PDS Biotechnology Corporation (PDSB) Earnings Call Transcript & Summary

Greetings, and welcome to the PDS Biotechnology Corporation Summer Investor Summit Webcast. It is now my pleasure to introduce your host, Frank Bedu-Addo. Thank you. You may begin.

Thank you very much for the introduction. PDS Biotechnology, as you note here, I have the forward-looking statements. Please be aware that this presentation contains some forward-looking statements about the company. And also please make sure that you are familiar with the risk factors associated with the company and the technology. PDS Biotechnology, as you may know, is a clinical stage biotech company developing novel cancer immunotherapies and transformative vaccines for infectious diseases. PDS Biotechnology has developed a proprietary versatile immunotherapy platform that's been applied to the development of novel cancer immunotherapies as well as infectious disease vaccines. This technology has demonstrated in a human clinical trial, potential for strong clinical efficacy and very well tolerated with minimal toxicity. The company is developing a diversified pipeline that's focused on these 2 areas and clinical studies are being performed in areas of high unmet medical need. And very importantly, and partnered with and supported by leaders in the field. PDS Biotechnology has an experienced management team, a team that each of us have at least 25 years of experience in the industry and have developed multiple products and taking products through commercialization. And so this is a team that is very well suited to develop the kinds of products that the company is currently developing. So another quick overview of the company. We have publicly listed, as you know, on the NASDAQ, approximately 15 employees, 15.3 million shares outstanding with $21 million approximately in cash as of our last filing at the end of March. I will talk quite a bit today about the proprietary Versamune immune platform technology. And this, as I mentioned, is a clinically validated technology that has demonstrated the potential to overcome some of the key limitations of immuno-oncology pertaining to induction of powerful tumor targeting killer T-cell. We've also demonstrated the potential to induce neutralizing antibodies. And we've demonstrated promising clinical efficacy in our early PDS0101 monotherapy trial, which I'll talk a little bit about today. The company also has a deep pipeline, which I will talk about again also. And this pipeline has been -- we have multiple partners, PDS has limited resources, and so our partnerships have been very significant in enabling us to rapidly develop this deep pipeline. Okay. So let's start with oncology and the Versamune platform. So what is this Versamune platform? So the Versamune platform is based on novel positively charged lipids. So if you see the screen, these are lipids that have 2 water-insoluble hydrocarbon chains attached to a positively charged head group. And these form spontaneously in aqueous environment with the water-insoluble regions being hidden in the inside and the water-soluble positively charged head group on the exterior of the nanoparticle. So these are essentially nanoparticles covered on the surface with a positive charge. Now what we do here is we size these nanoparticles to mimic viruses. Our immune systems are very well attuned to detecting and picking up viral particles. So this facilitates this highly effective uptake of these nanoparticles by the immune system. What's also very important is the fact that these lipids specifically activate what's known as the type I interferon pathway. I mention the type I interferon pathway because this is known to be highly important in inducing the right kinds of immune responses necessary to facilitate antiviral and anti-tumor T-cell immune responses. Also very important, the Versamune nanoparticle promotes facilitation or accumulation of the immunotherapy in the vaccine in our lymph nodes, which is also important based upon the fact that this is a site of acquired T-cell activation. So it facilitates both high potency and high safety. I mentioned the ability to overcome some of the critical limitations of immuno-oncology, so the ability to promote presentation of the unique disease-specific proteins. So whether it's a tumor-specific protein or a virus-specific protein, presenting this into the right immunological pathway to train the killer T-cells to recognize that foreign agent. And also activating the right immunological pathway, which is the type I interferon pathway, to promote effective proliferation of these trained T-cells as well as activation of these primed killer T-cells. This mechanism of action has been associated with regression of disease in human clinical studies, and I'll show you some of that data today and also associated with the lack of relevant clinical toxicity, so very well tolerated. So we have high potency, demonstration of clinical efficacy and also demonstrated safety in human clinical trials. So on this slide here, what I show this slide to really demonstrate the importance of the ability to generate the right type of tumor-targeting killer T-cell as well as the right quantity of killer T-cells. So both quantity and quality are critical in inducing an effective antitumor immune response. And so here on the left-hand side, I show the bar charts, and so the sum of the dark and the light green bars show us the total number of killer T-cells that are generated by the various technologies. Versamune on the left-hand side, and these are adjuvant technologies that have been evaluated in human clinical trials today. And so the dark green bar are