Hello, welcome to Virtual Investor Conferences. On behalf of OTC Markets, we're very pleased you're joining us for the Life Sciences Investor Forum. Our next presentation of the day is from Lipella Pharmaceuticals Inc. Please note, you may submit questions for the presenters in the box to the left of the slides, and you can also view a company's availability for one-on-one meetings by clicking "Book a Meeting" in the top toolbar. At this point, I'm very pleased to welcome Jonathan Kaufmann. He's the Chief Executive Officer, and Michael Chancellor is the Chief Medical Officer of Lipella Pharmaceuticals Inc., which trades on the OTC Markets under the symbol LIPO. Welcome, Jonathan and Michael.
Thank you so much for the introduction. It's a pleasure to be here today to present our company to the investors, as well as we're going to present our phase two clinical trial results. My name is Jonathan Kaufmann. I'm Chief Executive Officer of Lipella Pharmaceuticals Inc., and I'm also joined today by Michael Chancellor, our Chief Medical Officer. I'd like to start by describing what is unique about Lipella Pharmaceuticals Inc., and that is our proprietary liposomal formulations and our ability to differentiate ourselves by our ability to deliver active agents to mucosal tissue. Delivering drugs to mucosal tissue is not easy. Topical formulations are typically optimized for skin, which is a much different barrier. We use proprietary multi-lamellar liposomal technology that permits local fusion of large liposomes directly to mucosal tissue.
By limiting the distribution of the drug to the active site, we are able to achieve high concentrations at the site of interest with minimal systemic exposure. This minimal systemic exposure can avoid many systemic issues, and that's a major formulation advantage. For example, as we'll see later in the presentation, our product for oral lichen planus has the potential to spare patients from systemic corticosteroids, and this is meaningful to both clinicians and payers. Our formulation strategy is consistent with our regulatory strategy, which is to work on serious conditions that have no adequate treatment options and to utilize the 505(b)(2) regulatory pathway for efficient clinical development. Since we use agents that are already familiar to the FDA, we're able to move quickly into phase two clinical trials, especially given that we have in-house CMC. Our strategy involves advantages in efficacy, safety, and speed.
We take advantage of well-known mechanisms of action, increasing the probability of efficacy and safety, and our strategy has led to the following asset pipeline. We currently have two assets in phase two, a third asset which is IND approved, and a fourth asset which is preclinical. All of our assets are liposomal formulations of active agents, and all of our assets are intended to be delivered directly to the mucosal tissue of body cavities. Our three most advanced assets, variations of LP-10, are formulations of tacrolimus, a potent immunosuppressant, and specifically an inhibitor of T-cell activation. Our preclinical asset is a liposomal formulation intended for intravesical delivery of a PD-1 inhibitor. Our most advanced asset, LP-10 oral rinse, also referred to as LP-310, is intended to be indicated for oral lichen planus, a T-cell-mediated autoimmune disorder which I will describe in more detail on our next slide.
Oral lichen planus is a T-cell-mediated autoimmune disorder where the body's own immune system causes inflammatory lesions inside the mouth. Women are affected more than men. These lesions can be painful and sensitive. Patients report that it can hurt to eat, speak, and in some cases even breathe. These lesions also have a significant malignant transformation rate, causing cancers of the oral mucosa. It's important to note that there are no approved drug therapies for oral lichen planus. This indication thus fits our strategy of pursuing indications that are serious with no approved therapy. OLP affects up to 2% of U.S. adults, translating into a 2025 population of approximately 5.2 million, with approximately 3.9 million experiencing symptoms. Now I'd like to address the current treatment options. The first line of therapy for OLP patients are topical creams and gels that have been approved for skin indications.
These formulations are generally not well tolerated in the mouth. Patients report difficulty with retention in the oral cavity, issues with swallowing, and that it's difficult to apply. Approximately 40% of diagnosed and symptomatic OLP patients are refractory to treatment. Local corticosteroid creams, when applied to the oral mucosa, can burn, cause thinning of the oral mucosa, and immunosuppression in the oral cavity. The second line of therapy includes systemic corticosteroids and immunosuppressants, and this solution is used sparingly due to potential systemic toxicity. We estimate that approximately 40% of diagnosed OLP cases are not well controlled. This presents significant unmet demand for a new product that would be well received by both clinicians and payers. We intend to address this unmet demand with LP-10 oral rinse, our proprietary liposomal formulation of tacrolimus.
