Hello, and welcome to the Life Sciences Investor Forum. On behalf of OTC Markets and our co-host, Zacks Small Cap Research, we are very pleased you've joined us. The next presentation is from Phio Pharmaceuticals. Please note you may submit questions for the presenter at any time. You can also view a company's availability for one-on-one meetings by clicking "book a meeting." At this point, I am very pleased to welcome Robert Bitterman, President and Chief Executive Officer of Phio Pharmaceuticals, which trades on NASDAQ under the symbol PHIO. Welcome back, Robert.
Thank you, Lily, and thank you for tuning in to the Phio story today. Phio is an immuno-oncology company with a very special proprietary platform called INTASYL. INTASYL works in a way that makes our immune cells more effective in going after and killing cancer cells. First, let me share with you our forward-looking statements, and then we'll get into the meat of the matter. The Phio value proposition is really centered on two fundamental points and complemented by a third. It deals with a very significant market size and the special INTASYL technology, which is short interfering gene silencing technology. Our market is targeting cutaneous squamous cell carcinoma. It is the second largest incidence of solid tumors in the human body. It is a condition which is increasing due to aging population, as well as subgroups of immune-compromised patients.
There's also an unmet need, particularly in the area of improving surgical outcomes by actually doing pre-surgical intervention. We'll talk about that in a few minutes. Now, with respect to our technology, INTASYL is short interfering RNA. It is intratumoral therapy. It is surgery-modifying treatment, meaning that we are looking to, if not shrink, to eliminate the tumor, not surgically, but through intratumoral injection. This can be very significant depending on the size of the tumor, its placement on the body, as well as the general health of the patient. This particular technology and drug, as we call it, has been demonstrated safe and effective in a recently completed phase I-B trial under the name PH-762, and it is broadly patented into the year 2044.
Finally, these two characteristics are supported by an ultra-lean virtual management team and infrastructure that consists of seven employees and four to five subject matter experts, depending on the time, that basically work with us. All of the development people on the organization have worked with each other for a number of years, and so we're very familiar with the space and with each other. To speak about Phio, we have to speak about innovation because it was founded by an individual named Dr. Craig Mello, who was awarded the Nobel Prize for his discovery of RNA interference. From that discovery came the evolution of INTASYL, which is our current technology. It is patented short interfering RNA in a drug form. It is not a biologic, it is a drug, and it has the ability to precisely silence designated genes that appear in the human genome.
In so doing, it makes our body's immune cells become more effective in killing cancer cells. How does the mechanism work? We can selectively silence the signal from a designated gene, and in so doing, we can suppress the protein production that comes from that gene. When that protein in the presence of certain tumors can cause our immune cells to become ineffective or inert. INTASYL basically turning off that protein allows the body's immune cells to reactivate and go after and attack the tumor cells, in effect making our immune cells more effective in killing cancer cells. The design of this complex program is really an asymmetric double-helix design. It consists of two strands of synthetic fragments of RNA, a guide strand, and a passenger strand. I think it can best be described in terms of three words, its specificity, its safety, and its stability.
The specificity centers on its engineered design for exceptional gene targeting, meaning we can specifically identify and target a single gene and avoid targeting anything else that we don't want to target. From a safety point of view, it has the ability to deliver the drug intact across the cell membrane and into the desired target, and it can do so in the absence of any types of formulation enhancements, which oftentimes are viewed as being additional sources of toxicity. Lastly, it has stability that the drug can remain stable in its destination until it does what it has to do. It's not only these features that make the drug work, but it's also the basis of our intellectual property portfolio. We have a number of intellectual property or patents issued. We have more pending. The patents center on a number of different points.
That chemistry structure I just showed you, as well as their ability to target specific genes, the development of specific compounds from that chemistry, and finally, therapeutic applications in the form of use patents. These run out to the year 2044. The Phio strategy is technically two-tiered. We have an internal development strategy on two of our programs. For the remaining programs in the portfolio, we're looking to monetize these non-strategic programs through out-license. I'd like to talk to you about our two programs in internal development. The first is PH-762, which silences the PD-1 gene. That study is now completed as a phase I-B trial. We're in the process of taking next steps to move to the FDA for a second trial. The other program is PH-894. That is another gene-silencing drug.
