Family Office CEO.
Thank you, Callie, and thank you everyone for joining us today. We have a very pertinent Fireside Chat for you, primarily focusing on skin cancer. As we're entering spring and summer, I think it's very timely. I'm honored to welcome Robert Bitterman and Jennifer Phillips of Phio Pharmaceuticals. I'm very pleased to have Dr. R. Todd Plott. I want to read Dr. Plott's bio because it's kind of fun. Dr. R. Todd Plott is a board-certified dermatologist who possesses a rare combination of compassion, 30 years of experience, and good-natured humor. Dr. Plott loves coming to the clinic and seeing his patients each day. He takes caring for people seriously and makes the apprehensive and vulnerable patient feel comfortable. He enjoys diagnosing tough cases and has a special passion for treating patients suffering with acne.
His specialization and professional interests also include identifying and solving complex skin conditions such as psoriasis, rosacea, atopic dermatitis, as well as identifying and treating all types of skin cancers. His formal education and training include Lubbock Christian College, Southern Nazarene University of Texas Medical Branch, University of Arkansas for Medical Sciences, and the National Cancer Institute, where he was a dermatology fellow. So I think this is going to be a fantastic discussion. Bob, why don't you kick things off and just in general terms, talk about Phio's value proposition and why it's important, et cetera.
Okay. Thank you, Steve. Thank you, Dr. Plott, for joining us today, too. This brings a special dimension.
My pleasure.
To this program.
Thank you.
Our value proposition, first, we're a biopharma company. We're dealing in the realm of immuno-oncology. As you can probably guess from the intro, we spent a lot of time in the world of dealing with skin cancers. That's what our program is about, our development program. Our value proposition really centers on three key points, I think. The first of which is we're dealing with an incredibly large market in cutaneous squamous cell carcinoma. We also have a unique, broadly patented technology called INTASYL, which we'll probably talk about a little bit more in a few minutes. That as a unique way, it may be a way of breaking the paradigm for treating skin cancers and maybe other types of cancers as well.
Finally, the other thing that makes us different, I think, is that we have a very lean virtual organization. There's eight employees and four subject matter experts, and all of the development people, which include five of the eight, we have all worked together in previous companies and under my direction. We all know each other quite well. They have a good track record of developing programs and getting them approved. I would just say one point about the market size. That is, squamous cell carcinoma is the second largest incidence of solid tumors in the human body, and it has a mortality rate that is almost double that of melanoma. Most people don't understand that. With that, it is important to treat early, and because if you don't, those early signs will continue to advance to later stages and become quite problematic.
Dr. Plott, as a practicing dermatologist, how many patients do you come across who are affected with squamous cell carcinoma?
Well, I see about 60 people a day when I'm seeing patients. I diagnose five to six skin cancers every day. In preparation for this, I have the advantage of being the Chief Medical Officer for Epiphany Dermatology. We have 127 offices across 18 states. I wanted to, maybe if I could, answer that quite globally for our platform, which is a great cross-section of the country. We saw last year 193,000 patients.
Wow.
Patient visits, I should say.
Yeah.
We saw 770,000 patients, individuals. They had 893,000 visits. Of those 770,000 patients, we had about 92,000 that had surgeries for squamous cell. Primarily, any squamous cell is going to be.
Wow
Treated with some type of surgery, 92,000. In other words, 12% of the patients that we saw last year had a squamous cell carcinoma treated by surgery. We don't offer other modalities of treatment. There are some that you might imagine, not near as effective as surgery, but 12% of the patients going through our platform last year had a squamous cell that needed surgery.
Who gets it, and how fast does it progress?
Well, this starts usually as a small spot. It's in sun-exposed areas typically, or an area that's been sun-exposed. Often, the head and neck is a much higher risk area. There's a lot of vital structures there that it can get into. There's lots of factors that are involved, but it quite rapidly, and it could be a little bit slow. Usually these come to people's attention because they have a spot that's not going away, it's bleeding, it's their spouse. Somebody's saying, "You need to get that taken care of." It's not so uncommon, as you see.
