PDSB - NASDAQ

Laura Suriel - Alliance Global Partners Robert LeBoyer - Noble Capital

Greetings. Welcome to PDS Biotech's Third Quarter 2022 Earnings Conference Call and Webcast. At this time, all participants are in listen-only mode. A question-and-answer session will follow the formal presentation. [Operator Instructions] Please note this call is being recorded. At this time, I'll hand the conference over to Gabby DeGravina, CG Capital. Gabby, you may now begin.

Good morning. And welcome to PDS Biotechnology's third quarter 2022 earnings conference call and audio webcast. With me today from the company are Dr. Frank Bedu-Addo, Chief Executive Officer, Dr. Lauren B. Wood, Chief Medical Officer, and Matt Hill, Chief Financial Officer. Earlier this morning, PDS Biotech issued a press release announcing financial results for the quarter ended September 30, 2022. We encourage everyone to read the press release as well as PDS Biotech's report on Form 10-Q, which will be filed with the SEC shortly. The company's press release is available on PDS website at pdsbiotech.com. In addition, this conference call is being webcast and will be archived on the company website for future reference. Before we begin, we need to remind everyone that, on today's call, the company will be making forward-looking statements regarding regulatory and product candidate development plans, as well as research activity. Certain information in this presentation may include forward-looking statements, including within the meaning of Section 21E of the United States Securities Exchange Act of 1934 as amended, and Section 27A of the United States Securities Act of 1933 as amended, concerning PDS Biotechnology Corporation and other matters. These statements may discuss goals, intentions and expectations as to future plans, trends, events, results of operations, or financial condition or otherwise based on current beliefs of the company's management, as well as assumptions made by, and information currently available to, management. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in PDS Biotech's most recent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this conference call. Except to the required by applicable law or regulation, PDS Biotech undertakes no obligation to update the forward-looking statements included today to reflect subsequent events or circumstances. With that, I would now like to turn the call over to Dr. Frank Bedu-Addo. Frank?

