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spk02: Hello and welcome to the PDS Biotechnology fourth quarter 2022 and full year earnings call and conference call. If anyone should require operator assistance, please press star zero on your telephone keypad. A question and answer session will follow the formal presentation. As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to Gabby D. Gravina of CG Capital Investor Relations. Please go ahead.
spk03: Good morning and welcome to PDS Biotechnology's fourth quarter and year-end 2022 earnings conference call and audio webcast. On the call from the company are Dr. Frank Bedouinot, Chief Executive Officer, Dr. Lauren V. 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 and full year ended December 31st, 2022. We encourage everyone to read the press release as well as PDS Biotech's report on Form 10-K, which will be filed with the SEC shortly. The company's press release is available on the 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 activities. 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 conditions, 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. So, to the extent required by applicable law or regulation, PDSB undertakes no obligation to update the forward-looking statements included today to reflect subsequent events or circumstances. With that, I will hand the call over to Dr. Frank Situato. Frank?
spk07: Thank you, Gabby, and thank you all for joining us on our year-end call today. We have made tremendous progress this past year, achieving several significant milestones as we continue to advance our oncology pipeline, most importantly, progressing closer towards a registrational trial for our lead candidate, PDS0101. PDS0101 is a novel investigational human papillomavirus or HPV-targeted immunotherapy that stimulates a potent targeted T-cell attack against HPV-positive cancers. Our goal is to commercialize PDS0101 as rapidly as possible by performing a well-designed phase three trial that maximizes our potential for both speed and success. Therefore, our key priority in 2023 is to move forward efficiently with finalizing the development of PDS0101 for the treatment of HPV-positive head and neck cancer in immune checkpoint inhibitor for ICI-naive patients. Before we move into the fourth quarter updates, I would like to briefly mention the recent meetings we have had with the US Food and Drug Administration, also known as the FDA. These meetings were held to discuss the registrational pathways for our two most advanced phase two trials, Versatile 002 and the National Cancer Institute-led or NCI-led triple combination trial. In both meetings, the FDA provided very useful guidance on key elements of both trial designs. Therefore, we will be transitioning into phase three clinical development this year. informed by the ongoing and maturing data from Versatile 002. This randomized controlled phase three trial will investigate PDS0101 in combination with Keytruda versus Keytruda alone in ICI-naive patients with recurrent or metastatic HPV16 positive head and neck cancer. The phase three trial will be called Versatile 003. In parallel, we will continue activities necessary to progress the NCI-led triple combination of PDS-0101, PDS-0301, formerly known as M9241, or NHS IL-12, with an approved immune checkpoint inhibitor, or ICI. Let's now touch on the Versatile 002 Phase 2 trial update. The trial is investigating PDS0101 in combination with Merck's ICI Keytruda, also known as Pembrolizumab, in both ICI-naive and refractory patients. Interim results presented at ASCO 2022 demonstrated promising efficacy and safety profiles for the combination. Data from 17 patients with available imaging showed an objective response rate of 41%, which included confirmed and unconfirmed responses. At nine months of follow-up, the overall survival rate was 87%. In the published Keynote 048 study, the nine-month overall survival rate for Keytruda monotherapy was approximately 60%. We believe that the parameter of highest relevance to the FDA is the overall survival. As in many immunotherapies, improvements in objective response rate, or ORR, and progression-free survival, or PFS, have not translated to improved overall survival, or ROS. It should be noted that in recurrent or metastatic head and neck cancer, where an FDA-approved drug has been shown to improve survival, such as Keytruda has, overall survival becomes the most important criteria by which the new drug or combination will be evaluated. As a reminder, this program has received fast track designation from the FDA. Following our FDA meeting in the third quarter of 2022, we initiated a tech transfer of the PDS 0101 manufacturing process to our selected commercial manufacturer for the scale-up and production of PDS 0101 for Versatile 003. The transfer was successful, and the Phase III clinical product was successfully completed this quarter. The final sections of the Chemistry, Manufacturing, and Control section, also known as CMC, of the amended IND are in progress. Most importantly, We are gaining insight into the potential progression-free survival and overall survival data that continue to mature from Versatile 002. These PFS and overall survival data are critical to our ability to design the statistical portion of the phase three clinical study. The duration it has taken for us to begin to gain insight to these critical parameters and possible endpoints is highly encouraging as it signifies that the majority of patients are staying alive and not rapidly progressing. As I mentioned, overall survival is the most important parameter by which the FDA typically prefers to confirm approval of oncology products. We are hopeful, based upon previously presented and ongoing results, that we will be able to show improved PFS and OS with the PDS-0101-Ketruda combination. We are also currently in communication with the European regulatory agencies and expect feedback on the Versatile 003 Clinical Protocol and CMC section in the second quarter of this year. If possible, we intend to also incorporate their comments into the final protocol design that will be submitted to the FDA and other country-specific agencies for review. We therefore expect to file an amended IND in the third quarter of this year, which should allow us to present the protocols to