Provectus Biopharms

All right, as we have everyone loading in here, we will go ahead and get started. Good afternoon, good morning, good evening, depending on where you are. Welcome to Prevectus Biopharmaceuticals' fourth quarter investor update. My name is Alyssa Berry, co-founder and principal of investor relations firm Alliance Advisors IR. I am hosting today's call. Ed Pershing, chairman of Prevectus' board of directors and chief executive officer, and Dominic Rodriguez, board vice chairman and president, will provide company updates and their remarks today. Following the presentation, we will conduct a question and answer session. This presentation is being recorded and a replay will be available on Provectus' website. Management has cameras turned off at the moment, but we will be turning them on for the Q&A portion of today's call. Today's discussion includes forward-looking statements. As always, we want to caution you that such statements are based on management's assumptions and beliefs. These forward-looking statements are subject to uncertainties and other factors that could cause actual results to differ materially from such statements. Please see Provectus' public filings for a discussion of these risk factors. I will now turn the call over to Ed for his opening remarks.

Thank you, Alyssa. First, I want to express my appreciation to each of you in attendance for this update, as we appreciate your interest in Provectus and our future success. We believe Provectus' value will be determined by the unique capabilities of Rose Bengal Sodium RBS molecule, the company's proprietary synthesis process for manufacturing pharmaceutical-grade RBS, and the numerous potential global market opportunities to address different unmet medical needs in an affordable and accessible manner for patients. Provectus's worth would be driven by RBS's therapeutic strengths, patient impact, growth prospects, and market potential, rather than dictated strictly by financial-driven parties. Perfectus currently has a unique position as the world's sole provider of pharmaceutical-grade RBS API. Access to this API is essential for the development and commercialization of RBS-based therapeutics by Perfectus and or the company's future partners, underscoring Perfectus' potential strategic value in the biotech sector. We believe with numerous opportunities in front of us, that there is a dynamic opportunity and multifaceted business model for Provectus is essential to fully realizing RBS's capabilities and the company's intrinsic value, and consequently Provectus's market capitalization. One of the specific examples of that is the work we're doing in ophthalmology. This business model may have to be tailored to each specific disease area the company targets, potentially requiring different business strategies to maximize RBS therapeutic potential, Provectus' market growth, and thus the company's value. We look forward to guiding the evolution and design of these business structures to ensure the market value of Provectus is fully maximized. With that, I'll turn it over to Dominic.