Thank you, Gabby. And thanks to all of you for joining us on our quarterly call today. During the third quarter of this year, we achieved some major milestones as we continue to progress the development of our oncology pipeline, and particularly our lead candidate PDS0101 towards registrational trials. PDS0101 is an investigational immunotherapy designed to treat human papilloma virus or HPV positive cancers. Before going through our quarterly and other business updates, I want to remind everyone that there are two key obstacles that have limited broader application of immunotherapy in the treatment of cancer, despite the revolutionary success of checkpoint inhibitors. The first challenge has been the limited ability to induce in the body the right type of killer T cells with the right killing potency, meaning polyfunctional or multi cytokine inducing killer T cells as well as induction of these killer T cells in the right quantity. We refer to this as the critical three R's of T cell activation: right type; right potency; right quantity. We know today that induction of adequate active tumor infiltrating killer T cells is crucial for effective and durable or long-term immunotherapy. The second limitation is inability to overcome tumor immune suppression beyond the immune checkpoint specific mechanisms currently addressed by checkpoint inhibitors. We know today that tumors utilize a variety of mechanisms independent of the immune checkpoints to suppress T-cell attack. The ability to more broadly overcome tumor immune suppression, while also generating potent tumor attacking T-cells presents the potential to more effectively treat a broader percentage of cancer patients, including terminally ill cancer patients as our current data suggests. At PDS Biotech, our technology platforms are designed to specifically address these two critical limitations of immunotherapy. We believe this proprietary approach to immunotherapy could clearly differentiate PDS Biotech from our peers. With regards to in vivo CD8 killer T cell induction at the Society for Immunotherapy of Cancer Conference known as SITC this past week, our collaborators at the National Cancer Institute and at the MD Anderson Cancer Center, presented the results of immunological studies performed as part of their respectively lead Phase 2 clinical trials. These studies were aimed at further documenting the immunological mechanisms by which Versamune and Versamune plus IL-12 work. They also document the types of immune responses generated and their correlation with clinical efficacy. The MD Anderson poster reported the induction of polyfunctional CD8 T-cells, which were shown to infiltrate the tumors when PDS0101 is administered to locally advance cervical cancer patients in combination with standard of care chemoradiotherapy. No increase within the tumors of killer T-cells has been reported by MD Anderson in patients who only received chemoradiotherapy. In the MD Anderson presentation, they report an increase in the tumor DNA in the blood after chemo radiation. They also report an increase in the killer T-cell population as a result of PDS0101 dosing. The studies demonstrate subsequent elimination of the blood circulating tumor DNA. This increase in tumor infiltrating CD8 killer T-cells correlates with clinical responses in nine out of nine patients who had greater than 60% tumor shrinkage at midpoint evaluation. Complete responses with no evidence of disease in eight of the nine patients was seen by day 170. One patient due to events not related to treatment only received three of the five PDS0101 doses. This is the only patient whose treatment did not result in a complete response. The MD Anderson data is especially illuminating, because the immune responses are not confounded by the presence of any other immunotherapy. The observed immune responses are solely attributable to PDS0101. The National Cancer Institute also reported immunological data resulting from the administration of the PDS0101 base triple combination in checkpoint inhibitor refractory patients. This study also demonstrated the induction of HPV16 specific killer T-cells in the blood of treated patients confirming the immunological role of PDS0101. A significant increase in granzyme-b inducing CD8 T cells was also demonstrated. granzyme-b is associated with killer T-cells that have the ability to target and kill cancer cells. We believe the results reported at SITC support the potential of Versamune based products to successfully overcome the first critical limitation of immunotherapy by generating the right type, right quantity and right potency of tumor infiltrating killer T cells in advanced cancer patients. The second challenge is more broadly overcoming mechanisms used by tumors to evade detection by the immune system. As cancer progresses, multiple regulatory mechanisms are co-opted by the tumors to evade attack by T cells. Some of these mechanisms are independent of the immune checkpoints that are blocked by checkpoint inhibitors. For example, in the difficult to treat HPV positive cancer population, the response rate with checkpoint inhibitors is reported to be about 13% to 20%. In the VERSATILE-002 study, we appear to demonstrate in the early data in checkpoint inhibitor naive patients that by blocking the new checkpoints with KEYTRUDA and promoting HPV specific CD8 T-cell induction with PDS0101, that we improve the response rates to over 40%. In the National Cancer Institute's study, using the Versamune plus IL-12 platform in the triple combination study, in a similar population of HPV positive cancer patients who are naive to checkpoint inhibitor therapy, the National Cancer Institute reported an objective response rate of 88%. We believe this may be due to the fact that the triple combination is able to more effectively overcome the tumor immune suppression, therefore making a larger percentage of tumors more susceptible to attack by the PDS0101 induced killer T cells. Also, we see in this population, a 75% survival rate at 25 months. The KEYNOTE-048 study reports an overall survival of 51% at 12 months with the combination of chemotherapy and KEYTRUDA in recurrent metastatic head and neck cancer. Further evidence of this effect is seen in the checkpoint inhibitor refractory arm of the triple combination study. In this population, in the patients who received the optimal dose, the National Cancer Institute reported an objective response rate of 63%. Historically, this patient group has an objective response of less than 10%. Also in the full cohort, including those who receive both optimal and suboptimal dose combinations, the National Cancer Institute reports a 66% survival after a median of 16 months of follow-up. The historical median survival for this population is reported to be only three to four months. These results suggest that the triple combination may be effective in addressing one of the key limitations of immunotherapy, which is broadly overcoming tumor immune suppression beyond what is achievable with checkpoint inhibitors alone. As you can see in the table, we have strategically collaborated with some of the most respected cancer centers in the world to perform this broad range of studies to enable us to more quickly understand in which indications the various combinations may work better, and to allow us to select the most promising combinations and indications to rapidly progress into registrational trials. As we look ahead to 2023 and beyond, our key priority is to advance PDS0101 as rapidly as possible to commercialization in as many indications as feasible. To date, we have reported Phase 2 efficacy data from over 60 patients and safety data from over 100 patients in three trials. And we are encouraged by the fact that the clinical and immunological results continue to be consistent and to demonstrate the potential efficacy and safety of PDS0101. The data generated in the VERSATILE-002 trial to date, for example, has allowed us to determine that the dual combination of PDS0101 and KEYTRUDA may be most suitable to address recurrent metastatic checkpoint inhibitor naive HPV16 related head and neck cancer. However, in more advanced checkpoint inhibitor refractory disease, the data generated by the National Cancer Institute using diverse immune plus IL-12 platform in the triple combination suggest that in such advanced disease, the ability to more broadly overcome tumor immune suppression, while generating tumor attacking T-cells makes this our preferred combination to further evaluate in this patient population in a registrational trial. As you are aware, PDS0101 in combination with KEYTRUDA has been granted Fast Track designation by the FDA. We met in the third quarter with the FDA to discuss the potential to progress the combination into a registrational trial. We announced this quarter that based on a successful FDA meeting, PDS Biotech has begun the process of preparing next steps towards a registrational trial in 2023. The FDA provided guidance on key elements of the clinical and CMC program that will support the submission of the biologics license application for our lead assets PDS0101. The guidance received from the FDA ahead of completing the Phase 2 trial has the potential to speed up our development timeline by approximately one year. Similarly with the NCI, National Cancer Institute led triple combination. We announced this quarter that PDS Biotech and the National Cancer Institute has decided to end recruitment into the trial to focus our initial attention on progressing development of the triple combination in the checkpoint inhibitor refractory population. To this end, both PDS Biotech and the National Cancer Institute are encouraged by the data to date and remain hopeful that we will meet with the FDA before the end of the year, depending on the FDA meeting schedule, and upcoming holidays. As I alluded to in our last conference call, if we did get the go ahead from the FDA to progress the VERSATILE-002 trial into a registrational trial, it would take precedence over initiation of PDS0103. As a result, we have moved the preparation date for the PDS0103 IND to the first half of 2023. Clinical manufacturing of the product is progressing as previously stated. I would now like to turn the call over to Lauren, for her to take us through the clinical data recently presented at SITC by all collaborators at MD Anderson Cancer Center, and the National Cancer Institute. Lauren?