Is surgery the default treatment?
I think across all of dermatology, surgery would be the first line treatment.
What happens?
That's the only treatment we offer across our platform.
What happens if you don't treat it diligently?
Oh, it will be invasive, get large, metastasize, and eventually it would kill you.
What % of surgeries could you eliminate if you had an effective alternative?
Well, talking about just any alternative, I don't know. It kind of depends upon what it looks like. If it looks like the technology we're thinking about today, I think the opportunity's pretty fantastic to have a product that could eliminate or reduce the mortality of a surgery, because if some of your viewers may have ever known someone who's undergone a surgery that is involved in rearranging their face, pulling flaps and grafts and that kind of thing, and if it could be a treatment that just reduces that to a simple surgery, that would be fantastic for patients.
Bob, a lot of people know about monoclonal antibodies that target PD-1. How's your approach different?
Well, the approach is substantially different, Steven. Monoclonals are administered through infusion, systemic infusion throughout the entire body. The goal with that infusion is that the drug eventually attempts to knock off this PD-1 protein when it is already on the surface of the tumor cell. In our case, we are injecting the tumor directly, which is referred to as intratumoral. In this case, what we're able to do is, by injecting the T cell within the tumor, we are able to turn off the production of PD-1, almost like a faucet or a spigot turning off a water flow. The PD-1 is shut down before it has a chance to escape and migrate and lock into the surface of the tumor cell. The advantage of that is that, number one, you're directly going after the source as opposed to driving a treatment through the entire body.
The other thing is that monoclonal antibodies, which are biologics, have a very high incidence of serious adverse events. In fact, they're reported to be in the rate of about 37%. Now, a serious adverse event is very different than an adverse event. An adverse event could be your skin hurts because you got a needle point injection. Serious adverse events fall into the realm of autoimmune problems, colitis, myocarditis, gastritis. Anything that has an “-itis” on the end of it conceivably can be caused by a monoclonal antibody infusion.
You're using RNA interference, right? RNAi?
We use what is technically called a short interfering RNAi. Okay. There's a slight difference, but what we're doing is ours is a synthetic drug-like RNA interference.
It's called INTASYL?
INTASYL is the name of the technology platform, that is able to create a specific compound in siRNA that is specific and precisely targets the one gene out of, say, 15,000-20,000 genes in the human body that is the cause of this PD-1 production.
Got you. Okay. All right. You're delivering the drug directly, not via systemic infusion, right? The advantage of that is what?
Well, precise direction to the gene is basically avoiding all of the drug that otherwise, if it was a monoclonal, would be going through your entire body chemistry and hitting a bunch of other organ systems on the way to the point of where you want it to go. That's the biggest advantage. It's also a convenience factor as well, because it is injected, it can be done within the physician's office, as opposed to having to send the patient to an infusion center, which creates a lot more logistics. I would say there's one other advantage, which is at least an economic one, and that is that this is being done in the physician's office by the dermatologist.
It's driving patients into his office, and it enhances the practice economics of that doctor's practice. Those are some of the big differences. It just targets what you're looking to go after as opposed to getting all the collateral damage throughout the body.
Right. Okay. That's the concept of self basically. Bob? Not a problem. I said that's the concept of self-delivery.
We had a canine incursion here, sorry. Could you ask the question again, please?
That's the concept of self-delivering.
That's right.
Yeah.
Well, it's even a little bit more interesting than that, and I won't get too technical, but to say that many drugs that have to be injected through the skin into a source, they have to penetrate the cell membrane, and most of them have difficulty penetrating the membrane. What happens is that the drugs break down, okay, in terms of going through that membrane. We have the ability to basically get it through the membrane, through endocytosis. There's a special element in the formulation that allows us to get there. Unlike most other drugs, they have special formulation enhancements, things such as viral vectors or lipid nanoparticles that basically assist or carry the drug across the barrier.