Thank you, Ed. Hello, everyone. With regard to clinical stage PV10, our cancer immunotherapy drug candidate and its application to injectable solid tumor cancers, we wanted to provide updates on our two programs. The lead program, metastatic pancreatic ductal adenocarcinoma, or MPDAC, Our current goal is to secure an FDA type C meeting in the first half of next year, 2025, to secure the clearance of the program, which would then allow us to work with Moffitt to begin patient enrollment. In regard to an investigator-initiated study that another group at Moffitt was interested in pursuing, there remains significant interest by them and potential funding for this investigator-initiated study to commence, and our current objective is to try to initiate a penile squamous cell carcinoma clinical trial, Phase I clinical trial in 2025 that would focus on patients at the preoperative stage. In both of these cases, we wanted to highlight and we appreciate shareholder feedback and at times criticism that Provectus is pursuing the next new thing or shiny objects. When we look back at the clinical trials that have been run since Ed and I joined the company in 2017, the goal has been to fully understand what is the best clinical solution trial protocol, the protocol for delivering PV10 that best puts patients in a position to succeed. And by succeed, we mean durable responses that ultimately lead to overall, longer overall survival. When you consider or look at the many trials and patient cohorts, distinct patient cohorts that these trials have used, you realize that the two programs and their cohorts, one in cutaneous melanoma, one in uveal, identified or helped us identify that in order to have PB10 succeed for patients, we needed to be able to give as much drug as we could. PB10 is an intratumoral therapy, and so if there is disease to inject, i.e. a tumor, then we need to inject and, if necessary, re-inject. in order to essentially then when you don't need PV10 is when either there is no more disease to treat, a good thing, or on the negative side when the PV10 has failed the patient. And what we've seen from the cutaneous melanoma trial in combination with PD-1, Keytruda, the third cohort of that study, and then towards the end, the latter cohort of the metastatic uveal melanoma program, where PV10 was given in combination with CTLA-4, ipilimumab, or Yervoy, in combination with PD-1 or Obdevo, was that enough PV10 to given enough times over a long enough period of time, meaning, again, that there was the opportunity to inject and re-inject multiple lesions, that we saw the promise of potentially longer survival in these single-arm studies that would underscore our thesis. And so with respect to the MPDAC program, that is the time taken that we bring to this study as well as with high expectations that upon clearance and upon patient treatment, we feel very excited by this. The other aspect for choosing MPDAC, understandably so, when we first made comments about this study in 2018, again, was the needing to understand the clinical trial protocol and where we could maximize or optimize it for patient success, But also in those two studies, the cutaneous melanoma and uveal melanoma programs that I mentioned, PV10 was combined with a checkpoint inhibitor. Given the skepticism that some have with respect to the local treatment generating a systemic benefit, we have no skepticism. Our clinical and non-clinical data clearly support the systemic effects, benefits of the atrial tumoral administration of PV10. the MPDAC program in combination with chemotherapy essentially shines the light on PV10 in terms of if the study is successful for patients, then more credit, we hope, will be given to PV10 and its intratumoral administration than might be otherwise so if one were to combine it with a checkpoint inhibitor. A point to highlight with the penile SCC program is another strength of Again, here, coming in as a pseudo-scalpel to reduce or minimize the following surgery that may or may not need to be done for patients with this indication or this affliction. And so we've tried to be very careful in the studies that we are conducting. trying to put forth with, again, an optimized or maximized clinical trial protocol, which is to put PB10 in the best position to succeed patients where, should the data be successful, it would be very difficult to be skeptical about them. Alyssa, next slide, please. We have been talking since the earlier part of the year about the work in ophthalmology. And of course, many of you have been following the work at Baskin Palmer Eye Institute, the leading ophthalmology group in the US and very likely the world as part of the University of Miami Miller School of Medicine. We are forming a clinical stage biotechnology startup company in order to pursue this disease area of ophthalmology where the new company, which we are using for this presentation and sort of for sort of slang, NUCO, we've also referred to it in conversation and at meetings as ICO, to initially focus on treating infectious keratitis using rose bengal sodium. The current goal is to launch NUCO and close a seed round investment this quarter, the fourth quarter of 2024. Additionally, we currently anticipate a data readout of a phase three trial that involves Bascom Palmer's innovative ocular research, Rosbengel photodynamic antimicrobial therapy, in a setting where it is being compared to standard topical antibiotic treatment for infectious keratitis. In this case, the indication is fungal and parasitic infectious keratitis. And we expect that readout from that trial, funded by the National Institute of Health's National Eye Institute, using, again, Baskin-Palmer's therapy, Being run in India, we expect that Phase 3 randomized control trial to read out again this quarter. Finally, the new company currently aims to pursue a pre-IND submission meeting with the FDA in the first half of next year of 2025. So as we said, we talked with the University of Miami and part of getting to a license agreement that was mutually acceptable was to put forth that we would spin out or create a startup company to which Provectus would exclusively license companies. The license or assign the license from the University of Miami, as well as also create an exclusive supply arrangement for pharmaceutical grade Rose Bengal sodium to the new company. The seed round, which would be issuing common stock for investment, would be up to $3 million in milestone based funding tranches. Money up front, money based off of a couple of other milestones, where the post-money valuation of NUCO would range from $20 to $33 million, of which Provectus, through its common stock ownership of this subsidiary or affiliate, would be a substantial ownership that we hope would be reflected on our balance sheet. The valuation, of course, itself will be validated by the success of Muco and subsequent funding rounds that would provide investment for the new company to continue its path towards commercializing Baskin-Palmer's therapy. The funding at this point Initial stage would be to support completing the pre-IND submission meeting, which we will hope will clarify the pathway and define the timeline and cost for an initial approval for the treatment of an initial infectious keratitis indication. Again, it is taking all of the clinical data that has been generated in South Florida at Bascom Palmer, in India, Brazil, and Mexico, where clinical data using the therapy has been generated, together with foundational preclinical data in vitro or petri dish work, as well as in vivo safety data in rabbits, in order to create as a full package of information and data for FDA to help us understand what gap gaps remain, and what next steps, such as a bridging study, would then bridge from the current data set to what is required to achieve an approval. And of course, the funding would allow for us to secure the acceptance of an IMD for the use of rosemingle sodium in ophthalmology for the first time as a therapeutic. That's really important for us. Finally, NewCo may raise up to another $3 million under the same terms, conditions, and valuations, providing potential flexibility if we think that it is prudent to continue taking in money at these valuations with the hope and goal of raising money for what comes next at a much, much higher valuation than otherwise. So we wanted to give NewCo flexibility in terms of its business plan and its funding source. Alyssa, next slide, please. And Ed will talk here about how NUCO addresses an opportunity for Provectus monetization that reflects his earlier comments about the business model that we're employing at Provectus in order to really expand and monetize and make available Provectus' platform. Ed.