Thanks, Frank. Now turning to the data presented at SITC. Data from the NCI-led triple combinations were presented on immune responses in the checkpoint inhibitor refractory population in which there are very few treatment options available. Highlights presented included a more than two fold increase in circulating HPV16 specific T-cells in the blood of 79% or 11 of 14 of the evaluated patients on day 15 after treatment. Immune responses were associated with increases in natural killer cells, soluble granzyme-b, which is associated with active killer T cells, interferon-gamma and TNF-alpha, signaling a pro-inflammatory response. Immunogenicity findings highlight the potential role of the combination in altering immune suppressive forces and support previously announced results documenting promising clinical outcomes in the CPI refractory population receiving the triple combination and overall early increases in several monitored immune correlates such as granzyme-b and interferon gamma, for example, a day 16 were associated with a clinical response. The outcomes that we've seen in the expanded interim data along with the SITC 2022 presentation continue to demonstrate potential induction of high quality and relevant immune responses that may be associated with clinical efficacy, durability, and safety in a very challenging patient population with very few available treatment options. These results confirm the decision made by PDS Biotech and NCI to focus on the CPI refractory patient population for ongoing clinical development of the triple combination regimen. Turning now to the MD Anderson Phase 2 IMMUNOCERV trial, which is investigating PDS0101 in combination with standard of care chemoradiotherapy, also known as CRT, for the treatment of locally advanced cervical cancer. Highlights here include the following. 17 patients have been enrolled in the trial to date. Seven of the nine patients, 78%, has locally advanced FIGO Stage 3 and Stage 4 cervical cancer. Nine of the 17 patients have completed a day 170 post treatment positron emission tomography, computed tomography or PET-CT scan to assess the status of the cancer. 100% for all nine patients treated with a combination of PDS0101 and CRT demonstrated an objective response on day 170 by PET-CT. 89% or eight of these nine patients treated with the combination of PDS0101 and CRT demonstrated a complete response or CR with no evidence of disease on day 170 by PET-CT. One patient who only received three of the five scheduled doses of PDS0101 due to non treatment related events showed signs of residual disease. As a result, the disease free survival at one year is also 89%. The one year overall survival is 89%, or eight of nine patients, as one patient who had a complete response has died as a result of an event unrelated to either the treatment or their underlying disease. Patients treated with a combination of PDS0101 and CRT had a 71% increase in multi cytokine inducing also known as polyfunctional killer CD8 positive T cells within the tumors from baseline to the end of treatment. This increase went from 38% to 65%. This increase in activated T-cells was not seen in a prospective monitoring cohort of patients receiving similar standard care chemoradiation therapy alone. With respect to safety and tolerability of PDS0101, self-limited low grade local injection site reactions continue to predominate. We are pleased by these promising preliminary efficacy and safety results seen to date from the ongoing IMMUNOCERV trial and look forward to its continued progress. In late October, we hosted a key opinion leader roundtable with presentations by Dr. Neil D. Gross from the Department of Head and Neck Surgery, Division of Surgery, the University of Texas MD Anderson Cancer Center; Katharine A. Price, Co-Chair of the Head and Neck Disease Group at Mayo Clinic Comprehensive Cancer Center and Jared Weiss, Head and Neck Cancer Section Chief, Lineberger Comprehensive Cancer Center UNC School of Medicine. The well attended events focused on the current treatment of head and neck cancer and how PDS0101 might fit into the treatment paradigm. Notably, the PDS0101 KEYTRUDA combination shows the potential to treat patients with extremely debilitating, recurrent metastatic head and neck cancer and progress oncologist goals of improved clinical outcomes and quality of life. Now shifting to our preclinical programs, data on both PDS0102 and PDS0103 were recently presented at the 2022 American Association for Cancer Research, also known as AACR special conference on tumor immunology and immunotherapy. The poster presentation highlighted the development of Versamune based drug formulations containing multi epitope peptide antigen sequences of the tumor associated protein TARP, which is known as T cell receptor gamma chain alternate reading brain protein and modified sequence of the MUC1 oncoprotein or MUC1. The research presented provides the foundation for the development of PDS0102 as a potential treatment for TARP associated acute myeloid, leukemia, prostate and breast cancers and PDS0103 as a potential treatment for MUC1 associated breast, colon, lung, ovarian and other cancers. Key findings for PDS0102 were high levels of CD8 killer T cell responses against multiple TARP antigens and predominant induction of polyfunctional potent killer T cells. Key findings for PDS0103 were similar high levels of CD8 killer T cell responses against multiple MUC1 antigens and effective targeting and killing of MUC1 positive targets in the body in vivo. We are pleased with the preclinical research to date for these compounds confirming their biologic activity. The manufacture of PDS0102 clinical antigens is in progress as is the manufacture of PDS0103 clinical product. With respect to our Infectimune platform, data were presented at the American Society of Neurology Meeting in July. In this study, data highlighted that the vaccine Infectimune co-delivered with influenza, computationally-optimized broadly reactive antigens, known as COBRA antigens, generating T cells and antibodies against multiple strains of the flu, and importantly, provided full protection against lethal infection in animals. We remain excited by these data suggesting that PDS0202 has the potential to achieve the goal of providing the broad protection sought in a universal influenza vaccine. We are in discussions with NIAID regarding clinical funding for this vaccine. And we will keep you informed as decisions are made. At this time, this completes my data presentation and I'll now turn over the call to Matt to review our financial results. Matt?