It silences the BRD4 gene, which is implicated in a variety of different cancers as well. I will touch briefly on PH-894 later in the program, but ultimately, the bulk of this presentation will center on PH-762. Why do we choose a PD-silencing program as our primary or our lead program? I mentioned earlier that this is a very large market, and if we exclude basal cell carcinoma from the overall picture in the market or in the body, it represents the second largest incidence of solid tumors, representing over 51% of all solid tumors, excluding basal cell. Not only is it large, but when we were attempting to put together our initial program, we've had to look at how we could basically mitigate risk.
One of the things that we learned was that the PD-1 gene had already been validated by the large pharma companies like Merck and Regeneron in their monoclonal antibody studies. They had determined that they could affect PD-1, and in turn, they could affect skin cancer trials. The difference is that with the monoclonal antibodies, those drugs, or those biologics, I'm sorry, those biologics are systemically infused throughout the entire body to attack the PD-1 gene on the tumor surface. In contrast, INTASYL silences PD-1 by turning it off at its source in the T -cell. Think of it as turning water off with a faucet. It basically turns it off before it can get to the surface of the tumor cell.
When we were cleared for IND, back in 2023, we were given the opportunity to study the Stages 1, 2, and 4 of squamous cell, as well as melanoma and Merkel cell. In Stages 1 and 2, that represented about 70% of the total incidences of cutaneous squamous cell. It was a very large opportunity. Currently, there is no FDA drug approved for those stages, and if left untreated, those Stage 1 and Stage 2 will evolve to Stage 3 and Stage 4 and can ultimately result in mortality. The alternative, and it's a very good alternative, is invasive surgery. It is the standard of care. However, surgery oftentimes requires another option. I think when you look at addressing surgical outcomes, you're looking at recovery of the patient, and you're looking at physical disfigurement.
There are things that you have to take into consideration, such as the size of the tumor, the placement of that tumor on the body, and also the patient's age and his general health. Another way to put this more viscerally is that if you have a surgical intervention in a sensitive place, the question is, how much of a hole can you tolerate in your particular area of incision? With that, another interesting point is that many of the patients with cutaneous squamous cell are immune-compromised, whether in the form of transplant patients, hematologic cancers, autoimmune disease on different therapies, as well as HIV and AIDS. It's interesting that the incidence of cutaneous squamous cell is multifold greater in those type of immune-compromised patients. That's a very significant unmet need. Let's talk about Phase I-B study in 762 and how that came out.
The purpose of this study is a dose escalating trial, by the way. It was completed in January of this year, and the purpose of a Phase I study is to determine safety and tolerability. The Phase I design had five dose escalating cohorts. There were four intratumoral injections over three weeks with a resection or biopsy of the residual lesion at week five. The endpoints in the study were safety, meaning were there any adverse events, the tumor pathology, meaning was there any skin or cancer left remaining in the skin, and also pharmacokinetics, which looked at the dynamic of the drug in the body's metabolism. There were 22 patients that completed the trial. Everybody that entered, completed. There were 20 cutaneous squamous cell patients with one Merkel cell patient as well as one melanoma patient.
From the standpoint of safety and tolerability, there were no immune-related or treatment-related toxicities in any patients through the five dose escalating cohorts, that represented actually a 20-fold increase from the first cohort in terms of drug concentration. Also, there was no recurrence seen of any lesions at the end of the study at day 113 for the CSCC patients. What do we attribute the safety profile of the drug? There's a couple of things. Direct injection into the tumor essentially eliminates off-target serious events that could be associated with drugs that are systemically infused in the body, such as monoclonals. Additionally, INTASYL does not require any formulation adjustments or enhancers, such as lipid nanoparticles or viral vectors, to deliver it to the desired target.
This can further mitigate the risks of any serious adverse events and other toxicities often associated with those delivery enhancements. From an efficacy perspective, through the fifth cohort, we see that if we go to the right side of the screen, that in the highest dose, we had an 85% response rate. Six of the seven patients who were in that trial represented a total clearance. One patient was a greater than 90% clearance as well. Overall, across all cohorts, including lower doses, we had a 65% response rate, response rates being defined as 100% clear, greater than 90%, greater than 50%, or non-responder. Other interesting features about this drug, it's administered in the physician's office, it's convenient, avoiding the logistics of infusion centers. It minimizes recovery time associated with surgery, and there's flexible dosing to accommodate different lesion sizes with different patients.
