PDS Biotechnology Corporation

Hello, and welcome to the PDS Biotechnology second quarter 2023 earnings call and webcast. If anyone should require operator assistance, please press star zero on your telephone keypad. A question and answer session will follow the formal presentation. You may press star one at any time to be placed into question queue. As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to your host, Gabby DeGravina, Investor Relations. Please go ahead, Gabby.

Good morning, and welcome to PDS Biotechnology's second quarter 2023 earnings conference call and audio webcast. On the call from the company are Dr. Frank Bedouinot, Chief Executive Officer, Matt Hill, Chief Financial Officer, and Dr. Lauren V. Wood, Chief Medical Officer. Earlier this morning, PDS Biotech issued a press release announcing financial results for the quarter ended June 30th, 2023. 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 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 clinical candidate development plans, as well as research activities. Certain information in this presentation may include forward-looking statements, including within the meaning of Section 21 of the United States Securities Exchange Act of 1934, as amended, and Section 27 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 the 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 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. I will now hand the call over to Dr. Frank Feduetto. Frank?

Thank you, Gabby, and thanks to all for joining our second quarter 2023 call this morning. We are pleased with the progress we have made so far this year. Our primary goal is to create groundbreaking therapies that can significantly revolutionize cancer treatment. Our current primary focus is on advancing and commercializing our lead clinical candidate, PDS0101, designed for the treatment of recurrent or metastatic HPV16-positive head and neck cancer. EDS-0101 is an innovative, investigational HPV16-targeted immunotherapy that stimulates a potent and precise T-cell attack on HPV16-positive cancers. In the upcoming controlled and randomized Versatile 003 trial, we will examine PDS-0101 in combination with Merck's anti-PD-1 therapy Keytruda or Pembrolizumab compared to Keytruda monotherapy, which is the current standard of care for first-line treatment of recurrent or metastatic head and neck cancer. I am pleased to mention that we filed the final Versatile 003 Phase III protocol with supporting chemistry, manufacturing and controls or CMC information to our existing IND last week on schedule as planned and previously announced. I congratulate the PDS Biotech team on achieving another key milestone on our path to commercialization of PDS 0101. This filing moves us a step closer to another significant upcoming milestone. the initiation of the Phase III trial in the fourth quarter of this year. As you can imagine, we are all eagerly looking forward to the commencement of Versatile 003. This will hopefully move us towards the filing of a biologics license application, or BLA, and the increased potential to get PDS-0101 successfully commercialized and available to head and neck cancer patients who are in desperate need of safer and more effective therapies. Advanced head and neck cancer, as many of you may already know, is one of the most devastating and debilitating cancers, with one of the highest suicide rates, and unfortunately, low response rates to current treatments. This quarter, we made significant progress on our Phase 2 Versatile 002 trial. We presented positive interim data, and the data was selected and featured at an expert head and neck cancer panel discussion session at this year's ASCO annual meeting. The data demonstrated a 12-month survival rate of 87%, with only 8% of patients experiencing grade 3 treatment-related adverse events. and no reports of more severe grade four or grade five toxicities. Dr. Wood will provide more details on the ASCO data momentarily. Additionally, the naive arm of Versatile 002 reached its efficacy threshold based on best objective response as per investigator assessment. The threshold for efficacy was achieved when 14 of the 54 immune checkpoint inhibitor naive patients achieved a confirmed objective response, indicating tumor shrinkage of 30% or more in these patients. This achievement suggests that there is a statistically significant additive effect of PDS-0101 over immune checkpoint inhibitor monotherapy, and this gives us more confidence to move into the phase three registrational trial. Just last month, we announced that biomarker data demonstrating the induction of multifunctional HPV16-specific T cell responses in patients receiving the PDS0101 and Keytruda combination treatment has been accepted for presentation at the European Society for Medical Oncology Congress 2023 or ESMO, this October. The immunological clinical data will showcase the potential of this immunotherapy combination to generate clinically relevant multifunctional HPV16-targeted killer in healthy T cells in advanced head and neck cancer patients. Moreover, the treatment has demonstrated minimal toxicity further underlining its potential as an effective approach to treat this challenging cancer. Beyond the versatile 002 achievements, we've continued to successfully progress our three other PDS0101 clinical programs, as well as the development of our novel antibody-conjugated IL-12 cytokine therapy, PDS0301, in multiple National Cancer Institute or NCI-led Phase II clinical studies. We recently announced that an oral presentation by the lead investigator on the prostate cancer program at the National Cancer Institute will take place at the Cytokines 2023 Annual Meeting. The presentation will detail results for the ongoing clinical study of our antibody-conjugated IL-12 in combination with the FDA approved standard of care chemotherapy docetaxel for metastatic prostate cancer. This phase two trial, which is the first clinical study of an immunocytokine with docetaxel in prostate cancer, is being led by the National Cancer Institute and is investigating the safety, immune responses, and clinical activity of the combination in metastatic castration-sensitive and castration-resistant prostate cancer patients. As we look to the remainder of the year and the first half of next year, we expect a number of key data readouts and milestones. For Versatile 002, we anticipate providing additional data updates on both the immune checkpoint inhibitor Naive and immune checkpoint inhibitor refractory cohorts late this quarter. As recruitment of the naive arm has been completed, we project that the final data will be reported late in the second quarter of 2024. With Versatile 003, as already mentioned, we anticipate initiation of the trial later this year. High on our list is also the National Cancer Institute-led triple combination study of PDS-0101, our antibody-targeted IL-12, and an immune checkpoint inhibitor. We expect data from the immune checkpoint inhibitor refractory arm of Versatile 002, as well as updated triple combination survival data among head and neck cancer patients to inform the statistical design of the intended triple combination registrational study. We also anticipate providing updates to the highly encouraging survival data with the triple combination that we reported late last year. Dr. Anne Klopp of MD Anderson Cancer Center provided exciting data on the ImmunoServe trial in high-risk cervical cancer patients with large tumors of five centimeters or more at the SITC conference in November 2022. This is an investigator-initiated trial, and we expect to have a steady update before the end of the year. The Phase II trial of PDS0101 as a neoadjuvant treatment in HPV16-related oral cancer is also in progress at Mayo Clinic. This is an investigator-initiated trial, and we have little control over the timing of data releases. However, we are hopeful that presentation of preliminary data from the trial at a scientific meeting will occur in the near future. Although our primary focus is on Versatile 003, we are also working to file our IND for PDS 0103 our Mach 1 targeted immunotherapy before the end of this year. At this time, I will hand over to Lauren to walk us through the recent data. Lauren?