what we call the polyfunctional killer T-cells. The polyfunctional killer T-cells are known to be the most potent type of killer T-cell, most effective in killing the targets. And so what we see here is that with the Versamune technology, we are able to induce a significantly higher number of these powerful tumor-targeting killer T-cells than the competing approaches. So both a higher quality and a higher quantity of these killer T-cells. Now on the right-hand side, we see that this translates to more effective regression of tumors. And so here on the right-hand side, we're looking at the tumor regression plot. So this is specific to HPV-associated cancer, very relevant to our lead product, PDS0101 that addresses HPV-associated cancers. And so what we see here is if you look at the gray line, these are the untreated animals. So we see highly aggressive and very rapid tumor growth. Now if we inject these animals with the HPV16 protein that is associated with the cancer, that's the black line, we don't see much effect versus the untreated animals. The blue line, if we now take that same protein in the same amount and inject it or combine it with an adjuvant, a clinical stage adjuvant, what we see is the blue line. So what we see with the blue line is quite representative of the current top clinical stage HPV cancer immunotherapies. So we see an effective ability to slow down the rate of tumor growth progression, which extends the patient's life but does not effectively eliminate the disease. Now if we look at PDS0101, which is our Versamune platform, now combined with the same protein in the same amount. So PDS0101 is a Versamune plus the HPV cancer-associated protein. And what this does is to train the T-cells -- the killer T-cells to recognize this protein as a foreign agent. And so by doing this with a single dose, what you see here is that by day 35, we see complete elimination of the cancer. This has been done in hundreds of animals and has been done in multiple independent expert labs, highly consistent. So very powerful, the fact that we're able to induce the right type of killer T-cell with the right quantity and the right amount leads to an effective antitumor response. What's also very important here is the fact that we're able to induce a long-term memory T-cell response. The memory T-cell response is very important, not only in oncology, but also in infectious diseases, in being able to provide the patients or the individuals with long-term protection. So what you see over here is that if we come back and challenge these animals on day 60 with the HPV cancer tumor cells, these animals are completely protected because of the fact that the T-cells now remember that this is a foreign agent. It's shown up in the body again. It shouldn't be here and they immediately mobilize to eliminate the target. So very importantly, strong killer T-cell, strong memory T-cell response. This is a simple formulation, a 2-vial formulation for PDS0101. So we have in one vial our Versamune nanoparticles. And in the second vial, we have the mixture of HPV tumor-specific proteins. They're mixed together just before injection into the patients. This is an electron micrograph. You can see the circular Versamune and the string-like peptide micelles, which are the HPV proteins. And then these are given by simple subcutaneous injection beneath the skin. Okay. So let's go to our oncology programs. So here on the slide, you will see our pipeline. So we have PDS0101, 3 Phase II clinical trials are planned to be initiated very shortly with PDS0101. Going to Phase II, I mentioned the first addressing recurrent metastatic head and neck cancer. This is in collaboration with Merck. So this is combining Keytruda, which is now the standard of care for first-line treatment of advanced or metastatic head and neck cancer. The second trial is combination with 2 of EMD Serono's leading immunotherapeutic agents, M7824, which has been in a Phase II trial in advanced HPV-associated cancers and NHS-IL12. And this is based on studies that were done independently at the National Cancer Institute and demonstrated very strong potential of the triple combination of PDS0101 and 7824 and NHS-IL12. This trial will be run by our partner, the National Cancer Institute, and we anticipate that the trial should be starting in the next few weeks. And we have PDS0101 again now in advanced cervical cancer. And our partner on this program is the MD Anderson Cancer Center. And here we are combining, again, the standard of care chemo radiation with PDS0101 and so you can see here that we have very specific, very well-defined goals to proof-of-concept and commercialization of the product in 1 and 3, demonstrating -- hopefully, demonstrating security over the current standard of care. And with the second trial, combining with some of the top immunotherapeutic agents, and hopefully demonstrating superior clinical benefit in this clinical trial. The MD Anderson trials are also expected to begin in the next couple of few weeks. PDS0102 addresses prostate and breast cancers. It's based on the TARP protein that has been found by the National Cancer Institute to be present in about 90% of prostate cancers and about 50% of breast cancers. Again, what -- a key advantage here is that an initial clinical trial has already been run by the National Cancer Institute. And this protein has been demonstrated to be highly recognized in the patients with prostate cancer. And so we are now combining this with Versamune to hopefully present much more effectively to the immune system, activate the right immunological pathways and induce a very targeted and powerful antitumor