You would say, "Well, so what?" The answer to that really is, it does matter because some of those other factors are also locally toxic. In some cases, lipid nanoparticles can actually enhance, that's probably the wrong word, but they can promote liver toxicity as well. We have the advantage of this formulation that really deposits the drug where it has to go in nothing other than buffered sterile saline solution. It's basically going to where it's got to go in water with nothing else to help it get there. That's why we call it self-delivery.
By the way, you guys went to the FDA looking for approval on one indication, and they came back and gave you multiple indications, right?
Well, we went in believing that we were going to be able to treat what we thought would be the late stages, the advanced stages of melanoma, Merkel cell, and cutaneous squamous cell. The FDA came back and said, "Yes, you can treat the advanced stages of those three diseases, but we also would like you to treat the early stages of cutaneous squamous cell," for which, by the way, there is no approved FDA drug. The fallback treatment is really, as Dr. Plott had mentioned earlier, it's surgery. There's a big advantage to that. Just to elaborate, I always say the question that I always mention to investors is, say, "How large of a hole do you want cut in your skin to take these out?
If these are recurring in different parts of your body, how many times do you want to go through that?" I think Todd can probably talk about the concept of surgical fatigue for sure in terms of many patients. Being able to shrink or eliminate the tumors without going through that trauma is a clear advantage.
Todd, do you get patients that just say no more?
Oh, absolutely. You've had four, five, six surgeries on their face and neck. If you don't know about Mohs surgery, it's a pretty uncomfortable, horrifying experience where you sit there, somebody numbs up your face, they cut a hole. While they're looking at this under the microscope, you're sitting in this chair with a hole in your face. You might be put in a room with other people with bandages on their face, knowing that they're in the same sort of thing. When the area's not clear, they'll go in and cut off more, check it. Eventually, you're clear. Some physicians will send patients home that night with a hole in their head. Our practice doesn't do that, but they sit there, and then we'll rearrange skin to cover that hole. It's pretty unbelievable, pretty awful.
To what extent do you think PH-762 is an alternative to surgery?
Well, I think there's a lot to learn about that and a lot for us to explore. I think the promise of it is really incredible. We know so much about the PD-1 protein, right? That's acting as a brake for the body's immune system.
You know what? You're buffering a little. Can you say that again?
To prevent the body's immune system.
Can you?
We know a bit about PD-1 acting as a brake for the body's immune system.
Okay, yeah.
It also prevents then the tumor from being destroyed by the immune system, right? In reverse, it also causes the tumor to grow, to continue to grow and metastasize. The fantastic opportunity for this is that we'll have a very targeted treatment to allow the body's immune system to recognize the tumor and fight it, and block the growth of the tumor, much better than what's available with the antibodies right now. The antibodies that we have that are available for other tumors, they only are able to penetrate the outside, or they only touch on the outside of the tumor. This protein is developed inside the tumor, and this RNA technology can go inside the tumor cell and block that at the source.
That is really exciting, because now we've got something that's actually much better, has a much better opportunity to be effective than the products, the antibodies, and stuff that are given systemically. This is given locally. It's really very exciting.
I guess the obvious question and answer is, shrinking the tumor size then helps with the amount of physical surgery that the patient has to have.
Absolutely. If it just shrunk the tumor and we did a small surgery to be sure we've gotten everything, that would be fantastic. I think you'd have a lot of people sign up for that.
Right. Bob, I'm curious, what are your expectations for treatment outcomes?
Well, the expectations right now are based on what we've realized in the conclusion of this Phase I-B trial, because that's the only real concrete information that we have looking forward. This first trial was what's called a dose escalation trial, which means that over the course of five different cohorts of patients, we kept on attempting to increase the concentration of active ingredient in the injection. Ultimately, the FDA is always saying, "Let's find the dose-limiting toxicity," meaning, what is the point at which the patient cannot take this drug without having a serious adverse event? We increased the dose 20-fold in terms of concentration over five cohorts, and the fifth cohort at the highest concentration was just as safe, for all practical purposes, as the first cohort.
