PDS Biotechnology Corporation

Greetings and welcome to the PDS Biotechnology Third Quarter 2023 Earnings Call-In Webcast. At this time, all participants are in a listen-only mode. A 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. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Nicole Jones, Investor Relations for PDS Biotechnology. Thank you. You may begin.

Good morning, and welcome to PDS Biotechnology's third quarter 2023 earnings conference call and webcast. On the call from the company are Dr. Frank Baduado, Chief Executive Officer, Matt Hill, Chief Financial Officer, and Dr. Lauren V. Wood, Chief Medical Officer. Earlier this morning, PDS Biotech issued a press release announcing financial results for the quarter ended September 30th, 2023. We encourage everyone to read the press release as well as PDS Biotech's report on Form 10-Q, which will be filed with the SEC shortly. The company's press release is available on the PDS website at pdsbiotech.com. In addition, this conference call is being webcast and will be archived on the company website for future reference. Before we begin, we need to remind everyone that on today's call, the company will be making forward-looking statements regarding regulatory and clinical candidate development plans, as well as research activities. Certain information in this presentation may include forward-looking statements, including within the meaning of this Section 21 of the United States Securities Exchange Act of 1934, as amended, and Section 27 of the United States Securities Act of 1933, as amended. Biotechnology Corporation, and other matters. These statements may discuss goals, intentions, and expectations as to future plans, trends, events, results of operations, or financial condition or otherwise, based on current beliefs of the company's management, as well as assumptions made by and information currently available to management. These statements are subject to risk and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found on PDS Biotech's most recent filings with the SEC. Your caution not to place undue reliance on these forward-looking statements would speak only as of the date of this conference call. Except to the extent required by applicable law or regulation, PDS Biotech undertakes no obligation to update the forward-looking statements included today to reflect subsequent events or circumstances. I will now hand the call over to Dr. Frank Baduado. Frank?

Thank you, Nicole. and welcome to everyone to our third quarter 2023 conference call. We are excited about the strides we're making, fueled by our commitment to developing groundbreaking therapies that revolutionize cancer treatment based on our proprietary Versamune platform and IL-12 fused antibody drug conjugate PDS01-ADC, formerly known as PDS03-01 or M9241. The clinical data stemming from the PDS01 ADC asset, which we acquired nearly a year ago from Merck KGAA, Darmstadt, Germany, continues to advance and mature, reinforcing our belief that this innovative ADC could potentially address the safety and efficacy limitations that have been observed with cytokine therapy to date. The combination of versus immune-based approaches and our IL-12 ADC has demonstrated the potential to overcome the limitations of effectively treating advanced cancer and extending patients' lives with immunotherapy. Currently, we have safety data for over 250 patients who have been treated with PDS01-ADC, supporting the early data suggesting that this innovative ADC effectively directs the IL-12 into the tumor therefore reducing its presence in the circulating blood and subsequently limiting the adverse events that have been reported with other cytokines. In addition, the increased and sustained presence of IL-12 in the tumor has been shown in our ongoing trials to enhance the clinical activity. This novel modification of IL-12 therefore presents us with a unique opportunity to address a broad range of cancers. We continue to move this ADC forward with various promising approaches. It is being developed as a monotherapy. It's also being developed in combination with versamine-based approaches and also in combination with other standards of care. I will talk more about these updates on PDS01-ADC later on the call. We are pleased with our current progress driven by our mission to develop groundbreaking therapies that transform cancer treatment. Our immediate objective revolves around progressing our primary clinical candidate PDS0101 to the market. PDS0101 represents a novel investigational HPV16 targeted immunotherapy that triggers a potent and precise T cell response against HPV16 positive cancers. This quarter, we made significant progress on our Versamune platform, specifically with our Phase 2 Versatile 002 trial. We hosted a positive key opinion leader or KOL event