Thank you, Frank. Let's now turn to the high-level interim data presented in a poster at the ASCO 2023 Annual Meeting by Dr. Catherine Price of Mayo Clinic. and included as a featured poster reviewed by an expert panel in the head and neck cancer discussion session. The advocacy highlights include the following. A 12-month overall survival rate of 87% on the combination therapy. Published results document 12-month overall survival rates of 36% to 50% in patients with recurrent or metastatic head and neck cancer receiving approved immune checkpoint inhibitors used as monotherapy. The median progression-free survival was 10.4 months. Published median progression-free survival results report two to three months for approved immune checkpoint inhibitors when used as monotherapy in patients with similar PD-L1 level expression in their tumors. The disease control rate, which is defined as disease stabilization or tumor shrinkage, was seen in 71% of patients. In addition to the ASCO data, in July we announced that we had achieved 14 confirmed responses, suggesting that PDS0101 has an additive effect over published results seen with immune checkpoint inhibitor monotherapy. In addition to the previously mentioned 12-month overall survival rate of 87%, this provided us with further confidence moving forward with the Phase 3 randomized trial. Importantly, in the Versatile 003 Phase 3 trial, the primary efficacy endpoint will be overall survival rather than objective response. the endpoint that the FDA has prioritized for approval. Consequently, we have designed our phase three trial to show improved overall survival of PDS0101 plus Keytruda over Keytruda alone to maximize our opportunity to achieve BLA approval. With respect to safety, we are finding the combination to be well tolerated with only four of the 48 patients or 8.3% having grade 3 treatment-related adverse events, also known as TRAEs, at the time of ASCO. Furthermore, there were no grade 4 or higher treatment-related adverse events observed. The published treatment-related adverse event rate for Keytruda monotherapy is approximately 17%. We continue to ramp up through the initiation of the Versatile 003 trial. During the quarter, we completed the CMC required activities related to PDS 0101 to initiate a global multicenter phase three registrational trial. We have also received feedback from some European regulatory agencies on the Versatile 003 study design. As Frank mentioned previously, this morning, We announced submission of the clinical protocol and the CMC package to the FDA in preparation to initiate the study by the end of the year. The plan design of the controlled phase three trial will randomize subjects to PDS-0101 in combination with Keytruda as the active arm and Keytruda monotherapy as the comparator control arm. We intend to conduct the trial at 90 to 100 sites globally, the study will be powered for overall survival with an interim analysis for potential accelerated approval pending the data readout. Initiating this trial is a significant milestone for PDS Biotech, and we look forward to starting Versatile 003 in the fourth quarter of this year. In addition to the Versatile programs, we have been pleased with the ongoing results from the Phase II trial for the triple combination of PDS-0101, PDS-0301, which is our IL-12 tumor-targeting cytokine, and an investigational immune checkpoint inhibitor. This combination has been evaluated in all types of HPV-positive cancers, including anal, cervical, head and neck, penile, vaginal, and vulvar cancers in both immune checkpoint inhibitor naive as well as immune checkpoint inhibitor refractory patients. As we've mentioned previously, we plan to continue to develop and commercialize this combination using an approved checkpoint inhibitor in immune checkpoint inhibitor refractory patients. HPV 16 positive head and neck cancer is the largest and most rapidly growing of the HPV related cancer markets. The proprietary combination of Versaimmune and PDS-03-01 overcomes tumor immune suppression by a mechanism that's different from immune checkpoint inhibitors alone. We believe this technology represents a potentially transformative treatment approach for advanced cancer patients across multiple solid tumors. I would also like to highlight the advancement of are PDS-03-01 antibody conjugated IL-12 programs being led by the NCI. We continue to expand our relationship with the NCI and are now exploring the potential of PDS-03-01 both as a monotherapy and in combination with other agents in multiple clinical trials of advanced cancers. We are pleased to be able to evaluate PDS-03-01 with some of the leading experts in the field of immuno-oncology. During the Cytokine 2023 annual meeting in October, Dr. Ravi Madan of the NCI will provide interim safety and immune data based on 18 patients involved in a fierce and human phase two trial. The study is designed to evaluate PDS-03-01 in conjunction with docetaxel chemotherapy. We are excited about this trial as it represents a significant opportunity to understand the potential benefits of combining PDS-03-01 with chemotherapy and the opportunity to offer improved treatment possibilities for patients with metastatic castration sensitive and castration resistant forms of prostate cancer. The findings also have the potential to shed light on PDS-03-01 chemotherapy combinations in treating other solid tumors. With that, I'd like to now turn the call over to Matt to discuss the financial summary. Matt?

