PDS Biotechnology Corp. Aktie

Greetings, and welcome to the PDS Biotech First Quarter 2026 Earnings Conference Call. [Operator Instructions]

It is now my pleasure to introduce your host, [ Dean Schwartz ]. Thank you. You may begin.

Thank you, operator. Good morning, everyone, and welcome to PDS Biotech's First Quarter 2026 Results and Clinical Programs update call. I'm joined on the call today by the following members of the company's management team: Dr. Frank Bedu-Addo, Chief Executive Officer; Dr. Kirk Shepard, Chief Medical Officer; and Lars Boesgaard, Chief Financial Officer.

Dr. Bedu-Addo and Dr. Shepard will provide an overview of the company's recent highlights in its clinical development program, and Mr. Boesgaard will review the financial results for the quarter ended March 31, 2026. Following management's prepared remarks, we will take questions from covering analysts.

As a reminder, during this call, we will be making forward-looking statements, which are subject to various risks and uncertainties that could cause our actual results to differ materially from these statements. Any such statements should be considered in conjunction with cautionary statements in our press releases and risk factors discussed in our filings with the SEC, including our quarterly reports on Form 10-Q and annual report on Form 10-K and cautionary statements made during this call. We assume no obligation to update any of these forward-looking statements or information.

Now I'd like to turn the call over to Dr. Bedu-Addo. Frank?

Thank you, Dean, and good morning, everyone. It's our pleasure to speak with you again and to provide this brief update on our progress in advancing our clinical programs. This past quarter, our major focus was on advancing our clinical programs and we made significant progress.

So I will hand the call over to our Chief Medical Officer, Dr. Kirk Shepard, to provide an update. Kirk?

Thank you, Frank. During our first quarter, we adopted an amendment to our VERSATILE-003 trial, revising the design to incorporate progression-free survival as an interim primary endpoint which we believe has the potential to enable a more efficient path to accelerated approval. We also believe this amendment may shorten the trial's duration and reduce the overall costs, all while retaining overall survival as a basis for full approval in accordance with FDA requirements.

Additionally, this approach may also accelerate the availability of this promising treatment to the rapidly growing population of HPV16-positive patients in dire need of effective treatment. For patients living with HPV16-positive head and neck cancer, a disease with significant and growing unmet need, we believe PDS0101 represents a promising treatment option, and we remain focused on advancing it as efficiently as possible.

PDS0101 in combination with KEYTRUDA or pembrolizumab is the only late-stage investigational head and neck squamous cell carcinoma therapy that requires only 5 doses and also the only subcutaneous therapy. These characteristics of PDS0101, together with the tolerability and survival data reported to date, make PDS0101 a potential compelling option for these patients. Key opinion leaders at institutions such as Mayo Clinic, Dana-Farber and Yale Cancer Institute are involved in our trial.

HPV16-positive cancers are rapidly increasing in the U.S. and EU due to poor uptake of the human papillomavirus vaccine and other factors. Along with the unique pathophysiology of HPV16 cancers and the absence of approved targeted therapies, there is a significant unmet need we believe that PDS0101 is uniquely positioned to address.

Elsewhere in our program, we recently reported promising results from ongoing trials for the treatment of prostate and colorectal cancer with PDS01ADC, our novel investigational Interleukin-12 or IL-12 fused antibody drug conjugate that enhances the proliferation, potency and longevity of T cells in tumor microenvironment. In March, the Journal of Clinical Oncology, JCO, Oncology Advances published clinical and immunological biomarker data from Stage 1 of a Phase II trial, evaluating PDS01ADC in colorectal cancer with liver metastasis. We refer you to these press releases issued this morning.

Earlier in our first quarter, we also announced early results from the NCI-led trial investigating PDS01ADC at the AACR special conference on prostate cancer research. In patients with metastatic castration-resistant prostate cancer, the majority of whom received this therapy as a third-line option, the combination of PDS01ADC and docetaxel demonstrated encouraging results included in our press release this morning.

The results from these 2 trials reinforce the potential of PDS01ADC to enhance the efficacy of existing therapies across multiple solid tumor types. We remain focused on advancing PDS01ADC as a key component of our immuno-oncology pipeline.

I will now hand the call back to Frank.

Thank you, Kirk. Finally, during our first quarter, we also strengthened the intellectual property estate for PDS0101 with new patents granted in the United States and Japan. The new U.S. patent, combined with anticipated biologics exclusivity for PDS0101, extends our market protection into the 2040s. The Japanese patent adds broad composition of matter claims to existing protections across major markets.

Now I will turn it over to Lars for a review of our results for the 2026 first quarter. Lars?

Thanks, Frank, and good morning, everyone. We reported a net loss for the quarter ended March 31, 2026 of approximately $7.3 million or $0.13 per basic and diluted share. That compares to a net loss of $8.5 million or $0.21 per basic and diluted share for the quarter ended March 31, 2025.

Research and development expenses for the first quarter were $3.5 million compared to $5.8 million for the prior year period. Decrease was primarily due to lower clinical and manufacturing costs. General and administrative expenses for the first quarter were $3.1 million compared to $3.3 million for the prior year period. The decrease was primarily due to lower professional fees.

Total operating expenses for the first quarter were $6.5 million compared to $9.1 million for the prior year period. Net interest expense for the first quarter were $0.8 million compared to $0.6 million for the prior year period. The company's cash balance, as of March 31, 2026, was $21.7 million.

And with that, operator, we can open the call to questions from analysts.

[Operator Instructions] Our first question comes from the line of Mayank Mamtani with B. Riley Securities.

I appreciate the updates. On the VERSATILE-003 restart enrollment activity, could you remind us what remains sort of pending there? And is there a consideration also maybe of including subcu KEYTRUDA as a combination partner. And I don't, I think, fully follow what would be the procurement of KEYTRUDA considerations that were there last year versus what do you have today for VERSATILE-003. And then I have a follow-up.

Mayank, thanks a lot for your questions. I'll hand over to Kirk. Kirk, why don't you go ahead?

Thank you, Frank. Yes, regarding the enrollment, now that we have alignment with the FDA that we are going through the procedures of amending the protocol and going back to the sites to begin the study in the near future. We're happy to say that the sites all stayed with us during that period of a pause while we did the amendment and discussed it with the FDA. So we're very happy that we still have the momentum with us.

Regarding the possibilities of using the drug with the subcu pembrolizumab in the future, that's something that would be a possibility, but it's certainly not the target now of our research. Our research is with the pembrolizumab given IV in the usual amount that it has been in the past, but that option would remain open in the future for an entirely subcu regimen.

And then on the landscape external to you within HPV16-positive head and neck, it still seems like a relatively open white space or swim lane. Are there any emerging updates you've seen recently or you're expecting particularly from the EGFR bispecific class that you might be watching for? And then I also noticed the colorectal cancer cohort Stage 2 is now fully enrolled and you obviously published data from the Stage 1 cohort. Maybe just remind us when do you expect to have the next data update for Cohort 2. That would be very helpful.

Mayank, I'll start and I'll hand over to Kirk to add anything to it. But in terms of the HPV16 landscape, you're correct, we know that BioNTech is also in the Phase III trial. But both PDS and BioNTech remain the 2 late-stage studies in the space. So you are correct. There are very few potential opportunities for these patients at this present time.

And in terms of the colorectal cancer, yes, you are correct that we have completed enrollment into that colorectal cancer cohort of that study. And we are anticipating that by the end of the year, we should have some additional data on the full population of patients in the colorectal cancer study. Kirk, anything you want to add to that?

No, I would just refer them again to the article that was just published in our press release, but also we're very encouraged by the Stage 1 of the Phase II trial with the NCI. So we're anxious to move it on to the next trial, a controlled trial, with this therapy.

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

Great to see the recent amendment. So I wanted to actually dive into that a little bit. If you could talk about maybe a little more color on the benefits here. Obviously, Kirk, you mentioned about acceleration of the clinical time lines. I'm hoping you could hit that a little more with regard to attracting patients, anecdotes you may be getting from doctors to be able to quickly get to those reenrolling quicker.

And then next, sort of the second part of that is from Lars' standpoint, what do you believe the financial impact positively for these changes could be? And obviously, would you then look to put -- keep that money towards the filing path or put it towards a pathway sort of the ADC platform?

Yes. Thank you for your question. Regarding the amendments, as far as the protocol, of course, this all started when we did our final data cut back in September of last year. And we were very encouraged by those results. If anything, though, we needed to consider how long the trial will take because the median overall survival, I think you know, increased from around 30 months out to almost 40 months and the trial would take a long time to complete.

At the same time, too, we saw the robustness of our PFS. So we went to the FDA to discuss the possibility of a co-primary, which we have right now, having the PFS as a co-primary along with the median overall survival, which would be needed for full approval, but we'd have a chance for an accelerated review with the PFS. So we're very happy with that as far as the trial design that has come as a result of the latest results as well as discussions with the FDA.

Joe, this is Lars here. So to answer your question about the potential financial impact, the way we expect the amendment to the protocol to affect really the financial requirements for the trial is one, in terms of time and in terms of time to the interim readout in particular, so that we expect that to reduce cost, both external costs, but also our internal operating expenses simply due to that shorter time period.

And another aspect to bear in mind, Joe, is that we did -- as part of the amendment, we changed the randomization and the ratio from 2:1 to 1:1. And so that also allowed us to essentially lower the number of patients from approximately 350 to approximately 250 patients. So that also in and of itself will drive lower external costs associated with completing the trial.

Helpful detail. And then just a quick follow-up question. So look, things are late stage. They're progressing, right, very quickly. Can you talk about your manufacturing needs for Versamune and the pipeline in the near term and then heading beyond potential early commercialization?

Yes, Joe, I can talk a little bit about that. So as you know, we have a pretty straightforward manufacturing process. So in terms of scale-up and commercialization, some scale-up has been done already by the commercialization. Commercial process is already established. And so what we anticipate doing is one in parallel with the Phase III doing the traditional CMC activities, which involve validation of those processes. There may be some additional scale-up required. But since the process is now fixed and established, we would look at the validation process. We need to do a number of those validation budgets heading into the BLA filing.

So those are really the major CMC activities remaining for the program. But in terms of manufacturing itself, the processes are completed and established. So pretty straightforward path to the BLA filing as pertains to the manufacturing specifically.

We have reached the end of the question-and-answer session. I would like to turn the floor back to Frank Bedu-Addo for closing remarks.

Thank you, operator. Combined with early data from our PDS01ADC program and expanded patent protection extending into the 2040s for PDS0101, we believe we have meaningful opportunities ahead as we continue to execute against our priorities for 2026. We look forward to updating you on our progress, and thank you very much again. Have a great day.

Thank you. This concludes today's conference, and you may disconnect your lines at this time. We thank you for your participation.

Greetings, and welcome to the PDS Biotech Fourth Quarter 2025 Earnings Call. [Operator Instructions] As a reminder, this conference is being recorded.

I would now like to turn the conference over to your host, Mike Moyer with LifeSci Advisors. Thank you. You may begin.

Thank you, operator. Good morning, everyone, and welcome to PDS Biotech's Fourth Quarter 2025 Results and Clinical Programs Update Call. I'm joined on the call today by the following members of the company's management team: Dr. Frank Bedu-Addo, Chief Executive Officer; Dr. Kirk Shepard, Chief Medical Officer; and Lars Boesgaard, Chief Financial Officer. Dr. Bedu-Addo will begin with an overview of the company's recent highlights and its clinical development program. Dr. Shepard Will review the data and rationale behind the amendment the company recently adopted to its Phase III VERSATILE-003 trial, and Mr. Boesgaard will review the financial results for the quarter ended December 31, 2025. Following management's prepared remarks, we will open the call to questions from covering analysts.