Thank you, Dominic. Yes, NUCO really does reflect the structure that we've anticipated for quite some time, so you could consider it almost the first model with opportunities that Provectus has in front of it. It's a very dynamic business model. They may change from application to application, but it establishes basically a critical stage ophthalmology-focused biotech company in which Provectus will own a majority interest in it. and has been able to raise capital to perceive this opportunity without putting demands on Provectus. In fact, it has led to additional investment in Provectus by the interested parties. And so there's a two-phase benefit to this to Provectus shareholders. And when you consider the potential valuations of such a company, and Provectus owning a majority interest, I think it's really apparent in how this could be beneficial to Provectus investors, as it's basically a non-diluted form of capital raise. This is very much a high-growth area, as we've noted previously in discussing Baskin Palmer's work. In the field that it's focused on now, it's the second leading cause of blindness across the world, and Baskin Palmer continues to pursue other possible applications for the drug in the ophthalmology space. And this is basically an example of our willingness to employ a versatile business model and what that can mean for the company. We believe this business model may offer the opportunity to capture additional non-dilutive capital funding for Provectus as we continue to pursue this, particularly if we achieve the outcomes we expect in ophthalmology. And so, as shareholders, I think you should consider what this opportunity reflects in a unique way for better positioning Prevectus and its financial position and financial future.

In terms of manufacturing, thank you, Ed. We are currently working with our CMO partner to produce a new clinical supply of PV-10 vaccines. which of course is our immunotherapy drug product candidate for injectable solid tumor cancers. Importantly, for NUCO in ophthalmology, we are working with the same CDMO partner to produce an initial clinical supply of PV305, the name we've given to the topical rosebangle sodium-based ophthalmic drug that will be used in combination with their medical device for the treatment of infectious keratitis and potentially other indications and disease area and other diseases of the eye. We want to highlight the importance of CMC, chemistry manufacturing and control, as it relates to consistently manufacturing a highly pure version of rose bengal sodium, an active pharmaceutical ingredient, and the strong data and capabilities on the CMC side that protect us over more than a decade of producing lots of this product. is essential to achieving regulatory approval and ensuring drug quality, safety, and efficacy. We've seen examples, of course, of companies that stumble at the manufacturing stage. And while we are not saying that we are immune to challenges with manufacturing, one of Provectus' longstanding strengths is is the CMC data of having to learn how to produce what is essentially near 100% pure rose bengal sodium API. So it's an important component to any drug development program, and that's something that we want to highlight as well and that we work on clearly in the background, under the waterline, but almost as important as generating robust safety and efficacy data through the clinical trials. As many of you remember, we applied for a trademark of Veripure. This relates directly to the manufacturing, where Veripure represents the branding, the name of Provectus' proprietary technology and processes for producing pharmaceutical-grade rose bengal sodium API at near 100% purity. We plan in the first quarter of, sorry, the first half of next year, 2025, to introduce the idea of open source Rose Bingle sodium medical research. Many of you will have followed, we hear this from shareholders all the time, about research on the molecule, like there is obviously research on many other molecules around the world. And we aim to become the primary global source for or of this pharmaceutical-grade rose bengal sodium for any and all non-clinical medical research on the rose bengal sodium molecule. The reason and the approach behind this is simply to enable that third-party exploration of therapeutic and diagnostic applications in addition to our own. The message that we have for researchers is collaborate with us, Provectus, to create a potentially viable regulatory pathway for your innovation based on Rose-Bengel to become a treatment reality for patients. And, of course, the eventual creation of NUCO in ophthalmology is evidence of the collaboration work that we've done with Baskin-Palmer and the University of Miami in order to arrive at that. Despite hundreds and hundreds of patients being treated with Bascom polymer therapy, what Rose Bengal sodium pharmaceutical grade API provides them is the opportunity to make all of that work a reality and scalable should we be able to achieve an approval of their therapy. We've taken early steps to establish pharmaceutical grade Rose Bengal in academia in advance of a Veripure launch by, of course, journal articles that reference the notion that Provectus has this quality of API. Ed, would you round out the discussion of Veripure and the Provectus platform?

Sure. And basically in concluding this part of our presentation. I want to just share with you just this month I was approached by a medical research scientist with a technology they've developed for drug delivery and because of their awareness of Provectus' approach to drug development and the model we're using and I have a very unique program that they've spent almost 20 years in development and it's just one example of how as this space becomes aware of what Provectus is doing and are open us to consider basically open source technology. They were aware of our intertumoral therapy applications and from that and how we were advancing Provectus beyond that, made it a very attractive opportunity in their eyes to approach us about could we possibly work together. And so that's a very tangible recent example of why we believe this business model is going to be fundamental to Prevectus' ongoing success, but also in a way that will increase the value of Prevectus while also advancing new and better technologies for addressing cancer and other diseases. And so one thing I find so encouraging of this is the flexibility it provides us, not only for drug development but also for and the aspect of raising capital in a non-deleted fashion that directly benefits shareholders and investors. I'm going to turn it over to you, Adele, and other research.