Thank you, Lauren. Now turning to our financial results for the three months ended June 30, 2023. Net loss for the three months ended June 30, 2023 was approximately $11.5 million or 37 cents for basic and diluted share compared to a net loss of $5.8 million or 20 cents for basic and diluted share for the same period in 2022. The higher net loss this quarter was due to costs incurred in connection with the research, development, and versatile clinical programs. Research and development costs, which include clinical and manufacturing expenses for the quarter ended June 30, 2023, increased to approximately $8 million compared to the $3.8 million for the same period in 2022. The increase of $4.2 million is primarily attributable to an increase of $1.4 million in clinical trials, $.5 million in personnel costs, which include $.2 million in non-cash stock-based compensation, and $2.3 million in manufacturing expenses. General and administrative expenses for the second quarter of 2023 increased to approximately $4.7 million compared to $3.3 million for the same period in 2022. The increase of $1.4 million is primarily attributable to an increase of $0.5 million in personnel costs, including $0.4 million in non-cash stock-based compensation and $0.9 million in professional fees. Total operating expenses for the quarter ended June 30, 2023 were approximately $12.7 million compared to a total operating expenses of approximately $7.1 million for the same period in 2022. Our cash and cash equivalents as of June 30, 2023 totaled approximately $60.6 million. And based on the company's cash resources and projections, we believe this balance is sufficient to fund operations and our research and developing clinical programs for the 12 months following the filing of our June 2023 quarterly report on Form 10-Q, which will be filed today. We continue to be engaged in business development opportunities and will continue to manage our cash prudently. This completes my discussion, and at this time, I would like to hand the call back to the operator for the Q&A session. Operator?