the Investigational Review Boards, or IRB, for the various sites as we perform the process of site activation. Overall, these startup activities typically take four to six months. We are working towards the goal of opening up the trial in the fourth quarter of this year and expect the trial to be run at 90 to 100 global sites. There are a number of reasons why we have decided to progress the versatile 003 trial ahead of the triple combination. First of all, obtaining an approval for the PDS-0101 product specifically simplifies our development of future combinations of other agents such as PDS-03-01 with PDS-01-01 from a regulatory perspective. IND-related activities are further progressed with this program due to the earlier FDA meeting and also the clear regulatory pathway for combination of an investigational agent with a commercial approved product. Importantly, we have fast track for this program and with our clinical design have good potential for PDS0101 to become the first approved immunotherapy to address HPV-positive cancer. In parallel, we continue to aggressively work towards getting the triple combination to a similar position and will provide updates on progress in the future. So transitioning to updates on the NCI-led Phase II triple combination trial for patients with advanced HPV-positive cancers. Last month, we announced a successful meeting with the FDA for the triple combination of PDS0101 and PDS0301 with an SDA-approved ICI for the treatment of recurrent or metastatic HPV16-positive ICI refractory head and neck cancer. Our ability to replace the investigational ICI with a commercial ICI simplifies the regulatory pathway to develop the triple combination. Our strategic decision to acquire the novel antibody conjugated IL-12, now PDS-03-01, has mitigated operational risk and potential hurdles in moving the program forward. It has also encumbered the agent for broader use in our pipeline. Importantly, by replacing the investigational ICI with a commercial ICI, and acquiring PDS 0301, we also simplified and clarified the future economics pertaining to the current and future commercial combinations of PDS 0301 with our pipeline products or other products. It is also important to note that the PDS 0301 acquisition deal does not financially burden development of the product as very minimal payments are due ahead of successful commercialization. This agreement also includes the supply of the clinical PDS 0301 product by Merck KGAA, Darmstadt, Germany. This partnership, as you can see, therefore maximizes the potential for development and financial success for both parties. We are extremely pleased with our partnership with Merck KGAA and with the updated survival outcome results we reported from the triple combination last quarter. EDS Biotech has selected advanced ICI refractory HPV16 positive head and neck cancer as the initial indication for which the triple combination will be developed. These patients have few options and no clear effective standard of care therapy, despite the severity of the disease. Survival data from the trial has been encouraging and the triple combination therapy appears to be reasonably well tolerated with grade three adverse events reported in 43% of patients and grade four treatment related adverse events reported in only of patients. In December, we reported expanded National Cancer Institute interim data that included 50 patients. Of those, 37 HPV16 positive patients were evaluable, and 29 out of the 37 patients had failed ICI treatment and were therefore ICI refractory. Median overall survival was 21 months in the 29 ICI refractory patients who received the triple combination. Of note, the reported historical median overall survival in patients with HPV-positive ICI refractory disease and treated with an ICI is only three to four months. As we announced on February 27, after our FDA meeting, our trial of the triple combination will initially target ICI refractory HPV 16 positive head and neck cancer. The best published Median overall survival data to date in ICI refractory head and neck cancer is 8.2 months. The expanded data continue to demonstrate the durability and tolerability of the PDS0101-based triple combination therapy in advanced HPV-positive cancers, and it is exciting to see consistency in the data with each update. Moving on to the MD Anderson-led Immunocere Phase II trial. This study is being performed in patients with locally advanced cervical cancer with large tumors over five centimeters in size. Remarkable clinical and biomarker data were presented at SITC 2022. 100% of patients treated with the combination of PDS-0101 and standard of care chemoradiation therapy had a clinical response with tumor shrinkage greater than 60%. Eighty-nine percent or eight of the nine patients treated with the combination demonstrated a complete response or CR with no evidence of the disease on day 170. These results are encouraging, and we look forward to updating you when additional data becomes available. The Mayo Clinic continues studying PDS0101 in early stage pre-metastatic HPV16 positive oral cancer in a phase two trial. Patients continue to be recruited and treated, and we are hopeful that we'll see data before the end of this year. As we've mentioned before, the Mayo Clinic study is an investigator-initiated trial, meaning we do not have control over its progress, enrollment, and treatment or the timing around data readouts. However, our expectation is that study investigators would present preliminary data when available at a medical congress. Moving on to our broader oncology pipeline. Tech transfer for PDS01-03 is in progress. Pending availability of manufacturing slots and all the activities associated with initiating Versatile 003, we are hoping to file the IND in the second half of this year. We expect to file the IND for PDS 01-02 in 2024. Before I turn the call over to Lauren, I will reiterate that we plan to initiate the Versatile 003 phase three trial by the fourth quarter of this year. We continue to make significant progress with the program. Clinical manufacturing is complete. Late-stage CMC activities are ongoing, as well as finalization of the clinical protocol, and we expect to file the amended IND in the third quarter. I will now turn the call to Lauren to walk us through the clinical updates.