Thank you, Ed. Provectus has a third clinical stage drug candidate, PH10. and we are anticipating the initiation of a large animal study in the first quarter of 2025, which would really be the intersection of the company's research programs and a collaborative effort by the Rockefeller University in New York City and the University of Texas Medical Branch in Galveston. The non-clinical study will use a drug formulation to target a range of dermatological conditions, as well as treat full-thickness cutaneous wounds and showcasing, again, expanding applications in both dermatology and advanced wound care. What we feel very excited about, obviously, is this collaboration highlights our commitment to addressing indications, diseases, disorders that are global in nature, and in particular with dermatology itself. based also on foundational clinical and non-clinical work that has already been done, provides a particular opportunity for a very large growth opportunity for us that we hope once this work is wrapped up, we'll be in a position to have a fulsome data set and to be able to promote this program more. Finally, in canine cancers, as you know, we've been working with the University of Tennessee College of Veterinary and Medicine to establish a foundational non-clinical research data set in vitro activity and vivo safety of PV10 for treating soft tissue sarcomas in dogs. Unfortunately, that work has been surprisingly inefficient, notwithstanding a lot of non-clinical and very relevant data from Provectus and its collaborators, as well as in the literature. And so we're currently, our current objective is to refocus this program towards developing an investigational new animal drug application that leverages more of the existing human data and cross-references PV10's existing IMD investigational new drug form in order to streamline canine drug development. And we'll have more information on that in the coming quarters. And then in regards to pending journal articles, we expect articles to be published about the non-clinical head and neck squamous cell carcinoma work that was done by Moffitt and presented at AACR earlier this year. the clinical work done for treating metastatic neuroendocrine tumors that presented on the liver by Australian clinicians, and then, of course, work done in a non-clinical fashion looking at tissue generation and repair at the University of Nevada, Las Vegas. Again, the goal here is to continue putting forth research from the company, but also being able to then stand upon these as we reach out with Veripure and encouraging other researchers to collaborate with us to receive Rose Bengal sodium pharmaceutical grade from the company in order to power their own research and realize that their dreams of getting a treatment to patients can, we believe, can be made reality by partnering with us and having a sustainable, consistently produced, high purity version of the API for eventual acceptance by regulatory bodies. And then with that, I'd like to turn it over to Alyssa, who will moderate the Q&A with Ed and myself.

Thank you very much, Ed and Dominic. That was great. Appreciate the overview. I am going to open it up to the audience for questions. There is a Q&A function or chat that you can enter your questions into. So we'll just give it a minute and we will then open up to questions.

We'll be turning on our cameras.

Yes. Thanks, gentlemen. So question that has come in around collaboration work. Can you just – there's quite a few opportunities for collaborations underway. What else is there that might be cooking that you're able to share?

Sure, Ed, would you like me to just address the questions here?

Yeah. Dominic, I'll mention the one, different stages, and then Dominic, you can go into further details, but one of the things that is occurring is getting more inquiries because of how we've advanced this and the term that Dominic initiated, similar to technology companies, the open sourcing of our molecule, I think is creating interest. Even those that are not In drug development, knowing the approach we're taking for advancing this drug technology is leading to inquiries, and that's very exciting. The one I referenced in my earlier comments was something that's been the passion of a medical engineer for, well, over 20 years. And when I was contacted, I immediately recognized some of the benefits that could also prevent us in how we utilize PV10, particularly in very challenging medical cases.

Yeah, in regards to partnership, look, we have said at past meetings and past calls that we do have gone and shared select data with pharmaceutical companies and gone under CDA with them for their evaluation. Ultimately, what we feel is that the – at least in terms of PV10 for partnership – that the MPDAC study is the one that would fully display the vast potential of PV10 with an optimized clinical trial protocol that would maximize the outcome for patients and be able to demonstrate its immunotherapeutic capabilities, we hope, it being PV10, when combined with chemotherapy for a really tough indication. And so all of that work and the knowledge we've gained and the feedback, positive and critical, about the data that Provectus has generated since inception from patients third-party pharmaceutical companies puts us in the position where we believe that it's the MPDAC study that we need to focus on. It's a well-designed, well-developed protocol, and that from the data set that emerges from it will dictate the future of PB10 and its initial approval pathway.

One thing I would add to that for the shareholders to note that The PDAC is basically, we do not believe this first step we're taking will be that capital intensive, and it can be conducted over a relatively short period of time compared to most clinical trials, and yet can have enormous evidence of clinical benefit in these very challenging cases. And so there's a lot of reasons for going down that pathway.

Thank you, Ed. Dominic, maybe this is a segue to a question around timing for MPDAC. Is there anything we can comment on there?