As a reminder, during this call, we will be making forward-looking statements, which are subject to various risks and uncertainties that could cause our actual results to differ materially from these statements. Any such statements should be considered in conjunction with cautionary statements in our press releases and risk factors as discussed in our filings with the SEC, including our quarterly reports on Form 10-Q and annual report on Form 10-K and cautionary statements made during this call. We assume no obligation to update any of these forward-looking statements or information.

Now I'd like to turn the call over to Dr. Bedu-Addo. Frank?

Thank you, Mike, and good morning, everyone. It's our pleasure to speak with you again and to provide this brief update on our progress in advancing our clinical programs. The fourth quarter of 2025 capped a period of important progress for PDS Biotech, marked by meaningful advances across our clinical programs, along with financial discipline and expansion of our intellectual property portfolio. Building on the compelling top line data from our VERSATILE-002 Phase II trial, we believe the VERSATILE-003 protocol amendment we've adopted has the potential to create a more efficient path to accelerated approval. shortening the trial's duration, reducing costs and accelerating our time line to regulatory submission, while preserving overall survival as the basis for full approval.

For patients living with HPV16-positive head and neck cancer, a disease with significant and growing unmet need, we believe PDS0101 represents a genuinely promising treatment option, and we remain focused on advancing it as efficiently as possible.

In recent weeks, we also announced early results from the National Cancer Institute-led trial investigating PDS01ADC, our investigational IL-12 tumor-targeted immunocytokine at the American Association for Cancer Research, AACR, Special Conference on Prostate Cancer Research.

In patients with metastatic castration-resistant prostate cancer, the majority of whom had failed at least 2 prior treatments, the combination of PDS01ADC and standard of care docetaxel demonstrated encouraging and durable median progression-free survival or PFS of 9.6 months and a median prostate-specific antigen or PSA decline of 40%. 6 of 16 patients achieved greater than 50% PSA decline. These findings reinforce the potential of PDS01ADC as an immunocytokine that may be used to activate the immune system against multiple solid tumor types. We are encouraged by the progression-free survival and PSA declines observed in this difficult-to-treat population, and we remain focused on advancing PDS01ADC as a key component of our immuno-oncology pipeline.

Since we last spoke with you, we also strengthened the intellectual property estate for PDS0101 with new patents granted in the United States and Japan. The new U.S. patents, combined with anticipated biologics exclusivity for PDS0101 extends our market protection into the 2040s. The Japanese patent adds broad composition of matter claims to existing protections across major markets. To elaborate on progress with our VERSATILE-003 trial, in particular, the data and rationale behind the decision to amend the study protocol, I'll turn the call over to Dr. Kirk Shepard, our Chief Medical Officer. Kirk?

Thanks, Frank, and good morning, everyone. As most of you know, last August, we announced completion of our VERSATILE-002 trial with the final data further supporting the durable clinical benefit of PDS0101 in HPV16-positive recurrent and/or metastatic head and neck cancer. The strength of this final data and of the data in the sub-analysis, we announced in September led to our strategic decision to seek an amendment to our VERSATILE-003 trial to include progression-free survival or PFS as a primary endpoint. As you will recall, the VERSATILE-002 trial evaluated PDS0101 plus KEYTRUDA or pembrolizumab in patients with HPV16-positive head and neck cancer. A total of 53 patients were enrolled. The final data showed median overall survival was 39.3 months in patients with PD-L1 combined positive score or TPS of more than or equal to 1. The lower limit of the 95% confidence interval was 23.9 months and the upper limit was not yet estimable. The VERSATILE-002 trial is the first of patients in recurrent metastatic head and neck cancer population to report a median overall survival of almost 40 months. The PFS and survival results had important implications for the original design of our Phase III VERSATILE-003 trial. In the original trial protocol, as recommended by the FDA, median overall survival was the primary endpoint and progression-free survival was a secondary endpoint. It should be noted that the median overall survival relies on the occurrence of death events and that if a drug works well enough to prevent patient death, it may take a long time to get to the critical data readout. With further increase of the final median overall survival readout from 30 months to 39.3 months in the VERSATILE-002 trial and demonstration of the robustness of the PFS results, we felt we had an opportunity to revise the clinical design to enable a potentially faster readout and opportunity for accelerated approval using PFS as a primary endpoint. To address the potential for an extended trial duration while also abiding with the FDA's recommendation to use median overall survival as a primary endpoint, we approached the FDA to amend the protocol to convert PFS to an earlier interim primary endpoint. Following a productive dialogue with the FDA, we were pleased to announce that following the FDA's standard 30-day wait period since filing, the FDA raised no objections, and we are clear to proceed with the amended protocol. We believe this amendment provides us with an important opportunity to potentially shorten the time to regulatory submission while maintaining median overall survival as the endpoint for full FDA approval. Additionally, we also believe this approach may also accelerate the availability of this promising treatment to the rapidly growing population of HPV16-positive patients in dire need of effective therapy.

For added context, I'll point out that some additional factors that help explain why we and our investigators are so excited about our current path forward. First, PDS0101 is the only subcutaneous injection product currently in late-stage development for recurrent and/or metastatic head and neck squamous cell carcinoma, which is more convenient for the patient. Additionally, PDS0101 in combination with KEYTRUDA is the only late-stage head and neck squamous cell carcinoma therapy that requires only 5 doses. Most therapeutic approaches require over 20 doses. Our approach also presents convenient dosing intervals of 3 weeks and 6 months after the fourth dose. These characteristics of PDS0101, together with the reported tolerability and survival reported to date, make PDS0101 a compelling option for patients. It is, therefore, not surprising that several KOLs and investigators involved in our study and many of the institutions such as the Mayo Clinic, Dana-Farber and Yale Cancer Institute continue to voice their strong support for our approach. HPV16-positive cancers are rapidly increasing in the U.S. and EU due to the poor uptake of the human papillomavirus vaccine and other factors. Along with the unique pathogenesis, physiology of the HPV16-positive cancers and the absence of approved targeted therapies, there is a significant unmet need, we believe that PDS0101 is uniquely positioned to address.

With that, I'll turn the call back over to Frank.

Thank you, Kirk. To Kirk's comments, I would add that as stated by Merck, the subcutaneous version of KEYTRUDA, which was recently approved by the FDA, can be administered by a health care provider in as little as 1 minute. So a potential combination with subcutaneous PDS0101 may shorten administration time and be more convenient for patients. We are excited about the potential of this therapy for head and neck cancer patients. We are, therefore, confident in the potential of our HPV16-tailored approach and the potential of PDS0101 to ultimately provide a well-tolerated treatment without chemotherapy as an option for the growing population of HPV16-positive patients who currently have no effective therapies for this deadly disease and who will soon become the majority of head and neck cancer patients.

Now I will turn it over to Lars for a review of our financial results for the 2025 fiscal year. Lars?

Thanks, Frank, and good morning, everyone. Net loss for the year ended December 31, 2025, was approximately $34.5 million or $0.74 per basic and diluted share, which compares to a net loss of $37.6 million or $1.03 per basic and diluted share for the year ended December 31, 2024.

Research and development expenses for the year ended December 31, 2025, were $19 million compared to $22.6 million for the year ended December 31, 2024. The decrease of $3.6 million was primarily attributable to decreases in manufacturing costs of $2.5 million and personnel costs of $1.8 million. And those decreases were partially offset by an increase in clinical costs of $0.7 million.

General and administrative expenses for the year ended December 31, 2025, were $12.5 million compared to $13.8 million for 2024. The $1.3 million decrease was primarily attributable to a decrease in personnel costs.

Total operating expenses for the year ended December 31, 2025, were $31.5 million compared to $36.3 million for 2024. Net interest expense was $4.1 million for the year ended December 31, 2025, compared to $2.2 million for the year ended December 31, 2024. The change was primarily due to noncash expenses related to extinguishment of debt as well as lower interest income on our cash balances. The company's cash balance as of December 31, 2025, was $26.7 million.

And with that, operator, we can open the call to any questions.

[Operator Instructions] Our first question comes from the line of Joe Pantginis with H.C. Wainwright.

This is Josh on for Joe. So now that you have the amended protocol cleared, could you share what the revised enrollment target is going to look like and how that reduction compares to the original design?

Josh, thanks a lot. I'll hand it over to Kirk to answer your questions.

Yes, certainly. With the revised protocol, and also the increased median survival and robustness of the PFS in 002, we had a meeting with the FDA, which was a very good dialogue. And at that, we were able to shorten the trial to as much as a year as far as getting the final results. And of course, the PFS will be the interim analysis that will first be available most likely in a period of about 1.5 years. That will allow us to get an accelerated review, as you know, to make the drug available to patients. So with the decrease in the end as well as the increased results from the final analysis of the VERSATILE-002, we were able to shorten the duration with this -- a smaller end for the trial.

Great. And so now with this amended protocol, how should we expect R&D to be for 2026? Do you expect that to be a little bit lower than 2025 now with the smaller trial design?

Lars, I'll hand over to you.

Yes. So I think as far as the R&D expenses, we're not providing financial guidance per se. However, of course, once we reinitiate the trial, we do expect cost to pick up. The pickup will be commensurate with the amount of sites that we opened and patient enrollment and so forth. So it's tricky to forecast right now.

Our next question comes from the line of Mayank Mamtani with B. Riley Securities.

Could you touch on your plans to handle patients already enrolled prior to the 003 pause as part of your interim analysis and wonder if you remain blinded to those sort of patients? I assume they're continuing to dose on active drug and placebo.

And then my follow-up question to the prior question was anything you've learned last year from the execution of Phase III that could inform the enrollment pace from here? And sorry if I missed that, did you say what the sample size -- what the new sample size for the Phase III is? And are you willing to share any more details on the 2 -- it looks like you have the 2 PFS interim analysis. So I don't know what they are designed to hit on the first versus the second? If you can give any more details, that would be great.

Thanks, Mayank. Kirk, do you want to start?

Yes. Certainly, I'll [ do ]. There were many questions asked there. Well, we -- first, the patients who were started on the trial, they will all continue their treatment as indicated by the protocol. It was discussed with the FDA, and they said it was up to us as far as whether to include or not include these patients in the trial. They just wanted to be stated ahead of the protocol restart. But these patients will be on the trial as the treatment indicated. They will most likely be put in a special subset of the data that will be included for safety in the intent-to-treat data trial. So they will continue to receive their therapy. Let's see the other parts of the study. Sorry, could you repeat something else what Frank [indiscernible].

Yes. enrollment pace based on what you saw last year, and I believe there's no competitive trial now enrolling given the other trials that were accepting HPV16-positive are fully enrolled maybe.

And then if you can share with us the sample size of the new -- of the study and the interim analysis, PFS analysis that -- what are the underlying assumptions of separation between the 2 arms?

Yes. So the enrollment pace was very good and will continue to be good because we've had a very positive response from the sites that we've gone to, to run the study. As you've mentioned now, there's less competition than was when we first began the trial. so that we have a robust recruitment of sites. And we're happy to say, too, even with the pause we had while talking to the FDA, we didn't lose 1 site. They're all excited by this therapy and ready to begin again. So we're very happy about that. Also the fact that we figured out our time lines by looking at the VERSATILE-002 study, which was done at a certain rate. And now we expect even increased rate because most of the sites came back so that the VERSATILE-002 sites are now going to be involved in the 003 study, which is good because they know the workings of the protocol and the product, and we expect to have pretty brisk recruitment of the patients.

Got it. Mayank, I hope that answered your questions.

I -- sorry to push you, if you can share with us the powering assumptions for the interim PFS and the new sample size for the Phase III.

No. So we haven't made the sample size public yet, but the PFS, again, powered it high power to detect changes in -- statistically significant changes in PFS, 1 at completion of recruitment and the other about 6 months later. So both provide high power to detect statistically significant differences between the 2 arms.