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 one on your telephone keypad. You may press star two 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 one. One moment, please, while we poll for questions. Our first question today coming from Joe Pangenis from HC Wainwright. Your line is now live.

Good morning, everyone. Thanks for taking the question, and happy summer. So, first, just wanted to get a sense of the operational readiness for the phase three. I mean, fourth quarter is not too far away, so obviously everything's probably, you know, all set. Wanted to get a sense of what the target enrollment is. Randomization, is it one-to-one, assuming the supply's all ready to go, the diagnostic, and then, of course, Lauren already discussed the benchmarks. We'll start with that. Thanks a lot.

Hi, Joe. Thanks a lot for your question. With respect to the operational readiness, as you know, there are a number of things that have to happen beyond just the submission of the IND amendment and update to the IND. A number of those are actually actively ongoing currently. We have to activate the clinical sites. We're currently looking at, as Lauren said, at 90 to 100 clinical sites. So in the process of getting those sites up and running, we have had very good response, higher than expected. We actually have about 100 clinical sites who have already indicated interest in participating in the phase three data. And we believe that is directly related to the data that was presented at ASCO, the overall survival as well as the safety. As you know, head and neck cancer oncologists are really looking for something that can help their patients live longer with higher quality of life that's well tolerated. So we believe that's really largely responsible for the larger than expected interest that we've seen in these clinical sites. So really getting all those sites up and ready, waiting for the green light from the FDA, and then we actually have to start getting the institutional review boards at the various sites to also approve these trials. The good thing is that in terms of manufacturing, the manufacturing is done, the product has been manufactured, and so all that information is what was utilized to update the CMC section. So we're looking at the target enrollment of anywhere between, I would say, between 200 to 300 patients pending. We're waiting for the final feedback from the FDA. As you know, we submitted those documents last week to the IND. And so once we have the final either green light or any feedback from the FDA, we can then make the actual final protocol available. available to everyone. But we've submitted what we anticipate could be the final protocol, but we always want to wait to get the FDA's feedback before we say this is the absolute final protocol that's moving into the phase three trial. But so far, we are very pleased and we're excited to get this going. And we think this is a really solid protocol that was developed based upon inputs that we received from the FDA. So we actually took all the FDA's feedback into consideration in putting this protocol together. As in it's going to be a control trial, right, and with Keytruda as the control arm.

That's very helpful, Frank. Thank you for that. And then I guess just, well, maybe quickly on the 0301 study with docetaxel, very intriguing, and I was just curious, you know, what are the levels of translational data that you're looking to gather for that study? And then also, I guess, you know, talking to the – The immune approach in combination with docetaxel, I guess maybe you or Lauren can discuss sort of the approach that you're taking here because even going back years ago with, you know, data out of the Gully and Schlamm labs that talked about, you know, the benefit or lack thereof or what's best to do with regard to, say, concomitant dosing with docetaxel or sequencing or what have you. So looking to get more info on the translational info. And then lastly, just curious since it's, you know, not discussed today, but it's always in the forefront of people's minds in the world, is what's percolating in the background with regard to influenza? Thanks a lot.