spk06: Thanks, Frank. I'd like to recap some of the exciting data we announced in the last several months. With respect to PDS-03-01 monotherapy, clinical research conducted by the NCI was recently published in the peer-reviewed journal International Immunopharmacology. The study assessed immune changes in relation to the dose level and dosing schedule of PDS-03-01. The study also evaluated the correlates of several treatment-related immunologic changes with clinical responses. Researchers evaluated a subset of 23 patients with advanced cancers who participated in a phase one clinical trial of PDS-03-01. Patients receiving the higher dose of PDS-03-01 generated more robust immune responses. Importantly, stronger immune responses were seen at the higher dose level. These data highlight the immunological activity of PDS-03-01 which supports the immune response data seen to date in the NCI triple combination study. The ability to increase IL-12's presence within the tumors and to limit its exposure in the circulating blood constitutes a significant advancement in the development of cytokine-based immunotherapy. The research published by the NCI demonstrates the potential of PDS-0301 as a tumor-targeting IL-12 and its ability to stimulate immune activation and increase the frequency of immune responses that potentially overcome the immunosuppressive tumor microenvironment. Published studies of biologically active doses of PDS-03-01 monotherapy were associated with greater than or equal to grade 3 treatment-related adverse events in 20% of patients. and all of these were transient. One grade four treatment-related adverse event was observed and no grade five treatment-related adverse event occurred. This was published by Strauss and colleagues in 2019 in Clinical Cancer Research. Importantly, these biologically active doses are associated with increases in specific immune cells and improved clinical outcomes. Now, moving on to our preclinical program. Recently, data on both PDS0102 and PDS0103 were 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 versamine-based drug formulations containing multi-epitope peptide antigen sequences of the tumor-associated protein TARP, which is also known as T-cell receptor gamma chain alternate reading frame protein, as well as modified sequences of the mucin-1 oncoprotein, or MUC1. The preclinical research provided the foundation for the clinical development of PDS0102 as a potential treatment for TARP-associated acute myeloid leukemia, prostate, and breast cancers, and PDS-0103 as a potential treatment for MUC1-associated breast, colon, lung, ovarian, and other cancers. Key findings for PDS-0102 were high levels of CD8 killer T cell responses against multiple TARP antigens and predominant induction of multifunctional potent killer T cells, similar to what's been seen and observed with PDS0101. Key findings for PDS0103 were, again, similar to PDS0101 and PDS0102. The induction of high levels of CD8 killer T multifunctional responses against multiple MUC1 antigens and effective targeting and killing of MUC1-positive targets in vitro. We're pleased with the preclinical research to date for these compounds, confirming their biologic activity. The manufacture of PDS0102 antigens is complete, and the scale-up and manufacture of PDS0103 clinical products is in progress. There's been wide discussion among immunologists and infectious disease experts regarding the ability to develop more effective and more broadly acting vaccines against various infectious agents. One key area of research is the development of novel strategies to elicit CD4 T cells, also known as T helper cells, that can be much more broadly effective in providing protection against infection. An important advantage of CD4 T-cells is their ability to be less susceptible to viral mutations. Two important preclinical studies utilizing the infectamine platform were published in February 2023 in the peer-reviewed journal Viruses. New research performed in a laboratory of preeminent CD4 T-cell researcher Dr. Andrea Sainz at the University of Rochester Center for Vaccine Biology and Immunology, studied infecting immune and demonstrated the technology's potency in eliciting CD4G cells. The studies focused on comparing infecting immune-induced immune responses following primary vaccination against influenza with immune responses induced by leading commercial vaccine adjuvants. The study concluded that infectamine dramatically enhanced CD4 T-cell responses relative to two leading approved vaccine technologies that were evaluated in the study. The second publication in viruses from Dr. Siva Ganhatpudi and Gerald Woodward from the University of Kentucky College of Medicine demonstrated the ability of infectamine with protein viral antigens to generate a broad and protective immune response against viruses, including multiple strains of influenza. Infectivine was tested in animal models of influenza. The Investigational Universal Flu Vaccine, PDS-0202, demonstrated induction of T-cell and neutralizing antibodies against multiple strains of influenza. Q-cell responses were also generated against non-mutating regions of the flu virus. Importantly, PDS-0202 completely protected animals from lethal challenges with influenza viruses. These consistent preclinical results among the two studies are promising, and we continue discussions with NIAID regarding clinical funding for our universal flu vaccines. We will keep you posted as we move discussions forward. To summarize where we are today, first with our birth immune-based oncology program, we are highly encouraged by the consistency in the clinical response and survival data we see coming from the Versatile 002, ImmunoServe, and triple combination trials. The Phase II biomarker study results reported by both the NCI and MD Anderson at FITC 2022 demonstrated induction of the right type of potent tumor-infiltrating multifunctional killer T cells in the right quantity, which correlated with clinical responses in both cases. With our infecting-based infectious disease programs, we are similarly excited about the potential, especially considering the two studies independently reported in the journal viruses last month. Both studies demonstrate unique potential of infecting not only to induce CD8 T cells, but also to induce multifunctional CD4 T cells that are more broadly reactive and potentially less susceptible to viral mutations, while also inducing broadly reactive neutralizing antibodies. At this time, I'd like to turn the call over to Matt to review our financial summaries Matt?