Thank you, Lauren. This quarter was a tremendous one for the company. In late August, we completed a $35 million financing, receiving an initial tranche of $25 million, which immediately strengthened our balance sheet and provided the financial resources necessary to advance the company's clinical pipeline, specifically preparations for registrational trial for our lead candidate PDS0101. Looking at our summary financials for the third quarter ended September 30, 2022, research and development expenses increased to $4.4 million for the three months ended September 30, 2022 from $3.7 million for the three months ended September 30, 2021. The increase of $0.7 million in '22 was primarily attributable to an increase of $0.2 million in clinical study and research costs, $0.3 million in personnel costs and $0.4 million in manufacturing services partially offset by a decrease of $0.2 million in professional fees and facilities. General and administrative expenses decreased to $2.9 million for the three months ended September 30, 2022 from $3.3 million for the three months ended September 30, 2021. The decrease of $0.4 million is primarily attributable to a decrease of $0.5 million in personnel costs, a decrease of $0.1 million in facilities costs offset by an increase of $0.2 million in professional fees. We ended the quarter with approximately $71.6 million in cash, a strong position as a result of our partnering model and continuous financial discipline. With the registrational trial beginning in 2023, we estimate we will fund our operations through mid-2024. That concludes my portion of the call. And I'd like to turn the call over to the operator for a question-and-answer session. Operator?

[Operator Instructions] Our first question comes from the line of Louise Chen, Cantor Fitzgerald.

This is Carvey on for Louise from Cantor. Thank you for taking our questions. Our first question is on your HPV associate locally advanced cervical cancer. We wonder how the landscape might evolve overtime? And how does PDS0101 might fit within the treatment paradigm along with other potential treatments? Second is on your flu vaccine opportunity. Curious to know more about how you size or help us understand the opportunity for you. And lastly, what was the physician feedback on your pipeline at FIGC conference this year?