Really good questions, Joe. So I'll address the influenza, and then I'll hand over to Lauren to address the translational studies with PDS-03-01. So with the flu program, this program continues to progress under the NIAID civics program. So, as you know, this is typical with flu vaccines. After successful mouse studies, the vaccines are then usually tested in ferrets, and ferrets are considered the gold standard and the most relevant to human results. So, these studies in ferrets are currently ongoing with PDS0202 at the Civic Selected Centers. And so, based upon what's going on now in those ferret studies, we do intend to provide an update when these results are available. and also once the clinical studies are confirmed by NIAID. So those studies are continuing to progress. Lauren, I'll hand over to you to discuss the translational studies for PDS-03-01 and with docetaxel.

Great. Good morning, and thanks for your question, Joe. So your question is an excellent one, and one of the things that's coming out of Dr. Madan's study is there's actually concurrent dosing of PDS-03-01 and docetaxel. Specifically, there's also examination of different dose levels of PDS-03-01 in the docetaxel combination. And they're looking at both metastatic castration sensitive as well as castration-resistant prostate cancer. The translational relevance here is that we really want to, one, ensure the safety of the co-delivery of the combination together. More importantly, since NHS IL-12 is a tumor targeting immunocytokine, we really want to see if there are differences in terms of the magnitude of immune responses and clinical outcomes that we see with different doses when it's delivered in combination with docetaxel. Our hope is that since we know docetaxel induces tumor necrosis, that co-delivery of PDS-03-01 could actually augment this tumor necrosis. From a translational standpoint, our interest is not only in the fact that PDS-03-01 is a tumor targeting T-cell immunocytokine, that we see augmentation of these tumor-specific T-cell responses, but also the possibility of augmenting natural killer cell responses to this combination therapy. We're really looking forward to Dr. Madan's presentation at Cytokines 2023, and this would lead to building on further studies once we know what we see as far as the clinical outcomes and the immune responses.

Great. Thanks for all the color.

Thank you. Next question today is coming from Luis Chen from Cancer Pisterole. Your line is now live.

Hi, good morning and thank you for taking my questions and congratulations on the quarter. This is Lucas Duffy on for Louise Chen from Caner. So I have two quick questions. I guess they're more big picture strategy slash vision questions. So first question is with regards to your reverse immune platform. So you've had a lot of success to date leveraging it with PDS-01-01, 01-02, 03-04, et cetera. So I guess like what is your vision for the future of developing the platform or how do you hope to expand on the platform's success to date? And then the second question is if you could talk a little about your partnership with the NIH and if there's any like important developments there or how you see that progressing moving forward. Thank you.