spk09: Thank you, Lauren. We had an extraordinary year at PDS Biotech. As we move the business forward, our financial strategy continues to seek to mitigate financial risk while supporting our overall commercial strategy. Our goal remains to select the most promising combinations and indications and rapidly progress into a registration or trials. We're excited to prepare our lead candidate BDS 0101 for a registrational trial. We currently estimate our phase three versatile 003 trial will cost approximately $60 million, which is part of our operational budget and projections. Now let's take a look at our summary financials for the year ended December 31, 2022. Net loss for the year ended December 31, 2022 was approximately $40.9 million for $1 and 43 cents per basic and diluted chair, compared to a net loss of approximately $16.9 million, or 66 cents per basic and diluted chair, for the year ended December 31, 2021. The higher net loss was primarily due to personnel costs, clinical research and quality manufacturing costs, and the cost to license our PDS-03-01 asset. Research and development expenses for the year ended December 31, 2022, increased to approximately $29.4 million compared to approximately $11.3 million for the year ended December 31, 2021. The increase of $18.1 million was primarily attributable to an increase in personal costs of $2.3 million, clinical costs of $2.3 million, manufacturing costs of $3.6 million, and $10 million for the rights to PDS 0301 from Merck, KGA, Darmstadt, Germany. Of the $10 million, $5 million was in cash and the balance and shares of our common stock. General and administrative expenses for the year ended December 31, 2022 increased to approximately $12.2 million compared to approximately $10.2 million for the year ended December 31, 2021. The $2 million increase was primarily attributable to an increase in personnel costs of $1.3 million and professional fees of $.7 million. Total operating expenses for the year end of December 31, 2022 were approximately $41.7 million, compared to total operating expenses of approximately $21.4 million for the year end of December 31, 2021. Loss per basic and diluted share for the year ended December 31, 2022 was $1.43 as compared to a loss of 60 cents per basic and diluted share for the year ended December 31, 2021. This increase in loss per share can be primarily attributed to the investment in R&D and $10 million recorded to in-license PDS 03-01, which was all expensed in the fourth quarter and accounts for approximately 35 cents of loss per basic and diluted share. We ended the year with approximately $73.8 million in cash, which is attributed to our continued prudent financial discipline and efficient execution of our ATM. Based on the company's available cash resources and cash flow projections, the company believes this balance is sufficient to fund the company operations and research development programs into the third quarter of 2024. This concludes my portion of the call, and I'd like to turn the call over to the operator for our question and answer session. Operator?
spk02: Thank you, and I'll be conducting a question and answer session. If you'd like to be placed in the question queue, please press star 1 on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star 2 if you'd like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing star 1. One moment, please, while we poll for questions. Our first question today is coming from Leland Rochelle from Oppenheimer. Your line is now live.
spk08: Good morning. Thanks for taking my questions and congratulations on all the progress. Just a question maybe for Lauren. As we look forward to the Versatile 003 trial, I know you're still collecting data from 002 with respect to informing the, you know, the statistical considerations. But do you have a sense of the size of the enrollment of what O3 may look like? Thanks.
spk06: Thanks for your question, Leland. Go ahead, Frank.
spk07: Nothing, Lauren. Since Leland directed that question to you, I'll hand over to you.
spk06: Oh, okay. Thank you. I was trying to unmute. Thank you for your question, Leland. The design and the total sample size of Versatile 003 will be informed by the Versatile 002 data that's maturing in the ICI-naive population. We are looking for consistencies and trends, and we anticipate that we will have additional updates to that data in the spring that will allow us to finalize the protocol and give us a sample size to conduct the trial as efficiently as possible.