that included key opinion leaders who have been part of the Versatile 002 trial, and others who have not been part of the trial and are leaders in the head and neck cancer field. It was important to understand how head and neck cancer expert oncologists view the trial results and the potential for PDS0101 in Keytruda to become the standard of care for recurrent or metastatic head and neck cancer. Overall, the experts were enthusiastic about the updated Versatile 002 data and the planned initiation of the Phase III Versatile 003 trial. At this event, we presented data from both the immune checkpoint inhibitor-naive or ICI-naive and the ICI-resistant patient cohorts, both of which demonstrated impressive patient overall survival. For today's discussion on the Versatile 002 trial, we will focus on the ICI-naive group. With this population, we reported a 24-month overall survival rate of 74%, which means that on the combination of PDS-0101 and Keytruda, the probability that a patient will live at least two years is 74%. To put this number into perspective, published 24-month overall survival rates for approved ICIs is less than 30%, meaning that on today's approved therapies, the probability that the patient will live for at least two years is only about 30%. The Versatile 002 data suggests that patients are living longer when treated with the PDS-0101 plus Keytruda combination. It is important to note that disease control, which includes stable disease and tumor shrinkage, was seen in 81% of patients. Tumor shrinkage was reported in 60% of patients and a confirmed objective response rate or ORR of 27% was reported based on investigator assessment. With respect to safety, the combination continues to be well tolerated with 13% of patients having grade three treatment-related toxicities and no patients having any grade four or grade five treatment-related events. To put this in context, in Keynote 048, It is reported that 17% of patients on Keytruda monotherapy experience grade three to five treatment-related toxicities, and 72% of patients on Keytruda plus chemotherapy experience grade three to grade five treatment-related toxicities. With this data, we believe that we are on track to revolutionize the treatment of head and neck cancer with improved clinical outcomes and better tolerability. Furthermore, in October 2023, preliminary biomarker data from the VERSATILE-002 trial was presented at the European Society for Medical Oncology, or ESMO Congress, 2023. The combination of PDS-0101 incutruda appears to be promoting a predominant Th1 immunologic profile that is associated with enhanced CD8 killer T cell induction and activity. The combination also led to subsequent decreases in the population of CD8 killer T cells in the circulating blood. We are encouraged that these observations align with other Phase II studies reporting that PDS0101-induced polyfunctional CD8 killer T cells do not reside in the blood, but rather traffic to tumors. These data support the two-year 74% overall survival rate reported in Versatile 002. Beyond the Versatile 002 trial, our focus has remained on steadily advancing preparations for our Phase 3 Versatile 003 trial. In October 2023, we announced feedback from the FDA regarding the amended investigational new drug application and thereafter feedback on the final clinical trial protocol. We currently have up to 60 sites selected globally. and are going through the qualifying process. As anticipated, the FDA-reviewed Phase III clinical trial design has been pivotal to our business development discussions, which has yielded positive insights from prospective partners. Our clinical and medical teams are assessing final details of the trial, and therefore, we anticipate Versatile 003 will now start in the first quarter of 2024. We'll keep you updated on our next steps as we progress toward trial initiation. Now turning to ImmunoServe. In October 2023, data from the Phase II clinical trial were featured in an oral presentation of the American Society for Radiation Oncology Annual Meeting, known as ASTRO. These data demonstrated that PDS0101 in combination with standard-of-care chemoradiotherapy was associated with a rapid decline in HPV-positive circulating tumor DNA. At five weeks of treatment, ctDNA clearance of 92% was reported with PDS0101, whereas 53% clearance was observed in patients receiving standard-of-care chemoradiotherapy alone. These biomarker data support the 100% response rate in patients receiving PDS-0101 and standard of care, which was reported at SITC 2022. As this trial continues to progress, we will provide further updates. Now shifting to our IL-12 fused antibody drug conjugate known as PDS-01-ADC. PDS01-ADC is a novel ADC or antibody drug conjugate that enhances the proliferation, potency, and longevity of T cells and IL-12 in the