Yeah, so we would expect that the trial would start within a quarter or two quarters after we've received clearance from the FDA. And that assumes, of course, that trying to work in parallel that the study is teed up to go at Moffitt. As we said at the annual meeting, we'll endeavor to provide feedback or updates as the trial starts. And then to the second part of that question in terms of when the first data, you'll have a good sense once we start the study, these patients typically have a median survival of four to six months. And so from there, that will tell you that as patients are being recruited, we'll have a very good sense of how the study is doing, really measured in quarters, unfortunately. But the longer that the study can be pushed out, then presumably patients are doing better rather than worse. And so we'll provide those updates as much as we can when the study commences.

Thank you. A question here around the canine cancer work that we've been doing. Can you talk a little bit about the outcomes and the approach?

Sure, I'll give some comments, and then I think Ed has a more macro perspective as it relates to all of the research collaborations in the different areas that we've worked in. So you have heard us say over the years that The molecule is quirky, and it really takes a lot of effort and perseverance and sometimes resilience by the researcher to work through these quirks in order to understand what they're seeing and let their scientific curiosities and experiences in their specific specialty area expand and grow. And so, unfortunately, sometimes programs happen, such as some COVID work that was done with the University of Tennessee Regional Biocontainment Laboratory, where there's some initial hiccups that need to be overcome when they're working with the molecule, when they're trying to understand how it works with cell line strains or in administering it, let's say, to rabbits for safety. Sometimes clinicians or researchers with not a lot of experience with the molecule and making assumptions based off of their prior experience end up sort of stubbing their toe in terms of being efficient and effective. And so we often work with these researchers using, leveraging all of that vast amount of knowledge that the company has generated in order to help them through the program. Sometimes, most of the time it works, sometimes it just simply doesn't because sometimes They need to be a little bit more open-minded. They need to be sort of flexible in terms of working with the molecule. We have a very, very strong track record of reproducible, repeatable science, and so sometimes it just happens that the law of averages that the 1 in 100 physician just struggles with it, and we need to work with them to overcome that.

Looking at a couple of different – oh, sorry there. Ed, did you want to build on that?

Yeah, I'll just say I agree with Dominic's comments. At each step of the way, we have had to do a lot of coaching, and sometimes that just adds to the delays to getting outcomes. But we look forward to continuing to pursue collaborative arrangements, and we're very excited about what the future holds in that space.

Thank you, Ed. There's several questions around timing. I know we've got shareholders very excited and anxious about the various projects underway. Dominic and Ed, can you just talk a little bit about the approach of, I'm calling it the diversification of opportunities, and how I know these processes take time. Is there anything that you can comment on in terms of timing and approach for all of the different trials and projects underway?

I'm going to take the first part and then you jump in. I'm well aware of people's concerns. Some have posed the question, are you pursuing too many different areas of development or As Dominic and I use the phrase, you know, are we chasing the latest shiny object? And that is not the case. In each of these that we have pursued and some continuing to pursue, basically it is not in any way diverting us from our focus on the drug and in cancer applications. What it is, it's building out more knowledge And also, in each case, it's requiring minimal financial resources while creating the opportunity for potentially very significant financial gain in the future. And so it's something that we're very mindful of. I'll use the most recent example in which I encountered – And it's because of the direct potential benefits to Prevectus' use of PV10 and potentially other molecules that I saw potential synergistic benefits. But it would be a very, very low cost development pathway. And so I just want to, as we discuss opportunities, we are very mindful of the consideration of time, resources, and financial resources.

And I'll add, with respect to, for example, with MPDAC, we spent almost a year finalizing the clinical trial protocol. So there's a lot of component parts that need to be addressed, such as an FDA meeting, getting into the lane for Moffitt to begin the study. And so those are the things that we've been working on and we'll be very clear about when we will start that trial because you'll hear us give guidance that we will start the trial. And so hopefully you'll hear it from the horse's mouth. In regard to the Miami project, I mean, the new code for ophthalmology, we say the timing is this quarter. Work is being done. And when we're ready to announce that, again, to formally launch the company, we're working with Alliance Advisors to do that as well. They were consequential in a lot of our branding work, names, logos, et cetera. And so we'll be in a position to then, again, make more of a – of an announcement when we're ready. And to Ed's point, something like ophthalmology and UCO presents an opportunity to generate non-dilutive funding for the company. We have an incredibly bioactive synthetic small molecule. I think it's pretty clear the amount of research that Provectus and its collaborators, as well as unrelated and unaffiliated third parties have done, And so we're looking for different ways in which we can create shareholder value, promote or encourage the use of Rose Bengal, establish it with a strong science foundation that is reproducible and repeatable, and that essentially provides more shots on goal and more potential value for shareholders. And so that is what drives the the way in which we've been trying to increase the number of opportunities for Provectus to reward shareholders with value. And we understand the time that it's been taken, and we understand that shareholders at times may be impatient with us, but we continue to focus because we think that the science outcomes that we've seen and the data, non-clinical and clinical, clearly support the opportunity and will continue to execute while always being mindful of dilution potential for shareholders.