spk08: Okay, thanks. And then just with regard to the triple combo study, you know, you have yet to identify the ICI you'll be using except that it will be a commercially available one. Are there any information you are awaiting to learn that will allow you to settle on the choice of that ICI or at least allow us for the public to hear what that is. Thanks.
spk06: That's an excellent question, and thank you for that, Leland. Well, in terms of the design of the triple combination study, we plan to leverage and also have maturing data from the ICI refractory population of versatile 002. As Frank iterated, overall survival we know is going to be key. to informing the design of that trial and we would like to have maturing data from Versatile 002 in the ICI refractory population since that will be the focus of the triple combination study. As you're aware, there are two immune checkpoint inhibitors that have approval in the head and neck recurrent metastatic disease indication and we will be making that determination as we get more informed data on overall survival from ICI refractory patients.
spk07: Just to add a little bit to what Lauren said, as you know, there are two commercial checkpoint inhibitors that have been approved, right, Keytruda and Opdivo for head and neck cancer. So it's going to be one of those two. But also in terms of the strategy to design that trial, one of the things we want to do is to be prudent in getting all the information we need. So one of the reasons why we've seen the kind of data we've seen today in our clinical trials is that we were very systematic in our preclinical studies in making sure that we did all the necessary studies, understand exactly how this technology is working, select the optimal conditions, go into the clinical trials. And based upon that, we've seen very consistent results from trial to trial. That's the reason why we're running all these various Phase II clinical trials, right, to gain as much information as possible that can then inform design of these trials. And now since we're going to a commercial checkpoint inhibitor with PDS-0101, that's exactly what we're evaluating in the ICI refractory arm of Versatile 002. And so really having some information on how that's performing is could be very informative in terms of how we design the trial. So for example, assuming we design a 350 patient trial, but wait a few months later and understand exactly whether we actually see an improvement in overall survival potentially with a dual combination, maybe we end up starting a few months later, but with a much smaller design that's a lot more efficient which would then dramatically reduce our cost and speed to commercialization. So we just want to make sure that we're doing what's in the best interest of all shareholders, making sure we get the information that we specifically designed the trials to provide, and then based upon that information, progress into final design of that trial.
spk08: Okay, great. That all makes sense. Thanks for the added comment.
spk07: No problem.
spk02: Thank you. Next question is coming from Louise Chen from Cancer for Show. Your line is now live.
spk04: Hi, congratulations on all the progress this quarter and thanks for taking my questions. So I wanted to ask you a little bit more on the phase three versatile 003 study and see if you could provide some more details, maybe broadly speaking, how you wanted to design that study versus the versatile 002. And then how did the results of 002 inform, you know, your thinking on the phase three design for 003? And then secondly, are you expecting to present any new data at major medical oncology conferences or even for your virus, your infecting platform this year? And if so, where would you be presenting those and what venues? And then lastly, just thinking about OpEx for 2023 is the fourth quarter of 2022 a good starting point for thinking about how to build things in your starting a major study, so curious how you think about the cadence of R&D expense in 2023. Thank you.
spk07: Okay, Louise, thanks a lot for the question. I'll start and then hand over to Lauren to finish up. But in terms of the Phase 3 trial, you are correct. We are looking to get as much information as possible from the Versatile 002 trial. As I mentioned, overall survival is what we believe will be the key parameter that the FDA would want us to power the trial to really understand. But also, what we want to do as we design the trial is also take information from Versatile 002. For example, what do our PFS numbers look like? Does increasing PFS in Versatile 002 correlate with increasing overall survival, for example? And those were some of the key parameters that we needed to get insight into, because if that's the case, then we can design that with certain interim data points that may allow us to get data that we could then start discussing with the FDA sooner than later regarding a potential approval. So right now, for example, there has been recent guidance from the FDA in terms of how they would look at accelerated approvals and how they would look at single control trials for accelerated and final approvals. So with all that information, part of the key things that we would want to do is as we finalize this design, get input from the other countries into the design, finalize the numbers, but also give ourselves the opportunity to see data sooner than later And if positive, be able to start having discussions with the regulatory agencies. So that's one of the key reasons why we needed to really understand how our PFS numbers were beginning to look, as well as overall survival, and see if there was improvement over published Keytruda monotherapy data in terms of improvement in both sets of parameters. And so I'll hand over to Lauren to address the additional questions.