The following slides will provide more detail on this lead asset, including formulation details, clinical trial results, and finally market economics, after which we can break and answer questions you may have. Let's start with the formulation details. Tacrolimus is a potent immunosuppressant. The drug is so successful, virtually all transplant patients are on it. Transplanted organs are attacked by the body's immune system, and the main player in autoimmunity is the T cell. T cells are normally inactive, but when they encounter a host cell invaded by a foreign antigen, they activate. Their activation is mediated by the release of calcium into the cytoplasm. When tacrolimus gets inside of a latent T cell, it basically shuts off its ability to be activated, and it's the activated T cells that are responsible for most all of the tissue damage in OLP.
Tacrolimus can be difficult to formulate because it's highly hydrophobic, meaning it does not dissolve in water. Tacrolimus skin ointments are often thus oil-based, making them difficult to apply to the wet surface of the oral mucosa. Our oral rinse formulation of tacrolimus is aqueous, having liposomal tacrolimus suspended within. The liposomes in our formulation are different from liposomes in typical IV formulations. Our liposomes are large, multi-lamellar, and metastable. Our liposomal technology supporting LP-10 is patented through 2035. We have tested our oral rinse with a rinse period of three minutes and found very low whole blood levels of tacrolimus. This bodes well for the safety profile of our product and is a key parameter of differentiation.
This slide shows blood level concentrations over time after administration of tacrolimus by IV in the blue, oral tablets in the red, topical ointment in the orange, and the dotted green line is the blood level concentration over time for the LP-10 oral rinse. Notice that the topical ointment is less bioavailable than the IV in oral tablet formulations, but there's still significant systemic uptake, whereas our liposomal oral rinse shows a lack of systemic absorption. This is a consequence of our tacrolimus liposomes adhering to the oral mucosa instead of sliding off. Even with this low systemic absorption, we found significant signals of efficacy, and this demonstrates the potency of the drug at the active site. These results are part of our phase two clinical trial. I'd like to now turn the presentation over to our Chief Medical Officer, Michael Chancellor.
Thanks, John. Next slide, please. I'm very excited to share with you the final results from our phase two trial. This is a multi-center dose escalation study across seven U.S. sites. These were adult men and women with symptomatic oral lichen planus, and the treatment involved twice a day, 10 mL of LP-10 for three minutes, and the duration, the primary endpoints for four weeks. The primary objective is safety and tolerability. This is the first in human trial, and secondary are the efficacy, not only the physicians, the investigator's notation of the mouth ulcers and erythema, but also patient-reported symptoms and quality of life. On the bottom is the demographic of the patient in the study. It's dose escalation, so there's three groups: 0.25 mg, 0.5 mg, and 1 mg of tacrolimus in the LP-10. Total is 27 subjects.
Now, who would this really reflect the typical population of OLP? The median age is 62 years old. It's more women than men, about 80% women and about 20% men. This is a chronic inflammatory disease, and the average duration that the patient is suffering with it and continues to suffer with it is seven years. A quick overview: multi-center study, 27 subjects, dose escalation at the three doses that I noted in adult men and women, and the study site ranged from California to Massachusetts down to Florida. The drug is sort of similar to the mouth rinse, Listerine you have. It comes in a week's supply of bottle, sort of like the medicine, liquid medicine for children, and twice a day you withdraw out 10 mL, put in a cup, and rinse it in your mouth and spit it out. There's three phases to the study.
The first is the screening run-in phase. Make sure that they have OLP informed consent, and during the treatment phase, the first dose was done in the investigator's office whereby the PK whole blood test was done. It's three minutes twice a day. They're given a weekly supply of the medicine that they take with the log, and the follow-up is at one week and then at the primary finish line at four weeks. There's a follow-up phase where they were seen two weeks later, two weeks off of LP-10. Most people are not familiar with how oral lichen planus is measured, and it's really two approaches, and we use the parameters. The top, the dark blue, is the clinicians, the doctor, dermatologist, and the oral medicine doctor have two validated outcome measurements that they use to score the exam in the mouth.
The first is the investigator global assessment, IGA. It's rated from zero to four on the number of ulcers, the size of the ulcer, and how much erythema it is. Zero is clear, four is severe. Only patients with three and four, moderate to severe OLP, are included. Similarly, there's another REU score that's a difference. It records also similar the amount of white lines, plaque in the mouth, erythema, and ulceration, also validated scores. We have two scores that the investigators report at each time point compared to baseline. Just as important as FDA requires is, does it improve the patient? We have two 10-centimeter visual analog scales that the patient will self-report on zero, none, 10, worse than imaginable on pain and sensitivity in their mouth before and after treatment.