Ladies and gentlemen, that will conclude our question-and-answer session. I'll turn the floor back to Dr. Bedu-Addo for any final comments.

Thank you, operator. Combined with early data from our PDS01ADC program and expanded patient protections extending into the 2040s, we believe we have meaningful opportunities ahead as we continue to execute against our priorities in 2026. We look forward to updating you on our progress. Thank you very much.

Thank you. This concludes today's conference call. You may disconnect your lines at this time. Thank you for your participation.

Greetings. Welcome to the PDS Biotech's Third Quarter 2025 Earnings Conference Call. [Operator Instructions] Please note that this conference is being recorded.

At this time, I'll turn the conference over to Tom Johnson with LifeSci Advisors. Tom, you may now begin.

Thank you, operator. Good morning, everyone, and welcome to PDS Biotech's Third Quarter 2025 Results and Clinical Program Update Call. I'm joined on the call today by the following members of the company's management team Dr. Frank Bedu-Addo, Chief Executive Officer; Dr. Kirk Shepard, Chief Medical Officer; and Lars Boesgaard, Chief Financial Officer. Dr. Bedu-Addo will begin with an overview of the company's recent progress and its clinical development program. Mr. Boesgaard will review the financial results for the quarter ended September 30, 2025, and Dr. Shepard will then join the call to help address questions from covering analysts.

As a reminder, during this call, we will make forward-looking statements, which are subject to various risks and uncertainties that could cause our actual results to differ materially from these statements. Any statements should be considered in conjunction with the cautionary statements in our press release and risk factors as discussed in our filings with the SEC, including our quarterly reports on Form 10-Q and our annual report on Form 10-K and cautionary statements made during this call. We assume no obligation to update any of these forward-looking statements or information.

Now I'd like to turn the call over to Dr. Bedu-Addo. Frank?

Thank you, Tom, and good morning, everyone. It's our pleasure to speak with you again and to provide this brief update on our progress in advancing our clinical programs. During our third quarter of 2025 and recent weeks, we continued to advance PDS0101 or Versamune HPV in HPV16-positive recurrent and/or metastatic head and neck cancer. In August, we announced completion of our VERSATILE-002 trial with the final data further supporting the durable clinical benefit of PDS0101 in this patient population. The strength of this final data and of the data in sub-analysis we announced in September led to our strategic decision to seek an amendment to our VERSATILE-003 trial to include progression-free survival as a primary endpoint in addition to median overall survival. Our rationale for taking this step will be the focus of today's call.

Let's begin. Last August, we announced final top line survival data from the VERSATILE-002 Phase II clinical trial. As you will recall, the VERSATILE-002 trial evaluated PDS0101 plus KEYTRUDA or pembrolizumab in patients with HPV16-positive head in neck cancer. The final data showed median overall survival was 39.3 months, in patients with combined positive score or CPS of greater than or equal to 1. The lower limit of the 95% confidence interval was 23.9 months, and the upper limit was not yet estimable.

Importantly, the progression-free survival was 6.3 months among patients with CPS greater than or equal to 1. This PFS result is notable considering the fact that over 62% of patients in the VERSATILE-002 study had low CPS of 1 to 19. These patients have historically had significantly lower PFS results. A total of 53 patients were enrolled in the VERSATILE-002 trial. Unlike the VERSATILE-003 Phase III trial, the primary endpoint for the VERSATILE-002 trial was objective response rate or ORR. The VERSATILE-002 study included 9 censored patients who discontinued the study after the primary endpoint of ORR was reached and were, therefore, lost to follow up. To understand the potential impact of these 9 patients on PFS and MOS, a sensitivity analysis was performed in the second quarter of 2025 prior to our presentation at ASCO.

Our statistical experts obtained the survival records and disease progression status for these 9 patients. The resulting censoring analysis showed no negative impact on either PFS or MOS. The VERSATILE-002 trial is the first of patients in the recurrent and/or metastatic head and neck cancer population to report a median overall survival of almost 14 months. The PFS and survival results also have important implications for the current design of our Phase III VERSATILE-003 trial.

In the current trial protocol, median overall survival is the primary end point and progression-free survival is a secondary endpoint. However, even before our final readout of VERSATILE-002 a key concern external to PDS Biotech was the fact that MOS relies on the occurrence of death events. The concern being that if a drug works well enough to prevent patient death, it may take a long time to get to the critical data readout. With the further increased final MOS readout from VERSATILE-002 this concern was further exacerbated. To hopefully address the potential for an extended trial duration, while also abiding by the FDA's recommendation, to use MOS median overall survival as the primary endpoint, we have amended the protocol to convert PFS to a surrogate primary endpoint.

As announced, we have requested a meeting with the FDA to discuss the described amendment to the current trial protocol to include PFS as a surrogate primary endpoint independent of median overall survival, which will continue to remain as the primary endpoint for full approval. Our request to meet with the FDA to propose an amendment to VERSATILE-003 is based on careful consideration of the final data from VERSATILE-002. We believe the robust PFS data now presents us with an important opportunity to potentially shorten the time to regulatory submission while maintaining median overall survival as the endpoint for full FDA approval.

Importantly, we believe this approach may also accelerate the availability of this promising treatment to the rapidly growing population of HPV16-positive patients in dire need of effective treatment. Treatment with PDS0101 for currently enrolled patients in our VERSATILE-003 Phase III trial will continue during the temporary pause of the trial. We believe that the industry is waking up to the realization that HPV positive head and neck cancer is rapidly becoming a real problem, and several industry publications just in the last few months have reported on this developing situation.

Some of you might be familiar with independent market research published by DelveInsight on the oropharyngeal cancer market published this month. The article states that they performed interviews with KOLs at leading cancer research centers. And based on a quote from the publication with declining rates of head and neck cancers related to alcohol and tobacco, HPV has become the principal etiologic factor in oropharyngeal cancer, redefining prognostic outlooks and informing the development of tailored therapeutic approaches.

Based on established research, over 90% of HPV-positive oropharyngeal cancers, or HPV16-positive. We are, therefore, confident in the potential of our HPV16 tailored approach and the potential of PDS0101 to ultimately provide a well-tolerated treatment without chemotherapy as an option for the growing population of HPV16-positive patients who currently have no effective therapies for this daily disease, and who will soon become the majority of head and neck cancer patients. Elsewhere in our pipeline, we announced that the National Cancer Institute or NCI, presented new clinical data at the 2025 Society for Immunotherapy of Cancer SITC annual meeting. The NCI presented 3 abstracts highlighting emerging clinical and translational findings from PDS Biotechnologies novel investigational immunotherapy platforms, including PDS0101, our lead Phase III clinical stage HPV targeted immunotherapy and our tumor targeting IL-12 used antibody drug conjugate PDS01ADC.

The presented translational biomarker studies demonstrated the unique immunological properties of PDS0101 and PDS01ADC leading to antitumor immune responses and the predictability of clinical responses. PDS0101 combination immunotherapy was observed to induce broad immune activation and quantitative measurements of various blood analytes predicted clinical benefit with good accuracy. PDS01ADC monotherapy in patients with advanced solid malignancies was observed to increase blood frequencies of stem-like memory and effector CD8 and CD4 T cells that had self-renewing properties. We believe the data presented at SITC further validate the scientific underpinnings of our immunotherapy platforms and confirm that our development approach is achieving the intended immunological and clinical effects.

These findings provide a deeper understanding of how our immunotherapies are generating such promising results in advanced cancers. Earlier in the quarter, we announced that the colorectal cancer cohort of the Phase II clinical trial with PDS01ADC, met the criteria for expansion to Stage 2, following positive Stage 1 results. This trial is also being led by the National Cancer Institute. Our Phase II clinical collaborations with a National Cancer Institute, MD Anderson Cancer Center, the Mayo Clinic as well as our preclinical collaboration with NIAID allow us to focus our resources on our VERSATILE-003 Phase III clinical trial, while progressing development of our pipeline via these investigator-led studies.

Now I will turn it over to Lars for a review of our results for the third quarter of 2025. Lars?

Thanks, Frank, and good morning, everyone. We reported a net loss of $9 million or $0.19 per basic and diluted share for the 3 months ended September 30, 2025, that compared to $10.7 million or $0.29 per basic share in the prior year's quarter. Decrease in net loss was primarily due to lower operating expenses. Research and development expenses were $4.6 million for the 3 months ended September 30, 2025 compared to $6.8 million for the prior year period. The decrease was primarily due to lower manufacturing and clinical expenses and personnel costs.

General and administrative expenses were $3.6 million for the 3 months ended September 30, 2025, compared to $3.4 million for the prior year period. The increase was primarily due to higher professional fees, which were partially offset by lower personnel costs. Total operating expenses were $8.1 million for the 3 months ended September 30, 2025, compared to $10.2 million for the prior year period. Net interest expense was $0.9 million for the 3 months ended September 30, 2025, compared to $0.5 million for the prior year period. The increase was primarily due to lower interest income from our cash deposits. Our cash balance as of September 30, 2025, was $26.2 million, which compared to $41.7 million as of the beginning of the year. Yesterday, we completed the sale of $5.8 million of our common stock or prefunded warrants as well as $5.8 million company warrants for gross proceeds of approximately $5.3 million.

And with that, operator, we can open up the call for any questions.

[Operator Instructions] And our first question is from the line of Mayank Mamtani with B.Riley Securities.

I appreciate the update. So on the VERSATILE-003 protocol pause, can you touch on how you plan to handle the patients that are already enrolled and assume that they will make it to the -- this new PFS analysis that now you're going to propose to the agency? See if you could just give us an update logistically how patients enrolled will be included there? And then also, what's the new sample size, I believe you might be having some awareness of what the new protocol size would look like? And I was also curious what the net cost savings would be for you as a result of that?

Well, Mayank, thanks a lot for your question. So I think as we mentioned in the -- in the -- in the script that we just read through, we are going to continue to treat those patients who have already been enrolled on the trial -- on the study trial. In terms of incorporating them into the trial as a whole, these are not significant amendments, but these are part of the discussions that we will be having with the FDA. In terms of the new size, we have not disclosed that publicly yet. We don't want to do any of that until we have actually sat down with the FDA. We've made certain proposals to the FDA by the anticipation and the whole tier is that we will address some of those concerns by getting to those clinical trial readouts earlier than the currently designed trial will allow us to get there, right?

But I will -- I'll hand over to Kirk and see if he has anything to add to that.

No. Nothing to add, Frank. You said these discussions will take place soon. We think there are very reasonable amendments that we're asking for. We're also very happy that in reviewing these amendments and strategy for the study that the steering committee that we have as well as our investigators are with the program. They believe very much in what we're doing. And the emphasis here, as Frank said, is that these patients will be continued to receive drug on the protocol during the pause.

And are you able to share any information on what the expected PFS would be under control KEYTRUDA. It's obviously much lower than what we see relative to the OS, as you said, but just was curious what you're seeing in studies that have recently published on PFS control arm. And obviously, that feeds into your analysis for what you would power the Phase III study for?

My answer, I think I'll just reiterate something that Kirk just mentioned. These amendments and the work that's going into what we have suggested to the FDA is something that has been thoroughly discussed with the experts and principal investigators, and is very strongly supported by those experts in the field and also what we're proposing is nothing unusual in terms of clinical trial design. So we -- the goal here is to make sure that not only is it very well supported by investigators and experts in the field, but also that it is nothing unusual regarding the FDA regulations, everything we're suggesting should be -- should abide by the regulatory guidelines, right?

So we're making sure we stick with that. And in terms of the VERSATILE-003 trial, Mayank, just to make sure I address exactly what you asked, could you just repeat the last part of that section -- last part of your question?

The PFS for the control arm that you have incorporated and if that has changed relative to your prior assumption when you initially started the study?