Thanks a lot. Two very good questions. So the diversity platform is first being developed with PDS 0101. PDS 0101, we really see as a proof of concept study for the platform. Just based upon what's happened with the T cell activating technologies over the last couple of decades, we believe it's very important for us to really demonstrate this proof, strong proof of concept for the industry to really understand the potential of PDS0101. So as you know, we've also performed preclinical studies with PDS0102, which is utilizing the same platform in TARP-specific tumors. So these would address prostate cancer and breast cancer. We've also performed those preclinical studies with PDS0103 that addresses Mach 1 positive cancer. So these are cancers like ovarian cancer, non-small cell lung cancer, breast cancer, and colon cancer. And in preclinical studies, we have demonstrated that we can generate the same levels of multifunctional tumor-targeted killer T cells with each of these products. So really, with the PDS0101 now, our goal is really to get this rapidly into commercialization. PDS0101, as you know, addresses all types of HPV-associated cancers, however, we have an initial focus on head and neck cancer, which is the largest and most rapidly growing of these HPV indications, right? So as I mentioned, I think on the last call, we had a meeting with the FDA regarding the triple combination, which we intend to also move initially into head and neck cancer. We also have the studies ongoing currently at Mayo Clinic, which is looking at earlier stage as a neoadjuvant treatment in patients who have oral cancer ahead of their surgical removal of the lesions. So we're really looking to position, strongly position PDS-0101, which is the first versamine-based product, as a therapy for head and neck cancers, right from early stage treatment all the way through recurrent metastatic and checkpoint refractory patients. We want PDS0101 to be synonymous with head and neck cancer treatment. And we believe based on our partnerships with the National Cancer Institute, what we do with Mayo Clinic, that we will be able to successfully achieve this. We then also, as you know, have started studies in cervical cancer. The National Cancer Institute actually looked at all types of HPV associated cancers. So we have very strong evidence that PDS0101 has potential far beyond just head and neck cancer, but broadly applied in HPV-associated cancers. So as I mentioned, this is a proof-of-concept study, and we do intend to move PDS-0102 and 0103 also rapidly into the clinic. PDS-0103, as we mentioned on this call, we intend to file the IND for PDS-0103, which addresses MUC1-positive cancers to allow that to also go into the clinic after. So that would be the second product coming after PDS 0101. And we also have a business development strategy. So we are looking to selectively and advantageously partner some of these programs to move them rapidly into the commercialization path. And so moving on to the second question you asked, which is our partnerships with the NIH. So I think one of the key things that doesn't really become very obvious very often is the importance of the partnership with the National Cancer Institute, partnerships with folks like MD Anderson and Mayo Clinic. These partnerships have come about after several years of many of these partners actually independently in preclinical studies, studying our technology completely independent of PDS and convincing themselves that these technologies, our versamine technology, as well as our tumor antibody conjugated IL-12, have the potential to significantly advance the science of clinical oncology. These experts are looking for technologies that can advance clinical science. They're going to do their studies completely independent of what PDS is thinking. So from PDS or what PDS wants to see, so from PDS's perspective, we have to have enough confidence in our science and our technology that when we hand our technology over to experts such as the NIH, MD Anderson, and Mayo Clinic, that we are comfortable with them reporting whatever they find regarding our technology and our science. And so far as we can see from the results, they have provided strong validation and dependent validation of the science and technology. And the interest of these experts and key opinion leaders in actually transitioning this from preclinical studies into human clinical trials and being interested in putting some of their own capital into progressing these trials is a very strong validation of the science and the opinion of the key experts that this has the potential to significantly advance the science of clinical oncology. To date, we have eight phase two clinical trials ongoing, and five of these trials are partnered with the National Cancer Institute. And so what you can see here is that based upon these partnerships, And this buy-in to the science that PDS biotechnology is developing, we are able to progress a lot more clinical trials than we typically would, right, at a significantly lower cost to PDS biotechnology. So we are able to really advance these programs. And what this allows us to do now is to understand how PDS-03-01, for example, a tumor-targeted IL-12, behaves in certain kinds of solid tumors, how it synergizes with standard of care technologies, for example, with chemotherapy, docetaxel. We're also looking at combinations with radiation. We're looking at monotherapies. And we're doing the same with a triple combination. So this allows us then to look at the phase two data, determine in which combinations and which indications we have the best chance to rapidly commercialize these products. So we see this relationship with the National Cancer Institute as a really strong validation. They are key experts in these fields, and they also provide PDS with a lot of expert oversight and guidance in terms of how we design these trials and all things, what specific indications we look for. They have seen almost every technology that's been successful in oncology has actually gone through the National Cancer Institute. So it's a very valuable relationship to PDS biotechnology.

Okay. Thank you very much for the answers and the color. No follow-up questions for me. Thank you.

You're welcome.

Thank you. Next question is coming from Kalpit Patel from B. Reilly Securities. Your line is now live.

Yeah. Hey, good morning, and thanks for taking the question. First, for the additional updates that you expect to report later this quarter, as you said, How many more months of follow-up should we expect for the OOT trial?

So with PDS, you're talking about the Versatile 002 trial, Palpit, is that correct?

Correct, yeah.

Yeah, so I am not privy to the clinical data, but I am hopeful that when we provide the updates later this year, this quarter we'll hopefully have updates on the 12-month overall survival and hopefully also have an update on the 24-month overall survival. Those would be the two key updates that I would expect, especially since those were key for design of the phase three clinical trial. As you know, the FDA is most interested in the overall survival, and that's how the trial has been powered. So those would be two key updates that I would be hopeful that we get right before the end of the quarter.