There's a validated OLP symptom severity measure, OLP SSM, that asks over the last 24 hours, does it not bother you or maximally bother you when you talk, when you eat, when you brush your teeth, a validated questionnaire. Finally, the global response assessment on a score of zero, meaning, "Hey, I got much worse with treatment," to six, "I'm markedly improved with treatment." This was done at the four-week time point. Next. Key inclusion and exclusion. The study included moderate to severe OLP because they had to have an IGA score of three or greater. They have to have a pain or sensitivity of at least a three on a 10-centimeter log. There's no evidence by the investigators or history of oral cancer. The key exclusion is that since this is the first study of tacrolimus as a rinse, we exclude a patient who's failed previous tacrolimus.
If somebody's on steroids and still is bothered, they have to be willing to undergo a four-week washout period and stay off of steroids for the duration of the study. Next. Primary is the safety, and here's what the safety I'd like to share with you. If you look at the rightmost column, this is what we had with the study with the 27 subjects. This table reported adverse events, over 5% incidents. Just for a historical reference, this is what's noted with the oral and topical tacrolimus that's been FDA approved. This was a safe study. There were no serious adverse events or discontinued related adverse events. What are the side effects reported? There's 18.5% of dry mouth and 11.1% of oral dysesthesia or abnormal tingling sensation in the mouth. The key finding is it was with no serious adverse event and there was minimal systemic absorption.
John noted that the tacrolimus whole blood test, so we can measure if tacrolimus is absorbed, that it was undetectable in 76% of the subjects, and all the treatment emergent adverse events were mild to moderate. The AE, as a clinician of special interest, is that we never had a patient that had a whole blood tacrolimus level greater than 15 nanomolar, nanogram per mL. That would be potentially a concern for systemic safety because tacrolimus at high blood level could be toxic because it causes an arterial constriction. We had no patient that developed blood pressure during treatment over 145 systolic, 95 diastolic that would indicate an arterial constriction. We had no alterations, diminishment in renal function, which is the main systemic side effect of systemic tacrolimus. Moreover, there was no intractable pain. We had over 1,500 dosages twice a day, three-minute rinse, and it was tolerated.
We had no allergic reaction during the trial. Next. We're interested in the efficacy. The two figures here are the investigators reported, the validated IGA and the REU. Now let's look at the left side, the dark blue, the IGA score. Now, 0.146, meaning baseline, one week, the primary, that last day of treatment at week four, and two weeks after the final treatment, week six. The IGA is a zero to four score with the three being moderate and four severe. The baseline, and you can see the lines of the three groups, baseline is about a 3.5, and there was improvement statistically meaningful at week one and reached to about a little bit more than two at four weeks, and it still has efficacy two weeks after final treatment at week six. This matches the REU score, the other symptoms. Doctors saw, but what about the patients?
This is patient reported on a scale of zero to 10 on the pain in the mouth and sensitivity in the mouth. You can see that both were pretty close. It was about seven at baseline, and there was a significant four-point drop by week four. Within week one, you see the improvement in pain and sensitivity, and there's remained efficacy two weeks after the final dose. Next. This is the patient, the symptom severity score, OLP SSM, and it's asked over the last 24 hours, how terrible was it, was your OLP from none to terrible severe when you brush your teeth, when you're eating, when you're smiling, and when you're talking. You can see also similar to the other parameters, there was improvement in the symptom severity to the patients at week one, maximally at week four, and still improved by week six. Next.
The final figure that I'll show you is this is the patient asked at week four when they had their last dose, their GRA, the global response. It goes from zero, "I'm very much worse," three is no change, and six is very much better. No participant out of 27 reported that they got worse, and really every participant noticed some improvement across the dose group. Most was reported moderate to much improved. Next. I'd like to finish up with my slide, just sharing you with a few of the comments from our investigators and their site and three of the participants in this study that the study was positive. In fact, three of the patients who failed conventional steroid rinse in the mouth that participated in the study improved, requested that their doctor help them get the medicine with the compassionate use, and the doctors did.
They were granted expanded use access by the FDA, which is only granted for a serious disease when there's no viable alternative treatment, and they're doing well during the expanded use. Next. Now I'll turn it back to John. Thank you.
Thank you, Michael. I'd like to now describe the market economics of LP-10 for OLP. This slide illustrates anticipated market size and segmentation, starting with projected OLP prevalence of approximately 2% of the U.S. population, then funneling down to an estimate of the predicted addressable patient population of $1.2 million patients in the U.S. These are symptomatic patients that are poorly controlled by existing options. This estimate is based on primary market research, including interviews with 15 healthcare providers, including oral surgeons, dermatologists, rheumatologists. We anticipate the potential for significant penetration of this market as shown on our next slide that describes the anticipated utilization. The healthcare providers and payers described multiple unmet needs. There is no approved therapy for OLP. It's currently treated by off-label use of topical gels and creams that are unsuitable for the oral cavity.