Correct. So the PFS, as you know, in the KEYNOTE-048 study as well as the LEAP-010 study, it was 3.2 months for CPS greater than 1 in the KEYNOTE-048 study, and it was 2.8 months. in the LEAP-010 study. Now these studies were predominantly -- we assume the LEAP-010 study was predominantly HPV negative, that hasn't been published yet, but we know that the KEYNOTE-048 study was predominantly in HPV negative patients. We know that there are 2 studies that have been published that actually compared HPV-16 positive patients with HPV negative and other types of HPV infected head and neck cancer patients.

And so we know from those studies that the prognosis, if you have HPV-16 positive head and neck cancer appears to be worse than if you have HPV negative or other types of HPV positive head and neck cancer, right? And so at this point, we are conservatively assuming that the PFS in the control arm is going to be around the 3-month range, which has been reported for KEYNOTE-048 and also in the LEAP-010 study, which was 2.8 months.

That's a big delta. So Lastly, there's been a lot of strategic interest in the head and neck cancer space. A lot obviously -- on the bispecific or ADC side of things and including at ESMO, any thoughts on how you're looking at the broader landscape, especially on the HPV positive side where there's or HPV-16 positive side there is not a whole lot going on.

Right. Mayank, as you mentioned, there is quite a bit of work going on also with ADCs and so forth in head and neck cancer. But as you may know, those are really primarily targeted to HPV-negative patients. As I just mentioned, it appears that there is becoming that realization now in the industry that HPV positive head and the cancer is becoming a really serious medical problem, right? Just in the last few months, we've had several publications report on the growing incidents of HPV positive head and cancer, and this independent market research report I mentioned, specifically stated that HPV negative or the traditional head and neck cancers caused by tobacco and alcohol are on the decline and the new phase of head and neck cancer is HPV positive head and neck cancer, right. As I mentioned, we are very confident in the approach we've taken to focus on HPV-16 positive head and neck cancer, which again in oropharyngeal cancer, for example, over 90% of these HPV-positive oropharyngeal cancer are HPV-16 positive, right?

We've shown on our slide, the growing projection from some of the top medical journals such as Lancet, showing the significant increase in the prevalence of HPV-16 positive head and neck cancer. And so we are very encouraged with the results we've seen today. And we are also very encouraged that this growing population of patients will hopefully have a therapy that specifically addresses this growing type of head and neck cancer, which it appears from the expert reports could potentially be the dominant type of HPV of head and neck cancer in the next decade, right? So we continue to be pleased with the approach we've taken to really target and focus on HPV-16 positive head and neck cancer. But the majority of -- the majority of studies and the products are being developed in head and neck cancer are not focused on HPV positive head and neck cancer.

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

So 2 questions, if you don't mind. On 002, can you remind us or inform us on what have you, patients that have been such long-term survival, have they seen any additional therapeutic interventions? I don't believe they have? And then second, on 003, since you're looking at PFS, can you tell us about the conduct of that study with regard to physician training and awareness and to obviously have a lot more sites than 002 with regard to being able to adapt to and not make calls early based on potential pseudo progression of the tumors from the center immunotherapy.

Joe, I'll start and then I'll hand over to Kirk. Now in terms of what patients may go on after they come off the VERSATILE-002 trial, it is important to remember that at that stage, the patients are checkpoint inhibitor resistance. And in HPV-positive disease, this is published. The median overall survival is only 3 to 4 months, right? So we have to bear that in mind in this discussion, once you become checkpoint inhibitor resistance in HPV positive disease, your median overall survival is 3 to 4 months. And therefore, if you come off PDS0101 and go on to some other therapy, and all of a sudden, you see prolonged survival, then very likely, it's only reasonable to resume that, that prolonged survival came from was a result of the therapy, PDS0101 therapy, right?

Because it is very well established that if you're a checkpoint resistant, you are not going to have long survival. Right now, when patients come off the VERSATILE-002 trial, there is no FDA-approved therapy for checkpoint resistant patients. And so they will very likely go into any investigator choice chemotherapy. And that's the most likely therapy that anybody who comes of PDS0101 will go on to, right. In terms of the VERSATILE-003 design and investigators been trained in how they look at things like pseudo progression, that's something that's very important with an immunotherapy and some of the discussions that have been had with our steering committee.

So I'll hand over to Kirk to address that question.

Yes. Thank you, Frank. First of all, just a comment on the answer as far as the subsequent treatment after the protocol, you're correct. I mean there's really nothing, it's tragic that for those who are ICI resistant, that really, there's been nothing really to show that they have any survival benefit or even a high response rate. So unfortunately, we're comfortable with the fact that after the protocol, most likely any effects would be from our drug, PDS0101.

Regarding the PFS, that's a good question because it's very important as we look at these patients that the investigators are trained as far as the response. And also, this will be reviewed, as you know, by a central review from experts who will be reading the scans, et cetera. Where we've discussed this a lot, so people are sensitive to the fact that there may be pseudo progression. And so that with patients who are still clinically well and yet not determined yet as far as a response, we will continue to follow them. So this is very important and different than the 002 because now 002, remember the primary was ORR as far as response rate.

And after the patients had a response, some of them were not followed any further. We will be following these patients all along, not only for the response, but also for safety. So we're comfortable now with the training we've had and the discussions we've had with the steering committee that we will be able to properly judge these patients as far as PFS.

And also, we're very fortunate that with the current site accruals that we have, a lot of the sites are returning who were on VERSATILE-002. So they've been trained before. They are also familiar with the drug and we're very happy to know that a number of them want to be a part of now the VERSATILE-003. So we have a good core of sites that have had experience with the drug as well as judging these responses. Thanks for your question.

I appreciate all the feedback. Thanks a lot.

Thank you. At this time, I'll hand the floor back to management for further remarks.

Thank you, operator. So thank you to all for your time today. We are excited based on the strong VERSATILE-002 results and our fast-track designation about the potential for PDS0101 in head and neck cancer. Our engagement with multiple leading clinical investigators and oncology institutions has validated our approach and the long-term opportunity that we believe our HPV-16 targeted immunotherapy represents in the HPV-16 positive head and neck cancer indication. We look forward to keeping you updated on our progress, and thank you very much again.

Thank you. Ladies and gentlemen, thank you for your participation. This does conclude today's teleconference. You may now disconnect your lines, and have a wonderful day.

Greetings. Welcome to PDS Biotech Second Quarter 2025 Earnings Conference Call. [Operator Instructions] As a reminder, this conference is being recorded. It is now my pleasure to introduce Mike Moyer with Lifesci Advisors. Thank you. You may begin.

Thank you, operator. Good morning, everyone, and welcome to PDS Biotech's Second Quarter 2025 Results and Clinical Programs Update Call. I'm joined on the call today by the following members of the company's management team. Dr. Frank Bedu-Addo, Chief Executive Officer; Dr. Kirk Shepard, Chief Medical Officer; and Lars Boesgaard, Chief Financial Officer. Dr. Bedu-Addo will begin with an overview of the company's recent progress in its clinical development program. Mr. Boesgaard will then review the financial results for the quarter ended June 30, 2025, and Dr. Shepard will join the call to help address questions from covering analysts during the Q&A.

As a reminder, during this call, we will be making forward-looking statements, which are subject to various risks and uncertainties that could cause our actual results to differ materially from these statements. Any such statements should be considered in conjunction with cautionary statements in our press releases and risk factors discussed in our filings with the SEC, including our quarterly reports on Form 10-Q and annual report on Form 10-K, and cautionary statements made during this call. We assume no obligation to update any of these forward-looking statements or information.

Now I'd like to turn the call over to Dr. Bedu-Addo. Frank?

Thank you, Mike and good morning. Good morning, everyone. It's our pleasure to speak with you again and to provide this brief update on our progress in advancing our clinical programs. The second quarter of 2025 in recent weeks have been a productive period for PDS Biotech. During the quarter, we continued to advance our VERSATILE-003 Phase III clinical trial, evaluating PDS0101 or Versamune HPV in HPV16-positive recurrence and or metastatic head and neck cancer. We also presented positive updated data from our VERSATILE-002 trial, further demonstrating the durable clinical benefit of PDS0101 in this patient population. As reported in 2 separate peer-reviewed publications, which compared clinical responses and survival in the different types of head and neck cancer, HPV16-positive head and neck cancer patients were more difficult to treat with worse survival outcomes.

As recently reported in the Clinical Journal Lancet HPV16-positive oropharyngeal cancer represents a large and the fastest-growing type of head and neck cancer. There are currently no targeted therapies to treat the underlying course of HPV16-positive cancer. Based on independent market research conducted in November of 2024 among head and neck cancer oncologists, over 50% of head and neck cancer cases in the United States are HPV16-positive. HPV positive and HPV negative head and neck cancer are 2 distinct diseases with different underlying causes, origin, risk factors and contributions to the development of head and neck cancer. Current clinical guidelines do not differentiate between HPV positive and HPV negative patients despite the significant biological and pathophysiological differences in disease cause, development and progression thus presenting a significant opportunity for an effective HPV targeted immunotherapy.

Importantly, in addition to this, patients with HPV-positive head and neck cancer are generally not candidates for surgery due to the pathophysiology of the HPV-positive tumors and therefore, not anticipated by oncologists to benefit from the recent approval of KEYTRUDA as neoadjuvant and adjuvant therapy for locally advanced head and neck cancer. It is projected in the recent issue of the British Dental Journal that by the mid-2030s, HPV16-positive head and neck cancer will become the most prevalent type of head and cancer in the United States and Europe. All these reasons make the increasing prevalence of HPV16 positive head and neck cancer a growing and severe unmet medical need. PDS Biotech is specifically addressing head and neck cancer related to HPV16, which is confirmed to be the most carcinogenic type of HPV. HPV16 is a specific type of HPV that must be confirmed using a polymerase chain reaction or PCR test rather than the commonly used P16 histochemistry test.

Our VERSATILE-003 trial differs from other ongoing Phase III clinical trials addressing first-line recurrent and/or metastatic head and neck cancer in its specific targeting of the HPV16-positive head and neck cancer population and its therapeutic approach. The 2-arm registrational trial design includes approximately 350 patients. The 2 arms of the trial include a treatment arm of the PDS0101 pembrolizumab combination versus the control arm of pembrolizumab only. Patients are being enrolled in a 2:1 randomization. Median overall survival is the primary endpoint. An overview of this trial was presented as a poster at ASCO 2025 Annual Meeting. This trial has been informed and supported by the encouraging data and observed durability we continue to see from our VERSATILE-002 trial. The most recent data from this trial were also presented at the ASCO Annual Meeting and underscore our belief in the potential of the combination to be the first HPV16 targeted immunotherapy for head and neck cancer.

Median overall survival remains steady at 30 months over the last 1.5 years, suggesting durability of the PDS0101 induced clinical responses. The lower limit of the 95% confidence interval for median overall survival increased from 18.4 months in 2023 to 23.9 months as the data has matured. All data were reported according to RECIST version 1.1 criteria requiring clinical responses on at least 2 consecutive tumor scans at least 4 weeks apart. Enrollment in the trial is complete. 22 patients continue to be followed for survival. No new safety signals have emerged. Considering the strength and durability of the clinical responses observed in our VERSATILE-002 Phase II study to date, we are confident in the potential of the combination of PDS0101 and pembrolizumab to significantly improve outcomes for patients with recurrent and/or metastatic HPV16-positive head in cancer.