spk06: So in follow-up to Frank's comments, our intention, Louise, is to present updated data from Versatile 002 at scientific meetings. We are targeting to present data potentially either at ASCO, ESMO, and also potentially SITC, related not only to the updated clinical outcomes in the ICI-9 population as it relates to PFS, and overall survival, which again, Frank noted, will inform our design of Versatile 003, but also confirmation and examination of the immunogenicity parameters that we are seeing in Versatile 002. I think one of the most important things to come out last year was the demonstration that we see in patients, even in heavily treatment experienced patients, the induction of these HPV16-specific multifunctional potent CD8 killer T cells in patients. And we're looking to present that data from Versatile 002 as well during the course of 2022. So, yes, we will be presenting that data. I can't really comment regarding infectimmune presentations. The viruses publications were very, very impressive for us in terms of the ability to demonstrate broad antigen-specific CD4s and CD8 cells that can be protected from lethal influence challenge. And I think any scientific presentations during the rest of this year will be guided by additional preclinical studies that we may be pursuing with the goal of progressing our Infectimmune-Based Platform to Human Clinical Trials. And there was a third question that you had.
spk04: Could you just repeat that, Laura? Yeah, I actually, yeah, it was a financial question. So I wanted to ask you about OpEx for 2023. Is fourth quarter 2022 a good base to build off of? And then with the start, of this versatile 003 by fourth quarter 23, how should we think about the cadence of R&D expense this coming year? Thank you.
spk07: So, Lauren, I think that would be a good one for Matt to take since it's operation expenses. Matt? Sure.
spk09: Thanks, Frank. Thanks, Louise. Appreciate your question. I think in looking at Q4, you're starting to see the step up and increase in associated costs related to our trials, and that's going to continue into 2024. But I think if you take... You know, obviously, in the fourth quarter numbers, we've got $10 million that we spent with Merck KGAA. So after eliminating that, that's a good way to think about it. And also, obviously, we're going to have some additional R&D expenditures as well.
spk04: Thank you.
spk09: I'm sorry, general administrative expenses as well.
spk04: Okay, thank you.
spk02: Next question is coming from Kalpit Patel from B. Riley. Your line is now live.
spk05: Good morning. This is Andy Fleischer on for CalPIT. Thank you for taking questions and congratulations on the progress. We know that you had a successful initial meeting with the FDA for the doublet, but is the agency requiring any more data to be submitted along with the final trial protocol? And when should we expect this protocol to be submitted?
spk07: Andy, thanks a lot for the question. So I think with the triple, as we mentioned, we are looking to get some additional data. Hopefully that will inform how we design the statistical portion of that program. And also one of the key things that we would want to do, as the FDA would want to see, I think one of the key things we mentioned a number of times is the contribution of agents. We've talked about that quite a bit, right? And so pending what that information provides to us, we may be able to go in in terms of looking at PDS-0101 and PDS-0301 in addition to the triple combination. We anticipate that that may be possible, but again, that's something that we would have to discuss with the FDA. That's also important for us because if you recall, with the triple combination trial, there are two of the three agents which have been found to be critical in the clinical outcomes, PDS-0101 and PDS-0301. Right, both of those were found to be critical for those outcomes. And so part of what we may potentially do is assignment two stage where we look at a small number of patients as a lead-in to their bigger registrational trial. But again, those are things that we are looking, waiting for information for to finalize that design. We think based upon what we know today, we think it's going to be a smaller design than the Versatile 003. But until we have all the information to design that trial, I probably wouldn't be able to provide too much detail into what you're asking. But these are some of the key things that we're looking at to come up with the most efficient design possible.
spk05: Thanks, Frank. Sorry if I misspoke, but I was actually questioning the doublet study. if the agency is requiring more data before initiating that trial. Yeah, correct.
spk07: No, no, we don't require any more data before initiating that trial.
spk05: Okay, and do you have a sense of the timeline of when that protocol will be submitted?
spk07: Yes, so right now we're in discussions with the EU and the regulatory agencies from the other countries in order to get their feedback that we would then put into the final design that would then go to the FDA And so we're anticipating that by the time we have all that information from those other countries that we'll put into that protocol, so that's currently ongoing, that will probably be late Q2 or early Q3. So we anticipate that the final amended IND will be filed in Q3. And then once we get the FDA feedback, we'll then start activating the various investigation review boards, IRBs, for the various sites. We are hopeful that we will be able to convert a number of the sites, most of the sites we're working with today, into the Versatile 003 sites. And so those processes typically will take anywhere from four to six months. So with that timeline, what we are working towards and hopeful is that we will be able to get this trial up and running by Q4, right, considering all these other activities. As I mentioned, the clinical manufacturing has been successfully completed already. So we are finalizing the latest stage of the CMC section. So all those activities are progressing really successfully today. So that's our timeline in terms of when we anticipate we'll file the IND and when we'll get the IRB approvals, get the sites activated, and get the trial initiated by Q4.