response. PDS0103, this is again under collaboration with the National Cancer Institute. We announced recently that this has been included in our collaboration with the NCI that involves PDS0101. So a very similar approach is going to be evaluated here by the NCI, where it will be combined with other immunotherapeutic agents. And hopefully, the combination rapidly taken into a bigger Phase II human clinical trial. And PDS0104 addressing melanoma. Okay. So one of the questions that we have very often asked is why HPV-associated cancer. The assumption is that based upon the presence of the current HPV vaccines that the HPV-associated cancers will be eliminated in the next few years. Unfortunately, that is not the case. And there are 3 key reasons for that. The first being the fact that HPV is by far the most prevalent sexually-transmitted agent worldwide, about 14 million new infections in the U.S. alone every year. Secondly, the current HPV cancer vaccines are preventive, not therapeutic. And they are only effective if administered before the patient is infected with a virus. And so these have no ability to eliminate the virus or this cancer once it starts. It absolutely has to be administered before the patient is infected with the virus. And third is the very slow duration of progression of the disease from time of infection to advanced cancer. In many cases, it could take even a couple of decades for that process to occur. And so what has been projected is that in many of the patients that we will be treating over the next 20 years, these patients are very likely already infected with the HPV virus. And not surprisingly, head and neck cancer, for example, has recently been described as a silent epidemic, and this is based on the number of new incidences or rapidly increasing incidences of head and neck cancer, the vast majority of which are attributed to HPV infection. Very similar in case with anal cancer and cervical cancer cases have held steady for several years. Now our drug, as I mentioned earlier, is focused on HPV16, specifically HPV type 16 because 16 is by far the most prevalent in advanced HPV-associated cancers. So about 90% of HPV-positive oral cancers are reported to be HPV16-positive, approximately 70% to 80% of anal cancers and about 50% to 60% of cervical cancers. This slide shows our clinical results. So one of the key things I mentioned is -- one of the big limitations for immunotherapy has been the ability to induce these tumor-targeted killer T-cells in humans. In this study, what we demonstrate here, and these are patients who have precancer, we did not restrict these patients to HPV16 specifically so long as the patients had one of the 13 cancer-causing strains of HPV, they were allowed to enroll in the trial. Most of these -- most of the 12 patients came in with multiple HPV infections. However, in addition to demonstrating the safety, one of the key things we wanted to demonstrate here was the uniqueness of this platform and product in its ability to specifically activate and induce high numbers of these tumor-targeting killer T-cell. We essentially wanted to replicate our preclinical results in humans. And so what you see over here is all our competitors have looked at T-cell induction in humans, right? So induction of T-cells is not new. What's new and what's important is induction of the right phenotype or right type of killer T-cell. So everyone is looking at interferon gamma ELISpot, meaning T-cells that induce interferon gamma. Interferon gamma-inducing T-cells are unfortunately known to be the weakest type of T-cell. Also interferon gamma is not specific but it's not restricted to killer T-cells. Helper T-cells as well as natural killer cells all induce interferon gamma. And not surprisingly, this has never correlated with therapeutic or clinical benefit. What we decided to do on the other hand, in addition to interferon gamma, was to measure Granzyme B inducing T-cells. This is more specific to tumor recognizing activated killer T-cells. And what we demonstrate over here uniquely is the fact that within 14 days of treatment, we are able to induce large numbers of these tumor-targeting and active killer T-cells in the blood circulation of these patients. Again, confirming what we saw in our preclinical models, and again confirming translation of the mechanism of action from animals to human, okay? Now let's go to the next slide. So what we then did was we came back to -- we wanted to evaluate our ability to induce clinical benefit in these patients. Clinical benefit was not one of the criteria or the endpoints for the clinical trial. We came back to do a 2-year retrospective evaluation of these patients once we realized that we were able to induce these strong killer T-cells in humans. So remember here, our product is HPV16-specific. These patients were allowed to come in with multiple HPV infections. However, what was very interesting here was that at the patients' first evaluation after treatment, which occurred anywhere from 1 to 3 months after the treatment, in 60% of these patients, there was complete regression of the lesions. Now with these patients -- a number of these patients, there will be a spontaneous regression of the lesions. The physicians estimate anywhere from about 40% to 45% of these patients will experience a spontaneous regression, but it occurs very gradually over a 2- to 5-year period. And so it was very surprising to them that we would see regression -- complete regression, 60% of these patients within 1 to 3 months of treatment. In another 20% of the patients, we saw what we would call a partial regression, meaning that they will see complete regression by