At ASCO, a third abstract was presented as a poster by Dr. David M. Routman, MD, Assistant Professor of Radiation Oncology at the Mayo Clinic. This poster highlighted results of the MC-200710 study investigating PDS0101 alone or with pembrolizumab as a neoadjuvant treatment prior to surgery or radiation therapy for locally advanced HPV16-positive oropharyngeal cancer. In the prospective Phase II trial, newly diagnosed patients were administered 2 cycles of PDS0101 alone or in combination with pembrolizumab before surgical resection or chemoradiotherapy. Results show that clinical activity was seen with only 2 cycles of PDS0101 alone and also with 2 cycles of Versamune-HPV with pembrolizumab. 70% of patients who received 2 cycles of PDS0101 alone had clinical responses with stable disease and 100% of patients who received 2 cycles of PDS0101 with pembrolizumab had stable disease or partial response.

The combination of PDS0101 and pembrolizumab met the trial's primary endpoint of 50% reduction in circulating tumor DNA response. The biomarker ctDNA is measured as part of the protocol of our VERSATILE-003 Phase III trial. Elsewhere in our pipeline, we announced that the colorectal cancer cohort of the Phase II clinical trial with PDS01ADC met the criteria for expansion to Stage 2, following positive Stage 1 results. This trial is being led by the National Cancer Institute. In the metastatic colorectal cancer cohort of the study, a promising response rate of at least 6 out of 9 confirmed objective responses by RECIST version 1.1 criteria was observed. These encouraging results triggered enrollment expansion into Stage 2 under the Simon Two-Stage design of the trial. Colorectal cancer is among the most deadly and difficult-to-treat cancers.

In 2020, it was estimated that more than 930,000 deaths were due to colorectal cancer worldwide according to the World Health Organization and more effective treatments are desperately needed. This novel investigational approach to the targeting and use of our antibody fused IL-12 results in little or no systemic exposure to IL-12 and may allow patients to reap the benefits of cytokine therapy without the typical treatment limiting toxicities. We are delighted that the NCI has achieved this milestone and we anticipate completion of patient recruitment for the metastatic colorectal cancer cohort of the study by the fourth quarter of 2025.

Finally, during our second quarter, we also announced that preclinical efficacy and immune response data in mice and ferrets with a novel infect immune-based universal flu vaccine were featured in 2 presentations on universal influenza vaccine including an oral symposium at the American Association of Immunologists Immunology 2025 Annual Meeting. These studies were funded by and performed by investigators at the National Institute of Allergy and Infectious Disease Center for influenza vaccine research for high-risk populations. Our Phase II clinical collaborations with the National Cancer Institute, MD Anderson Cancer Center and the Mayo Clinic as well as our preclinical collaboration with NIAID allow us to focus our resources on our VERSATILE-003 Phase III clinical trial while progressing development of our pipeline via these investigator-led studies.

Now I will turn it over to Lars for a review of our results for the second quarter of 2025. Lars?

Thanks, Frank, and good morning, everyone. To brief you on our second quarter financial results, we reported a net loss of approximately $9.4 million or $0.21 -- $0.21 per basic and diluted share for the 3 months ended June 30, 2025, which compared to $8.3 million or $0.23 per share for the 3 months ended June 30, 2024. The increase in net loss was primarily due to higher net interest expenses, which were partially offset by lower personnel costs. Research and development expenses were $4.2 million for the 3 months ended June 30, 2025, compared to $4.5 million for the 3 months ended June 30, 2024. The decrease was primarily due to lower personnel costs, which were partially offset by higher manufacturing costs.

General and administrative expenses were $3.4 million for the 3 months ended June 30, 2025, compared to $4.2 million for the 3 months same period last year. The decrease was primarily due to lower personnel costs and lower professional fees. Total operating expenses were $7.6 million for the 3 months ended June 30, which compared to $8.7 million for the same period last year. Net interest expenses were $1.8 million for the 3 months ended June 30, 2025, which compared to $0.5 million for the 3 months ended June 30, 2024. This increase was primarily due to debt repayment costs. Our cash balance as of June 30, 2025, was $31.9 million compared to $41.7 million as of December 31, 2024.

And with that, operator, we can open the call to questions.

[Operator Instructions] Our first question is from Mayank Mamtani with B. Riley Securities.

Congrats on the progress. So regarding the VERSATILE-002 ASCO data presented, I wonder what's the plan for follow-up from that in, I believe, 22 patients you said are being followed for survival. When might we see you report or even published final results. And I guess the important question, how is the data dissemination helping drive enrollment in 003? And then I have a couple of follow-ups.

Mayank, thanks a lot for your question. So the VERSATILE-002 trial, as you mentioned, is still in progress. We anticipate that once the final patient gets their final dose of the treatment, meaning -- as you know, these patients continue on KEYTRUDA for a substantial period of time. But once the final patient gets their final treatment on the trial, we anticipate that the trial will be closed at that point. As we have stated in our projections, we do anticipate that the final data readout will be presented or published sometime before the end of this calendar year or very early next year pending how long it takes for review and all the usual things that occur with a peer-reviewed publication.

But we do anticipate that most likely the total data package, right, including ORR, PFS, safety, all inclusive, will be disseminated most likely through a peer-reviewed publication later this year or very early next year.

You talked about enrollment. I'll let Kirk chime in. But as you know, one of the key benefits of this approach to date has been the tolerability, ease of administration and of course, the very promising median overall survival. If you've listened to all our KOL events, the one key thing that the oncologists keep bringing up is they need something that's going to allow their patients to live long-term without providing significant toxicity. Quality of life and prolonged survival is one of the critical things that all oncologists are looking for. And that's one of the key benefits we have seen from this combination throughout the VERSATILE-002 trial and what keeps on coming out. The durability of the responses that these patients are seeing, the tolerability of the drug, the ease of administration. It's a simple subcutaneous injection and most importantly, survival, right? Those are key things that oncologists are looking for. But I'll hand over to Kirk because he has been dealing more directly with oncologists and the investigators. Kirk, anything you'd like to add?

Yes. Thank you, Frank. Yes, we've been very encouraged by the response of our investigators to go forth with the study, which began in March of this year, the VERSATILE-003 study. The sites have been very encouraged by the results, of course, with a 30-month median overall survival as well as Frank mentioned, the tolerability of this therapy. We have had a lot of feedback from the sites particularly around the fact that many of these sites took place were participating in the Phase II study. So they have signed on, which we're very encouraged by. So it's given us a nice core of sites to begin site accrual. And we're right on schedule as far as getting the number of sites that we'll need to do the study. So very encouraged. People are understanding the importance of the specificity of HPV16-positive therapy and are reacting to that and that they are signing up for the study.

And if you could confirm, Kirk, if there is any other large-scale trial out there seeking patients with this comparable screening criteria. And lastly, it would be great to also hear an update on the Mayo Clinic window of opportunity trial progress that obviously allows us to compare versus the KEYNOTE 689 neoadjuvant trial, which obviously focuses on HPV negative. I recognize you guys are obviously focused on the HPV16-positive in that earlier line study.

Certainly. Your question about competing trials, there are less competing trials than we had maybe a year ago because of a couple of companies dropping off their trials and also remember the specificity of our trial for HPV16-positive, there's really only 1 other major trial with BioNTech, who are also recruiting for their study. They are not as far as us. They are Phase II moving into Phase III. And even though we shouldn't compare results from Phase II studies, their median overall survival for the population so far reported is not as high as ours. So we feel really good about the lack of competition now compared to what it was a year ago with a number of companies that are trying to be in this space.

Your other question regarding the neoadjuvant therapy, the Mayo Clinic study are very important. As you said, it's a window of opportunity for us that only with 2 cycles of PDS0101 that we saw responses both with and without pembrolizumab and the neoadjuvant treatment of squamous cell head and neck cancer. This is important as far as the future design of our studies, Mayo Clinic and others who were participating in the study remain excited about pursuing this in the near future. Just one note to add about the Keynote 689, please remember that the population they treated for the successful study does not really apply to our studies in HPV16-positive. These were patients that the requirement was that they undergo surgery and most patients, if not all, are not treated with surgery in the stages that they treated. So that the trial 689 only had around 3% of the patients who are HPV positive. So this really applies mostly to HPV negative patients and not HPV positive. I hope I've answered your question.

And Mayank, I'll add a little bit to what Kirk also just said. Also, I think it's important to put that in perspective, right, in terms of the fact that we know today that the KEYNOTE 689 approach is addressing predominantly HPV negative patients. We know that the vast majority of head and neck cancer patients are going in the United States and Europe are going to be HPV16-positive right? So that window of opportunity trial was a really good insight to the potential of PDS0101 and PDS0101 plus pembro in addressing these locally advanced head and neck cancer patients. But one of the key reasons why that was so attractive to Mayo Clinic, as we've mentioned, is the tolerability and ease of administration, right? When you get [ high up ] or earlier in the treatment paradigm, safety becomes extremely important, right? And if you can replace chemotherapy with something a lot more tolerable and easy to administer you have a significant potential advantage in that particular space.

So that was very important for the oncologist to get comfortable that with even just 2 doses that they could see a strong clinical response. For PDS0101 specifically, it was also very important because we have performed a monotherapy study in our Phase I clinical trial, but was in pre-cervical cancer right? So this was, again, an opportunity to look at PDS0101 as a monotherapy in an advanced cancer population, right? And with just 2 doses we saw good clinical responses in those patients, right? So again, really understanding the contribution of these agents, right, in terms of the combination and really moving this potential forward potentially. So a really significant opportunity and also very enlightening in terms of the clinical responses that we saw with PDS0101 alone in the combination.

There are no further questions at this time. I would like to turn the call back over to Frank for closing remarks.

Thank you, operator. In closing, we are very pleased to continue advancing our VERSATILE-003 registrational trial of PDS0101 in HPV16-positive head and neck cancer. VERSATILE-003, as we mentioned, is the first Phase III clinical trial focused specifically on the growing population of HPV16-positive head and neck cancer. We are excited based on the strong VERSATILE-002 results and our fast track designation about the potential of PDS0101 in head and the cancer. We look forward, as we discussed, to publishing the full data set for VERSATILE-002 trial later this year. Our engagement with multiple leading clinical investigators and oncology institutions has validated our approach and the long-term opportunity that we believe our HPV16 targeted immunotherapy represents in the HPV16-positive head and neck cancer indication. We look forward to keeping you updated on our progress. Thank you very much again.

Thank you. This will conclude today's conference. You may disconnect your lines at this time, and thank you for your participation.

Good afternoon, and welcome to the PDS Biotechnology Virtual KOL Event. [Operator Instructions] As a reminder, this call is being recorded, and a replay will be made available on the PDS Biotechnology website following the conclusion of the event.

I'd now like to turn the call over to Dr. Kirk Shepard, Chief Medical Officer of PDS Biotechnology. Please go ahead, Kirk.

Thank you, Tara. Good morning, and good afternoon. As just said, I'm Dr. Kirk Shepard, Chief Medical Officer for PDS Biotechnology. And welcome to the webinar entitled Unmet Need in HPV16-positive Recurrent Metastatic Head and Neck Squamous Cell Carcinoma and Opportunity for Versamune HPV.

Next slide. This is our forward-looking statements. Next slide. And this is our disclaimer. PDS Biotech is the sponsor of this roundtable. Each KOL is speaking at the request of PDS Biotech under the terms of a consulting agreement. Information presented is consistent with FDA regulations and guidelines.

Next slide. Recently at the ASCO Annual Meeting, PDS was fortunate to have 3 poster presentations, which will be a part of the presentations and discussions today. The first ASCO poster was an update on the survival and other outcomes from our global Phase II VERSATILE-002 trial treating HPV16 positive recurrent metastatic head and neck squamous cell carcinoma patients with Versamune HPV plus pembrolizumab in a clinical trial demonstrating enduring median overall survival of 30 months unchanged now from past presentations.

The second ASCO presentation was a trial in progress poster showing the design of our currently ongoing Phase III pivotal trial VERSATILE-003, evaluating Versamune HPV plus pembrolizumab versus pembrolizumab alone in patients with HPV16 recurrent metastatic head and neck squamous cell carcinoma with activation of the clinical sites occurring in March of this year.