The first thing, our expectation is that this is probably going to be a safe drug. Certainly, the profile right now looks to be that case. The other factor is the outcome results. We measured efficacy in this trial based on what's called the pathology, meaning how much cancer is left at the end of this process. This study was fairly simple, at least as far as the injection part of it. Four injections over three weeks, and at the end of the fifth week after the first injection, patients were reviewed. If there was any cancer that was remaining, it was resected or removed. At that point in time, there was a measurement as to how well the drug performed or responded.
The patient responded. There were four measurements, okay? One of which was, does this patient have 100% total clearance? That was one measure. Does it have greater than 90% and less than 100%? Does it have greater than 50% and less than 90%, or does it have less than 50%? Anything in the first three categories I described represented a response. Anything less than 50% was called a non-responder. We looked at the fifth cohort, 85% of those patients were responders. That was six out of seven patients in that cohort. Four of the six were total 100% complete cancer removal based on pathology.
Even if you look at it across all five cohorts, on average, it was still a 65% response, and that takes into consideration that many of those patients were being injected at a much lower concentration of drug. Even in the fifth cohort, as I said, there was a safety factor there that did not reveal any dose-limiting toxicities, any adverse immune effects, or anything of that nature. Our expectations are that we are going to get a very good response rate as we continue to move forward in the study, hopefully. With that should ultimately provide a very interesting proposition to the medical community and, also for that matter, to the investment community, I would say.
Jennifer, from a regulatory perspective, what are the next steps? What do you see as the challenges over the next year or two?
Yeah, that's a great question, Steve. We are right now finalizing the database for our Phase I-B study, and we'll be compiling this for submission to FDA to request a guidance meeting with them, and that will be around the July time period. Our objective of that meeting is to get FDA's recommendations and advice on the design of our next clinical trial, which we will be proposing a Phase II-B/Phase III trial for submission of an NDA after that trial is completed. Once we get FDA's comments, then our next major activity will be setting up this Phase II-B/Phase III clinical trial, getting our investigators in place, and all of those activities that surround the next clinical trial initiation.
Bob, does that kind of overlay with the next inflection points for investors?
Yeah, essentially. I think probably the next obvious inflection point for investors is to have certainty as to exactly what the company will have to perform to move into the clinic, right? So based on the outcome of this advisory meeting or guidance meeting, actually, it's a guidance meeting, we will know essentially how many patients we need to put in that trial, what might be acceptable arms to put in there, and what the FDA is going to consider to be important primary as well as secondary endpoints in the study. I think once that's clear, that also clearly will define, with greater precision, what the cost will be to conduct the study. Because based on the number of patients, the more patients.
One of the other factors that's important in this too is what might be other elements in the trial that the FDA considers to be important for just added assurance and safety. The first trial was difficult because this was never used before in man, for all practical purposes. We didn't know exactly what the outcome was going to be. We believed that it was safe. Just to make sure, the FDA had at least 24 blood draws from each patient over the course of five weeks. That was not exactly a real stimulus to getting into the study, if you're going to think about it. With that behind us now, the recruitment process should be a lot simpler. There'll be so much more clarity.
We're directionally correct in terms of expecting what we're going to have to do. Getting that directional correctness down to 99.75%, directionally accurate, I think will be a big inflection point. We should know that sometime early in the Q3.
Great. Callie, there's a ton of audience questions.
Sure.
I'm just going to let you take it away.
Okay, that sounds great. Bob, what do you think sets Phio apart clinically and commercially?
What sets us apart? I guess, if that question is directed medically and commercially, it's maybe a different question than separating it from an investor perspective. I think the biggest thing, commercially, well, first of all, I think most people do not understand the magnitude of this particular condition called cutaneous squamous cell. They also don't understand, when I tell people that the mortality rate is almost double that of melanoma, they're shocked. What we're doing is we're going to be out there basically not only attempting to create a product, a drug, which is convenient, which is safe, and which is effective, but we're going to be educating the general public as well in terms of the importance of this.
There was a time when even people didn't even consider melanoma, they didn't have the awareness of that. I think with now the fact that people are seeing it more, they see a dermatologist, they get it treated. It certainly has helped in getting it earlier. Treating early is critical to survival. Commercially, I think we're coming in with a paradigm-breaking technology with the INTASYL platform, basically being able to treat this at its source, which is different than anyone else can do.