Topical steroids have limited efficacy, compliance challenges, and concerns with long-term exposure. Topical calcineurin inhibitors are difficult to apply and cause stinging and burning, which reduces compliance. Systemic immunosuppressants have safety monitoring requirements, insurance reimbursement challenges, and are not practical for milder patients. Off-label biologics have cost and access issues and have limited clinical evidence in OLP. LP-10 would be the first FDA-approved drug for this indication. Our minimal systemic absorption, which we believe is one of our key differentiating factors, will be an important market driver. Unlike existing off-label options, LP-10 is well tolerated and easy to use. Let's next take a look at pricing.
Pricing benchmarks include off-label use of VitaMA and Ophthalor creams currently reimbursed at $1,500 and $2,000 per patient per month, respectively, and Otezla, which is an oral systemic therapy at $5,000 per month, which is too expensive for off-label use, and patients only have access to samples. Payers view LP-10 as a convenient de-risked alternative for patients who fail topical steroids. The familiar mechanism of action reduces uncertainty, and the liposomal delivery is perceived to add value by improving local retention while limiting systemic exposure. Payers cite $1,000 as the most reasonable benchmark for LP-10 per patient monthly wholesale acquisition cost. While the monthly price is expected to be around $1,000, payers anticipate intermittent use with approximately three to five cycles per year, translating into an annual treatment cost per patient of $3,000 to $5,000.
LP-10 is thus projected to generate approximately $750 million in peak sales in 2035, driven by its first-to-market status and improved delivery of a familiar molecule. These sales projections translate into a $350 million risk-adjusted net present value for this asset alone. This completes our review of LP-10 oral rinse for OLP. Obviously, we're bullish on the future potential of this asset, and we're actively seeking an industry partnership in the next phase of development, which will be a placebo-controlled clinical trial. To briefly summarize the main points of today's presentation, we began with what makes us unique, and that's our proprietary liposomal formulations optimized for the delivery of active agents to the mucosal tissue of body cavities. We emphasized our corporate strategy, leveraging our formulation IP to develop products using the 505(b)(2) regulatory pathway, which accelerates clinical development and reduces efficacy and safety risks.
We've described our asset pipeline consisting of two phase two assets, an additional asset that's IND approved, and a fourth preclinical asset, all of which are liposomal formulations optimized for the delivery of drugs directly to the surface of the mucosal tissue. We then described our lead indication, oral lichen planus, and described the challenges patients have with the current standard of care. We're also happy to have had the opportunity today to present the positive results of our recently completed phase two clinical trial, evaluating the safety and efficacy of LP-10 oral rinse in refractory OLP patients. We've also presented primary market research, including interviews with a broad range of healthcare providers and payers, indicating a significant untapped market opportunity. We hope that you find our story to be compelling, and we look forward to now taking your questions. There are a few.
The first question is, can you discuss your capital position, your needs to support LP-10 through phase three and commercial launch? The capital position right now, we reported between $1 million and $2 million of cash in our last quarterly statement, and we anticipate approximately $20 million required to bring LP-10 oral rinse to commercialization. How large is the addressable global patient population for OLP? We anticipate that the global market is approximately 25% of the U.S. market in dollar terms. However, OLP is not race-specific. It's a little bit gender-specific, but it's experienced all over the world, and we have patent protection in multiple jurisdictions. I'm looking for the next question we can take. What regulatory milestones are you expecting over the next 18 months? The next regulatory milestone would be IND approval of the phase two placebo-controlled clinical trial.
This is a question for our Chief Medical Officer, Michael Chancellor. Based on phase two data, what patient-reported outcomes, for example, pain and the global response metrics, stand out versus historical controls?
Yeah. Thanks, John. There's no historical control because there's no drug approved for oral lichen planus. With our experience, groups of investigators were able to talk with them before, during, and after the trial, and they were surprised, very pleasantly surprised, that first, a medicine put in the mouth for a painful mouth condition doesn't cause any burning. The patient can tolerate it. They were very surprised that the patient can see the improvement on the very first office visit. The historical control is lacking, but there are validated pathway scores that we can discuss with the FDA to be the primary efficacy endpoint for the phase two trial. I think the most historic important issue is that the patient, after finishing the trial, spontaneously seeked out the process and getting approval by the FDA for expanded use access. Thank you.
Thank you, Michael. We've reached our 30-minute point, and I think we have to break now. I'll turn the presentation back over to the moderators. Before I do that, I just want to thank everybody who's on the call and who's listening to this afterwards. We appreciate your interest in Lipella Pharmaceuticals Inc.