And the third ASCO presentation was a report of data from a study performed by the Mayo Clinic using Versamune HPV as neoadjuvant treatment in locally advanced HPV-16 positive head and neck squamous cell carcinoma.

The agenda for today, as shown on the slide, we are very fortunate to have 2 renowned leaders in head and neck squamous cell carcinoma with us today to give presentations and to discuss questions. Our webinar will begin with a presentation by Dr. Kevin Harrington on the unmet need in HPV16 positive head and neck squamous cell carcinoma. Dr. Katharine Price will then present the VERSATILE-002 ASCO data update and the VERSATILE-003 clinical trial that is now ongoing.

Dr. Harrington will then return to present the VERSATILE-003 trial in context, particularly with other studies such as KEYNOTE-689 and other ongoing clinical trials. We will then close with question and answers, at which time we will take written questions. The total time for the webinar with Q&A will be about an hour.

Next slide. Our first speaker, Kevin Harrington, MD PhD is Head of the Division of Radiotherapy and Imaging at the Institute of Cancer Research in the United Kingdom. In addition to expertise in radiotherapy and chemoradiotherapy, he is an authority on therapeutic approaches to metastatic head and neck cancer. Dr. Harrington is a Professor of Biological Cancer Therapies at the Institute of Cancer Research. He was one of the principal investigators for KEYNOTE-048, the pivotal clinical trial that supported the U.S. FDA approval for the use of pembrolizumab in the first-line treatment of recurrent and/or metastatic head and neck squamous cell carcinoma.

Dr. Harrington was an investigator for the VERSATILE-002 clinical trial and is on the Steering Committee for VERSATILE-003. He studied medicine at St. Bartholomew's Hospital in London and began focusing on head and neck cancer as a PhD student at Hammersmith. He has published more than 600 articles on cancer treatment. Dr. Harrington, please proceed.

Many thanks for that kind introduction, Kirk, and thank you for having me at this webinar. I'm very excited to have this opportunity to discuss the data relating to the unmet need in HPV16 positive head and neck squamous cell carcinoma. So on this slide, I show you the scale of the problem that we are facing at the present time and that which we will be facing for nearly the next century.

As you can see, the incidence of HPV-positive cancer as a whole in the head and neck region is currently undergoing a rapid expansion with some contraction of that rate expected over the course of the next 40 or 50 years or so. But as you can see, that the number of annual cases of oropharyngeal carcinoma is going to remain high even into the next century.

I draw your attention to the fact in the light blue color the HPV16 burden of that disease is by far the most prominent problem and represents a significant problem for clinicians facing this disease, and of course, the patients who suffer that disease. Now of course, we are aware of the fact that there is a vaccination program against HPV-related malignancy, and there is a confident prediction that there will be a reduction in the risk and the incident rate of oropharyngeal carcinoma as a consequence of that of the burden of disease that patients face.

But here I show you model data looking at a number of potential scenarios in which vaccination rates may vary. So you can see the status quo, the current rate of vaccination still leads us to having a significant ongoing peak of this disease over the course of the next 30 years. If vaccination were to cease, the rate would continue to rise, and clearly, we hope that, that will not happen. You can see a number of modeled scenarios in which there are rates of vaccination, including female only, male and female at 80% and 100% coverage.

The stark message from this slide is that this is a problem that's here to stay into the next century and more pressingly over the course of the next 20 or 30 years, we can see we are still on the upslope of an increase in incidence of this disease, and this is going to continue to be a health care problem for those of us who treat head and neck cancer.

Now we know that HPV positive and HPV negative disease may have different prognosis in response to certain treatment types. Here, I show you data not from the KEYNOTE-048 dataset itself, but instead, I show you real-world data recently published earlier this year from the Flatiron Health database encompassing over 2,500 patients.

So I show you, first of all, the slide on the left-hand side indicating the fact that HPV negative disease carries a poor prognosis in relapsed metastatic status and that this is benefited by both PD-1 inhibition and PD-1 inhibition plus chemotherapy.

On the right-hand side of the slide, there are a number of messages. The first is that the overall survival is higher for those who are HPV positive. But I show you that even at 5 years, that survival rate falls as low as 25%, and there is not a clear winner between the various treatment options that are available. The take-home message I feel from these data is that anti-PD-1 therapy alone is not sufficient and represents an unmet need for patients with HPV16 related head and neck cancer.

Now the point I'm also making here is that in this dataset, there is not a separate analysis by HPV16 status. I'm going to show you that in the forthcoming slides. So let's look at what these 2 diseases are, because we are now in an era where we have to think about 2 different types of head and neck cancer.

The more historically conventional form of cancer, HPV-negative disease driven largely by alcohol and tobacco consumption with mutagenesis in the TP53 gene for instance, a pathology well recognized under the microscope with a well keratinized and a better differentiated appearance.

Current U.S. prevalence in the relapsed metastatic state is between 40% and 60%. And we predict in the 2030s, this may fall as low as the 40s -- less than 40%, both in U.S. and EU.

On the right-hand side of the slide, I show you the data of HPV positive disease. This is defined by P16 positivity. And you notice here that broken out for you are the different HPV genotypes. So a number of the high-risk genotypes but with HPV Type 16 in a separate box in green on the right-hand side of the slide, you can see that it has many features pathologically and epidemiologically that are indistinguishable from other types of HPV-related disease, but it is the dominant pathology currently, both in the U.S. and as predicted into the 2030s, with a rate of greater than 60% is the forthcoming incident rate.

So this is a problem that we need to wrestle with. There are some suggestions that HPV16 related forms of head and neck cancer may, in fact, carry a worse prognosis than other HPV genotypes. I emphasize the fact that these data in a relatively small single center Canadian cohort of patients show us interestingly that HPV16 related cancers have a prognosis both in terms of overall and progression-free survival that in this analysis was more approximate to that of HPV negative disease than to the other forms of HPV-positive cancer.

This is something that we need to drill down into and examine further. These evaluations are not statistically significant, but they are strongly hypothesis generating. We know that HPV-related cancer is thought of largely as a disease affecting the oropharynx, but there is increasing recognition of the incidence of HPV associated cancers in other head and neck sites, notably in the oral cavity.

And again, I show you data. Now these data as long ago as 13 years ago from a cohort of patients with oral cavity disease, 173 patients with accurate delineation of their HPV positivity and genotype specific delineation showing very interestingly that in terms of distant metastasis-free survival, disease-free and overall survival that those patients with HPV16 related cancers had a worse prognosis than either the HPV18 related or indeed the HPV negative disease.

So I think it's important that we recognize the fact that HPV16 associated head and neck cancers may be a type of disease that represents a significant unmet need and a problem potentially for our patients.

On this slide, I want to make the point around HPV positivity, in this case, HPV16 E6/E7 sero positivity as a predictor of a better outcome in patients. Now the reason I show you this slide is to make the very important point that in those patients who are capable of mounting an immune response against HPV16, they are likely to have a better prognosis. And of course, this leads naturally to the supposition that generating therapies capable of mediating that process may be advantageous for our patients.

Interestingly, it's important to consider that this is true in terms of the hazard ratio for pharyngeal but also oral cavity and intriguingly laryngeal cancers. So it may well be that HPV16 related disease represents a broader target than disease simply confined to the oropharynx.

So on this brief review, I come to my conclusion. So I hope I have shown you that both HPV16 positive and negative disease represent distinct entities in head and neck cancer. The rising instance of HPV-positive head and neck cancer is largely driven by HPV16 related disease. This problem is not going to go away for decades, as I've shown you, even with the advent of preventative HPV vaccination. There is evidence indeed that patients with HPV16 positive disease may, in fact, experience worse outcomes. In the future, it will be important for us to identify properly patients with HPV16 positive disease and to generate targeted treatments against them.

With that, I turn the stage over to Kirk to introduce the next speaker.

Thank you, Dr. Harrington. Our next speaker is Dr. Katharine A. Price, medical oncologist who specializes in treating patients with cancers of the head and neck. After her oncology fellowship at Memorial Sloan Kettering Cancer Center, she returned to the Mayo Clinic in Rochester, Minnesota as a head and neck medical oncologist. Dr. Price is an associate professor of Oncology and Tumor Group Chair of the Head and Neck Medical Oncology and the division of Medical Oncology at the Mayo Clinic.

Her primary interest include new and deep intensified treatments for those who have oropharyngeal cancer related to HPV. Besides investigating new therapies for patients with squamous cell cancer of the head and neck, Dr. Price is actively involved with efforts to decrease health disparities and increase access to cancer clinical trials for minority and underserved populations.

Dr. Price was an investigator for the VERSATILE-002 study and is the global principal investigator for the VERSATILE-003 trial. Dr. Price?

Thank you, Kirk for that kind introduction. It really has been a great pleasure to be involved in the VERSATILE-002 and 003 studies as well as the small study that looked at the combination in a preoperative setting. So I'm happy to share my insights here today. So just stepping back on a wide range of this, why are therapeutic vaccines really promising? Or why are they being studied for HPV-associated head and neck cancer?

So one of the main reasons is that the fact that it's a virally mediated cancer lends itself to a target antigen. So in the case of Versamune HPV, this is looking at late proteins that are expressed by the virus. So it allows us to have a uniform target for a specific patient population. When we look at the patient population overall that is affected by HPV-related head and neck cancer.

There are a couple of things that stand out. One is that on average, these patients tend to be younger than the patients who get smoking and alcohol related head and neck cancers. And they have fewer comorbidities. So this is extremely important because, one, it means that most of the patients that we see are in the middle of their active life. They're raising kids. They have careers and they have potentially years to live with their disease. And these are patients who typically don't have a lot of other comorbidities. So their life and their overall survival is driven primarily by their cancer and not so much by other medical conditions like heart disease.

Dr. Harrington outlined the difference between HPV-related head and neck cancer and HPV-negative head and neck cancer and how truly, we think about these as different distinct diseases. And one of the important distinctions is that when we look at HPV-related head and neck cancer, and we think about the number of patients who will develop recurrent and metastatic disease, we are primarily seeing that those recurrences are happening in distant organs. So these are patients who are developing metastases to the lung or the liver. And this is different from smoking and alcohol-related cancers where we typically will see recurrences in the head and neck.

So what does that mean? It means that we really do need to escalate or think differently or develop new treatments that will affect the distant disease. So that's where building on the current systemic therapy like pembrolizumab is very important to try and control these important influences on overall survival for these patients.

Before we go into the VERSATILE-002 data, I did just want to present a case scenario. I think it's important to remember that there are real people behind all of this data. So this is a patient of mine, a 71-year-old man who in March of 2021, noted to have an enlarged right tonsil and had a biopsy that confirmed HPV16 positive squamous cell carcinoma. He underwent imaging at that time, which showed the mass in the tonsil as well as right-sided cervical lymph nodes.

He received radiation and chemotherapy through June of 2021 at an outside hospital, and about 16 months later was noted to have enlarging lung nodules. A biopsy confirmed metastatic HPV16-positive squamous cell carcinoma with a PD-L1 score of 60%. So I met him in January 2023, and he enrolled in the VERSATILE-002 clinical trial, which was a combination of first-line pembrolizumab plus PDS0101.

Depicted here is a representative CT scan from this patient. So the images on the left, you can see there's a large blue arrow that points to a lung nodule and this was biopsy-proven head and neck squamous cell carcinoma. This is a patient that had a complete response to this combination. So you can see on the screen on the right that, that nodule has completely disappeared.

This patient completed the full 24 months on VERSATILE-002. And currently, he's now in observation. I'm seeing him every few months and just saw him about a month ago, and he remains without any evidence of active cancer.

So moving on to the data that was presented by my colleague, Dr. Weiss at the Annual Society of Clinical Oncology this past year. So we reported on the overall survival of HPV16 positive recurrent metastatic head and neck squamous cell carcinoma patients treated with PDS0101 and pembrolizumab.