Carvey, I'll take the first stab at the questions and I'll also hand over to Lauren to add anything she might want to add to the answer. So with the cervical cancer, the standard of care, as you may know is chemoradiotherapy, that has really been the standard of care for a few years now, for several years now. And despite the fact that there is, there are reasonably -- compared to other cancers, reasonably effective initial responses, one of the key limitations of the CRT approach is recurrence of the cancer. There is still a significant unmet need in the space, you may recall that less than a year ago, probably several months ago, there was an announcement by Astra

Yeah, I'm just curious to know more about the physicians’ feedback on your data.

Yes, I will, at this time hand over to Lauren. Lauren, do you have anything to add to what I said and also the physician feedback at SITC?

Yes, I think one of the greatest areas of interest is the fact that we now have clinical outcomes that include imaging outcomes as well as immunogenicity and importantly a surrogate biomarker for direct tumor measurement in terms of the circulating tumor DNA. This is particularly important in HPV associated cancers, because there is emerging in clinical practice, the availability to track circulating tumor DNA in HPV related cancers. And the fact that we see induction of these polyfunctional potent CD8 T-cells within the tumor microenvironment of the cervical cancer patients, and we see those cells increase and there is a corresponding decrease in circulating tumor DNA has the potential to be very exciting. I do know that the NCI is planning on measuring circulating tumor DNA in the triple combination study, we don't have that data yet. But that is really a key area of interest that we have seen in terms of feedback that we've received.

Our next question is from the line of Kalpit Patel with B. Riley.

Good morning. This is Andy on for Kalpit. Thank you for taking questions and congratulations on the progress. Maybe just to kind of build starting on the cervical cancer patients. Can you set expectations for what chemoradiotherapy would achieve in this patient population in terms of response rate and complete response? And are there any large-scale randomized trials that you can point to you in this area that can help us get a better sense of efficacy? And then I have a few follow-up questions.

Sure. So I'll start again and hand over to Lauren. But I think in terms of the cervical cancer and the potential and the combination here, I think one of the key things that we're looking at, as Lauren just mentioned, is understanding exactly how PDS0101 or Versamune is impacting the treatment regimen and exactly what PDS0101 could potentially be doing to improve the therapy for these patients. And with -- as Lauren mentioned, in these patients who are not treated with PDS0101, there was no evidence of increased CD8 T-cell induction in these patients. And you see that very clearly with the patients who are treated with PDS0101. Also in terms of the survival of these patients, so as Lauren also mentioned, the vast majority of these patients are Stage 3 and Stage 4 patients. So these are late stage cancer patients. Typically, the initial response in these patients, I think, as MD Anderson reported earlier in the abstract is about 70%. But what's most debilitating for these patients is the disease recurrence, which is really high as the stage of cancer progresses. So as you progress to Stage 3 and Stage 4, you see pretty high rates of recurrence starting before even a year. And so that's really, those are some of the key characteristics and outcomes that we're looking at. So we've seen a significant improvement in the clinical response from that 70%, or about 100%, and almost 90%, complete response. We also see 100% survival of these patients, one patient died from a non disease related or treatment related event, but really now monitoring these patients to see if we can significantly enhance the overall survival, as well as limit the disease recurrence. In terms of a similar large trial, the one I'll refer you to is the one I just referred to, recently concluded by Astra

I was just going to ask a follow-up on the T-cell abduction. We know that chemoradiotherapy, you don't see an increase in the tumor of these cells. Can you also confirm that you don't see an increase in blood and then maybe on the increases that you are seeing in the blood? Do you have a sense of how large a fold increase you believe is sufficient? And then also, were you able to kind of monitor the changes in T cells over time, or is it really just that 15-day data point that you looked at?