I would add one point of comment to Dominic's. I think the ICO is a great example of the benefit to this because, Imagine the fact that we should be seeing the results of approximately 330 patient random control trial here next month, which has been of no cost to Prevectus and has not impacted our time demands or financial demands. And yet we can be a direct beneficiary of that work done in India, as well as Baskin Palmer's work that they've already concluded.

Maybe that's a good segue to a couple of questions around how do we further improve or expand our patient recruitment. Can you comment on that?

Sure. In terms of patient recruitment, so both organizations, both oncology departments at Moffitt feel very comfortable with patient recruitment. And in large part, we're focused on single sites because we need to demonstrate very robust, and albeit they are single-arm studies, to generate high-quality data. And by high-quality data, we mean successful outcomes for patients. And so rather than have multi-site early-stage clinical trials at this stage, we'd rather work with sites and investigators who are passionate about the application of PV10 to a particular disease indication that they're trying to solve. And so we understand there were questions about past recruitment. We think that recruitment was generally okay, can always be better. But in these initial trials that we're running in MPDAC and Penile SCC, the goal is to make sure that there's a sound foundation, that the data makes sense, that there's a clear pathway based off of that data for approval, and then we can move to multicenter sites or studies where, again, the success of the data generates, we hope then, market capitalization and the ability to raise funds that would then fulfill those multicenter sites where we hope enrollment will be strong because of the results from the prior study.

Yeah, I'll just add, Don, to your comment. The specificity at which we look at probable patient enrollment is a key consideration as we make decisions. And so... We're not relying upon outsiders. We're actually looking directly at what the institution is able to recruit and the physicians involved in their past and current success in patient recruitment. And they're standing not from a national standpoint as far as their programs as we make these decisions. So as far as realized before we got control, there was in the, Prior melanoma trial, there was very poor patient recruitment, but I assure you we're very attuned to patient recruitment capabilities before we begin any initiative.

Thank you. Question around status of poetics.

Sure. So we appreciate that shareholders might project outcomes on us as it relates to programs. What we often do is encounter challenges with programs or partners or situations. In the case of Poetic, We were on the cusp of a clinical trial that had been finalized by one of their advisors and were ready to go. And unfortunately, due to circumstances that didn't appear related to the protocol or the pediatric relapsed and refractory cancer program, aspects of leadership of Poetic decided not to continue. Having said that, one of the component partners, one of the partners of Poetic, the University of Calgary, the Cummings School of Medicine, Dr. Arun Narendran, has been, as many of you have been following, one of the most prolific researchers for us as it relates to not only initially validating PB10 in non-clinical work for pediatric, relaxed, and refractory tumors, he also then continued to do work across a wide range of other areas at our behest where he showed oral administration for a hematological indication for solid tumor cancers, where he enabled in silico or computer modeling during the coronavirus. That led to work that we did to understand in in vitro and in vivo settings the potential to administer the drug in different ways in order to see its antiviral properties better. He's also been instrumental in some other proprietary targets that we've been working on. And so we have been in many respects working with Poetic, but its lead research site. And there will be references of a meeting that he held where there may be an opportunity to pursue a pediatric indication with probably a rather notable institution. But it will take some time for us to get to that point. But sometimes you're ready to go. and something other than strong science and a strong patient rationale might divert the program. We feel that the poetic relationship was fantastic because of what it produced in terms of a relationship with Dr. Narendran and the prolific work that he did that opened our eyes to the vast potential, the reason we call this a bioactive molecule. So hopefully that will give you some feedback on that. Ed, do you have any further comments to round that out?

No, I view the poetic relationship And I have my own personal observations as far as why it wasn't pursued across the poetic organization. I think it centered on just a couple of people. But the benefit of that relationship has been vast in identifying opportunities for Provectus to pursue and just a great, cannot ask for a better partner than Dr. Narendra. He is very instrumental in our success.

And I'll just throw in, sometimes prospective partners, partners don't understand the molecule that we have. We'll share a story where in the meeting where one of the leadership of Poetic and a pediatric oncologist liaison from a large pharmaceutical company that is quite well known, while Dr. Narendran was giving his presentation of his in vitro work, raised what I'll call rather unintelligent questions about his work, not understanding that the level of concentration in those studies using rose bengal sodium is higher than what they're familiar with with other compounds, meaning that you can use a higher level of dose for PB10 than you could with other drug agents. And they didn't understand or thought that there would be some systemically toxic outcome from the Petri dish work that he did, not understanding again that at that point in the late 2010s, early 2020s, when this meeting occurred, that Provectus had a significant amount of non-clinical toxicology data, PKPD data, as well as a strong amount of established safety data in clinical trials of people that would have given them a better understanding of how to use our molecule. And so sometimes, again, We need to work harder to show and to help partners understand and get and I guess let go of their preconceived notions and their assumptions. But ultimately, I think A study like the MPDAC one and the time it's taken and the careful design and trying to blow away or answer any and all skepticism, ultimately then it just boils down to the data where you're ready to push your chips into the middle of the table in a risk-calculated way, and you think that that study really will produce the answers we hope that prospective partners and other organizations are looking for. Ed, do you have any other comments on that?