As a reminder, this was the study design. So these were patients who had biopsy-proven recurrent or metastatic HPV16 positive head and neck squamous cell carcinoma. There were 2 arms for the study. But for the remainder of this presentation and what we presented at ASCO was just on the treatment naive cohort. These were adult patients who had good performance status, and they were required to have a CPS score of greater than or equal to 1 in order to enroll on the study.

The reason for this is that, that requirement is also needed to give pembrolizumab as standard monotherapy for this disease. So all patients received the same treatment on this study. They received pembrolizumab at standard doses every 3 weeks for up to 2 years. And then they received it in combination with the vaccine, PDS0101.

And there were 5 total doses of vaccine given. The first 4 were given concurrently with the immunotherapy. There is a brief period of time where patients then received immunotherapy alone. And then in cycle 12, they received a booster of the vaccine, and then the remainder of the study was with pembrolizumab alone. The primary endpoint was best overall response and secondary endpoints for overall survival, progression-free survival and safety and tolerability.

The patient demographics for VERSATILE-002 were similar to what is seen for many, head and neck oropharynx studies in this day and age. So this is a disease that predominantly affects men over women, and that is reflected in the 92% male participants. Predominantly in this study were -- was a Caucasian population. Very good performance statuses and as was required all patients needed to have a CPS score of 1 or higher, and you can see the breakdown here, with about 2/3 having a CPS between 1 and 19 and 1/3 greater than 20.

The primary endpoint was best overall response, and this is depicted here in a waterfall plot. So if you're not accustomed to looking at these graphs, this is a visual depiction of either tumor shrinkage or growth for each individual patient. So each individual patient is represented by a bar graph and the bar graph above the X axis represent tumor growth, and then those below the axis represent tumor shrinkage.

So you can see just visually that the majority of patients had some degree of tumor shrinkage. If they cross over the dotted line, which is a shrinkage of 30% or more, they're considered responders. And you can see that there were a large percentage of responders. And notably, 21% of patients had a complete or near complete response as represented by the bar graphs on the right.

What's also important is that response were seen both in the CPS 1 to 19 group as well as the greater than 20. This combination was very well tolerated. Depicted here are the percentages of adverse events or side effects that were felt to be related to either the vaccine or to pembrolizumab. And you can see that the majority were grade 1 and 2 toxicity. So this means either very mild toxicities that don't require any kind of treatment, they can just be observed or those that require simple interventions to manage.

The percentage of patients that had a higher side effects, grade 3, 4 or 5 was quite favorable when we think about what we see compared to standard chemotherapy regimens. And notably, there were no deaths on the study. By far and away, the most common side effect was an injection site reaction. So patients were administered vaccine on their upper arm. And so many patients would have a day or so of some redness or mild discomfort or swelling that was self-limited.

Some of the other common side effects included fatigue, headache, itching, diarrhea and the others are listed here. The progression-free survival in VERSATILE-002 was very encouraging. Of course, we did not have a direct head-to-head comparison in this study, but historically, this population will have a progression-free survival on the order of 1 to 3 months across studies. And you can see broken down by CPS score that the progression-free survival was quite encouraging for this population.

The overall survival is and remains very encouraging for these patients. Again, historically, head and neck cancer patients will have overall survivals on the average of around 1 year. And you can see that even going out to over 3 years, they were still approaching 40% of patients that were alive and well on this study. So this is very exciting, particularly when we think about that these are patients that we anticipate are going to be alive and are going to go on to receive other therapies.

And so one of the things that is so encouraging about this overall survival is to keep in mind that these -- this is the very first treatment that these patients received. And so all of the other options for treatment, including standard systemic chemotherapy, have not even been given yet. And so we would hope that starting off with this combination will lead to the ability for patients to live longer and to be candidates and be able to get additional treatment for a long time.

When we look at some of the responses based on the CPS score, you can see there is a difference, which is not unexpected that the overall response rate, the disease control rate, progression-free survival and overall survival are slightly better in the CPS greater than or equal to 20. But still, when we look at all-comers we can see that, that survival is very strong for the whole group, and we do very much see that patients in that CPS 1 to 19 do appear to benefit from this treatment.

So in terms of VERSATILE-002, the enrollment in this study is complete. We have seen excellent tolerability in this combination in our patient population. The median overall survival of 30 months is very encouraging, and the clinical activity remains very strong with an overall response rate for the whole population of 35.8 and disease control rate, which refers to the number of patients who had both responses and stable disease at 77.4%. And very exciting are the percentage of patients who had really deep tumor responses. As we will illustrate in the next slide, the Phase III study has just started to enroll patients.

So my final slide here is just a schema VERSATILE-003. So this is a global randomized controlled Phase III study of PDS0101 or Versamune HPV plus pembrolizumab versus pembrolizumab monotherapy in patients with first-line HPV16-positive recurrent metastatic head and neck squamous cell carcinoma. So similar to VERSATILE-002, these are patients with recurrent metastatic disease. They need to have a CPS score of greater than or equal to 1, and this has to be the first treatment they're receiving in the recurrent and metastatic setting.

Patients will be randomized in a 2:1 fashion, meaning that 2/3 of patients overall will get the combination and then 1/3 will get pembrolizumab alone, which is a current standard of care for this patient population. The primary endpoint is overall survival. Secondary endpoints include objective response rate, disease control rate, duration of response, progression-free survival and safety and toxicity.

And then there are a few exploratory endpoints that we're very excited about. One is the incorporation of HPV16 circulating tumor DNA to look at the molecular responses to this combination. Quality of life will be collected in a systematic fashion, and we're also looking at progression-free survival 2, which means the progression-free survival of patients after they start their second-line treatment, so after the study because we believe that there may be some ongoing benefit in terms of the immune response that could allow patients even if they develop progression on this combination to continue to do better.

Notably, there will be the development of a companion diagnostic tool to identify specifically the HPV16-positive patients.

And now at this point, I have pleasure in just setting in context, the VERSATILE-003 study. And I'm going to focus on 2 main areas. So the first is I'm going to discuss the recent presentation of data relating to the KEYNOTE-689 study. And I'm going to make the point that the success of this study, which will lead to practice change, there is no doubt of that, will actually have relatively little impact, if any, in patients with HPV-related cancers.

So in this study presented recently at the AACR and currently in press, patients were randomized between treatment with pembrolizumab or going directly to surgery. Now the patient group were those with resectable locally advanced head and neck squamous cell carcinoma. Tumors affecting the larynx, hypopharynx, oral cavity at Stage III and IVa, for patients with oropharyngeal cancer, for P16 negative disease, again, it was at Stage III and IVa. But for those with HPV-related P16 positive oropharyngeal cancer. The stipulation was that disease needed to be at T4 and 0 to 2. So really advanced disease in the oropharynx for the HPV-positive population.

Patients had a good performance status by ECOG and tissue was available for testing for PD-L1. Now patients 714 in total were randomized, roughly 1:1, as you can see, between a neoadjuvant phase in which they received 2 cycles of pembrolizumab at standard flat dose every 3 weeks and then surgery or directly going to surgery.

Subsequently, on evaluation of the surgical specimen, patients were treated with radiation or chemoradiation in a risk-adapted strategy based upon the pathology. And those who had initially been randomized to pembrolizumab continued with that treatment concomitantly and then adjuvantly for a total of 17 cycles. So just a year of treatment in total. For those who had been randomized to going straight to surgery, they completed the radiation or chemoradiation and then entered follow-up.

Patients were stratified as delineated here with fairly standard stratifications. The primary endpoint of this study was event-free survival per resist with a blinded independent central review. And there was a key secondary endpoint of major pathological response. Now many of you may be aware that this study met both of those endpoints, both the primary and the key secondary endpoint. And as a result of that, has led to a change in practice, which I'll discuss in a few moments.

But before that, I want to emphasize the reason I said at the beginning that I do not believe that this study is going to change practice in HPV-related disease. You can see here from the breakdown of patient entry into the study, a fairly typical population of patients entering into a study that was -- had surgery at the heart of it.

You can see that the majority of patients are current or former smokers, alcohol use was a fairly dominant feature. The majority of patients comprise those with oral cavity or laryngeal carcinoma. And indeed, you can see approximately 10% in total had oropharyngeal carcinoma, but critically about 4% of patients in total had HPV-related disease.

So this is not a study that is really speaking to that population of patients with HPV-related cancer. Nonetheless, it's important to recognize and to celebrate indeed, the fact that the FDA has approved the indication of this treatment, but I want to make key points here.

Pembrolizumab is now indicated for the treatment of adult patients who have resectable locally advanced head and neck squamous carcinomas, with disease expressing PD-L1 with a CPS greater than or equal to 1, and those patients will receive this treatment as a single agent therapy and then subsequently go on to an adjuvant treatment where they will also receive pembrolizumab either with radiation or with chemoradiation.

But it's important to recognize and to emphasize only 3% to 4% of the patients in the study had HPV-positive disease. And that group of patients are not typically candidates for curative intent resection.

The second area that I want to discuss to set the scene for discussion is that in relapsed metastatic disease. So the setting for the VERSATILE-003 study, which is, of course, the only Phase III clinical trial in the first-line setting in HPV16 positive relapsed metastatic head and neck cancer. I list here a number of currently active or recently completed Phase II and III clinical trials.

The LIGA study with petosemtamab, so a bispecific antibody targeting both eGFR and LGR5 will include a population of patients with HPV-positive disease, but it will largely be recruited from those with HPV negative disease. A number of the other studies, and I would like to emphasize the Amivantamab research here with the Origami 4 study will also include patients in limited cohorts with HPV-positive disease but the main emphasis being on HPV negative disease.

And at the bottom of the list, the FORTIFY HN study with ficerafusp alfa, a drug that targets TGF-beta by trapping that agent is exclusively for an HPV negative population. For a number of the other studies, you will see that they involve drugs that include antibody drug conjugates, so not chemotherapy-free options or multi-tyrosine kinase inhibitor agents such as zanzalintinib, which come with a significant toxicity burden.

You see I've also mentioned a number of studies that have already press released as being negative, and the work with tisotumab vedotin has closed, and it is unlikely that, that drug will proceed further in the development for relapsed metastatic disease. So the take-home message from this slide is that VERSATILE-003 represents a very important and almost unique offering and is in Phase III for patients with first-line HPV16-positive relapsed metastatic disease.

So with this, Kirk, I turn back to you, and I hope you're now going to lead us in the Q&A session.

Thank you very much, Dr. Harrington and also Dr. Price for your previous presentation.

Yes, let's look at some of the questions that have come in. And please a moment here to get to them.

So the first question, this is from Mayank Mamtani from B. Riley Securities. Could you touch on the mechanistic rationale for Versamune and pembro combination performing in low CPS score and first-line recurrent metastatic subjects, especially since pembro performs poorly in this cohort. What's your expected mix of CPS low versus high in the ongoing Phase III trial?

So I think I can start with that. I think it's challenging when we look at CPS score, which is widely used because it's what we have, and there's definitely a correlation between responses and CPS score. But we know that it's not a perfect biomarker. And so in practice, we see people who have good responses to immunotherapy really across the spectrum with the exception of CPS 0, where it's more unlikely.

The way I think about the combination or when I think about immunotherapy alone, when we look at patients where pembrolizumab as a monotherapy works, it's very likely that they already started to have some engagement of their immune system and adding the pembrolizumab is really just like putting lighter fluid on a fire.

When we think about the combination, what Versamune HPV is going to do is to really stimulate that fire, get that immune system engaged or increase the likelihood of that immune system engagement so that the pembrolizumab can have an additive effect. So I do think that as a clinician, when we think about pembrolizumab monotherapy, it's unfortunately a minority of patients who benefit from that. And so trying to increase the likelihood that the immune system is going to respond by something like a therapeutic vaccine than using the pembrolizumab as an adjunct.