Two trials, and Lauren is really the expert with circulating tumor DNA. So I'll hand over to Lauren shortly. But -- and we're looking at two trials here. So with the National Cancer Institute trial, they monitored those T cell responses. They looked at the immune correlates before initiation of treatment and 15 days after treatment. So there's we're limited to that time period. And they focus they have on the checkpoint inhibitor refractory population. And what they showed in that case is very clear induction of the multifunctional HPV16 specific T-cells. And so their T cell characterization was specific to what PDS0101 should induce and sure enough, what we see is an increase -- significant increase in that specific T cell population that targets HPV16 cancers in the responding patients. So they showed a very strong correlation between that and responses, as well as things like granzyme-b, which is specific to active tumor attacking CD8 killer T-cells. And they also look at things like interferon gamma showing increases in all those correlates. So it was very informative in terms of the role of PDS01 and those immune correlates that are induced by PDS0101. What’s very interesting about the MD Anderson study, but they did not look only at the circulating T cell responses, but they also looked at the T-cells that actually infiltrates the tumor microenvironment, which is very important. Because you can generate T cells which may increase in the blood but may not be effective in targeting and actually infiltrating the tumors. And so what the MD Anderson study tells us and shows us is that we see a strong correlation between what we have observed in the preclinical studies where we see these T cells effectively infiltrate the tumors lead to tumor death, we see a very similar thing happening in the humans. And this is the first study that we have done to date in humans characterizing the T-cell response within the tumor itself, so very informative studies really confirming what we've seen in our preclinical studies. What was also very interesting about the MD Anderson study as you mentioned, is the circulating tumor DNA. And so what they show in the poster that they presented was that the patients have circulating tumor DNA at the time of treatment, start of treatment. What they also showed and again, we haven't attributed any cause and effect to that, but what they showed was that after initiation of treatment, there was a significant increase and that the level of increase varies from patient to patient, but a significant increase in the circulating tumor DNA after the chemo radiation started. But what they also showed was that as the CD8 T-cell response builds, and they looked at the T cell responses in the tumor at T-0 and a number -- at a number of time points all the way through 170 days. So, this was a longer duration evaluation of the T cell response, but what they showed was that T-5, for example, you could see a very strong CD8 T-cell response. But by the time what they also showed was that the circulating tumor DNA had gone down to zero. So, it appears to suggest that as we generate that T-cell CD8 T cell response is effective in lowering and eliminating the circulating tumor DNA, which is very important and what you want to see for an effective T cell immunotherapy. Lauren, I'll hand over to you to add to anything you may want to add to that.

Right. Well, thank you, Frank, you did highlight the fact that one of the strengths of the MD Anderson study is that they are able to examine the time course of both these immune responses and the circulating tumor DNA responses at five different time points over the course of standard of care chemo radiation therapy, which has to be completed within a certain time course window. The other thing that I think is very important to note is, is that what we're really looking for is not only these early results, but we have preliminary survival at one year and it's going to continue to be very informative as the results and the clinical outcome from the study matures. The reason is, is that cervical cancer is really a disease of disenfranchisement as young women present with locally advanced disease. And it is this locally advanced disease that really results in sub optimal responses to initial chemo radiation therapy, as well as a predisposed risk for early disease recurrence and diminished survival outcomes. The trial that Frank had mentioned, performed by Astra

And I think one thing to add to that as the management team here, having these studies, actually independently performed by some of the world's leading experts in the field, we believe also generates confidence in the reports and very importantly for PDS Biotechnology independent expert validation of our science. What's also very important with the study, with the MD Anderson study, it highlights the breadth of the potential applications of adverse immune based products if they are able to significantly improve the efficacy of some of the most used cancer therapies without compounding their toxicity. So to date, I think we are highly encouraged by the immune correlate data generated and presented by both MD Anderson and the National Cancer Institute.

And then maybe one quick final question for Lauren. I think it's impressive and notable that she saw increases in granzyme-b and interferon gamma. Just maybe talking a little bit more about those, was there a kind of threshold that was associated with clinical response or any more color you can provide on the correlation there, would be helpful.

I wish, I could provide more correlation and your question is excellent. One of the things is that we do know is that, is it the presence or absence of a specific response? Or is it the magnitude of a specific response as well as its presence? And I think that, from the data that MD Anderson has presented, we don't have a sense of whether or not there's a certain minimum threshold that has to be achieved in terms of the magnitude of these responses, but it's something that we would definitely want to explore moving forward. The point that you highlighted that we see both granzyme-b as well as interferon gamma, historically, in the past, when we had been characterizing immune responses, we always measured interferon gamma, we tend to measure it as just a monotherapy response. But we clearly now have an understanding that when you see induction of antigen specific responses, that are polyfunctional, so you see induction of multiple different cytokines, such as interferon gamma. But in addition to granzyme-b, which is specifically characteristic of cytotoxic functional T cells as well as TNF-alpha and IL-2, it is this polyfunctional potent T cells that really appear to be able to have the anti-efficacy that we're looking for.