tumor. Let's begin by discussing the compelling updated data from the National Cancer Institute-led triple combination trial that was reported on November 9th. This study is a Phase II trial of PDS-0101, PDS-01-ADC, and an investigational ICI. This combination has undergone evaluation across multiple HPV-positive cancers encompassing anal, cervical, head and neck, vaginal, and vulva cancers in two groups of advanced cancer patients. The ICI-naive group constituted patients unresponsive to standard of care treatments that have not yet received ICI therapy. The ICI resistant group included individuals who had shown no response to multiple prior treatments, including ICI therapy. Regarding the ICI naive group, the chart shows the confirmed objective responses reported in Versatile 002 and the triple combination based on investigator assessment, both shown in green, as well as published Keynote 048 data. Notable is the objective response rate of 75% with the triple combination and 27% with the dual combination. With Keytruda monotherapy and Keytruda Plus chemotherapy, the published objective response rates were 19% and 36% respectively. The next figure contains updated survival data from Versal 002 and the triple combination trial in green, as well as published data from Keynote 048. What is notable here? is the fact that despite the lower objective response rate with PDS-0101 plus Keytruda, the survival benefit seen with the PDS-0101 plus Keytruda combination, as well as the triple combination, appears to be similar, with 24-month survival rates of 74 and 75% respectively. The triple combination also shows a compelling three-year survival of 75%. These data suggest that PDS01-01 may play a significant role in extended survival in the ICI-naive population, independent of objective response rate, while PDS01-ADC appears to promote strong objective responses in this population. The median overall survival has not yet been reached in either the Versatile 002 or the triple combination studies. To contextualize, published data on standard of care immune checkpoint inhibitors, or ICIs, report that at 12 months, only 30 to 50% of these patients would typically be expected to remain alive. And less than 30% of the patients could be expected to remain alive at 24 months. Therefore, survival associated with the PDS-0101 combination regimen at two years for Versatile 002 and three years for the triple combinations is notable. Now looking at the ICI resistant group, where there's a significant unmet medical need and no FDA-approved product. These are the patients who have failed all treatment options including ICIs. In these ICI-resistant patients with HPV-positive cancers, the reported median overall survival is only about three to four months. In the ICI-resistant patients, this slide shows that the published objective response rate with systemic therapies including high-dose chemotherapy is 42%. The objective response rate was 0% with PDS01-01 plus Keytruda in Versatile 002, 5% in patients who received PDS01-01 with low doses of PDS01-ADC and or ICI therapy, and 63% in patients who received PDS01-01 with initial high doses of PDS01-ADC and ICI therapy. Again, these data appear to demonstrate the role of PDS01-ADC in promoting strong and compelling objective response rates, even in late-stage ICI-resistant cancer patients. Let's now take a look at the overall survival rate in ICI-resistant patients. On the slide, we will see that irrespective of objective response rate, the PDS0101 containing therapies shown by the green bars provide durable survival results. Despite the lack of confirmed objective responses with PDS0101 plus Keytruda, the 12-month overall survival rate was 56% for Versal 002 and 72% in the triple combination. With systemic therapies, the published 12-month overall survival rate is 36%. This data provides compelling evidence regarding the role of PDS01-01 in the survival of ICI-naive and ICI-refractory HPV16-positive patients and the potential role of PDS01-ADC in further extending survival responses in this population. This study provides compelling evidence that supports the potential synergy between our versamine-based targeted T-cell immunotherapies and our IL-12 fused antibody drug conjugate that provides the sustained presence of IL-12 in the tumor, thus providing further expansion and activation of the versamine-induced multifunctional killer T-cells within the patient's tumor. We believe that this data supports broader application of this combination beyond HPV-positive cancer and provides a unique potential to effectively address multiple advanced cancers in our development pipeline. As a reminder, a safety update for this trial was announced in late December 2022 in 50 patients. 