Yeah, I can't help but comment on that with Dominic, because if you've got your screens on, you'll see me smiling, because I was considering telling that story that Dominic just shared in my earlier, and I thought I'd back away. So let me just be blunt about it. Literally witnessed what Dominic, we were in the room when that occurred and realized, and I watched that impact of those statements, which basically were made without adequate knowledge of what we have. And I saw it bias a poetic leader. And to me, it distills what we encounter and I've encountered across my career so many times in medicine. There's some inherent biases just because of past experience and lack of knowledge of something new and unique. It ends up leading to a bad decision. What it did related to the but it ended up being a benefit for us because it really allowed us to drill into a much deeper relationship with Dr. Narendran, and we were able to move faster, quicker, and further, I think, as a result of that as far as what are the capabilities of the drug. And so there was a lot of great things that have come out of that. But what Dominic just shared was the key event in which, across POETIC, we quit pursuing a broad relationship and focused on Dr. Narendra, just to be totally transparent.

Thanks, Ed. Quick one for you here. Are we still pursuing approval in Australia? Oh, you're on mute, Dominic. I'm on mute, Dominic, yeah.

We were looking at that as an avenue with the data that we have, and again, I think we mentioned this at the annual meeting, that running an approval or looking at a drug approval pathway for cutaneous melanoma, given all of the approvals and the landscape of it now, would require 500 to 700, maybe more patients, and several years, because it's more than likely that the primary endpoint would be overall survival. And when you look at the financial component of that in terms of the cost to run that study, and opportunity for a PD10-led combination, because it ultimately would be a combination study using the various standards of care that have been approved over time, the results would not be, the spending of money on that as opposed to, let's say, MPDAC would where you're partnering with chemo and you have the opportunity to demonstrate, we hope, success with progression-free survival than an ultimately overall survival in a pivotal or confirmatory study. It just simply makes more sense for protectors to, from a financial resources perspective, to pursue MPDAC rather than looking at a melanoma study, whether the approval is sought in Australia or globally.

I will share this. We did develop even broader relationships with the leading oncologists and oncology surgeons and even oncology pathologists across Australia. I think the total significant relationship now is at 12. And they are strong supporters of what the molecule's capabilities are. And I think we have an expected paper coming out. related to neuroendocrine tumors in the near future.

Right. So we value the work that we've done there. And it has contributed to, again, optimizing a clinical trial protocol that we think has the potential to put each and every patient that gets PV10 in a position to succeed with the disease that they have. But we've got to pick and choose our spots in terms of being prudent about financial resources and how we move the company forward.

Great, thank you. Question here, please expand on the details of a bridge trial. Is this the same as a P4 trial?

Yeah, so we don't have, so again, we'll provide more information when the new company approaches the FDA for a pre-IND submission meeting. We need to hear FDA's feedback on the situation, which is essentially the It's the same molecule, but Provectus has the clean API and the prior data was generated from commercial grade material or non-pharmaceutical grade. And that will help define what the parameters of that bridging study are. Certainly the readout from the India study, the phase three, will contribute. And so once we have that feedback, the minutes from that meeting certainly will be in a much better position to update shareholders.

Great, thank you. A question here around which programs do we believe are the furthest along in approval maturity? And is there an estimated deadline to see revenue generation from RBS?

Sure, it's always good that we can get something related to RBS to generate revenue and hopefully profit. In terms of the maturity of the programs, you'll see that we have a phase one trial in metastatic pancreatic cancer, even though the company has had prior to Ed and I joining that was already embarked on a phase three randomized trial, which we look at the bright side of that, which a study we had to terminate, because of the vast analysis that was done on the CMC features of PV10, whether it was FDA, whether it was Germany's Bee Farm, which has a long reputation for being very focused on CMC. So we went to a phase one study, which while it would seem that it's sort of going a steps back, it's simply filling out the dose escalation, dose optimization checkboxes of Project Optimus for FDA in terms of designing clinical trials. Hopefully, with the existing data that we have, together with the new data generated in that study, and hopefully positive outcomes, you're then in a position to move and design some program that either is accelerated approval or a phase three for MPDAC. Ironically or interestingly, what the work that's probably the farthest ahead would be the work that comes out of Bass and Palmer is, in terms of the hundreds of patients that have been treated for infectious keratitis, but interestingly, a NIH-funded Phase III RCT, where for the first time you would be comparing rose bengal in a therapeutic setting in a randomized control trial. And so that's why we're very excited by that work. understanding that we're all on pins and needles as it relates to the outcome of that study, but it does provide an opportunity when you're in any randomized clinical trial to demonstrate clinical benefit. comparing a treatment with standard of care versus standard of care alone. So in terms of which is farther ahead, it's interesting that Baskin Palmer may have generated or developed a program that is farther ahead in terms of its generating sort of comparative data than what we have. And so that's probably the way we'd look at it.