spk05: That's helpful. Thank you for taking questions.
spk07: No problem.
spk02: Thank you. Next question is coming from James Malloy from Alliance Global Partners, your line is now live.
spk10: Hey, guys. Thank you for taking my questions. I had a quick question. On the amended IND and the Phase III versatile 003 trial, did you walk through the amendments to the IND, what exactly you're amending on there, and then what sort of breakpoints should we anticipate? I know the trial is going to take a little bit of time to run. Do we anticipate some interim looks at some point or any way to guide to where – So the next catalyst to be looking for once the trial gets up and running, potential data coming out.
spk07: Well, James, thanks for the question. Well, we call it an amended IND, but you're really updating your IND. The initial IND was filed for the phase two trial, which was a single arm trial. And now we're going into a controlled phase three trial, right? So those updates have to be made. We have to update the manufacturing process. We've now selected our commercial manufacturer. We've transferred the process. We're going to have to update the manufacturing process. We update the manufacturing process for phase three, manufacture of the peptides. Those have to be updated in the CMC. The manufacture of the R-DOTA, the raw material for the versamine, that's also being scaled up to the phase three. all those updates have to be made to the IND. And so that's why we call it the amended IND. It's really look at it as an updated IND with all the new information transitioning from the phase two to the phase three with a lot of those pertaining to what the commercial manufacturing and CMC package would look like. So that's really what we're doing there. James, did that answer your question?
spk10: It did indeed. And then any, thank you. Any thoughts on expectations for potential interim looks or data points here, you know, once the trial gets up and running, what you would be thinking on timing, potential certain season data coming out?
spk07: Yeah, so I think that's what we're looking at, for example, with PFS, right? So I think one of the key things you mentioned is whatever interim data points you come up with, it would have to give some indication that you are prolonging overall survival. As I mentioned during the presentation, objective response rates, for example, haven't really correlated with overall survival in most immunotherapies or many of the immunotherapies that the FDA has been evaluating recently. And so one of the key reasons we are looking at the data for PFS and overall survival is that in Versatile 002, do we see an improvement in PFS as well as overall survival? And based upon that, that improvement, what's the delta between what we're seeing with our Versalve 002 versus what's reported in Keynote 048 with Keytruda monotherapy? And then based upon that delta for both the PFS and the overall survival, that will inform us in determining how we design the trial and what we could use as an interim data log. And so that delta is really going to determine the statistics, right, in terms of what's the size of the patient population that we're going to need before we see PFS, if we are seeing an increase in PFS. But very importantly, we would also want that to be associated with an increase in overall survival, at least an indication that we improve in overall survival, right? And that's why those numbers were very important, and that's why we had to wait to get some clarity to those numbers before being able to design the trial. We are now waiting for the feedback from the various countries, and then that may cause us to tweak things a little bit before we finalize that design. But we are absolutely looking to design this trial to get some early looks. to be able to go and have discussions with the FDA rather than waiting to go through the entire trial to completion of the trial before having discussions with the FDA. So we are looking specifically at that design, in our design.
spk10: Excellent. Thank you. The final question would be, on the triple combo. I know that you highlighted earlier how it's somewhat out of your hands with a partner running the trial. Can you walk through expectations or the current expectations for some of the data, next data from this, and then, you know, any, I know all three is clearly the focus here, but any thoughts on potentially a phase three starting the triple combo at some point in the near, at some point in the future?
spk07: Absolutely. I think with the triple combination, The triple combination is not out of our hands, right? The NCI trial is essentially completed, right? So right now, what we have done is we have acquired the PDS-03-01. So really, it's now in our control, right, in terms of our partnership with Merck KGA. They are providing us with the material. We're designing the trial. However, to complete design of that trial and to have an efficient trial, we're also looking at PDS0101 plus Keytruda, which is a commercial checkpoint inhibitor in this exact patient population we're going to be treating, which is recurrent metastatic head and neck cancer. And therefore, we anticipate that we should see this data sometime in Q3. That data, even though we're looking at PDS0101 in Keytruda without IL-12, we know that IL-12 is critical in these checkpoint inhibitor refractory patients. So that data will not necessarily be essentially what we would anticipate seeing in the Phase 3 trial, but it will be very informative if, for example, we already see an improvement in overall survival even without IL-12 in that patient population. That information then allows us to more efficiently design the statistical portion of that Phase 3 clinical trial, right? So those are the key pieces of information we're looking for. We are also, at the same time, doing the work needed to identify the correct commercial manufacturer for that product as we take it over, right? So essentially what we want to do as we go into our phase three clinical trials is to make sure that it's going to be pretty much very similar to what the commercial product is going to look like in terms of the manufacturing, right? That mitigates your risk significantly and speeds up going from your BLA to actually producing and selling your commercial product. Right. So those are some of the key things that we did for Versatile 003 and would like to take the same approach with the triple combination to make that process much more efficient once we started from beginning to end. So currently we are prioritizing getting Versatile 003 up and running. But once that's happened, our then primary primary goal is also in primary focus would then be getting the triple combination also up and running. Our key here is commercialization of PDS-0101 and commercialization of PDS-0101 plus PDS-0301, right? So that's really the approach we're taking just to make sure that we mitigate risk as much as possible and make sure that we can execute the most efficient trial possible.