48% of patients experienced grade three treatment-related adverse events, or AEs, and 4% of patients experienced grade four related adverse events. To put the safety profile in context, in the Keynote 048 study, it is reported that the combination of Keytruda and chemotherapy resulted in 72% of patients having grade three through grade five treatment-related adverse events. We are therefore pleased with the tolerability profile that is emerging for PDS01-ADC, even when administered in combination with other oncology agents. As I mentioned earlier, to date, we have safety data from over 250 patients dosed with PDS01-ADC. This provides further evidence that this novel modification of IL-12 may be effective in mitigating previously observed cytokine side effects while promoting improved clinical benefit and further justifies its continued development by PDS biotech. PDS01-ADC is also being studied independently of diverse immune immunotherapies. The National Cancer Institute recently presented data for the ongoing Phase II clinical trial of PDS01-ADC in combination with docetaxel chemotherapy in advanced metastatic castration-sensitive and castration-resistant prostate cancer patients at the Cytokines 2023 annual meeting. This trial is the first clinical study of an immunocytokine with docetaxel in prostate cancer. The study is investigating the safety, immune responses, and preliminary clinical activity of the combination in advanced prostate cancer patients. The trial evaluated three doses of PDS01-ADC in combination with docetaxel, and showed that the combination was well tolerated at all tested doses with less than 10% of patients having a grade 4 toxicity. Most importantly, over 60% of patients had a prostate-specific antigen or PSA level reduction of greater than 60%, with some patients having a 90 to 100 PSA reduction. As shown, reduced PSA levels were documented in all 18 patients. PDS01-ADC activates T cells, natural killer cells, and natural killer T cells while reducing the presence of immune-suppressive regulatory T cells. As a result, we believe that we now also have an opportunity to apply PDS01-ADC to advanced and difficult-to-treat tumors by combining PDS01-ADC with standard-of-care chemotherapy and radiation therapy. PDS01-ADC is also being investigated by the National Cancer Institute in a Phase I-II study in patients with intermediate and high-risk locally advanced prostate cancer in combination with radiation therapy. As mentioned previously, PDS01-ADC is also being studied as a monotherapy by the National Cancer Institute in an ongoing Phase II clinical trial in Kaposi's sarcoma. At PDS Biotech, we are highly optimistic about the potential of this novel PDS01-ADC asset in cancer therapy. Switching now to preclinical development studies. The National Cancer Institute has developed a second novel approach to treating immune checkpoint inhibitor-resistant cancers by using versamine-based immunotherapy and PDS01-ADC in combination with histone deacetylase or HDAC inhibitors, another oncology standard of care. The preclinical data were presented during the recently concluded 2023 annual meeting of the Society for Immunotherapy of Cancer, or SITC. In this preclinical study, superior anti-tumor activity was observed in ICI-resistant tumor models with aversive-based immunotherapy, PDS01-ADC, and antenostat, a class I HDAC inhibitor. This novel triple combination proof-of-concept study is under consideration as a potential approach for initial clinical studies of PDS0103 to treat Mach 1 specific cancers. We are encouraged by the potential of this combination. The National Cancer Institute will lead this clinical trial under our established cooperative research and development agreement, and we anticipate that it will begin in the first half of 2024. PDS Biotech has had a fruitful quarter and we are preparing to finish out the year strong as we move into 2024. To summarize, we hosted a successful KOL event where we announced positive updated overall survival and safety data from the Versatile 002 trial and gained important insights from head and neck oncology leaders about the potential of PDS-0101 in the treatment of HPV-positive head and neck cancer. Preliminary biomarker data presented at ESMO from the VERSYL-002 trial supports the reported overall survival results. The biomarker data from the Immunoserve trial presented at ASTRO demonstrates the role of PDS-0101 in eliminating circulating tumor HPV DNA. The updated triple combination data demonstrates the role of PDS01-ADC in promoting durable overall survival and objective responses even in difficult to treat ICI resistant patients. Data from the PDS01-ADC and docetaxel trial presented at cytokine demonstrated tolerability of the combination and encouraging PSA biomarker results and immune responses. With that, I'd now like to turn the call over to Matt to discuss the financial summary. Matt.