Also, there's an economic factor here. Office visits realistically drive physician practice economics. Additionally, for the physician, there's no capital outlay required for this type of treatment by the doctor. Finally, from the standpoint of sourcing, our active pharmaceutical ingredient as well as the drug product are sourced in U.S. sites, so there's no risk of pricing differentials associated with tariff changes. At this point, we look at what we have completed through that study, and we see ourselves with a potential positioning of 762. It is a tissue-sparing treatment with safety and convenience. It reduces, if not eliminates, the tumor, minimizing surgical excision and potential disfigurement. It preserves skin integrity, promotes faster healing and recovery time, and it decreases the need for potentially reconstructive plastic surgery as well. As I mentioned, it has a favorable safety profile.
It's convenient for the doctor, and it also plays to the doctor's practice economics. With that said, what are the next steps that we're looking at now? Currently, we're looking deeply at the design of the next clinical trial to present to the FDA in very short order, sometime early in this next quarter. What we're doing in this design is taking into consideration all of the potential favorable positioning that we've seen in this first study, and taking careful diligence and being very measured in terms of how we can design that trial to bring out the best and accentuate and augment the results that we've gotten in the first trial. With that, we expect that trial will commence sometime after the beginning of the year in the first quarter of next year.
Other programs that we're involved, not other programs, but activities associated with the program, is that we just went to commercial scale production of API this past week, and that's a major step up from the laboratory scale. That drug will be available to put into drug product in the fourth quarter of this year to support the clinical trial in Q1 next year. Finally, we do have an ongoing non-clinical toxicology program in a non-human primate to also support the next clinical trial. Those are the major activities that are occurring as we speak from now to the end of the year. A quick comment about PH-894, our other program. PH-894 is a silencer of the BRD4 gene, which is implicated in a number of different types of cancers. 894 is special because it has a dual mode of action.
It can not only directly kill the tumor, but it also can activate the immune cells to go after and attack the tumor. In the case of 894, it is precisely selective only for the BRD4 gene, and this eliminates toxicity that has been associated with previously studied non-selective programs to try to go after the BRD4 gene. Also, this program does have a very clean tox profile in the non-human primate study. We are currently at a situation where we have completed the IND enabling studies for this program, and with a few additional steps to take place, including finally deciding on the final indication for this, we will then move forward and file an IND for this program. A quick comment about our secondary strategy, which is to maximize the value of our non-strategic portfolio.
We're looking at these compounds, which I'll show you in a moment, that have an opportunity in other geographies or in the portfolios of other companies, or therapeutic application sweet spots of other companies, through different types of out-licensing or business development activities. Specifically, we have oncology targets for both solid tumors as well as hematologic cancers, and also a number of different infectious diseases, including but not limited to HPV, HSV, and HCV. Over in the right side, you can see these are the number of compounds that we have actually confirmed can silence different types of genes within the genome. It's very prolific. Our research scientists in years past were very effective in targeting a number of these. Some of these hopefully will be of potential interest for other companies that we're seeking to explore with.
Let me move now into some metrics to wrap up the program and say that right now, as of our last filing, we had $17 million in cash on hand, with an additional self-capacity in our ATM worth $6.3 million. There are exercisable common warrants of $24 million that are exercisable at a price of $2.05 a share. We also, in our cap structure, there are 11.6 million shares outstanding. Those fixed price strike price warrants, which I cited above in the dollar value of $24 million, they expire in 12/2027, and there's 13.4 million of those. Other than that, we have no debt, and that's really the summary of our capitalization.
With that, I will conclude and close with saying that Phio Pharmaceuticals is fortunate to have cutting-edge technology with INTASYL as a short interfering RNA precision silencing program, which has now established safety in a phase I-B study, as well as efficacy for the 762 program. We have extensive intellectual property, and all of this leads to a very interesting world where we believe we can make our immune cells more effective in killing tumor cells. With that, I thank you for your attention, and I'm open to any questions that you would like to ask. Question number one. If PH-762's next trial replicates or improves on current response and safety data, what kind of commercial opportunity in CSCC do you believe is realistic over time?
To answer that question, Tom, there are a number of subsections in cutaneous squamous cell carcinoma that, whether it be immune compromised, could be also affecting the size of the lesion that we're treating. Realistically, we're not going to capture the entire marketplace. It is huge, but a fraction of that market is still extremely significant. If we take a 10% share of, say, 1.4 million incidents of different cutaneous squamous cells, that certainly provides for a significant opportunity and certainly one that would be very attractive for the investor's return on investment. Let's see. For existing shareholders, what gives you the most confidence that 762 can ultimately become a commercial product in skin cancer rather than just an interesting early-stage asset? Realistically, we know that phase I trials have limited amount of data. We had 20 patients in cutaneous squamous cell carcinoma.