spk10: Great. Thank you for taking the questions.
spk07: No problem.
spk02: Thank you. As a reminder, that's star one to be placed in the question queue. Our next question is coming from Robert LaBoyer from Noble Capital Markets. Your line is now live.
spk01: Good morning, and thank you for all the details you've given on the Versatile and the Triple Therapy trials. My question has to do with the MDA Anderson and the Mayo Clinic data that's been coming out and whether you have plans to include those in trials or any milestones going forward or things to look forward to from those indications.
spk07: Thanks, Robert. Lauren, do you want to take this one first?
spk06: Yes. Thanks, Robert. So, as Frank mentioned, both the MD Anderson-led ImmunoServe trial as well as the Mayo Clinic trial are investigator-initiated studies, so we don't have control over the accrual rates or actually the publication or presentation of scientific data from those trials. However, we do know that there has been significant interest and enrollment and accrual to the Mayo IIT trial, just reminding everyone that this is using and investigating PDS0101 alone for combination with Keytruda prior to definitive curative surgical resection in individuals who are presenting for initial treatment of HPV16 oropharyngeal cancer. Our hope is that we will be hearing from investigators and that they'll be able to present some interim data hopefully this year regarding preliminary findings in this population. It's very important to us because this study is going to provide us insight into not only immunogenicity, tumor shrinkage prior to surgery, pathologic response in tissues, but also an important examination of the biomarker of circulating tumor HPV16 DNA. The ImmunoServe data from MD Anderson was on the first nine subjects who had actually completed their day 170 evaluations. We know that there are additional patients from this study that have already undergone treatment, but were not at that time point to allow presentation of their data at the end of 2022. So we look forward to additional data as that matures from that study as well.
spk01: Okay, great, thank you very much.
spk07: Lauren, do you want to add a little bit about the Mayo Clinic and how it could be translated into a potential randomized trial? I think that may also help.
spk06: Okay, so one of the things that we're very interested in is seeing whether or not we can impact differentiating outcomes for patients earlier in disease. And so we hope to see, in addition to whether or not we see tumor shrinkage and decline in circulating tumor DNA, and whether or not those are predictive of disease recurrence, we would potentially design a randomized trial to look at PDS0101 alone versus PDS0101 in combination with Keytruda in this neoadjuvant treatment setting. Merck has published studies examining Keytruda alone in the neoadjuvant treatment setting with some evidence of preliminary evidence of tumor shrinkage and minimal pathologic response, and we would hope to improve on that.
spk07: All right. Thanks a lot, Lauren. So, Robert, really here with both of them, there is a significant commercial opportunity in both trials. And so the key here is really getting that basic information that will say, okay, yes, move forward. And if it's yes, move forward, how do we design that control trial based upon the information that we receive from both trials? So both provide us with a significant commercial opportunity that we are currently waiting for the data to make the next decisions.
spk02: Thank you. We've reached the end of our question and answer session. I'd like to turn the floor back over to management for any further closing comments.
spk07: Thank you very much. Well, thank you very much for joining us today on a fourth quarter and full year-ended earnings conference call. So while 2022 was a year of tremendous progress for both our clinical and preclinical development programs, 2023 is poised to be transformational for our platform technologies in PDS Biotech. I will reiterate that our key goal this year is to prioritize rapid commercialization of PDS 0101, first in the Versatile 003 study. We have selected and completed manufacturing of PDS 0101 at our preferred commercial manufacturer for Versatile 003, We will also progress activities needed to commercialize PDS0101 in combination with PDS0301. We will continue with activities necessary to progress PDS0103 to IND this year. And we also plan to continue progressing discussions with the NIAID towards hopefully getting PDS0202 for universal flu into the clinic. We thank you for your continued interest, and we will continue to update you as we advance through this exciting journey. Thank you very much.
spk02: Thank you. That does conclude today's teleconference webcast. You may disconnect your line at this time and have a wonderful day. We thank you for your participation today.
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