And, Lauren, to add to that, is it correct that with these patients, every patient is going to have very different kinetics. And so measuring the maximum immune response in each patient is quite tricky because the fact that one patient has the maximum response on day 10 doesn't necessarily mean that patient two will have the maximum response on day 10. It may be on day 15 for that patient or maybe on day 5, right? So taken with the approach that you have to take in human clinical trials where you look at a specific time point, you may be able to monitor increases in that patient's immune correlates, but you may not necessarily be able to determine that this is the maximum that this patient actually generated. Just based upon the different kinetics you'll see in each patient.

That's absolutely correct, Frank, and it's why with given the inherent biologic variability that there is in every patient's individual immune responses, when we're able to look at them collectively together and see these trends, where across multiple patients we see increases in these HPV16 specific granzyme-b positive CD8 T cells over the course of treatment and a corresponding decrease in the observed circulating tumor DNA. It suggests to us that the responses that are being induced whenever they're being induced and to whatever magnitude they're being induced, are having an anti tumor effect. And again, early data, but very, very interesting in things that we want to follow.

Our next question is from line of Joe Pantginis with H. C. Wainwright.

Everybody, good morning. This is Joe for Joe. So I just wanted to you know what, Frank and Lauren, let me ask question about the multifactorial components of immunotherapy and cancer vaccines over the years. And I'll link to one of the components of the IMMUNOCERV study. And feel free to let me know if I'm getting too much into the weeds. But you're sharing today a lot of correlates about the T-cell activation, which I think is extremely important? And then when you look at even in the background, and how this study was conducted, they're talking about targeting tumors that are over 5 centimeters. Now, if you look at the past by another studies, 5 centimeters always has seemed to be a sort of a boundary that, a lot of cancer vaccine companies for example, would want to target under 5 centimeter. So I'm just curious, where previously the bulk of the tumor might have been viewed as a problem for cancer vaccine efficacy, your T cell activation here really talks to your original thesis from Frank's prepared comments regarding the T cell activation data that you have?

Definitely, I think what you said is very true. I think one of the key things you mentioned is that there have been lots of failures in the cancer vaccine space, a lot of which we believe is attributed to the inability to induce the right type of killer T cells in the right quantity. And I think what is also very important for PDS is just based upon the history in the space for us, our technology to really show a differentiation, it was important for us to go to the more difficult to treat cancers. Because we had shown in our preclinical studies clear differentiation between the induction of the right type of T-cell and tumor aggression in preclinical studies. And so our approach by looking at these patients who have this large high tumor burden was really twofold: to be able to get a quick read on whether or not this is working; and also to be able to show differentiation, that these T cells are active enough to really treat the difficult to treat cancer patients that most immunotherapies won't address. If you go all the way from there to what we're looking at with the NCI, where we're looking at checkpoint inhibitor refractory patients. Again, this is a population of patients that almost no immunotherapy looks at simply because of the tumor burden and the difficulty in treating those patients. So, I think what we're trying to establish here, our approach is to really clearly say, look, this appears to be working. We've looked at the most difficult to treat patient populations that no therapy, forget immunotherapy, no therapy is able to effectively treat. And it was very important in the early days for us and data has been very encouraging. But I think what we now have, from both the NCI and MD Anderson is now really explaining why these combinations have worked as effectively as we've seen today in providing some validation of the clinical data that we have been seen in terms of this is exactly what PDS0101 is doing, this is the kind of immune responses generating. And also very importantly, this is exactly what we see in the preclinical studies, and that data appears to translate very well based upon the technologies mechanism of action into humans. So it's a deliberate approach that we've taken in terms of really establishing the potential efficacy of our platform by looking at the more difficult to treat patient populations, that not just immunotherapy, but cancer drugs in general, really haven't been able to effectively address. Lauren, you were going to say something when I started.

Right. The only thing I would echo is that this difficult to treat cancer population, particularly with cervical cancer, that present with locally advanced disease, it is the real world population where there is incredible unmet medical need. So that again, for all the reasons that Frank has already iterated, but importantly it's where the patients are, this is how they present with unfortunately, locally advanced disease that is very difficult to treat and allow continued good clinical outcomes.

And those sizes of tumors, if I hear you correctly?

That's correct.

Perfect. And I guess, just looking forward, does IMMUNOCERV has the beginning of the design here, where you would just do a randomized study plus or minus chemorad, or is it do you have visions towards another type of study based on how difficult this population is based on the recurrence rates?