Great. Thank you. Where do you fit in the treatment landscape? Are you aiming to replace checkpoint inhibitors or enhance them in combination?
The latter part of that comment is interesting because there is eventually the opportunity for people who have checkpoint inhibitors, in the form of monoclonal antibodies, to have their efficacy enhanced, if you will. Right now, if you look at the response rate of monoclonal antibodies, and monoclonals right now are basically being used for Stage III and Stage IV in the advanced and late stages of the disease. They're not always that effective. I think the response rate can be anywhere between 30% and 40%, and the total clearance rate is somewhere down in the range, depending on which one, the monoclonal you're talking about, 11% or 12%, up to 17%. There's a lot of room for improvement. Now, putting drugs in combination is a rather complicated subject, and certainly from a regulatory perspective.
I would add to that that there was an interesting article in Wall Street Journal, I think it was today or it was yesterday, that talked about the FDA basically giving a particular company a difficult time about a combination product. In fact, I think the article actually didn't quite capture the real issue here. Some of your investors, some of the people attending this session might have seen that. Combination therapy requires typically that, the best way to describe this, you have to demonstrate that the combination of two of the drugs or actives combined is greater than either one alone. That's a complicated trial, and it's expensive, but there's a possibility for that. Now, with regard to the first part of your question, which is where do we see it?
Right now, there is no drug available approved by FDA to treat Stage I and Stage II. We don't really see ourselves competing with monoclonals in Stage I and Stage II squamous cell at the moment. I think that that's an opportunity for us to place or position the product in the minds of the dermatologist as where it is best used, as opposed to surgery. We're not taking anything away from derm surgery. We don't want to remove a lot of Dr. Plott's business here intentionally. There is a place for this, depending on the size of the lesion, the placement, the ability of the lesion to heal, general health of the patient.
It's going to have a place, and it'll take up, whether it's a major market share or even a minimal market share. The opportunity here at reasonable pricing is a huge opportunity in the market for the company.
Thank you. This question goes along the lines of that. As someone who had a diagnosis of actinic keratosis, and they're treating it to prevent the squamous cell carcinoma, would Phio replace that current treatment that prevents or come in after it becomes squamous cell carcinoma?
That's a question that would probably be better professionally answered by Dr. Plott. Actinic keratosis are not skin cancers per se. Todd, maybe you can just comment on that.
Sure
Modalities, right?
Right. Actinic keratosis are considered pre-skin cancer places. If you've got about, let's say, 100 of those, there's probably one of them that will change each year into a squamous cell carcinoma. The AKs are like the precursor for a squamous cell carcinoma, and those are happening in some exposed areas. I think that the answer is this a preventative? I'll let Bob answer that, but we're not studying it right now as a preventative. Not that it couldn't be, but right now we're using it to treat the squamous cell, not prevent squamous cell.
That's well said. That's our objective. Treat the cancer cell that has already manifested itself. There are other means of treating precancerous lesions that are probably effective. Certainly, derms do it all the time.
Thank you. With someone who has thinning hair or bald, how often should they get checked? This is for you, Dr. Plott. Should it be more often? Is there a way to self-diagnose on the scalp by touch?
Well, the textbook answer is you should get checked every year. If you've gotten a skin cancer, then we typically see you in six months, and then again six months after that. If you've not gotten anything, then we'll push it out to a year. For the typical average person, it's pretty difficult for them to self-diagnose, and even for us as dermatologists, we may have a high level of suspicion, but it's really a biopsy diagnosis often, and particularly things on the head, we want to do a biopsy and get that definitive diagnosis.
Great. Can you see this being utilized all over the world? Will you attempt to license it or other companies that will white label it as their own?
Well, interestingly, if you look at the incidence of skin cancers, and cutaneous squamous cell in particular, once you get past the top three countries, they represent about 87% of all of the skin cancers, and that includes the U.S., number one, Australia, number two, and Germany, number three. This particular drug, specifically for skin cancers, is probably not the best. The cost to get this developed in other countries may not merit in terms of the value. I don't think that that's attractive, but there is another angle to this. The INTASYL platform, and let's talk about this particular compound, which is PH-762.