Kirk, maybe I could just add a few words. And I agree with everything that Dr. Price has said, of course. But I think the other important thing to recognize is that the PD-L1 score is an indication actually that this is a tumor microenvironment that was once experiencing interferon gamma, and that gamma probably came from an initial immune response. And unfortunately, that will have triggered expression of PD-L1 within the tumor microenvironment that can snuff out that immune response.

The strength of the Versamune HPV approach is that it runs -- it offers the prospect of generating new activated T cells and it offers the prospect therefore, of reinvigorating what might already be a rather stagnant immune microenvironment. Now if those activated immune cells go to that microenvironment where the tumor is capable potentially of putting up the barriers of PD-L1, adding in the pembrolizumab makes perfect sense in terms of taking that barrier down and unleashing those T cells.

So I think it is a very strong rationale to combine these 2 treatments. And we could predict that the PD-L1 will be some form of a predictor, but it won't necessarily dictate. So I don't think it's a given that the 1 to 19 population won't be able to benefit from this treatment. I think it's highly likely that we'll see good responses due to new T cell reactivities that we will generate.

Great. Thank you. Next question from Joe Pantginis, H.C. Wainwright. Anything in the competitive landscape to consider when enrolling patients in VERSATILE-003?

Maybe if I may have first go that, I'm sure, we'll have slightly different views on this from different sides of the Atlantic, Katharine. We consider all options when looking at patient options for treatment. And of course, we run a portfolio of studies where we have both first and second and third line offerings. And of course, in the first-line setting, for me, the most advantageous thing to consider, if possible, is a chemotherapy-free option.

Dr. Price made the really important point actually that you reserve those treatments, you keep them up your sleeve. You keep them there for the patient. And so for me, if there is a chemotherapy-free option that is all the stronger. And if that can employ an antigen that we know is expressed in the tumor because it's a HPV16 related oropharyngeal cancer, so much greater strength for that strategy with a chemo-free option.

So that is something that I will always take into account and when possible, I will offer those sorts of trials to patients, especially when the tumor burden is relatively modest, when the disease is not causing a strong burden of symptoms. Now when we see those sorts of scenarios where patients have a high volume of disease or have lots of symptoms relating to that, you may need something that is a little bit more than just an I-O plus something else like a vaccine strategy.

But generally speaking, I will always prioritize a non-chemotherapy containing regimen where it is possible for a patient to derive benefit and HPV-positive related cancers. Those particularly, I think, are a group of patients who really stand the chance of deriving long-term durable benefit there we even begin to dream about this curing of their disease.

I agree with what Dr. Harrington said. There always will be a small percentage of patients that just require more aggressive treatment upfront. But in general, we're trying to look at both activity and also tolerability. And so the VERSATILE-003 study and we know from the VERSATILE-002 that patients just tolerated this combination so well. And so they weren't having toxicities that then took them out from being able to get second, third, fourth line treatment.

There's a lot of interesting drugs out there. Most of them are showing promise predominantly in the HPV negative space. But I think important to note, some of the antibody drug conjugates, for example, these are not easy drugs to take. They might be promising, but they're not drugs that patients can be on for an extended period of time.

And so the way I look at it and when I approach a patient who has recurrent metastatic disease, I want to have a list of treatment options because right now, none of these are curative options. So we know that we have to sequence them appropriately. And so I always try to approach treatment. What are the -- what is the order that's going to get the most mileage out of every treatment and give us the most number of options down the line? And so the VERSATILE-003 combination is an excellent one from that standpoint.

Excellent. The next question is from James Molloy, AGP. And he's asking where would you see Versamune in the treatment algorithm should it ultimately be approved? You've answered that a little bit already, but maybe go on to the effects of the companion diagnostic now, being able to identify a patient population with HPV16 positivity. Maybe what do you see the future like with both the approval of drug and then a companion diagnostic?

Katharine, you go, please.

Well, I think the companion diagnostic is going to be really helpful as a clinician because many of the HPV assays out there, they don't necessarily tell you the subtype right off the bat. So you don't always know. So I think it will be very important to have that companion diagnostic to be able to flag, okay, these are patients that will can benefit from this combination.

I think looking, hopefully, at approval would be primarily in the first-line setting with an immunotherapy agent again, so that then subsequent treatments that may be more toxic can be kind of held in the back pocket.

Kevin, anything to add?

Yes. I think it adds huge strength. A companion diagnostic is a wonderful thing to have. It adds some level of complexity to treatment selection. But assuming that we got a positive setting, we got an approval of the agent, then that suggests that you've really got a valuable treatment option for the patient and knowing that the patient has an HPV16 specifically positive tumor and therefore, is likely to derive benefit and potentially the sort of durability and also the depth of the responses that you saw.

So we saw 21% of patients having really very substantial reductions in volume of disease. That is well worth having. And so I think that most clinicians will take the view and the patients, I think, will be comfortable with that notion, that actually getting the information that allows you to make the rational selection with a good predictive possibility that the patient is going to derive durable benefit.

I think that is absolutely essential to correct patient treatment sequencing. And again, I agree with Dr. Price, it's got to the point now in head and neck oncology where it's about trying to maximize the gains of all of the treatments that you deploy and the order in which you use them in order to keep the patient as well as possible for as long as possible.

And for some of those patients to begin to think that beyond 5 years, actually, they may not die of this disease and you actually may be able to think about curing a small number of patients.

Excellent. Thank you. As you alluded to, Dr. Harrington, it's been reported in the medical journal asset, there's an increase in incidents now confirmed driven almost exclusively by HPV16 and some publications have suggested will go as high as 30% a year, as you've talked about. Do you have any insight either why this growing health concern is not well understood by many people outside of the medical community as well as maybe some within the medical community?

Yes, you addressed that to me, Kirk, and I'm happy to give some thoughts on this in the first instance because it's a conundrum, isn't it? This is a rapidly growing incidence disease. I hesitate to use the word epidemic because that's often overblown. But nonetheless, for those of us who treat this disease, it's been a complete change in our practice over the last decade to how we see the patients presenting first with newly diagnosed and then with relapsed metastatic disease.

And why this doesn't gain more traction and why the discussion around vaccination has not led to greater public health efforts to emphasize the benefits against not just cervix cancer and genitourinary disease, but also against oropharyngeal carcinomas, frankly, is a bit of a mystery to me.

Nonetheless, I think we have to continue to try to push those efforts. Of course, in the absence of a demonstrable reduction through vaccination yet, and as I showed you in those epidemiological data, the fact we can confidently expect unfortunately for the next 10, 20 years, we're going to still see an upstroke or even a plateau phase of high incidents, it's incumbent upon us to give our efforts to try to develop the most effective therapies that we can.

So no answer, I'm afraid, to why society and why governments don't take greater efforts in terms of or at least recognition of this. But there's no doubt that the medical community understands the scale of the problem, and it is engaged in trying to develop the treatments that will make a difference.

Katharine, I know you've been especially focused on the population of preventative vaccines for HPV. And there you see the mix of what's going on. You're trying to get people to accept the vaccination. But at the same time, you have this -- as I said, I hesitate to call it back a epidemic also coming, but it's a huge increase in the HPV16 positive. Any insights there that you can see why people have been resistant to accepting this?

Yes. I mean it is a bit of a conundrum in the outreach that we've done sort of both out in the community as well as with health care providers, I think there is pretty good understanding or people think about HPV-related cervical cancer and they think about girls and think about women, but there's -- they really -- it just has not been on the radar that it's our boys and men that are affected by the head and neck cancer epidemic.

And I think epidemic is fair. I mean, if we look in the United States, the incidence continues to rise. And it's been the 8th most common cancer in men in the United States for many, many years now. So I don't know why there is such a barrier, but that barrier is really there. And I think just as a whole, as a society, as health care providers, we need to, one, just normalize the HPV vaccination as a preventive measure.

I did just want to highlight when we think about therapies that are easy to administer and don't have a lot of toxicity and just think about it from a standpoint of health disparities. So in the United States, and I suspect this is true in Europe as well, one of the things that we see with the HPV-related head and neck cancer epidemic is that those numbers continue to really climb in rural areas. And the vaccination rates, particularly for boys, is dismally low in rural areas, and those 2 things track together.

So we're starting to see in the United States in more urban areas, some leveling off of the incidence of HPV-related head and neck cancer, but we're seeing this growing disparity where our rural populations are more and more affected. And so then if you think about this combination, which is well tolerated, easy to give, that is something that could be deployed in less well-served areas compared to a complicated trial or a trial that -- or a drug that results in a lot of toxicity.

So I don't have an answer for the psyche. I'm continuously sort of amazed by the lack of knowledge and the lack of vaccination uptake, but we're doing the best we can. And I think it's just a societies, we need to just do a better job at just advocating for vaccination and normalizing that.

Great. Just a question about mechanism of attacking it. A couple of studies ongoing to have eGFR mechanism. I mean, what is your thoughts about the MOA of the eGFR in the HPV positive population?

Well, maybe I'll have a first stab at that. And -- we've got a fairly robust literature now backing up the fact that HPV-related and HPV-driven cancer is not recognizably an eGFR-driven disease. And so those data, I think, are -- go all the way from the relative mutual exclusivity of expression of HPV positivity and eGFR levels, although those don't necessarily predict response to an eGFR-targeted therapy.

And I think in the second, third line setting, the recent presentation of the Interlink 1 data in which cetuximab with monalizumab or cetuximab monotherapy was used in an HPV-related and an HPV unrelated separate population, what we really saw in that study was actually cetuximab has very poor activity in patients with HPV-related disease.

So we take that and we look at those data through the lens of the petosemtamab study, which is enrolling patients with HPV-related cancers. Now petosemtamab, as I've discussed, eGFR times LGR5. I think the literature around LGR5, which is putatively a stem cell marker feeding into the wind signaling pathway potentially involved in mechanisms, including epithelial mesenchymal transition.

I don't know that there is a very clear line of sight to why that drug might necessarily turn around that relative lack of activity of eGFR targeted treatments in HPV-related disease. We will, of course, see the results of the LIGA-1 study. And indeed, the LIGA-2 study that includes patients with HPV-related disease, and we'll get an answer for that.

But it's interesting to note that, I guess, probably the front runner competitor to petosemtamab, ficerafusp alfa, which is an eGFR times -- well, within TGF-Beta trapping moiety, they're not even going there. They're not even looking to recruit patients with HPV-positive disease. So I think that company has taken a view. So I am not convinced as yet that there is a clear line of sight to using eGFR targeted therapies in HPV-related disease. So time will tell. But again, I don't know what Dr. Price's view of this is, but I think it's not the strongest rationale.

I agree. And I think clinically, if we just look at it from just pure clinician perspective, we know that the cetuximab studies in HPV-related cancers in combination with radiation in the definitive setting did worse than chemotherapy and radiation. And I never use eGFR agents as single agents for HPV patients in the recurrent metastatic setting. I mean -- and the newer agents I look at primarily as HPV negative as well.

So I think there are some patients that are very sensitive to cetuximab, which is a standard of care eGFR antibody. But in my experience, those are always oral cavity patients, HPV negative patients. It's never been for HPV positive.

Great. Thank you. Well, it's hard to believe an hour has gone by. Thank you very much for your excellent discussions. This concludes our webinar for today. We at PDS Biotech are really excited about our current data and future studies in helping our patients. And we're very pleased that we've initiated the VERSATILE-003 registrational trial this quarter. And especially, we like to thank today our 2 experts, Dr. Price and Dr. Harrington for their excellent presentations and discussions. And I also want to thank you for your participation in the webinar today. So we look forward in the future to giving you updates on our progress. So again, thank you, and have a great day.