I think now we are in a information -- obtaining information stage. It's still early, we would like to see data from some more patients. And I think at that point, just like we've done with VERSATILE-002, if the data continues to look encouraging, as encouraging as it is, we will definitely want to sit down with the FDA and discuss how we could move that into a registrational trial and what the right type of registrational trial for this patient population would actually look like. But I think it's a little bit early now the data is highly encouraging, but we would like to see a little bit more data from these patients and then make -- hopefully make the right decision at that point in terms of where we go, and how we designed that trial.

Next question is from the line of James Malloy with Alliance Global Partners.

Hi, this is Laura Suriel on for Jim Malloy. Thank you for taking our questions. So for the end of Phase 2 meeting that was recently completed for the VERSATILE-002 trial, what are the next steps that you're looking into taking for this trial in particular and what is just an overview of its timeline? And also looking forward, what might the ideal registration trial for this specific indication look like? And is it still in line for a mid 2023 start? Thank you.

I'll have Lauren start, and then I'll end up with the timelines and so forth. So Lorena I hand over to you first.

Great, thank you, Frank. So our discussions with the FDA were very helpful in terms of identifying what the key elements of our design should be in terms of a pivotal registrational trial, we've initiated feasibility in order to be able to determine what needs to happen as far as we know that this is going to be a global trial and that's one of the things that we are in the process of investigating. We do look to anticipate having the trial initiated in the first half of 2023. Again, it would be dependent upon feedback that we're receiving not only from the FDA, but also from European agencies and countries where we would be conducting the trial. Frank?

Thanks, Lauren. Yeah, so, really as Lauren said, really, we are now in the clinical design stage right in terms of designing what this trial will look like working with the statisticians to understand the population and the population size. And then we would definitely want to run that by the FDA again, and just make sure that the FDA is in agreement, that if we run those trials as designed and meet the endpoints, that it will be acceptable to the FDA. So we are at that stage now, and hopefully, the goal is to hopefully get this started sometime around the middle of next year.

Our next question is from the line of Robert LeBoyer with Noble Capital.

In Dr. Wood's discussion, there was a mention of 0102 and 0103 with a mention of manufacturing process for clinical trials. Is there any estimate at this point of when you might be able to file an IND or move forward to clinical trials?

Yes, so -- and between PDS0102 and PDS0103 we prioritize PDS0103. So PDS0103, as I mentioned, is in our -- is going through clinical manufacturing. And we expect that that would very likely be the next product that goes into human clinical trials. We had initially projected that we will be filing the IND for that program by the end of this calendar year; however as I mentioned in the earlier remarks, based upon the FDA's agreement that we move PDS0101 into a pivotal trial and the amount of regulatory work that goes towards getting a registrational trial up and running, we are prioritizing PDS0101 at this point. And therefore because of that prioritization of PDS0101, what we decided to do is to, I wouldn't want to say deprioritize, but PDS0101 has taken precedence and therefore we anticipate that the PDS0103 will be ready for IND sometime in the first half of next year just because of the prioritization now, of all the regulatory work we have to do to get a global registrational trial going. Did that answer your question?

Yes, it did. Any comments on 0102?

0102 should be filling 0103, that's also in clinical manufacturing, PDS0103 is further. With PDS0102, we are at the antigen manufacturing stage, PDS0103 is actually in the final clinical product manufacturing stage. This is a little bit ahead of PDS0103. But as we continue with our business development discussions, everything we have discussed here today in terms of our understanding of how this technology is working, really helps us with also business development activities and having discussions with other potential and prospective partners. And so we’re keeping all our options open in terms of how quickly or how slowly those programs get into the clinic, and also being opportunistic in terms of what the financial situation of the company is. And so all those are being taken to consideration in terms of the timing of both PDS0103 and PDS0102, but the goal right now is to get our product into the commercialization part to reach its registrational trials as quickly and as efficiently as possible. And again, we’re also having that discussion with the FDA regarding the triple combination. So the goal here is to also understand what the regulatory pathway would be for that triple combination and also how quickly we can move that into commercialization. So all those have been taken into consideration as we determine how quickly we move the pipeline also into clinical trials. But with both of them, preclinical studies are complete and we’re in the clinical manufacturing stage towards IND filing and progression.

[Operator Instructions] At this time, I'll now turn the floor back to Dr. Frank Bedu-Addo for closing remarks.

Thank you. Well, thank you very much for joining our third quarter earnings and update call. We made extraordinary progress in both our clinical and preclinical development programs, showing the potential of our Versamune and Infectimune platforms. We plan to continue the momentum as we move through the fourth quarter and into 2023. And we look forward to updating you as we progress. Thank you very much again for your time and have a great day.