one method, but there will still be some residual disease by a second method. And so in this case, we call it a partial regression. So this was not a conclusive study because these were 12 patients, but it was really important in demonstrating as a monotherapy that we are seeing the right kinds of immune responses in humans and the mechanism of action appears to translate very well into humans. So the question was, where do we go from here and how do we rapidly demonstrate proof of concept? And so what we decided to do then was we decided to go into larger Phase II clinical trials in combination with therapies that have demonstrated clinical benefit, that have been shown to work in humans. And in the combination of PDS0101 in these agents demonstrate superior clinical benefit over the current standard of care or over that agent alone. The first trial, as I mentioned earlier, was in combination with Keytruda, looking at recurrent metastatic head and neck cancer. Combination immunotherapies are usually restricted to second and third-line treatment of these cancer patients. Keytruda is the only immunotherapy to date approved for first-line treatment, and this is in head and neck cancer. And so our combination will be addressing recurrent head and neck first-line treatment of metastatic or recurrent head and neck cancer. Unfortunately, initiation of this trial is to be determined at a later day, just based upon the COVID-19. We had qualified approximately 22 sites to get this trial up and running. And due to the inability of these sites to start enrolling and starting new oncology trials, we have this trial on hold and we're waiting to see when we can get this trial up and running. The next trial I mentioned was the partnership with the National Cancer Institute, where PDS0101 is being combined with 2 of EMD Serono's agents, the M7824 and NHS-IL12. This will be done at the National Cancer Institute. It's being run by the NCI, and we are still anticipating as of this week, that this trial will start on schedule, hopefully in the next few weeks. And very similarly with the MD Anderson Cancer Center trial, and this is combination with chemo radiotherapy, which is the standard of care. And again, we're anticipating that this will also start on schedule in the next few weeks. And so as you can see over here, with 2 out of the 3 trials we are combining with the current standard of care, a very well-defined path to commercialization with the goal of being able to demonstrate superior clinical benefit over the standard of care. And in the second trial, we're combining with 2 of the leading immunotherapeutic agents with the goal of demonstrating that with the Versamune platform, we can dramatically enhance the antitumor responses due to these immunotherapeutic agents. Okay. So moving on to infectious disease. With infectious disease, we are looking at 3 key indications: tuberculosis and universal influenza and COVID-19. So PDS has really focused primarily on demonstrating proof-of-concept in oncology. However, we've always known that we would be branching and taking this versatile platform into infectious diseases. COVID-19 presented a unique opportunity for the company. And we had one trial that's been put on hold, and we decided to focus some resources on really understanding the COVID-19 space, understanding what is known today, what others are doing and how we can utilize our technology to develop a superior and transformative COVID-19 vaccine. One of the key things we know today is the fact that going from the previous SARS infection, the original SARS-CoV to COVID-19, which is the SARS-CoV-2, a significant portion of the viral sequences are conserved between the 2 viruses. And what's also known is that there are specific proteins and sequences in those conserved regions that are recognized by our killer T-cells. And so studies that were done on the original SARS-CoV patients found out that patients whose immune systems generated these killer T-cells had a significantly longer protective period, sometimes up to 10 years and beyond, versus those whose immune systems only generated neutralizing antibodies. Now what we have here is a technology that has demonstrated the ability to induce not only neutralizing antibodies but to induce powerful and strong killer T-cells as well as memory T-cell responses. And so what we're doing now is we've started initial preclinical studies to confirm what we can do this with the COVID-19 virus. And also we started discussions with potential funding, governmental and nongovernmental agencies, to really help them understand our technology, how it's differentiated and how we can apply this to developing a vaccine that provides a much broader range of protective immune responses and how we can also provide a much longer duration of immune responses. So it's important to note that a lot of the mutations occur within that -- as what we call the S protein of the virus, and that is the region that most of the vaccines are targeting to generate these neutralizing antibodies. It should also be noted that these -- within this region is where a number of the mutations actually occur. So what we're hoping to develop here is what we would call a transformative COVID-19 vaccine, and we're taking a very similar approach with our -- taking a very similar approach with our influenza vaccine. So here, I show you some -- just quick results of some of the early studies we've done with influenza. So here, we're looking at Fluzone and we're simply combining Fluzone with the Versamune technology. And so on the Y-axis, you see the amount or number of neutralizing antibodies that are generated. And with [ fluid ] level up to about 40 is considered to be an effective vaccine. And so what you see over here is that by simply combining different amounts of Versamune with Fluzone, we can enhance the neutralizing antibody efficacy about 40 fold. It's a dramatic enhancement of the efficacy of Fluzone simply by combining it with Versamune and we see this for each of the 3 viral strains contained in Versamune. Now what's also very important here is that what we're looking at developing with COVID-19 is a vaccine based on recombinant proteins, which would be able -- which we are projecting should be able to induce not only antibody responses, but also specifically T-cell responses to that particular COVID-19 protein. And so here was a quick demonstration of the fact that with a single recombinant protein, we can induce neutralizing antibodies as well as induce strong T-cell responses against a set of specific regions of that protein. Now here, we are performing a head-to-head comparison with complete Freund's adjuvant, which is known to be one of the most powerful immune activators and one of the most powerful adjuvants. It's not used in any human vaccines because of its extreme toxicity. But we were able to use it as a comparator in the study. And so what you see over here is that Versamune is able to induce antibody responses similar to what you'll see with this very powerful adjuvant Versamune -- with complete Freund's adjuvant. However, when we look at the T-cell responses, here is where adjuvants have always fallen short. What you see is that the CFA is unable to induce significant quantities of these killer T-cell responses as well as the helper T-cell responses. However, with Versamune, we see very powerful killer T-cell and helper T-cell responses in addition to the antibodies. Therefore, generating a much broader range of potentially protective immune responses. And so this is the approach that we have taken into development of our transformative preventive vaccines. Okay. So really, what we're doing here now with these COVID-19 vaccines, as I mentioned, demonstrating high levels of both T-cell and antibody responses, those studies are currently underway; demonstrate the fact that these are very well tolerated; and rapidly potentially head into human clinical trials as well as preparation and scale up for commercial production. This would all -- all going to depend on how rapidly we can bring in some, hopefully, non-dilutive funding through some of the government agencies or the nongovernmental agencies. And as I mentioned, those discussions are currently ongoing. This technology is fully owned by PDS Biotechnology. We have several patents, many of them already issued in several markets in the world today. And we have 10 patent families total. The currently issued patents will provide protection through approximately 2034. However, we have patents that have been submitted as recently as last year, which should, if issued, should provide the technology and platform with protection through the end of the 2030s. Okay. So several layers of patent protection. The company is in a strong financial position to support our near-term milestones. As I mentioned, we have approximately -- we had approximately $21 million on hand at the end of March. And this has been really focused today on our current oncology pipeline. As I mentioned just a few minutes ago, we're talking to some of the other agencies to hopefully bring in the financing to progress the COVID-19 vaccine. So I hope I have provided you with some insight into the company, what we're doing and what's the advantages of the versatile Versamune immune platform, a powerful immunotherapy platform that activates critical therapeutic and preventive pathways, activation of the critical type I interferon pathway as well as the ability to present these unique disease-specific proteins into the right immunological pathways for training of the T-cells and induction of antibodies. We have demonstrated in our first human clinical trial the potential for strong clinical efficacy and durability of the immune response with minimal toxicity. And we're developing a diversified oncology and infectious disease pipeline, together with top players and leaders in the field of immuno-oncology and focus on areas of high unmet medical need. And so I would like to thank you for your time. And at this time, I'll be happy to answer any questions. So I will move over to the Q&A.

So the first question is, is there any primate data for PDS0103? So we do most of our animal studies in rodents. So we don't have any data as such in nonhuman primates because a lot of these tumor models are developed for mice. And so that's really what we focused on for PDS0103. But in these animal models, we have definitely shown strong CD8 killer T-cell responses in the animal models. Your website says that PDS0203 stimulates a broad potent and rapid immune response. In which species? All our preclinical work today has been done in mice. The second question I have is, how is the COVID-19 vaccine development going? That is progressing. We have not made any of the results public yet. But the preclinical studies are currently ongoing, and we hope to be able to make some public statements regarding that work in the near future. So I think that is -- those are the 2 questions that I have received. And so I would like to thank the audience for your participation and also for the questions. And thank you very much, and I will hand over back to the moderators.

Thank you so much. This does conclude today's webcast. You may disconnect your lines at this time. Thank you for your participation, and have a great evening.