Okay. And then based on your expectations of enrolling 90 to 100 sites in the phase three. Assuming, let's assume you start in the fourth quarter, when would you expect the interim analysis to hit and the primary endpoint as well?

The primary endpoint for the trial is overall survival. The planned interim analysis will be conducted after enrollment is complete. and after a pre-specified number of events have occurred. So since this endpoint is overall survival, the events will be death events, and a certain number of death events have to occur to meet either the interim endpoint or the final endpoint. And so really the enrollment projections were informed by our CRO feasibility analysis, and they estimate about an 18 to 24 month accrual period pending the actual enrollment rate and the actual occurrence of these events. So it's not very easy to predict exactly when that time will occur, but the initial interim endpoint will be right after the completed enrollment for the trial. So that could be anywhere between an 18 to 24 month accrual period.

Okay, perfect. Thanks very much, Frank, for getting the question.

You're welcome.

Thank you. As a reminder, that's star one to be placed in the question queue. Our next question is coming from Leland Urschel from Oppenheimer. Your line is now live.

Hi. Thanks for taking our questions. I'm wondering, Frank and Lauren, what your view may be on accelerated approval potential for PDSO 101 and the Versatile-03 study you know following the fda draft guidance that came out in march as you may be aware with recommendations on development of drugs for accelerated approval in oncology randomized trials such as versatile o3 you know could use the orr as a submissible endpoint for for affiliated approval so given the robust responses you've seen so far in that population Wondering if there may be an opportunity for you to submit earlier ahead of the mature OS data and then use the OS data from 03 as confirmation of efficacy. Thanks.

I'll take a stab at it and then I'll also hand over to Lauren to add to my response. So I think, Lynn, as you know, we do have fast-track designation, and we would like to take advantage of that to have more frequent discussions with the FDA as the data becomes available. So we do understand that currently the Versatile 002 data is extremely encouraging, and we are hopeful that if, as we get to the interim data points, if the data looks anything close to what we're seeing currently with Versatile 002, that we'll have the opportunity to discuss an accelerated approval with the FDA. So even though overall survival is the primary endpoint, we also do have secondary endpoints such as objective response rates and PFS that we will be monitoring. But in head and neck cancer specifically, the FDA made it very clear to us that since objective response rates have not really correlated with overall survival, they are primarily interested in overall survival in head and neck cancer. And so that's why we powered this trial specifically for overall survival. But we'll definitely take advantage of the fast track to have discussions with the FDA earlier on as the data begins and continues to emerge. Lauren, anything you'd like to add to that?

Yes. The only thing I'd like to echo, Leland, is that ultimately, With accelerated approval, like you mentioned, a confirmatory trial is required. So while Versatile 003 is powered for the primary endpoint of overall survival, once we have our final data cut and follow-up from Versatile 002 next year and also have those final overall survival rates for 12 months and 24 months, as well as the objective response rates, that will be another opportunity for discussions with the agency in terms of additional accelerated approval discussions. That's all.

Okay, that's helpful. And then with respect to MUC1, when might we see initial data from the MUC1 study?

Oh, well, we have not actually started that study yet. So at this point, I will not provide any timelines as to when we're going to see data. We are hopeful that we will file the IND by the end of this calendar year, which will allow us to get the clinical trial going probably by early next year. And so once we have more clarity on exactly what the clinical design is going to look like, and we'll be able to provide more information on when we should expect to see data. So hopefully on the next call, we'll have some more clarity around that question. All right. Thanks for the questions. You're welcome.

Thank you. Next question is coming from Robert LaBoyer from Noble Capital Markets. Your line is now live.

Good morning. Just one more follow-up question on the design of Versatile 003. And in the interim analysis, OS and PFS had been mentioned previously. Is PFS still going to be an interim analysis factor or endpoint that you can discuss with the FDA?

We will certainly be collecting the PFS information, but both the interim and the final endpoints have been powered for overall survival.