Well, just add to that, Dominic, the fact that, you know, in India, It's going to be over 300 patients. And that was NIH-initiated, so that brings a connection of our drug to NIH that would not have existed absent the eye care work. And then also, one of the things I've found in talking to potential investors, there's nothing more effective about proving the non-toxic nature of drugs rose bengal sodium, they talk about it being used in the eye. From a layman's perspective, that pretty well indicates just how safe it is. And so it has a number of benefits to our efforts in advancing the company. The ophthalmology work is as far along as it is, and it's been at virtually no cost to the company.

That's great. Thank you. Question here around the type of organization that will be needed to move ICO program forward. Have we had large medical companies such as Merck show any interest in forming a company with Provect?

Sure. So we're trying to do a private company, C-Corp, down the middle of the fairway that would essentially be the vehicle for ICO or NUCO. Again, we'll unveil the name this quarter. And it'll be a straightforward organization that can raise money from venture capital organizations, whether private or corporate, can raise money from companies as it advances. In terms of, we see companies like the question raised, Merck, looking for revenue sources, and I think earlier this year closed a transaction with an ophthalmology company. And so there is a good number of prospective partners from the obvious, Alcon, Novartis, Bausch & Lomb, et cetera, as well as other smaller public companies, smaller meaning measured in billions of dollars of market cap. And so, again, once we are in a position where we have a – and we have an investor slide deck and we're really candidly just waiting to launch the company – and be in a position to then start knocking on doors to generate interest. We have work to do and we're grateful to the prospective seed investors for the funding that they provided to pull together data, go to the FDA, get a perspective on the size, scope, timeline, cost of the bridging study. But even though you may not be immediately asking for money today, you certainly want to make prospective partners aware of this work, particularly because, again, Baskin-Palmer's reputation precedes itself. And so we need to get out and do that, but we're waiting for the timing in order to be able to knock on doors and introduce people to the new company.

I would just emphasize it could be a relatively short timeline to seeing if we achieve the results we hope to achieve, to seeing a dramatic increase in the valuation of ICO, which benefits Provectus. with minimal cost to protect us. And so it's something I would call on the immediate to intermediate horizon that can have a very significant positive impact.

Thanks, Ed. Lots of really great questions. I wanted to keep – I know we're right at the hour, but I wanted to keep running through the questions. But, Ed, I'm going to turn it over to you for closing remarks. I'll pull up your slides here, but please go ahead.

Okay. In closing, Dominic and I and our team recognize, you know, one of the key interests and most common questions we get from shareholders that centers around value, whether that's reflected in capped value or the share price, most commonly the share price. And hopefully we've conveyed today why we're so confident about the value of the company, the future value of the company. And it all comes back to the molecule and its unique capabilities. And the fact that we're the only company in the world that can manufacture it to pharmaceutical-grade products. So we're in a unique position and cannot be more excited about that. I think also today's meeting, and again, we appreciate your time, gives us an opportunity to use the ICO model as an example of the various business models that may be initiated as we continue to advance Provectus' interest in bringing this drug agent to treat various diseases and be so in a fashion that is as being sound stewards of the company and trying to do things in a in as prompt and as reasonable fashion as possible, but also being mindful of risk, whether it be financial risk or market risk or medical risk, be so in a responsible way to advance the company to achieve its full valuation. And I'll close. We are always trying to consider all aspects, and so as my closing comment, I would just call to your attention the macro environment. The country's recently had a presidential election. There's a lot of speculation about what that's going to mean to the various agencies, one of which is oftentimes mentioned is the FDA. And I would say as we consider those, we don't know what the impact of that will be, but hopefully, We feel like we're well positioned, regardless of the impact, to be able to approach FDA with sound information and do so in a fashion that we've tried to execute across this journey to where we can be successful and do so in as timely a fashion as possible. And so we just appreciate your support, your interest in it, and hopefully you understand why Dominic, I, and others are so confident about the future of Provectus and what it holds for shareholders.

Great. Well, Dominic and Ed, thank you very much for today, and thank you to our shareholders for being here, for your support and for your questions. Wishing everyone a really great rest of your day and holiday season ahead. Thank you.