This is turning off the PD-1 protein. The PD-1 protein is involved in a number of other cancers. It's involved in liver, in head and neck, breast, bladder. I think other companies that have interests in those type of cancer treatments that are focusing on that this compound, whether it's in the U.S. or in other markets, has a potential to be very effective as opposed to a lot of the existing treatments in these other cancers. Therein rests an opportunity for this compound, but not so much in skin cancer per se, but in what it can do in other cancers as well.
Thank you. Dr. Plott, based on what you've seen clinically in this, is this something that you feel could actually change the way we treat skin cancers? What does Phio need to demonstrate to actually change the way that you would treat patients?
Oh, absolutely. What we've seen is that we've had quite a few patients in this clinical trial that have been clear or almost clear with their skin cancer. We know that because we cut out that spot, and we look for it. In an instance where, let's just say conservatively, that it only shrunk up the tumor, having a treatment that can cause the tumor size to be significantly reduced so that we only have to do a small surgery and not a big surgery, would be attractive to everybody that has a skin cancer that needs surgery.
The chance that maybe we could make it go away altogether, as we saw for some of those patients in the clinical trial, that would be very exciting because then it would be a very small incision to check that, oh yes, the tumor's all gone, and we put a couple stitches in this, and off you go. That's very exciting. There's really not anything quite like this technology and this molecule to do this. If I could just expand a little bit about what Bob was saying also with regard to its use, it's important to understand that the PD-1 protein is pretty widely essential for tumor expansion of all different types of tumors.
There are PD-1 antibodies that are widely used now for systemic metastases and in very extensive cancer in patients that have had cancer from head to toe. We know so much about this mechanism as being essential to tumor growth. It's exciting to have something that could be effective inside and outside the cell. It's exciting to have something that could be localized in this case. Not having to expose patients to that extensive antibody exposure and have all that is really very exciting. My colleagues, when they see this technology, they think this is pretty cool, pretty exciting.
Great. Bob, you suggested that, and I'm sorry if I butcher this, INTASYL is a platform applicable across various tumor types. Can you elaborate on that?
Well, I think Todd made a point about the PD-1 having impact on other cancers, but let's talk about INTASYL as a platform. The INTASYL is a series of what we call nucleotides that are spread across two different strands. They're very selectively sequenced in a particular order, and it's that order that allows the protein, the specific protein that you want to shut down, to go after that. We can basically alter the sequence of the nucleotides and do that in a way that we can target a different gene that may be causing a different type of cancer.
The platform itself really has the flexibility of being adapted in the sequencing of these nucleotides, which are just really synthetic fragments of RNA, to go after maybe any gene you would like to down-regulate and to reduce the signal. In that sense, it is a very versatile platform. The question is, which one do you want to target? I mentioned earlier, there's 15,000-20,000 genes in the human body. Our research scientists in the past basically confirmed the silencing of about maybe 30 of them. I don't think we'll ever get around to doing 15,000 of them, and I'm not sure which ones are the most important. It's in that flexibility, however, that you can basically have a platform that could target maybe anything that you really want to go after.
Great. Thank you. Can you talk about any meaningful pharma partnerships that you might be having or any strategic partners that you're speaking with?
Sure. Well, from the standpoint of selective disclosure, I can't get into too much specifics on individuals. Let me say this in general, that strategically, we would like to have a strategic partner or more. Can't have too many because then it becomes very complicated in terms of the who gets what and where. Strategic partnering is a great source of non-dilutive funding, for one thing. Secondly, we don't have the expertise. All of the people involved in our business on the development side, we all have a dermatology background. If you ask us, we certainly don't have the knowledge of Dr. Plott or many of his medical colleagues. We can talk to it, and we sort of know what we don't know. We can't talk constructively about what's involved in glioblastoma or breast cancer or bladder cancer. Those are outside of our league.