Okay, and one question on the triple combination. You had mentioned that the design of the phase three was in progress. Any timing on the submission of an IND for that or the start of the phase three?

So with that trial specifically, we are waiting to get, so this is going to be, as I mentioned, patients' checkpoint refractory head and neck cancer. And checkpoint refractory head and neck cancer is the indication that we're evaluating in the second arm of the BIRST-L002 study. And so as we mentioned on the last call, we expect that this quarter we will be obtaining initial information from the first 21 patients who are being treated, the first 21 checkpoint refractory head and neck cancer patients in the BIRST-L002 trial. Primarily, what we're looking for from that trial is overall survival and how it impacts and how additional PDS-0101 to Keytruda may allow those patients to respond and continue to survive. That information is going to be critical together with the information we have from the triple combination trial to design the final, what we intend and hope to be a registrational study. One of the things we will do with that design is something very similar to what we did with Keytruda, really maximize our interactions with the FDA, get the FDA's feedback. We would like to understand what key elements the FDA would like to see in that trial to allow it to be a registrational trial. And so that's interaction that we expect to be having with the FDA probably starting later this year. And so based upon those interactions and getting a really good understanding of what they would like to see in that trial to make it registrational, we'll then be able to then project exactly when we start. But we would like to start initiate those, get the initial protocol done and start those interactions with the FDA before the end of this year.

Okay, thank you very much.

You're very welcome.

Thank you. Next question is coming from James Malloy from Alliance Global Partners. Your line is now live.

Hello, this is Laura Suriel calling for Jim Molloy. Thank you for taking the questions. So for the Phase 3 Versatile 003 trial, with it being set to be initiated by the end of the year, if it's not too early to tell, when do you think you might complete enrollment here or announce a first look or interim data?

As we discussed earlier, the actual That timing is we expected based upon what the potential enrollment projections are. So we looked at what our CRO projected the enrollment could potentially be for the various sites. And also based upon the actual accrual and occurrence of the events that we expect to see for the trial, we anticipate that the enrollment could take anywhere between 18 to 24 months to be completed. And at that point, we would then have our first interim analysis.

Got it. And then also for the NCI-led Phase II trial of O301, when might we get additional data for this trial following, you know, the cytokine meeting that's going to be held this October and some of the other timelines here as well?

I'll hand that question over to Lauren since she has more information on that trial.

So, as it relates to the NCI triple combination, study that examines TDS-0101, O301, and... I think, Lorne, I think that was the docetaxel trial she was asking about. Oh, okay. I thought there was interest in updated data. So I just wanted to highlight the fact that there will be updated survival data before the end of this quarter. And then following the cytokines meeting presentation, I think there will be... additional discussions in terms of further expansion of the study at the dose levels of PDS-03-01 and docetaxel that yielded optimum tolerability as well as immune responses that are being examined and that will be presented at Cytokines 2023.

Got it. Thank you for taking the questions.

Thank you. We have reached the end of our question and answer session. I'd like to turn the floor back over for any further or closing comments.

Well, thank you very much, Lauren and Matt. And to our attendees, we very much appreciate you joining our second quarter earnings conference call today. This quarter's progress has been truly exciting, and we remain enthusiastic about what lies ahead for the rest of the year. Before concluding the call, I would like to mention that we're planning a key opinion leader event in the near future. The webcast will include experts who will provide their perspectives on PDS 0101, any data updates, and its potential in the treatment of advanced head and neck cancer. Please look out for more details as we get closer to the event. As you have seen from our press releases, and as I have reiterated here on this call, we are excited to share the many data readouts that are on the horizon and that hold significant promise and potential value to our investors. We have made great strides on the path to achieve our goal of advancing a paradigm shift in the way head and neck cancer is treated with a potentially well-tolerated, safe and effective treatment that extends the survival of advanced head and neck cancer patients. We strongly believe that in the very near future, these patients who have a critical unmet medical need will live longer, and have a higher quality of life as a result of the work we're doing here today. Thank you very much for your continued support and we look forward to updating you on our progress. Thanks a lot.

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.