The indications so far indicate that with that highest dose, we have a significant response rate. Also, the other important factor is that the drug appears to be very safe given its profile. Also, its PK profile is additionally safe in terms of its characteristics. Given no serious adverse events or dose-limiting toxicities in the phase I-B, do you see for a faster path to pivotal studies in skin cancer? Safety is critically important. The fastest paths are usually given to those drugs that have a clear unmet need. For example, those drugs that could treat late stage or terminal cancers, that would probably be the likelihood.
We are examining different types of what we would call clinical expedited or expedited programs with FDA, of which there are a handful of them that they look at, and we're looking at all of those to see which might be most applicable in our particular case. Next question. INTASYL was recognized as Immunomodulatory Solution of the Year. How does that external validation translate into partnering or BD interest that you're seeing? This is still a very early innovative drug, and with that comes a certain degree of wait and see with the larger players. That's why this next study will be critically important to refine what we found in the first study. Certainly, this is an opportunity to break the paradigm of existing treatments for skin cancer because it's not being infused, it's not cutting it out, it's not basically irradiating it, and it's not chemotherapy.
It could be first line. It could also be used at time as a complement or an adjunct therapy with existing therapies as well. I think the safety profile bodes extremely well, and the initial pictures of efficacy are important in attracting a partner. Could you tell us how your monoclonal antibody or how your technology differs from monoclonal antibodies? Well, the main difference is that monoclonal antibodies are systemically infused, and they treat the lesion that's on the surface of the tumor cell. Our drug, in contrast, is injected into the tumor itself, not systemically infused into the body. It basically turns off, as I mentioned in the presentation, it turns off the production of that PD-L1 protein like water turning off at a faucet.
What it does is it provides for a much better safety profile because you're not going to have off-target events, as evidenced by the fact that we increased our dose 20-fold, and in the process, we did not have anything in the way of a serious adverse event or an immune response. Let's see. How does new U.S. drug substance manufacturing for PH-762 de-risk CMC and support scalability as you look ahead to potential registration trials? That's an interesting question, and I'm glad you asked that. CMC gets minimal attention in the world of drug development. It's probably the least understood, and it's probably not as glitzy as talking about pure science or the outcome of human clinical results.
It's a critical element in this mix, and if you follow CMC issues with other companies, oftentimes it's the result of an FDA rejecting an application for a new drug approval. We've worked with this facility that's an expert in oligonucleotides. There were 12 months worth of laboratory scale documentation, testing, retesting, validation that has gone into this. It's a major step to go from lab to commercial scale in the major out of the pilot plant and into the major scale. We're working with people that have experience not only in the company, but also people in our company today who I've worked with in my former companies who have much CMC experience and have supported CMC sections of new drug applications in our former companies that eventually where those drugs were approved. I think that this is a critical thing that we're doing at this point.
Having the ability to make registration quality type batches at commercial scale is a significant look ahead to what we're going to be capable of looking down the road. Let's see. Given no serious adverse events or dose-limiting toxicities, do you envision PH-762 being used broadly in community dermatology practices, not just in large academic centers? Yes, I do. I believe that this is something that would be very well received by rank-and-file dermatologists who do derm surgery. Not necessarily Mohs surgery, but just derm surgery. Anything that is viewed that can shrink the size of the tumor, if not eliminate it, and reduce, as they refer, the size of the closure or the size of the hole, is a major benefit to these doctors for the improvement of their patients as they have to recover from the surgical wound.
The feedback that we are getting as we talk to a number of physicians, that this will be a very well-received procedure in the doctor's offices. I'm trying to see if we have any more that I haven't answered here. What are the most important characteristics of this technology? First, I think it's the design that selectively, precisely targets exactly what you want to shut down. It also is safe, which we've been now able to demonstrate through the dose escalations. It also has this unique ability to deliver exactly to where it has to go without the use of different types of delivery vehicle enhancements. It goes into the targeted cell through endocytosis and eliminates the toxicities associated with a number of these other types of drug delivery vehicles. I'm looking at my time here. I think I have one minute left.
Comment on the versatility of INTASYL. Remember, we can change the nucleotide sequences to target other genes within a given program like 762. The versatility is that you can shut down PD-1 and other programs as well, other disease states, and you can also use these in combination with other drugs. I think it's time for me to wrap up at this point. I'm getting that message. I'm going to thank everybody for their attention and appreciate your interest. If you want to reach out to talk to me on the side, I can be reached at rbitterman@phioparmma.com. I would also say take care of your skin, everybody. It's an important task. Thank you.