PDS Biotechnology Q3 2025 Earnings Call - Strategic Protocol Amendment to Expedite Head and Neck Cancer Treatment Approval

Operator: Greetings. Welcome to the PDS Biotechnology third quarter 2025 earnings conference call. At this time, all participants are in listen-only mode. The question-and-answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please note that this conference is being recorded. At this time, we’ll turn the conference over to Tom Johnson with LifeSci Advisors. Tom, you may now begin.

Tom Johnson, Moderator/Advisor, LifeSci Advisors: Thank you, Operator. Good morning, everyone, and welcome to PDS Biotechnology’s third 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 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 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. Frank Bedu-Addo.

Dr. Frank Bedu-Addo, Chief Executive Officer, PDS Biotechnology: 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 HPV-16 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 two clinical trial. As you will recall, the VERSATILE-002 trial evaluated PDS0101 plus Keytruda or pembrolizumab in patients with HPV-16 positive head and 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 one. 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 one. This PFS result is notable considering the fact that over 62% of patients in the VERSATILE-002 study had low CPS of 1-19. 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 three trial, the primary endpoint for the VERSATILE-002 trial was objective response rate or ORR. The VERSATILE-002 study included nine sensitive 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 nine 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 nine patients. The resulting sensitivity 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 40 months.

The PFS and survival results also have important implications for the current design of our phase three VERSATILE-003 trial. In the current trial protocol, median overall survival is the primary endpoint, and progression-free survival is a secondary endpoint. However, even before our final readout of VERSATILE-002, a key concern external to PDS Biotechnology 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 a 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 HPV-16 positive patients in dire need of effective treatment.

Treatment with PDS0101 for currently enrolled patients in our VERSATILE-003 phase three 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 Delvin Insights 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 are HPV-16 positive. We are therefore confident in the potential of our HPV-16 tailored approach and the potential of PDS0101 to ultimately provide a well-tolerated treatment without chemotherapy as an option for the growing population of HPV-16 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.

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 three abstracts highlighting emerging clinical and translational findings from PDS Biotechnology’s novel investigational immunotherapy platforms, including PDS0101, our lead phase three clinical stage HPV-targeted immunotherapy, and our tumor-targeting IL-12 fused antibody drug conjugate, PDS01ADC. The presented translational biomarker studies demonstrated the unique immunological properties of PDS0101 and PDS01ADC, leading to anti-tumor 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 two clinical trial with PDS01ADC met the criteria for expansion to stage two following positive stage one results. This trial is also being led by the National Cancer Institute. Our phase two clinical collaborations with the National Cancer Institute, MD Anderson Cancer Center, Mayo Clinic, as well as our preclinical collaboration with NIAID, allow us to focus our resources on our VERSATILE-003 phase three 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.

Lars Boesgaard, Chief Financial Officer, PDS Biotechnology: Thanks, Frank, and good morning, everyone. We reported a net loss of $9 million or $0.19 per basic and diluted share for the three months ended September 30, 2025. That compared to $10.7 million or $0.29 per basic share in the prior year’s quarter. The decrease in net loss was primarily due to lower operating expenses. Research and development expenses were $4.6 million for the three 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 three 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 three months ended September 30, 2025, compared to $10.2 million for the prior year period. Net interest expense was $0.9 million for the three 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 pre-funded warrants, as well as $5.8 million accompanying warrants for gross proceeds of approximately $5.3 million. Operator, we can open up the call for any questions.

Operator: Thank you. We’ll now be conducting a question-and-answer session. If you’d like to ask a question at this time, you may press star one from your telephone keypad, and the confirmation tone will indicate your line is in the question queue. You may press star two if you’d like to withdraw your question from the queue. For participants that are using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, while we pull for questions. Thank you. Our first question is from the line of Maya Mamtani with B. Riley Securities. Please proceed with your questions.

Maya Mamtani, Analyst, B. Riley Securities: Yes, good morning, Deanne. Thanks for taking our questions and appreciate the update. 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 this new PFS analysis that now you’re going to propose to the agency? If you could just give us an update logistically how patients enrolled will be included there. 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 was also curious what the net cost savings would be for you as a result of that.

Lars Boesgaard, Chief Financial Officer, PDS Biotechnology: Maya, thanks a lot for your question. I think, as we mentioned 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 do not want to do any of that until we have actually sat down with the FDA. We have made certain proposals to the FDA, but the anticipation and the hope here 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.

I’ll hand over to Kirk and see if he has anything to add to that.

Dr. Kirk Shepard, Chief Medical Officer, PDS Biotechnology: 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. The emphasis here, as Frank said, is that these patients will be continued to receive drug on the protocol during the pause.