Other companies who can see this as value could very well say, "We'd like to have a product like this in our portfolio." Ideally, we picked squamous cell because it was the second-largest incidence. It was unsatisfactorily treated with existing methods, and people are dying from it if they let it go. It was a logical place for us to target. We would like to keep that which has the greatest value for us in terms of value creation in our hands. We're more than happy to look at other applications of the technology and discuss this with other parties who have an interest, whether in the U.S. or in other countries around the world where there may be an interest.
Great. Last question is, how much runway do you have? How should investors think about dilution risk over the next 12 months to 18 months? What milestones do you see in the next six months-12 months that will be meaningful to shareholders?
Okay. Well, they're actually two different questions. Let me deal with the runway first, all right?
Sure.
Right now, we've stated publicly that our runway carries us into the first half of next year, in 2027. The cash that we reported on hand as of our 10-K was $21 million in change as of December 31. We know very specifically where our cash expenditures are going to be going over the course of the next eight months. We have other programs to complement, not complement, but they have to support the steps toward the advancement of starting our next clinical trial sometime in the Q1 of next year, including making what's called cGMP grade registration material for making the drug product.
We also have one other toxicology requirement that's required as well. Having said that, we've got a cash need that will come up sometime probably in the Q4 , middle of the Q4 of this year. We don't want to basically get ourselves down to a reserve tank before we go out to look for additional money. What have we done to plan about that? This is something that we think about a lot early on now in terms of what might we be doing sometime later in the Q4 or even in the Q1 of next year. We recently opened up an ATM, which some people may be aware of. We reported this on an 8-K, I think, last week.
This allowed us to take advantage of our baby shelf registration, our S-3, to the tune of an additional $6.3 million. I know that some comments on the stock chat rooms were, they're going to basically dilute the hell out of everybody with this. That's not the intent. This was an insurance policy. We're not going to be raising money at these prices out of that shelf, but it's something that as the values through inflection points increase, we may tap into that at much higher prices to basically bring additional cash into the mix. I think that Steve had asked a question about the next major inflection point, and I think that that comes when we get clarity from FDA out of that guidance meeting.
That'd probably be a pretty good indication of exactly what the FDA and what we know is going to be required for us to move forward. It's possible that we may use that as an opportunity to go out and raise funding. I think a lot will depend on where the value of the stock is. Because I'm very conscious of the dilutive impact on the investors that have been in place. One other factor that should be brought up is the issue of outstanding warrants. Okay? Because the financing in November of last year, along with that came a significant amount of pure, straightforward, vanilla-type warrants, no special revaluations or ratchets or anything like that. Those warrants are convertible at $2.05.
If the investors choose to convert some of those, we're going to get $2.05 for every one that's converted, and that could be worth upwards of close to over $20 million. That could be a source of additional cash. I think the overhang on that is already in the fact that that is in our capitalization. Everybody can see that those warrants sit out there. To get through the end of 2027 and through 2028, we're probably looking at an extra $15 million to $20 million coming somewhere in some place. If we can get it through non-dilutive strategic investor funding, we'll try to do everything we can to minimize dilution, but can never make a guaranteed promise. Sometimes you have to do what you have to do.
Great. Okay, well, thank you. Thank you to the audience for all the great questions. Thank you, Dr. Plott, for joining us today. This was really a wonderful discussion, very informative. For the audience, if you have additional questions or you want to reach out, please, everyone out there has my email address. I'm happy to facilitate that. Bob, I'm going to turn it back over to you for any final words before we close out.
Okay. Thank you. Well, first, let me thank everyone for taking time out of their day to be an active participant in this exercise. I'll follow up on something that Dr. Plott alluded to, and that is the textbook answer is everyone out there should probably be getting a skin check from a dermatologist once a year. We've talked about the consequences of what happens if you don't catch these early. The longer you wait, the more serious they become. I would just strongly urge each of you to think consciously about the fact that the sun is not always your friend, and especially prolonged exposure, multiple sunburns at a younger time in your age, get it checked out. You'll be much better off. I'll leave you with that thought.
Great. Thank you, everyone, and have a great day.
Thank you.