Maya Mamtani, Analyst, B. Riley Securities: Thank you. Are you able to share any information on what the expected PFS would be on the 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 three study for. Thanks for taking our questions.

Lars Boesgaard, Chief Financial Officer, PDS Biotechnology: Sure, Maya. 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. Also, what we’re proposing is nothing unusual in terms of clinical trial design. 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 abide by the regulatory guidelines. We’re making sure we stick with that. In terms of the VERSATILE-003 trial, Maya, 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.

Maya Mamtani, Analyst, B. Riley Securities: Yes. 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?

Lars Boesgaard, Chief Financial Officer, PDS Biotechnology: Correct. Correct. The PFS, as you know, in the KEYNOTE-048 study, as well as the LEAP-10 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-10 study. These studies were predominantly, we assume the LEAP-10 study was predominantly HPV negative. That has not been published yet, but we know that the KEYNOTE-048 study was predominantly in HPV negative patients. We know that there are two 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. 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.

At this point, we are conservatively assuming that the PFS in the control arm is going to be around the three-month range, which has been reported for KEYNOTE-048 and also in the LEAP-10 study, which was 2.8 months.

Maya Mamtani, Analyst, B. Riley Securities: Thank you. That’s a big delta. 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, including at ESMO. Any thoughts on how you’re looking at the broader landscape, especially on the HPV positive side where there’s not, or the HPV-16 positive side where there’s not a whole lot going on? Thanks for taking our questions.

Lars Boesgaard, Chief Financial Officer, PDS Biotechnology: Right. Maya, 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 neck cancer is becoming a really serious medical problem. Just in the last few months, we’ve had several publications report on the growing incidence of HPV positive head and neck cancer. 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.

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 cancers are HPV-16 positive. We’ve shown on our slides 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. 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 head and neck cancer in the next decade.

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 studies and products being developed in head and neck cancer are not focused on HPV positive head and neck cancer.

Operator: Thank you. Our next question is from the line of Joe Pampena with H.C. Wainwright. Please proceed with your question.

Joe Pampena, Analyst, H.C. Wainwright: Hey, guys. Good morning. Thanks for taking the questions. Two questions, if you don’t mind. On 002, can you remind us or inform us or what have you, the patients that have had such long-term survival, have they seen any additional therapeutic interventions? I don’t believe they have. 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 since you obviously have a lot more sites than 002 with regard to being able to adapt to and not make calls early based on potential pseudoprogression of the tumors from the cancer immunotherapy? Thanks.

Lars Boesgaard, Chief Financial Officer, PDS Biotechnology: Hey, Joe, I’ll start it, and 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 resistant. In HPV positive disease, this is published, the median overall survival is only three to four months. We have to bear that in mind in this discussion. Once you become checkpoint inhibitor resistant in HPV positive disease, your median overall survival is three to four months.

Therefore, if you come off PDS0101 and go on to some other therapy, and all of a sudden you’ve seen prolonged survival, then very likely it’s only reasonable to assume that that prolonged survival came from, was a result of, the therapy, PDS0101 therapy, because it is very well established that if you’re checkpoint resistant, you are not going to have long survival. Now, when patients come off the VERSATILE-002 trial, there is no FDA-approved therapy for checkpoint resistant patients. They will very likely go on to any investigator-choice chemotherapy. That’s the most likely therapy that anybody who comes off PDS0101 will go on to.

In terms of the VERSATILE-003 design and investigators being trained and how they look at things like pseudoprogression, that’s something that’s very important with an immunotherapy and some of the discussions that have been had with our steering committee. I’ll hand over to Kirk to address that question.

Dr. Kirk Shepard, Chief Medical Officer, PDS Biotechnology: 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. 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. Also, this will be reviewed, as you know, by a central review from experts who will be reading the scans, etc. We’ve discussed this a lot. People are sensitive to the fact that there may be pseudoprogression.

With patients who are still clinically well and yet not determined yet as far as the response, we will continue to follow them. This is very important and different than the 002 because 002, remember, the primary was ORR as far as response rate. 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. We are comfortable now with the training we have had and the discussions we have had with the steering committee that we will be able to properly judge these patients as far as PFS. We are also very fortunate that with the current site accruals that we have, a lot of the sites are returning who were on VERSATILE-002. They have 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. We have a good core of sites that have had experience with the drug as well as judging these responses. Thanks for your question.

Joe Pampena, Analyst, H.C. Wainwright: Appreciate all the feedback. Thanks a lot.

Operator: Thank you. At this time, I’ll hand the floor back to Matthew for further remarks.

Lars Boesgaard, Chief Financial Officer, PDS Biotechnology: Thank you, Operator. 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.

Operator: 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.